a LANGE medical book

CURRENT
Pediatric Diagnosis
& Treatment
17th Edition
Edited by

William W. Hay, Jr., MD Judith M. Sondheimer, MD

Professor, Department of Pediatrics Professor, Department of Pediatrics, and Head, Section
Section of Neonatology and the Division of Perinatal of Pediatric Gastroenterology, Hepatology, and Nutrition
Medicine and Research University of Colorado School of Medicine and
University of Colorado School of Medicine and The Children’s Hospital, Denver
The Children’s Hospital, Denver
Robin R. Deterding, MD
Myron J. Levin, MD Associate Professor, Department of Pediatrics, Section of
Professor, Departments of Pediatrics and Medicine Pediatric Pulmonary Medicine
University of Colorado School of Medicine and University of Colorado School of Medicine and
The Children’s Hospital, Denver The Children’s Hospital, Denver

and Associate Authors

The Department of Pediatrics at the University of
Colorado School of Medicine is affiliated with
The Children’s Hospital of Denver, Colorado.

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Contents
Authors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xi

Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xix

1. The Newborn Infant . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

Elizabeth H. Thilo, MD, & Adam A. Rosenberg, MD
Evaluation of the Newborn Infant History 1 Infections in the Newborn Infant 49
Care of the Well Newborn Infant 8 Hematologic Disorders in the Newborn Infant 58
Common Problems in the Term Newborn Infant 11 Renal Disorders in the Newborn Infant 61
Neonatal Intensive Care 26 Neurologic Problems in the Newborn Infant 62
Cardiac Problems in the Newborn Infant 43 Metabolic Disorders in the Newborn Infant 64
Gastrointestinal & Abdominal Surgical Conditions in the Newborn
Infant 46

2. Child Development & Behavior. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66

Edward Goldson, MD, & Ann Reynolds, MD
Normal Development 66 Common Developmental Concerns 86
Behavioral & Developmental Variations 85 Developmental Disorders 93
Normality & Temperament 85

3. Adolescence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102
David W. Kaplan, MD, MPH, & Kathryn Love-Osborne, MD
Guidelines for Adolescent Preventive Services 104 Breast Disorders 125
Growth & Development 113 Gynecologic Disorders in Adolescence 128
Behavior & Psychological Health 115

4. Substance Abuse. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147

Paritosh Kaul, MD, & Catherine Stevens-Simon, MD
Scope of the Problem 147 Predicting the Progression From Use to Abuse 155
Morbidity Associated with Substance Abuse 152 Management of Substance Abuse 156
Supplement Use and Abuse 154 Treatment & Referral 160
Response to the Problem 155 Prevention of Substance Abuse 164

5. Eating Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165

Eric J. Sigel, MD
Etiology 165 Complications 170
Incidence 166 Treatment 172
Predisposing Factors 166 Prognosis 175
Diagnosis 166

6. Child & Adolescent Psychiatric Disorders & Psychosocial Aspects of Pediatrics . . . . . . . . . . . . . . . 176
Jennifer Hagman, MD, & Donald W. Bechtold, MD
Psychosocial Aspects of Child Development & Family Life 176 Screening for Psychosocial Problems & Psychiatric Disorders Within
Challenges in Parenting Related to Child & Adolescent the Context of Health Maintenance Visits 184
Development 179 Psychiatric Disorders of Childhood & Adolescence 188
The Chronically Ill Child 182 Overview of Pediatric Psychopharmacology 210

iii
iv / CONTENTS

7. Child Abuse & Neglect . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 221

Andrew P. Sirotnak, MD, & Richard D. Krugman, MD
Forms of Child Maltreatment 221 Management & Reporting of Child Abuse & Neglect 225
Recognition of Abuse & Neglect 222 Prevention of Child Abuse & Neglect 225

8. Ambulatory & Community Pediatrics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 227

Robert M. Brayden, MD, Matthew F. Daley, MD, & Jeffrey M. Brown, MD, MPH
Pediatric History 227 Other Types of General Pediatric Services 240
Pediatric Physical Examination 228 Common General Pediatric Issues 244
Health Supervision Visits 230

9. Immunization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 248
Matthew F. Daley, MD, Ann-Christine Nyquist, MD, MSPH, & Eric A. F. Simoes, MD, DCH
The Composition of Immunizing Agents 249 Passive Prophylaxis 282
Safety of Immunization 250 Legal Issues in Immunization 283
Vaccinations for Special Situations 276

10. Normal Childhood Nutrition & Its Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 284

Nancy F. Krebs, MD, MS, Laura E. Primak, RD, CNSD, CSP,
& K. Michael Hambidge, MD, BChir, ScD
Nutritional Requirements 284 Pediatric Undernutrition 304
Infant Feeding 299

11. Emergencies & Injuries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 317

F. Keith Battan, MD, & Marsha S. Anderson, MD
I. Emergencies & Injuries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 317
Advanced Life Support for Infants & Children 317 Burns 331
Emergency Pediatric Drugs 323 Hypothermia 334
Approach to the Seriously Ill Child 323 Submersion Injuries 335
Approach to the Pediatric Trauma Patient 325 Bites: Animal & Human 336
Head Injury 329
II. Bioterrorism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 337
Anthrax 337 Plague 343
Smallpox 340 Botulinum Toxin 344

12. Poisoning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 346

Richard C. Dart, MD, PhD, & Barry H. Rumack, MD
Management of Specific Common Poisonings 350

13. Critical Care. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 372

Todd C. Carpenter, MD, Emily L. Dobyns, MD, Stephanie N. Mateev, MD, Peter M. Mourani, MD,
Margaret A. Ferguson, MD, & Kurt R. Stenmark, MD
Acute Respiratory Failure 372 Brain Injury/Cerebral Edema 397
Mechanical Ventilation 377 Ethical Deliberation and End-of-Life Care in the PICU 401
Acute Respiratory Distress Syndrome 380 Nutritional Support of the Critically Ill Child 402
Asthma (Life-Threatening) 384 Pain & Anxiety Control 406
Shock 386
Indications for Central Venous and Arterial Cannulation 393
 CONTENTS / v

14. Skin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 411

Joseph G. Morelli, MD, & William L. Weston, MD
General Principles of Diagnosis of Skin Disorders 411 Disorders of the Skin in Newborns 413
General Principles of Treatment of Skin Disorders 411 Common Skin Diseases in Infants, Children, & Adolescents 417

15. Eye . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 432

Rebecca Sands, MD, Arlene Drack, MD, & Allan M. Eisenbaum, MD
Common Nonspecific Signs & Symptoms 432 Disorders of the Cornea 450
Refractive Errors 433 Disorders of the Lens 451
Examination 434 Disorders of the Retina 452
Ocular Trauma 438 Diseases of the Optic Nerve 454
Injuries to the Eyelids 439 Diseases of the Orbit 456
Disorders of the Ocular Structures 441 Nystagmus 457
Disorders of the Nasolacrimal System 443 Amblyopia & Strabismus 457
Diseases of the Conjunctiva 444 Unexplained Decreased Vision in Infants & Children 460
Disorders of the Iris 447 The Blind Child 460
Glaucoma 448 Learning Disabilities & Dyslexia 460
Uveitis 448 Vision Screening 460
Acquired Immunodeficiency Syndrome & the Eye 450

16. Oral Medicine & Dentistry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 462

William A. Mueller, DMD
Oral Examination of the Newborn & Infant 462 Antibiotics in Pediatric Dentistry 469
Eruption of the Teeth 464 Special Patient Populations 469
Dental Caries & Periodontal Disease 466 Maternal-Fetal Relationship 470
Orofacial Trauma 468 Dental Referral 471
Dental Emergencies 469

17. Ear, Nose, & Throat . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 472

Candice E. Johnson, MD, PhD, Peggy Kelley, MD, & Norman R. Friedman, MD
I. The Ear . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 472
II. The Nose & Paranasal Sinuses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 488
III. The Throat & Oral Cavity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 494

18. Respiratory Tract & Mediastinum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 506

Gwendolyn S. Kerby, MD, Gary L. Larsen, MD, Frank J. Accurso, MD, Robin R. Deterding, MD,
Vivek Balasubramaniam, MD, & Scott D. Sagel, MD
Respiratory Tract 506 Acquired Disorders of the Intrathoracic Airways 518
Growth & Development 506 Congenital Malformations of the Lung 528
Diagnostic Aids 507 Acquired Disorders Involving Alveoli 531
General Therapy of Pediatric Lung Diseases 510 Diseases of the Pulmonary Circulation 544
Disorders of the Conducting Airways 511 Disorders of the Chest Wall 548
Congenital Disorders of the Extrathoracic Airway 512 Disorders of the Pleura & Pleural Cavity 549
Acquired Disorders of the Extrathoracic Airway 513 Disorders of the Control of Breathing 551
Congenital Disorders of the Intrathoracic Airways 517 Mediastinum 555

19. Cardiovascular Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 558

Anji T. Yetman, MD, Shelley D. Miyamoto, MD, & Henry M. Sondheimer, MD
Diagnostic Evaluation 558 Cardiac Transplantation 613
Congenital Heart Disease 571 Disorders of Rate & Rhythm 615
Acquired Heart Disease 599
vi / CONTENTS

20. Gastrointestinal Tract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 625

Judith M. Sondheimer, MD
Evaluation of the Child with Vomiting 625 Acute Abdomen 635
Gastroesophageal Reflux 625 Peritonitis 635
Achalasia of the Esophagus 626 Acute Appendicitis 636
Caustic Burns of the Esophagus 627 Intussusception 637
Hiatal Hernia 627 Foreign Bodies in the Alimentary Tract 638
Pyloric Stenosis 628 Anal Fissure 638
Peptic Disease 628 Inguinal Hernia 638
Congenital Diaphragmatic Hernia 629 Umbilical Hernia 639
Congenital Duodenal Obstruction 630 Tumors of the Gastrointestinal Tract 639
Congenital Intestinal Atresias & Stenoses 630 Acute Infectious Diarrhea (Gastroenteritis) 641
Annular Pancreas 631 Chronic Diarrhea 642
Intestinal Malrotation With or Without Volvulus 631 The Malabsorption Syndromes 643
Meckel Diverticulum & Omphalomesenteric Duct Remnants 632 Constipation 650
Duplications of the Gastrointestinal Tract 632 Gastrointestinal Bleeding 651
Congenital Aganglionic Megacolon (Hirschsprung Disease) 633 Recurrent Abdominal Pain 654
Chylous Ascites 634 Inflammatory Bowel Disease 654
Congenital Anorectal Anomalies 634

21. Liver & Pancreas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 660

Ronald J. Sokol, MD, & Michael R. Narkewicz, MD
Liver 660 Wilson Disease (Hepatolenticular Degeneration) 683
Prolonged Neonatal Cholestatic Jaundice 660 Reye Syndrome (Encephalopathy with Fatty Degeneration
Intrahepatic Cholestasis 660 of the Viscera) 685
Progressive Familial Intrahepatic Cholestasis (Byler Disease) 668 Cirrhosis 686
Extrahepatic Neonatal Cholestasis 668 Portal Hypertension 688
Other Neonatal Hyperbilirubinemic Conditions (Noncholestatic Biliary Tract Disease 693
Nonhemolytic) 670 Pyogenic & Amebic Liver Abscess 695
Hepatitis A 673 Hepatoma 697
Hepatitis B 675 Liver Transplantation 698
Hepatitis C 677 Pancreas 699
Hepatitis D (Delta Agent) 678 Acute Pancreatitis 699
Hepatitis E 678 Chronic Pancreatitis 700
Other Hepatitis Viruses 678 Gastrointestinal & Hepatobiliary Manifestations of Cystic
Fulminant Hepatic Failure (Acute Massive Hepatic Necrosis, Fibrosis 701
Acute Liver Failure) 679 Syndromes with Pancreatic Exocrine Insufficiency 701
Autoimmune Hepatitis (Lupoid Hepatitis) 680 Isolated Exocrine Pancreatic Enzyme Defect 705
Steatohepatitis 682 Pancreatic Tumors 706

1-Antitrypsin Deficiency Liver Disease 682

22. Kidney & Urinary Tract. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 707

Gary M. Lum, MD
Evaluation of the Kidney & Urinary Tract 707 Renal Failure 718
Congenital Anomalies of the Urinary Tract 711 Inherited or Developmental Defects of the Urinary Tract 725
Hematuria & Glomerular Disease 712 Urinary Tract Infections 729
Diseases of the Renal Vessels 716

23. Neurologic & Muscular Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 732

Paul G. Moe, MD, & Tim A. Benke, MD, PhD
Neurologic Assessment & Neurodiagnostic Procedures 732 Disorders of Childhood Affecting Muscles 794
Disorders Affecting the Nervous System in Infants & Children 739 Miscellaneous Neuromuscular Disorders 805
Infections & Inflammatory Disorders of the Central Nervous
System 786
 CONTENTS / vii

24. Orthopedics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 810

Robert E. Eilert, MD
Disturbances of Prenatal Origin 810 Trauma 818
Growth Disturbances of the Musculoskeletal System 814 Infections of the Bones & Joints 821
Degenerative Problems (Arthritis, Bursitis, & Tenosynovitis) 817 Miscellaneous Diseases of Bone 827

25. Rehabilitation & Sports Medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 829

Pamela E. Wilson, MD, & Dennis J. Matthews, MD,
Basic Principles 829
Common Sports Medicine Issues and Injuries 834

26. Rheumatic Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 846

J. Roger Hollister, MD
Juvenile Rheumatoid Arthritis (Juvenile Chronic Arthritis) 846 Polyarteritis Nodosa 852
Spondyloarthropathy 848 Scleroderma 852
Enteropathic Arthritis 849 Raynaud Phenomenon 852
Systemic Lupus Erythematosus 849 Hypermobility Syndrome 853
Dermatomyositis (Polymyositis) 851

27. Hematologic Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 855

Daniel R. Ambruso, MD, Taru Hays, MD, Peter A. Lane, MD, & Rachelle Nuss, MD
Bone Marrow Failure 855 Bleeding Disorders 885
Anemias 858 Thrombotic Disorders 898
Polycythemia & Methemoglobinemia 879 Splenic Abnormalities 900
Disorders of Leukocytes 880 Transfusion Medicine 900

28. Neoplastic Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 911

Edythe A. Albano, MD, Mylène Bassal, MDCM, Christopher C. Porter, MD, Brian S. Greffe, MD,
Nicholas K. Foreman, MD, & Linda C. Stork, MD
Major Pediatric Neoplastic Diseases 911

Douglas K. Graham, MD, PhD, Roger H. Giller, MD, & Ralph R. Quinones, MD
Hematopoietic Stem Cell Transplantation 939 Late Effects of Pediatric Cancer Therapy 941

29. Immunodeficiency . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 944

Anthony R. Hayward, MD, PhD
Nonspecific Factors in Resistance to Infection 944 Other Disorders Associated with Immunodeficiency 954
Deficiencies of Specific Immunity 946 Secondary Immunodeficiency 956
Combined Immunodeficiency Disorders 952 Investigation of Immunodeficiency 958

30. Endocrine Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 961

Philip S. Zeitler, MD, PhD, Sharon H. Travers, MD, Jennifer Barker, MD, Kristen Nadeau, MD,
& Michael S. Kappy, MD, PhD
General Concepts 961 Disorders of Calcium Homeostasis 979
Disturbances of Growth 963 The Gonads (Ovaries & Testes) 987
The Posterior Pituitary Gland 971 Adrenal Cortex 995
The Thyroid Gland 973
viii / CONTENTS

31. Diabetes Mellitus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1006

H. Peter Chase, MD, & George S. Eisenbarth, MD, PhD
General Considerations 1006 Treatment 1007
Etiology 1006 Laboratory Evaluations 1010
Prevention 1007 Acute Complications 1011
Diagnosis 1007 Chronic Complications 1013

32. Inborn Errors of Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1014

Carol L. Greene, MD, Janet A. Thomas, MD, & Stephen I. Goodman, MD
Diagnosis 1014 Disorders of Fatty Acid Oxidation & Carnitine 1030
Management of Metabolic Emergencies 1018 Lysosomal Diseases 1033
Newborn Screening 1018 Peroxisomal Diseases 1033
Disorders of Carbohydrate Metabolism 1019 Carbohydrate-Deficient Glycoprotein Syndromes 1036
Primary Lactic Acidemias & Other Disorders of Energy Smith—Lemli—Opitz Syndrome and Disorders of Cholesterol
Metabolism 1021 Synthesis 1036
Disorders of Amino Acid Metabolism 1022 Disorders of Neurotransmitter Metabolism 1037
Organic Acidemias 1027

33. Genetics & Dysmorphology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1039

Ellen Roy Elias, MD, Anne Chun-Hui Tsai, MD, MSc, & David K. Manchester, MD
Principles of Genetics 1039 Mendelian Disorders 1064
Foundations of Genetic Diagnosis 1039 Nonmendelian Inheritance 1069
Principles of Inherited Human Disorders 1048 Multifactorial Inheritance 1071
Dysmorphology and Human Embryology 1056 Common Recognizable Disorders with Variable or Unknown
Clinical Features of Common Genetic Disorders 1061 Cause 1074
Chromosomal Disorders: Abnormal Number 1061 Perinatal Genetics 1076
Sex Chromosomes 1062 Evaluation of the Developmentally Delayed Child 1078
Chromosomal Abnormalities: Structural 1063

34. Allergic Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1080

Mark Boguniewicz, MD
The Allergic Cascade 1080 Urticaria & Angioedema 1098
Major Allergic Disorders Seen in Pediatric Practice 1080 Anaphylaxis 1100
Asthma 1080 Adverse Reactions to Drugs & Biologicals 1102
Allergic Rhinoconjunctivitis 1091 Food Allergy 1107
Atopic Dermatitis 1094 Insect Allergy 1108

35. Antimicrobial Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1110

John W. Ogle, MD
Principles of Antimicrobial Therapy 1110 Prophylactic Antimicrobial Agents 1119
Antimicrobial Susceptibility Testing 1111 Initial Empiric Antimicrobial Choices for Selected
Alteration of Dose & Measurement of Blood Levels 1113 Conditions 1121
The Use of New Antimicrobial Agents 1119 Specific Antimicrobial Agents 1122

36. Infections: Viral & Rickettsial . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1130

Myron J. Levin, MD, & Adriana Weinberg, MD
I. Viral Infections. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1130
Respiratory Infections 1130 Viral Infections Spread by Insect Vectors 1157
Infections Due to Enteroviruses 1142 Other Major Viral Childhood Exanthems 1162
Infections Due to Herpesviruses 1146 Infections Due to Other Viruses 1166

II. Rickettsial Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1170

 CONTENTS / ix

37. Human Immunodeficiency Virus Infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1174

Elizabeth J. McFarland, MD
General Considerations 1174 Prevention 1179
Mode of Transmission 1174 Treatment 1179
Pathogenesis 1175 Prognosis 1184
Clinical Findings 1176 Public Health Issues 1184
Differential Diagnosis 1178 Conclusion 1185

38. Infections: Bacterial & Spirochetal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1186

John W. Ogle, MD, & Marsha S. Anderson, MD
I. Bacterial Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1186
II. Spirochetal Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1241

39. Infections: Parasitic & Mycotic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1250

Adriana Weinberg, MD, & Myron J. Levin, MD
I. Infections: Parasitic. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1250
Protozoal Infections 1253 Metazoal Infections 1267

II. Infections: Mycotic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1275

40. Sexually Transmitted Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1290

Ann-Christine Nyquist, MD, MSPH, Myron J. Levin, MD, & Eric J. Sigel, MD
The Most Common Antibiotic-Responsive Sexually Transmitted Evaluation of Sexually Transmitted Infections in Sexual Abuse and
Infections 1292 Assault 1309
The Spectrum of Sexually Transmitted Infections 1299

41. Drug Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1311

Patricia Orma, PharmD, Jerrod Milton, RPh, BSc, & Douglas N. Fish, PharmD
Developing a Pediatric Drug Regimen 1311 Preventing Medication Errors 1317
Drug Interactions 1317 Sources of Pediatric Drug Information 1319

42. Fluid, Electrolyte, & Acid-Base Disorders & Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1320

Douglas M. Ford, MD
Regulation of Body Fluids, Electrolytes, & Tonicity 1320 Potassium Disorders 1326
Fluid & Electrolyte Management 1322 Acid-Base Disturbances 1327
Acid—Base Balance 1322 Metabolic Acidosis 1327
Dehydration 1323 Metabolic Alkalosis 1328
Hyponatremia 1325 Respiratory Acidosis 1328
Hypernatremia 1326 Respiratory Alkalosis 1328

43. Information Technology in Pediatrics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1330

Carol S. Kamin, MS, EdD, & David W. Kaplan, MD, MPH
Continuing Medical Education 1330 Patient Education 1337
Clinical Support 1333

44. Chemistry & Hematology Reference Ranges . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1339

Iris M. Osberg, MT
Interpretation of Laboratory Values 1339 Laboratory Values 1340

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1353
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 Authors

Frank J. Accurso, MD Jennifer Barker, MD

Professor, Department of Pediatrics, and Head, Section Fellow in Pediatric Endocrinology, Department of
of Pediatric Pulmonary Medicine, University of Pediatrics, Section of Pediatric Endocrinology,
Colorado School of Medicine; The Mike McMorris Barbara Davis Center for Childhood Diabetes,
Cystic Fibrosis Center and The Children’s Hospital, University of Colorado Health Sciences Center,
Denver Denver
[email protected] [email protected]
Respiratory Tract & Mediastinum Endocrine Disorders
Edythe A. Albano, MD Mylène Bassal, MDCM
Associate Professor, Department of Pediatrics, Section Fellow in Pediatric Hematology, Oncology and Bone
of Pediatric Hematology, Oncology and Bone Marrow Transplantation, Department of Pediatrics,
Marrow Transplantation, University of Colorado Section of Pediatric Hematology, Oncology and
School of Medicine and The Children’s Hospital, Bone Marrow Transplantation, University of Col-
Denver orado School of Medicine and The Children’s
[email protected] Hospital, Denver
Neoplastic Disease [email protected]
Daniel R. Ambruso, MD Neoplastic Disease
Professor, Department of Pediatrics, Section of F. Keith Battan, MD
Pediatric Hematology, Oncology and Bone Marrow
Associate Professor, Department of Pediatrics, Section
Transplantation, University of Colorado School of
of Emergency Medicine, University of Colorado
Medicine and The Children’s Hospital; Associate
School of Medicine; Associate Director, Emergency
Medical Director, Bonfils Blood Center, Denver
and Trauma Services, The Children’s Hospital,
[email protected]
Denver
Hematologic Disorders
Emergencies & Injuries
Marsha S. Anderson, MD
Assistant Professor, Department of Pediatrics, Section Donald W. Bechtold, MD
of Pediatric Infectious Diseases, University of Medical Director, Jefferson Center for Mental Health,
Colorado School of Medicine and The Children’s Arvada, Colorado; Associate Clinical Professor, Uni-
Hospital, Denver versity of Colorado School of Medicine, Denver
[email protected] [email protected]
Emergencies & Injuries: Bioterrorism Section; Infections: Child & Adolescent Psychiatric Disorders & Psychosocial
Bacterial & Spirochetal Aspects of Pediatrics

Vivek Balasubramaniam, MD Tim A. Benke, MD, PhD

Assistant Professor, Department of Pediatrics, Section Assistant Professor, Departments of Pediatrics,
of Pediatric Pulmonary Medicine, Pediatric Heart Neurology & Pharmacology, University of Colorado
Lung Center, University of Colorado School of School of Medicine and The Children’s Hospital,
Medicine and The Children’s Hospital, Denver Denver
[email protected] [email protected]
Respiratory Tract & Mediastinum Neurologic & Muscular Disorders

xi
Copyright © 2005, 2001, by The McGraw-Hill Companies, Inc. Click here for terms of use.
xii / AUTHORS

Mark Boguniewicz, MD Robin R. Deterding, MD

Professor, Department of Pediatrics, University of Associate Professor, Department of Pediatrics, Section
Colorado School of Medicine and National Jewish of Pediatric Pulmonary Medicine, University of Col-
Medical and Research Center, and The Children’s orado School of Medicine and The Children’s Hos-
Hospital, Denver pital, Denver
[email protected] [email protected]
Allergic Disorders Respiratory Tract & Mediastinum
Emily L. Dobyns, MD
Robert M. Brayden, MD
Associate Professor, Department of Pediatrics, Section
Associate Professor, Department of Pediatrics, Section of Pediatric Critical Care Medicine, University of
of General Academic Pediatrics, University of Colorado School of Medicine and The Children’s
Colorado School of Medicine and The Children’s Hospital, Denver
Hospital, Denver [email protected]
[email protected] Critical Care
Ambulatory & Community Pediatrics
Arlene Drack, MD
Jeffrey M. Brown, MD, MPH Associate Professor, Department of Ophthalmology;
Professor, Department of Pediatrics, University of Chief, Section of Pediatric Ophthalmology, Univer-
Colorado School of Medicine; Director, General sity of Colorado School of Medicine and The
Pediatrics Division, Denver Health Medical Center, Children’s Hospital, Denver
Denver Eye
[email protected]
Ambulatory & Community Pediatrics Robert E. Eilert, MD
Professor, Department of Pediatrics, University of
Colorado Health Sciences Center; Rose Brown
Todd C. Carpenter, MD Professor, Department of Orthopedic Surgery, Uni-
Assistant Professor, Department of Pediatrics, versity of Colorado School of Medicine; Chairman,
Section of Pediatric Critical Care Medicine, Department of Orthopedic Surgery, The Children’s
University of Colorado School of Medicine Hospital, Denver
and The Children’s Hospital, Denver [email protected]
[email protected] Orthopedics
Critical Care
George S. Eisenbarth, MD, PhD
H. Peter Chase, MD Professor, Departments of Pediatrics, Medicine, and
Professor of Pediatrics, University of Colorado Health Immunology, University of Colorado School of
Sciences Center, Barbara Davis Center for Child- Medicine; Executive Director, Barbara Davis Center
hood Diabetes, Denver for Childhood Diabetes, Denver
[email protected] [email protected]
Diabetes Mellitus Diabetes Mellitus

Matthew F. Daley, MD Allan M. Eisenbaum, MD

Pediatric Ophthalmologist, Wichita Clinic, Wichita,
Assistant Professor, Department of Pediatrics, Section
Kansas; Clinical Assistant Professor, Departments of
of General Academic Pediatrics, University of Col-
Internal Medicine and Pediatrics, University of
orado School of Medicine and The Children’s Hos-
Kansas School of Medicine, Wichita
pital, Denver
[email protected]
[email protected] Eye
Ambulatory & Community Pediatrics; Immunization
Ellen Roy Elias, MD
Richard C. Dart, MD, PhD Associate Professor, Departments of Pediatrics and
Professor of Surgery, Medicine, and Pharmacy, Genetics, Section of Clinical Genetics and Metabo-
University of Colorado School of Medicine; Director, lism, University of Colorado School of Medicine;
Rocky Mountain Poison and Drug Center, Denver Director, Special Care Clinic, The Children’s Hos-
Health Authority, Denver pital, Denver
[email protected] [email protected]
Poisoning Genetics & Dysmorphology
 AUTHORS / xiii

Margaret A. Ferguson, MD Edward Goldson, MD

Assistant Professor, Department of Pediatrics, Professor, Department of Pediatrics, Section of
Section of Pediatric Critical Care Medicine, University Developmental and Behavioral Pediatrics, University
of Colorado School of Medicine and The Children’s of Colorado School of Medicine and The Children’s
Hospital, Denver Hospital, Denver
[email protected] [email protected]
Critical Care Child Development & Behavior

Douglas N. Fish, PharmD Stephen I. Goodman, MD

Professor, Department of Pediatrics, Head, Section of
Associate Professor, Department of Pharmacy Practice Clinical Genetics and Metabolism, University of
and Division of Pulmonary Sciences & Critical Care Colorado School of Medicine and The Children’s
Medicine, University of Colorado Schools of Hospital, Denver
Pharmacy and Medicine; Clinical Pharmacy [email protected]
Specialist in Critical Care/Infectious Diseases, Inborn Errors of Metabolism
University of Colorado Hospital, Denver
[email protected] Douglas K. Graham, MD, PhD
Drug Therapy Assistant Professor, Department of Pediatrics, Section
of Hematology, Oncology and Bone Marrow Trans-
Douglas M. Ford, MD plant, University of Colorado Health Sciences Cen-
Professor, Department of Pediatrics, Section of Pedi- ter and The Children’s Hospital, Denver
atric Nephrology, University of Colorado School of [email protected]
Medicine and The Children’s Hospital, Denver Neoplastic Disease: Hematopoietic Stem Cell Transplan-
[email protected] tation
Fluid, Electrolyte, & Acid-Base Disorders & Therapy
Carol L. Greene, MD
Clinical Professor, Department of Pediatrics, George
Nicholas K. Foreman, MD Washington University School of Medicine, Wash-
Associate Professor, Department of Pediatrics, ington, D.C.
Section of Pediatric Hematology, Oncology and [email protected]
Bone Marrow Transplantation, University of Inborn Errors of Metabolism
Colorado School of Medicine; Seebaum-Tschetter
Chair of Pediatric Neuro-Oncology and Director Brian S. Greffe, MD
of Neuro-Oncology, The Children’s Hospital, Associate Professor, Department of Pediatrics, Section
Denver, Colorado of Pediatric Hematology, Oncology and Bone Mar-
[email protected] row Transplantation, University of Colorado School
Neoplastic Disease of Medicine and The Children’s Hospital, Denver
[email protected]
Norman R. Friedman, MD Neoplastic Disease
Assistant Professor, Departments of Otolaryngology
and Pediatrics, University of Colorado School Jennifer Hagman, MD
of Medicine and The Children’s Hospital, Associate Professor, Department of Psychiatry,
Denver University Of Colorado School of Medicine;
[email protected] Co-Director, Eating Disorders Treatment Program;
Ear, Nose, & Throat Medical Director, Clinical Services, Department of
Psychiatry and Behavioral Sciences, The Children’s
Hospital, Denver
Roger H. Giller, MD [email protected]
Professor, Department of Pediatrics, Section of Child & Adolescent Psychiatric Disorders & Psychosocial
Pediatric Hematology, Oncology and Bone Aspects of Pediatrics
Marrow Transplantation, University of Colorado
School of Medicine; Director, Pediatric Bone Mar- K. Michael Hambidge, MD, BChir, ScD
row Transplant Program, The Children’s Hospital, Professor Emeritus, Department of Pediatrics, Section
Denver of Nutrition, University of Colorado Health
[email protected] Sciences Center, Denver
Neoplastic Disease: Hematopoietic Stem Cell Transplan- [email protected]
tation Normal Childhood Nutrition & Its Disorders
xiv / AUTHORS

Taru Hays, MD Peggy Kelley, MD

Professor of Pediatrics, Department of Pediatrics, Assistant Professor, Department of Otolaryngology,
Section of Hematology, Oncology and Bone Marrow University of Colorado School of Medicine and The
Transplant, University of Colorado Health Sciences Children’s Hospital, Denver
Center and The Children’s Hospital, Denver [email protected]
[email protected] Ear, Nose, & Throat
Hematologic Disorders
Anthony R. Hayward, MD, PhD Gwendolyn S. Kerby, MD
Previously Professor of Pediatrics, University of Assistant Professor, Department of Pediatrics, Section
Colorado Health Sciences Center, Denver of Pediatric Pulmonary Medicine, University of
[email protected] Colorado School of Medicine and The Children’s
Immunodeficiency Hospital, Denver
[email protected]
J. Roger Hollister, MD Respiratory Tract & Mediastinum
Professor, Department of Pediatrics, University of
Colorado School of Medicine; Head, Section of Nancy F. Krebs, MD, MS
Pediatric Rheumatology, University of Colorado Professor, Department of Pediatrics, and Head, Section
School of Medicine and The Children’s Hospital, of Nutrition, University of Colorado School of
Denver Medicine and The Children’s Hospital, Denver
Rheumatic Diseases [email protected]
Candice E. Johnson, MD, PhD Normal Childhood Nutrition & Its Disorders
Professor, Department of Pediatrics, Division of
General Academic Pediatrics, University of Colorado Richard D. Krugman, MD
School of Medicine and The Children’s Hospital, Professor, Department of Pediatrics, and Dean,
Denver University of Colorado School of Medicine,
Ear, Nose, & Throat Denver
[email protected]
Carol S. Kamin, MS, EdD Child Abuse & Neglect
Associate Professor, Department of Pediatrics, Section
of Medical Education and Director, Project L.I.V.E., Peter A. Lane, MD
University of Colorado School of Medicine, Denver Professor, Department of Pediatrics, Emory University
[email protected] School of Medicine; Director of Hematology,
Information Technology in Pediatrics AFLAC Cancer Center and Blood Disorders
David W. Kaplan, MD, MPH Service, Children’s Healthcare of Atlanta, Atlanta,
Professor, Department of Pediatrics, and Head, Section Georgia
of Adolescent Medicine, University of Colorado [email protected]
School of Medicine and The Children’s Hospital, Hematologic Disorders
Denver
[email protected] Gary L. Larsen, MD
Adolescence; Information Technology in Pediatrics Professor, Department of Pediatrics, Section of
Pediatric Pulmonary Medicine, University of
Michael S. Kappy, MD, PhD Colorado School of Medicine; Senior Faculty
Professor, Department of Pediatrics, and Head, Section Member and Head, Division of Pediatric Pulmonary
of Pediatric Endocrinology, University of Colorado Medicine, National Jewish Medical and Research
Health Sciences Center and The Children’s Hospi- Center, Denver
tal, Denver Respiratory Tract & Mediastinum
Endocrine Disorders
Paritosh Kaul, MD Myron J. Levin, MD
Assistant Professor, Department of Pediatrics, Professor, Departments of Pediatrics and Medicine,
Section of Adolescent Medicine, University of University of Colorado School of Medicine and The
Colorado Health Sciences Center; Westside Teen Children’s Hospital, Denver
Clinic, Denver Health and Hospitals [email protected]
[email protected] Infections: Viral & Rickettsial; Infections: Parasitic &
Substance Abuse Mycotic; Sexually Transmitted Infections
 AUTHORS / xv

Kathryn Love-Osborne, MD Shelley D. Miyamoto, MD

Assistant Professor, Department of Pediatrics, Section Fellow in Pediatric Cardiology, Department of
of Adolescent Medicine, University of Colorado Pediatrics, Section of Pediatric Cardiology,
Health Sciences Center; Medical Director, Eastside University of Colorado School of Medicine and
Teen Clinic, Denver Health and Hospitals, Denver The Children’s Hospital, Denver
[email protected] [email protected]
Adolescence Cardiovascular Diseases
Gary M. Lum, MD Paul G. Moe, MD
Professor, Departments of Pediatrics and Medicine, Professor, Departments of Pediatrics and Neurology,
and Head, Section of Pediatric Nephrology, University of Colorado School of Medicine and
University of Colorado School of Medicine and The The Children’s Hospital, Denver
Children’s Hospital, Denver [email protected]
[email protected] Neurologic & Muscular Disorders
Kidney & Urinary Tract
David K. Manchester, MD Joseph G. Morelli, MD
Professor, Department of Pediatrics and Director, Professor, Departments of Dermatology and Pediatrics,
Clinical Services, Section of Clinical Genetics and University of Colorado School of Medicine,
Metabolism, The Children’s Hospital, Denver, Denver
Colorado [email protected]
[email protected] Skin
Genetics & Dysmorphology
Peter M. Mourani, MD
Stephanie N. Mateev, MD Instructor, Department of Pediatrics, Section of
Instructor, Department of Pediatrics, Section of Pediatric Critical Care Medicine, University of
Pediatric Critical Care Medicine, University of Colorado School of Medicine and The Children’s
Colorado School of Medicine and The Children’s Hospital, Denver
Hospital, Denver [email protected]
[email protected] Critical Care
Critical Care
William A. Mueller, DMD
Dennis J. Matthews, MD Clinical Associate Professor of Applied Dentistry,
Associate Professor and Chairman, Department of University of Colorado School of Dentistry,
Rehabilitation Medicine, University of Colorado Denver
School of Medicine; Chairman and Medical [email protected]
Director, The Children’s Hospital Rehabilitation Oral Medicine & Dentistry
Center, Denver
[email protected] Kristen Nadeau, MD
Rehabilitation & Sports Medicine
Fellow in Pediatric Endocrinology, Department of
Elizabeth J. McFarland, MD Pediatrics, Section of Pediatric Endocrinology,
Associate Professor, Department of Pediatrics, Section University of Colorado School of Medicine and The
of Pediatric Infectious Diseases, University of Children’s Hospital, Denver
Colorado School of Medicine; Director, Children’s [email protected]
Hospital HIV Program, The Children’s Hospital, Endocrine Disorders
Denver
[email protected] Michael R. Narkewicz, MD
Human Immunodeficiency Virus Infection Professor of Pediatrics, Section of Pediatric
Gastroenterology, Hepatology and Nutrition,
Jerrod Milton, RPh, BSc University of Colorado School of Medicine;
Adjunct Assistant Clinical Professor, Department of Hewit-Andrews Chair in Pediatric Liver Disease;
Pharmacy Services, The Children’s Hospital, Medical Director, The Pediatric Liver Center,
Denver, Colorado The Children’s Hospital, Denver
[email protected] [email protected]
Drug Therapy Liver & Pancreas
xvi / AUTHORS

Rachelle Nuss, MD Laura E. Primak, RD, CNSD, CSP

Professor, Department of Pediatrics, Section of Professional Research Assistant, Department of
Pediatric Hematology, Oncology and Bone Marrow Pediatrics; University of Colorado School of
Transplantation, University of Colorado School of Medicine and The Children’s Hospital, Denver
Medicine and The Children’s Hospital, Denver Nutritionist, Nutrition Academic Award Program,
[email protected] University of Colorado Health Sciences Center,
Hematologic Disorders Denver
[email protected]
Ann-Christine Nyquist, MD, MSPH Normal Childhood Nutrition & Its Disorders
Assistant Professor, Departments of Pediatrics and
Preventive Medicine/Biometrics, Section of Ralph R. Quinones, MD
Pediatric Infectious Diseases, University of Colorado Associate Professor, Department of Pediatrics;
School of Medicine; Medical Director, Infection Director, Scientific Development, Blood and
Control and Epidemiology, The Children’s Marrow Processing Laboratory, Bone Marrow
Hospital, Denver Transplant Program, Section of Pediatric Hematol-
[email protected] ogy, Oncology and Bone Marrow Transplantation,
Immunization; Sexually Transmitted Infections University of Colorado School of Medicine and The
Children’s Hospital, Denver
John W. Ogle, MD [email protected]
Professor and Vice Chairman, Department of Neoplastic Disease: Hematopoietic Stem Cell Transplan-
Pediatrics, University of Colorado School of tation
Medicine; Director, Department of Pediatrics,
Denver Health Medical Center, Denver Ann Reynolds, MD
[email protected] Assistant Professor, Department of Pediatrics, Child
Antimicrobial Therapy; Infections: Bacterial Development Unit, University of Colorado School
& Spirochetal of Medicine and The Children’s Hospital, Denver
Patricia Orma, PharmD [email protected]
Adjoint Professor, School of Pharmacy, University Child Development & Behavior
of Colorado Health Sciences Center, Denver;
Pediatric Clinical Pharmacist, The Children’s Adam A. Rosenberg, MD
Hospital, University of California Davis Medical Professor, Department of Pediatrics, Section of
Center, Sacramento Neonatology; Medical Director, Newborn Service,
[email protected] University of Colorado Hospital; Director,
Drug Therapy Training Program in Pediatrics; University of
Colorado School of Medicine and The Children’s
Iris M. Osberg, MT Hospital, Denver
Technical Director, Pediatrics General Clinical [email protected]
Research Center Core Laboratory, and Director, The Newborn Infant
Cystic Fibrosis Foundation/Therapeutics
Development Network Labs, University of Barry H. Rumack, MD
Colorado School of Medicine and The Children’s Clinical Professor of Pediatrics, University of Colorado
Hospital, Denver School of Medicine, Denver; Director Emeritus,
[email protected] Rocky Mountain Poison and Drug Center, Denver
Chemistry & Hematology Reference Ranges [email protected]
Poisoning
Christopher C. Porter, MD
Fellow in Pediatric Hematology, Oncology and Bone Scott D. Sagel, MD
Marrow Transplantation, Department of Pediatrics, Assistant Professor, Department of Pediatrics, Section
Section of Pediatric Hematology, Oncology and of Pediatric Pulmonary Medicine, University of
Bone Marrow Transplantation, University of Colorado School of Medicine and The Children’s
Colorado School of Medicine and The Children’s Hospital, Denver
Hospital, Denver [email protected]
Neoplastic Disease Respiratory Tract & Mediastinum
 AUTHORS / xvii

Rebecca Sands, MD Judith M. Sondheimer, MD

Assistant Professor, Department of Ophthalmology, Professor, Department of Pediatrics, and Head, Section
University of Colorado Health Sciences Center, of Pediatric Gastroenterology, Hepatology, and
Denver; Pediatric Ophthalmologist, Rocky Nutrition, University of Colorado School of
Mountain Lions Eye Institute and The Children’s Medicine and The Children’s Hospital, Denver
Hospital, Aurora, Colorado [email protected]
[email protected] Gastrointestinal Tract
Eye
Eric J. Sigel, MD Kurt R. Stenmark, MD
Associate Professor, Department of Pediatrics, Section Professor, Department of Pediatrics, and Head, Section
of Adolescent Medicine; Co-Director, Eating of Pediatric Critical Care Medicine, University of
Disorders Program at The Children’s Hospital, Colorado School of Medicine and The Children’s
Denver, and Clinical Director, Adolescent Clinic, Hospital, Denver
University of Colorado School of Medicine and The [email protected]
Children’s Hospital, Denver Critical Care
[email protected]
Eating Disorders; Sexually Transmitted Infections Catherine Stevens-Simon, MD
Associate Professor, Department of Pediatrics, Section
Eric A. F. Simoes, MD, DCH
of Adolescent Medicine, University of Colorado
Professor, Department of Pediatrics, Section of
School of Medicine and The Children’s Hospital,
Pediatric Infectious Diseases, University of Colorado
Denver
School of Medicine and The Children’s Hospital,
Denver; Professor of Paediatric Infectious Diseases [email protected]
and Tropical Child Health, Departments of Substance Abuse
Paediatrics and Obstetrics and Gynaecology,
Imperial College, London, England Linda C. Stork, MD
[email protected] Associate Professor, Department of Pediatrics, Oregon
Immunization Health and Science University, Portland
[email protected]
Andrew P. Sirotnak, MD Neoplastic Disease
Associate Professor, Department of Pediatrics,
University of Colorado School of Medicine; Director, Elizabeth H. Thilo, MD
Kempe Child Protection Team, The Children’s
Associate Professor, Department of Pediatrics, Section
Hospital and Kempe Children’s Center, Denver
of Neonatology, University of Colorado School of
[email protected]
Medicine and The Children’s Hospital, Denver
Child Abuse & Neglect
[email protected]
Ronald J. Sokol, MD The Newborn Infant
Professor, Department of Pediatrics, Section of Pediatric
Gastroenterology, Hepatology, and Nutrition and the Janet A. Thomas, MD
Pediatric Liver Center and Liver Transplantation Assistant Professor, Department of Pediatrics, Section
Programs; Program Director, Pediatric General of Genetics and Metabolism, University of Colorado
Clinical Research Center, University of Colorado School of Medicine and The Children’s Hospital,
School of Medicine and The Children’s Hospital, Denver
Denver [email protected]
[email protected] Inborn Errors of Metabolism
Liver & Pancreas
Henry M. Sondheimer, MD Sharon H. Travers, MD
Professor, Department of Pediatrics, Section of Pedi- Associate Professor, Department of Pediatrics, Section
atric Cardiology, University of Colorado School of of Pediatric Endocrinology, University of Colorado
Medicine; Clinical Director, Pediatric Cardiology, School of Medicine and The Children’s Hospital,
The Children’s Hospital, Denver Denver
[email protected] [email protected]
Cardiovascular Diseases Endocrine Disorders
xviii / AUTHORS

Anne Chun-Hui Tsai, MD, MSc Pamela E. Wilson, MD

Assistant Professor, Department of Pediatrics, Section Assistant Professor, Department of Rehabilitation
of Clinical Genetics and Metabolism, University of Medicine, University of Colorado School of
Colorado School of Medicine and The Children’s Medicine and The Children’s Hospital, Denver
Hospital, Denver [email protected]
[email protected] Rehabilitation & Sports Medicine
Genetics & Dysmorphology
Anji T. Yetman, MD
Adriana Weinberg, MD Associate Professor, Department of Pediatrics, Section
Professor, Departments of Pediatrics and Medicine, of Pediatric Cardiology; Director, Adult Congenital
University of Colorado School of Medicine; Cardiac Program, University of Colorado School of
Director, Clinical Virology Laboratory, University Medicine and The Children’s Hospital, Denver
of Colorado Hospital, Denver [email protected]
[email protected] Cardiovascular Diseases
Infections: Viral & Rickettsial; Infections: Parasitic
& Mycotic Philip S. Zeitler, MD, PhD
Associate Professor, Department of Pediatrics, Section
William L. Weston, MD of Pediatric Endocrinology, University of Colorado
Professor, Departments of Dermatology and Pediatrics, School of Medicine and The Children’s Hospital,
University of Colorado School of Medicine, Denver Denver
[email protected] [email protected]
Skin Endocrine Disorders
 Preface

The seventeenth edition of Current Pediatric Diagnosis & Treatment features practical, up-to-date, well-referenced in-
formation on the care of children from birth through infancy and adolescence. CPDT emphasizes the clinical aspects
of pediatric care while also covering the important underlying principles. Its goal is to provide a guide to diagnosis,
understanding, and treatment of the medical problems of all pediatric patients in an easy-to-use and readable format.

INTENDED AUDIENCE
Like all Lange medical books, CPDT provides a concise yet comprehensive source of current information. Students
will find CPDT an authoritative introduction to pediatrics and an excellent source for reference and review. CPDT
provides excellent coverage of The Council on Medical Student Education in Pediatrics (COMSEP) Curriculum
used around the country in Pediatric clerkships. Residents in pediatrics (and other specialties) will appreciate the de-
tailed descriptions of diseases and diagnostic and therapeutic procedures. Pediatricians, family practitioners, nurses
and nurse practitioners, and other health-care providers who work with infants and children also will find CPDT a
useful reference on management aspects of pediatric medicine.

COVERAGE
Forty-four chapters cover a wide range of topics, including neonatal medicine, child development and behavior,
emergency and critical care medicine, and diagnosis and treatment of specific disorders according to major problems
and organ systems. A wealth of tables and figures summarizes important information, such as acute and critical care
procedures in the delivery room, the office, the emergency room, and the critical care unit; anti-infective agents;
drug dosages; immunization schedules; differential diagnosis; and developmental screening tests. The final chapter is
a handy guide to normal laboratory values.

NEW TO THIS EDITION

The seventeenth edition of CPDT has been revised comprehensively by the editors and contributing authors. New
references as well as up-to-date and useful Web sites have been added, permitting the reader to consult original ma-
terial and to go beyond the confines of the textbook. As editors and practicing pediatricians, we have tried to ensure
that each chapter reflects the needs and realities of day-to-day practice.

New Editor: We are delighted to welcome Dr. Robin Deterding as a CPDT Editor. Robin brings a wealth of experi-
ence in pediatric education methods and in-depth experience in pulmonary medicine and patient diagnosis and
management protocols.

Chapter Revisions: Eight chapters have been extensively revised, with new authors added in several cases, reflecting
substantial new information in each of their areas of pediatric medicine. Especially important is new material added
to the chapters on infectious diseases, including information on methicillin-resistant staphylococcus, SARS, human
metapneumovirus, and West Nile virus infections. Chapters with major revisions include:
15. Eye
28. Neoplastic Disease
35. Antimicrobial Therapy
36. Infections: Viral & Rickettsial
37. Human Immunodeficiency Virus (HIV) Infections
38. Infections: Bacterial & Spirochetal
39. Infections: Parasitic & Mycotic
40. Sexually Transmitted Infections
43. Information Technology in Pediatric Practice
xix
Copyright © 2005, 2001, by The McGraw-Hill Companies, Inc. Click here for terms of use.
xx / PREFACE

All other chapters are substantially revised and references have been updated. Seventeen new authors have con-
tributed to these revisions.

Acknowledgment: The Editors would like to thank Dr. Anthony Hayward—-who has assumed a position with the
General Clinical Research Centers program at the National Institutes of Health—-for his work as Editor of CPDT.
Anthony served CPDT with outstanding scholarship and editorship for five editions (twelfth-sixteenth). We miss his
attention to detail in the editorial work, but especially his friendship.

William W. Hay, Jr., MD

Myron J. Levin, MD
Judith M. Sondheimer, MD
Robin R. Deterding, MD

Denver, Colorado
October, 2004
 The Newborn Infant 1
Elizabeth H. Thilo, MD, & Adam A. Rosenberg, MD

The first 28 days of life are usually considered the new- analgesia used, reason for operative or forceps delivery,
born period. In practice, however, neonatal care may and condition of the infant at birth, including any re-
extend to many months for sick or very immature in- suscitation needed and Apgar scores.
fants. Levels of newborn care are classified from level
1 (well newborns) to level 3 (critically ill newborns).
Level 3 nurseries are often part of a perinatal center of- ASSESSMENT OF GROWTH
fering critical care to the mother and fetus as well as the & GESTATIONAL AGE
newborn infant.
It is important to know an infant’s gestational age be-
cause its behavior and anticipated problems can be pre-
dicted on this basis. Accurate recall of the date of the
last menstrual period is the best indicator of gestational
EVALUATION OF THE age. Other obstetric observations, such as fundal height
NEWBORN INFANT HISTORY and early ultrasound examination, provide supporting
information. A postnatal examination can also be used
because fetal physical characteristics and neurologic de-
Taking the history in newborn medicine involves three velopment progress in predictable fashion. Table
key areas: (1) the medical history of the mother and fa- 1–1 lists the physical and neurologic criteria to be ex-
ther, including a relevant genetic history; (2) the history amined. The upper panel is the neuromuscular exami-
of the mother’s previous pregnancies; and (3) the his- nation, assessing primarily muscle tone and strength.
tory of the current pregnancy, including antepartum The lower panel catalogs a variety of physical character-
and intrapartum events. istics. Adding the scores assigned to each characteristic
The mother’s medical history should include any yields a total score that corresponds to the gestational
chronic medical conditions, medications taken during age.
pregnancy, unusual dietary habits, smoking history, oc- Disappearance of the anterior vascular capsule of the
cupational exposures to chemicals or infections of po- lens is also helpful in determining gestational age. Until
tential risk to the fetus, and pertinent aspects of the so- 27–28 weeks’ gestation, the lens capsule is covered by
cial history that may suggest increased risks for vessels; by 34 weeks, this vascular plexus is completely
parenting problems and child abuse. Family illnesses atrophied. Foot length, measured carefully from the
with genetic implications should be sought. The past heel to the tip of the longest toe, also correlates with
pregnancy history should include maternal age, gravid- gestational age in appropriately grown infants. The foot
ity and parity, blood type, and pregnancy outcomes. measures 4.5 cm at 25 weeks’ gestation and increases by
The current obstetric history should include documen- 0.25 cm/week until term.
tation and results of procedures such as ultrasound, am- By convention, unless the physical examination in-
niocentesis, screening tests (eg, hepatitis B surface anti- dicates a gestational age more than 2 weeks different (in
gen [HBsAg], antibody screen, serum alpha fetoprotein either direction) from the obstetric dates, the gesta-
[AFP], human immunodeficiency virus [HIV]), and tional age is as assigned by the dates. The birth weight
antepartum tests of fetal well-being (eg, biophysical and gestational age must be plotted on an appropriate
profiles nonstress tests, or Doppler assessment of fetal standard to determine if the infant’s weight is appropri-
blood flow patterns). Information should be sought re- ate for gestational age (AGA), small for gestational age
garding pregnancy-related illnesses in the mother such (SGA) or intrauterine growth restricted (IUGR), or
as urinary tract infection, pregnancy-induced hyperten- large for gestational age (LGA) (Figure 1–1). Birth
sion or preeclampsia, eclampsia, vaginal bleeding, and weight and gestational age distributions vary from one
preterm labor. Peripartum events of importance include population to the next, depending on factors such as
duration of ruptured membranes, maternal fever, fetal those listed in Table 1–2. Whenever possible, standards
distress or meconium-stained amniotic fluid, type of should be prepared from data derived from the local
delivery (vaginal or cesarean section), anesthesia and population, but when such information is not available,
1
Copyright © 2005, 2001, by The McGraw-Hill Companies, Inc. Click here for terms of use.
Table 1–1. New Ballard Score for assessment of fetal maturation of newly born infants.a

Neuromuscular Maturity
Neuromuscular Score Record
Maturity Sign −1 0 1 2 3 4 5 Score Here
Posture

Square window
(wrist)

Arm recoil

Popliteal angle

Scarf sign

Heel to ear

Total Neuromuscular
Maturity Score
Physical Maturity

Physical Score Record

Maturity Sign −1 0 1 2 3 4 5 Score Here
Skin Sticky, Gelatinous, Smooth, Superficial Cracking, Parchment, Leathery,
friable, red, trans- pink, visible peeling pale areas; deep crack- cracked,
transparent lucent veins &/or rash; rare veins ing; no ves- wrinkled
few veins sels
Lanugo None Sparse Abundant Thinning Bald areas Mostly bald
Plantar surface Heel toe > 50 mm: Faint red Anterior Creases Creases
40–50 mm: no crease marks transverse anterior 2⁄3 over entire
−1 < 40 mm: crease only sole
−2
Breast Impercepti- Barely Flat areola; Stippled Raised Full areola;
ble perceptible no bud areola; areola; 5- to 10-mm
1- to 2-mm 3- to 4-mm bud
bud bud
Eye/Ear Lids fused Lids open; Slightly Well-curved Formed & Thick carti-
loosely: −1 pinna flat; curved pinna; soft firm instant lage; ear
tightly: −2 stays folded pinna; soft; but ready recoil stiff
slow recoil
recoil
Genitals (male) Scrotum Scrotum Testes in Testes des- Testes Testes
flat, smooth empty; upper cending; down; good pendulous;
faint rugae canal; rare few rugae rugae deep rugae
rugae
Genitals (female) Clitoris Prominent Prominent Majora & Majora Majora
prominent clitoris & clitoris & minora large; cover clitoris
& labia flat small labia enlarging equally minora & minora
minora minora prominent small
Total Physical
Maturity Score
Maturity Score −10 −5 0 5 10 15 20 25 30 35 40 45 50
Rating Weeks 20 22 24 26 28 30 32 34 36 38 40 42 44
a
See text for a description of the clinical gestational age examination.
Reproduced, with permission, from Ballard JL et al: New Ballard Score, expanded to include extremely premature infants. J Pediatr 1991;119:417.
2
 THE NEWBORN INFANT / 3

24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43
CM CM
Intrauterine head growth circumference
53 90% 37
Intrauterine length chart both sexes 90%
52 36
both sexes 75%
51 75% 35
50%
50 50% 34
25%
49 33
25% 10%
48 32
47 31
46 10% 30
45 29
44 28
43 27
42 26
41 25
40 24
39 23
38 22
37 0
36
35 CM
34 4200 3.50
33 4000 3.40
32
90%
3800 3.30
Intrauterine weight: length ratio 100 g/L3 cm
both sexes
31 75% 3600 3.20
30 3400 3.10 90%
Intrauterine weight chart 50%
3200
0 3.00
both sexes
25% 3000 2.90 75%
2800 2.80
10%
CM 2600 2.70
50%
2400 2.60
2200 2.50 25%
2000 2.40
1800 2.30 10%
1600 2.20
1400 2.10
1200 2.00
1000 1.90
800 1.80
600 1.70
400 1.60
0 0
24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43
Week of gestation Week of gestation

Figure 1–1. Intrauterine growth curves for weight, length, and head circumference for singleton births in Col-
orado. (Reproduced, with permission, from Lubchenco LO et al: Intrauterine growth in length and head circumference as
estimated from live births at gestational ages from 26 to 42 weeks. Pediatrics 1966;37:403.)

any regional standard may be used. The birth weight- order is symmetrical (weight, length, and occip-
gestational age distribution of an infant is a screening itofrontal circumference [OFC] all ≤ 10%) or asym-
tool that should be supplemented by clinical data con- metrical (only weight ≤ 10%). Asymmetrical growth re-
firming a tentative diagnosis of intrauterine growth re- tardation implies a problem late in the pregnancy, such
striction or excessive fetal growth. These data include as pregnancy-induced hypertension or placental insuffi-
not only the clinical features of the infant determined ciency. Symmetrical growth restriction implies an event
during the physical examination but also factors such as of early pregnancy: chromosomal abnormality, drug or
the size of the parents and the birth weight-gestational alcohol use, congenital viral infections. In general, the
age distribution of infants previously born to the par- outlook for normal growth and development is better
ents. in the asymmetrically growth-restricted infant whose
Table 1–3 lists causes of variations in neonatal size intrauterine brain growth has been spared.
in relation to gestational age. An important distinction, The fact that SGA infants have fewer problems (such
particularly in SGA infants, is whether the growth dis- as respiratory distress syndrome) than AGA infants of
4 / CHAPTER 1

Table 1–2. Factors affecting birth Thureen PJ et al: The small-for-gestational age infant. Neoreviews
2001;2:e139.
weight/gestational age distributions.

1. Socioeconomic factors that affect nutritional level and ac- EXAMINATION AT BIRTH
cess to health care The extent of the newborn physical examination de-
2. Altitude pends on the condition of the infant and the environ-
3. Environmental factors that affect birth weight (eg, smok- ment in which the examination is being performed. In
ing, alcohol, illicit drug use) the delivery room, the examination consists largely of
4. Race observation plus auscultation of the chest and inspec-
tion for congenital anomalies and birth trauma. Major
congenital anomalies are present in 1.5% of live births
the same birth weight but a lower gestational age has led and account for 20–25% of perinatal and neonatal
to the common misconception that SGA infants have deaths. Because the infant is recovering from the stress
accelerated maturation. SGA infants, when compared of birth, the examination should not be extensive. The
with AGA infants of the same gestational age, actually Apgar score (Table 1–4) should be recorded at 1 and
have increased morbidity and mortality rates. 5 minutes of age. In the case of severely depressed in-
Knowledge of a baby’s birth weight in relation to fants, a 10-minute score should also be recorded. Al-
gestational age is also helpful in anticipating neonatal though the 1- and 5-minute Apgar scores have almost
problems. LGA babies are at risk for birth trauma, hy- no predictive value for long-term outcome, serial scores
poglycemia, polycythemia, congenital anomalies, car- do provide a useful shorthand description of the sever-
diomyopathy, hyperbilirubinemia, and hypocalcemia. ity of perinatal depression and the quality of the resus-
SGA babies are at risk for fetal distress during labor and citative efforts needed.
delivery, polycythemia, hypoglycemia, and hypocal- The color of the skin is a useful indicator of cardiac
cemia. output. Normally there is a high blood flow to the skin.
Any stress that triggers a catecholamine response redi-
American Academy of Pediatrics: Guidelines for Perinatal Care, 5th rects cardiac output away from the skin to preserve oxy-
ed. American Academy of Pediatrics, 2002. gen delivery to more critical organs. Cyanosis and pal-
Ballard JL et al: New Ballard score, expanded to include extremely
premature infants. J Pediatr 1991;119:417 [PMID:1880657].
Cowett RM: Neonatal care of the infant of the diabetic mother.
Neoreviews 2002;3:e190. Table 1–4. Infant evaluation at birth—
McIntire DD et al: Birth weight in relation to morbidity and mor-
tality among newborn infants. N Engl J Med 1999;340:
Apgar score.a
1234 [PMID: 10210706].
Score
0 1 2
Table 1–3. Causes of variations in neonatal size
in relation to gestational age. Heart rate Absent Slow (< 100) > 100
Respiratory Absent Slow, irregular Good, crying
Infants large for gestational age effort
Infant of a diabetic mother Muscle tone Limp Some flexion Active
Infants small for gestational age motion
Asymmetrical
Placental insufficiency secondary to pregnancy-induced Response to No response Grimace Cough or
hypertension or other maternal vascular disease catheter in sneeze
Maternal age > 35 years nostrilb
Poor weight gain during pregnancy Color Blue or pale Body pink; ex- Completely
Multiple gestation tremities blue pink
Symmetrical
Maternal drug use © 1958 American Medical Association.
a
One minute and 5 minutes after complete birth of the infant
Narcotics
(disregarding the cord and the placenta), the following objective
Cocaine
signs should be observed and recorded.
Alcohol b
Tested after oropharynx is clear.
Chromosomal abnormalities Reproduced, with permission, from Apgar V et al: Evaluation of
Intrauterine viral infection (eg, cytomegalovirus) the newborn infant—Second report. JAMA 1958;168:1985.
 THE NEWBORN INFANT / 5

lor are thus two signs reflecting inadequate skin oxy- fewer café-au-lait spots in a white infant or five or fewer
genation and cardiac output. in an African American infant.
The skeletal examination immediately after delivery
serves two purposes: (1) to detect any obvious congeni-
tal anomalies and (2) to detect signs of birth trauma,
Skin
particularly in LGA infants or those born after a pro- Observe for bruising, petechiae (common over the pre-
tracted second stage of labor—in whom a fractured senting part), meconium staining, and jaundice. Pe-
clavicle or humerus might be found. ripheral cyanosis is commonly present when the ex-
The umbilical cord should be examined for the tremities are cool or the infant is polycythemic.
number of vessels. Normally, there are two arteries and Generalized cyanosis merits immediate evaluation. Pal-
one vein. In 1% of deliveries (5–6% of twin deliveries), lor may be caused by acute or chronic blood loss or by
the cord has only two vessels: an artery and a vein. The acidosis. In dark-skinned infants, pallor and cyanosis
latter configuration may be considered a minor anom- should be assessed in the oral region and nail beds.
aly and, as with other minor anomalies, carries a Plethora suggests polycythemia. Note vernix caseosa (a
slightly increased risk of associated defects. The pla- whitish, greasy material covering the body that de-
centa is usually examined by the physician delivering it. creases as term approaches) and lanugo (the fine hair
Small placentas are always associated with small infants. covering the preterm infant’s skin). Dry skin with
The placental examination emphasizes the identifica- cracking and peeling of the superficial layers is common
tion of membranes and vessels—particularly in multi- in postterm infants. Edema may be generalized (hy-
ple gestations—as well as the presence and severity of drops) or localized (eg, on the dorsum of the feet in
placental infarcts or evidence of clot (placental abrup- Turner syndrome). Check for birthmarks such as capil-
tion) on the maternal side. lary hemangiomas (lower occiput, eyelids, forehead)
and mongolian spot (bluish black pigmentation over
GENERAL EXAMINATION the back and buttocks). Milia—small white keratoge-
nous cysts—can be found scattered over the cheeks,
IN THE NURSERY forehead, nose, and nasolabial folds. Miliaria (blocked
It is important that the examiner have warm hands and ducts of sweat glands) occurs in intertriginous areas and
a gentle approach. Start with observation, then auscul- on the face or scalp. It can appear as small vesicles (crys-
tation of the chest, and then palpation of the abdomen. tallina), small erythematous papules (rubra), or pus-
Examination of the eyes, ears, throat, and hips should tules. Erythema toxicum is a benign rash characterized
be done last, since these maneuvers are most disturbing by fleeting erythematous papules and pustules filled
to the infant. The heart rate should range from 120 to with eosinophils. Pustular melanosis leaves pigmented
160 beats/min, and the respiratory rate from 30 to macules when the pustules rupture. The pustules are
60 breaths/min; blood pressure is affected by perinatal noninfectious but contain neutrophils. Jaundice pre-
asphyxia and the need for mechanical ventilation more senting in the first 24 hours is considered abnormal and
than by gestational age or birth weight. Systolic blood should be evaluated (see section on Neonatal Jaundice).
pressure on day 1 ranges from 50 to 70 mm Hg and in-
creases steadily during the first week of life. Note: An Head
irregularly irregular heart rate, usually caused by prema-
ture atrial contractions, is common. This irregularity Check for cephalohematoma (a swelling over one or
should resolve in the first days of life and is not of both parietal bones contained within suture lines) and
pathologic significance. caput succedaneum (edema over the presenting part
The presence of minor anomalies (those occurring that crosses suture lines). Subgaleal hemorrhages (be-
in < 4% of the population) should be noted. Approxi- neath the scalp) are uncommon but can lead to exten-
mately 15–20% of healthy newborns have one minor sive blood loss into this large potential space with resul-
anomaly, with a 3% risk of having an associated major tant hypovolemic shock. Skull fractures may be linear
anomaly. Approximately 0.8% of newborns have two or depressed and may be associated with cephalohe-
minor anomalies, and 0.5% have three or more, with a matoma. Check the size and presence of the fontanelles.
risk of 10% and 20%, respectively, of a major malfor- The anterior fontanelle varies from 1 to 4 cm in any di-
mation. Common minor anomalies that require no fur- rection, whereas the posterior fontanelle should be less
ther diagnostic evaluation if isolated in an otherwise than 1 cm. A third fontanelle is a bony defect along the
normal infant include preauricular pits (although hear- sagittal suture in the parietal bones and may be a fea-
ing should be assessed), a sacral dimple without other ture of certain syndromes, such as trisomy 21. Sutures
cutaneous abnormality that occurs within 2.5 cm of the should be freely mobile. Craniosynostosis is a prema-
anus, a single transverse palmar crease, and three or turely fused suture.
6 / CHAPTER 1

Face Mouth
Odd facies may be associated with a specific syndrome. Epithelial (Epstein) pearls are retention cysts along the
Bruising from birth trauma (especially with face presen- gum margins and at the junction of the hard and soft
tation) and forceps marks should be identified. Face palates. Natal teeth may be present and sometimes need
presentation may be associated with considerable soft to be removed to avoid the risk of aspiration. Check the
tissue swelling around the nose and mouth, causing integrity and shape of the palate; rule out cleft lip and
considerable distortion. Facial nerve palsy is observed cleft palate. A small mandible and tongue with cleft soft
when the infant cries; the unaffected side of the mouth palate is seen with Pierre-Robin syndrome and can re-
moves normally, giving a distorted grimace. sult in respiratory difficulty as the tongue occludes the
airway. Prone positioning can be very beneficial. A
prominent tongue can be seen in trisomy 21 and Beck-
with–Wiedemann syndrome. Excessive drooling sug-
Eyes gests esophageal atresia.
Subconjunctival hemorrhages are seen frequently as a
result of the birth process. Less commonly, a corneal
tear may occur, presenting as a clouded cornea. Oph- Neck
thalmologic consultation is indicated in such cases. Ex-
traocular movements should be assessed. Occasional Redundant skin or webbing is seen in Turner syn-
uncoordinated eye movements are common, but persis- drome. Sinus tracts may be seen as remnants of
tent irregular movements are abnormal. The iris should branchial clefts. Check for masses: midline (thyroid),
be inspected for abnormalities such as Brushfield spots anterior to the sternocleidomastoid (branchial cleft
(trisomy 21) and colobomas. Examine for the red reflex cysts), within the sternocleidomastoid (hematoma, tor-
of the retina. The red reflexes should be symmetrical. ticollis), and posterior to the sternocleidomastoid (cys-
Dark spots, a blunted reflex on one side, lack of a re- tic hygroma).
flex, and a white reflex are all indications for referral to
an ophthalmologist. Leukokoria can be caused by glau-
coma (cloudy cornea), cataract, or tumor (retinoblas-
toma). Infants at risk for chorioretinitis (congenital Chest & Lungs
viral infection) should undergo a formal retinal exami- Check for fractured clavicles (crepitus, bruising, and
nation with pupils dilated prior to nursery discharge or tenderness). Increased anteroposterior diameter (barrel
as an outpatient. chest) can be seen with aspiration syndromes. Check air
entry bilaterally and the position of the mediastinum
and heart tones. Decreased breath sounds with respira-
tory distress and a shift in the mediastinum suggests
Nose pneumothorax (tension) or a space-occupying lesion
Examine the nose for size and shape. In utero compres- (eg, diaphragmatic hernia). With pneumomediastinum,
sion can cause deformities. Because babies under age the heart sounds are muffled. Expiratory grunting and
1 month are obligate nose breathers, any nasal obstruc- decreased air entry are observed in hyaline membrane
tion (eg, bilateral choanal atresia or stenosis) can cause disease. Rales are not of clinical significance at this age.
respiratory distress. Unilateral choanal atresia can be di-
agnosed by occluding each naris. Patency is best
checked by holding a cold metal surface (eg, a chilled
laryngoscope blade) under the nose, and observing the Heart
fog from both nares on the metal. Purulent nasal dis- Examination of the heart is described in detail in Chap-
charge at birth suggests congenital syphilis. ter 19. Note: Murmurs are commonly present in the
first hours and are most often benign. Severe congenital
heart disease in the newborn infant may be present with
no murmur at all. The two most common presenta-
Ears tions of heart disease in the newborn infant are cyanosis
Malformed or malpositioned (low-set or posteriorly ro- and congestive heart failure with abnormalities of
tated) ears are often associated with other congenital pulses. In hypoplastic left heart and critical aortic steno-
anomalies. The tympanic membranes should be visual- sis, pulses are diminished at all sites. In aortic coarcta-
ized. Preauricular pits and tags are also common minor tion and interrupted aortic arch, pulses are diminished
variants that can be associated with hearing loss. in the lower extremities.
 THE NEWBORN INFANT / 7

Abdomen extremities should result in spontaneous recoil to the

flexed position. Assess the character of the cry; a high-
Check for softness, distention, and bowel sounds. If pitched cry may be indicative of disease of the central
polyhydramnios was present or excessive oral secretions nervous system (CNS) (eg, hemorrhage). Hypotonia
are noted, pass a soft catheter into the stomach to rule and a weak cry are indicative of systemic disease or a
out esophageal atresia. Palpate for kidneys—most ab- congenital neuromuscular disorder. Check for newborn
dominal masses in the newborn infant are associated reflexes:
with kidney disorders (eg, multicystic or dysplastic, hy-
dronephrosis). When the abdomen is relaxed, normal- 1. Sucking reflex in response to a nipple or the ex-
sized kidneys may be felt but are not prominent. A aminer’s finger in the mouth. This reflex is ob-
markedly scaphoid abdomen plus respiratory distress served by 14 weeks’ gestation.
suggests diaphragmatic hernia. Absence of abdominal 2. Rooting reflex: Head turns to the side of a facial
musculature (prune belly syndrome) may occur in asso- stimulus. This reflex develops by 28 weeks’ gesta-
ciation with renal abnormalities. Check the size of the tion.
liver and the spleen. These organs are superficial and 3. Traction response: The infant is pulled by the
discernible by light palpation in the newborn infant. arms to a sitting position. Initially, the head lags,
The outline of a distended bladder may be seen and then with active flexion comes to the midline
palpated above the pubic symphysis. briefly before falling forward.
4. Palmar grasp with placement of the examiner’s fin-
Genitalia & Anus ger in the palm. This reflex develops by 28 weeks’
Male and female genitals show characteristics according gestation and disappears by age 4 months.
to gestational age (see Table 1–1). In the female during 5. Deep tendon reflexes: Several beats of ankle
the first few days, a whitish vaginal discharge with or clonus and an upgoing Babinski reflex may be
without blood is normal. Check the patency and loca- normal.
tion of the anus. 6. Placing: Rub the dorsum of one foot on the un-
derside of a surface. The infant will flex the knee
Skeleton and bring the foot up.
Check for obvious anomalies, for example, the absence 7. Moro (startle) reflex: Hold the infant and support
of a bone, clubfoot, fusion or webbing of digits, and the head. Allow the head to drop 1–2 cm sud-
extra digits. Examine for hip dislocation by attempting denly. The arms will abduct at the shoulder and
to dislocate the femur posteriorly and then abducting extend at the elbow. Adduction with flexion will
the legs to relocate the femur. Look for extremity frac- follow. The hands show a prominent spreading or
tures and for palsies (especially brachial plexus injuries). extension of the fingers. This reflex develops by
Rule out myelomeningoceles and other spinal deformi- 28 weeks’ gestation (incomplete) and disappears
ties (eg, scoliosis). Arthrogryposis (multiple joint con- by age 3 months.
tractures) results from chronic limitation of movement 8. Tonic neck reflex: Forcibly turn the infant’s head
in utero, which may result from lack of amniotic fluid to one side, and the arm and leg on that side
or from a congenital neuromuscular disease. extend while the opposite arm and leg flex (“fenc-
ing position”). This reflex disappears by age
8 months.
Neurologic Examination
Normal newborns are endowed with a set of reflexes Adam M, Hudgins L: The importance of minor anomalies in the
that facilitate survival (eg, rooting and sucking reflexes), evaluation of the newborn. Neoreviews 2003;4:e99.
as well as sensory abilities (eg, hearing and smell) that Ackerman LL, Menezes AH: Spinal congenital dermal sinuses: A
allow them to recognize their mother within a few 30-year experience. Pediatrics 2003;112:641 [PMID:
weeks of birth. Although the retina is well developed at 12949296].
birth, visual acuity is poor (20/400) because of a rela- American Academy of Pediatrics Committee on Quality Improve-
tively immobile lens. Acuity improves rapidly over the ment, Subcommittee on Developmental Dysplasia of the
Hip: Early detection of developmental dysplasia of the hip.
first 6 months, with fixation and tracking becoming Pediatrics 2000;105:896 [PMID: 10742345].
well developed by 2 months. American Academy of Pediatrics Section on Ophthalmology: Red
In examining the newborn, observe resting tone reflex examination in infants. Pediatrics 2002;109:980
(normal-term newborns should exhibit flexion of the [PMID: 11986467].
upper and lower extremities) and spontaneous move- Eichenfield LF et al (editors): Textbook of Neonatal Dermatology.
ments. Look for symmetry of movements. Extension of WB Saunders, 2001.
8 / CHAPTER 1

Hernandez JA, Morelli JG: Birthmarks of medical significance. Neo- roidism, and cystic fibrosis) is performed just prior to
reviews 2003;4:e270. discharge, after 24–48 hours in hospital if possible. In
many states, a repeat test is required at 8–14 days of age
because the PKU test is often falsely negative when ob-
tained before 48 hours of age. Not all state-mandated
CARE OF THE WELL screens include the same panel of diseases; the most re-
NEWBORN INFANT cent addition in some states is a screen for congenital
adrenal hyperplasia. In infants with prolonged hospital
stays, the test should be performed by 1 week of age. In
The primary responsibility of the level 1 nursery is care addition to the state-mandated screen, some centers
of the well infant. This includes promoting mother–in- offer expanded newborn screening by tandem mass
fant bonding, establishing feeding, and teaching the spectrometry that looks for a variety of other inborn er-
techniques of newborn care. Surveillance of the infant rors such as fatty acid oxidation defects.
is a key function of the staff; they must be alert for the Infants should routinely be positioned supine or
signs and symptoms of illness, including temperature lying on the right side with the dependent arm forward
instability, change in activity, refusal to feed, pallor, to minimize the risk of sudden infant death syndrome
cyanosis, early or excessive jaundice, tachypnea and res- (SIDS). Prone positioning is contraindicated unless
piratory distress, delayed (beyond 24 hours) passage of specific problems, such as gastroesophageal reflux or
first stool or voiding of urine, and bilious vomiting. respiratory distress, are present. Bed sharing with adults
Several preventive measures are undertaken routinely in and prone positioning are both associated with in-
the normal newborn nursery. creased risk of SIDS.
Eye prophylaxis to prevent gonococcal ophthalmia
is routinely administered within 1 hour after birth with FEEDING THE WELL NEWBORN INFANT
either erythromycin ointment or silver nitrate 1%
drops. Because of the severe chemical conjunctivitis Indications that the baby is ready for feeding include
caused by silver nitrate, erythromycin is preferred. (1) alertness and vigor, (2) absence of abdominal dis-
Vitamin K, 1 mg, is given intramuscularly or subcu- tention, (3) good bowel sounds, and (4) normal hunger
taneously within 4 hours after birth to prevent hemor- cry. All of these usually occur within 6 hours after
rhagic disease of the newborn. The area to be injected birth, but fetal distress or traumatic delivery may pro-
must be cleansed thoroughly before injection to prevent long this period.
infection. The healthy full-term infant should be allowed to
All infants should be vaccinated against hepatitis B, feed every 2–5 hours on demand. The first feeding usu-
but the first dose can wait until 1–2 months of age if ally occurs by 3 hours of life, often as early as in the de-
the mother is HBsAG-negative. Hepatitis B vaccine livery room. Breast milk or formula (20 kcal/oz) can be
and hepatitis B immune globulin (HBIG) are adminis- given. For formula-fed babies, the volume generally in-
tered if the mother is known to be HBsAg-positive. If creases from 0.5–1 oz per feeding initially to 1.5–2 oz
maternal HBsAg status is unknown at birth, the vaccine per feeding on day 3. By day 3, the average full-term
should be given. The mother’s blood should be tested newborn takes in about 100 mL/kg/d of milk.
and HBIG given at less than 7 days of age if the test is Although a wide range of infant formulas can satisfy
positive. the nutritional needs of most neonates, breast milk is
Cord blood is collected on all infants at birth and the standard on which formulas are based (see also
used for blood typing and Coombs’ testing if the Chapter 10). The distribution of calories in human
mother is type O or Rh-negative. Cord blood is useful milk is 55% fat, 38% carbohydrate, and 7% protein,
also for other tests, such as toxicology screens. with a whey-to-casein ratio of 60:40, allowing for easy
Rapid glucose testing should be performed in in- protein digestion. Despite the low concentrations of
fants at risk for hypoglycemia (eg, infants of diabetic several vitamins and minerals, their bioavailability is
mothers [IDMs], preterm, SGA, LGA, or stressed in- high. All of the necessary nutrients, vitamins, minerals,
fants). Values less than 45 mg/dL should be confirmed and water are provided by human milk for the first
by laboratory blood glucose testing and treated. Hemat- 6 months of life except vitamin K (thus, 1 mg IM is ad-
ocrit should be measured at age 3–6 hours in infants at ministered at birth), vitamin D (200–300 IU/d if mini-
risk for or those who have symptoms of polycythemia mal sunlight exposure), fluoride (0.25 mg/d after
or anemia. 6 months if water supply not fluoridated), and vitamin
The state-sponsored newborn genetic screen (for in- B12 (0.3–0.5 mg/d if the mother is a strict vegetarian
born errors of metabolism such as phenylketonuria and takes no B12 supplement). Other advantages of
[PKU], galactosemia, sickle cell disease, hypothy- breast milk include (1) the presence of immunologic,
 THE NEWBORN INFANT / 9

antimicrobial, and antiinflammatory factors, including EARLY DISCHARGE

IgA, cellular, and protein or enzymatic components OF THE NEWBORN INFANT
that decrease the incidence of upper respiratory and
gastrointestinal (GI) infections in infancy; (2) the possi- Discharge at 24–36 hours of age appears safe and ap-
bility that breast feeding may decrease the frequency propriate for most infants if there are no contraindica-
and severity of childhood eczema and asthma; (3) pro- tions (Table 1–6) and a follow-up visit at 48–72 hours
motion of mother–infant bonding; and (4) evidence after discharge is ensured. Most infants with severe car-
that breast milk as a nutritional source improves neu- diorespiratory disorders and infections are identified in
rodevelopmental outcomes. the first 6 hours of life. The exception may be the in-
Although approximately 65% of mothers in the fant treated with intrapartum antibiotic prophylaxis for
United States initiate breast feeding, only 25% con- maternal group B streptococcal (GBS) colonization or
tinue to breastfeed at 6 months. Hospital practices that infection. The Centers for Disease Control and Preven-
facilitate the successful initiation of breast feeding in- tion (CDC) and the American Academy of Pediatrics
clude rooming-in, nursing on demand, and avoiding (AAP) have recommended that these infants be ob-
the use of pacifiers and supplemental formula (unless served in hospital for 48 hours because of the possibility
medically indicated). The nursery staff must be cog- of “partial treatment” with delayed onset of symptoms
nizant of problems associated with breast feeding and of infection. However, recent data show that exposure
be able to provide help and support for mothers in the to antibiotics in labor does not appear to change the
hospital. It is essential that an experienced professional type or timing of symptoms related to GBS infection in
observe and assist with at least one feeding to document full-term infants, and that hospital observation beyond
good latch-on, important in preventing the common 24 hours is unnecessary for the asymptomatic full-term
breast-feeding problems of sore nipples, unsatisfied ba- infant who received intrapartum chemoprophylaxis.
bies, engorgement, poor milk supply, and excessive hy- Other problems, such as jaundice and difficulties in
perbilirubinemia (“lack-of-breast-milk jaundice”). breast feeding, typically occur after 48 hours and can
Table 1–5 presents recommendations the nursing usually be dealt with on an outpatient basis provided
mother and health care provider can use to achieve suc- good follow-up has been arranged.
cessful breast feeding. The AAP recommends a follow-up visit within
48–72 hours for any newborn discharged before
48 hours of age. Infants who are small or slightly pre-
American Academy of Pediatrics Committee on Fetus and New- mature—especially if breast feeding—are at particular
born: Controversies concerning vitamin K and the newborn.
Pediatrics 2003;112:191 [PMID: 12837888].
risk for inadequate intake. Suggested guidelines for the
American Academy of Pediatrics Committee on Nutrition: Iron
follow-up interview and physical examination are pre-
fortification of infant formulas. Pediatrics 1999; sented in Table 1–7. The optimal timing of discharge
104:119 [PMID: 10390274]. must be determined in each case based on medical, so-
American Academy of Pediatrics Task Force on Infant Sleep Posi- cial, and financial factors.
tion and Sudden Infant Death Syndrome: Concepts of sud-
den infant death syndrome: Implications for infant sleeping
environment and sleep position. Pediatrics 2000; CIRCUMCISION
105:650 [PMID: 10699127].
Circumcision is an elective procedure to be performed
Anderson JW et al: Breast-feeding and cognitive development: A
meta-analysis. Am J Clin Nutr 1999;70:525 [PMID:
only in healthy, stable infants. The procedure probably
10500022]. has medical benefits, including prevention of phimosis,
Dewey KG et al: Risk factors for suboptimal infant breastfeeding paraphimosis, balanoposthitis, and urinary tract infec-
behavior, delayed onset of lactation, and excess neonatal tion. Later benefits include decreased incidence of can-
weight loss, Pediatrics 2003;112:607 [PMID: 12949292]. cer of the penis, cervical cancer (in partners of circum-
Hoffman DR et al: Visual function in breast-fed term infants cised men), and sexually transmitted diseases (including
weaned to formula with or without long-chain polyunsatu- HIV). Most parents decide on circumcision for non-
rates at 4 to 6 months: A randomized clinical trial. J Pediatr medical reasons. The risks of the procedure include
2003;142:669 [PMID: 12838196]. local infection, bleeding, removal of too much skin,
Kunz C et al: Nutritional and biochemical properties of human and urethral injury. The combined incidence of these
milk. Part 1: General aspects, proteins, and carbohydrates.
Clin Perinatol 1999;26:307 [PMID: 10394490].
complications is less than 1%. Local anesthesia (dorsal
Neifert MR: Clinical aspects of lactation: Promoting breast feeding
penile nerve block or circumferential ring block with
success. Clin Perinatol 1999;26:281 [PMID: 10394489]. 1% lidocaine without epinephrine) or topical applica-
Rodriquez-Palmero M et al: Nutritional and biochemical properties tion of an anesthetic cream are safe and effective and
of human milk. II: Lipids, micronutrients, and bioactive fac- should always be used. Techniques that allow visualiza-
tors. Clin Perinatol 1999;26:335 [PMID: 10394491]. tion of the glans throughout the procedure (eg, Plas-
 Table 1–5. Guidelines for successful breast feeding.

First 8 Hours 8–24 Hours Day 2 Day 3 Day 4 Day 5 Day 6 Onward
Milk supply You may be able to express a few drops of milk. Milk should come in between the second and fourth days. Milk should be in. Breasts should feel softer
Breasts may be firm after feedings.
or leak milk.
Baby’s activity Baby is usually wide- Wake up your baby. Baby should be Look for early feeding cues such as rooting, lip smacking, and Baby should appear satis-
awake in the first Babies may not wake more cooperative hands to face. fied after feedings.
hour of life. Put baby up on their own to and less sleepy.
to breast within 30 feed.
min after birth.
Feeding routine Baby may go into a Use chart to write down time of each feeding. May go one
deep sleep 2–4 h longer interval (up
after birth. Feed your baby every 1–4 h or as often as wanted—at least 8–12 times a day. to 5 h between
feeds) in a 24-h
period.
10

Breast feeding Baby will wake up As long as the mother is Try to nurse both Consider hand Nurse a minimum of 10–30 min per Mother’s nipple tenderness
and be alert and comfortable, nurse at sides each feed- expressing or side every feeding for the first few is improving or is gone.
responsive for both breasts as long ing, aiming at 10 pumping a few weeks of life.
several more hours as baby is actively min per side. drops of milk to
after initial deep sucking. Expect some nip- soften the nipple Once milk supply is well established,
sleep. ple tenderness. if the breast is allow baby to finish the first breast
too firm for the before offering the second.
baby to latch on.
Baby’s urine Baby must have a Baby must have You should see Baby’s urine Baby should have
output minimum of one wet at least one wet an increase in should be light six to eight wet
diaper in first 24 h. diaper every wet diapers (up yellow. diapers per day of
8–11 h. to four to six) in colorless or light
24 h. yellow urine.
Baby’s stool Baby should have a Baby may have Baby’s stools should be in transition Baby should have The number of stools may
black-green (meco- a second very from black-green to yellow. three or four yellow, decrease gradually after
nium) stool. dark (meconium) seedy stools a day. 4–6 wk of life.
stool.
Modified, with permission, from Gabrielski L: Lactation support services. The Children’s Hospital, Denver, 1999.
 THE NEWBORN INFANT / 11

Table 1–6. Criteria for early newborn discharge. Table 1–7. Guidelines for early outpatient
follow-up evaluation.
Contraindications to early newborn discharge
1. Jaundice at ≤ 24 h History
2. High risk for infection (eg, maternal chorioamnionitis); dis- Rhythmic sucking and audible swallowing for at least 10
charge allowed at 24 h with a normal transition minutes total per feeding?
3. Known or suspected narcotic addiction or withdrawal Baby wakes and demands to feed every 2–3 h (at
4. Physical defects requiring evaluation least eight to ten feedings per 24 h)?
5. Oral defects (clefts, micrognathia) Do breasts feel full before feedings, and softer after?
Relative contraindications to early newborn discharge Are there at least six noticeably wet diapers per 24 h?
(infants at high risk for feeding failure, excessive Are there yellow bowel movements (no longer meco-
jaundice) nium)—at least four per 24 h?
1. Prematurity or borderline prematurity (< 38 weeks’ gesta- Is baby still acting hungry after nursing (frequently sucks
tion) hands, rooting)?
2. Birth weight < 2700 g (6 lb) Physical assessment
3. Baby difficult to arouse for feeding; not demanding regu- Weight, unclothed: should not be more than 8–10% below
larly in nursery birth weight
4. Medical or neurologic problems that interfere with feeding Extent and severity of jaundice
(Down syndrome, hypotonia, cardiac problems) Assessment of hydration, alertness, general well-being
5. Twins or higher multiples Cardiovascular examination: murmurs, brachial and
6. ABO blood group incompatibility or severe jaundice in pre- femoral pulses, respirations
vious child
7. Mother whose previous breast-fed infant gained weight
poorly
8. Mother with breast surgery involving periareolar areas (if adrenal hyperplasia. Pediatrics 2000;106:1511 [PMID:
attempting to nurse) 11099616].
American Academy of Pediatrics Task Force on Circumcision:
Circumcision policy statement. Pediatrics 1999;103:686
[PMID: 10049981].
tibell and Gomco clamp) are preferred to a blind tech- Bromberger P et al: The influence of intrapartum antibiotics on the
nique (eg, Mogen clamp) because occasional amputa- clinical spectrum of early-onset group B streptococcal infec-
tion of the glans can occur with the latter technique. tion in term infants. Pediatrics 2000;106:244 [PMID:
Circumcision is contraindicated in infants with genital 10920146].
abnormalities (eg, hypospadias). Coagulation screen Farrell PA et al: SIDS, ALTE, apnea and the use of home monitors.
should be performed prior to the procedure in infants Pediatr Rev 2002;23:3 [PMID: 11773587].
with a confirmed family history of serious bleeding dis- Schulze A et al: Expanded newborn screening for inborn errors of
orders. metabolism by electrospray ionization–tandem mass spec-
trometry: Results, outcome, and implications. Pediatrics
2003;111:1399 [PMID: 12777559].
HEARING SCREENING Sokol J, Hyde M: Hearing screening. Pediatr Rev 2002;23:
155 [PMID: 11986491].
Normal hearing is critical to normal language develop-
ment. Significant bilateral hearing loss is present in Thompson DC et al: Universal newborn hearing screening.
Summary of evidence. JAMA 2001;286:2000 [PMID:
1–3 infants per 1000 in the well nursery and in 2–4 in- 11667937].
fants per 100 in the neonatal intensive care unit popu-
lation. All infants should be screened for hearing loss by
auditory brainstem evoked responses or evoked oto-
acoustic emissions as early as possible. Primary care COMMON PROBLEMS IN THE
providers and parents need to be advised of the possi-
bility of hearing loss and offered ready referral in sus- TERM NEWBORN INFANT
pect cases.
NEONATAL JAUNDICE
American Academy of Pediatrics Joint Committee on Infant Hear-
ing: Year 2000 position statement: Principles and guidelines General Considerations
for early hearing detection and intervention programs. Pedi-
atrics 2000;106:798 [PMID: 11015525]. Jaundice is a common neonatal problem. Sixty-five per-
American Academy of Pediatrics Section on Endocrinology and cent of newborns develop clinical jaundice with a
Committee on Genetics: Technical report: Congenital bilirubin level above 5 mg/dL during the first week of
12 / CHAPTER 1

life. From an evolutionary standpoint, hyperbilirubine- and a high-pitched cry. Long-term sequelae include
mia ought to confer some biologic advantage if it oc- athetoid cerebral palsy, sensorineural deafness, limita-
curs so often. Bilirubin is a potent antioxidant and per- tion of upward gaze, and dental dysplasia—a syndrome
oxyl scavenger that may help the newborn, who is that has been described as an intelligent mind trapped
deficient in most antioxidant substances such as vita- within an uncontrollable body wracked by painful
min E, catalase, and superoxide dismutase, to avoid spasms. Whether or not bilirubin causes more subtle
oxygen toxicity in the days after birth. Hyperbilirubine- neurologic abnormalities remains debatable.
mia can also be toxic, with high levels resulting in an Bilirubin encephalopathy is rare with current neona-
encephalopathy known as kernicterus. tal management, although upwards of 120 cases have
been reported to an informal registry since 1990. A spe-
cific bilirubin level of 20 mg/dL [344 mmol/L] and
Metabolism of Bilirubin above has been associated with an increased risk of ker-
Heme (iron protoporphyrin) is broken down by heme nicterus in the Rh-isoimmunized infant. For decades,
oxygenase to iron, which is conserved; carbon monox- the strategy of keeping bilirubin under 20 mg/dL with
ide, which is exhaled; and biliverdin, which is then fur- phototherapy and exchange transfusion if needed elimi-
ther metabolized to bilirubin by the enzyme bilirubin nated kernicterus in the United States. The reappear-
reductase. Each 1 g of hemoglobin breakdown results ance of kernicterus over the past decade has been as-
in the production of 34 mg of bilirubin (1 mg/dL = cribed to early discharge of breast-feeding infants
17.2 mmol/L of bilirubin). Bilirubin is carried bound without appropriate follow-up or appreciation of the
to albumin to the liver, where, in the presence of early signs of bilirubin encephalopathy. The risk of
the enzyme uridyldiphosphoglucuronyl transferase bilirubin encephalopathy is probably very small for full-
(UDPGT; glucuronyl transferase), it is taken up by the term infants without hemolysis even at bilirubin levels
hepatocyte and conjugated with two glucuronide mole- of 25 mg/dL (430 mmol/L). Premature infants are
cules. The conjugated bilirubin is then excreted probably at some increased risk because of associated
through the bile to the intestine. In the presence of nor- illnesses that may affect the integrity of the blood–brain
mal gut flora, the conjugated bilirubin is metabolized barrier as well as because of reduced albumin levels. For
further to stercobilins and excreted in the stool. In the this reason, a lower level of bilirubin is generally as-
absence of gut flora—and with slow intestinal motility, sumed to represent the “exchange level” in these infants
as in the first few days of life—the conjugated bilirubin and is usually determined arbitrarily based on the in-
remains in the intestinal lumen, where a mucosal en- fant’s birth weight and gestational age. One common
zyme (β-glucuronidase) can cleave off the glucuronide approach is to use 1% of the birth weight in grams as
molecules, leaving unconjugated bilirubin to be reab- the exchange level in milligrams per deciliter (mg/dL)
sorbed (the enterohepatic circulation of bilirubin). (eg, 12 mg/dL for a 1200-g infant) down to a low of
10 mg/dL. Many other arbitrary approaches exist as
well.
Bilirubin Toxicity
The exact mechanism by which bilirubin is toxic to Causes of Unconjugated
cells is unknown. It is assumed that if the amount of Hyperbilirubinemia
lipid-soluble unconjugated bilirubin exceeds the avail-
able binding sites on albumin, “free” bilirubin will be The causes of unconjugated hyperbilirubinemia can
available to enter neurons and damage them. The be grouped into two main categories: overproduction
blood–brain barrier probably plays an important role in of bilirubin and decreased conjugation of bilirubin
protecting an individual from brain damage, but its in- (Table 1–8).
tegrity is impossible to measure clinically. It is un-
known whether a level of bilirubin exists above which A. INCREASED BILIRUBIN PRODUCTION
brain damage always occurs even in a healthy individ- Increased production of bilirubin results from an in-
ual. creased rate of red blood cell destruction (hemolysis)
The syndrome of bilirubin encephalopathy was well due to the presence of maternal antibodies against fetal
described in the era before exchange transfusion as cells (Coombs’ test-positive), abnormal red cell mem-
treatment for Rh isoimmunization (see later discus- brane shape (ie, spherocytosis), or abnormal red cell en-
sion). The pathologic correlate is known as kernicterus, zymes (ie, glucose-6-phosphate dehydrogenase [G6PD]
named for the yellow staining of the subthalamic nuclei deficiency). Antibodies can be directed against the
(kerns) seen at autopsy. The early symptoms of biliru- major blood group antigens (the type A or type B in-
bin encephalopathy consist of lethargy, hypotonia, and fant of a type O mother) or the minor antigens (the Rh
poor sucking, progressing to hypertonia, opisthotonos, system: D, E, C, d, e, c, Kell, Duffy, and so on).
 THE NEWBORN INFANT / 13

Table 1–8. Causes of jaundice secondary mia over the first several weeks and on occasion may
to unconjugated hyperbilirubemia. need to be transfused at a few weeks of age.
Rh isoimmunization is much less common and in-
Overproduction of bilirubin creases in severity with each immunized pregnancy be-
1. Increased rate of hemolysis (reticulocyte count elevated) cause of an increased maternal IgG antibody produc-
a. Patients with a positive Coombs test tion each time. Most Rh disease can be prevented by
Rh incompatibility administering high-titer Rho (D) immune globulin to
ABO blood group incompatibility an Rh-negative woman after any invasive procedure
Other blood group sensitizations during pregnancy as well as after any miscarriage, abor-
b. Patients with a negative Coombs test tion, or delivery of an Rh-positive infant. In severe
Abnormal red cell shapes cases, erythroblastosis fetalis (hydrops or generalized
Spherocytosis edema with heart failure related to severe anemia in the
Elliptocytosis fetus) occurs, often resulting in fetal or neonatal death
Pyknocytosis without appropriate antenatal intervention. In less se-
Stomatocytosis vere cases, hemolysis is the main problem, with resul-
Red cell enzyme abnormalities tant hyperbilirubinemia and anemia. The cornerstone
Glucose-6-phosphate dehydrogenase deficiency of antenatal management once isoimmunization has
Pyruvate kinase deficiency been diagnosed is transfusion of the fetus with Rh-neg-
Hexokinase deficiency ative cells, either directly into the umbilical vein via
Other metabolic defects percutaneous cordocentesis or into the fetal abdominal
c. Patients with bacterial or viral sepsis cavity. Following delivery, phototherapy is usually
2. Nonhemolytic causes of increased bilirubin load (Unconju-
started immediately, with exchange transfusion (see
gated bilirubin elevated, reticulocyte count normal.)
a. Extravascular hemorrhage
later discussion) as needed. A 500–750 mg/kg dose of
Cephalohematoma intravenous immune globulin (IVIG) given to the in-
Extensive bruising fant as soon after delivery as the diagnosis is made has
Central nervous system hemorrhage been shown to decrease the need for exchange transfu-
b. Polycythemia sion. Ongoing hemolysis will still occur until all mater-
c. Exaggerated enterohepatic circulation of bilirubin nal antibody is gone; therefore, these infants need to be
Gastrointestinal tract obstruction followed carefully over the first 2 months of life for de-
Functional ileus velopment of anemia severe enough to require transfu-
sion. The role of erythropoietin therapy in treating late
Decreased rate of conjugation anemia is under investigation.
(Unconjugated bilirubin elevated, reticulocyte count normal.)
Physiologic jaundice
2. Nonimmune hemolysis (Coombs’ test-nega-
Crigler-Najjar syndrome tive)—Hereditary spherocytosis is the most common
Type I glucuronyl transferase deficiency, autosomal- red cell membrane defect, resulting in hemolysis be-
recessive cause of decreased red cell deformability. These infants
Type II glucuronyl transferase deficiency, autosomal- may have hyperbilirubinemia severe enough to require
dominant exchange transfusion. Mild to moderate splenomegaly
Gilbert syndrome may be present. Diagnosis is suspected by peripheral
?Hypothyroidism blood smear and confirmed by red cell osmotic fragility
study. A family history of anemia, jaundice, and gall-
stones may be elicited.
1. Antibody-mediated hemolysis (Coombs’ test- G6PD deficiency is the most common red cell en-
positive)—ABO blood group incompatibility is com- zyme defect resulting in hemolysis and should be sus-
mon, usually not severe, and can accompany any preg- pected in a male (it is X-linked) of African, Mediter-
nancy in a type O mother. The severity is unpredictable ranean, or Asian descent, particularly when the onset of
because of variability in the amount of naturally occur- jaundice is later than usual. The importance of this en-
ring anti-A or anti-B IgG antibodies in the mother. Al- zyme deficiency in cases of severe neonatal jaundice has
though 20% of pregnancies are the appropriate “set- likely been underestimated. In most cases, no triggering
ups” for ABO incompatibility (mother O, baby A or agent is found, although those infants who develop se-
B), only about 33% of such infants are Coombs’ test- vere jaundice with G6PD deficiency also are found to
positive and only about 20% of these develop excessive have Gilbert syndrome.
jaundice. In addition to hyperbilirubinemia in the first 3. Nonhemolytic increased bilirubin production—
days of life, these infants may develop a significant ane- Enclosed hemorrhage, such as cephalohematoma, in-
14 / CHAPTER 1

tracranial hemorrhage, or extensive bruising in the skin, dice that requires treatment—is not physiologic and
can lead to jaundice as the red blood cells are broken must be evaluated further (see later discussion).
down and removed. Polycythemia leads to jaundice by 2. High altitude—Infants at 3100 m (10,000 ft) have
increased red cell mass, with increased numbers of cells twice the frequency of bilirubin > 12 mg/dL
reaching senescence daily. Ileus, either paralytic or me- (206 mmol/L) as infants at 1600 m (5200 ft) and four
chanical, related to a bowel obstruction, leads to hyper- times that of infants at sea level: 39% versus 16% ver-
bilirubinemia secondary to increased enterohepatic cir- sus 8%, respectively. Possible mechanisms include in-
culation. creased bilirubin production secondary to increased
hematocrit and decreased clearance caused by hypox-
B. DECREASED RATE OF CONJUGATION emia.
1. UDPGT deficiency [Crigler–Najjar syndrome 3. Racial differences—Asians are more likely than
type I (complete deficiency, autosomal recessive) whites or blacks to have a bilirubin level > 12 mg/dL
and type II (partial deficiency, autosomal domi- (206 mmol/L): 23% versus 10–13% versus 4%, respec-
nant)]—These syndromes result from a mutation in tively.
the exon or encoding region of the gene that codes for
the enzyme UDPGT, resulting in complete absence or 4. Prematurity—Premature infants frequently have
nearly complete absence of the enzyme. Both are rare poor enteral intake, delayed stooling, and increased en-
and result in severe unconjugated hyperbilirubinemia, terohepatic circulation. Even at 37 weeks’ gestation,
bilirubin encephalopathy, and death without therapy. they are four times more likely than at 40 weeks to have
In type II, the enzyme can be induced with phenobar- a bilirubin > 13 mg/dL (224 mmol/L).
bital, lowering bilirubin levels 30–80%. There is no 5. Breast feeding and jaundice—Two syndromes of
cure, although phototherapy and hepatic transplanta- jaundice are associated with breast feeding: breast milk
tion prolong survival in type I. jaundice and breast feeding-associated jaundice (“lack-
of-breast-milk jaundice”).
2. Gilbert syndrome—This syndrome is a mild auto- a. Breast milk jaundice—This uncommon syn-
somal dominant disorder affecting 6% of the popula- drome of prolonged unconjugated hyperbilirubinemia
tion and is characterized by decreased hepatic UDPGT is believed to be caused by a prolonged increased en-
levels, resulting from a genetic variant of polymorphism terohepatic circulation of bilirubin in some breast-fed
in the promoter region (a noncoding area that regulates infants, perhaps related to increased free fatty acids in
the amount of structurally normal enzyme produced) of the milk. Homozygosity for the Gilbert syndrome
the UDPGT gene. Affected individuals have a greater 7/7 promoter genotype may also be involved. The pres-
propensity in the presence of other icterogenic factors ence of moderate unconjugated hyperbilirubinemia for
such as G6PD deficiency, hereditary spherocytosis, or 6–8 weeks in a thriving infant without evidence for he-
other factors that increase bilirubin production to de- molysis, hypothyroidism, or other disease strongly sug-
velop significant hyperbilirubinemia. They may also be gests this diagnosis.
more likely to manifest prolonged jaundice.
b. Breast feeding-associated jaundice—This com-
mon entity is also known as “lack-of-breast-milk jaun-
C. HYPERBILIRUBINEMIA CAUSED BY UNKNOWN dice.” Breast-fed infants have a higher incidence (9%)
OR MULTIPLE FACTORS of unconjugated serum bilirubin levels > 13 mg/dL
1. Physiologic jaundice—The contributing factors to (224 mmol/L) than formula-fed infants (2%) and
physiologic jaundice include UDPGT inactivity at are more likely to have bilirubin > 15 mg/dL
birth, a relatively high red cell mass even in the non- (258 mmol/L) than formula-fed infants: 2% versus
polycythemic neonate, and an absence of intestinal 0.3%. The pathogenesis appears to be decreased enteral
flora, with initially slow intestinal motility leading to an intake and increased enterohepatic circulation. No in-
active enterohepatic circulation of bilirubin. For jaun- crease in bilirubin production is seen, as measured by
dice to be physiologic rather than pathologic, the fol- carbon monoxide exhalation. Although rarely severe
lowing criteria should be satisfied: (1) clinical jaundice enough to result in bilirubin encephalopathy, nearly
appears after 24 hours of age; (2) total bilirubin rises by 100% of the infants with kernicterus reported to the
less than 5 mg/dL (86 mmol/L) per day; (3) peak registry were breast-fed, and in 50% of them breast
bilirubin occurs at 3–5 days of age, with a total biliru- feeding was the only known risk factor. Jaundice
bin of no more than 15 mg/dL (258 mmol/L); and should be considered a possible sign of failure to estab-
(4) clinical jaundice is resolved by 1 week in the full- lish an adequate milk supply and should prompt spe-
term infant and by 2 weeks in the preterm infant. Hy- cific inquiries into this possibility (Table 1–9). If intake
perbilirubinemia outside of these parameters—or jaun- is inadequate, the infant should receive supplementa-
 THE NEWBORN INFANT / 15

Table 1–9. Signs of inadequate breast clinical jaundice on the first day of life or who develop
milk intake. excessive jaundice require evaluation. The minimal
evaluation consists of a feeding and elimination history,
Weight loss of > 8–10% from birth weight (and comparison with birth weight), examina-
Fewer than six noticeably wet diapers per day tion for any source of excessive heme breakdown, and
Fewer than four stools per day laboratory evaluation for blood type, Coombs’ testing,
Nursing fewer than eight times per 24 h for at least 10 min complete blood count (CBC) with smear, and total
each feed bilirubin level. A G6PD test should be considered if the
infant is a male of African, Asian, or Mediterranean
racial background, particularly if the jaundice presents
later than usual. A fractionated bilirubin level should be
tion with formula if needed, and the mother should be obtained if the infant appears acutely ill, if jaundice is
instructed to nurse more frequently and to pump her prolonged, or if the infant has dark urine with light
breasts with an electric breast pump every 2 hours to stools.
enhance milk production. A consultation with a certi- Because of large interlaboratory variability, serial
fied lactation specialist should be considered, because bilirubin levels should be obtained from a single labora-
many physicians feel inadequately prepared to handle tory whenever possible to make interpretation of serial
these situations. Because hospital discharge of normal measurements more accurate.
newborns occurs before the milk supply is established, a
follow-up visit 2–3 days after discharge is of obvious Treatment of Hyperbilirubinemia
importance.
These two entities may sometimes overlap in the A. PROTOPORPHYRINS
same infant, because prolonged jaundice is common in Tin and zinc protoporphyrin or mesoporphyrin (Sn-
breast-fed infants (20–30%), and high bilirubin levels PP, Zn-PP; Sn-MP, Zn-MP) are inhibitors of heme
in many of these infants with high initial levels also per- oxygenase, the enzyme that begins the catabolism of
sist longest. heme (iron protoporphyrin). Studies are underway in-
volving a single injection of these substances shortly
D. PROLONGED HYPERBILIRUBINEMIA after birth to prevent the formation of bilirubin. Al-
Causes of prolonged unconjugated hyperbilirubinemia though early results are promising, these drugs are still
include hemolytic disease, breast milk jaundice, experimental in the United States.
Crigler–Najjar or Gilbert syndrome, bowel obstruction,
and congenital hypothyroidism. Galactosemia generally B. PHOTOTHERAPY
presents with hepatomegaly in an ill-appearing, often Phototherapy is used most commonly, because it is rel-
septic infant, and the hyperbilirubinemia is usually atively noninvasive and safe. Light at a wavelength ab-
mixed. sorbed by bilirubin (blue or white spectrum) is used.
The unconjugated bilirubin in the skin is converted by
such light to a stereoisomer compound that is water-
Evaluation of Hyperbilirubinemia soluble and able to be excreted in the bile without con-
Because most newborns are discharged at 24–36 hours jugation. A minimum of 10–14 mW/cm2 irradiance is
of age prior to establishing a good milk supply or show- required, and efficacy is dose-dependent. The dose can
ing the extent of their jaundice, a predischarge bilirubin be raised by increasing the body surface area exposed to
measurement, either transcutaneous or drawn with the light and by moving the lights closer to the baby.
the newborn genetic screen, may help predict which in- Fiberoptic blankets are effective, but are inadequate
fants are at risk for severe hyperbilirubinemia. Clinical alone for full-term infants. The infant’s eyes should be
jaundice appears at a bilirubin level of 5 mg/dL shielded from the light to prevent damage to retinal
(86 mmol/L) and appears first on the head, progressing cells. A frequent side effect of phototherapy is diarrhea,
down the chest and abdomen as the level increases. By which is managed by feeding a non-lactose-containing
the time jaundice is noted on the distal extremities, the formula for the duration of the treatment.
level is likely to be at least 15 mg/dL (258 mmol/L). Phototherapy is started when the bilirubin level is
When checking serum bilirubin levels, the level should approximately 3–5 mg/dL (52–86 mmol/L) lower than
be assessed based on the age in hours at which the sam- the exchange level for that infant (eg, at levels of
ple was obtained. Infants with a total serum bilirubin 15–18 mg/dL [258–310 mmol/L] for a full-term in-
level greater than the 95th percentile for age in hours fant), depending also on the infant’s age. Guidelines for
have a 40% risk of developing subsequent significant the use of phototherapy in the full-term infant with and
hyperbilirubinemia (Figure 1–2). Infants who develop without ABO incompatibility are shown in Tables
16 / CHAPTER 1

25

20
High risk zone
95th percentile
Total serum bilirubin (mg/dL)

entile
75th perc
15 n e
zo
isk
ter
dia rcentile
me zo
ne 40th pe
er k
h int e ris
Hig iat
ed
rm
10 nte
wi
Lo

Low risk zone

5

0
0 12 24 36 48 60 72 84 96 108 120 132 144 156 168
Age (h)

Figure 1–2. Risk designation of full-term and near-term newborns based on their hour-specific bilirubin values.
(Reproduced, with permission, from Bhutani VK et al: Predictive ability of a predischarge hour-specific serum bilirubin test
for subsequent significant hyperbilirubinemia in healthy term and near-term newborns. Pediatrics 1999;103:6.)

1–10 and 1–11. Although phototherapy has been

shown to decrease the likelihood of exchange transfu-
sion, the long-term benefits of its use in infants with
less severe jaundice are unknown. Table 1–10. Guidelines for treatment
C. EXCHANGE TRANSFUSION of the full-term infant with ABO blood
Double-volume exchange transfusion (approximately group incompatibility.
160–200 mL/kg body weight) remains necessary in
some cases of hemolysis resulting from Rh isoimmu- Phototherapy if–
nization, ABO incompatibility, or hereditary spherocy- Bilirubin ≥ 10 mg/dL at < 12 h
tosis. In addition to decreasing the bilirubin level by ap- Bilirubin ≥ 14 mg/dL at 12–24 h
proximately 50% acutely, the exchange also removes Bilirubin ≥ 15 mg/dL at > 24 h
nearly 80% of the sensitized or abnormal red blood Consider IVIG if hemoglobin is ≤ 13 g/dL and despite ≥ 4 h of
cells and offending antibody so that ongoing hemolysis phototherapy:
will be decreased. The procedure is invasive and not Bilirubin ≥ 12 mg/dL at < 12 h
without risk. The risk of mortality is 1–5% and is Bilirubin ≥ 16 mg/dL at 12–24 h
greatest in the smallest, most immature, and otherwise Bilirubin ≥ 18 mg/dL at 24–72 h
unstable infants, but sudden death during the proce- IVIG = intravenous immune globulin.
 THE NEWBORN INFANT / 17

Table 1–11. Guidelines for use of phototherapy Stevenson DK et al: Prediction of hyperbilirubinemia in near-term
and term infants. Pediatrics 2001;108:31 [PMID:
in the full-term infant without hemolysis. 11433051].

Bilirubin ≥ 15 mg/dL, age < 2 d: Evaluation, phototherapy

Bilirubin ≥ 18 mg/dL, age > 2–3 d: Evaluation, phototherapy HYPOGLYCEMIA
Bilirubin ≥ 20 mg/dL: Evaluation, phototherapy; consider
interruption of nursing and formula supplementation; have
mother use electric breast pump during interruption of ESSENTIALS OF DIAGNOSIS
breast feeding & TYPICAL FEATURES
Bilirubin ≥ 25 mg/dL: As above, plus consider exchange
transfusion • Defined as blood glucose < 40–45 mg/dL.
• LGA, SGA, preterm, and stressed infants at risk.
• May be asymptomatic.
dure can occur in any infant. Risk of serious complica- • Infants can present with lethargy, poor feeding,
tions such as necrotizing enterocolitis (NEC), infection, irritability, or seizures.
electrolyte disturbances, or thrombocytopenia is 12%.
Because of the rarity of the procedure and its inherent
risk, it should be performed very cautiously, preferably
at a referral center.
For the typical exchange transfusion, the umbilical General Considerations
vein is catheterized, and reconstituted whole blood with Blood glucose concentration in the fetus is approxi-
a hematocrit of approximately 50% is used in aliquots of mately 15 mg/dL less than the maternal glucose con-
8–10 mL per pass. Albumin 1 g/kg can be given first to centration. Glucose concentration normally decreases
aid in binding and removal of bilirubin. Hypocalcemia in the immediate postnatal period, with concentrations
occurs during the procedure because of binding to the below 40–45 mg/dL being considered indicative of hy-
citrate-phosphate-dextrose anticoagulant and needs to poglycemia. By 3 hours, the glucose concentration in
be corrected periodically. Hypoglycemia is common fol- normal full-term babies stabilizes between 50 and
lowing the procedure and requires close monitoring. 80 mg/dL. After the first few hours of life, concentra-
Thrombocytopenia occurs because of the removal of tions below 40–45 mg/dL should be considered abnor-
platelets. The entire procedure should take 1–2 hours mal. The two most commonly encountered groups of
and should be performed using aseptic technique. full-term newborn infants at high risk for neonatal hy-
poglycemia are IDMs and IUGR infants.
American Academy of Pediatrics Subcommittee on Neonatal Hy-
perbilirubinemia: Neonatal jaundice and kernicterus. Pedi-
atrics 2001;108:763 [PMID: 11533348]. Infants of Diabetic Mothers
Davidson L, Thilo E: How to make kernicterus a never event. Neo-
reviews 2003;4:e308.
The IDM has abundant glucose stores in the form of
glycogen and fat but develops hypoglycemia because of
Dennery PA et al: Neonatal hyperbilirubinemia. N Engl J Med
2001;344:581 [PMID: 11207355]. hyperinsulinemia induced by maternal and fetal hyper-
Gottstein R, Cooke RWI: Systematic review of intravenous immu-
glycemia. Other tissues also grow abnormally in utero,
noglobulin in hemolytic disease of the newborn. Arch Dis probably as a consequence of increased flow of nutri-
Child Fetal Neonatal Ed 2003;88:F6 [PMID: 12496219]. ents from the maternal circulation. The result is a
Gourley GR: Breast feeding, diet, and neonatal hyperbilirubinemia. macrosomic infant who is at increased risk for trauma
Neoreviews 2000;1:e25. during delivery. Other problems related to the in utero
Hammerman C, Kaplan M: Recent developments in the manage- metabolic environment include a cardiomyopathy
ment of neonatal hyperbilirubinemia. Neoreviews 2000; (asymmetrical septal hypertrophy), which can present
1:e19. as a murmur with or without cardiac failure and respi-
Johnson LH, Bhutani VK: System-based approach to management ratory distress, and, more rarely, microcolon, which
of neonatal jaundice and prevention of kernicterus. J Pediatr presents as low intestinal obstruction. Infants whose
2002;140:396 [PMID: 12006952].
mothers have diabetes at conception are also at in-
Kaplan M et al: Bilirubin genetics for the nongeneticist: Hereditary
defects of neonatal bilirubin conjugation. Pediatrics
creased risk for congenital anomalies probably related
2003;111:886 [PMID: 12671128]. to first-trimester glucose control. Other neonatal prob-
Newman TB et al: Infants with bilirubin levels of 30 mg/dL or lems include a hypercoagulable state and polycythemia,
more in a large managed care organization. Pediatrics a combination that predisposes the infant to large ve-
2003;111:1303 [PMID: 12777545]. nous thromboses (eg, renal vein thrombosis). Finally,
18 / CHAPTER 1

these infants are somewhat immature for their gesta- the less common causes of hypoglycemia. This work-up
tional age and are at increased risk for hyaline mem- should include evaluation for inborn errors of metabo-
brane disease, hypocalcemia, and hyperbilirubinemia. lism, hyperinsulinemic states, and deficiencies of coun-
terregulatory hormones.
Intrauterine Growth Restricted Infants
Treatment
The IUGR infant has reduced glucose stores in the
form of glycogen and body fat and therefore is prone to Therapy is based on provision of glucose either enter-
hypoglycemia despite relatively appropriate endocrine ally or intravenously. Table 1–12 presents suggested
adjustments at birth. In addition to hypoglycemia, treatment guidelines. In hyperinsulinemic states, bo-
marked hyperglycemia and a transient diabetes melli- luses of glucose should be avoided and a higher glucose
tus-like syndrome may occasionally develop, particu- infusion rate used. After initial correction with a bolus
larly in the very premature SGA infant. These problems of D10W, 2 mL/kg, glucose infusion should be in-
can usually be handled by adjusting glucose intake, creased gradually as needed from a starting rate of
though insulin is sometimes needed transiently. 6 mg/kg/min. Finally, in both IDMs and IUGR in-
fants, those with high hematocrits and hypoglycemia
are most likely to show clinical signs of hypoglycemia.
Other Causes of Hypoglycemia In such infants, both the hypoglycemia and the poly-
Hypoglycemia occurs with disorders associated with cythemia should be treated—with IV glucose infusion
islet cell hyperplasia (Beckwith–Wiedemann syndrome and partial exchange transfusion, respectively.
[macroglossia, omphalocele, macrosomia], erythro-
blastosis fetalis, nesidioblastosis], inborn errors of me-
tabolism [glycogen storage disease, galactosemia], and
endocrine disorders [panhypopituitarism, other defi- Table 1–12. Hypoglycemia: suggested
ciencies of counterregulatory hormones]). It may also therapeutic regimens.
occur as a complication of birth asphyxia, hypoxia, or
other stresses, including bacterial and viral sepsis. Pre- Presence of
mature infants are also at risk for hypoglycemia because Screening Testa Symptoms Action
of decreased glycogen stores.
20–45 mg/dL No symptoms Draw blood glucose;b
of hypogly- if the infant is alert and
Clinical Findings cemia vigorous, feed; follow
The signs of hypoglycemia in the newborn infant are with frequent glucose
relatively nonspecific and may be subtle: lethargy, poor monitoring. If the baby
continues to have blood
feeding, irritability, tremulousness, jitteriness, apnea,
glucose < 40 mg/dL or
and seizures. The disorder is most severe and resistant is unable to feed, pro-
to treatment if due to hyperinsulinemia. Cardiac failure vide intravenous glu-
may occur in severe cases, particularly in IDMs with cose at 6 mg/kg/min
cardiomyopathy. Infants with hyperinsulinemic states (D10W at 3.6 mL/kg/h).
can experience the onset of hypoglycemia very early
(within the first 30–60 minutes of life). < 45 mg/dL Symptoms of Draw blood glucose;b
Blood glucose can be measured by heelstick using a hypoglycemia provide bolus of D10W
bedside glucometer. All infants at risk should be present (2 mL/kg) followed by
screened, including IDMs, IUGR infants, premature an infusion of 6 mg/kg/
min (3.6 mL/kg/h).
infants, and any infant with symptoms that could be
due to hypoglycemia. All low or borderline values < 20 mg/dL With or without Draw blood glucose;b
should be confirmed by direct measurement of blood symptoms of provide bolus of D10W
glucose concentration determined in the laboratory. It hypoglycemia followed by an infusion
is important to continue surveillance of glucose concen- of 6 mg/kg/min. If intra-
tration until the baby has been on full enteral feedings venous access cannot
without intravenous (IV) supplementation for a be obtained immedi-
24-hour period. Relapse of hypoglycemia thereafter is ately, an umbilical vein
unlikely. line should be used.
Infants with hypoglycemia requiring IV glucose in- a
Rapid bedside determination.
b
fusions for more than 5 days should be evaluated for Laboratory confirmation.
 THE NEWBORN INFANT / 19

Prognosis Table 1–13. Causes of respiratory distress

The prognosis of hypoglycemia is good if therapy is in the newborn.
prompt. CNS sequelae are seen in infants with neonatal
seizures resulting from hypoglycemia and are more Noncardiopulmonary
likely in neonates with persistent hyperinsulinemic hy- Hypothermia or hyperthermia
poglycemia. Hypoglycemia
Polycythemia
Cornblath M: A personal view of a bittersweet journey, Neoreviews
Metabolic acidosis
2003;4:e2. Drug intoxications or withdrawal
Cornblath M et al: Controversies regarding definition of neonatal
Insult to the central nervous system
hypoglycemia: Suggested operational thresholds. Pediatrics Asphyxia
2000;105:1141 [PMID: 10790476]. Hemorrhage
Cornblath M, Ichord R: Hypoglycemia in the neonate. Semin Peri- Neuromuscular disease
natol 2000;24:136 [PMID: 10805169]. Phrenic nerve injury
Cowett RM: Neonatal care of the infant of the diabetic mother. Asphyxiating thoracic dystrophy
Neoreviews 2002;3:e190. Cardiovascular
Menni F et al: Neurologic outcomes of 90 neonates and infants Left-sided outflow tract obstruction
with persistent hyperinsulinemic hypoglycemia. Pediatrics Hypoplastic left heart
2001;107:476 [PMID: 11230585]. Aortic stenosis
Sunehag AL, Haymond MW: Glucose extremes in newborn in- Coarctation of the aorta
fants. Clin Perinatol 2002;29:245 [PMID: 12168240]. Cyanotic lesions
Transposition of the great vessels
Total anomalous pulmonary venous return
RESPIRATORY DISTRESS Tricuspid atresia
IN THE TERM NEWBORN INFANT Right-sided outflow obstruction
Pulmonary
Upper airway obstruction
ESSENTIALS OF DIAGNOSIS Choanal atresia
& TYPICAL FEATURES Vocal cord paralysis
Lingual thyroid
Meconium aspiration
• Tachypnea, respiratory rate > 60 breaths/min. Clear fluid aspiration
• Retractions (intercostal, sternal). Transient tachypnea
• Expiratory grunting. Pneumonia
Pulmonary hypoplasia
• Cyanosis on room air.
Hyaline membrane disease
Pneumothorax
Pleural effusions
Mass lesions
Lobar emphysema
General Considerations Cystic adenomatoid malformation
Respiratory distress is among the most common symp- Reproduced, with permission, from Rosenberg AA: Neonatal
tom complexes seen in the newborn infant. It may re- adaptation. In Gabbe SG et al (eds): Obstetrics: Normal and Prob-
sult from both noncardiopulmonary and cardiopulmo- lem Pregnancies. Churchill Livingstone, 1996.
nary causes (Table 1–13). Chest radiography, arterial
blood gases, and pulse oximetry are useful in assessing
both the cause and the severity of the problem. It is im-
portant to consider the noncardiopulmonary causes aspiration syndromes, congenital pneumonia, and air
listed in Table 1–13 because the natural tendency is to leaks.
focus on the heart and lungs. Most of the noncardio-
pulmonary causes can be ruled out by the history, phys- A. TRANSIENT TACHYPNEA
ical examination, and a few simple laboratory tests. The (RETAINED FETAL LUNG FLUID)
evaluation of cardiovascular disorders is discussed in a Respiratory distress is typically present from birth, usu-
subsequent section. ally associated with a mild to moderate oxygen require-
The most common pulmonary causes of respiratory ment (25–50% O2). The infant may be full-term or
distress in the full-term infant are transient tachypnea, near-term, nonasphyxiated, and born following a short
20 / CHAPTER 1

labor or cesarean section without labor. Chest radi- certainty, all infants with respiratory distress should re-
ograph shows perihilar streaking and fluid in interlobar ceive a blood culture and broad-spectrum antibiotic
fissures. Resolution usually occurs within 12–24 hours. therapy (ampicillin 100 mg/kg in two divided doses
and gentamicin 4 mg/kg q24h or 2.5 mg/kg q12h)
B. ASPIRATION SYNDROMES until the diagnosis of a bacterial infection can be ruled
The infant is typically full-term or near-term, fre- out.
quently with some fetal distress prior to delivery or de-
pression at delivery. Blood or meconium is usually pre- D. SPONTANEOUS PNEUMOTHORAX
sent in the amniotic fluid, but occasionally the fluid is Respiratory distress (primarily tachypnea) is present
clear. Respiratory distress is present from birth, in many from birth, typically not severe, and requires mild to
cases manifested by a barrel chest appearance and coarse moderate supplemental O2. Breath sounds may be de-
breath sounds. An increasing O2 need from pneumoni- creased on the affected side; heart tones may be shifted
tis may require intubation and ventilation. Chest radi- toward the opposite side and may be distant. Chest ra-
ograph shows coarse irregular infiltrates, hyperexpan- diograph will show pneumothorax or pneumomedi-
sion, and, in the worst cases, lobar consolidation. In astinum.
some cases, secondary surfactant deficiency can ensue, This entity occurs in 1% of all deliveries. The risk is
with progression to a diffuse homogeneous infiltrate increased by manipulations such as positive-pressure
pattern. ventilation in the delivery room. Treatment usually
When the amniotic fluid contains meconium or consists of supplemental O2 and watchful waiting.
blood, suctioning of the infant’s mouth and nose as the Breathing 100% O2 for a few hours may accelerate re-
head is delivered and before delivery of the chest is rec- absorption of the extrapulmonary gas by creating a dif-
ommended to prevent aspiration of these secretions fusion gradient for nitrogen across the surface of the
with the onset of breathing. If the infant is not vigorous lung (nitrogen washout technique). This is effective
at birth, suctioning of the trachea under direct vision is only if the infant was breathing room air or O2 at low
recommended, especially before commencing resuscita- concentration at the time of the pneumothorax.
tion with positive-pressure ventilation. Although these Drainage by needle thoracentesis or tube thoracostomy
procedures are recommended, they will not prevent all is occasionally required. A small increased risk of renal
cases of meconium or blood aspiration. Aspiration abnormalities is associated with spontaneous pneu-
often occurs in utero as the stressed infant gasps. Babies mothorax; therefore, a careful physical examination of
with aspirations are at risk of air leak (pneumothorax) the kidneys and observation of urine output are indi-
because of uneven aeration with segmental overdisten- cated. If pulmonary hypoplasia with pneumothorax is
tion and are at risk for persistent pulmonary hyperten- suspected, renal ultrasound would also be indicated.
sion (see section on Cardiac Problems). Standard treat-
ment includes ventilatory support, antibiotics, and E. OTHER PULMONARY CAUSES
pressor support of systemic blood pressure. The other pulmonary causes of respiratory distress are
fairly rare. Bilateral choanal atresia should be suspected
C. CONGENITAL PNEUMONIA if there is no air movement when the infant breathes
Infants may be of any gestational age, with or without a through the nose. These infants present in the delivery
maternal history of prolonged rupture of the mem- room with good color and heart rate while crying but
branes, chorioamnionitis, or maternal antibiotic admin- become cyanotic and bradycardiac when they quiet
istration. Onset of respiratory distress may be at birth down and resume normal nasal breathing. Other causes
or may be delayed for several hours. Chest radiograph of upper airway obstruction are usually characterized by
may resemble that of retained lung fluid or hyaline some degree of stridor or poor air movement despite
membrane disease; rarely, there may be a lobar infil- good respiratory effort. Pleural effusions can be sus-
trate. pected in hydropic infants (eg, those with erythroblas-
The lungs are the most common site of infection in tosis fetalis or nonimmune hydrops). Space-occupying
the neonate. Most commonly, infections ascend from lesions cause a shift of the mediastinum and asymmetri-
the genital tract before or during labor, with the vaginal cal breath sounds and would be apparent on chest radi-
or rectal flora the most likely infectious agents (group B ograph.
streptococci, Escherichia coli, Klebsiella). Shock, poor
perfusion, absolute neutropenia (< 2000/mL), and an Treatment
elevated C reactive protein provide corroborating evi-
dence for pneumonia. Gram stain of tracheal aspirate Whatever the cause, the cornerstone of treatment of
may be helpful. Because no signs or laboratory findings neonatal respiratory distress is provision of adequate
can confirm the presence or absence of pneumonia with supplemental oxygen to maintain a PaO2 of 60–70 mm
 THE NEWBORN INFANT / 21

Hg and a saturation by pulse oximetry (SpO2) of HEART MURMURS (SEE ALSO SECTION
92–96%. PaO2 levels less than 50 mm Hg are associated ON CARDIAC PROBLEMS)
with pulmonary vasoconstriction, which can exacerbate
hypoxemia, whereas those greater than 100 mm Hg Heart murmurs are common in the first days of life and
may increase the risk of oxygen toxicity without addi- do not usually signify structural heart problems. If a
tional benefit. Oxygen should be warmed, humidified, murmur is present at birth, however, it should be con-
and delivered through an air blender. Concentration sidered a valvular problem until proved otherwise be-
should be measured with a calibrated oxygen analyzer. cause the common benign transitional murmurs (eg,
An umbilical or peripheral arterial line should be con- patent ductus arteriosus) are not audible until minutes
sidered in any infant requiring more than 45% FiO2 by to hours after birth.
4–6 hours of life to allow frequent blood gas determina- If an infant is pink, well-perfused, and in no respira-
tions. Noninvasive monitoring with a pulse oximeter tory distress and has palpable and symmetrical pulses
should be used. (right brachial pulse no stronger than the femoral
Other supportive treatment includes IV provision of pulse), the murmur is most likely transitional. Transi-
glucose and water. Unless infection can be unequivo- tional murmurs are soft (grade 1–3/6), heard at the left
cally ruled out, blood cultures should be obtained and upper to midsternal border, and generally loudest dur-
broad-spectrum antibiotics started. Volume expansion ing the first 24 hours. If the murmur persists beyond
(normal saline) can be given in infusions of 10 mL/kg 24 hours, blood pressure in the right arm and a leg
over 30 minutes for low blood pressure, poor perfu- should be determined. If there is a difference of more
sion, and metabolic acidosis. Sodium bicarbonate than 15 mm Hg (arm > leg) or if the pulses in the lower
(1–2 mEq/kg) is indicated for treatment of docu- extremities are difficult to appreciate, cardiology con-
mented metabolic acidosis that has not responded to sultation should be arranged to evaluate for coarctation
oxygen, ventilation, and volume. Specific work-up of the aorta. If there is no difference, the infant can be
should be pursued as indicated by the history and phys- discharged home with follow-up in 2–3 days for auscul-
ical findings. In most cases, a chest radiographic study, tation and evaluation for signs of congestive failure. If
blood gas measurements, CBC, and blood glucose signs of failure or cyanosis are present, the infant should
allow a diagnosis. be referred for evaluation without delay. If the murmur
Intubation and ventilation should be undertaken for persists without these signs, the infant can be referred
signs of respiratory failure (PaO2 < 60 mm Hg in for elective evaluation at age 2–4 weeks. Some centers
60–80% FiO2, PaCO2 > 60 mm Hg, or repeated apnea). now recommend routine pulse oximetry screening in
Peak pressures should be adequate to produce chest the nursery to identify infants with congenital heart dis-
wall expansion and audible breath sounds (usually ease, with a saturation < 95% at sea level triggering an
18–24 cm H2O). Positive end-expiratory pressure echocardiogram. Further studies will need to be per-
(4–6 cm H2O) should also be used. Ventilation rates of formed to document the accuracy, specificity, and cost-
20–50 breaths/min are usually required. The goal is to effectiveness of this technique.
maintain a PaO2 of 60–70 mm Hg and a PaCO2 of
45–55 mm Hg. Koppel RI et al: Effectiveness of pulse oximetry screening for con-
genital heart disease in asymptomatic newborns. Pediatrics
2003;111:451 [PMID: 12612220].
Prognosis Reich JD et al: The use of pulse oximetry to detect congenital heart
disease. J Pediatr 2003;142:268 [PMID: 12640374].
Most of the respiratory conditions affecting the full-
term infant are acute and resolve in the first several
days. Meconium aspiration syndrome and congenital BIRTH TRAUMA
pneumonia are associated with significant long-term
Most birth trauma is associated with difficult delivery,
pulmonary morbidity (chronic lung disease) and mor-
particularly with a large infant, abnormal position, or
tality (approximately 10–20%). Mortality rates in these
fetal distress requiring rapid extraction. The most com-
disorders have been reduced by use of high-frequency
mon injuries are soft tissue bruising, fractures (clavicle,
ventilation, inhaled nitric oxide to treat pulmonary hy-
humerus, or femur), and cervical plexus palsies, al-
pertension, and extracorporeal membrane oxygenation
though skull fractures, intracranial hemorrhage (pri-
(ECMO).
marily subdural and subarachnoid), and cervical spinal
cord injuries can also occur.
Ghidini A, Spong CY: Severe meconium aspiration syndrome is Fractures are often diagnosed by the obstetrician,
not caused by aspiration of meconium. Am J Obstet Gynecol who may feel and hear a snap during delivery. Clavicu-
2001;185:931 [PMID: 11641681]. lar fractures may cause decreased spontaneous move-
22 / CHAPTER 1

ment of the arm, with tenderness and crepitus over the pressure of the baby’s head against the mother’s
area. Humeral or femoral fractures may cause tender- sacrum. The infant has asymmetrical mouth move-
ness and swelling over the shaft with a diaphyseal frac- ments and eye closure with poor movement on the af-
ture, with limited spontaneous extremity motion in all fected side. Most cases resolve spontaneously within a
cases. Epiphyseal fractures are harder to diagnose radio- few days to 3 weeks.
graphically owing to the cartilaginous nature of the epi- Subgaleal hemorrhage into the large potential space
physis. After 8–10 days, callus appears and is visible on under the scalp (Figure 1–3) is associated with difficult
radiographs. Treatment in all cases is gentle handling, vaginal deliveries and repeated attempts at vacuum ex-
with immobilization for 8–10 days: the humerus traction. It can lead to hypovolemic shock and death
against the chest with elbow flexed; the femur with a from ongoing blood loss and severe coagulopathy trig-
posterior splint from below the knee to the buttock. gered by both consumption of clotting factors and re-
Brachial plexus injuries may result from traction as lease of thromboplastin from accompanying brain in-
the head is pulled away from the shoulder during deliv- jury. This is an emergency requiring rapid replacement
ery. Injury to the C5-6 roots is most common and re- of blood and clotting factors.
sults in Erb–Duchenne paralysis. The arm is limp, ad-
ducted and internally rotated, extended and pronated at
the elbow, and flexed at the wrist (so-called waiter’s tip Gardella C et al: The effect of sequential use of vacuum and forceps
posture). Grasp is present. If the lower nerve roots for assisted vaginal delivery on neonatal and maternal out-
comes. Am J Obstet Gynecol 2001;185:896 [PMID:
(C8-T1) are involved, the hand is flaccid (Klumpke 11641674].
palsy). Isolated involvement of these roots is rare. If the Rosenberg AA: Traumatic birth injuries. Neoreviews 2003;4:e270.
entire plexus is injured, the arm and hand are flaccid,
Towner D et al: Effect of mode of delivery in nulliparous women
with an associated sensory deficit. on neonatal intracranial injury. N Engl J Med 1999;341:
Early treatment for brachial plexus injury is conserv- 1709 [PMID: 10580069].
ative, because function usually returns over several
weeks. Referral should be made to a physical therapist
so that the parents can be instructed on range-of-mo- INFANTS OF MOTHERS
tion exercises and splinting and for further evaluation if
needed. Return of function begins in the deltoid and WHO ABUSE DRUGS
biceps, with recovery by 3 months in most cases. The problem of newborn infants born to mothers who
Spinal cord injury can occur at birth, especially in abuse drugs is increasing in all communities. The drugs
difficult breech extractions with hyperextension of the most commonly abused are tobacco, alcohol, mari-
neck, or in midforceps rotations when the body fails to juana, and cocaine. Because these mothers may abuse
turn with the head. Infants are flaccid, quadriplegic, many drugs and give an unreliable history of drug
and without respiratory efforts at birth, although facial usage, it may be difficult to pinpoint which drug is
movements are preserved. The long-term outlook for causing the morbidity seen in a newborn infant. Early
such infants is grim. hospital discharge makes discovery of these infants
Facial nerve palsy is sometimes associated with for- based on physical findings and abnormal behavior
ceps use but more often results from chronic in utero much more difficult.

Caput
Cephalhematoma
Subgaleal hemorrhage

Extradural hemorrhage
Skin
Epicranial
aponeurosis
Figure 1–3. Sites of extracranial
Periosteum bleeding in the newborn. (Adapted
Skull and reproduced, with permission, from
Dura Pape KE, Wigglesworth JS: Haemor-
rhage Ischemia and the Perinatal Brain.
JB Lippincott, 1979.)
 THE NEWBORN INFANT / 23

1. Cocaine ogy, but results will be negative unless the last drug
dose was within a few days before delivery. Meconium
Cocaine is currently the most commonly abused hard can also be tested for illicit drugs and is more likely to
drug, identified in up to 20–40% of infants on urban be positive because the substances accumulate through-
delivery services by anonymous screening of urine or out pregnancy.
meconium; moreover, cocaine is often used in associa-
tion with other drugs. The obstetric effects include ma-
ternal hypertension, decreased uterine blood flow, fetal Treatment
hypoxemia, and uterine contractions. The rates of still- Careful observation of the infant is a requirement. If
birth, placental abruption, and preterm delivery are in- opioid abuse or withdrawal is suspected, the baby is not
creased two- to fourfold over rates for nonusers, and a candidate for early discharge. Supportive treatment
IUGR is increased two- to fourfold over that for includes swaddling the infant and providing a quiet,
nonusers. In high-risk populations (no prenatal care, dimly lighted environment. In general, specific treat-
placental abruptions, and preterm labor), urine toxicol- ment should be avoided unless the infant has severe
ogy screens should be performed in mothers and in- symptoms or excessive weight loss. No single drug has
fants. Analysis of meconium enhances diagnosis by in- been uniformly effective, and the first choice varies
dicating cumulative drug use prior to delivery. among nurseries. The drugs that have been used in-
As with other illegal drugs, cocaine may have long- clude phenobarbital at an initial loading dose of
term neurobehavioral effects, but multiple drug use and 15–20 mg/kg IM, followed by a maintenance dose of
environmental factors preclude assigning specific effects 5 mg/kg/d in two divided doses, usually given orally.
to cocaine with certainty. The risk of SIDS is increased Opioids, diazepam, and clonidine have also been used,
three to seven times over the risk in nonusers (0.5–1% although the present authors prefer phenobarbital for
of exposed infants), but may be lessened by supine in- irritability alone because of its safety and predictability.
fant positioning. If diarrhea and weight loss are prominent findings, or if
adequate control of symptoms has not been achieved,
2. Opioids tincture of opium (25-fold dilution to 0.4 mg/mL mor-
phine equivalent; 0.1 mL/kg qh4 to start) titrated to
improve symptoms or methadone 0.05–0.1 mg/kg
ESSENTIALS OF DIAGNOSIS q6h will be more beneficial than phenobarbital alone.
Treatment can be tapered over several days to a week.
& TYPICAL FEATURES Both handling and procedures in the nursery should be
kept to a minimum. It is also important to review ma-
• Irritability, hyperactivity, incessant hunger and ternal tests for syphilis, HIV, hepatitis B, and gonor-
salivation. rhea as all are common in women who use cocaine or
• Vomiting, diarrhea, excessive weight loss. opiates.
• Tremors, seizures.
• Nasal stuffiness, sneezing. Prognosis
• Often IUGR. These infants demonstrate long-term neurobehavioral
handicaps. However, it is difficult to distinguish the ef-
fects of in utero drug exposure from those of environ-
mental influences during upbringing. Infants of opioid
abusers have a four- to fivefold increased risk of SIDS.
Clinical Findings
The withdrawal signs in infants born to mothers who
are addicted to heroin or who have been in mainte-
3. Alcohol
nance methadone programs are similar. The clinical The legal substances alcohol and tobacco have much
findings in infants born to methadone-maintained greater effects on perinatal outcome than any illicit sub-
mothers may actually be more severe and prolonged stances. Alcohol is the only recreational drug of abuse
than those seen with heroin. Clinical manifestations that is clearly teratogenic and is the most common pre-
begin usually within 1–2 days. The clinical picture is ventable cause of mental retardation. The effects of al-
typical enough to suggest a diagnosis even if a maternal cohol on the fetus and the newborn are roughly propor-
history of drug abuse has not been obtained, although tionate to the degree of ethanol abuse, but there is no
onset may not occur prior to discharge at 24 hours. established safe dose. Fetal growth and development are
Confirmation should be attempted with urine toxicol- adversely affected, and infants can experience with-
24 / CHAPTER 1

Table 1–14. Features observed in fetal alcohol 6. Marijuana

syndrome in the newborn.
Marijuana is the most frequently used illegal drug. It
does not appear to be teratogenic, and although a mild
Craniofacial abstinence-type syndrome has been described, infants
Short palpebral fissures exposed to marijuana in utero rarely require treatment.
Short, upturned nose Some long-term neurodevelopmental problems, partic-
Flat midface ularly disordered sleep patterns, have been noted.
Thin vermillion of upper lip
Flattened philtrum
Growth
Prenatal and postnatal growth deficiency (SGA, failure to 7. Other Drugs
thrive) Drugs and their effects on the newborn should be con-
Central nervous system sidered in two categories. In the first are drugs to which
Microcephaly the fetus is exposed because of the mother’s exposure.
Partial or complete agnesis of the corpus callosum In many cases these are drugs prescribed for therapy of
Optic nerve hypoplasia maternal conditions. The human placenta is relatively
Hypotonia, poor feeding permeable, particularly to lipophilic solutes. Whenever
possible, maternal drug therapy should be postponed
until after the first trimester. Drugs with potential fetal
toxicity include antineoplastics, antithyroid agents,
benzodiazepines, warfarin, lithium, angiotensin-con-
drawal similar to that associated with maternal opioid verting enzyme inhibitors (eg, captopril, enalapril), and
abuse. Features observed are listed in Table 1–14. Clin- immunosuppressants.
ical features of fetal alcohol syndrome (FAS) are often In the second category are drugs the infant acquires
not obvious in the newborn period. from the mother during breast feeding. Most drugs
Children with full-blown FAS demonstrate postna- taken by the mother at this time achieve some concen-
tal growth deficiency and mild to moderate mental re- trations in breast milk, although they usually do not
tardation. Those with lesser effects are at increased risk present a problem to the infant. If the drug is one that
for attention-deficit/hyperactivity disorder and subtle could have adverse effects on the baby, timing breast
developmental delays. feeding to coincide with trough concentrations in the
mother may be useful. The AAP (see second reference
4. Tobacco Smoking in the following list) has reviewed drugs contraindi-
cated in the breast-feeding mother.
Smoking has been shown to have a negative effect on
the growth rate of the fetus. The more the mother
smokes, the greater the degree of IUGR. There is a American Academy of Pediatrics Committee on Drugs. Neonatal
twofold increase in low birth weight even in light drug withdrawal. Pediatrics 1998;101:1079 [PMID:
smokers (< 10 cigarettes/day). More recently, smoking 9614425].
during pregnancy has been associated with mild neu- American Academy of Pediatrics Committee on Drugs: The trans-
rodevelopmental handicaps. The possible effects of fer of drugs and other chemicals into human milk. Pediatrics
2001;108:776 [PMID: 11533352].
multiple drug abuse apply to this category as well, and
American Academy of Pediatrics Committee on Drugs: Use of psy-
the potential interaction of multiple factors on fetal choactive medication during pregnancy and possible effects
growth and development must be considered. on the fetus and newborn. Pediatrics 2000;105:880 [PMID:
10742343].
American Academy of Pediatrics Committee on Substance Abuse
5. Toluene Embryopathy and Committee on Children with Disabilities: Fetal alcohol
Solvent abuse (paint, lacquer, or glue sniffing) is rela- syndrome and alcohol-related neurodevelopmental disorders.
tively common. The active organic solvent in these Pediatrics 2000;106:358 [PMID: 10920168].
agents is toluene. Features attributable to in utero Boyle RJ: Effects of certain prenatal drugs on the fetus and new-
born. Pediatr Rev 2002;23:17 [PMID: 11773589].
toluene exposure include prematurity, IUGR, micro-
Coyle MG et al: Diluted tincture of opium (DTO) and phenobar-
cephaly, craniofacial abnormalities similar to those asso- bital versus DTO alone for neonatal opiate withdrawal in
ciated with in utero alcohol exposure (see Table 1–14), term infants. J Pediatr 2002;140:561 [PMID: 12032522].
nail hypoplasia, and renal anomalies. Long-term effects Frank DA et al: Growth, development, and behavior in early child-
include postnatal growth deficiency and developmental hood following prenatal cocaine exposure. A systematic re-
delay. view. JAMA 2001;285:1613 [PMID: 11268270].
 THE NEWBORN INFANT / 25

Gleason CA: Fetal alcohol exposure: Effects on the developing one twin’s circulation to that of the other (twin–twin
brain. Neoreviews 2001;2:e231. transfusion syndrome). The infant on the venous side
Holmes LB et al: The teratogenicity of anticonvulsant drugs. becomes plethoric and considerably larger than the
N Engl J Med 2001;344:1132 [PMID: 11297704]. smaller anemic twin. Morbidity and mortality rates are
Ito S: Drug therapy for breast-feeding women. N Engl J Med 2000; considerable in twin–twin transfusion syndrome. Dis-
343:118 [PMID: 10891521].
cordance in size—birth weights that are significantly
Johnson K et al: Treatment of neonatal abstinence syndrome. Arch
Dis Child Fetal Neonatal Ed 2003;88:F2 [PMID:
different—can also occur when separate placentas are
12496218]. present. One placenta develops poorly, presumably be-
Singer LT et al: Cognitive and motor outcomes of cocaine-exposed cause of a poor implantation site. In this instance, no
infants. JAMA 2002;287:1852 [PMID: 11960537]. fetal exchange of blood takes place but the growth rates
Sokol RH et al: Fetal alcohol spectrum disorder. JAMA of the two infants are significantly different.
2003;290:2996 [PMID: 14665662].
Thackray HM, Tifft C: Fetal alcohol syndrome. Pediatr Rev 2001;
22:47 [PMID: 11157101]. B. PRETERM DELIVERY
Ventura SJ et al: Trends and variations in smoking in pregnancy Gestation length tends to be inversely related to the
and low birth weight: Evidence from the birth certificate, number of fetuses. The prematurity rate is 5 –10 times
1999–2000. Pediatrics 2003;111:1176 [PMID: 12728134]. that of singletons, with 50% of twins and 90% of
triplets born before 37 weeks. The prematurity rate
MULTIPLE BIRTHS tends to increase the mortality or morbidity rates occur-
ring in twin pregnancies.
Twinning has historically occurred as a demographic
variation in one of 80 pregnancies (1.25%). The inci-
dence of twinning and higher-order multiple births in C. OBSTETRIC COMPLICATIONS
the United States has been increasing as a consequence Polyhydramnios, pregnancy-induced hypertension, pre-
of the increased use of in vitro fertilization and other as- mature rupture of membranes, abnormal fetal presenta-
sisted reproductive technologies. In 1999, twins oc- tions, and prolapsed umbilical cord occur more fre-
curred in 1/43 live births in the United States, with the quently in women with multiple fetuses. In general,
multiple births accounting for 3% of all births. most of the complications can be avoided or minimized
A clear distinction should be made between dizy- by good obstetric management. Multiple pregnancy
gotic (fraternal) and monozygotic (identical) twins. should always be identified prenatally with ultrasound
Race, maternal parity, and maternal age affect the inci- examinations; doing so allows the obstetrician and pe-
dence only of dizygotic twinning. Drugs that induce diatrician or neonatologist to plan management jointly.
ovulation, such as clomiphene citrate and go- The neonatal complications are usually related to pre-
nadotropins, increase the incidence of dizygotic or maturity. Prolongation of pregnancy, therefore, leads to
polyzygotic twinning quite strikingly. Monozygotic a significant reduction in neonatal morbidity.
twinning can be viewed as a birth defect; the incidence Follow-up studies of twin pregnancies have yielded
of malformations is also increased in identical twins and conflicting results. In general, the studies do not suggest
may affect only one of the twins. If a defect is found in that twinning has a significant effect on later develop-
one, the other should be examined carefully for lesser ment, especially if prematurity is excluded as a separate
degrees of the same defect. risk factor.
Examination of the placenta can help establish the
type of twinning: Two amnionic membranes and two
chorionic membranes are found in all cases of dizygotic
Banek CS et al: Long-term neurodevelopmental outcome after in-
twins and in one third of monozygotic twins; a single trauterine treatment for severe twin–twin transfusion syn-
chorionic membrane always indicates monozygotic drome. Am J Obstet Gynecol 2003;188:876 [PMID:
twins. 1272079].
Blondel B, Kaminski M: Trends in the occurrence, determinants
Complications of Multiple Births and consequences of multiple births. Semin Perinatol
2002;26:239 [PMID: 12211614].
A. INTRAUTERINE GROWTH RESTRICTION Mari G et al: Perinatal morbidity and mortality rates in severe
twin–twin transfusion syndrome: Results of the International
There is some degree of IUGR in most multiple preg- Amnioreduction Registry. Am J Obstet Gynecol
nancies after 34 weeks. If prenatal care is good, how- 2001;185:708 [PMID: 11568802].
ever, the growth restriction is rarely significant. There Reynolds MA et al: Trends in multiple births conceived using as-
are two exceptions: The first is the monochorial twin sisted reproductive technology, United States, 1997–2000.
pregnancy in which an arteriovenous shunt occurs from Pediatrics 2003;111:1159 [PMID: 12728130].
26 / CHAPTER 1

Primary Last Onset of

NEONATAL INTENSIVE CARE apnea gasp gasping
6

Gasps/min
4
PERINATAL RESUSCITATION
2 Secondary or
Perinatal resuscitation consists of the steps taken by the terminal apnea
0
obstetrician to support the infant during labor and de-
livery as well as the traditional resuscitative steps taken HEART RATE
by the pediatrician after delivery. Intrapartum support 200
includes maintaining maternal blood pressure with vol-
ume expanders if needed, maternal oxygen therapy, po-

Beats/min
150
sitioning the mother to improve placental perfusion,
readjusting oxytocin infusions or administering a to- 100
colytic if appropriate, minimizing trauma to the infant
(particularly important in infants of very low birth 50 Resuscitation
weight), suctioning the nasopharynx upon delivery of
BLOOD PRESSURE
the head if meconium is present in the amniotic fluid,
obtaining all necessary cord blood samples, and com- 80
pleting an examination of the placenta.
Steps taken by the pediatrician or neonatologist mm Hg 60
focus on temperature support, initiation and mainte-
nance of effective ventilation, maintenance of perfusion 40
and hydration, and glucose regulation.
A number of conditions associated with pregnancy, 20
labor, and delivery place the infant at risk for birth as- Brain damage
phyxia: (1) maternal diseases such as diabetes, preg- 0
nancy-induced hypertension, heart and renal disease, 0 5 10 15 20
and collagen–vascular disease; (2) fetal conditions such Time from onset of asphyxia (min)
as prematurity, multiple births, growth retardation, and
fetal anomalies; and (3) labor and delivery conditions, Figure 1–4. Schematic depiction of changes in rhesus
including fetal distress with or without meconium in monkeys during asphyxia and on resuscitation by posi-
the amniotic fluid, and administration of anesthetics tive-pressure ventilation. (Adapted and reproduced, with
and opioid analgesics. permission, from Dawes GS: Fetal and Neonatal Physiology.
Year Book, 1968.)

Physiology of Birth Asphyxia

Birth asphyxia can be the result of several mechanisms:
(1) acute interruption of umbilical blood flow (eg, pro- organ injury. A cardinal feature of the defense against
lapsed cord with cord compression), (2) premature pla- hypoxia is the underperfusion of certain tissue beds (eg,
cental separation, (3) maternal hypotension or hypoxia, skin, muscle, kidneys, GI tract), which allows the per-
(4) chronic placental insufficiency, and (5) failure to ex- fusion of core organs (ie, heart, brain, adrenals) to be
ecute newborn resuscitation properly. maintained.
The neonatal response to asphyxia follows a pre- The response to resuscitation also follows a pre-
dictable pattern that has been demonstrated in a variety dictable pattern. During the period of primary apnea,
of species (Figure 1–4). The initial response to hypoxia almost any physical stimulus causes the baby to initiate
is an increase in frequency of respiration and a rise in respirations. Infants in secondary apnea require posi-
heart rate and blood pressure. Respirations then cease tive-pressure ventilation. The first sign of recovery is an
(primary apnea) as heart rate and blood pressure begin increase in heart rate, followed by an increase in blood
to fall. This initial period of apnea lasts 30–60 seconds. pressure with improved perfusion. The time required
Gasping respirations (3–6/min) then begin, while heart for rhythmic, spontaneous respirations to occur is re-
rate and blood pressure gradually decline. Secondary or lated to the duration of the secondary apnea. As a
terminal apnea then ensues, with further decline in rough rule, for each 1 minute past the last gasp, 2 min-
heart rate and blood pressure. The longer the duration utes of positive-pressure breathing is required before
of secondary apnea, the greater the risk for hypoxic gasping begins, and 4 minutes is required to reach
 THE NEWBORN INFANT / 27

rhythmic breathing. These times can vary depending A. STEPS IN THE RESUSCITATION (SEE FIGURE 1–5.)
on the degree and duration of intrauterine asphyxia.
1. Dry the infant well, and place him or her under
Not until some time later do spinal and corneal reflexes
the radiant heat source. Do not allow the infant
return. Muscle tone gradually improves over the course
to become hyperthermic.
of several hours.
2. Gently suction the mouth, then the nose.
3. Quickly assess the infant’s condition. The best
Delivery Room Management criteria are the infant’s respiratory effort (apneic,
When asphyxia is anticipated, a resuscitation team of at gasping, regular) and heart rate (> 100 or
least two persons should be present: one to manage the < 100 beats/min). A depressed heart rate—indica-
airway and one to monitor the heartbeat and provide tive of hypoxic myocardial depression—is the sin-
assistance. The necessary equipment and drugs are gle most reliable indicator of the need for resusci-
listed in Table 1–15. tation.
4. Infants who are breathing and have heart rates
over 100 beats/min usually require no further in-
Table 1–15. Equipment for neonatal tervention. Infants with heart rates less than
100 beats/min and apnea or irregular respiratory
resuscitation. efforts should be stimulated vigorously. The
baby’s back should be rubbed with a towel while
Clinical Needs Equipment oxygen is provided near the baby’s face.
Thermoregulation Radiant heat source with platform, mat- 5. If the baby fails to respond to tactile stimulation
tress covered with warm sterile blankets, within a few seconds, begin bag and mask ventila-
servocontrol heating, temperature probe tion, using a soft mask that seals well around the
Airway manage- Suction: Bulb suction, mechanical suc-
mouth and nose. For the initial inflations, pres-
ment tion with sterile catheters (6F, 8F, 10F), sures of 30–40 cm H2O may be necessary to over-
meconium aspirator come surface-active forces in the lungs. Adequacy
Ventilation: Manual infant resuscitation of ventilation is assessed by observing expansion
bag connected to manometer or with of the infant’s chest accompanied by an improve-
a pressure-release valve capable of ment in heart rate, perfusion, and color. After the
delivering 100% oxygen, appropriate first few breaths, lower the peak pressure to
masks for term and preterm infants, 15–20 cm H2O. The baby’s chest movement
oral airways, stethoscope should resemble that of an easy breath rather than
Intubation: Neonatal laryngoscope with a deep sigh. The rate of bagging should be
No. 0 and No. 1 blades; endotracheal 40–60 breaths/min.
tubes (2.5, 3.0, 3.5 mm outer diameter 6. Most neonates can be resuscitated effectively with
with stylet): extra bulbs and batteries a bag and mask. If the infant does not respond to
for laryngoscope; scissors, adhesive bag and mask ventilation, try to reposition the
tape, gloves, end tidal CO2 detection head (slight extension), reapply the mask to
device
achieve a good seal, consider suctioning the
Gastric decom- Nasogastric tube: 8F with 20-mL syringe mouth and the oropharynx, and try ventilating
pression with the mouth open. If the infant does not re-
Administration of Sterile umbilical catheterization tray, um- spond within 30 seconds, intubation is appropri-
drugs and vol- bilical catheters (3.5F and 5F), volume ate.
ume replace- expanders, normal saline, drug boxa Failure to respond to intubation and ventila-
ment with appropriate neonatal vials and tion can result from (1) mechanical difficulties
dilutions, sterile syringes, needles, and (Table 1–16), (2) profound asphyxia with myo-
alcohol sponges cardial depression, and (3) inadequate circulating
Transport Warmed transport isolette with oxygen blood volume.
source Quickly rule out the mechanical causes listed
a in Table 1–16. Check to ensure the endotracheal
Epinephrine 1:10,000; naloxone hydrochloride 1 mg/mL; sodium
bicarbonate 4.2% (5 mEq/10 mL); 10% dextrose.
tube passes through the vocal cords. A CO2 detec-
Modified, with permission, from Rosenberg AA: Neonatal adapta- tor placed between the endotracheal tube and the
tion. In: Gabbe SG et al (eds). Obstetrics: Normal and Problem Preg- bag can be very helpful as a rapid confirmation of
nancies. Churchill Livingston, 1996. tube position in the airway. Occlusion of the tube
28 / CHAPTER 1

APPROXIMATE Birth Table 1–16. Mechanical causes

TIME of failed resuscitation.
• Clear of meconium?
• Breathing or crying?
• Good muscle tone? Cause Examples
• Color pink?
• Term gestation? Equipment failure Malfunctioning bag, oxygen
not connected or running
30 SECONDS

No Endotracheal tube malposition Esophagus, right main stem

bronchus
• Provide warmth
• Position; clear airway* Occluded endotracheal tube
(as necessary)
• Dry, stimulate, reposition Insufficient inflation pressure
• Give O2 (as necessary)
to expand lungs
Space-occupying lesions in Pneumothorax, pleural effu-
• Evaluate respirations, the thorax sions, diaphragmatic hernia
heart rate (HR), and color
Pulmonary hypoplasia Extreme prematurity,
oligohydramnios
30 SECONDS

Apnea or HR < 100

Reproduced, with permission, from Rosenberg AA: Neonatal
• Provide positive-pressure ventilation*
adaptation. In: Gabbe SG et al (eds): Obstetrics: Normal and Prob-
lem Pregnancies. Churchill Livingstone, 1996.
HR < 60 HR > 60
30 SECONDS

• Provide positive-pressure ventilation* should be suspected when there is resistance to

• Administer chest compressions
bagging and no chest wall movement. Very few
neonates (approximately 0.1%) require either car-
HR < 60 diac massage or drugs during resuscitation. Al-
most all newborns respond to ventilation with
• Administer 100% oxygen if done effectively.
epinephrine* HR < 60
7. If mechanical causes are ruled out and the heart
*Endotracheal intubation may rate remains below 60 beats/min after intubation
be considered at several steps and positive-pressure ventilation for 30 seconds,
cardiac compression should be initiated. Si-
Recheck effectiveness of multaneous delivery of chest compressions and
• Ventilation
• Chest compressions
positive-pressure ventilation is likely to decrease
• Endotracheal intubation the efficiency of ventilation. Therefore, chest
• Epinephrine delivery compressions should be interspersed with ventila-
Consider possibility of
• Hypovolemia
tion at a 3:1 ratio (90 compressions and
• Severe metabolic acidosis 30 breaths/min).
8. If drugs are needed (rarely), the drug and dose of
HR < 60 or persistent cyanosis choice is epinephrine 1:10,000 solution,
or failure to ventilate 0.1–0.3 mL/kg given via the endotracheal tube or
through an umbilical venous line. Sodium bicar-
Consider:
• Depressed respiratory bonate, 1–2 mEq/kg of the neonatal dilution
neuromuscular drive (0.5 mEq/mL), can be used in prolonged resusci-
• Airway malfunctions tation efforts in which the response to other mea-
• Lung problems, such as
– Pneumothorax sures is poor. If volume loss is suspected,
– Diaphragmatic hernia 10 mL/kg of a volume expander (normal saline)
• Congenital heart disease
should be administered through an umbilical vein
line.
Figure 1–5. Delivery room management. (Repro-
duced, with permission, from American Heart Association,
B. CONTINUED RESUSCITATIVE MEASURES
American Academy of Pediatrics: Neonatal Resuscitation The appropriateness of continued resuscitative efforts
Textbook, 4th ed, 2000.) should be reevaluated in an infant who fails to respond
 THE NEWBORN INFANT / 29

to the previously described efforts. In current practice, Treatment of the Asphyxiated Infant
resuscitative efforts are made even in apparent stillbirths
(ie, infants whose Apgar score at 1 minute is 0–1). Asphyxia is manifested by multiorgan dysfunction,
Modern resuscitative techniques have led to an increas- seizures and hypoxic-ischemic encephalopathy, and
ing survival rate for these infants, with 60% of survivors metabolic acidemia. The infant who has experienced a
showing normal development. It is clear from a number significant episode of perinatal hypoxia and ischemia is
of studies that initial resuscitation of these infants at risk for dysfunction of multiple end organs (Table
should proceed; however, subsequent continued sup- 1–17). The organ of greatest concern is the brain.
port must depend on response to resuscitation. All The clinical features of hypoxic-ischemic en-
studies emphasize that if the Apgar score is not improv- cephalopathy progress over time: birth to 12 hours, de-
ing markedly over the first 10–15 minutes of life, the creased level of consciousness, poor tone, decreased
mortality rate and the incidence of severe developmen- spontaneous movement, periodic breathing or apnea,
tal handicaps among survivors are high. and possible seizures; 12–24 hours, more seizures, ap-
neic spells, jitteriness, and weakness; after 24 hours, de-
C. SPECIAL CONSIDERATIONS creased level of consciousness, further respiratory ab-
normalities (progressive apnea), onset of brainstem
1. Preterm infants- signs (oculomotor and pupillary disturbances), poor
a. Minimizing heat loss improves survival, so pre- feeding, and hypotonia.
warmed towels should be available. The environmental The severity of clinical signs and the length of time
temperature of the delivery suite should be raised to the signs persist correlate with the severity of the insult.
> 25°C (especially for infants weighing < 1500 g). Other evaluations helpful in assessing severity in the
b. In the extremely low birth weight infant full-term infant include electroencephalogram (EEG),
(< 1000 g), proceed quickly to intubation. computed tomography (CT) scan, and evoked re-
c. Volume expanders and sodium bicarbonate (if sponses. Magnetic resonance imaging (MRI), particu-
needed) should be infused more slowly to minimize larly diffusion-weighted imaging, is becoming useful,
rapid swings in blood pressure and serum osmolality. especially in the early evaluation of the infant with peri-
2. Narcotic depression—In the case of opioid admin- natal asphyxia.
istration to the mother during labor, perform the resus- Markedly abnormal EEGs with voltage suppression
citation as described earlier. When the baby is stable and slowing evolving into a burst-suppression pattern
with good heart rate, color, and perfusion but still has are associated with severe clinical symptomatology. A
poor respiratory effort, a trial of naloxone (0.1 mg/kg CT scan early in the course may demonstrate diffuse
IM, SQ, IV, or IT) is indicated. Naloxone should not hypodensity and loss of gray/white matter tissue differ-
be administered in place of positive-pressure ventila- entiation, whereas later scans may demonstrate brain
tion. Naloxone should not be used in the infant of an atrophy and focal ischemic lesions. Visual and so-
opioid-addicted mother because it will precipitate with-
drawal.
3. Meconium-stained amniotic fluid— Table 1–17. Signs and symptoms caused
a. The obstetrician carefully suctions the orophar- by asphyxia.
ynx and the nasopharynx after delivery of the head with
a suction apparatus attached to wall suction.
b. The delivery is then completed, and the baby is Hypoxic-ischemic encephalopathy, seizures
given to the resuscitation team. Respiratory distress due to aspiration or secondary surfactant
c. If the baby is active and breathing, requiring no deficiency, pulmonary hemorrhage
resuscitation, and if obstetric suctioning has been per- Persistent pulmonary hypertension
Hypotension due to myocardial dysfunction
formed, the airway need not be inspected—only further
Transient tricuspid valve insufficiency
suctioning of the mouth and nasopharynx is required. Anuria or oliguria due to acute tubular necrosis
d. The airway of any depressed infant requiring ven- Feeding intolerance; necrotizing enterocolitis
tilation must be checked and cleared (by passage of a Elevated aminotransferases due to liver injury
tube below the vocal cords) before positive-pressure Adrenal insufficiency due to hemorrhage
ventilation is instituted. Special adapters are available Disseminated intravascular coagulation
for use with regulated wall suction to allow suction to Hypocalcemia
be applied directly to the endotracheal tube. Hypoglycemia
Persistent metabolic academia
4. Universal precautions—In the delivery room, uni- Hyperkalemia
versal precautions should always be observed.
30 / CHAPTER 1

matosensory evoked potentials provide information American Heart Association and American Academy of Pediatrics:
about function. In most instances, it is not necessary to Textbook of Neonatal Resuscitation, 4th ed. American Heart
Association/American Academy of Pediatrics, 2000.
use all of these tests, but some are obtained to confirm
an ominous prognosis. Management is directed at sup- Battlin MR et al: Treatment of term infants with head cooling and
mild hypothermia (35.0 degrees C and 34.5 degrees C) after
portive care and treatment of specific abnormalities. perinatal asphyxia. Pediatrics 2003;111:244 [PMID:
Fluids should be restricted initially to 60–80 mL/kg/d; 12563046].
oxygenation should be maintained (with mechanical Croen LA et al: Congenital abnormalities among children with
ventilation if necessary); blood pressure should be sup- cerebral palsy: More evidence for prenatal antecedents. J Pe-
ported with judicious volume expansion (if hypov- diatr 2001;138:804 [PMID: 11391320].
olemic) and pressors; and glucose should be in the nor- Grow J, Barks JDE: Pathogenesis of hypoxic-ischemic cerebral in-
mal range of 40–100 mg/dL. Hypocalcemia, jury in the term infant: Current concepts. Clin Perinatol
coagulation abnormalities, and metabolic acidemia 2002;29:585 [PMID:12516737].
should be corrected and seizures treated with IV pheno- Gunn AJ, Bennet L: Cerebral hypothermia in the management of
barbital (20 mg/kg as loading dose, with total initial hypoxic–ischemic encephalopathy. Neoreviews 2002;3:e116.
24-hour dosing up to 40 mg/kg). Phenobarbital in Hamkins GDV, Spear M: Defining the pathogenesis and patho-
physiology of neonatal encephalopathy and cerebral palsy.
large doses (40 mg/kg IV 1–6 hours after the event) Obstet Gynecol 2003;102:628 [PMID: 12962954].
given as a neuroprotective therapy is associated with Huppi PS: Advances in postnatal neuroimaging: Relevance to
improvement in neurologic outcome with minimal ad- pathogenesis and treatment of brain injury. Clin Perinatol
verse effects on blood pressure, respirations, or blood 2002;29:827 [PMID: 12516748].
gases. Other anticonvulsants should be reserved for re- Mosler D et al: The association of Apgar score with subsequent
fractory seizures. The role of hypothermia (in particu- death and cerebral palsy: A population-based study in term
lar, selective head cooling), free oxygen radical scav- infants. J Pediatr 2001;138:798 [PMID: 11391319].
engers, excitatory amino acid antagonists, and calcium Niermeyer S: Evidence based guidelines for neonatal resuscitation.
channel blockers in minimizing cerebral injury after as- Neoreviews 2001;2:e38.
phyxia is under active investigation. Shankaran S: The postnatal management of the asphyxiated term
infant. Clin Perinatol 2002;29:675 [PMID: 12516741].
Willoughby RE Jr, Nelson KB: Chorioamnionitis and brain injury.
Birth Asphyxia: Long-Term Outcome Clin Perinatol 2002;29:603 [PMID: 12516738].
Wiswell TE et al: Delivery room management of the apparently
Fetal heart rate tracings, cord pH, and 1-minute Apgar vigorous meconium-stained neonate: Results of the multicen-
scores are imprecise predictors of long-term outcome. ter, international collaborative trial. Pediatrics 2000;105:1
Apgar scores of 0–3 at 5 minutes in full-term infants re- [PMID: 10617696].
sult in an 18–35% risk of death in the first year of life
and an 8% risk of cerebral palsy among survivors. The
risks of mortality and morbidity increase with more THE PRETERM INFANT
prolonged depression of the Apgar score. The single
best predictor of outcome is the severity of clinical hy- Premature infants account for the majority of high-risk
poxic-ischemic encephalopathy (severe symptomatol- newborns. The preterm infant faces a variety of physio-
ogy including coma carries a 75% chance of death and logic handicaps:
a 100% rate of neurologic sequelae among survivors).
The major sequela of hypoxic-ischemic encephalopathy 1. The ability to suck, swallow, and breathe in a
is cerebral palsy with or without associated mental re- coordinated fashion is not achieved until
tardation and epilepsy. Other prognostic features in- 34–36 weeks’ gestation. Therefore, enteral feed-
clude elevated nucleated red blood cell counts, pro- ings must be provided by gavage. Furthermore,
longed seizures refractory to therapy, markedly preterm infants frequently have gastroesophageal
abnormal EEGs, and CT or MRI scans with evidence reflux and an immature gag reflex, which in-
of major ischemic injury. Other clinical features re- creases the risk of aspiration of feedings.
quired to support perinatal hypoxia as the cause of cere- 2. Decreased ability to maintain body temperature.
bral palsy include the presence of fetal distress prior to 3. Pulmonary immaturity-surfactant deficiency,
birth, a low cord pH of < 7.00, evidence of other end often with structural immaturity in infants of less
organ dysfunction, and absence of a congenital brain than 26 weeks’ gestation. Their condition is com-
malformation. plicated by the combination of noncompliant
lungs and an extremely compliant chest wall.
Allan WC: The clinical spectrum and prediction of outcome in hy- 4. Immature control of respiration, leading to apnea
poxic-ischemic encephalopathy. Neoreviews 2002;3:e108. and bradycardia.
 THE NEWBORN INFANT / 31

5. Persistent patency of the ductus arteriosus, lead- muscle activity (shivering), and thermogenesis not
ing to further compromise of pulmonary gas ex- caused by shivering. Newborns produce heat mainly
change because of overperfusion of the lungs. through the last of these three mechanisms. This meta-
6. Immature cerebral vasculature, predisposing the bolic heat production depends on the quantity of
infant to subependymal or intraventricular hem- brown fat present, which is very limited in the preterm
orrhage and periventricular leukomalacia. infant. Heat loss to the environment can occur through
7. Impaired substrate absorption by the GI tract, the following mechanisms: (1) radiation—transfer of
compromising nutritional management. heat from a warmer to a cooler object not in contact;
(2) convection—transfer of heat to the surrounding
8. Immature renal function (including both filtra- gaseous environment, influenced by air movement and
tion and tubular functions), complicating fluid temperature; (3) conduction—transfer of heat to a
and electrolyte management. cooler object in contact; and (4) evaporation—cooling
9. Increased susceptibility to infection. secondary to water loss through the skin. Heat loss in
10. Immaturity of metabolic processes, predisposing the preterm newborn is accelerated because of a high
to hypoglycemia and hypocalcemia. ratio of surface area to body mass, reduced insulation of
subcutaneous tissue, and water loss through the imma-
Delivery Room Care ture skin.
The thermal environment of the preterm neonate
See section on Perinatal Resuscitation. must be regulated carefully. The infant can be kept
warm in an isolette, in which the air is heated and con-
Care in the Nursery vective heat loss is minimized. Alternatively, the infant
can be kept warm on an open bed with a radiant heat
A. THERMOREGULATION source. Although evaporative and convective heat losses
Maintaining a stable body temperature is a function of are greater when the radiant warmer is used, this system
heat production and conservation balanced against heat allows easy access to a critically ill neonate. Ideally, the
loss. Heat production in response to cold stress can infant should be kept in a neutral thermal environment
occur through voluntary muscle activity, involuntary (Figure 1–6). The neutral thermal environment allows
Body temperature

37°C

Inevitable
Inevitable body cooling Thermoregulatory range
Heat production or oxygen consumption

body heating

Summit
metabolism
Range of
thermal
neutrality

Figure 1–6. Effect of environmental

temperature on oxygen consumption
Increasing and body temperature. (Adapted and
Decreasing Chemical
body temperature regulation
body reproduced, with permission, from
temperature Klaus MH, Fanaroff AA, Martin RJ: The
Death from Death from physical environment. In: Klaus MH, Fa-
cold heat naroff AA [editors]: Care of the High-Risk
Environmental temperature
Neonate, 5th ed. WB Saunders, 2001.)
32 / CHAPTER 1

the infant to maintain a stable core body temperature quently elevated, increasing the infant’s requirement for
with a minimum of metabolic heat production through these electrolytes.
oxygen consumption. The neutral thermal environ- Initial fluid management after birth is determined
ment for a given infant depends on size, gestational age, by the infant’s size. Infants weighing more than 1500 g
and postnatal age. The neutral thermal environment should start at 80–100 mL/kg/d of 10% dextrose in
(for either isolette or radiant warmer care) can be ob- water (D10W), whereas those weighing less should start
tained by maintaining an abdominal skin temperature at 100–120 mL/kg/d of either D10W or 5% dextrose in
of 36.5°C. Generally, when infants reach 1700–1800 g, water (D5W) (infants < 800 g and < 26 weeks’ gestation
they can maintain temperature while bundled in an often become hyperglycemic on D10W). The most crit-
open crib. ical issue in fluid management is monitoring. Measure-
ments of body weight, urine output, fluid and elec-
B. MONITORING THE HIGH-RISK INFANT trolyte intake, serum and urine electrolytes, and glucose
Care of the high-risk preterm infant requires sophisti- allow fairly precise determinations of the infant’s water,
cated monitoring techniques. At a minimum, equip- glucose, and electrolyte needs. Parenteral nutrition
ment to monitor heart rate, respirations, and blood should be started early and continued until an adequate
pressure should be available. Oxygen saturation can be enteral intake is achieved.
assessed continuously using pulse oximetry. This deter-
mination can be correlated with arterial oxygen tension D. NUTRITIONAL SUPPORT
(PaO2) as needed. Transcutaneous PO2 and PCO2 can The average caloric requirement for the growing pre-
also be used to assess oxygenation and ventilation. Fi- mature infant is 120 kcal/kg/d. Expected weight gain
nally, arterial blood gases, electrolytes, glucose, calcium, for the adequately nourished preterm infant is
bilirubin, and other chemistries must be measured on 10–30 g/d. Infants initially require IV glucose infusions
small volumes of blood. Early in the care of a sick to maintain blood glucose concentration in the range of
preterm infant, the most efficient way to sample blood 60–100 mg/dL. Infusions of 5–7 mg/kg/min (approxi-
for tests as well as to provide fluids and monitor blood mately 80–100 mL/kg/d of a D10W solution) are usu-
pressure is through an umbilical arterial line. Once the ally needed. Nutritional support in the very low birth
infant is stable and the need for frequent blood samples weight infant should be started as soon as possible after
is reduced (usually 4–7 days), the umbilical line should birth, with parenteral alimentation solutions given ei-
be removed. All indwelling lines are associated with ther peripherally or centrally via an umbilical vein line
morbidity from thrombosis or embolism, infection, and or percutaneous catheter (Table 1–18). Small-volume
bleeding. trophic feeds with breast milk or 20 kcal/oz of prema-
ture formula should be started by gavage at ≤ 10% of
C. FLUID AND ELECTROLYTE THERAPY the infant’s nutritional needs as soon as possible. After
Fluid requirements in preterm infants are a function of several days of trophic feeds the infant can be slowly ad-
(1) insensible losses (skin and respiratory tract), vanced to full caloric needs over 5–7 days. Even ex-
(2) urine output, (3) stool output (< 5% of total), and tremely small feed volumes can enhance intestinal
(4) others, such as nasogastric losses. In most circum- readiness to ultimately accept larger feeding volumes.
stances, the fluid requirement is determined largely by Intermittent bolus feedings are preferred because these
insensible losses plus urine losses. The major contribu- appear to stimulate the release of gut-related hormones
tion to insensible water loss is evaporative skin loss. The and may accelerate maturation of the GI tract. A more
rate of water loss is a function of gestational age (body rapid advancement schedule is used for infants weigh-
weight), environment (losses are greater under a radiant ing over 1500 g and the slowest schedule in the infant
warmer than in an isolette), and the use of photother- weighing less than 1000 g. Note: In the extremely low
apy. Respiratory losses are minimal when infants are birth weight infant (< 1000 g) or the postsurgical
breathing humidified oxygen. The renal contribution neonate, continuous-drip feeds are sometimes better
to water requirement is influenced by the decreased tolerated.
ability of the preterm neonate to concentrate the urine In general, long-term nutritional support for infants
and conserve water. of very low birth weight consists either of breast milk
Electrolyte requirements are minimal for the first supplemented to increase protein, caloric density, and
24–48 hours until there is excretion in the urine. Basal mineral content or of infant formulas modified for
requirements are as follows: sodium, 3 mEq/kg/d; preterm infants. In all of these formulas, protein con-
potassium, 2 mEq/kg/d; chloride, 2–3 mEq/kg/d; and centrations (approximately 2 g/dL) and caloric concen-
bicarbonate, 2–3 mEq/kg/d. trations (approximately 24 kcal/oz) are relatively high.
In the infant born before 30 weeks’ gestation, In addition, premature formulas contain some of the
sodium and bicarbonate losses in the urine are fre- fat as medium-chain triglycerides—which do not re-
 THE NEWBORN INFANT / 33

Table 1–18. Use of parenteral alimentation solutions.

Volume Carbohydrate Protein Lipid Calories

(mL/kg/d) (g/dL) (g/kg) (g/kg) (kcal/kg)
Peripheral: Short-term (7–10 days)
Starting solution 100–150 D10W 2 1 46–64
Target solution 150 D12.5W 3–3.5 3 102
Central: Long-term (>10 days)
Starting solution 100–150 D10W 2 1 46–64
Target solution 130 D20W 3–3.5 3 123
Notes:
1. Protein calories should be no more than 10% of total calories.
2. Advance dextrose in central hyperalimentation as tolerated by 2.5% per day as long as blood glucose remains normal.
3. Advance lipids by 1.0 g/kg/d as long as triglycerides are normal. Use 20% concentration.
4. Total water should be 100–150 mL/kg/d, depending on the child’s fluid tolerance.
Monitoring:
1. Blood glucose two or three times a day when changing dextrose concentration, then daily.
2. Electrolytes daily, then twice a week when the child is receiving a stable solution.
3. Every other week blood urea nitrogen and serum creatinine; total protein and serum albumin; serum calcium, phosphate, magnesium,
direct bilirubin, and CBC with platelet counts.
4. Triglyceride level after 24 h at 2 g/kg/d and 24 h at 3 g/kg/d; then every other week.

quire bile for emulsification—as an energy source. In- Berseth CL et al: Prolonging small feeding volumes early in life de-
creased amounts of calcium and phosphorus are pro- creases the incidence of necrotizing enterocolitis in very low
birth weight infants. Pediatrics 2003;111:529 [PMID:
vided to enhance bone mineralization. In addition, as 12612232].
with formula for full-term infants, formulas for prema-
Carver JD et al: Growth of preterm infants fed nutrient-enriched or
ture infants are now being enriched with long-chain term formula after hospital discharge. Pediatrics 2001;107:
polyunsaturated fatty acids in the hope of enhancing 683 [PMID: 11335744].
brain and retinal development. The infant should be Embleton NE et al: Postnatal malnutrition and growth retardation:
advanced gradually to feedings of higher caloric density An inevitable consequence of current recommendations in
after a substantial volume (100–120 mL/kg/d) of either preterm infants. Pediatrics 2001;107:270 [PMID: 11158457].
breast milk or formula (20 kcal/oz) is tolerated. Success Innis SM et al: Docosahexaenoic acid and arachidonic acid enhance
of feedings is assessed by passage of feeds out of the growth with no adverse effects in preterm infants fed formula.
stomach, abdominal examination free of distention, J Pediatr 2002;140:547 [PMID: 12032520].
and normal stool pattern. Thureen PJ, Hay WW: Intravenous nutrition and postnatal growth
When the preterm infant approaches term, the nu- of the micropremie. Clin Perinatol 2000;27:197 [PMID:
10690572].
tritional source for the bottle-fed infant can be changed
Williams AF: Early enteral feeding of the preterm infant. Arch Dis
to a transitional formula (22 kcal/oz) until age Child Fetal and Neonatal Ed 2000;83:F219 [PMID:
6–9 months. Iron supplementation (2–4 mg/kg/d) is 11040173].
recommended for premature infants, beginning at Yeung MY: Nutritionally regulated hormonal factors in prolonged
about age 2 months. This can be provided by iron-sup- postnatal growth retardation and its associated adverse neu-
plemented formulas. In some infants, iron supplemen- rodevelopmental outcome in extreme prematurity. Biol
tation may be indicated earlier. In particular, infants Neonate 2003;84:1 [PMID: 12890931].
treated with erythropoietin (epoetin alfa) for prevention Zeigler EE et al: Aggressive nutrition of the very low birth weight
or treatment of anemia of prematurity require a higher infant. Clin Perinatol 2002;29:225 [PMID: 12168239].
dosage of 4–8 mg/kg/d.

Anderson JW et al: Breast-feeding and cognitive development: A

meta-analysis. Am J Clin Nutr 1999;70:525 [PMID:
10500022].
34 / CHAPTER 1

1. Apnea in the Preterm Infant processes should at least be considered before a diagno-
sis of apnea of prematurity can be established.
Apnea of prematurity is the most frequent cause of
ESSENTIALS OF DIAGNOSIS apnea. Most apnea of prematurity is mixed apnea char-
& TYPICAL FEATURES acterized by a centrally (brainstem) mediated respira-
tory pause preceded or followed by airway obstruction.
• Respiratory pause of sufficient duration to result Less common is pure central or pure obstructive apnea.
in cyanosis or bradycardia. Apnea of prematurity is the result of immaturity of
both the central respiratory regulatory centers and pro-
• Most common in infants born at < 34 weeks’ ges-
tective mechanisms that aid in maintaining airway pa-
tation with onset at < 2 weeks of age. tency.
• Methylxanthines (eg, caffeine) provide effective
treatment for apnea of prematurity.
Clinical Findings
Onset, typically during the first 2 weeks of life, is grad-
ual, with the frequency of spells increasing over time.
Pathologic apnea can be suspected in an infant with a
General Considerations sudden onset of frequent or very severe apneic spells.
In preterm infants, recurrent apneic episodes are a com- Apnea presenting from birth or on the first day of life is
mon problem. Apnea is defined as a respiratory pause unusual but can occur in the preterm infant who does
lasting more than 20 seconds—or any pause accompa- not require mechanical ventilation for respiratory dis-
nied by cyanosis and bradycardia. Shorter respiratory tress syndrome. In the full-term or near-term infant,
pauses associated with cyanosis or bradycardia also this presentation can suggest neuromuscular abnormali-
qualify as significant apnea but must be differentiated ties of an acute (asphyxia, birth trauma, or infection) or
from periodic breathing, which is common in full-term chronic (eg, congenital hypotonia, structural CNS le-
as well as preterm infants. Periodic breathing is defined sion) nature.
as regularly recurring ventilatory cycles interrupted by The work-up depends on the clinical presentation.
short pauses not associated with bradycardia or color All infants—regardless of the severity and frequency of
change. Although apnea in premature infants is often apnea—require a minimum screening evaluation, in-
not associated with a predisposing factor, a variety of cluding a general assessment of well-being (eg, tolerance
processes may precipitate apnea (Table 1–19). These of feedings, stable temperature, normal physical exami-
nation), a check of the association of spells with feed-
ing, measurement of PaO2 or SaO2, blood glucose,
hematocrit, and a review of the drug history. Infants
Table 1–19. Causes of apnea in the with severe apnea of sudden onset may require a more
preterm infant. extensive evaluation, including a work-up for infection.
Other specific tests are dictated by relevant signs, for
Temperature instability—both cold and heat stress example, evaluation for necrotizing enterocolitis in an
Response to passage of a feeding tube infant with apnea and abdominal distention or feeding
Gastroesophageal reflux intolerance.
Hypoxemia
Pulmonary parenchymal disease Treatment
Patent ductus arteriosus
?Anemia The physician should first address any underlying
Infection cause. If the apnea is due simply to prematurity, treat-
Sepsis (viral or bacterial) ment is dictated by the frequency and severity of apneic
Necrotizing enterocolitis spells. Apneic spells frequent enough to interfere with
Metabolic causes other aspects of care (eg, feeding), or severe enough to
Hypoglycemia necessitate bag and mask ventilation to relieve cyanosis
Hyponatremia and bradycardia, require treatment. First-line therapy is
Intracranial hemorrhage with methylxanthines. Caffeine citrate (20 mg/kg as
Posthemorrhagic hydrocephalus loading dose and then 5–10 mg/kg/d) is the drug of
Seizures choice because of once-daily dosing, wider therapeutic
Drugs (eg, morphine) index, and fewer side effects than theophylline. Side ef-
Apnea of prematurity
fects of methylxanthines include tachycardia, feeding
 THE NEWBORN INFANT / 35

intolerance, and (with overdosing) seizures. The dose 35–36 weeks’ gestation to more than 50% of infants
used should be the smallest dose necessary to decrease born at 26–28 weeks’ gestation. This condition is
the frequency of apnea and eliminate severe spells. De- caused by a deficiency of surfactant. Surfactant de-
sired drug levels are usually in the range of creases surface tension in the alveolus during expiration,
10–20 mg/mL for caffeine. Nasal CPAP (continuous allowing the alveolus to remain partly expanded and in
positive airway pressure), by treating the obstructive that way maintaining a functional residual capacity.
component of apnea, can be effective treatment for The absence of surfactant results in poor lung compli-
some infants. Intubation and ventilation can eliminate ance and atelectasis. The infant must expend a great
symptomatic apneic spells but carry the risks associated deal of effort to expand the lungs with each breath, and
with long-term endotracheal intubation. respiratory failure ensues (Figure 1–7).

Prognosis Clinical Findings

In the majority of premature infants, apneic and brady- Infants with hyaline membrane disease demonstrate all
cardiac spells cease by 34–37 weeks postconception. the clinical signs of respiratory distress. On ausculta-
Spells that require intervention cease prior to self-re- tion, air movement is diminished despite vigorous res-
solved episodes. In infants born at less than 28 weeks’ piratory effort. Chest radiograph demonstrates diffuse
gestation, episodes may continue past term postconcep- bilateral atelectasis, causing a ground-glass appearance.
tual age. Whether to provide home monitoring or out- Major airways are highlighted by the atelectatic air sacs,
patient methylxanthine therapy for such infants is con- creating air bronchograms. In the unintubated child,
troversial. Apneic and bradycardiac episodes in the doming of the diaphragm and underexpansion occur.
nursery are not predictors of later SIDS. However,
home monitoring in infants still experiencing self-re-
solving apnea and bradycardia at the time of hospital Treatment
discharge may be indicated in some cases. The inci- Supplemental oxygen, use of nasal CPAP, early intuba-
dence of SIDS is slightly increased in preterm infants. tion for surfactant administration and ventilation, and
Research in full-term infants has shown an increased in- placement of umbilical artery and vein lines are the ini-
cidence of SIDS in infants who sleep in the prone posi- tial interventions required. A ventilator that can deliver
tion. Whether this can be extrapolated to the preterm breaths synchronized with the infant’s respiratory ef-
infant (in particular those with gastroesophageal reflux forts (synchronized intermittent mandatory ventilation)
or persistent respiratory symptoms) is unclear. When should be used if available. High-frequency ventilators
possible, a supine sleeping position or one that is
slightly to the right side seems prudent unless con-
traindicated by reflux or respiratory symptoms.
Lung volume (mL/kg body wt)

2. Hyaline Membrane Disease 80

– Natural
surfactant
ESSENTIALS OF DIAGNOSIS 60
& TYPICAL FEATURES –
40
+
• Tachypnea, cyanosis, and expiratory grunting. Control
20 –
• Poor air movement despite increased work of
breathing.
0
• Chest radiograph showing hypoexpansion and 0 5 10 15 20 25 30 35
air bronchograms. Pressure (cm H2O)

Figure 1–7. Pressure-volume relationships for the in-

flation and deflation of surfactant-deficient and surfac-
tant-treated preterm rabbit lungs. (Reproduced, with
General Considerations permission, from Jobe AH: The developmental biology of
The most common cause of respiratory distress in the the lung. In: Fanaroff AA, Martin RJ [editors]: Neonatal-Peri-
preterm infant is hyaline membrane disease. The inci- natal Medicine: Diseases of the Fetus and Infant, 6th ed.
dence increases from 5% of infants born at Mosby, 1997.)
36 / CHAPTER 1

are also available for rescue of infants doing poorly on 3. Chronic Lung Disease
conventional ventilation or who have air leak problems. in the Premature Infant
Four exogenous surfactants (colfosceril palmitate
[Exosurf Neonatal], beractant [Survanta], calf lung sur-
factant extract [Infasurf]), and poractant a (Curosurf)
are approved in the United States by the Food and ESSENTIALS OF DIAGNOSIS
Drug Administration for use in infants with hyaline & TYPICAL FEATURES
membrane disease. Surfactant replacement therapy,
used both in the delivery room as prophylaxis and with • Oxygen requirement, respiratory symptoms, and
established hyaline membrane disease as rescue, de- abnormal chest radiograph at age 1 month.
creases the mortality rate in preterm infants and de- • Incidence greatest in infants of the lowest gesta-
creases air leak complications of the disease. During the tional ages.
acute course, ventilator settings and oxygen require-
ments are significantly less in surfactant-treated infants
than in control subjects. The dose of the bovine-de-
rived Survanta is 4 mL/kg, the calf-derived Infasurf is
3 mL/kg, and the porcine-derived Curosurf is General Considerations
1.25–2.5 mL/kg, given intratracheally. When the first
dose is given in the delivery room to prevent hyaline Chronic lung disease in the premature infant, defined
membrane disease the usual dosing schedule is a total of as respiratory symptoms, oxygen requirement, and
two or three doses given 6–12 hours apart as long as the chest radiograph abnormalities at age 1 month, occurs
infant remains ventilated on over 30–40% inspired in about 20% of infants ventilated for surfactant
oxygen concentration. Rescue surfactant is given as two deficiency. The incidence is higher at lower
to four doses 6–12 hours apart. The first dose is admin- gestational ages. The development of chronic lung dis-
istered as soon as possible after birth, preferably before ease is a function of lung immaturity at birth and expo-
2–4 hours of age. As the disease process evolves, pro- sure to high oxygen concentrations and ventilator volu-
teins that inhibit surfactant function leak into the air trauma. The use of surfactant replacement therapy or
spaces, making surfactant replacement less effective. early nasal CPAP has, in general, diminished the sever-
The second dose should be administered to infants who ity of the chronic lung disease. The mortality rate from
continue to require ventilation and more than 30–40% this complication is now very low, but significant mor-
inspired oxygen concentration. A prophylactic strategy bidity still exists secondary to reactive airway symp-
offers some advantage in those infants born at toms, hospital readmissions during the first 2 years of
26 weeks’ gestation or less. For infants over 26 weeks’ life for intercurrent respiratory infection, and systemic
gestation, early rescue therapy (as soon as a diagnosis of hypertension.
surfactant deficiency can be made) is the strategy of
choice. In stable infants, a trial of nasal CPAP at
5–6 cm H2O pressure can be attempted prior to intu-
Treatment
bation and surfactant administration. For those who do The mainstay of therapy for chronic lung disease has
ultimately require intubation, extubation to nasal been dexamethasone, 0.3–0.5 mg/kg/d, used to de-
CPAP should be done as early as possible to minimize crease lung inflammation. Recently, however, more at-
lung injury and evolution of chronic lung disease. Ante- tention has been focused on the detrimental effects of
natal administration of corticosteroids to the mother is dexamethasone therapy on long-term neurodevelop-
an important strategy used by obstetricians to accelerate ment. Attempts are being made to avoid this interven-
lung maturation. Infants whose mothers were given tion unless the infant is on very high concentrations of
corticosteroids more than 24 hours prior to preterm supplemental oxygen and ventilator support with little
birth have less respiratory distress syndrome and a lower response to other therapies such as diuretics
mortality rate. Antenatal corticosteroids and exogenous (furosemide [Lasix] 1–2 mg/kg/d), inhaled β2-adrener-
surfactant administration after birth appear to have a gic bronchodilators, and inhaled corticosteroids. In-
synergistic effect on outcome. haled steroids such as beclomethasone, fluticasone, or
budesonide are unproven treatments, but may be help-
ful without the risk of systemic side effects. If it is nec-
essary to use dexamethasone, a dose of 0.2 mg/kg/d for
no more than 3 days is recommended. After hospital
discharge, some of these infants will continue to require
 THE NEWBORN INFANT / 37

oxygen at home. This can be monitored by pulse Vaucher Y: Bronchopulmonary dysplasia: An enduring challenge.
oximetry with a target SaO2 of 94–96%. Pediatr Rev 2002;23:349 [PMID: 12359869].

4. Patent Ductus Arteriosus

American Academy of Pediatrics Committee on Fetus and New-
born, Canadian Paediatric Society: Postnatal corticosteroids
to treat or prevent chronic lung disease in preterm infants. ESSENTIALS OF DIAGNOSIS
Pediatrics 2002;109;330 [PMID: 11826218]. & TYPICAL FEATURES
American Academy of Pediatrics Committee on Fetus and New-
born: Apnea, sudden infant death syndrome, and home mon-
itoring. Pediatrics 2003;111:914 [PMID: 12671135]. • Hyperdynamic precordium.
Baird TM et al: Clinical association, treatment, and outcome of • Widened pulse pressure.
apnea of prematurity. Neoreviews 2002;3:e66. • Hypotension.
Bancalari E: Epidemiology and risk factors for the “new” bron-
chopulmonary dysplasia. Neoreviews 2000;1:e2.
• Presence of a systolic heart murmur in many
Cole CH, Fiascone JM: Strategies for prevention of neonatal
cases.
chronic lung disease. Semin Perinatol 2000;24:445 [PMID:
11153905].
Durand M et al: A randomized trial of moderately early low-dose
dexamethasone therapy in very low birth weight infants: Dy-
namic pulmonary mechanics, oxygenation, and ventilation. General Considerations
Pediatrics 2002;109:962 [PMID: 11826205].
Clinically significant patent ductus arteriosus usually
Eichenwald EC et al: Apnea frequently persists beyond term gesta-
tion in infants delivered at 24–28 weeks. Pediatrics 1997;
presents on days 3–7 as the respiratory distress from
100:354 [PMID: 9282705]. hyaline membrane disease is improving. Presentation
Herting E et al: Surfactant treatment of neonates with respiratory can be on days 1 or 2, especially in infants born at less
failure and group B streptococcal infection. Pediatrics 2000; than 28 weeks’ gestation and in those who have re-
106:957 [PMID:11061760]. ceived surfactant replacement therapy. The signs in-
Jobe AH, Bancalari E: Bronchopulmonary dysplasia. Am J Respir clude a hyperdynamic precordium, increased peripheral
Crit Care Med 2001;163:1723 [PMID: 11401896]. pulses, and a widened pulse pressure with or without a
Kattwinkel J et al: High- versus low-threshold surfactant replace- systolic heart murmur. Early presentations are some-
ment for neonatal respiratory distress syndrome. Pediatrics times manifested by systemic hypotension without a
2000;106:282 [PMID: 10920152]. murmur or hyperdynamic circulation. These signs are
Kotecha S, Allen J: Oxygen therapy for infants with chronic lung often accompanied by an increase in respiratory sup-
disease. Arch Dis Child Fetal Neonatal Ed 2002;87:F11
[PMID: 12091281].
port. The presence of significant patent ductus arterio-
sus can be confirmed by echocardiography. Before un-
Martin RJ et al: Pathophysiologic mechanisms underlying apnea of
prematurity. Neoreviews 2002;3:e59. dertaking medical or surgical ligation, other structural
Merrill JD, Ballard RA: Clinical use of antenatal corticosteroids:
heart disease should be ruled out.
Benefits and risks. Neoreviews 2000;1:e91.
Murphy BP et al: Impaired cerebral cortical gray matter growth Treatment
after treatment with dexamethasone for neonatal chronic lung
disease. Pediatrics 2001;107:217 [PMID: 11158449]. The ductus arteriosus is managed by medical or surgical
Narendran V et al: Early bubble CPAP and outcomes in ELBW ligation. A clinically significant ductus causing compro-
preterm infants. J Perinatol 2003;23:195 [PMID: mise in the infant can be closed (in about two thirds of
12732855]. cases) with indomethacin, 0.1–0.2 mg/kg IV q12–24h
Peter CS et al: Gastroesophageal reflux and apnea of prematurity: for three doses. If the ductus reopens or fails to close
No temporal relationship. Pediatrics 2002;109:8 [PMID: completely, a second course of drug may be used. If in-
11773535]. domethacin fails to close the ductus or if a ductus re-
Ramanathan R et al: Cardiorespiratory events recorded on home opens a second time, surgical ligation is called for. In
monitors: Comparison of healthy infants with those at in- some cases, a more prolonged course of indomethacin is
creased risk for SIDS. JAMA 2001;285:2199 [PMID:
11325321].
being used to prevent recurrences. In addition, in the
Suresh GK, Soll RF: Current surfactant use in premature infants.
extremely low birth weight infant (< 1000 g) who is at
Clin Perinatol 2001;28:671 [PMID: 11570160]. very high risk of developing a symptomatic ductus, a
Tauman R, Sivan Y: Duration of home monitoring for infants dis- prophylactic strategy starting indomethacin (0.1 mg/kg
charged with apnea of prematurity. Biol Neonate 2000; q24h for 3–5 days) on the first day of life can be used.
78:168 [PMID: 11044764]. The major side effect of indomethacin is transient olig-
38 / CHAPTER 1

uria, which can be managed by fluid restriction until ness, temperature instability, increased apnea and
urine output improves. There may also be an increased bradycardia, decreased urine output, and poor perfu-
incidence of necrotizing enterocolitis with more pro- sion. The CBC may show an increased white blood cell
longed therapy. Transient decreases in intestinal and count with an increased band count or, as the disease
cerebral blood flow caused by indomethacin can be progresses, absolute neutropenia. Thrombocytopenia is
ameliorated by giving the drug as a slow infusion over often observed along with stress-induced hyperglycemia
1–2 hours. The drug should not be used if the infant is and metabolic acidosis. Diagnosis is confirmed by the
hyperkalemic, if the creatinine is > 2 mg/dL, or if the presence of pneumatosis intestinalis (air in the bowel
platelet count is < 50,000/mL. wall) on radiograph. There is a spectrum of disease, and
milder cases may exhibit only distention of bowel loops
Lee J et al: Randomized trial of prolonged low dose versus conven- with bowel wall edema (thickened-appearing walls on
tional dose indomethacin for treating patent ductus arteriosus radiograph).
in very low birth weight infants. Pediatrics 2003;112:345
[PMID: 12897285].
Narayan-Sankar M, Clyman RI: Pharmacologic closure of patent
Treatment
ductus arteriosus in the neonate. Neoreviews 2003;4:e215. A. MEDICAL TREATMENT
Schmidt B et al: Long-term effects of indomethacin prophylaxis in
extremely-low-birth-weight infants. N Engl J Med 2001;344: Necrotizing enterocolitis is managed by decompression
1966 [PMID: 11430325]. of the gut by nasogastric tube, maintenance of oxygena-
tion, mechanical ventilation if necessary, and IV fluids
(normal saline) to replace third-space GI losses. Enough
5. Necrotizing Enterocolitis fluid should be given to restore a good urine output.
Other measures consist of broad-spectrum antibiotics
(usually ampicillin, a third-generation cephalosporin, or
ESSENTIALS OF DIAGNOSIS an aminoglycoside and possibly additional anaerobic
& TYPICAL FEATURES coverage), close monitoring of vital signs, serial physical
examinations, and laboratory studies (blood gases,
• Feeding intolerance with gastric aspirates or white blood cell count, platelet count, and radi-
vomiting. ographs).
• Bloody stools.
B. SURGICAL TREATMENT
• Abdominal distention and tenderness.
Indications for surgery are evidence of perforation (free
• Pneumatosis intestinalis on abdominal radi- air present on a left lateral decubitus or crosstable lateral
ograph. film), a fixed dilated loop of bowel on serial radi-
ographs, abdominal wall cellulitis, or progressive deteri-
oration despite maximal medical support. All of these
signs are indicative of necrotic bowel. In the operating
General Considerations room, necrotic bowel is removed and ostomies are cre-
ated. Reanastomosis is performed after the disease is re-
Necrotizing enterocolitis is the most common acquired solved and the infant is bigger (usually > 2 kg and after
GI emergency in the newborn infant; it most often af- 4–6 weeks).
fects preterm infants, with an incidence of 10% in in-
fants of birth weight < 1500 g. In full-term infants, it Course & Prognosis
occurs in association with polycythemia, congenital
heart disease, and birth asphyxia. The pathogenesis of Infants treated either medically or surgically should not
the disease is multifactorial. Previous intestinal is- be refed until the disease is resolved (normal abdominal
chemia, bacterial or viral infection, and immunologic examination, resolution of pneumatosis on radiograph),
immaturity of the gut are thought to play a role in the usually in 10–14 days. Nutritional support during this
genesis of the disorder. In up to 20% of affected in- time should be provided by total parenteral nutrition.
fants, the only risk factor is prematurity. Death occurs in 10% of cases. Surgery is needed in
less than 25% of cases. Long-term prognosis is deter-
mined by the amount of intestine lost. Infants with
Clinical Findings short bowel require long-term support with IV nutri-
The most common presenting sign is abdominal dis- tion and therefore have very long hospitalizations. Even
tention. Other signs include vomiting or increased gas- for those infants, however, the outcome is favorable be-
tric residuals, heme-positive stools, abdominal tender- cause of improved parenteral nutrition formulations.
 THE NEWBORN INFANT / 39

Late strictures—about 3–6 weeks after initial diagno- 7. Intraventricular Hemorrhage

sis—occur in 8% of patients whether treated medically
or surgically and generally require operative manage-
ment. ESSENTIALS OF DIAGNOSIS
& TYPICAL FEATURES
Berseth CL et al: Prolonged small feeding volumes early in life de- • Large bleeds are accompanied by hypotension,
creases the incidence of necrotizing enterocolitis in very low metabolic acidosis, and altered neurologic status.
birth weight infants. Pediatrics 2003:111:529 [PMID:
12612232]. Smaller bleeds can be asymptomatic.
Caplan MS, Jilling T: The pathophysiology of necrotizing entero- • Routine cranial ultrasound scanning is essential
colitis. Neoreviews 2001;2:e103. for diagnosis in infants born at less than
Dimmit RA, Moss LR: Clinical management of necrotizing entero- 32 weeks’ gestation.
colitis. Neoreviews 2001;2:e110.

6. Anemia in the Premature Infant General Considerations

General Considerations Periventricular-intraventricular hemorrhage occurs al-
In the premature infant, the hemoglobin reaches its most exclusively in premature infants. The incidence is
nadir at approximately 8–12 weeks and is 2–3 g/dL 20–30% in infants born at less than 31 weeks’ gestation
lower than that in the full-term infant. The lower nadir and weighing less than 1500 g at birth. The highest
in premature infants appears to be the result of a de- incidence is observed in babies of the lowest gestational
creased erythropoietin response to the low red cell age (< 26 weeks). Bleeding most commonly occurs in
mass. Symptoms of anemia include poor feeding, the subependymal germinal matrix (a region of un-
lethargy, increased heart rate, poor weight gain, and differentiated cells adjacent to or lining the lateral
perhaps apnea. ventricles). Bleeding can extend into the ventricular
cavity. The proposed pathogenesis of bleeding is pre-
sented in Figure 1–8. The critical event is ischemia with
Treatment reperfusion injury to the capillaries in the germinal ma-
trix that occurs in the immediate perinatal period.
The decision to transfuse is based on the presence of The actual amount of bleeding is also influenced by a
clinical symptoms. Transfusion is not indicated in an variety of factors that affect the pressure gradient across
asymptomatic infant simply because of an arbitrary the injured capillary wall. This pathogenetic scheme ap-
hematocrit number. Most infants become symptomatic plies also to intraparenchymal bleeding (venous infarc-
if the hematocrit drops below 20%. With risks of trans- tion in a region rendered ischemic) and to periventricu-
fusion, alternative therapies have been explored. Epo- lar leukomalacia (ischemic white matter injury in a
etin alfa, 250 units/kg, given subcutaneously three watershed region of arterial supply). Central nervous
times per week or added daily with iron dextran to par- system complications in preterm infants are more fre-
enteral nutrition, has been shown to increase hemat- quent in infants exposed antenatally to intrauterine in-
ocrit and reticulocyte count and to decrease the fre- fection.
quency and volume of transfused blood. This treatment
should be reserved for the highest risk infants (those Clinical Findings
born at less than 28–30 weeks’ gestation and below
1000–1200 g). For optimal effect, supplemental iron at Up to 50% of hemorrhages occur at less than 24 hours
a dosage of 4–8 mg/kg/d should be given. Other op- of age, and virtually all occur by the fourth day. The
tions include rescue epoetin alfa at 300 IU/kg/d for clinical syndrome ranges from rapid deterioration
7–10 days for hematocrits < 28% or a late transfusion (coma, hypoventilation, decerebrate posturing, fixed
from the same blood unit used for an infant’s early pupils, bulging anterior fontanelle, hypotension, acido-
transfusions. sis, acute drop in hematocrit) to a more gradual deterio-
ration with more subtle neurologic changes to absence
of any specific physiologic or neurologic signs.
Ohls RK: Human recombinant erythropoietin in the preterm and The diagnosis can be confirmed by real-time ultra-
treatment of anemia of prematurity. Paediatr Drugs sound scan. This can be performed whenever bleeding
2002;4:111 [PMID: 11888358]. is clinically suspected. If symptoms are absent, routine
40 / CHAPTER 1

Ischemic insult to regions of

low baseline cerebral blood flow
(eg, germinal matrix)

Reperfusion

Free oxygen radical injury to

tissue and capillaries

Increased arterial flow:

Impaired venous outflow: Decreased interstitial tissue
Hypoxia
Myocardial failure pressure:
Hypercapnia
Positive-pressure ventilation Infusion of hypertonic agents
Blood pressure surges

Increased gradient across the wall of

injured capillaries

Vessel rupture

Figure 1–8. Pathogenesis of periventricular and intraventricular hemorrhage.

scanning should be done at 10–14 days in all infants Treatment

born at < 29 weeks’ gestation. Hemorrhages are graded
as follows: grade I, germinal matrix hemorrhage only; During acute hemorrhage, supportive treatment (in-
grade II, intraventricular bleeding without ventricular cluding restoration of volume and hematocrit, oxygena-
enlargement; grade III, intraventricular bleeding with tion, and ventilation) should be provided to avoid fur-
ventricular enlargement; and grade IV, any infant with ther cerebral ischemia. Progressive posthemorrhagic
intraparenchymal bleeding. The amount of bleeding is hydrocephalus (if it develops) is treated initially with a
minor (grade I or II) in 75% of infants and major in subgaleal shunt. When the infant is large enough, this
the remainder. can be converted to a ventriculoperitoneal shunt.
Follow-up ultrasound examinations are based on the Although the incidence and severity of intracranial
results of the initial scan. Infants with no bleeding or bleeding have decreased in premature infants, strategies
germinal matrix hemorrhage require only a single late to prevent this complication are still needed. Use of an-
scan at age 4–6 weeks to look for periventricular leuko- tenatal corticosteroids appears to be important in de-
malacia. Any infant with blood in the ventricular sys- creasing this complication, and phenobarbital may have
tem is at risk for posthemorrhagic ventriculomegaly. a role in the mother who has not been prepared with
This is usually the result of impaired absorption of cere- steroids and is delivering at less than 28 weeks’ gesta-
brospinal fluid (CSF), but it can also occur secondary tion. The route of delivery may also play a role, with
to obstructive phenomena. An initial follow-up scan babies delivered by cesarean section showing a de-
should be done 1–2 weeks after the initial scan. Infants creased rate of intracranial bleeds, but this issue remains
with intraventricular bleeding and ventricular enlarge- controversial. Postnatal strategies appear less promising.
ment should be followed every 7–10 days until ventric- Early indomethacin administration may have some
ular enlargement stabilizes or decreases. Infants without benefit in minimizing bleeding, but does not affect
ventriculomegaly should have one additional scan at long-term outcome.
age 4–6 weeks. In addition, all infants born at
29–32 weeks’ gestation should have at least a late scan
Prognosis
(4–6 weeks) to look for ventriculomegaly and periven- No deaths occur as a result of grade I and grade II hem-
tricular leukomalacia. orrhages, whereas grade III and grade IV hemorrhages
 THE NEWBORN INFANT / 41

carry a mortality rate of 10–20%. Posthemorrhagic tachment (I–V), by the zone of the eye involved (1–3,
ventricular enlargement is rarely seen with grade I hem- with zone 1 the posterior region around the macula),
orrhages but is seen in 54–87% of grade II—IV hemor- and by the amount of the retina involved, in “clock
rhages. Very few of these infants will require a ventricu- hours” (eg, a detachment in the upper, outer quadrant
loperitoneal shunt. Long-term neurologic sequelae are of the left eye would be defined as affecting the left
seen no more frequently in infants with grade I and retina from 12 to 3 o’clock).
grade II hemorrhages than in preterm infants without Initial eye examination should be performed at
bleeding. In infants with grade III and grade IV hemor- 4–6 weeks of age in infants with a birth weight
rhages, severe sequelae occur in 20–25% of cases, mild < 1500 g or in those born at < 28 weeks’ gestation, as
sequelae in 35% of cases, and no sequelae in 40% of well as in infants weighing > 1500 g with an unstable
cases. The presence of severe periventricular leukomala- clinical course. Follow-up is done at 2- to 4-week inter-
cia, large parenchymal bleeds, and progressive ventricu- vals until the retina is fully vascularized. Infants with
lomegaly greatly increases the risk of neurologic seque- zone 1 disease need to be followed at 1- to 2-week in-
lae. tervals. Infants with threshold disease (stage III, zone
1 or 2, in five or more continuous clock hours, with in-
Bada HS: Prevention of intracranial hemorrhage. Neoreviews flammatory changes of “plus” disease) are candidates
2000;1:e48. for laser therapy. Although this treatment does not al-
Ment LR et al: Outcome of children in the indomethacin intraven- ways prevent retinal detachment, it reduces the inci-
tricular hemorrhage prevention trial. Pediatrics 2000;105: dence of poor outcomes based on visual acuity and ana-
485 [PMID: 10699097]. tomic outcomes.
Ramsey PS, Rouse DJ: Therapies administered to mothers at risk
for preterm birth and neurodevelopmental outcome in their American Academy of Pediatrics Section on Ophthalmology:
infants. Clin Perinatol 2002;29:725 [PMID: 12616743]. Screening examination of premature infants for retinopathy
Schmidt B et al: Long-term effects of indomethacin prophylaxis in of prematurity. Pediatrics 2001;108:809 [PMID: 11533356].
extremely-low-birth-weight infants. N Engl J Med 2001;344: Phelps DL: Retinopathy of prematurity: History, classification, and
1966 [PMID: 11430325]. pathophysiology. Neoreviews 2001;2:e153.
Shankaran S: Complications of neonatal intracranial hemorrhage. The STOP-ROP Multicenter Study Group: Supplemental thera-
Neoreviews 2000;1:e44. peutic oxygen for prethreshold retinopathy of prematurity
Thorp JA et al: Perinatal factors associated with severe intracranial (STOP-ROP), a randomized, controlled trial. I: Primary out-
hemorrhage. Am J Obstet Gynecol 2001;185:859 [PMID: comes. Pediatrics 2000;105:295 [PMID: 10654946].
11641666].
Volpe JJ: Cerebral white matter injury of the premature infant—
More common than you think. Pediatrics 2003;112:176 9. Discharge & Follow-Up
[PMID: 12737883]. of the Premature Infant
Whitelaw et al: Post haemorrhagic ventricular dilation. Arch Dis
Child Fetal Neonatal Ed 2002;86:72 [PMID: 11882544]. Hospital Discharge
Medical criteria for discharge of the premature infant
8. Retinopathy of Prematurity include the ability to maintain temperature in an open
crib, nippling all feeds and gaining weight, and the ab-
Retinopathy of prematurity occurs only in the incom- sence of apneic and bradycardiac spells requiring inter-
pletely vascularized retina of the premature infant. The vention. Infants going home on supplemental oxygen
incidence of any acute retinopathy in infants weighing should not desaturate too badly (< 80%) in room air or
< 1250 g is 66%, whereas only 6% have retinopathy se- should demonstrate the ability to arouse in response to
vere enough to warrant intervention. The incidence is hypoxia. Factors such as support for the mother at
highest in babies of the lowest gestational age. The con- home and the stability of the family situation play a
dition appears to be triggered by an initial injury to the role in the timing of discharge. Home nursing visits
developing retinal vessels. Hypoxia, shock, asphyxia, vi- and early physician follow-up can be used to hasten dis-
tamin E deficiency, and light exposure have been asso- charge.
ciated with this initial injury. After the initial injury,
normal vessel development may follow or abnormal Follow-Up
vascularization may occur with ridge formation on the
retina. The process can still regress at this point or may With advances in obstetric and maternal care, survival
continue, with growth of fibrovascular tissue into the for infants born at < 28 weeks’ gestation or with birth
vitreous associated with inflammation, scarring, and weights as low as 1000 g is now better than 90%. Sev-
retinal folds or detachment. The disease is graded by enty to 80% survive at 26–27 weeks’ gestation and
stages of abnormal vascular development and retinal de- birth weights of 800–1000 g. Survival at gestational age
42 / CHAPTER 1

Mortality by birthweight
Vermont Oxford Network 2001
100

90

80

70

60
Mortality (%)

50

40

30

20

10

0
501– 601– 701– 801– 901– 1001– 1101– 1201– 1301– 1401–
600 700 800 900 1000 1100 1200 1300 1400 1500
Birthweight (g)

Figure 1–9. Mortality rates before discharge by 100-g birth weight subgroups in 2001. (Reproduced, with permis-
sion, from the Vermont Oxford Network, 2002.)

25 weeks and birth weight 700–800 g is 50–70%, with acuity and strabismus, hearing loss, and growth failure.
a considerable drop-off below this level (Figure 1–9). All of these issues require close multidisciplinary outpa-
These high rates of survival do come with a price in tient follow-up. Infants with residual lung disease are
terms of morbidity. Major neurologic sequelae, includ- candidates for monthly palivizumab (Synagis) injec-
ing cerebral palsy, cognitive delay, and hydrocephalus, tions during their first winter after hospital discharge to
is reported in 10–25% of survivors with birth weights prevent severe infection with respiratory syncytial virus.
< 1500 g. The rate of these sequelae tends to be higher Routine immunizations should be done by chronologic
in infants with lower birth weights. In addition to a age and not age-corrected for prematurity.
higher incidence of severe neurologic sequelae, infants
with birth weights < 1000 g have an increased rate of
American Academy of Pediatrics. Committee on Infectious Dis-
lesser disabilities, including learning and behavioral eases and Committee on Fetus and Newborn: Revised indica-
problems. Risk factors for neurologic sequelae include tions for the use of palivizumab and respiratory syncytial virus
seizures, grade III or IV intracranial hemorrhage, immune globulin intravenous for the prevention of respira-
periventricular leukomalacia, severe IUGR, poor early tory syncytial virus infection. Pediatrics 2003;112:1442
head growth, need for mechanical ventilation, and low [PMID: 14654628].
socioeconomic class. In addition, maternal fever and Bhutta AT et al: Cognitive and behavioral outcomes of school-aged
chorioamnionitis have been associated with an in- children who were born preterm. A meta-analysis. JAMA
2002;288:728 [PMID: 12169077].
creased risk of cerebral palsy. Other morbidities in these
infants include chronic lung disease and reactive airway D’Angio CT et al: Longitudinal, 15-year follow-up of children
born at less than 29 weeks gestation after introduction of sur-
disease, resulting in an increased risk from respiratory factant therapy into a region: Neurologic, cognitive, and edu-
infections and hospital readmissions in the first 2 years, cational outcomes. Pediatrics 2002;110:1094 [PMID:
retinopathy of prematurity with associated loss of visual 12456905].
 THE NEWBORN INFANT / 43

Doyle LW and the Victorian Infant Collaborative Study Group:

Outcome at 5 years of age of children 23–27 weeks gestation:
Refining the prognosis. Pediatrics 2001;108:134 [PMID: CARDIAC PROBLEMS
11433066].
Gross SJ et al: Impact of family structure and stability on academic
IN THE NEWBORN INFANT
outcome in preterm children at 10 years of age. J Pediatr
2001;138:169 [PMID: 11174612].
STRUCTURAL HEART DISEASE
Hack M et al: Functional limitations and special health care needs
of 10- to 14-year old children weighing less than 750 grams 1. Cyanotic Presentations
at birth. Pediatrics 2000;106:554 [PMID: 10969102].
Hack M et al: Outcomes in young adulthood for very-low-birth-
weight infants. N Engl J Med 2002;346:149 [PMID:
11796848]. ESSENTIALS OF DIAGNOSIS
Horbar JD et al: Trends in mortality and morbidity for very low & TYPICAL FEATURES
birth weight infants 1991–1999. Pediatrics 2002;110:143
[PMID: 12093960]. • Cyanosis, initially without associated respiratory
Lorenz JM: Survival of the extremely preterm infant in North distress.
America in the 1990s. Clin Perinatol 2000;27:255 [PMID:
10863649]. • Failure to increase PaO2 with supplemental oxy-
Ment LR et al: Change in cognitive function over time in very-low- gen.
birth-weight infants. JAMA 2003;289:705 [PMID: • Chest radiograph with decreased lung markings
12585948].
suggests right heart obstruction, while increased
O’Connor AR et al: Long-term ophthalmic outcome of low birth
lung markings suggest transposition or venous
weight children with and without retinopathy of prematurity.
Pediatrics 2002;109:12 [PMID: 11773536]. obstruction.
Saari TN and the Committee on Infectious Diseases: Immuniza-
tion of preterm and low birth weight infants. Pediatrics
2003;112:193 [PMID: 12837889].
Saigal S et al: School difficulties at adolescence in a regional cohort
of children who were extremely low birth weight. Pediatrics General Considerations
2000;105:325 [PMID: 10654950].
Saigal S et al: Physical growth and current health status of infants The causes of cyanotic heart disease that occur in the
who were of extremely low birth weight and controls at ado- newborn period are transposition of the great vessels
lescence. Pediatrics 2001;108:407 [PMID: 11483807]. (TOGV), total anomalous pulmonary venous return
Schmidt B et al: Impact of bronchopulmonary dysplasia, brain in- (TAPVR), truncus arteriosus (some types), tricuspid atre-
jury, and severe retinopathy on the outcome of extremely sia, and pulmonary atresia or critical pulmonary stenosis.
low-birth-weight infants at 18 months: Results from the trial
of indomethacin prophylaxis in preterms. JAMA
2003;289:1124 [PMID: 12622582]. Clinical Findings
Vohr BR et al: Neurodevelopmental and functional outcomes of
extremely low birth weight infants in the National Institute
Infants with these disorders present with early cyanosis.
of Child Health and Human Development Neonatal Re- The hallmark of many of these lesions is cyanosis in an
search Network 1993–1994. Pediatrics 2000;105:1216 infant without associated respiratory distress. In most of
[PMID: 10835060]. these infants, tachypnea develops over time either be-
Wood NS et al: Neurologic and developmental disability after ex- cause of increased pulmonary blood flow or secondary
tremely preterm birth. N Engl J Med 2000;343:378 [PMID: to metabolic acidemia from progressive hypoxemia. Di-
10933736]. agnostic aids include comparing the blood gas or oxygen
saturation in room air to that in 100% FiO2. Failure of
Pao2 or SaO2 to increase suggests cyanotic heart disease.
Note: A PaO2, if feasible, is the preferred measure. Satu-
ration in the newborn may be misleadingly high due to
the left-shifted oxyhemoglobin dissociation curve seen
with fetal hemoglobin. Other useful aids are chest radi-
ograph, electrocardiography, and echocardiography.
TOGV is the most common form of cyanotic heart
disease presenting in the newborn period. Examination
generally reveals a systolic murmur and single S2. Chest
radiograph shows a generous heart size and a narrow
mediastinum with normal or increased lung markings.
44 / CHAPTER 1

There is little change in PaO2 or SaO2 with supplemen- Tachypnea, tachycardia, congestive heart failure, and
tal oxygen. Total anomalous pulmonary venous return, metabolic acidosis develop. On examination, all of
in which venous return is obstructed, presents early these infants have abnormalities of the pulses. In aortic
with severe cyanosis and tachypnea because the pul- atresia (hypoplastic left heart syndrome) and stenosis,
monary venous return is obstructed, resulting in pul- pulses are all diminished, whereas in coarctation syn-
monary edema. The chest radiograph typically shows a dromes, differential pulses (diminished or absent in the
small to normal heart size with marked pulmonary lower extremities) are evident. Chest radiographic films
edema. Infants with right heart obstruction (pulmonary in these infants show a large heart and pulmonary
and tricuspid atresia, critical pulmonary stenosis, and edema. Diagnosis is confirmed with echocardiography.
some forms of truncus arteriosus) have decreased lung
markings on chest radiograph and, depending on the 3. Treatment of Cyanotic
severity of hypoxia, may develop metabolic acidemia.
Those forms with an underdeveloped right heart will & Acyanotic Lesions
have left-sided predominance on electrocardiography. Early stabilization includes supportive therapy as
Although tetralogy of Fallot is the most common form needed (eg, IV glucose, oxygen, ventilation for respira-
of cyanotic heart disease, the obstruction at the pul- tory failure, pressor support). Specific therapy includes
monary valve is often not severe enough to result in infusions of prostaglandin E1, 0.025–0.1 µg/kg/min, to
cyanosis in the newborn. In all cases, diagnosis can be maintain ductal patency. In some cyanotic lesions (eg,
confirmed by echocardiography. pulmonary atresia, tricuspid atresia, critical pulmonary
stenosis) in which lung blood flow is ductus-dependent,
2. Acyanotic Presentations this improves pulmonary blood flow and PaO2 by al-
lowing shunting through the ductus to the pulmonary
artery. In left-sided outflow tract obstruction, systemic
blood flow is ductus-dependent; prostaglandins im-
ESSENTIALS OF DIAGNOSIS prove systemic perfusion and resolve the acidosis. Fur-
& TYPICAL FEATURES ther specific management—including palliative surgical
and cardiac catheterization procedures—is discussed in
• Most newborns who present with acyanotic heart Chapter 19.
disease have left-sided outflow obstruction.
• Differentially diminished pulses (coarctation) or PERSISTENT PULMONARY
decreased pulses throughout (aortic atresia).
HYPERTENSION IN
• Metabolic acidemia. THE NEWBORN INFANT
• Chest radiograph showing large heart and pul-
monary edema.
ESSENTIALS OF DIAGNOSIS
& TYPICAL FEATURES
• Onset of symptoms on day 1 of life.
General Considerations
• Hypoxia with poor response to high concentra-
Newborn infants who present with serious acyanotic tions of inspired oxygen.
heart disease usually have congestive heart failure sec- • Right-to-left shunts through the foramen ovale,
ondary to left-sided outflow tract obstruction. Infants ductus arteriosus, or both.
with left-to-right shunt lesions (eg, ventricular septal
defect) may have murmurs in the newborn period, but • Most often associated with parenchymal lung dis-
clinical symptoms do not occur until pulmonary vascu- ease.
lar resistance drops enough to cause significant shunt-
ing and subsequent congestive heart failure (usually at
3–4 weeks of age).
General Considerations
Clinical Findings Persistent pulmonary hypertension (PPHN) results
Infants with left-sided outflow obstruction generally do when the normal decrease in pulmonary vascular resis-
well the first day or so until the ductus arteriosus—the tance after birth does not occur. Most infants so af-
source of all or some of the systemic flow—narrows. fected are full term or postterm, and many have experi-
 THE NEWBORN INFANT / 45

enced perinatal asphyxia. Other clinical associations in- mild respiratory alkalosis may improve oxygenation.
clude hypothermia, meconium aspiration syndrome, Pulmonary vasodilation can be enhanced using the in-
hyaline membrane disease, polycythemia, neonatal sep- haled gas nitric oxide, which is identical or very similar
sis, chronic intrauterine hypoxia, and pulmonary hy- to endogenous endothelium-derived relaxing factor, at
poplasia. doses of 5–20 ppm. In addition, use of high-frequency
There are three causes of PPHN: (1) acute vasocon- oscillatory ventilation has proved effective in many of
striction resulting from perinatal hypoxia, (2) prenatal these infants, particularly those with severe associated
increase in pulmonary vascular smooth muscle develop- lung disease.
ment, and (3) decreased cross-sectional area of the pul- Infants for whom conventional therapy is failing
monary vascular bed because of inadequate vessel num- (poor oxygenation despite maximum support) may re-
ber. In the first, an acute perinatal event leads to quire extracorporeal membrane oxygenation (ECMO).
hypoxia and failure of the pulmonary vascular resis- The infants are placed on bypass, with blood exiting the
tance to drop. In the second, abnormal muscularization baby from the right atrium and returning to the aortic
of the pulmonary resistance vessels results in persistent arch after passing through a membrane oxygenator.
hypertension after birth. The third category includes The lungs are essentially at rest during the procedure,
infants with pulmonary hypoplasia (eg, diaphragmatic and with resolution of the pulmonary hypertension the
hernia). infants are weaned from ECMO back to ventilator
therapy. This therapy can save infants who might oth-
erwise die but has major side effects that must be con-
Clinical Findings sidered prior to its institution. Neurodevelopmental
Clinically, the syndrome is characterized by onset on outcome among survivors of ECMO is similar to that
the first day of life, usually from birth. Respiratory dis- of infants with PPHN managed without the procedure.
tress is prominent, and PaO2 is usually poorly respon- Approximately 10–15% of survivors have significant
sive to high concentrations of inspired oxygen. Many of neurologic sequelae, with cerebral palsy or cognitive de-
the infants have associated myocardial depression with lays. Other sequelae such as chronic lung disease, senso-
resulting systemic hypotension. Echocardiography re- rineural hearing loss, and feeding problems have also
veals right-to-left shunting at the level of the ductus ar- been described in this population.
teriosus or foramen ovale (or both). Chest radiograph
usually shows lung infiltrates related to associated pul-
monary pathology (eg, meconium aspiration, hyaline
ARRHYTHMIAS
membrane disease). If the majority of right-to-left Irregularly irregular heart rates, commonly associated
shunt is at the ductal level, pre- and postductal differ- with premature atrial contractions and less commonly
ences in PaO2 and SaO2 will be observed. with premature ventricular contractions, are noted
often in the first days of life in well newborns. These ar-
rhythmias are benign and of no consequence. Clinically
Treatment significant bradyarrhythmias are seen in association
Therapy for PPHN involves supportive therapy for with congenital heart block. Heart block can be seen in
other postasphyxia problems (eg, anticonvulsants for an otherwise structurally normal heart (associated with
seizures, careful fluid and electrolyte management for maternal lupus) or with structural cardiac abnormali-
renal failure). IV glucose should be provided to main- ties. If fetal hydrops is absent, the bradyarrhythmia has
tain normal blood sugar, and antibiotics should be ad- been well tolerated. Indications for cardiac pacing in-
ministered for possible infection. Specific therapy is clude symptoms of inadequate cardiac output.
aimed at both increasing systemic arterial pressure and On electrocardiography, tachyarrhythmias can be ei-
decreasing pulmonary arterial pressure to reverse the ther wide complex (eg, ventricular tachycardia) or nar-
right-to-left shunting through fetal pathways. First-line row complex (eg, supraventricular tachycardia).
therapy includes oxygen and ventilation (to reduce pul- Supraventricular tachycardia is the most common tachy-
monary vascular resistance) and crystalloid infusions arrhythmia in the neonate and may be a sign of struc-
(10 mL/kg, up to 30 mL/kg) to improve systemic pres- tural heart disease, myocarditis, left atrial enlargement,
sure. Ideally, systolic pressure should be greater than and aberrant conduction pathways. Acute treatment is
60 mm Hg. With compromised cardiac function, sys- ice to the face and, if unsuccessful, adenosine given IV
temic pressors can be used as second-line therapy (eg, at a dose of 50–200 µg/kg. If there is no response, the
dopamine, 5–20 µg/kg/min; dobutamine, 5–20 µg/ dose can be increased up to 300 µg/kg. Long-term ther-
kg/min; or both). Metabolic acidemia should be cor- apy is with digoxin or propranolol. Digoxin should not
rected with sodium bicarbonate because acidemia exac- be used in cases with Wolff–Parkinson–White syn-
erbates pulmonary vasoconstriction. In some cases, a drome. Cardioversion is rarely needed for supraventric-
46 / CHAPTER 1

ular tachycardia but is needed acutely for hemodynami- Clinical Findings

cally unstable ventricular tachycardia.
Infants present in the first hours of life with copious se-
cretions, choking, cyanosis, and respiratory distress. Di-
Beck AE, Hudgins L: Congenital cardiac malformations in the agnosis can be confirmed with chest radiograph after
neonate: Isolated or syndromic? Neoreviews 2003;4:e105. careful placement of a nasogastric tube to the point at
Kinsella JP, Abman SH: Inhaled nitric oxide: Current and future which resistance is met. On chest radiograph, the tube
uses in neonates. Semin Perinatol 2000;24:387 [PMID: will be seen in the blind pouch. If a tracheoesophageal
11153900]. fistula is present to the distal esophagus, gas will be pre-
Marino BS et al: Diagnosis and management of the newborn with sent in the bowel. In cases of esophageal atresia without
suspected congenital heart disease. Clin Perinatol 2001;28: tracheoesophageal fistula, there is no gas in the bowel.
91 [PMID: 11265513].
Schumacher RE, Baumgart S: Extracorporeal membrane oxygena-
tion 2001: The odyssey continues. Clin Perinatol 2001;28: Treatment
629 [PMID: 11570158].
Tanel RE, Rhodes LA: Fetal and neonatal arrhythmias. Clin Peri- The tube in the proximal pouch should be placed on
natol 2001;28:187 [PMID: 11265506]. continuous suction to drain secretions and prevent as-
Walsh MC, Stork EK: Persistent pulmonary hypertension of the piration. The head of the bed should be elevated to pre-
newborn: Rationale therapy based on pathophysiology. Clin vent reflux of gastric contents through the distal fistula
Perinatol 2001;28:609 [PMID: 11570157]. into the lungs. IV glucose and fluids should be pro-
vided and oxygen administered as needed. Definitive
treatment is by operation and depends on the distance
between the segments of esophagus. If the distance is
GASTROINTESTINAL not too great, the fistula can be ligated and the ends of
the esophagus anastomosed. In instances in which the
& ABDOMINAL SURGICAL ends of the esophagus cannot be brought together, the
CONDITIONS IN THE initial surgery entails fistula ligation and a gastrostomy
NEWBORN INFANT for feeding. Echocardiography should be performed
prior to surgery to rule out a right-sided aortic arch. In
(SEE ALSO CHAPTER 20.) those cases, a left-sided thoracotomy would be pre-
ferred.
ESOPHAGEAL ATRESIA &
TRACHEOESOPHAGEAL FISTULA Prognosis
Prognosis is determined primarily by the presence or
absence of associated anomalies. Vertebral, anal, car-
ESSENTIALS OF DIAGNOSIS diac, renal, and limb anomalies are the most likely
& TYPICAL FEATURES anomalies to be observed (VACTERL association).
Evaluation for associated anomalies should be done
early.
• Polyhydramnios.
• Baby with excessive drooling and secretions,
choking with attempted feeding. INTESTINAL OBSTRUCTION
• Unable to pass an orogastric tube to the stomach.

ESSENTIALS OF DIAGNOSIS
& TYPICAL FEATURES

General Considerations • Infants with high intestinal obstruction present

soon after birth with emesis.
These associated conditions are characterized by a blind
esophageal pouch and a fistulous connection between • Bilious emesis represents a malrotation with
the proximal or distal esophagus (or both) and the air- midgut volvulus until proved otherwise.
way. In 85% of affected infants, the fistula is between • Low intestinal obstruction is characterized by ab-
the distal esophagus and the airway. Polyhydramnios is dominal distention and late onset of emesis.
common because of the high level of GI obstruction.
 THE NEWBORN INFANT / 47

General Considerations (high obstruction suspected) or contrast enema (lower

obstruction apparent) to define the area of obstruction.
A history of polyhydramnios is common, and the fluid, if Table 1–20 summarizes the findings expected.
bile-stained, can easily be confused with thin meconium All infants with meconium ileus are presumed to
staining. The higher the obstruction in the intestine, the have cystic fibrosis. Infants with pancolonic
earlier the infant will present with vomiting and the less Hirschsprung disease, colon pseudo-obstruction syn-
prominent the distention will be. The opposite is true for drome, or colonic dysgenesis or atresia may also present
lower intestinal obstructions. Most obstructions are with meconium impacted in the distal ileum. Defini-
bowel atresias, believed to be caused by an ischemic event tive diagnosis of cystic fibrosis is by the sweat chloride
during development. Approximately 30% of cases of test (Na+ and Cl− concentration > 60 mEq/L) or by ge-
duodenal atresia are associated with Down syndrome. netic testing. Approximately 10–20% of infants with
Meconium ileus is a distal small bowel obstruction cystic fibrosis present with meconium ileus. Infants
caused by the exceptionally viscous meconium produced with cystic fibrosis and meconium ileus generally have a
by fetuses with cystic fibrosis. Hirschsprung disease is normal immunoreactive trypsinogen test result on their
caused by a failure of neuronal migration to the myen- newborn screen because of the associated severe ex-
teric plexus of the distal bowel so that the distal bowel ocrine pancreatic insufficiency in utero.
lacks ganglion cells, causing a lack of peristalsis in that re- Any in utero perforation results in meconium peri-
gion with a functional obstruction. tonitis with residual intraabdominal calcifications.
Malrotation with midgut volvulus is a surgical emer- Many of these are completely healed at birth. If the in-
gency that appears in the first days to weeks as bilious fant has no signs of obstruction, no further immediate
vomiting without distention or tenderness. If malrota- evaluation is needed. A sweat test to rule out cystic fi-
tion is not treated promptly, torsion of the intestine brosis should be done at a later date.
around the superior mesenteric artery will lead to Low intestinal obstruction may present with delayed
necrosis of the entire small bowel. For this reason, bil- stooling (> 24 hours in term infants is abnormal) with
ious vomiting in the neonate always demands immedi- mild distention. Radiograph findings of gaseous disten-
ate attention and evaluation. tion should prompt contrast enema to diagnose (and
treat) meconium plug syndrome. If no plug is found,
Clinical Findings the diagnosis may be small left colon syndrome (occur-
Diagnosis of intestinal obstructions depends on plain ring in IDMs) or Hirschsprung disease. Rectal biopsy
abdominal radiographs with either upper GI series will be required to make this diagnosis. Imperforate

Table 1–20. Intestinal obstruction.

Site of Obstruction Clinical Findings Plain Radiographs Contrast Study

Duodenal atresia Down syndrome (30%); “Double bubble” (dilated Not needed
early vomiting, sometimes stomach and proximal
bilious duodenum, no air distal)
Malrotation and Bilious vomiting with onset Dilated stomach and proximal UGI shows displaced duodenojejunal
volvulus anytime in the first few duodenum; paucity of air junction with “corkscrew” deformity
weeks distally (may be normal gas of twisted bowel
pattern)
Jejunoileal atresia, Bilious gastric contents Multiple dilated loops of bowel; Barium or osmotic contrast enema
meconium ileus > 25 mL at birth; progressive intraabdominal calcifications shows microcolon; contrast refluxed
distention and bilious if in utero perforation occurred into distal ileum may demonstrate and
vomiting (meconium peritonitis) relieve meconium obstruction (success-
ful in about 50%)
Meconium plug Distention, delayed stooling Diffuse bowel distention Barium or osmotic contrast enema out-
syndrome; Hirsch- (> 24 h) lines and relieves plug; may show trans-
sprung’s disease ition zone in Hirschsprung’s disease;
delayed emptying (> 24 h) suggests
Hirschsprung’s disease
UGI = upper gastrointesinal tract
48 / CHAPTER 1

anus should be apparent on physical examination, al- alies except intestinal atresias in approximately 10%.
though a rectovaginal fistula with a mildly abnormal-ap- The herniation is thought to be related to abnormal in-
pearing anus can occasionally be confused with normal. volution of the right umbilical vein, although the exact
cause is unknown.
Treatment Therapy is as described for omphalocele.
Nasogastric suction to decompress the bowel, IV glu-
cose, fluid and electrolyte replacement, and respiratory DIAPHRAGMATIC HERNIA
support as necessary should be instituted. Antibiotics This congenital malformation consists of herniation of
are usually indicated. The definitive treatment for most abdominal organs into the hemithorax (usually left)
of these conditions (with the exception of meconium through a posterolateral defect in the diaphragm. It pre-
plug syndrome, small left colon syndrome, and some sents in the delivery room as severe respiratory distress
cases of meconium ileus) is surgery. in an infant with poor breath sounds and scaphoid ab-
domen. The rapidity and severity of presentation—as
Prognosis well as ultimate survival—depend on the degree of pul-
monary hypoplasia, which is a result of compression by
Up to 10% of infants with meconium plug syndrome the intrathoracic abdominal contents in utero. Affected
are subsequently found to have cystic fibrosis or infants are prone to development of pneumothorax.
Hirschsprung disease. For this reason, some surgeons Treatment includes intubation and ventilation as
advocate performance of a sweat chloride test and rectal well as decompression of the GI tract with a nasogastric
biopsy in all of these infants before discharge. The infant tube to intermittent suction. An IV infusion of glucose
with meconium plug syndrome who is still symptomatic and fluid should be started. Chest radiograph confirms
after contrast enema should have a rectal biopsy. the diagnosis. Surgery to reduce the abdominal con-
In cases of duodenal atresia associated with Down syn- tents from the thorax and to close the diaphragmatic
drome, the prognosis will depend on associated anomalies defect is performed after the infant is stabilized. The
(eg, heart defects) and the severity of prestenotic duodenal postoperative course is often complicated by severe pul-
dilation. Otherwise, these conditions usually carry an ex- monary hypertension, requiring therapy with high-fre-
cellent prognosis after surgical repair. quency ventilation, inhaled NO, or ECMO. The mor-
tality rate for this condition is 25–40%, with survival
ABDOMINAL WALL DEFECTS dependent on the degree of pulmonary hypoplasia and
presence of congenital heart disease.
1. Omphalocele
Omphalocele is a membrane-covered herniation of ab- GASTROINTESTINAL BLEEDING
dominal contents into the base of the umbilical cord.
There is a high incidence of associated anomalies (car- Upper Gastrointestinal Bleeding
diac, GI, chromosomal—eg, trisomy 13). The sac may Upper GI bleeding is not uncommon in the newborn
contain liver and spleen as well as intestine. nursery. Old blood (“coffee-ground” material) may be
Acute management of omphalocele involves cover- either swallowed maternal blood or infant blood from a
ing the defect with a sterile dressing soaked with warm bleeding gastric irritation such as gastritis or stress ulcer.
saline to prevent fluid loss, nasogastric decompression, Bright red blood from the stomach is most likely acute
IV fluids and glucose, and antibiotics. If the contents of bleeding, again due to gastritis. Treatment generally
the omphalocele will fit into the abdomen, a primary consists of gastric lavage (a sample can be sent for Apt
surgical closure is done. If not, a staged closure is per- testing to determine if it is mother’s or baby’s blood)
formed, with gradual reduction of the omphalocele and antacid medication. If the volume of bleeding is
contents into the abdominal cavity and a secondary clo- large, intensive monitoring, fluid and blood replace-
sure. Postoperatively, third-space fluid losses may be ex- ment, and endoscopy are indicated (see Chapter 20).
tensive; fluid and electrolyte therapy, therefore, must be
monitored carefully. Lower Gastrointestinal Bleeding
Rectal bleeding is less common than upper GI bleeding
2. Gastroschisis in the newborn and is associated with infections (eg,
In gastroschisis, the intestine extrudes through an ab- Salmonella acquired from the mother perinatally), milk
dominal wall defect lateral to the umbilical cord. There intolerance (blood streaks with diarrhea), or, in stressed
is no membrane or sac and no liver or spleen outside infants, necrotizing enterocolitis. An abdominal radi-
the abdomen. Gastroschisis is associated with no anom- ograph should be obtained to rule out pneumatosis in-
 THE NEWBORN INFANT / 49

testinalis (air in the wall of the bowel) or other abnor- infection: (1) blood-borne transplacental infection of
malities in gas pattern (eg, obstruction). If the radi- the fetus (eg, cytomegalovirus [CMV], rubella,
ograph is negative and the examination is benign, a syphilis); (2) ascending infection with disruption of the
protein hydrolysate or predigested formula (eg, Nu- barrier provided by the amniotic membranes (eg, bacte-
tramigen or Pregestamil) should be tried or the mother rial infections after 12–18 hours of ruptured mem-
instructed to avoid all dairy products in her diet if nurs- branes); and (3) infection on passage through an in-
ing. If the amount of rectal bleeding is large or persis- fected birth canal or exposure to infected blood at
tent, endoscopy will be needed. delivery (eg, herpes simplex, hepatitis B, HIV, bacterial
infections).
GASTROESOPHAGEAL REFLUX Susceptibility of the newborn infant to infection is
related to immaturity of both the cellular and humoral
(See also Chapter 20.) immune systems at birth. This feature is particularly ev-
All people reflux occasionally, and physiologic regurgi- ident in the preterm neonate. Passive protection against
tant reflux is extremely common in infants. Reflux is some organisms is provided by transfer of IgG across
pathologic and should be treated when it results in fail- the placenta during the third trimester of pregnancy.
ure to thrive owing to excessive regurgitation, poor in- Preterm infants, especially those born at less than
take due to dysphagia and irritability, apnea or cyanotic 30 weeks’ gestation, do not have the benefit of the full
episodes (acute life-threatening events), or chronic res- amount of this passively acquired antibody.
piratory symptoms of wheezing and recurrent pneumo-
nias. Diagnosis is clinical, with confirmation by barium BACTERIAL INFECTIONS
swallow or pH probe study.
Initial steps in treatment include prone positioning 1. Bacterial Sepsis
and thickened feeds (rice cereal, 1 tbsp/oz of formula)
for those with frequent regurgitation and poor weight
gain. Gastric acid suppressants such as ranitidine ESSENTIALS OF DIAGNOSIS
(2 mg/kg bid) or lansoprazole (1.5 mg/kg/d), along with & TYPICAL FEATURES
a prokinetic agent such as metaclopramide (0.1 mg/kg
tid–qid), can also be used. Because most infants improve • Most infants with early-onset sepsis present at
by 12–15 months of age, surgery is reserved for the most < 24 hours of age.
severe cases, especially those with chronic neurologic or • Respiratory distress is the most common present-
respiratory conditions that exacerbate reflux and those ing symptom.
who have life-threatening events caused by reflux.
• Hypotension, acidemia, and neutropenia are as-
Bohn D: Congenital diaphragmatic hernia. Am J Respir Crit Care
sociated clinical findings.
Med 2002;166:911 [PMID: 12359645]. • The presentation of late-onset sepsis is more sub-
Cass DL, Wesson DE: Advances in fetal and neonatal surgery for tle.
gastrointestinal anomalies and disease. Clin Perinatol
2003;29:1 [PMID: 11917733].
Cohen MS et al: Influence of congenital heart disease on survival in
children with congenital diaphragmatic hernia. J Pediatr
2002;141:25 [PMID: 12091847]. General Considerations
Jadcherla SR: Gastroesophageal reflux in the neonate. Clin Perina-
tol 2002;29:135 [PMID: 11917735]. The incidence of early-onset (< 5 days) neonatal bacter-
Rodgers BM: Upper gastrointestinal hemorrhage. Pediatr Rev ial infection is 4–5 per 1000 live births. If rupture of
1999;20:171 [PMID: 10233176]. the membranes occurs more than 24 hours prior to de-
Squires RH: Gastrointestinal bleeding. Pediatr Rev 1999; livery, the infection rate increases to 1 per 100 live
20:95 [PMID: 10073071]. births. If early rupture of membranes with chorioam-
nionitis occurs, the infection rate increases further to
1 per 10 live births. Irrespective of membrane rupture,
infection rates are five times higher in preterm than in
INFECTIONS IN THE NEWBORN full-term infants.
INFANT
Clinical Findings
The fetus and the newborn infant are very susceptible Early-onset bacterial infections appear most commonly
to infections. There are three major routes of perinatal on day 1 of life, and the majority of cases appear at <
50 / CHAPTER 1

12 hours. Respiratory distress due to pneumonia is the Table 1–21. Guidelines for evaluation of neonatal
most common presenting sign. Other features include bacterial infection in the full-term infant.
unexplained low Apgar scores without fetal distress,
poor perfusion, and hypotension. Late-onset bacterial Clinical
infection (at > 5 days of age) presents in a more subtle Signs of Evaluation and
manner, with poor feeding, lethargy, hypotonia, tem- Risk Factor Infection Treatment
perature instability, altered perfusion, new or increased
oxygen requirement, and apnea. Late-onset bacterial Delivery 12–18 h None Observation
sepsis is more often associated with meningitis or other after rupture of
localized infections. membranes
Low total white counts, absolute neutropenia Delivery > 12–18 h None Complete blood count
(< 1000/mL), and elevated ratios of immature to ma- after rupture of (CBC), blood culture,
ture neutrophils are suggestive of neonatal bacterial in- membranes, broad-spectrum antibiot-
fection. Thrombocytopenia is also a common feature. chorioamnionitis ics for 48–72 hc
Other laboratory signs are hypoglycemia or hyper- Delivery > 12–18 h None CBC, blood culture,
glycemia with no change in glucose administration, un- after rupture broad-spectrum antibi-
explained metabolic acidosis, and elevated C reactive of membranes, otics for 48–72 hc
protein. In early-onset bacterial infection, pneumonia is chorioamnionitis,
invariably present; chest radiograph films show infil- maternal antibioticsa
trates, but these infiltrates cannot be distinguished from
those resulting from other causes of neonatal lung dis- With or without risk Present CBC, blood and CSF
factors cultures, perhaps urine
ease. Definitive diagnosis is made by positive cultures
culture (see below);
from blood, CSF, and the like. broad-spectrum
Early-onset infection is most often caused by group antibioticsb
B β-hemolytic streptococci (GBS) and gram-negative a
enteric pathogens (most commonly Escherichia coli). Minimum of 24 h of observation is indicated if no treatment is
Other organisms to consider are Haemophilus influen- given.
b
zae and Listeria monocytogenes. Late-onset sepsis is Irrespective of age at presentation, any infant who appears in-
fected by clinical criteria should undergo cerebrospinal fluid (CSF)
caused by coagulase-negative staphylococci (most com- examination. Urine culture is indicated in the evaluation of infants
mon in infants with indwelling central venous lines), who were initially well but have developed symptoms after 2–3 d
Staphylococcus aureus, GBS, Enterococcus, Pseudomonas, of age.
and other gram-negative organisms. c
If clinical signs are absent, close observation without treatment
may be sufficient.
Treatment
A high index of suspicion is important in the diagnosis
and treatment of neonatal infection. Table 1–21 pre- 2.5 mg/kg/dose q12–24h (depending on gestational
sents guidelines for the evaluation and treatment of age), or cefotaxime, 100 mg/kg/d divided q12h. In in-
full-term infants with risk factors or clinical signs of in- fants > 34 weeks’ gestation, gentamicin can also be
fection. Because the risk of infection is greater in the given at a dose of 4 mg/kg q24h. Late-onset infections
preterm infant and because respiratory disease is a can also be caused by the same organisms, but coverage
common sign of infection, any preterm infant with res- may need to be expanded to include staphylococci. In
piratory disease requires blood cultures and broad- particular, the preterm infant with an indwelling line is
spectrum antibiotic therapy for 48–72 hours pending at risk for infection with coagulase-negative staphylo-
the results of cultures. An examination of CSF should cocci, for which vancomycin is the drug of choice in
be performed when infection is highly suspected on a a dosage of 10–15 mg/kg q8–24h depending on
clinical basis (eg, associated hypotension, persistent gestational and postnatal ages. Initial broad-spectrum
metabolic acidosis, neutropenia) or if the blood culture coverage should also include a third-generation
is positive. Antibiotic coverage should be directed cephalosporin (cefotaxime or ceftazidime 100 mg/kg/day
initially toward suspected organisms. Early-onset sepsis divided q12h when Pseudomonas aeruginosa is strongly
is usually caused by GBS or gram-negative enteric or- suspected). To prevent the development of van-
ganisms; broad-spectrum coverage, therefore, should comycin-resistant organisms, vancomycin should be
include ampicillin plus an aminoglycoside or third- stopped as soon as cultures and sensitivities indicate it is
generation cephalosporin—for example, ampicillin, not needed for ongoing therapy. Other supportive
100–150 mg/kg/d divided q12h, and gentamicin, therapy includes the administration of IVIG
 THE NEWBORN INFANT / 51

(500–750 mg/kg) to infants with known overwhelming 2. Meningitis

infection. The duration of treatment for proved sepsis
is 10–14 days of IV antibiotics. In addition, recombi- Any newborn with bacterial sepsis is also at risk for
nant human granulocyte colony-stimulating factor meningitis. The incidence is low in infants with early-
(rhG-CSF) is under investigation for treatment of neu- onset sepsis but much higher in infants with late-onset
tropenia in the septic infant. In sick infants, the essen- infection. The work-up for any newborn with signs of
tials of good supportive therapy should be provided: IV infection should include a spinal tap. Diagnosis is
glucose and nutritional support, volume expansion, use suggested by a CSF protein > 150 mg/dL, glucose
of pressors as needed, and oxygen and ventilator sup- < 30 mg/dL, > 25 leukocytes/mL, and a positive Gram
port. stain. The diagnosis is confirmed by culture. The most
Prevention of neonatal GBS infection has been common organisms are GBS and gram-negative enteric
achieved with intrapartum administration of penicillin bacteria. Although sepsis can be treated with antibiotics
given > 4 hours prior to delivery. The current clinical for 10–14 days, meningitis often requires 21 days. The
guideline (Figure 1–10) is to perform a vaginal and rec- mortality rate of neonatal meningitis is approximately
tal GBS culture at 35–37 weeks’ gestation for all preg- 10%, with significant neurologic morbidity present in
nant women. Prophylaxis with penicillin is given to one third of the survivors.
GBS-positive women as well as those who have un-
known GBS status at delivery with risk factors for in-
fection. Figure 1–11 presents a suggested strategy for
3. Pneumonia
the infant born to a mother who received intrapartum The respiratory system can be infected in utero or on
prophylaxis for prevention of early-onset GBS or for passage through the birth canal. Early-onset neonatal
suspected chorioamnionitis. Some authors also recom- infection is usually associated with pneumonia. Pneu-
mend selective neonatal prophylaxis with 50,000 U/kg monia should also be suspected in older neonates with a
of penicillin G given IM if adequate intrapartum treat- recent onset of tachypnea, retractions, and cyanosis. In
ment has not been given. infants already receiving respiratory support, an in-

Vaginal and Rectal GBS Cultures at 35–37 Weeks' Gestation

for ALL Pregnant Womena

IAP INDICATED IAP NOT INDICATED

• Previous infant with invasive GBS disease • Previous pregnancy with a positive GBS screening
• GBS bacteriuria during current pregnancy culture (unless a culture also was positive during the
• Positive GBS screening culture during current current pregnancy or previous infant with invasive
pregnancy (unless a planned cesarean delivery is GBS disease)
performed in the absence of labor or membrane • Planned cesarean delivery performed in the absence
rupture) of labor or membrane rupture (regardless of GBS
• Unknown GBS status AND any of the following: culture status)
• Delivery at <37 weeks' gestation • Negative vaginal and rectal GBS screening culture in
• Membranes ruptured for ≥18 hours late gestation, regardless of intrapartum risk factors
• Intrapartum fever (temperature ≥38.0°C [≥100.4°F])b
a
Exceptions: women with GBS bacteriuria during the current pregnancy or women with a previous infant with invasive GBS disease.
b
If chorioamnionitis is suspected, broad-spectrum antimicrobial therapy that includes an agent known to be active against GBS should replace GBS IAP.
GBS = group B streptococcus, IAP = intrapartum antimicrobial prophylaxis.

Figure 1–10. Indications for intrapartum antimicrobial prophylaxis to prevent early-onset GBS disease using a uni-
versal prenatal culture screening strategy at 35–37 weeks’ gestation for all pregnant women. (Reproduced, with per-
mission, from the American Academy of Pediatrics: Red Book 2003 Report of the Committee on Infectious Disease, 2003.)
52 / CHAPTER 1

Maternal IAP for GBS?a Maternal Antimicrobial Agents for Suspected

Chorioamnionitis?
Yes
Yes
Signs of Neonatal Sepsis?
No Yes
Full Diagnostic Evaluationb
Empiric Therapyc
Gestational Age < 35 weeks?
No Yes

Duration of IAP Before Delivery < 4 h?e Limited Evaluationd

Observe ≥48 Hours
No Yes
If Sepsis Is Suspected, Full Diagnostic Evaluationb
No Evaluation and Empiric Therapyc
No Therapy
Observe ≥ 48 hourf
a
If no maternal IAP for GBS was administered despite an indication being present, data are insufficient on which to recommend a single management
strategy.
b
Includes complete blood cell (CBC) count with differential, blood culture, and chest radiograph if respiratory abnormalities are present. When signs
of sepsis are present, a lumber puncture, if feasible, should be performed.
c
Duration of therapy varies depending on results of blood culture, cerebrospinal fluid findings (if obtained), and the clinical course of the infant.
If laboratory results and clinical course do not indicate bacterial infection, duration may be as short as 48 hours.
d CBC including (WBC) count with differential and blood culture.
e
Applies only to penicillin, ampicillin, or cefazolin and assumes recommended dosing regimens.
f
A healthy-appearing infant who was ≥ 38 weeks' gestation at delivery and whose mother received ≥ 4 hours of IAP before delivery may be discharged
home after 24 hours if other discharge criteria have been met and a person able to comply fully with instructions for home observation will be present.
If any one of these conditions is not met, the infant should be observed in the hospital for at least 48 hours and until criteria for discharge are achieved.

Figure 1–11. Empiric management of a neonate born to a mother who received intrapartum antimicrobial pro-
phylaxis (IAP) for prevention of early-onset GBS (group B streptococcal) disease or chorioamnionitis. (Reproduced,
with permission, from the American Academy of Pediatrics: Red Book 2003 Report of the Committee on Infectious Disease,
2003.)

crease in the requirement for oxygen or ventilator sup- anomalies, starting with an ultrasound examination and
port may indicate pneumonia. Not only common bac- a voiding cystourethrogram, should be done subse-
teria but also viruses (CMV, respiratory syncytial virus, quently.
adenovirus, influenza, herpes simplex, parainfluenza)
and Chlamydia can cause the disease. In infants with 5. Otitis Media
preexisting respiratory disease, intercurrent pulmonary
infections may contribute to the ultimate severity of Otitis media occurs in a significant number of long-
chronic lung disease. term nursery occupants. It is particularly common in
infants who have had prolonged endotracheal intuba-
4. Urinary Tract Infection tion or an indwelling nasogastric feeding tube. Evalua-
tion for infection in such an infant is not complete
Infection of the urine is uncommon in the first days of without an ear examination. Gram-negative enteric
life. Urinary tract infection in the newborn can occur in pathogens are more commonly found infecting agents
association with genitourinary anomalies and is caused in nursery occupants than in outpatients.
by gram-negative enteric pathogens, Enterococcus, or
other organisms. Urine should be evaluated as part of
the work-up for late-onset infection. Culture should be
6. Omphalitis
obtained either by suprapubic aspiration or bladder A normal umbilical cord stump will atrophy and sepa-
catheterization. Antibiotic IV therapy is continued for rate at the skin level. A small amount of purulent mate-
7–10 days if the blood culture is negative and clinical rial at the base of the cord is common but can be mini-
signs resolve quickly. Evaluation for genitourinary mized by keeping the cord open to air and cleaning the
 THE NEWBORN INFANT / 53

base with alcohol several times a day. The cord can be- of colonization. A much smaller percentage (2–5%) de-
come colonized with streptococci, staphylococci, or velop systemic disease.
gram-negative organisms that can cause local infection. Clinical features of fungal sepsis can be indistin-
Infections are more common in cords manipulated for guishable from those of late-onset bacterial sepsis but
venous or arterial lines. Omphalitis is diagnosed when may be more subtle. Thrombocytopenia may be the
redness and edema develop in the soft tissues around earliest and only sign. Deep organ involvement (renal,
the stump. Local and systemic cultures should be ob- eye, endocarditis) is commonly associated with systemic
tained. Treatment is with broad-spectrum IV antibi- candidiasis. Treatment is with amphotericin B
otics (usually nafcillin 50–75 mg/kg/d divided q8–12h (0.5–1.5 mg/kg/d). In severe infections, flucytosine
and a third-generation cephalosporin). Complications (50–150 mg/kg/d) can be added for synergistic cover-
are determined by the degree of infection of the cord age. (See Chapter 39.) Prophylaxis with oral mycostatin
vessels and include septic thrombophlebitis, hepatic ab- at 0.5–1 mL PO qid or fluconazole at 3–6 mg/kg/d as a
scess, necrotizing fasciitis, and portal vein thrombosis. single dose diminishes intestinal colonization with yeast
Surgical consultation should be obtained because of the and decreases the frequency of systemic disease.
potential for necrotizing fasciitis. Malassezia furfur is also seen in infants with central
lines receiving IV fat emulsion. To eradicate this organ-
ism, as well as Candida species, it is necessary to remove
Baltimore RS et al: Early-onset neonatal sepsis in the era of group B the indwelling line.
streptococcal prevention. Pediatrics 2001;108:1094 [PMID:
11694686].
Philip AGS: Neonatal meningitis in the new millennium. Neore- Benjamin DK et al: When to suspect fungal infection in neonates:
views 2003;4:e73. A clinical comparison of Candida albicans and Candida
parasilosis fungemia with coagulase-negative staphylococcal
Schrag S et al: Prevention of perinatal group B streptococcal dis-
bacteremia. Pediatrics 2000;106:712 [PMID: 11015513].
ease: Revised guidelines from CDC. MMWR Aug 16,
2002;51(RR11):1 [PMID: 12211284]. Kicklighter SD: Antifungal agents and fungal prophylaxis in the
neonate. Neoreviews 2002;3:e249.
Schrag SJ et al: Group B streptococcal disease in the era of intra-
partum antibiotic prophylaxis. N Engl J Med 2000;342:
15 [PMID: 10620644].
Schrag SJ et al: A population based comparison of strategies to pre-
CONGENITAL VIRAL & PARASITIC
vent early-onset group B streptococcal disease in neonates. INFECTIONS (SEE ALSO
N Engl J Med 2002;347:233 [PMID: 12140298]. CHAPTERS 36 & 39.)
Sinha A et al: Intrapartum antibiotics and neonatal invasive infec-
tions caused by organisms other than group B streptococcus. 1. Cytomegalovirus Infection
J Pediatr 2003;142:492 [PMID:12756379].
Stoll BJ et al: Late onset sepsis in very low birth weight neonates:
CMV is the most common virus transmitted in utero.
The experience of the NICHD neonatal research network. The incidence of congenital infection ranges from
Pediatrics 2002;110:285 [PMID: 12165580]. 0.2% to 2.2% of live births. Transmission of CMV can
Stoll BJ et al: Changes in pathogens causing early onset sepsis in occur during either primary or reactivated infection in
very-low-birth-weight infants. N Engl J Med 2002;347: the mother. An important source of infection is chil-
240 [PMID: 12140299]. dren (especially those in a day care setting), who trans-
Velaphi S et al: Early-onset group B streptococcal infection after a mit the virus to parents and workers. The incidence of
combined maternal and neonatal group B streptococcal primary infection in pregnancy is 1–4%, with a
chemoprophylaxis strategy. Pediatrics 2003;111:541 [PMID: 40% transplacental transmission rate to the fetus. Of
12612234].
these infants, 85–90% are asymptomatic at birth,
Young TE: Aminoglycoside therapy in neonates: With particular
reference to gentamicin. Neoreviews 2002;3:e243.
whereas 10–15% have clinically apparent disease—he-
patosplenomegaly, petechiae, small size for gestational
age, microcephaly, direct hyperbilirubinemia, thrombo-
cytopenia, intracranial calcifications, and chorioretini-
FUNGAL SEPSIS tis. The risk of neonatal disease is higher when the
With the survival of smaller, sicker infants, infection mother acquires the infection in the first half of preg-
with Candida species has become more common. In- nancy. The incidence of reactivated infection in preg-
fants of low birth weight with central lines who have nancy is less than 1%, with an incidence of clinically
had repeated exposures to broad-spectrum antibiotics apparent disease of 0–1%. Diagnosis in the neonate
are at highest risk. For infants of birth weight < 1500 g, should be confirmed by culture of the virus from urine.
colonization rates of 27–64% have been demonstrated, Rapid diagnosis is possible with antigen detection tech-
with many of these infants developing cutaneous le- niques and polymerase chain reaction (PCR) testing.
sions although the GI tract appears to be the initial site Diagnosis can also be confirmed in utero from an am-
54 / CHAPTER 1

niocentesis specimen. Although experimental and not varicella infection develops within this perinatal risk pe-
routinely recommended, ganciclovir therapy has been riod, 1.25 mL of varicella immune globulin should be
used in some severely ill neonates. given to the newborn. If this has not been done, the ill-
The mortality rate in patients with symptomatic ness can be treated with IV acyclovir (30 mg/kg/d di-
congenital CMV may be as high as 20%. Sequelae such vided q8h).
as hearing loss, mental retardation, delayed motor de- Hospitalized premature infants of at least 28 weeks’
velopment, chorioretinitis and optic atrophy, seizures, gestation whose mothers have no history of chicken-
language delays, and learning disability occur in 90% of pox—and all infants of less than 28 weeks’ gestational
symptomatic survivors. The incidence of complications age—should receive varicella immune globulin follow-
is 5–15% in asymptomatic infants; the most frequent ing any postnatal exposure. Susceptible women of child-
complication is hearing loss, which can be progressive. bearing age should be immunized with varicella vaccine.
Perinatal infection can also occur with acquisition of
virus around the time of delivery. These infections are 4. Toxoplasmosis
generally asymptomatic and without sequelae. Postnatal
infection is usually asymptomatic but can cause hepati- Toxoplasmosis is caused by the protozoan Toxoplasma
tis, pneumonitis, and neurologic illness in compro- gondii. Maternal infection occurs in 0.1–0.5% of preg-
mised seronegative premature infants. The virus can be nancies and is usually asymptomatic. When primary in-
acquired postnatally through transfusions or ingestion fection occurs during pregnancy, up to 40% of the fetuses
of CMV-infected breast milk. Transfusion risk can be become infected, of whom 15% have severe damage. The
minimized by using frozen, washed red blood cells or sources of transmission include exposure to cat feces and
CMV antibody-negative donors. ingestion of raw or undercooked meat. Although the risk
of transmission increases to 90% near term, fetal damage
is most likely to occur when maternal infection occurs in
2. Rubella the second to sixth month of gestation.
Congenital rubella infection occurs as a result of rubella Clinical findings include growth retardation, chori-
infection in the mother during pregnancy. The fre- oretinitis, seizures, jaundice, hydrocephalus, micro-
quency of infection and damage in the fetus is as high cephaly, cerebral calcifications, hepatosplenomegaly,
as 80% in mothers infected during the first trimester. adenopathy, cataracts, maculopapular rash, thrombocy-
Fetal infection rates decline in the second trimester be- topenia, and pneumonia. The majority of affected in-
fore increasing again in the third trimester. Fetal dam- fants are asymptomatic at birth but show evidence of
age generally does not occur in infections acquired after damage (chorioretinitis, blindness, low IQ, hearing
18 weeks’ gestation. Clinical features of congenital loss) at a later time. The serologic diagnosis is based on
rubella include adenopathy, bone radiolucencies, en- a positive IgA or IgM in the first 6 months of life or a
cephalitis, cardiac defects (pulmonary arterial hypopla- persistent IgG beyond 12 months. Infants with sus-
sia and patent ductus arteriosus), cataracts, retinopathy, pected infection should have eye and auditory examina-
growth retardation, hepatosplenomegaly, thrombocy- tions and a CT scan of the brain. Organism isolation
topenia, and purpura. Affected infants can be asympto- from placenta or cord blood and PCR tests are also
matic at birth but develop clinical sequelae during the available for diagnosis in the neonate and from amnio-
first year of life. The diagnosis should be suspected in centesis specimens.
cases of a characteristic clinical illness in the mother Spiramycin treatment of primary maternal infection
(rash, adenopathy, arthritis) confirmed by serologic is used to try to reduce transmission to the fetus.
testing. Diagnosis can be confirmed by an increase in Neonatal treatment using pyrimethamine and sulfadi-
serum rubella-specific IgM or culture of pharyngeal se- azine with folinic acid can improve long-term outcome.
cretions in the baby. Congenital rubella is now rare be- (See Chapter 39.)
cause of widespread immunization.
PERINATALLY ACQUIRED VIRAL
3. Varicella INFECTIONS
Congenital varicella infection is rare (< 5% after infec- 1. Herpes Simplex
tion acquired during the first or second trimester) but
may cause a constellation of findings, including limb
(See also Chapter 36.)
hypoplasia, cutaneous scars, microcephaly, cortical at- Herpes simplex virus (HSV) infection is most com-
rophy, chorioretinitis, and cataracts. Perinatal exposure monly acquired at the time of birth during transit
(5 days before to 2 days after delivery) can cause severe through an infected birth canal. The mother may have
to fatal disseminated varicella in the infant. If maternal either primary or reactivated secondary infection. Pri-
 THE NEWBORN INFANT / 55

mary maternal infection, because of the high titer of or- infection. In these cases, infection in the neonate is cur-
ganism and the absence of maternal antibodies, poses rently not preventable. Therefore, any infant who pre-
the greatest risk to the infant. The risk of neonatal in- sents at the right age with symptoms consistent with
fection with vaginal delivery in this setting is 33–50%. neonatal herpes should be cultured and started on acy-
Seventy percent of mothers with primary herpes at the clovir pending the results of those cultures.
time of delivery are asymptomatic. The risk to an infant The prognosis is good for localized skin and mu-
born to a mother with recurrent herpes simplex is much cosal disease that does not progress. The mortality rate
lower (< 0–5%). Time of presentation of localized for both disseminated and CNS herpes is high, with
(skin, eye, mouth) or disseminated disease (pneumonia, significant rates of morbidity among survivors despite
shock, hepatitis) in the infant is usually 5–14 days of treatment.
age. CNS disease usually presents at 14–28 days with
lethargy and seizures. In about 10% of cases, presenta- 2. Hepatitis B & C
tion can be as early as day 1 of life. Disease appearing
this early suggests in utero infection. In about one third (See also Chapter 21.)
of patients, localized skin, eye, and mouth disease is the Infants can be infected with hepatitis B at the time of
first indication of infection. In another third, dissemi- birth. Clinical illness is rare in the neonatal period, but
nated or CNS disease precedes skin, eye, and mouth infants exposed in utero are at high risk of becoming
findings, whereas the remaining third have dissemi- chronic HBsAg carriers, developing chronic active hep-
nated or CNS disease in the absence of skin, eye, and atitis and, later, hepatocellular carcinoma. The presence
mouth disease. Preliminary diagnosis can be made by of HBsAg should be determined in all pregnant
scraping the base of a vesicle and finding multinucle- women. If the result is positive, the infant should re-
ated giant cells. Viral culture from vesicles, usually posi- ceive HBIG and hepatitis B vaccine as soon as possible
tive in 24–72 hours, makes the definitive diagnosis. after birth, followed by two subsequent vaccine doses at
PCR technology can assist in diagnosis. 1 and 6 months of age. If HBsAg has not been tested
Acyclovir (60 mg/kg/d given q8h) is the drug of prior to birth in a mother at risk, the test should be run
choice for neonatal herpes infection. Localized disease is after delivery and hepatitis B vaccine given within
treated for 14 days, and a 21-day course is used for dis- 12 hours after birth. If the mother is subsequently
seminated or CNS disease. Treatment improves sur- found to be positive, HBIG should be given as soon as
vival of neonates with CNS and disseminated disease possible (preferably within 48 hours, but not later than
and prevents the spread of localized disease. Prevention 1 week after birth). Subsequent vaccine doses should be
is possible by not allowing delivery through an infected given at 1 and 6 months of age. In premature infants
birth canal (eg, by cesarean section within 6 hours after born to HBsAg-positive mothers, vaccine and HBIG
rupture of the membranes). However, antepartum cer- should be given at birth, but a three-vaccine hepatitis B
vical cultures are poor predictors of the presence of series should be given after a weight of 2000 g is at-
virus at the time of delivery. Furthermore, given the tained.
low incidence of infection in the newborn from sec- Hepatitis C perinatal transmissions occur in about
ondary maternal infection, cesarean section is not indi- 5% of infants born to mothers who carry the virus. At
cated for asymptomatic mothers with a history of her- the present time, no prevention strategies exist. Up to
pes. Cesarean sections are performed in mothers with 12 months of age, the only reliable screen for hepatitis
active lesions (either primary or secondary) at the time C infection is PCR. After that time, the presence of
of delivery. Infants born to mothers with a history of hepatitis C antibodies in the infant strongly suggests
HSV infection but no active lesions can be observed that infection has occurred.
closely after birth. Cultures should be obtained and
acyclovir treatment initiated only for clinical signs con-
sistent with herpes virus infection. Infants born to
3. Enteroviral Infection
mothers with active lesions—irrespective of the route of Enteroviral infections occur with greatest frequency in
delivery—should be cultured (eye, oropharynx, umbili- the late summer and early fall. Infection is usually ac-
cus, rectum) 24 hours after delivery. If the infant is col- quired in the perinatal period. There is often a history
onized (positive cultures) or if symptoms consistent of maternal illness (fever, diarrhea, rash) in the week
with herpes infection develop, treatment with acyclovir prior to delivery. The illness appears in the infant in the
should be started. In cases of maternal primary infec- first 2 weeks of life and is most commonly characterized
tion at the time of vaginal delivery, the infant should be by fever, lethargy, irritability, diarrhea, and rash but is
cultured and started on acyclovir pending the results of not severe. More severe forms occasionally occur, espe-
cultures. The major problem facing perinatologists is cially if infection occurs before 1 week of age, including
the high percentage of asymptomatic primary maternal meningoencephalitis and myocarditis, as well as a dis-
56 / CHAPTER 1

seminated illness with hepatitis, pneumonia, shock, and be used. Gloves should be worn during all procedures
disseminated intravascular coagulation. Diagnosis can involving blood and blood-contaminated fluids, intu-
be confirmed by culture (rectum, CSF, blood) or by the bation, and any invasive procedures using needles.
more rapid PCR techniques. When a splash exposure is possible (eg, in the delivery
No therapy has proved efficacy. The prognosis is room), a mask and eye covers should be used.
good for all symptom complexes except severe dissemi-
nated disease, which carries a high mortality rate.
OTHER INFECTIONS
4. HIV Infection 1. Congenital Syphilis
(See also Chapter 37.) The infant is usually infected in utero by transplacental
Human immunodeficiency virus (HIV) can be ac- passage of Treponema pallidum. Active primary and sec-
quired in utero or at the time of delivery, or can be ondary maternal syphilis leads to fetal infection in
transmitted postpartum via breast milk. The majority nearly 100% of infants; latent disease in 40%; and late
of transmission occurs during the 2 weeks prior to de- disease in 10%. Fetal infection is rare at under
livery and during delivery. Transmission of virus occurs 18 weeks’ gestation. Fetal infection can result in still-
in 13–30% of births. Administration of zidovudine birth or prematurity. Findings consistent with early
during pregnancy starting at 14–34 weeks’ gestation, congenital syphilis (presentation at under 2 years) in-
intrapartum, and for the first 6 weeks of life in the new- clude mucocutaneous lesions, lymphadenopathy, he-
born at a dosage of 2 mg/kg PO qid decreases vertical patosplenomegaly, bony changes, and hydrops. How-
transmission to 7%. Shorter courses of zidovudine are ever, in the newborn period, infants are often
also associated with decreased disease transmission, as is asymptomatic, so that diagnosis is based on maternal
cesarean delivery. The combination of zidovudine treat- and infant serologic testing and is only presumptive.
ment and cesarean delivery can lower transmission to Later manifestations (at over age 2 years) include
2%. The addition of other anti-HIV therapy may fur- Hutchinson teeth and mulberry molars, keratitis, chori-
ther reduce the risk of ante- and intrapartum viral oretinitis, glaucoma, hearing loss, saddle nose, saber
transmission. Current guidelines for use of antiretrovi- shins, and mental retardation. An infant should be eval-
ral drugs in pregnant HIV-infected women are similar uated for congenital syphilis if it is born to a mother
to those for nonpregnant patients (eg, highly active with positive nontreponemal tests confirmed by a posi-
retroviral combination therapy). The risk of transmis- tive treponemal test but without documented adequate
sion is increased in mothers with advanced disease, high treatment (parenteral penicillin G), including the ex-
viral loads, low CD4 counts, and p24 antigenemia. Pre- pected fourfold decrease in nontreponemal antibody
maturity, vaginal delivery, ruptured membranes over titer. Infants of mothers treated less than 1 month be-
4 hours, and chorioamnionitis also increase the trans- fore delivery also require evaluation. Evaluation should
mission rate. Diagnosis is based on clinical, immuno- include physical examination, a quantitative nontre-
logic, and serologic findings. Newborns with congeni- ponemal serologic test for syphilis, CSF examination
tally acquired HIV are often free of symptoms. for cell count, protein and VDRL, long bone radi-
Jaundice, neonatal giant-cell hepatitis, and thrombocy- ographs, and antitreponemal IgM. A definitive diagno-
topenia have been reported at birth. Failure to thrive, sis can be made on rare occasions when the organism is
lymphadenopathy, hepatosplenomegaly, oral thrush, identified by dark-field microscopy or pathologic exam-
chronic diarrhea, bacterial infections with common or- ination of the placenta. Guidelines for therapy are pre-
ganisms, and an increased incidence of upper and lower sented in Table 1–22. Infants should be treated for
respiratory diseases, including lymphoid interstitial congenital syphilis if they have proven or probable dis-
pneumonitis, may appear early in life or may be delayed ease, as evidenced by (1) physical or radiographic evi-
for months to years. dence, (2) quantitative nontreponemal antibody titers
Infants born to HIV-infected women should be four times higher than the mother, (3) elevated CSF
tested by HIV DNA PCR at < 48 hours, at 1–2 months protein or cell count or positive VDRL, or (4) a posi-
of age, and at 2–4 months old. In an infant who is age tive antitreponemal IgM test. Asymptomatic infants
4 months with no positive PCR, infection can be rea- should be treated if the mother did not receive adequate
sonably excluded. HIV-positive mothers should be treatment for syphilis.
counseled not to breast-feed their infants.
Protection of health care workers is an important
issue. Testing should be performed in all pregnant
2. Tuberculosis (See also Chapter 38.)
women. Because such testing will fail to identify some Congenital tuberculosis (TB) is rare but may occur in
infected patients, however, universal precautions should the infant of a mother with hematogenously spread TB
 THE NEWBORN INFANT / 57

Table 1–22. Recommended treatment of neonates (≤ 4 wk of age) with proven or possible

congenital syphilis.

Clinical Status Antimicrobial Therapya

Proven or highly probable diseaseb Aqueous crystalline penicillin G, 100,000–150,000 U/kg/d,
administered as 50,000 U/kg per dose, IV, every 12 h during
the first 7 d of life and every 8 h thereafter for a total of 10 d
OR
Penicillin G procaine,c 50,000 U/kg/d, IM, in a single dose for
10 d
Asymptomatic: normal CSF examination results, CBC and
platelet count, and radiographic examination; and
follow-up is certain with the following maternal treatment
history:
• (a) No penicillin treatment or inadequate or no Aqueous crystalline penicillin G, IV, for 10–14 db
documentation of penicillin treatmentd; (b) mother OR
was treated with erythromycin or other nonpenicillin Penicillin G procaine,c 50,000 U/kg/d, IM, in a single dose for
regimen; (c) mother received treatment ≤ 4 wk 10 d
before delivery; (d) sequential serologic tests on the OR
mother do not demonstrate a fourfold or greater Clinical, serologic follow-up, and penicillin G benzathine,c
decrease in a nontreponemal antibody titer 50,000 U/kg, IM in a single dose
• (a) Adequate therapy given >1 mo before delivery; Clinical, serologic follow-up, and penicillin G benzathine,
(b) mother’s nontreponemal titers decreased 50,000 U/kg, IM in a single dosee
fourfold after appropriate therapy for early syphilis
and remained stable and low for late syphilis;
(c) mother has no evidence of reinfection or relapse
IV indicates intravenously; IM, intramuscularly; CSF, cerebrospinal fluid; and CBC, complete blood cell.
a
See text for details.
b
If more than 1 day of therapy is missed, the entire course should be restarted.
c
Penicillin G benzathine and penicillin G procaine are approved for IM administration only.
d
See text for definition (includes infants in whom a serum quantitative nontreponemal serologic titer is the same or less than fourfold the
maternal titer). If any part of the infant’s evaluation is abnormal or not performed or if the CSF analysis is uninterpretable, the 10-day
course of penicillin is required.
e
Some experts would not treat the infant but would provide close serologic follow-up.
Reprinted, with permission, from the American Academy of Pediatrics: Red Book 2003 Report on Infectious Diseases; 2003.

or by aspiration of infected amniotic fluid in cases of aration until the mother is receiving antituberculo-
tuberculous endometritis. Women with pulmonary TB sis therapy for 2 weeks. Investigate family contacts.
are not likely to infect the fetus until after delivery. 3. Mother with clinical or radiographic evidence of
Postnatal acquisition is the most common mechanism acute and possibly contagious TB: Evaluate the
of neonatal infection. Management in these cases is infant for congenital TB (skin test, chest radi-
based on the mother’s evaluation. ograph, lumbar puncture, cultures) and HIV.
1. Mother or other household contact with a posi- Treat the mother and infant. If the infant is re-
tive skin test and negative chest radiograph, or ceiving INH and the mother has no risk for mul-
mother with an abnormal chest radiograph but no tidrug-resistant TB, separation is not necessary.
evidence of tuberculous disease after clinical eval- If congenital TB is suspected, multidrug therapy
uation: Investigate family contacts. Treat the should be initiated.
mother with isoniazid (INH).
2. Mother has an abnormal chest radiograph consis-
tent with tuberculous disease: Mother and infant
3. Conjunctivitis
should be separated until the mother is evaluated Neisseria gonorrhoeae may colonize an infant during
for active TB. If active TB is found, maintain sep- passage through an infected birth canal. Gonococcal
58 / CHAPTER 1

ophthalmitis presents at 3–7 days with copious puru- Michelow IC et al: Central nervous system infection in congenital
lent conjunctivitis. The diagnosis can be suspected syphilis. N Engl J Med 2002;346:1792 [PMID: 12050339].
when gram-negative intracellular diplococci are seen on Noyola DE et al: Early predictors of neurodevelopmental outcome
a Gram-stained smear and confirmed by culture. Treat- in symptomatic congenital cytomegalovirus infection. J Pedi-
atr 2001;138:325 [PMID: 11241037].
ment is with IV or IM ceftriaxone, 25–50 mg/kg (not
Pass RF: Cytomegalovirus infection. Pediatr Rev 2002;23:163
to exceed 125 mg) given once. Prophylaxis at birth is [PMID: 11986492].
with 1% silver nitrate or 0.5% erythromycin ointment. Peters V et al: Missed opportunities for perinatal HIV prevention
Infants born to mothers with known gonococcal disease among HIV-exposed infants born 1996–2000, pediatric spec-
should also receive a single dose of ceftriaxone. trum of HIV disease cohort. Pediatrics 2003;111:1186
Chlamydia trachomatis is another important cause of [PMID: 12728136].
conjunctivitis, appearing at 5 days to several weeks of Tuomala RE et al: Antiretroviral therapy during pregnancy and the
age with congestion, edema, and minimal discharge. risk of an adverse outcome. N Engl J Med 2002;346:1863
The organism is acquired at birth after passage through [PMID: 12063370].
an infected birth canal. Acquisition occurs in 50% of Watts H: Management of human immunodeficiency virus infec-
infants born to infected women, with a 25–50% risk of tion in pregnancy. N Engl J Med 2002;346:1879 [PMID:
12063373].
conjunctivitis. Prevalence in pregnancy is over 10% in
some populations. Diagnosis is by isolation of the or-
ganism or by rapid antigen detection tests. Treatment is
with oral erythromycin (30 mg/kg/d in divided doses
q8–12h) for 14 days. Topical treatment alone will not HEMATOLOGIC DISORDERS
eradicate nasopharyngeal carriage, leaving the infant at
risk for the development of pneumonitis. IN THE NEWBORN INFANT
American Academy of Pediatrics Committee on Infectious Dis-
eases: Report of the committee on infectious diseases, 26th
BLEEDING DISORDERS
ed. Red Book 2003. American Academy of Pediatrics, 2003. Neonatal coagulation is discussed in Chapter 27. Bleed-
Boppana SB et al: Intrauterine transmission of cytomegalovirus to ing in the newborn infant may result from inherited
infants of women with preconceptional immunity. N Engl clotting deficiencies (eg, factor VIII deficiency) or ac-
J Med 2001;344:1366 [PMID: 12359792].
quired disorders—hemorrhagic disease of the newborn,
Brown ZA et al: Effect of serologic status and cesarean delivery on
transmission rates of herpes simplex virus from mother to in-
disseminated intravascular coagulation (DIC), liver fail-
fant. JAMA 2003;289:203 [PMID: 12517231]. ure, and thrombocytopenia.
Centers for Disease Control and Prevention. US Public Health Ser-
vice Task Force recommendations for use of antiretroviral
drugs in pregnant HIV-1 infected women for maternal health 1. Vitamin K Deficiency Bleeding
and interventions to reduce perinatal HIV-1 transmission in
the US. MMWR 2002;51(RR-18):1 [PMID: 12489844]. of the Newborn
Darville T: Syphilis. Pediatr Rev 1999;20:160 [PMID: 10233174]. Vitamin K deficiency bleeding (VKDB) is caused by
Foulon W et al: Treatment of toxoplasmosis during pregnancy: A the deficiency of the vitamin K-dependent clotting fac-
multicenter study of impact on fetal transmission and chil- tors (II, VII, IX, and X). Bleeding occurs in 0.25–1.7%
dren’s sequelae at age 1 year. Am J Obstet Gynecol 1999;
180:410 [PMID:9988811].
of newborns who do not receive vitamin K prophylaxis
Fowler KB et al: Maternal immunity and prevention of congenital
after birth, generally in the first 5 days to 2 weeks but as
cytomegalovirus infection. JAMA 2003;289:1008 [PMID: late as 12 weeks in an otherwise well infant. Early
12597753]. VKDB (0–2 weeks) can be prevented by either par-
Hadzic N: Hepatitis C in pregnancy. Arch Dis Childhood Fetal enteral or oral vitamin K administration, whereas late
Neonatal Ed 2001;84:F201 [PMID: 11320050]. disease is most effectively prevented by administering
International Perinatal HIV Group: The mode of delivery and the parenteral vitamin K. Sites of ecchymoses and surface
risk of vertical transmission of human immunodeficiency bleeding include the GI tract, umbilical cord, circumci-
virus type 1. N Engl J Med 1999;340:977 [PMID: sion site, and nose, although devastating intracranial
10099139]. hemorrhage can occur. Bleeding from vitamin K defi-
Kimberlin DW et al: Natural history of neonatal herpes simplex ciency is more likely to occur in exclusively breast-fed
virus infections in the acyclovir era. Pediatrics
2001;108:223 [PMID: 11483781].
infants because of very low amounts of vitamin K in
breast milk, with slower and more restricted intestinal
Kimberlin DW et al: Effect of ganciclovir therapy on hearing in
symptomatic cytomegalovirus disease involving the central colonization. Differential diagnosis includes dissemi-
nervous system: A randomized, controlled trial. J Pediatr nated intravascular coagulation (DIC) and hepatic fail-
2003;143:16 [PMID: 12915819]. ure, both occurring in ill infants (Table 1–23).
 THE NEWBORN INFANT / 59

Table 1–23. Features of infants bleeding from Table 1–24. Differential diagnosis
vitamin K deficiency (VKDB), disseminated of neonatal thrombocytopenia.
intravascular coagulation (DIC), or liver failure.
Disorder Clinical Tips
VKDB DIC Liver Failure Immune
Clinical Well infant; Sick infant; Sick infant; Passively acquired anti- Proper history, maternal
no prophy- hypoxia, sep- hepatitis, body; idiopathic throm- thrombocytopenia
lactic sis, etc inborn errors bocytopenic purpura,
vitamin K of metabo- systemic lupus erythe-
lism, shock matosus, drug-induced
liver Isoimmune sensitization No rise in platelet count from
to HPA-1a antigen random donor platelet trans-
Bleeding GI tract, Generalized Generalized fusion. Positive antiplatelet
umbilical antibodies in baby’s serum,
cord, circum- sustained rise in platelets by
cision, nose transfusion of mother’s plate-
Onset 2–3 d Any time Any time lets
Platelet count Normal Decreased Normal or Infections
decreased Bacterial infections Sick infants with other signs
Congenital viral infections consistent with infection
Prothrombin Prolonged Prolonged Prolonged
time (PT) Syndromes
Absent radii Congenital anomalies, asso-
Partial throm- Prolonged Prolonged Prolonged Fanconi’s anemia ciated pancytopenia
boplastin
time (PTT) Disseminated intravascular Sick infants, abnormalities of
coagulation (DIC) clotting factors
Fibrinogen Normal Decreased Decreased
Giant hemangioma
Factor V Normal Decreased Decreased
Thrombosis Hyperviscous infants, vascu-
GI = gastrointestinal. lar catheters
High-risk with respira- Isolated decrease in platelets
tory distress syndrome, is not uncommon in sick
pulmonary hypertension, infants even in the absence
Treatment consists of 1 mg of vitamin K SQ or IV. etc of DIC (? localized trapping)
IM injections should be avoided in infants who are ac-
tively bleeding. HPA = human platelet antigen.

2. Thrombocytopenia Isoimmune thrombocytopenia (analogous to Rh

Infants with thrombocytopenia have generalized pe- isoimmunization, with a human platelet antigen
techiae (not just on the presenting part) and platelet (HPA)-1a-negative mother and HPA-1a-positive fetus)
counts < 150,000/mL (usually < 50,000/mL, may be requires transfusion of maternal platelets, because 98%
< 10,000/mL). Neonatal thrombocytopenia can be iso- of the random population will also be HPA-1a-positive.
lated or may occur in association with a deficiency of The mother would be the most readily available known
clotting factors. The differential diagnosis for thrombo- HPA-1a-negative donor. Treatment with steroids has
cytopenia with distinguishing clinical features is pre- been disappointing. Treatment with IVIG infusion,
sented in Table 1–24. Treatment of neonatal thrombo- 1 g/kg/d for 2–3 days or until the platelet count has
cytopenia is transfusion of platelets (10 mL/kg of doubled or is over 50,000/mL, is recommended. Ante-
platelets increases the platelet count by approximately natal therapy of the mother with IVIG with or without
70,000/mL). Indications for transfusion in the full- steroids is also beneficial, since 20–30% of infants with
term infant are clinical bleeding or a total platelet count isoimmune thrombocytopenia will experience intracra-
< 10,000–20,000/mL. In the preterm infant at risk for nial hemorrhage, half of them before birth.
intraventricular hemorrhage, transfusion is indicated Infants born to mothers with idiopathic thrombocy-
for counts < 40,000–50,000/mL. topenic purpura are at low risk for serious hemorrhage
60 / CHAPTER 1

despite the thrombocytopenia, and treatment is usually Table 1–25. Organ-related symptoms
unnecessary. If bleeding does occur, IVIG can be used. of hyperviscosity.

ANEMIA Central nervous Irritability, jitteriness, seizures, lethargy

system
The newborn infant with anemia from acute blood loss
presents with signs of hypovolemia (tachycardia, poor Cardiopulmonary Respiratory distress, secondary to conges-
perfusion, hypotension), with an initially normal hema- tive heart failure, or persistent pulmonary
tocrit that falls after volume replacement. Anemia from hypertension
chronic blood loss is evidenced by pallor without signs Gastrointestinal Vomiting, heme-positive stools, disten-
of hypovolemia, with an initially low hematocrit and tion, necrotizing enterocolitis
reticulocytosis.
Renal Decreased urinary output, renal vein
Anemia can be caused by hemorrhage, hemolysis, or thrombosis
failure to produce red blood cells. Anemia occurring in
the first 24–48 hours of life is the result of hemorrhage Metabolic Hypoglycemia
or hemolysis. Hemorrhage can occur in utero (fetopla- Hematologic Hyperbilirubinemia, thrombocytopenia
cental, fetomaternal, or twin-to-twin), perinatally (cord
rupture, placenta previa, incision through placenta at
cesarean section), or internally (intracranial hemor-
rhage, cephalohematoma, ruptured liver or spleen). He-
molysis is caused by blood group incompatibilities, en- a peripheral venous hematocrit should be measured.
zyme or membrane abnormalities, infection, and DIC Values greater than 65% should be considered consis-
and is accompanied by significant hyperbilirubinemia. tent with hyperviscosity.
Initial evaluation should include a review of the Treatment is recommended for symptomatic in-
perinatal history, assessment of the infant’s volume sta- fants. Treatment for asymptomatic infants based
tus, and a complete physical examination. A Kleihaur- strictly on hematocrit is controversial. Definitive treat-
Betke test for fetal cells in the mother’s circulation ment is accomplished by an isovolemic partial exchange
should be done. A CBC, blood smear, reticulocyte transfusion with normal saline, effectively decreasing
count, and direct and indirect Coombs’ tests should be the hematocrit. The amount to exchange (in milliliters)
performed. This simple evaluation should suggest a di- is calculated using the following formula:
agnosis in most infants. It is important to remember
that hemolysis related to blood group incompatibility PVH − DH BV
can continue for weeks after birth. Serial hematocrits × × Wt
PVH kg
should be followed.
where PVH = peripheral venous hematocrit, DH = de-
POLYCYTHEMIA sired hematocrit, BV = blood volume, and Wt =
Polycythemia in the newborn is manifested by plethora, weight.
cyanosis, mild respiratory distress with tachypnea and Blood is withdrawn at a steady rate from an umbili-
oxygen need, hypoglycemia, poor feeding, emesis, and cal venous line while the replacement solution is in-
lethargy. The capillary hematocrit is > 68%, the venous fused at the same rate through a peripheral IV line over
hematocrit > 65%. 15–30 minutes. The desired hematocrit value is
Elevated hematocrits occur in 2–5% of live births. 50–55%; the assumed blood volume is 80 mL/kg.
Although 50% of polycythemic infants are AGA, the
prevalence of polycythemia is greater in the SGA and American Academy of Pediatrics Committee on the Fetus and
LGA populations. Causes of increased hematocrit in- Newborn: Controversies concerning vitamin K and the new-
born. Pediatrics 2003;122:191 [PMID: 12837888].
clude (1) twin–twin transfusion, (2) maternal–fetal
transfusion, (3) intrapartum transfusion from the pla- Manco-Johnson M, Nuss R: Hemostasis in the neonate. Neore-
views 2000;1:e191.
centa, and (4) chronic intrauterine hypoxia (SGA in-
Murray NA: Evaluation and treatment of thrombocytopenia in the
fants, LGA infants of diabetic mothers). neonatal intensive care unit. Acta Paeditr Scand Suppl
The consequence of polycythemia is hyperviscosity 2002;438:74 [PMID: 12477267].
with decreased perfusion of the capillary beds. Clinical Nuss R, Manco-Johnson M: Bleeding disorders in the neonate. Ne-
symptomatology can affect several organ systems (Table oreviews 2000;e196.
1–25). Screening can be done by measuring a capillary Sackey K: Hemolytic anemia: Part 1. Pediatr Rev 1999;
(heelstick) hematocrit. If the value is greater than 68%, 20:152 [PMID: 10233172].
 THE NEWBORN INFANT / 61

Widness JA: Pathophysiology, diagnosis, and prevention of neona- out added electrolytes, plus milliliter-for-milliliter urine
tal anemia. Neoreviews 2000;1:e61. replacement, should be instituted. Serum and urine
electrolytes and body weights should be followed fre-
quently. These measures should be continued through
the polyuric phase. After urine output has been reestab-
RENAL DISORDERS lished, urine replacement should be decreased to be-
IN THE NEWBORN INFANT tween 0.5 and 0.75 mL for each milliliter of urine out-
put to see if the infant has regained normal function. If
that is the case, the infant can be returned to mainte-
Renal function depends on postconceptional age. The nance fluids.
glomerular filtration rate (GFR) is 20 mL/min/1.73 m2 Finally, many of these infants experience fluid over-
in full-term neonates and 10–13 mL/min/1.73 m2 in load and should be allowed to lose enough water
infants born at 28–30 weeks’ gestation. The speed of through urination to return to birth weight. Hyper-
maturation after birth also depends on postconcep- kalemia, which may become life-threatening, may occur
tional age. Creatinine can be used as a clinical marker in this situation despite the lack of added IV potassium.
of GFR. Values in the first month of life are shown in If the serum potassium reaches 7–7.5 mEq/L, therapy
Table 1–26. Creatinine at birth reflects the maternal should be started with glucose and insulin infusion, giv-
level and should decrease slowly over the first ing 1 unit of insulin for every 3 g of glucose adminis-
3–4 weeks. An increasing serum creatinine is never nor- tered, in addition to binding resins. Calcium chloride
mal. The ability to concentrate urine and retain sodium (20 mg/kg bolus) and correction of metabolic acidosis
also depends on gestational age. Infants born at less with bicarbonate are also be helpful for arrhythmia re-
than 28–30 weeks’ gestation are compromised in this sulting from hyperkalemia.
respect and if not observed carefully can become dehy- Peritoneal dialysis is occasionally needed for the
drated and hyponatremic. Preterm infants also have an management of neonatal acute renal failure.
increased bicarbonate excretion and a low tubular maxi-
mum for glucose (approximately 120 mg/dL).
URINARY TRACT ANOMALIES
Abdominal masses in the newborn are most frequently
RENAL FAILURE caused by renal enlargement. Most common is a multi-
Renal failure is most commonly seen in the setting of cystic or dysplastic kidney; congenital hydronephrosis is
birth asphyxia, hypovolemia, or shock from any cause. second in frequency. Chromosomal abnormalities and
The normal rate of urine flow is 1–3 mL/kg/h. After a syndromes with multiple anomalies frequently include
hypoxic or ischemic insult, acute tubular necrosis may renal abnormalities. An ultrasound examination is the
ensue. Typically, 2–3 days of anuria or oliguria is asso- first step in diagnosis. In pregnancies associated with
ciated with hematuria, proteinuria, and a rise in serum oligohydramnios, renal agenesis or obstruction sec-
creatinine. The period of anuria or oliguria is followed ondary to posterior urethral valves should be consid-
by a period of polyuria and then gradual recovery. Dur- ered. Only bilateral disease or disease in a solitary kid-
ing the polyuric phase, excessive urine sodium and bi- ney is associated with oligohydramnios, significant
carbonate losses may be seen. morbidity, and death. Such infants will generally also
The initial step in management is restoration of the have pulmonary hypoplasia and die from pulmonary
infant’s volume status as needed. Thereafter, restriction rather than renal insufficiency.
of fluids to insensible water loss (40–60 mL/kg/d) with- Prenatal ultrasonography identifies infants with
renal anomalies (most often hydronephrosis) prior to
birth. Postnatal evaluation of these infants should in-
Table 1–26. Normal values of serum clude renal ultrasound and a voiding cystourethrogram
at about 1–6 weeks of age, depending on the severity of
creatinine (mg/dL). the antenatal findings. Until genitourinary reflux is
ruled out, these infants should receive antibiotic pro-
Postnatal Age (days) phylaxis with low-dose penicillin or amoxacillin.
Gestational Age at Birth
(weeks) 0–2 28
< 28 1.2 0.7 RENAL VEIN THROMBOSIS
29–32 1.1 0.6 Renal vein thrombosis occurs most often in IDMs and
33–36 1.1 0.45 in the context of dehydration and polycythemia. Of
36–42 0.8 0.3
particular concern is the IDM who is also poly-
62 / CHAPTER 1

cythemic. If fetal distress is superimposed on these movements; and apneic spells. Strictly tonic or multifo-
problems, prompt reduction in blood viscosity is indi- cal clonic episodes are also seen.
cated. Thrombosis usually begins in intrarenal venules
and can extend into larger veins. Clinically, the kidney
may be enlarged, and blood and protein may be in the Clinical Findings
urine. With bilateral renal vein thrombosis, anuria en- The differential diagnosis of neonatal seizures is pre-
sues. Diagnosis can be confirmed with an ultrasound sented in Table 1–27. Most neonatal seizures occur be-
examination that includes Doppler flow studies of the tween 12 and 48 hours of age. Later onset seizures sug-
kidneys. Treatment involves correcting the predispos- gest meningitis, benign familial seizures, or
ing condition and systemic heparinization for the hypocalcemia. Information regarding antenatal drug
thrombosis. Use of thrombolytics for this condition is use, the presence of birth asphyxia or trauma, and fam-
controversial. Prognosis for a full recovery is uncertain. ily history (regarding inherited disorders) should be ob-
Some infants will go on to develop significant atrophy tained. Physical examination focuses on neurologic fea-
of the affected kidney and systemic hypertension. tures, other signs of drug withdrawal, concurrent signs
of infection, dysmorphic features, and intrauterine
Kennedy WA: Assessment and management of fetal hydronephro- growth. Screening work-up should include blood glu-
sis. Neoreviews 2002;3:e214.
Saphier CJ et al: Prenatal diagnosis and management of abnormali-
ties in the urologic system. Clin Perinatol 2000;27:921
[PMID: 11816494]. Table 1–27. Differential diagnosis
Schmidt B: The etiology, diagnosis, and treatment of thrombotic of neonatal seizures.
disorders in newborn infants: A call for international and
multi-institutional studies. Semin Perinatol 1997;21:86 Diagnosis Comment
[PMID: 9190037].
Hypoxic-ischemic Most common cause (60%), on-
encephalopathy set in first 24 hours
Intracranial hemorrhage Up to 15% of cases, periventric-
NEUROLOGIC PROBLEMS ular-intraventricular hemor-
IN THE NEWBORN INFANT rhage, subdural or subarach-
noid bleeding, stroke
Infection 12% of cases
SEIZURES
Hypoglycemia Small for gestational age, in-
fant of a diabetic mother (IDM)
ESSENTIALS OF DIAGNOSIS Hypocalcemia, Infant of low birth weight, IDM
& TYPICAL FEATURES hypomagnesemia
Hyponatremia Rare, seen with syndrome of
• Usual onset at 12–48 hours inappropriate secretion of
• Most common seizure type is characterized by a antidiuretic hormone (SIADH)
constellation of findings Disorders of amino and Associated acidosis, altered
• Most common causes include hypoxic-ischemic organic acid metabolism, level of consciousness
encephalopathy, intracranial bleeds, and infec- hyperammonemia
tion Pyridoxine dependency Seizures refractory to routine
therapy; cessation of seizures
after administration of pyri-
doxine
Newborns rarely have well-organized tonic-clonic Developmental defects Other anomalies, chromosomal
seizures because of their incomplete cortical organiza- syndromes
tion and a preponderance of inhibitory synapses. The
most common type of seizure is characterized by a con- Drug withdrawal
stellation of findings, including horizontal deviation of No cause found 10% of cases
the eyes with or without jerking; eyelid blinking or flut-
tering; sucking, smacking, drooling, and other oral- Benign familial neonatal
buccal movements; swimming, rowing, or paddling seizures
 THE NEWBORN INFANT / 63

cose, ionized calcium, and electrolytes in all cases. Fur- INTRACRANIAL HEMORRHAGE1
ther work-up depends on diagnoses suggested by the
history and physical examination. If there is any suspi- 1. Subdural Hemorrhage
cion of infection, a spinal tap should be done. Hemor-
rhages and structural disease of the CNS can be ad- Subdural hemorrhage is related to birth trauma; the
dressed with real-time ultrasound and CT scan. bleeding is caused by tears in the veins that bridge the
Infarctions are most easily seen on diffusion-weighted subdural space. Prospective studies relating incidence to
MRI scan. Metabolic work-up should be pursued when specific obstetric complications are not available.
appropriate. EEG should be done; the presence of spike The most common site of subdural bleeding is in
discharges must be noted and the background wave ruptured superficial cerebral veins with blood over the
pattern evaluated. Not infrequently, correlation be- cerebral convexities. These hemorrhages can be asymp-
tween EEG changes and clinical seizure activity is ab- tomatic or may cause seizures, with onset on days
sent. 2–3 of life, vomiting, irritability, and lethargy. Associ-
ated findings include retinal hemorrhages and a full
fontanelle. The diagnosis is confirmed by CT scan.
Specific treatment entailing needle drainage of the
Treatment subdural space is rarely necessary. Most infants survive;
Adequate ventilation and perfusion should be ensured. 75% are normal on follow-up.
Hypoglycemia should be treated immediately with a
2 mL/kg infusion of D10W followed by 6 mg/kg/min of 2. Primary Subarachnoid Hemorrhage
D10W (100 mL/kg/d). Other treatments such as cal- Primary subarachnoid hemorrhage is the most common
cium or magnesium infusion and antibiotics are indi- type of neonatal intracranial hemorrhage. In the full-
cated to treat hypocalcemia, hypomagnesemia, and sus- term infant, it can be related to trauma of delivery,
pected infection. Electrolyte abnormalities should be whereas subarachnoid hemorrhage in the preterm in-
corrected. Phenobarbital, 20 mg/kg IV, should be ad- fant is seen in association with germinal matrix hemor-
ministered to stop seizures. Supplemental doses of rhage. Clinically, these hemorrhages can be asympto-
5 mg/kg can be used if seizures persist, up to a total of matic or can present with seizures and irritability on
40 mg/kg. In most cases, phenobarbital controls day 2 or, rarely, a massive hemorrhage with a rapid
seizures. If seizures continue, therapy with phenytoin, downhill course. The seizures associated with subarach-
sodium valproate, or lorazepam may be indicated. For noid hemorrhage are very characteristic—usually brief,
refractory seizures, a trial of pyridoxine is indicated. with a normal examination interictally. Diagnosis can
be suspected on spinal tap and confirmed with CT
scan. Long-term follow-up is uniformly good.
Prognosis
Outcome is related to the underlying cause of the 3. Neonatal Stroke
seizure. The outcomes for hypoxic-ischemic en- Focal cerebral ischemic injury can occur in the context
cephalopathy and intraventricular hemorrhage have of intraventricular hemorrhage in the premature infant
been discussed earlier in this chapter. In these settings, and hypoxic ischemic encephalopathy. Neonatal stroke
seizures that are difficult to control carry a poor prog- has also been described in the context of underlying
nosis for normal development. Seizures resulting from disorders of thrombolysis and maternal drug use (co-
hypoglycemia, infection of the CNS, some inborn er- caine). In some cases, the origin is unclear. The injury
rors of metabolism, and developmental defects also often occurs antenatally. The most common clinical
have a high rate of poor outcome. Seizures caused by presentation of an isolated cerebral infarct is with
hypocalcemia or isolated subarachnoid hemorrhage seizures, and diagnosis can be confirmed acutely with
generally resolve without sequelae. diffusion-weighted MRI scan. The most frequently de-
scribed distribution is that of the middle cerebral artery.
Treatment is directed at controlling seizures. Long-
HYPOTONIA term outcome is variable, ranging from normal to
hemiplegias and cognitive deficits.
One should be alert to the diagnosis of congenital hy-
potonia when a mother has polyhydramnios and a his-
tory of poor fetal movement. The newborn may present
with poor respiratory effort and birth asphyxia. For a 1
Intraventricular hemorrhage is discussed in the section on Care of
discussion of causes and evaluation, see Chapter 23. the Premature Infant.
64 / CHAPTER 1

Brunquell PJ et al: Prediction of outcome based on clinical seizure Hypocalcemia tends to occur at two different times
type in newborn infants. J Pediatr 2002;140:707 [PMID: in the neonatal period. Early-onset hypocalcemia oc-
12072874].
curs in the first 2 days of life and has been associated
Hill A: Neonatal seizures. Pediatr Rev 2000;21:117 [PMID: with prematurity, maternal diabetes, asphyxia, and,
10756174].
rarely, maternal hypoparathyroidism. Late-onset
Levene M: The clinical conundrum of neonatal seizures. Am J Dis
Child Fetal Neonatal Ed 2002;86:F75 [PMID: 11882546].
hypocalcemia occurs at approximately 7–10 days and is
Mercuri E et al: Prothrombotic disorders and abnormal neurode-
observed in infants receiving modified cow’s milk
velopmental outcome in infants with neonatal cerebral infarc- rather than infant formula (high phosphorus intake) or
tion. Pediatrics 2001;107:1400 [PMID: 11389264]. in infants with hypoparathyroidism (DiGeorge syn-
drome, 22q11 deletion). Mothers in Third-World
countries often have vitamin D deficiency, which can
also contribute to late-onset hypocalcemia.
METABOLIC DISORDERS
IN THE NEWBORN INFANT2
TREATMENT
HYPERGLYCEMIA A. ORAL CALCIUM THERAPY
Hyperglycemia may develop in preterm infants, partic- The oral administration of calcium salts, often along
ularly those of extremely low birth weight who are with vitamin D, is the preferred method of treatment
also SGA. Glucose concentrations may exceed for chronic forms of hypocalcemia resulting from hy-
200–250 mg/dL, particularly in the first few days of poparathyroidism (see Chapter 30).
life. This transient diabetes-like syndrome usually lasts
approximately 1 week.
Management may include simply reducing glucose B. INTRAVENOUS CALCIUM THERAPY
intake while continuing to supply IV amino acids to IV calcium therapy is usually needed for infants with
prevent protein catabolism with resultant gluconeogen- symptomatic hypocalcemia or an ionized calcium less
esis. IV insulin infusions will be needed in infants who than 0.9 mmol/L. A number of precautions must be
remain hyperglycemic despite glucose infusion rates of observed when calcium gluconate is given intra-
only 5–6 mg/kg/min or less. venously. The infusion must be given slowly so that
there is no sudden increase in calcium concentration of
HYPOCALCEMIA blood entering the right atrium, which could cause se-
vere bradycardia and even cardiac arrest. Furthermore,
Calcium concentration in the immediate newborn pe- the infusion must be observed carefully, because an IV
riod decreases in all newborn infants. The concentra- infiltrate containing calcium can cause full-thickness
tion in fetal plasma is higher than that of the neonate or skin necrosis requiring grafting. For these reasons, IV
adult. Hypocalcemia is usually defined as a total serum calcium therapy should be given judiciously and
concentration less than 7 mg/dL (equivalent to a cal- through a central venous line if possible. IV administra-
cium activity of 3.5 mEq/L), although the physiologi- tion of 10% calcium gluconate is usually given as a
cally active fraction, ionized calcium, should be mea- bolus of 100–200 mg/kg (1–2 mL/kg) over approxi-
sured whenever possible. Ionized calcium is usually mately 10–20 minutes, followed by a continuous infu-
normal even when total calcium is as low as sion (0.5–1 g/kg/d) over 1–2 days. Ten percent calcium
6–7 mg/dL. An ionized calcium of greater than chloride (20 mg/kg or 0.2 mL/kg per dose) may result
0.9 mmol/L (1.8 mEq/L; 3.6 mg/dL) is not likely to be in a larger increment in ionized calcium and greater im-
detrimental. provement in mean arterial blood pressure in sick
hypocalcemic infants and thus may have a role in the
Clinical Findings newborn. Note: Calcium salts cannot be added to IV
solutions that contain sodium bicarbonate because they
The clinical signs of hypocalcemia and hypocalcemic precipitate as calcium carbonate.
tetany include a high-pitched cry, jitteriness, tremu-
lousness, and seizures.
Prognosis
2
Hypoglycemia is discussed in the section on Common Problems The prognosis is good for neonatal seizures entirely
in the Term Newborn Infant. caused by hypocalcemia that is promptly treated.
 THE NEWBORN INFANT / 65

INBORN ERRORS OF METABOLISM REFERENCES

The individual inborn errors of metabolism are rare, Christensen RD (ed): Hematologic Problems of the Neonate. WB
but collectively have an incidence of 1/1000 live births. Saunders, 2000.
Expanded newborn genetic screening will undoubtedly Eichenfeld LF et al (eds): Textbook of Neonatal Dermatology. WB
aid in the diagnosis of these disorders. Nevertheless, Saunders, 2001.
many infants will present prior to these results being Fanaroff AA, Martin RJ (eds): Neonatal-Perinatal Medicine. Dis-
available. The diseases are considered in detail in Chap- eases of the Fetus and Infant, 7th ed. Mosby, 2002.
ter 32. These diagnoses should be entertained when in- Goldsmith JP, Karotkin EH (eds): Assisted Ventilation of the
Neonate, 4th ed. WB Saunders, 2003.
fants who were initially well present with sepsis-like
syndromes, recurrent hypoglycemia, neurologic syn- Jones KL (ed): Smith’s Recognizable Patterns of Human Malforma-
tion, 5th ed. WB Saunders, 1997.
dromes (seizures, altered levels of consciousness), or un-
Klaus MH, Fanaroff AA (eds): Care of the High-Risk Neonate, 5th
explained acidosis (suggestive of organic acidemias). ed. WB Saunders, 2001.
In the immediate neonatal period, urea cycle disor- Remington JS, Klein JO (eds): Infectious Diseases of the Fetus and
ders present as an altered level of consciousness sec- Newborn Infant, 5th ed. WB Saunders, 2001.
ondary to hyperammonemia. A clinical clue that sup- Thureen PJ et al (eds): Assessment and Care of the Well Newborn.
ports this diagnosis is hyperventilation with primary WB Saunders, 1999.
respiratory alkalosis, along with a lower than expected Volpe JJ (ed): Neurology of the Newborn, 4th ed. WB Saunders, 2000.
blood urea nitrogen. The other major diagnostic cate- Young TE, Mangum OB (ed): Neofax 2002, 15th ed. Acorn Pub-
gory to consider consists of infants with severe acidemia lishing, 2000.
secondary to organic acidemias.
Web Resources
[Cochrane neonatal database]
Burton BK: Inborn errors of metabolism in infancy: A guide to di-
agnosis. Pediatrics 1998;102:e69 [PMID: 9832597]. www.nichd.nih.gov/cochraneneonatal/
Enns GM, Packman S: Diagnosing inborn errors of metabolism in [Neoreviews]
the newborn: clinical features. Neoreviews 2001;2:e183. http://neoreviews.aapjournals.org/
Hemachandra AH, Cowett RM: Neonatal hyperglycemia. Pediatric [Neonatal resuscitation program]
Rev 1999;20:e16. www.aap.org/profed/nrp/nrpmain.html
 Child Development & Behavior 2
Edward Goldson, MD, & Ann Reynolds, MD

Child development encompasses all aspects of pedi- age 21⁄2 to 3 years. The child progresses from a totally
atrics. It applies to somatic, psychological, and cogni- dependent infant at birth to a mobile, verbal person
tive growth and to behavior. The developmental princi- who is able to express his or her needs and desires by
ple, that is, the concept of ongoing change and age 2–3 years. In the ensuing 2–3 years the child fur-
maturation, is integral to the daily practice of pedi- ther develops the capacity to interact with peers and
atrics. For example, we recognize that a 3-month-old adults, achieves considerable verbal and physical
infant is very different from a 3-year-old and from a prowess, and becomes ready to enter the academic
13-year-old adolescent, not only with respect to what world of learning and socialization.
the child can do but also in terms of the kind of illness It is critical for the clinician to identify disturbances
he or she might have. This perspective is unique to pe- in development during these early years because there
diatrics, separating it from other fields of medicine. Al- may be windows of time or sensitive periods when ap-
though the principles of child development have been propriate interventions may be instituted to effectively
the domain of the general pediatrician, the field of de- treat developmental problems. Numerous screening
velopmental and behavioral pediatrics has emerged as a tools are available to identify children with develop-
subspecialty that addresses not only typical develop- mental disturbances; however, the clinician can use cer-
ment but also the diagnosis and evaluation of atypical tain principles to identify problems without resorting to
behavior and development. formal screening measures. From a motor perspective,
This chapter does not attempt to cover the entire children develop in a cephalocaudal direction. They can
field of developmental and behavioral pediatrics. In- lift their heads with good control at 3 months, sit inde-
stead, it focuses on three distinct areas. First, it dis- pendently at 6 months, crawl at 9 months, walk at
cusses normal development but does not cover the new- 1 year, and run by 18 months. The child learning to
born period or adolescence (see Chapters 1 and 3, walk has a wide-based gait at first. Next, he or she walks
respectively). Second, it addresses behavioral variations, with legs closer together, the arms move medially, a
emphasizing that these variations reflect the spectrum heel–toe gait develops, and the arms swing symmetri-
of normal development and not pathology. Third, it cally by 18 to 24 months.
deals with developmental and behavioral disorders and Clinicians often focus on gross motor development,
their treatment. but an appreciation of fine motor development and
dexterity, particularly the grasp, can be instructive not
only in monitoring normal development but also in
identifying deviations in development. The grasp be-
I. NORMAL DEVELOPMENT gins as a raking motion involving the ulnar aspect of
the hand at age 3–4 months. The thumb is added to
this motion at about age 5 months as the focus of the
THE FIRST YEAR movement shifts to the radial side of the hand. The
Normal children follow a trajectory of increasing physi- thumb opposes the fingers for picking up objects just
cal size (Figures 2–1 to 2–10) and increasing complex- before age 7 months, and the neat pincer grasp emerges
ity of function (Figures 2–7, 2–8 and Tables 2–1, 2–2). at about age 9 months. Most young children have sym-
Growth charts provide an overview of the normal metrical movements. Asymmetries of movement noted
growth trajectory of children, thus alerting the clinician in the first 2–3 years of life, be they facial asymmetries
to what is atypical. Table 2–3 provides the theoretical or gross motor asymmetries, should be investigated.
perspectives of human behavior, taking into considera- This is particularly true if other developmental delays
tion the work of Freud, Erikson, and Piaget. are present or if the child has a history of adverse expe-
The first 5 years of life are a period of extraordinary riences such as prematurity or intracranial hemorrhage.
physical growth and increasing complexity of function. Children should not have a hand preference at 1 year of
The child triples his or her birth weight within the first age and typically develop handedness between 18 and
year and achieves two thirds of his or her brain size by 30 months.
66
Copyright © 2005, 2001, by The McGraw-Hill Companies, Inc. Click here for terms of use.
 CHILD DEVELOPMENT & BEHAVIOR / 67

Figure 2–1. Percentile standards for length for age and weight for age in girls, birth to age 36 months. (Centers for
Disease Control and Prevention.)
68 / CHAPTER 2

Figure 2–2. Percentile standards for head circumference for age and weight for length in girls, birth to age
36 months. (Centers for Disease Control and Prevention.)
 CHILD DEVELOPMENT & BEHAVIOR / 69

Figure 2–3. Percentile standards for length for age and weight for age in boys, birth to age 36 months. (Centers for
Disease Control and Prevention.)
70 / CHAPTER 2

Figure 2–4. Percentile standards for head circumference for age and weight for length in boys, birth to age
36 months. (Centers for Disease Control and Prevention.)
 CHILD DEVELOPMENT & BEHAVIOR / 71

Figure 2–5. Percentile standards for stature for age and weight for age in girls, 2–20 years. (Centers for Disease Con-
trol and Prevention.)
72 / CHAPTER 2

Figure 2–6. Percentile standards for body mass index for age in girls, 2–20 years. (Centers for Disease Control and
Prevention.)
 CHILD DEVELOPMENT & BEHAVIOR / 73

Figure 2–7. Percentile standards for stature for age and weight for age in boys, 2–20 years. (Centers for Disease
Control and Prevention.)
74 / CHAPTER 2

Figure 2–8. Percentile standards for body mass index for age in boys, 2–20 years. (Centers for Disease Control and
Prevention.)
 CHILD DEVELOPMENT & BEHAVIOR / 75

62
24
60
58 23
56 22
54 21

Circumference (inches)
52 +2 SD (98%)
Circumference (cm)

20
50
0%)
48 Mean (5 19
46 18
44 –2 SD (98%) 17
42
16
40
38 15
36 14
34
13 Figure 2–9. Head circumference of
32
30 12 girls. (Modified and reproduced, with
2 4 6 8 10 12 14 16 18 2 4 6 8 10 12 14 16 18 permission, from Nelhaus G: Pediatrics
Months Years 1968;41:106.)

Language is a critical area to consider as well. Chil- ingful and clinically useful if placed in empirical and
dren usually have 5–10 comprehensible words by age theoretical contexts. The work of Piaget and others is
1 year; by age 2 years they are putting 2–3 words into quite instructive and provides some insight into behav-
phrases, 50% of which their caregivers can understand ioral and affective development (see Table 2–3). Piaget
(see Tables 2–1 and 2–2 and Figure 2–11). described the first 2 years of life as the sensorimotor pe-
One may easily memorize the developmental mile- riod, during which infants learn with increasing sophis-
stones that characterize the trajectory of the typical tication how to link sensory input from the environ-
child; however, these milestones become more mean- ment with a motor response. Infants build on primitive

62
24
60
58 23
56 22
54 21
Circumference (inches)

+2 SD (98%)
52
Circumference (cm)

20
50 0%)
Mean (5 19
48
46 18
44 –2 SD (98%)
17
42
16
40
38 15
36 14
34
13 Figure 2–10. Head circumference
32
30 12 of boys. (Modified and reproduced,
2 4 6 8 10 12 14 16 18 2 4 6 8 10 12 14 16 18 with permission, from Nelhaus G: Pedi-
Months Years atrics 1968;41:106.)
76 / CHAPTER 2

Table 2–1. Developmental charts.

1–2 months Gives toys on request.

Activities to be observed: Tries to build a tower of 2 cubes.
Holds head erect and lifts head. Activities related by parent:
Turns from side to back. Points to desired objects.
Regards faces and follows objects through visual field. Says 1 or 2 other words.
Drops toys.
Becomes alert in response to voice. 18 months
Activities related by parent: Activities to be observed:
Recognizes parents. Builds tower of 3–4 cubes.
Engages in vocalizations. Throws ball.
Smiles spontaneously. Scribbles spontaneously.
Seats self in chair.
3–5 months Dumps pellet from bottle.
Activities to be observed: Activities related by parent:
Grasps cube—first ulnar then later thumb opposition. Walks up and down stairs with help.
Reaches for and brings objects to mouth. Says 4–20 words.
Makes “raspberry” sound. Understands a 2-step command.
Sits with support. Carries and hugs doll.
Activities related by parent: Feeds self.
Laughs. 24 months
Anticipates food on sight.
Turns from back to side. Activities to be observed:
Speaks short phrases, 2 words or more.
6–8 months Kicks ball on request.
Activities to be observed: Builds tower of 6–7 cubes.
Sits alone for a short period. Points to named objects or pictures.
Reaches with one hand. Jumps off floor with both feet.
First scoops up a pellet then grasps it using thumb Stands on either foot alone.
opposition. Uses pronouns.
Imitates “bye-bye.” Activities related by parent:
Passes object from hand to hand in midline. Verbalizes toilet needs.
Babbles. Pulls on simple garment.
Activities related by parent: Turns pages of book singly.
Rolls from back to stomach. Plays with domestic mimicry.
Is inhibited by the word no. 30 months
9–11 months Activities to be observed:
Activities to be observed: Walks backward.
Stands alone. Begins to hop on one foot.
Imitates pat-a-cake and peek-a-boo. Uses prepositions.
Uses thumb and index finger to pick up pellet. Copies a crude circle.
Points to objects described by use.
Activities related by parent: Refers to self as I.
Walks by supporting self on furniture. Holds crayon in fist.
Follows one-step verbal commands, eg,
”Come here,” “Give it to me.” Activities related by parent:
Helps put things away.
1 year Carries on a conversation.
Activities to be observed: 3 years
Walks independently.
Says “mama” and “dada” with meaning. Activities to be observed:
Can use a neat pincer grasp to pick up a pellet. Holds crayon with fingers.
Releases cube into cup after demonstration. Builds tower of 9–10 cubes.
(continued)
 CHILD DEVELOPMENT & BEHAVIOR / 77

Table 2–1. Developmental charts. (continued)

Imitates 3-cube bridge. Knows right and left hand.

Copies circle. Draws recognizable person with at least 8 details.
Gives first and last name. Can describe favorite television program in some detail.
Activities related by parent: Activities related by parent:
Rides tricycle using pedals. Does simple chores at home (eg, taking out garbage, dry-
Dresses with supervision. ing silverware).
Goes to school unattended or meets school bus.
3–4 years Good motor ability but little awareness of dangers.
Activities to be observed:
Climbs stairs with alternating feet. 6–7 years
Begins to button and unbutton. Activities to be observed:
“What do you like to do that’s fun?” (Answers using Copies a ∆.
plurals, personal pronouns, and verbs.) Defines words by use. (“What is an orange?” “To eat.”)
Responds to command to place toy in, on, or under table. Knows if morning or afternoon.
Draws a circle when asked to draw a person. Draws a person with 12 details.
Knows own sex. (“Are you a boy or a girl?”) Reads several one-syllable printed words. (My, dog, see,
Gives full name. boy.)
Copies a circle already drawn. (“Can you make one like Uses pencil for printing name.
this?”)
7–8 years
Activities related by parent:
Feeds self at mealtime. Activities to be observed:
Takes off shoes and jacket. Counts by 2s and 5s.
Ties shoes.
4–5 years Copies a ◊.
Activities to be observed: Knows what day of the week it is. (Not date or year.)
Runs and turns without losing balance. Reads paragraph #1 Durrell:
May stand on one leg for at least 10 seconds. Reading:
Buttons clothes and laces shoes. (Does not tie.) Muff is a little yellow kitten. She drinks milk. She sleeps on
Counts to 4 by rote. a chair. She does not like to get wet.
“Give me 2 sticks.” (Able to do so from pile of 4 tongue Corresponding arithmetic:
depressors.) 7 6 6 8
Draws a person. (Head, 2 appendages, and possibly 2 +4 +7 −4 −3
eyes. No torso yet.)
Knows the days of the week. (“What day comes after No evidence of sound substitution in speech (eg, fr for thr).
Tuesday?”) Adds and subtracts one-digit numbers.
Gives appropriate answers to: “What must you do if you Draws a man with 16 details.
are sleepy? Hungry? Cold?”
Copies + in imitation. 8–9 years
Activities related by parent: Activities to be observed:
Self-care at toilet. (May need help with wiping.) Defines words better than by use. (“What is an orange?”
Plays outside for at least 30 minutes. “A fruit.”)
Dresses self except for tying. Can give an appropriate answer to the following:
“What is the thing for you to do if . . .
5–6 years —you’ve broken something that belongs to someone
Activities to be observed: else?”
Can catch ball. —a playmate hits you without meaning to do so?”
Skips smoothly. Reads paragraph #2 Durrell:
Copies a + already drawn. Reading:
Tells age. A little black dog ran away from home. He played with two
Concept of 10 (eg, counts 10 tongue depressors). big dogs. They ran away from him. It began to rain. He
May recite to higher number by rote. (continued)
78 / CHAPTER 2

Table 2–1. Developmental charts. (continued)

went under a tree. He wanted to go home, but he did faster than a steamboat had ever gone before. Crowds
not know the way. He saw a boy he knew. The boy took gathered on both banks of the river to see this new kind
him home. of boat. They were afraid that its noise and splashing
Corresponding arithmetic: would drive away all the fish.
45 Corresponding arithmetic:
67 16 14 84 420
+ 4 +27 – 8 –36 × 29 9) 72 31)62
Is learning borrowing and carrying processes in addition Answer: “What river was the trip made on?”
and subtraction. Ask to write the sentence: “The fishermen did not like the
boat.”
9–10 years Should do multiplication and simple division.
Activities to be observed:
Knows the month, day, and year. 12–15 years
Names the months in order. (15 seconds, 1 error.) Activities to be observed:
Makes a sentence with these 3 words in it: (1 or 2. Can Reads paragraph #7 Durrell:
use words orally in proper context.) Reading:
1. work . . . money . . . men Golf originated in Holland as a game played on ice. The game
2. boy . . . river . . . ball in its present form first appeared in Scotland. It became
Reads paragraph #3 Durrell: unusually popular and kings found it so enjoyable that it
Reading: was known as “the royal game.” James IV, however,
Six boys put up a tent by the side of a river. They took things thought that people neglected their work to indulge in
to eat with them. When the sun went down, they went this fascinating sport so that it was forbidden in 1457.
into the tent to sleep. In the night, a cow came and James relented when he found how attractive the game
began to eat grass around the tent. The boys were afraid. was, and it immediately regained its former popularity.
They thought it was a bear. Golf spread gradually to other countries, being introduced
Corresponding arithmetic: in America in 1890. It has grown in favor until there is
5204 23 837 hardly a town that does not boast of a private or public
– 530 × 3 × 7 course.
Corresponding arithmetic:
Should comprehend and answer the question: “What was 536)4762 1
⁄3 71⁄6
the cow doing?” + ⁄3
1
– 3⁄4
Learning simple multiplication.
Reduce fractions to lowest forms.
10–12 years
Activities to be observed: Ask to write a sentence: “Golf originated in Holland as a
Should read and comprehend paragraph #5 Durrell: game played on ice.”
Reading: Answers questions:
In 1807, Robert Fulton took the first long trip in a steam- “Why was golf forbidden by James IV?”
boat. He went one hundred and fifty miles up the Hud- “Why did he change his mind?”
son River. The boat went five miles an hour. This was Does long division, adds and subtracts fractions.
Modified from Leavitt SR, Goodman H, Harvin D: Pediatrics 1963;31:499.

reflex patterns of behavior (termed schemata; sucking is tion of reality revolves around itself and what it can see
an example) and constantly incorporate or assimilate or touch. The infant follows the trajectory of an object
new experiences. The schemata evolve over time as in- through the field of vision, but before age 6 months the
fants accommodate new experiences and as new levels object ceases to exist once it leaves the infant’s field of
of cognitive ability unfold in an orderly sequence. En- vision. At age 9–12 months, the infant gradually devel-
hancement of neural networks through dendritic ops the concept of object permanence, or the realiza-
branching occurs in spurts throughout the sensorimo- tion that objects exist even when not seen. The devel-
tor period. In the first year of life, the infant’s percep- opment of object permanence correlates with enhanced
 CHILD DEVELOPMENT & BEHAVIOR / 79

Table 2–2. Normal speech and language development.

Age Speech Language Articulation

1 month Throaty sounds Vowels: \ah\, \uh\, \ee\
2 months Vowel sounds (“eh”), coos
2 ⁄2 months
1
Squeals
3 months Babbles, initial vowels
4 months Guttural sounds (“ah,” “go”) Consonants, m, p, b
5 months Vowels: \o\, \u\
7 months Imitates speech sounds
8 months Syllables: da, ba, ka
10 months “Dada” or “mama” nonspecifically Approximates names: baba/bottle
12 months Jargon begins (own language) One word other than “mama” or Understandable: 2–3 words
“dada
13 months Three words
16 months Six words Consonants: t, d, w, n, h
18–24 months Two-word phrases Understandable 2-word phrases
24–30 months Three-word phrases Understandable 3-word phrases
2 years Vowels uttered correctly Approximately 270 words; uses Approximately 270 words; uses
pronouns phrases
3 years Some degree of hesitancy Approximately 900 words; intelligible Approximately 900 words; intelligible
and uncertainty common 4-word phrases 4-word phrases
4 years Approximately 1540 words; intelligi- Approximately 1540 words; intelligible
ble 5-word phrases or sentences 5-word phrases
6 years Approximately 2560 words; intelligi- Approximately 2560 words; intelligible
ble 6- or 7-word sentences 6- or 7-word sentences
7–8 years Adult proficiency
Data on articulation from Berry MF: Language Disorders of Children. Appleton-Century-Crofts, 1969; and from Bzoch K, League R: Receptive-
Expressive Emergent Language Scale. University Park Press, 1970.

frontal activity on the electroencephalogram. The con- scribed as manifesting “narcissistic possessiveness” of
cept attaches first to the image of the mother or pri- the infant. This is a very positive interaction in the bidi-
mary caregiver because of his or her emotional impor- rectional attachment process called bonding. The par-
tance and is a critical part of attachment behavior ents learn to be aware of and to interpret the infant’s
(discussed later). In the second year, children extend cues, which reflect its needs. A more sensitive emo-
their ability to manipulate objects by using instru- tional interaction process develops that can be seen in
ments, first by imitation and later by trial and error. the mirroring of facial expressions by the primary care-
Freud described the first year of life as the oral stage giver and infant and in their mutual engagement in cy-
because so many of the infant’s needs are fulfilled by cles of attention and inattention, which further develop
oral means. Nutrition is obtained through sucking on into social play. A parent who is depressed or cannot re-
the breast or bottle, and self-soothing occurs through spond to the baby’s expressions and cues can have a
sucking on fingers or a pacifier. During this stage of profoundly adverse effect on the child’s future develop-
symbiosis with the mother, the boundaries between ment. Erikson’s terms of basic trust versus mistrust are
mother and infant are blurred. The baby’s needs are to- another way of describing the reciprocal interaction
tally met by the mother, and the mother has been de- that characterizes this stage.
80 / CHAPTER 2

Table 2–3. Perspectives of human behavior.

Theories of Development Skill Areas

Age Freud Erikson Piaget Language Motor Psychopathology
Birth to 18 Oral Basic trust versus Sensorimotor Body actions; cry- Reflex sitting, Autism; anaclitic depres-
months mistrust ing; naming; point- reaching, grasp- sion, colic; disorders of
ing ing, walking attachment; feeding,
sleeping problems
18 months– Anal Autonomy versus Symbolic Sentences; tele- Climbing, running Separation issues; nega-
3 years shame, doubt (preoperational) graph jargon tivism; fearfulness; con-
stipation; shyness, with-
drawal
3–6 years Oedipal Initiative versus Intuition Connective Increased coordi- Enuresis; encopresis; an-
guilt (preoperational) words; can be nation; tricycle; xiety; aggressive acting
readily understood jumping out; phobias; nightmares
6–11 years Latency Industry versus Concrete Subordinate sen- Increased skills; School phobias; obses-
inferiority operational tences; reading sports, recrea- sive reactions; conversion
and writing; lan- tional cooperative reactions; depressive
guage reasoning games equivalents
12–17 years Adoles- Identity versus Formal Reason abstract; Refinement of Delinquency; promis-
cence role confusion operational using language; skills cuity; schizophrenia;
(genital) abstract manipula- anorexia nervosa; suicide
tion
Adapted and reproduced, with permission, from Dixon S: Setting the stage: Theories and concepts of child development. In Dixon S,
Stein M (eds): Encounters with Children, 2nd ed. Year Book, 1992.

Turn-taking games, which occur between ages 3 and giver’s presence and her absence by remembering the
6 months, are a pleasure for both the parents and the schema of her presence. Perceiving the inconsistency,
infant and are an extension of mirroring behavior. They the child first becomes uncertain and then anxious and
also represent an early form of imitative behavior, fearful. This begins at age 8 months, reaches a peak at
which is important in later social and cognitive devel- 15 months, and disappears by the end of 2 years in a
opment. More sophisticated games, such as peek-a-boo, relatively orderly progression as central nervous system
occur at approximately age 9 months. The infant’s (CNS) maturation facilitates the development of new
thrill at the reappearance of the face that vanished mo- skills. A parent can put the child’s understanding of ob-
mentarily demonstrates the emerging understanding of ject permanence to good use by placing a picture of the
object permanence. mother near the child or by leaving an object (eg, her
Age 8–9 months is also a critical time in the attach- sweater) where the child can see it during her absence.
ment process because this is when separation anxiety A visual substitute for the mother’s presence may com-
and stranger anxiety become marked. The infant at this fort the child.
stage is able to appreciate discrepant events that do not
match previously known schemata. These new events THE SECOND YEAR
cause uncertainty and subsequently fear and anxiety.
The infant must be able to retrieve previous schemata Once the child can walk independently, it can move
and incorporate new information over an extended away from the parent and explore the environment. Al-
time. These abilities are developed by age 8 months and though the child uses the mother as “home base,” re-
give rise to the fears that subsequently develop: stranger turning to her frequently for reassurance, he or she has
anxiety and separation anxiety. In stranger anxiety, the now taken a major step toward independence. This is
infant analyzes the face of a stranger, detects the mis- the beginning of mastery over the environment and an
match with previous schemata, and responds with fear emerging sense of self. The “terrible twos” and the fre-
or anxiety, leading to crying. In separation anxiety, the quent self-asserting use of “no” are the child’s attempt
child perceives the difference between the primary care- to develop a better idea of what is or might be under its
 DOT NAME

ELM SCALE–2 EARLY LANGUAGE MILESTONE SCALE–2 DOB

CA
Examiner
Location
MONTHS 1 2 3 4 5 6 7 8 9 10 11 12 14 16 18 20 22 24 26 28 30 32 34 36

H
O 1 Coo 15About one-half H
O
H
Understood 37
H
T
O
2 Reciprocal vocalization by strangers 19Three-fourths O 47
H
H
O 3 Laugh 20 All/Almost All O

EXPRESSIVE H
Raspberry 11 Tells 2 wants OH 18 Objects: Name and Use
AUDITORY
O 4
12 2-Wd sentences H (2/4) Name Use
5 Mono. babbling H
O O
Cup
6 Polysyllabic babbling H
O
13 50 + Single wds H
O
Ball
Spoon
Crayon
7 "Mama/Dada": Any H
O
14 "Me/you": Any H
O

H
8 "Mama/Dada": Correct
H
O 16 Prepositions O

H
9 First word (not "Mama/Dada") H
O 17 Conversations O

10 4–6 Single words H

O
T

H
T
O
1 Alerts to voice 11 Points to named objects T

H
T
O
2 Orients laterally to voice
(2/3) Cup Drink with (2/4)
H
O 3 Recognizes sounds
Ball Throw
RECEPTIVE

Orients laterally to bell

AUDITORY

T 4
Spoon Eat with
T 5 Bell, over & down Crayon Write with
81

H
6Inhibits to "No" T
O 12 Points to objects
7 Bell, diagonal T described by use T

H
8 1-Step command w/o gesture T 13 Prepositional commands T
O
H
(2/3) Me spoon / Mom ball 9 Points to >1 body parts T
O
Under
On Top
(2/4)
Me ball / Mom spoon H Behind
Mom ball / Me cup 10 2-Step commands w/o gesture T
O Beside

H
T
O
1 Smiles Global
H
AE AR V Intell. Lang.
O 2 Recognizes parents
H
Pass/Fail
O 3 Recognizes objects
H
T 4 Responds to facial expressions Raw Score + + (NA) =
O
VISUAL

T 5 Visual tracking (H,V) Percentile * (NA)

T 6 Blinks to threat
H Std. S. Equiv. * (NA)
7 Imit. gest. games T
O

8 1-Step comm. w. gest. H Age Equiv. * (NA)

O
H
9 Initiates gest. games T
O
H
* Only if age or developmental level is 12 months or less
10 Points to desired objects O

MONTHS 1 2 3 4 5 6 7 8 9 10 11 12 14 16 18 20 22 24 26 28 30 32 34 36
© 1993, 1983 by James Coplan, MD Additional copies of this form (#6582) may be ordered from PRO-ED, 8700 Shoal Creek Blvd., Austin, TX 78757

Figure 2–11. Early Language Milestone Scale-2. (Reproduced, with permission, from Coplan J: Early Language Milestone Scale. Pro Ed, 1993.)
82 / CHAPTER 2

control. The child is starting to assert his or her auton- milestone can become a battle between parent and
omy. Ego development during this time should be fos- child. Freud termed this period the anal stage because
tered but with appropriate limits. the developmental issue of bowel control is the major
As children develop a sense of self, they begin to un- task requiring mastery. It encompasses a more general-
derstand the feelings of others and develop empathy. ized theme of socialized behavior and overall body
They hug another child who is in perceived distress or cleanliness, which is usually taught or imposed on the
become concerned when one is hurt. They begin to un- child at this age.
derstand how another child feels when he or she is
harmed, and this realization helps them to inhibit their LANGUAGE DEVELOPMENT:
own aggressive behavior. Children also begin to under-
stand right and wrong and parental expectations. They
AGES 1–4 YEARS
recognize that they have done something “bad” and Communication is important from birth (see Table
may signify that awareness by saying “uh-oh” or with 2–2 and Figure 2–11), particularly the nonverbal, reci-
other expressions of distress. They also take pleasure in procal interactions between infant and caregiver. By age
their accomplishments and become more aware of their 2 months, these interactions begin to include vocaliza-
bodies. tions such as cooing and reciprocal vocal play between
An area of child behavior that has often been over- parent and child. Babbling begins by age 6–10 months,
looked is play. Play is the child’s work and a significant and the repetition of sounds such as “da-da-da-da” is
means of learning. Play is a very complex process whose facilitated by the child’s increasing oral muscular con-
purpose can include the practice and rehearsal of roles, trol. Babbling reaches a peak at age 12 months. The
skills, and relationships; a means of revisiting the past; a child then moves into a stage of having needs met by
means of actively mastering a range of experiences; and using individual words to represent objects or actions.
a way to integrate the child’s life experiences. It involves It is common at this age for children to express wants
emotional development (affect regulation, gender iden- and needs by pointing to objects or using other ges-
tification and roles), cognitive development (nonverbal tures. The acquisition of expressive vocabulary varies
and verbal function, executive functioning and creativ- greatly between 12 and 24 months of age. As a group,
ity), and social/motor development (motor coordina- males and children who are bilingual tend to develop
tion, frustration tolerance, and social interactions such expressive language more slowly during that time. It is
as turn taking). Of interest is the fact that play has a de- important to note, however, that for each individual,
velopmental progression. The typical 6- to 12-month- milestones should still fall within the expected range.
old engages in the game of peek-a-boo, which is a form Gender and exposure to two languages should never be
of social interaction. During the next year or so, al- used as an excuse for failing to refer a child who has sig-
though children engage in increasingly complex social nificant delay for further evaluation. It is also important
interactions and imitation, their play is primarily soli- to note that most children are not truly bilingual. Most
tary. However, they do begin to engage in symbolic children have one primary language, and any other lan-
play such as by drinking from a toy cup and then by guages are secondary.
giving the doll a drink from a toy cup. By the second to Receptive language usually develops more rapidly
third year children begin to engage in parallel play (en- than expressive language. Word comprehension increases
gaging in behaviors that are imitative). This form of at age 9 months, and by age 13 months the child’s recep-
play gradually evolves into more interactive or collabo- tive vocabulary may be as large as 20–100 words. After
rative play by the fourth year and is also more thematic age 18 months, expressive and receptive vocabularies in-
in nature. There are of course wide variations in the de- crease dramatically, and by the end of the second year a
velopment of play, reflecting cultural, educational, and quantum leap in language development permits a major
socioeconomic variables. Nevertheless, the development advance in cognitive development. The child begins to
of play does follow a sequence that can be assessed and put together words and phrases and begins to use lan-
can be very informative in the evaluation of the child. guage to represent a new world, the symbolic world. At
Brain maturation sets the stage for toilet training. this time, children begin to put verbs into their phrases
After age 18 months, toddlers have the sensory capacity and focus much of their language on describing their
for awareness of a full rectum or bladder and are physi- new abilities, for example, “I go out.” They incorporate
cally able to control bowel and urinary tract sphincters. prepositions into speech and ask “why?” and “what?”
They also take great pleasure in their accomplishments, questions more frequently. They also begin to appreciate
particularly in appropriate elimination, if it is rein- time factors and to understand and use this concept in
forced positively. Children must be given some control their speech (see Table 2–1).
over when elimination occurs. If parents impose severe The Early Language Milestone (ELM) Scale (see
restrictions, the achievement of this developmental Figure 2–11) is a simple tool for assessing early lan-
 CHILD DEVELOPMENT & BEHAVIOR / 83

guage development in the pediatric office setting. It is ated in the preschool years. The child is ready to relate
scored in the same way as the Denver II (Figure 2–12) to peers in a more interactive manner. The brain has
but tests receptive and expressive language areas in reached 90% of its adult weight. Sensorimotor coordi-
greater depth. nation abilities are maturing and facilitating pencil-
Piaget characterized the 2- to 6-year-old stage as pre- and-paper tasks and sports, both part of the school
operational. This stage begins when language has facili- experience. Cognitive abilities are still at the preopera-
tated the creation of mental images in the symbolic tional stage, and children focus on one variable in a
sense. The child begins to manipulate the symbolic problem at a time. However, most children have mas-
world; sorts out reality from fantasy imperfectly; and tered conservation of length by age 51⁄2 years, conserva-
may be terrified of dreams, wishes, and foolish threats. tion of mass and weight by 61⁄2 years, and conservation
Most of the child’s perception of the world is egocen- of volume by 8 years.
tric or interpreted in reference to his or her needs or in- By first grade, there is more pressure on the child to
fluence. Cause–effect relationships are confused with master academic tasks—recognizing numbers, letters,
temporal ones or interpreted egocentrically. For exam- and words and learning to write. Piaget described the
ple, children may focus their understanding of divorce stage of concrete operations beginning after age 6 years,
on themselves (“My father left because I was bad” or when the child is able to perform mental operations
“My mother left because she didn’t love me”). Illness concerning concrete objects that involve manipulation
and the need for medical care are also commonly misin- of more than one variable. The child is able to order,
terpreted at this age. The child may make a mental con- number, and classify because these activities are related
nection between a sibling’s illness and a recent argu- to concrete objects in the environment and because
ment, a negative comment, or a wish for the sibling to these activities are stressed in early schooling. Magical
be ill. The child may experience significant guilt unless thinking diminishes greatly at this time, and the reality
the parents are aware of these misperceptions and take of cause–effect relationships is better understood. Fan-
time to deal with them. tasy and imagination are still strong and are reflected in
At this age, children also endow inanimate objects themes of play.
with human feelings. They also assume that humans
cause or create all natural events. For instance, when MIDDLE CHILDHOOD:
asked why the sun sets, they may say, “The sun goes to
his house” or “It is pushed down by someone else.”
AGES 7–11 YEARS
Magical thinking blossoms between ages 3 and 5 years Freud characterized ages 7–11 years as the latency years,
as symbolic thinking incorporates more elaborate fan- during which children are not bothered by significant
tasy. Fantasy facilitates development of role playing, aggressive or sexual drives but instead devote most of
sexual identity, and emotional growth. Children test their energies to school and peer group interactions. In
new experiences in fantasy, both in their imagination reality, throughout this period there is a gradual in-
and in play. In their play, children often create magical crease in sex drive, manifested by increasingly aggressive
stories and novel situations that reflect issues with play and interactions with the opposite sex. Fantasy still
which they are dealing, such as aggression, relation- has an active role in dealing with sexuality before ado-
ships, fears, and control. Children often invent imagi- lescence, and fantasies often focus on movie and music
nary friends at this time, and nightmares or fears of stars. Organized sports, clubs, and other activities are
monsters are common. At this stage, other children be- other modalities that permit preadolescent children to
come important in facilitating play, such as in a display socially acceptable forms of aggression and sex-
preschool group. Play gradually becomes more coopera- ual interest.
tive; shared fantasy leads to game playing. Freud de- For the 7-year-old child, the major developmental
scribed the oedipal phase between ages 3 and 6 years, tasks are achievement in school and acceptance by
when there is strong attachment to the parent of the peers. Academic expectations intensify and require the
opposite sex. The child’s fantasies may focus on play- child to concentrate on, attend to, and process increas-
acting the adult role with that parent, although by age ingly complex auditory and visual information. Chil-
6 years oedipal issues are usually resolved and attach- dren with significant learning disabilities or problems of
ment is redirected to the parent of the same sex. attention span may have difficulty in these tasks and
subsequently may receive negative reinforcement from
EARLY SCHOOL YEARS: teachers and even parents. Such children may develop a
poor self-image manifested as behavioral difficulties.
AGES 5–7 YEARS The pediatrician must evaluate potential learning dis-
Attendance at kindergarten at age 5 years marks an ac- abilities in any child who is not developing adequately
celeration in the separation–individuation theme initi- at this stage or who presents with emotional or behav-
 Denver II Examiner:
Date:
Name:
Birthdate:
ID No.:
YEARS
MONTHS
2 4 6 9 12 15 18 24 3 4 5 6

R PREPARE CEREAL

R BRUSH TEETH, NO HELP

Percent of children passing R PLAY BOARD/CARD GAMES

25 50 75 90 R
4 DRESS, NO HELP
May pass by report R
TEST ITEM R PUT ON T-SHIRT
Footnote no. T 86%
(See back of form)
NAME FRIEND
15 COPY
R WASH & DRY HANDS 16 DRAW PERSON 6 PARTS
R
3 BRUSH TEETH WITH HELP 15 COPY DEMONSTR.
R PUT ON CLOTHING
13 PICK LONGER LINE
FEED DOLL 14 COPY +
R REMOVE GARMENT
16 DRAW PERSON 3 PTS
R USE SPOON/FORK
12 COPY
R HELP IN HOUSE 88%
11 THUMB WIGGLE
R DRINK FROM CUP 25 DEFINE 7 WORDS
TOWER OF 8 CUBES
R IMITATE ACTIVITIES 26 OPPOSITES-2
10 IMITATE VERTICAL LINE
PLAY BALL WITH EXAMINER 23 COUNT 5 BLOCKS
TOWER OF 6 CUBES
R WAVE BYE-BYE 21 KNOW 3 ADJECTIVES
TOWER OF 4 CUBES
25 DEFINE 5 WORDS
R INDICATE WANTS
TOWER OF 2 CUBES
PERSONAL - SOCIAL

NAME 4 COLORS
R PLAY PAT-A-CAKE
DUMP RAISIN, DEMONSTRATED
24 UNDERSTAND 4 PREPOSITIONS
R FEED SELF
SCRIBBLES
SPEECH ALL UNDERSTANDABLE
WORK FOR TOY PUT BLOCK IN CUP
R 20 KNOW 4 ACTIONS
2 REGARD OWN HAND R BANG 2 CUBES
HELD IN HANDS 22 USE OF 3 OBJECTS
R SMILE
SPONTANEOUSLY 9 THUMB-FINGER 23 COUNT 1 BLOCK
GRASP
1 SMILE
RESPON- 22 USE OF 2 OBJECTS
SIVELY TAKE 2 CUBES
NAME 1 COLOR
REGARD 8 PASS CUBE
FACE 21 KNOW 2
RAKE RAISIN ADJECTIVES

7 LOOK FOR YARN 20 KNOW 2 ACTIONS

BALANCE EACH FOOT 6 SECONDS
REACHES 18 NAME 4 PICTURES
30 HEEL-TO-TOE WALK
REGARD RAISIN SPEECH HALF UNDERSTANDABLE
BALANCE EACH FOOT 5 SECS.
5 FOLLOW 180° 18 POINT 4 PICTURES
FINE MOTOR - ADAPTIVE

BALANCE EACH FOOT 4 SECS.

HANDS 19 BODY PARTS-6
TOGETHER BALANCE EACH FOOT 3 SECONDS
18 NAME 1 PICTURE
HOPS
6 GRASP
RATTLE R COMBINE WORDS
BALANCE EACH
FOOT 2 SECONDS
FOLLOW PAST 15 POINT 2 PICTURES
5
MIDLINE BALANCE EACH
R 6 WORDS FOOT 1 SECOND
FOLLOW
5 TO
MIDLINE R 3 WORDS 29 BROAD JUMP

R 2 WORDS 28 THROW BALL OVERHAND

R ONE WORD
JUMP UP

©1969, 1989, 1990 W.K. Frankenburg and J. B. Dodds ©1978 W. K. Frankenburg

R DADA/MAMA SPECIFIC
KICK BALL FORWARD
R JABBERS R
27 WALK UP STEPS
R COMBINE SYLLABLES
RUNS
TEST BEHAVIOR
R DADA/MAMA
NON SPECIFIC R WALK BACKWARDS (Check boxes for 1st, 2nd, or 3rd test)
R IMITATE SPEECH SOUNDS WALK WELL
Typical 1 2 3
R SINGLE SYLLABLES STOOP AND RECOVER Yes
TURN TO VOICE STAND ALONE No
STAND 2 SECS.
TURN TO
17 RATTLING SOUND Compliance (See Note 31) 1 2 3
R GET TO
SITTING Always Complies
LANGUAGE

R SQUEALS

R LAUGHS
PULL TO Usually Complies
STAND
Rarely Complies
R "OOO/AAH"
STAND
R VOCALIZES HOLDIND ON Interest in Surroundings 1 2 3
RESPOND TO BELL SIT-NO
SUPPORT Alert
Somewhat Disinterested
PULLTO SIT- NO HEAD-LAG
Seriously Disinterested
R ROLL OVER

CHEST UP-ARM Fearfulness 1 2 3

SUPPORT
None
BEAR WEIGHT ON LEGS
Mild
SIT-HEAD STEADY Extreme
GROSS MOTOR

HEAD UP 90°
Attention Span
HEAD UP 45° 1 2 3
R LIFT Appropriate
HEAD Somewhat Distractable
EQUAL Very Distractable
MOVEMENTS

MONTHS
2 4 6 9 12 15 18 24 3 4 5 6
YEARS

Figure 2–12. Denver II. (Copyright © 1969, 1989, 1990 WK Frankenburg and JB Dodds. © 1978 WK Frankenberg.)

84
 CHILD DEVELOPMENT & BEHAVIOR / 85

ioral problems. The developmental status of school-age the parents’ understanding of the child and the child’s
children is not documented as easily as that of younger relationship to the environment. These strategies also
children because of the complexity of the milestones. In facilitate the parents’ care of the growing infant and
the school-age child, the quality of the response, the at- child.
tentional abilities, and the child’s emotional approach The last section of this chapter discusses develop-
to the task can make a dramatic difference in success at mental disorders of cognitive and social competence.
school. The clinician must consider all of these aspects Diagnosis and management of these conditions requires
in the differential diagnosis of learning disabilities. a comprehensive and often multidisciplinary approach.
The health care provider can play a major role in diag-
Bayley N (ed): Bayley Scales of Infant Development, 2nd ed. Psycho- nosis, in coordinating the child’s evaluation, in inter-
logical Corporation, 1993. preting the results to the family, and in providing reas-
Billeaud FP: Communication Disorders in Infants and Toddlers, An- surance and support.
dover Medical, 1993.
Bjorklund FP: Children’s Thinking. Brooks/Cole, 1995. Capute AJ, Accardo PJ (eds): Developmental Disabilities in Infancy
Dixon SD, Stein MT: Encounters with Children: Pediatric Behavior and Childhood, 2nd ed. Vol 1, Neurodevelopmental Diagnosis
and Development, 3rd ed. Mosby-Year Book, 2000. and Treatment. Vol. 2, The Spectrum of Developmental Dis-
abilities. Brookes/Cole, 1996.
Frankenberg WK et al. The Denver II: A major revision and re-
standardization of the Denver Developmental Screening Test. Greydanus DE, Wolraich ML (eds): Behavioral Pediatrics. Springer,
Pediatrics 1991;89:91. 1992.
Glascoe FP, Dworkin PH: The role of parents in the detection of Levine MD, Carey WB, Crocker AC (eds): Developmental-Behav-
developmental and behavioral problems. Pediatrics ioral Pediatrics, 3rd ed. WB Saunders, 1999.
1995;95:829 [PMID: 7539122]. Parker S, Zuckerman B (eds): Behavioral and Developmental Pedi-
Green M, Palfrey JS (eds): Bright Futures: Guidelines for Health Su- atrics: A Handbook for Primary Care. Little, Brown, 1995.
pervision of Infants, Children, and Adolescents, 2nd ed revised. Wolraich ML (ed): Disorders of Development and Learning: A Prac-
National Center for Education in Maternal and Child Health tical Guide to Assessment and Management, 2nd ed. Mosby,
Georgetown University, 2002. 1996.
Levine MD, Carey WB, Crocker AC (eds): Developmental-Behav- Wolraich ML, Felice ME, Drotar D: The Classification of Child
ioral Pediatrics, 3rd ed. WB Saunders, 1999. and Adolescent Mental Diagnoses in Primary Care: Diagnostic
Parker S, Zuckerman B (eds): Behavioral and Developmental Pedi- and Statistical Manual for Primary Care (DSM-PC) Child and
atrics: A Handbook for Primary Care. Little, Brown, 1995. Adolescent Version. American Academy of Pediatrics, 1996.

II. BEHAVIORAL & NORMALITY & TEMPERAMENT

DEVELOPMENTAL VARIATIONS The physician confronted by a disturbance in physio-
logic function rarely has doubts about what is abnor-
mal. Variations in temperament and behavior are not as
Behavioral and developmental variations and disorders straightforward. Labeling such variations as disorders
encompass a wide range of issues of importance to pedi- implies that a disease entity exists.
atricians. Practitioners will be familiar with most of the The behaviors described in this section are viewed as
problems discussed in this chapter; however, with in- part of a continuum of responses by the child to a vari-
creasing knowledge of the factors controlling normal ety of internal and external experiences. Variations in
neurologic and behavioral development in childhood, temperament have been of interest to philosophers and
new perspectives on these disorders and novel ap- writers since ancient times. The Greeks believed there
proaches to their diagnosis and management are emerg- were four temperament types: choleric, sanguine,
ing. melancholic, and phlegmatic. In more recent times,
Variations in children’s behavior reflect a blend of folk wisdom has defined temperament as a genetically
intrinsic biologic characteristics and the environments influenced behavioral disposition that is stable over
with which the children interact. The next section fo- time. Although a number of models of temperament
cuses on some of the more common complaints about have been proposed, the one usually used by pediatri-
behavior encountered by those who care for children. cians in clinical practice is that of Thomas and Chess,
These behavioral complaints are by and large normal who describe temperament as being the “how” of be-
variations in behavior, a reflection of each child’s indi- havior as distinguished from the “why” (motivation)
vidual biologic and temperament traits and the parents’ and the “what” (ability). Temperament is an indepen-
responses. There are no cures for these behaviors, but dent psychological attribute that is expressed as a re-
management strategies are available that can enhance sponse to an external stimulus. The influence of tem-
86 / CHAPTER 2

perament is bidirectional: The effect of a particular ex- highly emotional and another less so (ie, calmer) in re-
perience will be influenced by the child’s temperament, sponse to a variety of experiences, stressful or pleasant.
and the child’s temperament will influence the re- The clinician must recognize that each child brings
sponses of others in the child’s environment. Tempera- some intrinsic, biologically based traits to its environ-
ment is the style with which the child interacts with the ment and that such characteristics are neither good nor
environment. bad, right nor wrong, normal nor abnormal; they are
The perceptions and expectations of parents must be simply part of the child. Thus, as one looks at varia-
considered when a child’s behavior is evaluated. A child tions in development, one should abandon the illness
that one parent might describe as hyperactive might not model and consider this construct as an aid to under-
be characterized as such by the other parent. This tru- standing the nature of the child’s behavior and its influ-
ism can be expanded to include all the dimensions of ence on the parent–child relationship.
temperament. Thus, the concept of “goodness of fit”
comes into play. For example, if the parents want and Barr RG: Normality: A clinically useless concept: The case of infant
expect their child to be predictable but that is not the crying and colic. J Dev Behav Pediatr 1993;14:264 [PMID:
child’s behavioral style, the parents may perceive the 8408670].
child as being bad or having a behavioral disorder Goldsmith HH et al: Roundtable: What is temperament? Four ap-
rather than as having a developmental variation. An ap- proaches. Child Dev 1987;58:505 [PMID: 3829791].
preciation of this phenomenon is important because Prior M: Childhood temperament. J Child Psychol Psychiatr
the physician may be able to enhance the parents’ un- 1992;33:249 [PMID: 1737829].
derstanding of the child and influence their responses Thomas A, Chess S: Temperament and Development.
Brunner/Mazel, 1977.
to the child’s behavior. When there is goodness of fit,
there will be more harmony and a greater potential for
healthy development not only of the child but also of
the family. When goodness of fit is not present, tension COMMON DEVELOPMENTAL
and stress can result in parental anger, disappointment,
frustration, and conflict with the child. CONCERNS
Other models of temperament include those of
Rothbart, Buss and Plomin, and Goldsmith and Cam-
COLIC
pos (Table 2–4). All models seek to identify intrinsic Infant colic is characterized by severe and paroxysmal
behavioral characteristics that lead the child to respond crying that occurs mainly in the late afternoon. The in-
to the world in particular ways. One child may be fant’s knees are drawn up and its fists are clenched, fla-
tus is expelled, the facies is “pained,” and there is mini-
mal response to attempts at soothing. Studies in the
United States have shown that among middle-class in-
fants, crying occupies about 2 hours per day at 2 weeks
Table 2–4. Theories of temperament. of age, about 3 hours per day by 6 weeks, and gradually
decreases to about 1 hour per day by 3 months. The
Thomas and Temperament is an independent psychol- word “colic” is derived from Greek kolikos (“pertaining
Chess ogic attribute, biologically determined, which to the colon”). Although colic has traditionally been at-
is expressed as a response to an external tributed to gastrointestinal disturbances, this has never
stimulus. It is the child’s behavioral style: an been proved. Colic is a behavioral sign or symptom that
interactive model. begins in the first few weeks of life and peaks at age
Rothbart Temperament is a function of biologically 2–3 months. In about 30–40% of cases, colic continues
based individual differences in reactivity and into the fourth and fifth months.
self-regulation. It is subsumed under the A colicky infant, as defined by Wessel, is one who is
concept of “personality” and goes beyond healthy and well fed but cries for more than 3 hours a
mere “behavioral style.” day, for more than 3 days a week, and for more than
Buss and Temperament is a set of genetically deter- 3 weeks—commonly referred to as the rule of threes.
Plomin mined personality traits that appear early in The important word in this definition is “healthy.”
life and are different from other inherited Thus, before the diagnosis of colic can be made, the pe-
and acquired personality traits. diatrician must rule out diseases that might cause cry-
ing. With the exception of the few infants who respond
Goldsmith and Temperament is the individual’s differences to elimination of cow’s milk from its own or the
Campos in the probability of experiencing emotions
mother’s diet, there has been little firm evidence of an
and arousal.
association of colic with allergic disorders. Gastroesoph-
 CHILD DEVELOPMENT & BEHAVIOR / 87

ageal reflux is often suspected as a cause of colicky cry- made aware that crying increases normally into
ing in young infants. Undetected corneal abrasion, uri- the second month and abates by the third to
nary tract infection, and unrecognized traumatic in- fourth month.
juries including child abuse must be among the physical 2. Parents may need reassurance, based on a complete
causes of crying considered in evaluating these infants. history and physical examination, that the infant is
Some attempts have been made to eliminate gas with not sick. Although these behaviors are stressful,
simethicone and to slow gut motility with dicyclomine. they are a normal variant and are usually self-lim-
Simethicone has not been shown to ameliorate colic. ited. This discussion can be facilitated by having
Dicyclomine has been associated with apnea in infants the parent keep a diary of crying and weight gain.
and is contraindicated. If there is a diurnal pattern and adequate weight
This then leaves characteristics intrinsic to the child gain, an underlying disease process is less likely to
(ie, temperament) and parental caretaking patterns as be present. Parental anxiety must be relieved, be-
contributing to colic. Behavioral states have three fea- cause it may be contributing to the problem.
tures: (1) they are self-organizing—that is, they are 3. For parents to effectively soothe and comfort the
maintained until it is necessary to shift to another one; infant, they need to understand the baby’s cues.
(2) they are stable over several minutes; and (3) the The pediatrician can help by observing the in-
same stimulus elicits a state-specific response that is dif- fant’s behavior and devising interventions aimed
ferent from other states. The behavioral states are at calming both the infant and the parents. One
(among others) a crying state, a quiet alert state, an ac- can encourage a quiet environment without exces-
tive alert state, a transitional state, and a state of deep sive handling. Rhythmic stimulation such as gen-
sleep. The states of importance with respect to colic are tle swinging or rocking, soft music, drives in the
the crying state and the transitional state. During tran- car, or walks in the stroller may be helpful, espe-
sition from one state to another, infant behavior may be cially if the parents are able to anticipate the onset
more easily influenced. Once an infant is in a stable of crying. Another approach is to change the feed-
state (eg, crying), it becomes more difficult to bring ing habits so that the infant is not rushed, has
about a change (eg, to soothe). How these transitions ample opportunity to burp, and, if necessary, can
are accomplished is probably influenced by the infant’s be fed more frequently so as to decrease gastric
temperament and neurologic maturity. Some infants distention if that seems to be contributing to the
move from one state to another easily and can be di- problem.
verted easily; other infants sustain a particular state and
are resistant to change. 4. Medications such as phenobarbital elixir and di-
The other component to be considered in evaluating cyclomine have been found to be somewhat help-
the colicky infant is the feeding and handling behavior of ful, but their use is to be discouraged because of
the caregiver. Colic is a behavioral phenomenon that in- the risk of adverse reactions and overdosage. A
volves interaction between the infant and the caregiver. trial of ranitidine hydrochloride might be of help
Different caregivers perceive and respond to crying be- if gastroesophageal reflux is contributing to the
havior differently. If the caregiver perceives the crying in- child’s discomfort.
fant as being spoiled and demanding and is not sensitive 5. For colic that is refractory to behavioral manage-
to or knowledgeable about the infant’s cues and ment, a trial of changing the feedings, eliminating
rhythms—or is hurried and “rough” with the baby—the cow’s milk from the formula, or from the
infant’s ability to organize and soothe itself or respond to mother’s diet if she is nursing, may be indicated.
the caregiver’s attempts at soothing may be compro-
mised. Alternatively, if the temperament of an infant Barr RG et al (eds): Crying as a Sign, a Symptom, and a Signal: Clin-
with colic is understood and the rhythms and cues deci- ical, Emotional, and Developmental Aspects of Infant and Tod-
phered, crying can be anticipated and the caregiver can dler Crying. MacKeith Press, 2000.
intervene before the behavior becomes “organized” in the Barr RG, Geertsma MA: Colic: The pain perplex. In: Schechter NL
crying state and more difficult to extinguish. et al (eds): Pain in Infants, Children and Adolescents. Williams
& Wilkins, 1993.
Barr RG: Colic and crying syndromes in infants. Pediatrics
Management of Colic 1998;102:1282 [PMID: 9794970].
Dhigo SK: New strategies for the treatment of colic: Modifying the
A number of approaches can be taken to the manage- parent–infant interaction. J Pediatr Health Care
ment of colic. 1998;12:256.
Lucassen PL et al: Effectiveness of treatments for infantile colic: A
1. Parents may need to be educated about the devel- systematic review. Br Med J 1998;316:1563 [PMID:
opmental characteristics of crying behavior and 1945549].
88 / CHAPTER 2

Miller AR, Barr RG: Infantile colic: Is it a gut issue? Pediatr Clin interaction. One of the most striking manifestations of
North Am 1991;38:1407. food refusal occurs during the stage of separation and
Treem WR: Infant colic: A pediatric gastroenterologist’s perspec- individuation. Conflict may arise if the parent seeks to
tive. Pediatr Clin North Am 1994;41:1121 [PMID: dominate the child by intrusive and controlling feeding
7936776].
behavior at the same time the child is striving to achieve
autonomy. The scenario then observed is of the parent
FEEDING DISORDERS IN INFANTS forcing food on the child while the child refuses to eat.
This often leads to extreme parental frustration and
& YOUNG CHILDREN anger, and the child may be inadequately nourished
Children have feeding problems for various reasons. and developmentally and emotionally thwarted.
The common denominator, however, is usually food When the pediatrician is attempting to sort out the
refusal. Infants and young children may refuse to eat if factors contributing to food refusal, it is essential first to
they find eating painful or frightening. They may have obtain a complete history, including a social history.
had unpleasant experiences (emotional or physiologic) This should include information concerning the par-
associated with eating, they may be depressed, or they ents’ perception of the child’s behavior and their expec-
may be engaged in a developmental conflict with the tations of the child. Second, a complete physical exami-
caregiver that is being played out in the arena of feed- nation should be performed, with emphasis on
ing. The infant may refuse to eat if the rhythm of the oral–motor behavior and other clues suggesting neuro-
feeding experience with the caregiver is not harmo- logic, anatomic, or physiologic abnormalities that could
nious. The child who has had an esophageal atresia re- make feeding difficult. The child’s emotional state and
pair and has a stricture may find eating uncomfortable. developmental level must be determined. This is partic-
The very young infant with severe oral candidiasis may ularly important if there is concern about depression or
refuse to eat because of pain. The child who has had a a history of developmental delays. If evidence of
choking experience associated with feeding may be ter- oral–motor difficulty is suspected, evaluation by an oc-
rified to eat (oral motor dysfunction or aspiration). The cupational therapist is warranted. Third, the feeding in-
child who is forced to eat by a maltreating parent or an teraction needs to be observed live, if possible. Finally,
overzealous caregiver may refuse feeds. Children who the physician needs to help the parents understand that
have required nasogastric feedings or who have required infants and children may have different styles of eating
periods of fasting and intravenous nutrition in the first and different food preferences and may refuse foods
1–2 months of life are more likely to display food re- they do not like. This is not necessarily abnormal but
fusal behavior upon introduction of oral feedings. reflects temperamental differences and variations in the
Depression in children may be expressed through child’s way of processing olfactory, gustatory, and tac-
food refusal. Food refusal may develop when the in- tile stimuli.
fant’s cues around feeding are not interpreted correctly
by the parent. The baby who needs to burp more fre- Management of Feeding Disorders
quently or who needs time between bites but instead is
rushed will often passively refuse to eat. Some will be The goal of intervention is to identify factors contribut-
more active refusers, turning their heads away to avoid ing to the disturbance and to work to overcome them.
the feeder, spitting out food, or pushing away food. The parents may be encouraged to view the child’s be-
Chatoor and coworkers have proposed a develop- havior differently and try not to impose their expecta-
mental and interactive construct of the feeding experi- tions and desires. Alternatively, the child’s behavior
ence. The stages through which the child normally pro- may need to be modified so that the parents can pro-
gresses are establishment of homeostasis (0–2 months), vide adequate nurturing.
attachment (2–6 months), and separation and individ- When the chief complaint is failure to gain weight, a
uation (6 months to 3 years). During the first stage, different approach is required. The differential diagno-
feeding can be accomplished most easily when the par- sis should include not only food refusal but also med-
ent allows the infant to determine the timing, amount, ical disorders and maltreatment. The most common
pacing, and preference of food intake. During the at- reason for failure to gain weight is inadequate caloric
tachment phase, allowing the infant to control the feed- intake. Excessive weight loss may be due to vomiting or
ing permits the parent to engage the infant in a positive diarrhea, to malabsorption, or to a combination of
manner. This paves the way for the separation and indi- these factors. In this situation more extensive diagnostic
viduation phase. When a disturbance occurs in the par- evaluation may be needed. Laboratory studies may in-
ent–child relationship at any of these developmental clude a complete blood count; erythrocyte sedimenta-
levels, difficulty in feeding may ensue, with both the tion rate; urinalysis and urine culture; blood urea nitro-
parent and the child contributing to the dysfunctional gen; serum electrolytes and creatinine; and stool
 CHILD DEVELOPMENT & BEHAVIOR / 89

examination for fat, occult blood, and ova and para- lescents. The circadian clock has a 25-hour cycle. Envi-
sites. Some practitioners also include liver and thyroid ronmental cues entrain the sleep–wake cycle into a
profiles. Occasionally an assessment of swallowing 24-hour cycle. The cues are light–dark, ambient tem-
function or evaluation for the presence of gastroesopha- perature, core body temperature, noise, social interac-
geal reflux may be indicated. Because of the complexity tion, hunger, pain, and hormone production. Without
of the problem, a team approach to the diagnosis and the ability to perceive these cues (ie, blindness, autism)
treatment of failure to thrive, or poor weight gain, may a child might have difficulty entraining a 24-hour
be most appropriate. The team should include a physi- sleep–wake cycle. Two major sleep stages have been
cian, nurse, social worker, and dietitian. Occupational identified clinically and with the use of polysomnogra-
and physical therapists, developmentalists, and psychol- phy (electroencephalography, electro-oculography, and
ogists may be required. electromyelography): rapid eye movement (REM) and
The goals of treatment of the child with poor weight nonrapid eye movement (NREM) sleep. In REM sleep,
gain are to establish a normal pattern of weight gain muscle tone is relaxed, the sleeper may twitch and gri-
and to establish better family functioning. Guidelines mace, and the eyes move erratically beneath closed lids.
to accomplishing these goals include the following: In adults and children, REM sleep occurs throughout
(1) establish a comprehensive diagnosis that considers the night but is increased during the latter half of the
all factors contributing to poor weight gain; (2) moni- night. NREM sleep is divided into four stages. In the
tor the feeding interaction and ensure appropriate process of falling asleep, the individual enters stage 1,
weight gain; (3) monitor the developmental progress of light sleep, characterized by reduced bodily movements,
the child and the changes in the family dynamics that slow eye rolling, and sometimes opening and closing of
facilitate optimal weight gain and psychosocial develop- the eyelids. Stage 2 sleep is characterized by slowing of
ment; and (4) provide support to the family as they eye movements, slowing of respirations and heart rate,
seek to help the child. and relaxation of the muscles but with repositioning of
the body. Some dreaming may occur in this stage. Most
Benoit D: Phenomenology and treatment of failure to thrive. Child
mature individuals spend about half of their sleep time
Adolesc Psychiatr Clin North Am 1993;2:61. in this stage. Stages 3 and 4 (also called delta or slow-
Macht J: Poor Eaters. Plenum, 1990. wave sleep) are the deepest NREM sleep stages, during
Reilly SM et al: Oral–motor dysfunction in children who fail to which the body is relaxed, breathing is slow and shal-
thrive: Organic or non-organic. Dev Med Child Neurol low, and the heart rate is slow.
1999;41:115. The deepest NREM sleep occurs during the first
Skuse D: Epidemiologic and definitional issues in failure to thrive. 1–3 hours after going to sleep. Parasomnias occur dur-
Child Adolesc Psychiatr Clin North Am 1993;2:37. ing deep NREM sleep. Dreams and nightmares occur
Stevenson RD: Failure to thrive. In Greydanus DE, Wolraich ML during REM sleep.
(eds): Behavioral Pediatrics. Springer, 1992. Sleep is clearly a developmental phenomenon. In-
Wolraich ML (ed): Disorders of Development and Learning, 3rd ed. fants are not born with a sleep–wake cycle. REM sleep
Hamilton: BC Decker, 2003 is more common than NREM sleep in newborns and
decreases by 3 to 6 months of age. Sleep spindles and
vertex waves are usually not seen until 9 weeks of age.
SLEEP DISORDERS By 3 to 6 months, stage 1 through 4 NREM sleep can
Sleep is a complex physiologic process influenced by in- be seen. By 6 to 12 months an infant’s electroen-
trinsic biologic properties, temperament, cultural cephalogram (EEG) can be read using adult criteria. In-
norms and expectations, and environmental conditions. fants also do not make melatonin until 9 to 12 weeks of
Between 20% and 30% of children experience sleep age. Melatonin is a hormone that decreases core body
disturbances at some point in the first 4 years of life. temperature and that appears to play a role in sleep
The percentage decreases to 10–12% in school-age onset and sleep maintenance. This hormone is sensitive
children. Sleep disorders fall into two categories. Dys- to light, does cross the placenta, and is present in breast
somnias refer to problems with initiating and maintain- milk.
ing sleep or to excessive sleepiness. Parasomnias refer to
abnormalities of arousal, partial arousal, and transitions
between stages of sleep.
Sleep is controlled by two different biologic clocks.
1. Parasomnias
The first is a circadian rhythm–-sleep occurs daily. The Parasomnias, consisting of arousal from deep NREM
second is an ultradian rhythm that occurs several times sleep, are probably the most frightening for parents.
per night—the stages of sleep. Sleep stages cycle every They include night terrors, sleeptalking, and sleepwalk-
50 to 60 minutes in infants to every 90 minutes in ado- ing (somnambulism) (see Chapter 22).
90 / CHAPTER 2

Night Terrors & Sleepwalking frightening, dyssomnias tend to be only annoying and
frustrating. They can result in daytime fatigue for both
Night terrors commonly occur within 2 hours after the parents and the child, parental discord about man-
falling asleep, during the deepest stage of NREM sleep, agement, and family disruption. A number of factors
and are often associated with sleepwalking. They occur contribute to these disturbances. The quantity and tim-
in about 3% of children. During a night terror, the ing of feeds in the first years of life will influence night-
child may sit up in bed screaming, thrashing about, and time awakening. Most infants beyond age 6 months
exhibiting rapid breathing, tachycardia, and sweating. can go through the night without being fed. Thus,
The child is often incoherent and unresponsive to com- under normal circumstances, night waking for feeds is
forting. The episode may last up to half an hour, after probably a learned behavior and is a function of the
which the child goes back to sleep and has no memory child’s arousal and the parents’ response to that arousal.
of the event the next day. The parents must be reas- Cosleeping (ie, sleeping with the parents) can play a
sured that the child is not in pain and that they should role in night waking. In many cultures, cosleeping is ac-
let the episode run its course. cepted behavior. It is inappropriate behavior when it
Management of night terrors is by reassurance of the intrudes on the parents’ rest and their sexual relation-
parents plus measures to avoid emotional and psy- ship. Bedtime habits can influence settling in for the
chosocial stressors that might be contributing to the night as well as nighttime awakening. If the child learns
problem. Because sleepwalking can result in injury, the that going to sleep is associated with pleasant parental
parents should determine, if possible, when the attacks behavior such as rocking, singing, reading, or nursing,
usually occur and awaken the child to full arousal about going back to sleep after nighttime arousal without
15 minutes before that time. After 4–5 minutes, the these pleasant parental attentions may be difficult. The
child may be allowed to return to sleep. The waking is child’s temperament is another factor contributing to
discontinued once the terrors stop, which is usually sleep. It has been reported that children with low sen-
within a week. In severe cases, pharmacologic interven- sory thresholds and less rhythmicity are more prone to
tions may be needed temporarily. Imipramine night waking. Children who have had perinatal diffi-
(25–50 mg at bedtime) may be useful. However, be- culties such as intracranial hemorrhage and hyaline
havioral approaches to increase the total amount of membrane disease have a greater incidence of night
sleep and to address the sources of anxiety and stress are waking and difficulties returning to sleep. Finally, psy-
of more long-term benefit. chosocial stressors can play a role in night waking.

Nightmares
Management of Sleep Disorders
Nightmares are frightening dreams during REM sleep,
typically followed by awakening, which usually occur in A complete medical and psychosocial history should be
the latter part of the night. The peak occurrence is be- obtained and a physical examination performed. A de-
tween ages 3 and 5 years, with an incidence between tailed sleep history and diary should be maintained to
25% and 50%. A child who awakens during these which both parents contribute. Some clinicians use
episodes is usually alert. He or she can often describe polysomnography to complete the evaluation. Problems
the frightening images, recall the dream, and talk about often arise when parents try to put the child to bed be-
it during the day. The child seeks and will respond pos- fore he or she is biologically ready. The child might
itively to parental reassurance. The child will often have then lie awake and cry. In managing sleep difficulties,
difficulty going back to sleep and will want to stay with the child’s individual sleep behavior characteristics
the parents. Nightmares are usually self-limited and must be taken into account and the parents’ expecta-
need little treatment. If the child has recurrent night- tions and fears identified and addressed. Counseling is
mares, the pediatrician may have to make a more exten- then provided on the following basis:
sive investigation. Nightmares are often associated with
stressful or frightening daytime events or anxieties such 1. Sleep is a highly active and organized process that
as frightening television programs, traumatic life events, matures during the first years of life. One-week-
and chronic stresses in the family. In severe cases, a psy- old infants sleep about 16 hours a day, 6 of those
chologist or psychiatrist should be consulted. hours during the daylight hours. A 2-year-old
child sleeps a total of 13 hours a day, only 1 hour
during the day.
2. Dyssomnias 2. Individual circadian rhythms do not change im-
The dyssomnias include problems going to sleep and mediately; they require consistency and regularity
nighttime awakenings. Although parasomnias are over a period of time before change will occur.
 CHILD DEVELOPMENT & BEHAVIOR / 91

3. The duration of sleep for a given individual does Chervin RD et al: Inattention, hyperactivity, and symptoms of
not vary significantly from day to day, but there is sleep-disordered breathing. Pediatrics 2002;109(3):449 [PMID:
11875140].
a wide range of normal.
Ferber R: Clinical assessment of child and adolescent sleep disorder.
4. The duration of nighttime sleep is correlated in- Child Adolesc Psychiatr Clin North Am 1996;5:569.
versely with daytime sleep, and bedtimes and France KG et al: Fact, act, and tact: A three-stage approach to treat-
awakening times are correlated positively with ing the sleep problems of infants and young children. Child
each other. Adolesc Psychiatr Clin North Am 1996;5:581 .
5. Night waking occurs in 40–60% of infants and Mindel JA, Owens JA: A Clinical Guide to Pediatric Sleep: Diagnosis
young children. If the child does not cry or wake and Management of Sleep Problems. Lippincott Williams &
up the parents, such behavior should not be con- Wilkins, 2003.
sidered a sleep disturbance. Mindell JA: Treatment of child and adolescent sleep disorders.
Child Adolesc Psychiatr Clin North Am 1996;5:741.
Rosen GM et al: Evaluation of parasomnias in children. Child
Adolesc Psychiatr Clin North Am 1996;5:601.
Parents need to set limits for the child while ac- Wolfson AR: Sleeping patterns of children and adolescents: Devel-
knowledging the child’s individual biologic rhythms. opment trends, disruptions and adaptations. Child Adolesc
Psychiatr Clin North Am 1996;5:549.
They should resist the child’s attempts to put off bed-
www.kidzzzsleep.org
time or to engage them during nighttime awakenings.
Putting a child to bed after prolonged rocking, feeding,
or when the child has already fallen asleep frequently
results in disturbances of settling down at night or TEMPER TANTRUMS
going back to sleep after a nighttime awakening. The & BREATH-HOLDING SPELLS
goal is to establish clear bedtime rituals, to put the child
to bed while still awake, and to create a quiet, secure 1. Temper Tantrums
bedtime environment. Temper tantrums are common between ages
For the child who has a delayed sleep phase—that is, 12 months and 4 years, occurring about once a week in
difficulty in falling asleep and waking at desired times 50–80% of children in this age group. The child may
but no difficulty at a later hour—a regular schedule and throw himself or herself down, kick and scream, strike
consistent, nonstimulating bedtime rituals must be pro- out at people or objects in the room, and hold his or
vided. Approaches used to alter the child’s behavior in- her breath. These behaviors may be considered normal
clude having the parents withdraw the attention elicited as the young child seeks to achieve autonomy and mas-
by the wakeful child and having them offer positive re- tery over the environment. They are often a reflection
inforcement of the desired behavior. Another strategy of immaturity as the child strives to accomplish age-ap-
to alter this sleep pattern is to gradually move the bed- propriate developmental tasks and meets with difficulty
time to an earlier hour and awaken the child earlier in because of inadequate motor and language skills, im-
the morning. However, there is nothing intrinsically pulsiveness, or parental restrictions. In the home, these
normal or abnormal in the delayed sleep phase. It be- behaviors may be annoying. In public, they are embar-
comes a problem only when it differs from parental ex- rassing.
pectations. Some children tolerate frustration well, are able to
Some children are afraid to go to sleep. The parents persevere at tasks, and cope easily with difficulties; oth-
need to help the child identify what is frightening ers have a much greater problem dealing with experi-
about going to sleep and may need to stay near the ences beyond their developmental level. Parents can
child, reassuring the child that he or she is safe. Over a minimize tantrums by understanding the child’s tem-
period of time, the child can be reassured and the par- perament and what he or she is trying to communicate.
ents may not need to be so involved. This also applies Parents must also be committed to supporting the
to nighttime awakenings. child’s drive to master his or her feelings.
The key to treatment of children who have difficulty
going to sleep or who awaken during the night and dis-
turb others is to recognize that both the child and the
parents play significant roles in initiating and sustaining
Management of Temper Tantrums
what may be an undesirable behavior. Thus, it becomes Appropriate intervention can provide an opportunity
important for the physician and parents to understand for enhancing the child’s growth. The tantrum is a loss
normal sleep patterns, the parents’ responses that inad- of control on the child’s part that may be a frightening
vertently reinforce undesirable sleep behavior, and the event and a blow to the child’s self-image. The parents
child’s individual temperament traits. and the physician need to view these behaviors within
92 / CHAPTER 2

the child’s developmental context rather than from a prolonged inspiration. In fact, breath-holding occurs
negative, adversarial, angry perspective. during expiration and is reflexive—not volitional—in
Several suggestions can be offered for parents and nature. It is a paroxysmal event occurring in 0.1–5% of
physicians in managing tantrums: healthy children from age 6 months to 6 years. The
spells usually start during the first year of life, often in
1. Minimize the need to say “no” by “child-proof- response to anger or a mild injury. The child is pro-
ing” the environment so that fewer restrictions voked or surprised, starts to cry—briefly or for a con-
need be enforced. siderable time—and then falls silent in the expiratory
2. Use distraction when frustration increases; direct phase of respiration. This is followed by a color change.
the child to other, less frustrating activities; and Spells have been described as either pallid (acyanotic) or
reward the positive response. cyanotic, with the latter usually associated with anger
3. Present options within the child’s capabilities so and the former with an injury such as a fall. The spell
that he or she can achieve mastery and autonomy. may resolve spontaneously, or the child may lose con-
sciousness. In severe cases, the child may become limp
4. Fight only those battles that need to be won, and and progress to opisthotonos, body jerks, and urinary
avoid those that arouse unnecessary conflict. incontinence. Only rarely does a spell proceed to asys-
5. Do not abandon the preschool child when a tole or a seizure.
tantrum occurs. Stay nearby during the episode
without intruding. A small child may need to be
restrained. An older child can be asked to go to Management of Breath-Holding Spells
his or her room. Threats serve no purpose and
should not be used. For the child with frequent spells, underlying disorders
6. Do not use negative terms when the tantrum is such as seizures, orthostatic hypotension, obstructive
occurring. Instead, point out that the child is out sleep apnea, abnormalities of the CNS, tumors, familial
of control and give praise when he or she regains dysautonomia, and Rett syndrome need to be consid-
control. ered. An association exists among breath-holding spells,
pica, and iron deficiency anemia. These conditions can
7. Never let a child hurt himself or herself, or others. be ruled out on the basis of the history, physical exami-
8. Do not “hold a grudge” after the tantrum is over, nation, and laboratory studies. Once it has been deter-
but do not grant the child’s demands that led to mined that the child is healthy, the focus of treatment
the tantrum. is behavioral. Parents should be taught to handle the
9. Seek to maintain an environment that provides spells in a matter-of-fact manner and monitor the child
positive reinforcement for desired behavior. Do for any untoward events. The reality is that parents can-
not overreact to undesired behavior, but set rea- not completely protect the child from upsetting and
sonable limits and provide responsible direction frustrating experiences and probably should not try to
for the child. do so. Just as in temper tantrums, parents need to help
10. Approximately 5–20% of young children have se- the child control his or her responses to frustration.
vere temper tantrums that are frequent and dis- Parents need to be careful not to be too permissive and
ruptive. Such tantrums may result from a distur- submit to the child’s every whim for fear the child
bance in the parent–child interaction, poor might have a spell. If loss of consciousness occurs, the
parenting skills, lack of limit-setting, and permis- child should be placed on his or her side to protect
siveness. They may be part of a larger behavioral against head injury and aspiration. Maintaining a
or developmental disorder or may emerge under patent oral airway is essential, but cardiopulmonary re-
adverse socioeconomic conditions, in circum- suscitation should be avoided. There are no prophylac-
stances of maternal depression and family dys- tic medications. Atropine, 0.01 mg/kg given subcuta-
function, or when the child is in poor health. Re- neously, has been used with some benefit in spells
ferral to a psychologist or psychiatrist is accompanied by bradycardia or asystole.
appropriate while the pediatrician continues to
support and work with the family.
Breningstall GN: Breath holding spells. Pediatr Neurol
1996;14:91 [PMID: 8703234].
2. Breath-Holding Spells DiMario FJ Jr: Breath-holding spells in childhood. Am J Dis Child
1992;146:125 [PMID: 1736640].
Whereas temper tantrums can be frustrating to parents, Greene RW: The Explosive Child. Quill, 2001.
breath-holding spells can be terrifying. The name for Needleman R et al: Temper tantrums: When to worry. Contempo-
this behavior may be a misnomer in that it connotes rary Pediatrics 1989;6:12.
 CHILD DEVELOPMENT & BEHAVIOR / 93

Needleman R et al: Psychosocial correlates of severe temper must also obtain a detailed medical and developmental
tantrums. J Dev Behav Pediatr 1991;12:77. history and conduct the physical and neurologic exam.

Medical and Neurodevelopmental

III. DEVELOPMENTAL Examination
DISORDERS The medical history should begin with pregnancy,
labor, and delivery to identify conditions that might
compromise the child’s CNS. The physician must ask
Developmental disorders include problems with one or the child’s parents about exposures to toxins, alcohol,
more aspects of development, such as verbal, motor, vi- drugs, smoking, and infections; maternal chronic ill-
sual–spatial, attentional, and social abilities. These ness; prematurity; subsequent newborn course; and
problems are diagnosed by comparing the child’s per- complications (eg, intraventricular hemorrhage or hy-
formance level with norms accumulated from observa- poxic insult). Problems such as failure to thrive, chronic
tion and testing of children of the same age. Problems illnesses, hospitalizations, and abuse can interfere signif-
with development are often noted by parents when a icantly with normal development. If the newborn
child does not meet normal motor and language mile- course has been complicated, then information should
stones. Developmental disorders may also include diffi- be obtained from the hospital where treatment was pro-
culties with behavior or attention. Attention-deficit/hy- vided. The occurrence of problems such as apnea,
peractivity disorder (ADHD) is the most common bradycardic episodes, and hyperbilirubinemia should be
neurodevelopmental problem known. ADHD occurs in documented.
2–10% of school-age children and may occur in combi- The physician should review and document the
nation with a variety of other learning or developmen- child’s temperament, difficulties with feeding, and sub-
tal problems. Mild developmental disorders are often sequent developmental milestones. The child’s develop-
not noted until the child is of school age. ment in expressive and receptive language skills, motor
Many biologic and psychosocial factors may influ- coordination, and emotions should be discussed in de-
ence a child’s performance on developmental tests. In tail. The child’s difficulties with tantrums, attentional
the assessment of the child, it is important to document problems, impulsivity, hyperactivity, or aggression
adverse psychosocial factors, such as neglect or poverty, should be documented.
which can negatively influence developmental progress. Major illnesses or hospitalizations should be dis-
Many of the biologic factors that influence develop- cussed. Any CNS problems, such as trauma, infection,
ment are genetic and are discussed throughout this sec- or encephalitis should be documented. The presence of
tion. metabolic diseases, such as diabetes or phenylketonuria,
and exposure to environmental toxins such as lead
Evaluation should be determined. Chronic diseases such as chronic
otitis media infections, hyper- or hypothyroidism, and
The neurodevelopmental evaluation must focus on chronic renal failure can interfere with normal develop-
(1) defining the child’s level of developmental abilities ment. The presence of motor or vocal tics, seizures, or
in a variety of domains, including language, motor, vi- sleep disturbances should be documented. In addition,
sual–spatial, attentional, and social abilities; (2) charac- parents should be questioned about any motor, cogni-
terizing the reason for the child’s developmental delays; tive, or behavioral regression.
and (3) planning a treatment program for the develop- A detailed history of school-related events should be
mental problems. These objectives are best achieved by recorded, including previous special education support,
a multidisciplinary team that includes the physician, a evaluations through the school, history of repeating
psychologist, a speech or language therapist, an occupa- grades, difficulties with specific academic areas, prob-
tional therapist, and an educational specialist. The psy- lems with peers, and the teacher’s impressions of the
chologist will usually carry out standardized testing of child’s difficulties, particularly related to attentional
intellectual ability appropriate to the child’s age. The problems, impulsivity, or hyperactivity.
motor and language specialists will also carry out clini- Perhaps the most important aspect of the medical
cal testing to document the deficits in their areas and to history is a detailed family history of learning strengths
organize a treatment program. The educational special- and weaknesses, emotional or behavioral problems,
ist will usually carry out academic testing for the learning disabilities, or mental retardation. The pres-
school-age child and plan a course of special education ence of more severe psychopathology, such as schizo-
support through the school. The physician is usually phrenia, bipolar disorder, depression, anxiety, or
the integrator of the information from the team and ADHD, should be noted for all family members.
94 / CHAPTER 2

Parental learning strengths and weaknesses, tempera- Levine MD et al (eds): Developmental-Behavioral Pediatrics, 3rd ed.
ment difficulties, or attentional problems may be WB Saunders, 1999.
passed on to the child. For instance, dyslexia (deficits in Reynolds CR, Mayfield JW: Neuropsychological assessment in ge-
decoding skills resulting in reading difficulties) may be netically linked neurodevelopmental disorders. In Goldstein
S, Reynolds CR (eds): Handbook of Developmental and Ge-
genetic. Autosomal dominant genes on chromosomes netic Disorders in Children. Guilford, 1999.
6 and 15 have been associated with dyslexia. Wolraich ML (ed): Disorders of Development and Learning, 3rd
The neurodevelopmental examination should in- ed. Hamilton: BC Decker, 2003
clude a careful assessment of dysmorphic features such http://www.nichcy.org
as epicanthal folds, palpebral fissure size, shape of the
philtrum, low set or posteriorally rotated ears, promi-
nent ear pinnae, unusual dermatoglyphics (eg, a single ATTENTION-DEFICIT/HYPERACTIVITY
palmar crease), hyperextensibility of the joints, syn- DISORDER
dactyly, clinodactyly, or other unusual features. A de- ADHD is a common neurodevelopmental disorder that
tailed physical and neurologic examination needs to be may affect 2–10% of school-age children and may per-
carried out with an emphasis on both soft and hard sist into adolescence and adulthood. It is associated with
neurologic findings. Soft signs can include motor inco- a triad of symptoms: impulsivity, inattention, and hy-
ordination, which can relate to handwriting problems peractivity. DSM-IV has described two ADHD sub-
and academic delays in written language or drawing. types: impulsive and inattentive. To be classified accord-
Visual motor coordination abilities can be assessed by ing to either subtype, the child must exhibit six or more
having the child write, copy designs, or draw a person. of the symptoms listed in Table 2–5. The majority of
The child’s growth parameters, including height, children with ADHD have a combined type with symp-
weight, and head circumference, need to be assessed, toms of inattention as well as hyperactivity and impul-
along with hearing and visual acuity. Cranial nerve ab- sivity. Although symptoms begin in early childhood,
normalities and oral motor coordination problems need they can diminish between ages 10 and 25 years. Hyper-
to be noted. The examiner should watch closely for activity declines more quickly, and impulsivity and inat-
motor or vocal tics, which are quite common in indi- tentiveness often persist in adolescence and adulthood.
viduals with Tourette syndrome. Both fine and gross ADHD may be combined with other psychiatric condi-
motor abilities should be assessed. Dyspraxic move-
ments in fine motor coordination are fairly common.
Tandem walking, one-foot balancing, and coordinating Table 2–5. Attention deficit/hyperactivity
a skip may often show surprising abnormalities. disorder subtypes.
The developmental aspects of the examination can
include an assessment of auditory processing and per-
ceptual ability with simple tasks, such as twofold to Subtype Symptomsa
fivefold directions, assessing right and left directional- Impulsivity- Fidgetiness
ity, memory for a series of spoken words or digit span, hyperactivity Difficulty remaining seated in the class
and comprehension of a graded paragraph. In assessing Excessive running or climbing
expressive language abilities, the examiner should look Difficulty in engaging quiet activities
for difficulties with word retrieval, formulation and ar- Excessive talking and blurting out answers
ticulation, and adequacy of vocabulary. Visual–percep- before questions have been completed
tual abilities can be assessed by simple visual memory Difficulty awaiting turns
tasks, puzzles, or object assembly, evaluating the child’s Interrupting and intruding on others
ability to decode words or organize math problems. Vi- Inattentive Failure to give close attention to detail
sual motor integration and coordination can be assessed Difficulty sustaining intention in task
again with handwriting, design copying, and drawing a Failure to listen when spoken to directly
person. Throughout the assessment the clinician should Failure to follow instructions
pay special attention to the child’s ability to focus at- Difficulty organizing tasks and activities
tention and concentrate, and to other aspects of behav- Reluctance to engage in tasks
ior such as evidence of depression or anxiety. Losing utensils necessary for tasks or activi-
Additional questionnaires and checklists—such as ties
the Child Behavior Checklist by Achenbach; ADHD Easy distractibility
scales such as the Conners’ (or Parent/Teacher) Rating Forgetfulness in daily activities
Scale; and the SNAP-IV, which includes the Diagnostic a
The child must exhibit six or more of these symptoms.
and Statistical Manual (DSM-IV) criteria for ADHD— Adapted, with permission, from American Psychiatric Association,
can be used to help with this assessment. 1994.
 CHILD DEVELOPMENT & BEHAVIOR / 95

tions, such as mood disorder in approximately 20% of It is most important that, no matter what medica-
patients, conduct disorders in 20%, and oppositionally tion is used, the diagnosis is correct and the correct
defiant disorder in up to 40%. Approximately 25% of dosage is prescribed. A recent study has demonstrated
children with ADHD seen in a referral clinic have tics or that one of the major factors contributing to treatment
Tourette syndrome. Conversely, well over 50% of indi- failure is inadequate dosing or the failure to recognize
viduals with Tourette syndrome also have ADHD. the presence of comorbid conditions such as learning
ADHD has a substantial genetic component, with a disability, anxiety disorders, and depression.
heritability of 0.75 to 0.91. Several candidate genes In children with normal intellectual abilities,
have been identified, although there is strong evidence 70–90% respond well to stimulant medications. Stimu-
that ADHD is a disorder involving multiple genes. lants enhance both dopamine and norepinephrine neu-
ADHD is also associated with a variety of genetic disor- rotransmission, which seems to improve impulse con-
ders related to developmental disorders, including frag- trol, attention, and hyperactivity. Metabolic studies of
ile X syndrome, Williams syndrome, Angelman syn- the CNS (eg, using positron emission tomography
drome, XXY syndrome (Klinefelter syndrome), and scanning) have demonstrated enhanced metabolism in
Turner syndrome. Fetal alcohol syndrome (FAS) is also several areas of the brain, including the caudate and the
strongly associated with ADHD. CNS trauma, CNS frontal regions.
infections, prematurity, and a difficult neonatal course The side effects of methylphenidate and dextroam-
with brain injury can also be associated with later phetamine include appetite suppression and resulting
ADHD. Metabolic problems such as hyperthyroidism weight loss as well as sleep disturbances. Some individ-
can sometimes cause ADHD. These organic causes of uals experience increased anxiety, particularly with
ADHD should be considered in the evaluation of any higher doses of stimulant medications. Stimulants may
child presenting with attentional problems, hyperactiv- exacerbate psychotic symptoms. They may also exacer-
ity, or impulsivity. However, in the majority of chil- bate motor tics in 30% of patients, but in 10% motor
dren who have ADHD the cause remains unknown. tics may be improved. Long-acting and short-acting
forms of stimulant medication are available. The initial
dose of methylphenidate is 0.3 mg/kg/dose given two
Treatment or three times daily. Adderall is a relatively new stimu-
The treatment of ADHD varies depending on the com- lant that combines four dextro and levo amphetamine
plexity of the individual case. It is important to educate salts. This is a long-acting medication, and often a sin-
the family regarding the symptoms of ADHD and to gle morning dose suffices for the day.
clarify that this is a neurologic disorder that at times is Alternative medications for the treatment of ADHD
difficult for the child to control. Behavior modification include clonidine or guanfacine, which are α2-adrener-
techniques usually help these children and should in- gic presynaptic agonists that decrease norepinephrine
clude structure with consistency in daily routine, posi- levels. They are particularly helpful for individuals who
tive reinforcement whenever possible, and time out for are hyperreactive to stimuli and may be helpful in de-
negative behaviors. It is important to try to boost the creasing motor tics in patients who have Tourette syn-
child’s self-esteem because psychological complications drome. Tricyclic antidepressant medications such as
are common in this disorder. imipramine may also be an effective treatment for
A variety of educational interventions can be help- ADHD, but the cardiovascular side effects at high
ful, including preferential seating in the classroom, a dosage can include severe arrhythmias. Bupropion is an
system of consistent positive behavior reinforcement, antidepressant medication that can also be effective for
consistent structure, the repetition of information when treatment of ADHD symptoms. Its use is contraindi-
needed, and the use of instruction that incorporates cated in patients with a history of seizures, because it
both visual and auditory modalities. Many children will lower the seizure threshold. It has also been known
with ADHD have significant social difficulties, and so- to cause seizures in individuals who have anorexia or
cial skills training can be helpful. Individual counseling bulimia. It is used more commonly in adolescents and
is beneficial in alleviating poor self-esteem, oppositional adults with ADHD than in children with the disorder.
behavior, and conduct problems.
The use of medication, specifically stimulant med-
ication such as methylphenidate (Ritalin) and dex- American Academy of Pediatrics: Clinical practice guideline: Diag-
nosis and evaluation of the child with attention-deficit/hyper-
troamphetamine, can be helpful. A new medication, activity disorder. Pediatrics 2000;105:1117 [PMID:
atomoxatine a noncontrolled substance, has been found 10836893].
to be effective in some children with ADHD. Pemoline American Psychiatric Association: Diagnostic and Statistical Manual
is no longer recommended because of its association of Mental Disorders, 4th ed. American Psychiatric Association,
with liver injury. 1994.
96 / CHAPTER 2

Barkley RA: Attention Deficit Hyperactivity Disorder: A Clinical states have reported a prevalence of less than 2%. Mild
Workbook, 2nd ed. Guilford, 1998. levels of mental retardation are more common and
Barkley RA: Your Defiant Child: Eight Steps to Better Behavior. more likely to have a sociocultural cause than are more
Guilford, 1998. severe levels. Poverty, deprivation, or a lack of exposure
Elia J et al: Treatment of attention deficit hyperactivity disorder. to a stimulating environment can contribute to devel-
N Engl J Med 1999;340:780 [PMID: 1007214].
opmental delays and poor performance on standardized
Goldman LS et al: Diagnosis and treatment of attention deficit hy-
peractivity disorder in children and adults. JAMA
tests. In addition, physical problems such as hearing
1998;79:1100 [PMID: 9546570]. loss, blindness, and brain trauma can lead to develop-
Goldstein S, Mather N: Overcoming Underachieving: An Action mental delays and low IQ test scores. Great strides in
Guide to Helping Your Child Succeed in School. Wiley, 1998. our identification of genetic causes of mental retarda-
Jensen PS et al. Findings from the NIMS Multimotal Treatment tion have been made since the 1990s because of the
Study of ADHD (MTA): Implications and applications for Human Genome Project. Over 750 genetic disorders
primary care providers. J Develop Behav Pediatr have been associated with mental retardation, and over
2001;22:60 [PMID: 11265923]. 200 of those disorders are carried on the X chromo-
http://www.chadd.org some alone. In approximately 60% of cases, the cause
http://www.add.org of the mental retardation can be identified. Table
2–7 summarizes the findings of several studies on the
MENTAL RETARDATION causes of mental retardation.
Severe deficits in the development of language, motor Evaluation
skills, attention, abstract reasoning, visual–spatial skills,
and academic or vocational achievement are associated Children who present with developmental delays
with mental retardation. Deficits on standardized test- should be evaluated by a team of professionals as
ing in cognitive and adaptive functioning greater than described at the beginning of this section. For
2 standard deviations below the mean for the popula- children 0–31⁄2 years of age, the Bayley Scales of Infant
tion are considered to fall in the range of mental retar- Development, second edition, is a well-standardized
dation (Table 2–6). The most common way of report- developmental test. For children older than 3 years of
ing the results of these tests is by using an intelligence age standardized cognitive testing, such as the Wechsler
quotient (IQ). The IQ is a statistically derived number Preschool and Primary Scale of Intelligence–Revised
reflecting the ratio of age-appropriate cognitive func- (WPPSI-R), the WISC-III, the Stanford–Binet IV,
tion and the child’s level of cognitive function. A num- or the Kaufman Assessment Battery for Children (K-
ber of accepted standardized measurement tools, such ABC) should be administered to assess cognitive func-
as the Wechsler Intelligence Scale for Children, 3rd edi- tion over a broad range of abilities, including verbal and
tion (WISC-III), can be used to assess these capacities.
To receive a diagnosis of mental retardation a child
must not only have an IQ of less than 70, but also must
demonstrate adaptive skills more than 2 standard devia- Table 2–7. Causes of mental retardation.
tions below the mean. Adaptive function refers to the
child’s ability to function in his or her environment and Cause Percentage of Cases
can be measured by a parent or teacher interview-
Chromosomal abnormalities 4–28
recorded using an instrument such as the Vineland
Adaptive Behavior Scales. Fragile X syndrome 2–5
The prevalence of mental retardation is approxi- Monogenetic conditions 4–14
mately 3% in the general population, although some
Structural CNS abnormalities 7–17
Complications of prematurity 2–10
Table 2–6. Categories of mental retardation.
Environmental or teratogenic causes 5–13
Mental Retardation Range Intelligence Quotient (IQ) “Cultural-familial” mental retardation 3–12
Mild mental retardation 50–69 Metabolic or endocrine causes 1–5
Moderate mental retardation 35–49 Unknown 30–50
Severe mental retardation 20–34 Adapted from Curry CJ et al: Evaluation of mental retardation:
Recommendations for a consensus conference. Am J Med Genet
Profound mental retardation < 20 1997;72:468.
 CHILD DEVELOPMENT & BEHAVIOR / 97

nonverbal scales. For the nonverbal patient, a scale such and documentation of the abnormalities usually does
as the Leiter-R will assess skills that do not involve lan- not add to management.
guage. Metabolic screening has a relatively low yield
A full psychological evaluation in school-age (0–5%) in children who present with developmental
children should include an emotional assessment if psy- delay or mental retardation. Many patients with meta-
chiatric or emotional problems are suspected. Such bolic disorders such as hypothyroidism, phenylke-
problems are common in children with developmen- tonuria, and galactosemia are identified through new-
tal delays or mental retardation. A hearing test and a vi- born screening. Most patients with metabolic problems
sion screening or ophthalmologic evaluation are impor- will present with specific indications for more focused
tant to determine whether hearing and vision are testing, such as failure to thrive, recurrent unexplained
normal. illnesses, plateauing or loss of developmental skills,
Diagnostic testing should be carried out in an effort coarse facial features, cataracts, recurrent coma, abnor-
to find the cause of mental retardation. Because chro- mal sexual differentiation, arachnodactyly, he-
mosomal abnormalities occur in 4–28% of patients patosplenomegaly, deafness, structural hair abnormali-
with mental retardation, cytogenetic testing is impor- ties, muscle tone changes, and skin abnormalities.
tant in cases without a known cause. A consensus panel Thyroid function studies should be carried out in any
has recommended a high-resolution karyotype so that patient who has a palpably abnormal thyroid or exhibits
small deletions or duplications can be visualized. In ad- clinical features associated with hypothyroidism. Serum
dition, fluorescent in situ hybridization (FISH) studies amino acids, urine organic acid, and mucopolysaccha-
are available. These studies use a fluorescent DNA ride screens should be considered in children with de-
probe that hybridizes to a region of DNA where a dele- velopmental delays and a suggestive history. Prelimi-
tion or duplication is suspected. Microdeletion syn- nary laboratory findings such as lactic acidosis,
dromes—such as Prader–Willi syndrome or Angelman hyperuricemia, hyperammonemia, or a low or high
syndrome, caused by a deletion at 15q; velocardiofa- cholesterol level require additional metabolic work-up.
cial syndrome, caused by a deletion at 22q; Smith–Ma- Serial follow-up of patients is important because the
genis syndrome, caused by a deletion at 17p; and physical and behavioral phenotype changes over time
Williams syndrome, caused by a 7p deletion—can be and diagnostic testing improves with time. Although
assessed with FISH studies. Sometimes the deletion is cytogenetic testing may have been negative 10 years
so small that it may not be visualized through the mi- earlier, advances in high-resolution techniques, FISH
croscope even with high-resolution cytogenetic studies. testing, and fragile X DNA testing may now reveal an
If clinical features consistent with any of the microdele- abnormality that was not identified previously. A step-
tion syndromes are present, then FISH studies should wise approach to diagnostic testing may also be more
be ordered to look for a small deletion in a specific re- cost-effective, so that the test most likely to be positive
gion. In addition, duplications may be present. For ex- is done first.
ample, a duplication at 15q has been associated with
pervasive developmental disorder or autistic spectrum
disorders and with general mental retardation. This du- Treatment
plication can be identified by FISH testing.
Structural abnormalities of the brain can occur in Once a diagnosis of mental retardation is made, treat-
many individuals with mental retardation. Magnetic ment should include a combination of individual thera-
resonance imaging (MRI) is superior to computed to- pies, such as speech and language therapy, occupational
mography (CT) in identifying structural and myelina- therapy or physical therapy, special education support,
tion abnormalities. CT is the study of choice in evalua- behavioral therapy or counseling, and medical interven-
tion of intracranial calcifications, such as those seen in tion, which may include psychopharmacology. To illus-
congenital infections or tuberous sclerosis. The value of trate how these interventions work together, three dis-
CT and MRI studies in a child with a normal-sized orders are described in detail in the next section.
head and no focal neurologic signs is unclear, and they
are not routinely carried out. Neuroimaging is impor-
Burack JA et al (eds): Handbook of Mental Retardation and Develop-
tant in patients with microcephaly, macrocephaly, ment. Cambridge University Press, 1999.
seizures, loss of psychomotor skills, or specific neuro- Curry CJ et al: Evaluation of mental retardation: Recommenda-
logic signs such as spasticity, dystonia, ataxia, or abnor- tions of a consensus conference. Am J Med Genet
mal reflexes. Neuroimaging is not routinely carried out 1997;72:468 [PMID: 9375733].
in known genetic disorders such as Down syndrome, Hagerman RJ: Neurodevelopmental Disorders: Diagnosis and Treat-
fragile X syndrome, or microdeletion syndromes be- ment. Oxford University Press, 1999.
cause the CNS abnormalities have been well described http:www//TheArc.org
98 / CHAPTER 2

SPECIFIC FORMS OF MENTAL lays alone. As the boys move into puberty, macro-
RETARDATION & ASSOCIATED orchidism develops with an average adult volume of
50 mL, or twice the normal volume. The child’s face
TREATMENT ISSUES may become longer during puberty, and the majority of
1. Fragile X Syndrome these children continue to have prominent ears.
The most common inherited cause of mental retarda-
tion is fragile X syndrome, which is caused by a trinu- Treatment
cleotide expansion (CGG repeated sequence) within All young children with fragile X syndrome benefit
the fragile X mental retardation I (FMR1) gene. Indi- from language and motor therapy because delays in
viduals with mental retardation of unknown origin these areas are universal. Because approximately 10% of
should receive FMR1 DNA testing to see if they have boys with the syndrome will be nonverbal at age
an expansion of the CGG repeat causing dysfunction of 5 years, the use of augmentative communication tech-
this gene. The CGG sequence at FMR1 in the normal niques—such as signing; the use of pictures to represent
population includes 5–50 repeats. Carriers of the pre- food, toys, or activities; or the use of computers that
mutation have 54–200 repeats, and have been consid- can be programmed for communication—are helpful.
ered unaffected. However, there is mounting evidence Tantrums and hyperarousal to stimuli, along with hy-
for a specific phenotype in these individuals. Women peractivity, are common. Sensory integrative occupa-
with the premutation have a higher incidence of prema- tional therapy can be helpful in calming hyperarousal
ture ovarian failure, anxiety, and mild facial dysmor- to stimuli and in improving the child’s fine and gross
phisms. Individuals with the premutation have normal motor coordination and motor planning. Speech and
levels of FMR1 protein but increased levels of mRNA. language therapy can decrease oral hypersensitivity, im-
It should be noted that seemingly unaffected females prove articulation, enhance verbal output and compre-
can pass an expansion of the CGG repeat to the next hension, and stimulate abstract reasoning skills.
generation. Approximately 1 in 250 women and 1 in If the behavioral problems are severe, it can be help-
700 men in the general population are premutation car- ful to involve a behavioral psychologist who emphasizes
riers. When a premutation of more than 90 repeats is positive reinforcement, time outs, consistency in rou-
passed on by a female to her offspring, it will expand to tine, and the use of both auditory and visual modalities,
a full mutation (more than 200 repeats) 100% of the such as a picture sequence, to help with difficult transi-
time, which usually causes mental retardation or learn- tion times and new situations.
ing disabilities. The full mutation is associated with Psychopharmacology can also be useful to treat
methylation of the gene, which turns off transcription, ADHD, aggression, anxiety, or severe mood instability.
resulting in a deficiency in the FMR1 protein product. Clonidine or guanfacine may be helpful in low doses,
These deficiencies result in mental retardation or signif- beginning in the preschool period to treat hyperarousal,
icant learning and emotional problems. tantrums, or severe hyperactivity. Stimulant medica-
Fragile X syndrome includes a broad range of symp- tions such as methylphenidate, dextroamphetamine,
toms. Patients can present with shyness, social anxiety, and Adderall are usually beneficial by age 5 years and
and learning problems, or they can present with mental occasionally earlier. Relatively low doses are used (eg,
retardation. Girls are usually less affected by the syn- 0.2–0.3 mg/kg/dose of methylphenidate) because irri-
drome because they have a second X chromosome that tability is often a problem with higher doses.
is producing FMR1 protein. Approximately 70% of Shyness and social anxiety combined with mild
girls with the full mutation have cognitive deficits in ADHD are commonly seen in girls who have fragile X
addition to emotional problems, such as mood lability, syndrome. The social anxiety is sometimes so severe
ADHD, anxiety, and shyness. Approximately 85% of that selective mutism (refusal to speak in some environ-
males with the syndrome have mental retardation and ments, especially school) is seen in girls who have the
autistic-like features, such as poor eye contact, hand full mutation. The treatment for selective mutism in-
flapping, hand biting, and tactile defensiveness. About cludes fluoxetine, language therapy, and counseling.
20% of fragile X males meet the criteria for autism. Anxiety may also be a significant problem for boys
Children with fragile X syndrome usually present with fragile X syndrome, and the use of a selective sero-
with language delays, hyperactivity, and tantrum be- tonin reuptake inhibitor (SSRI) such as fluoxetine, ser-
havior in early childhood. Although prominent ears traline, fluvoxamine, or paroxetine is often helpful.
and hyperextensible finger joints are common, approxi- SSRIs may also decrease aggression or moodiness, al-
mately 30% of children with the syndrome may not though in approximately 25% of cases, an increase in
have these features, and the diagnosis must be suspected agitation or even hypomania may occur. The use of a
because of behavioral problems and developmental de- more limited serotonin agent, buspirone, may also be
 CHILD DEVELOPMENT & BEHAVIOR / 99

helpful for anxiety, particularly if the patient cannot from learning disabilities to severe mental retardation.
tolerate SSRIs. The Institute of Medicine has carefully defined diag-
Anticonvulsants such as carbamazepine, valproic nostic categories in patients with documented prenatal
acid, and gabapentin can be used to treat seizures, maternal alcohol consumption as follows:
which occur in 20% of children with fragile X syn-
drome. They can also be helpful in treating more severe
mood instability that does not improve with an SSRI, A. FETAL ALCOHOL SYNDROME
clonidine, or a stimulant medication. The use of carba- The diagnosis of FAS requires growth retardation; evi-
mazepine and valproic acid requires careful monitoring dence of CNS neurodevelopmental abnormalities; and
of blood levels, liver function studies, electrolytes, a characteristic pattern of facial anomalies, including
blood count, and platelet level. short palpebral fissures, thin upper lip, indistinct or
Aggression may become a significant problem in smooth philtrum, and midface hypoplasia.
childhood or adolescence for boys with fragile X syn-
drome. Counseling can often be helpful, although med-
ication may be needed. Stimulants, clonidine, and an B. PARTIAL FETAL ALCOHOL SYNDROME
SSRI may decrease aggression, although sometimes an The diagnosis of partial fetal alcohol syndrome (PFAS)
atypical antipsychotic may be needed. If psychotic fea- requires the presence of some but not all components of
tures are present, such as paranoia, delusions, or hallu- the facial anomalies as well as growth retardation, CNS
cinations, or if thinking is severely disorganized, then neurodevelopmental abnormalities, or behavioral or
an atypical antipsychotic is usually helpful. Risperidone cognitive abnormalities that are inconsistent with the
has been used most frequently in pediatrics and has a child’s developmental level and cannot be explained by
low risk for extrapyramidal symptoms. Side effects in- familial background or environment.
clude sedation, excessive appetite and subsequent
weight gain, and an increase in prolactin, which can
cause breast tenderness and gynecomastia in boys. Usu- C. ALCOHOL-RELATED NEURODEVELOPMENTAL
ally a low dose of risperidone is well tolerated, and DISORDER
0.5–2 mg at bedtime usually improves aggression, de- Alcohol-related neurodevelopmental disorder (ARND)
creases hyperactivity, and stabilizes mood. does not require the presence of facial dysmorphic fea-
An important component of treatment is genetic tures, but it does require the presence of CNS neurode-
counseling. Parents should meet with a genetic coun- velopmental abnormalities (eg, microcephaly, CNS
selor after the diagnosis of fragile X syndrome is made structural defects, neurologic hard and soft signs) or ev-
because there is a high risk that other family members idence of a complex pattern of behavioral or cognitive
are carriers or may be affected by the syndrome. A de- abnormalities as outlined earlier. These abnormalities
tailed family history is essential, and all siblings of the may include learning disabilities; poor impulse control;
proband should have FMR1 DNA testing. If the and problems in memory, attention, or judgment.
mother received the gene from her father, then all of
her sisters are obligate carriers, and their children are at
50% risk of having the fragile X mutation. D. ALCOHOL-RELATED BIRTH DEFECTS
It is also helpful to link up a newly diagnosed family to The diagnosis of alcohol-related birth defects (ARBD)
a parent support group. Educational materials and parent requires the presence of congenital anomalies including
support information may be obtained by calling The Na- malformations and dysplasias in cardiac, skeletal, renal,
tional Fragile X Foundation at 1-800-688-8765. ocular, or auditory areas (ie, sensorineural hearing loss).
Strong animal and human evidence supports all of
Hagerman RJ: Fragile X Syndrome in Neurodevelopmental Disorders: these diagnostic categories, including the controversial
Diagnosis and Treatment. Oxford University Press, 1999. ARND diagnosis, which does not involve dysmorphic
Hagerman RJ, Cronister AC (eds): Fragile X Syndrome: Diagnosis, features. The prevalence of FAS, PFAS, and ARND
Treatment, and Research, 3rd ed. Johns Hopkins University combined is approximately 1 per 100 in the general
Press, 2001. population. These are common problems, and the
http://www.FragileX.org physician must always ask about alcohol intake during
http://www.fraxa.org pregnancy in a nonjudgmental way to obtain an accu-
rate answer. The exact amount of alcohol consumption
that leads to teratogenesis remains unclear. There is
2. Fetal Alcohol Syndrome strong evidence that binge drinking during early critical
Significant alcohol exposure in utero is associated with periods of embryogenesis leads to alcohol-related syn-
a broad spectrum of developmental problems, ranging dromes.
100 / CHAPTER 2

Evaluation & Treatment Streissguth AP: Fetal Alcohol Syndrome: A Guide for Families and
Communities. Brookes/Cole, 1997.
The majority of children with alcohol-related syn- http://www.nofas.org
dromes present with ADHD symptoms, with or with-
out significant developmental delays. To adequately as-
sess involvement in other organs the following tests are 3. Autistic Spectrum Disorders
recommended: an ophthalmologic examination, a hear- Autism is a neurologic disorder characterized by
ing test, and a careful cardiac examination, with ultra- (1) qualitative impairments in social interaction;
sonography if abnormalities are detected. A careful ex- (2) qualitative impairments in communication; and
amination for dysmorphic features and bony (3) restricted repetitive and stereotyped patterns of be-
abnormalities is necessary. Renal function studies (ie, havior, interests, and activities. It is a relatively com-
creatinine) should be conducted and a renal ultrasound mon disorder, occurring in approximately 1 in
obtained. Mental health problems are observed in over 500 children. There is a higher incidence of autistic
90% of children and adolescents affected by alcohol in spectrum disorders in disorders such as fragile X syn-
utero. Depression, panic attacks, anxiety, and mood in- drome, tuberous sclerosis, Cornelia de Lange syn-
stability are common. Because psychotic ideation is drome, Down syndrome, and 15q duplication. Despite
present in 20–40% of individuals with alcohol-related this, in as many as 90% of cases of autism, no cause can
syndromes, a thorough emotional or psychiatric evalua- be identified. There is a strong familial component.
tion is essential. Long-term therapy and special educa- Parents of one child with autism have a 2–9% chance
tion services are usually needed, and psychopharmaco- of having a second child with autism. The concordance
logic intervention may be helpful. rate among monozygotic twins is high, and there is an
For treatment of ADHD symptoms, a dextroam- increased incidence of speech, language, reading, atten-
phetamine preparation should be tried initially, al- tion, and affective disorders in family members of chil-
though methylphenidate may also be helpful. SSRI dren with autism.
agents can help relieve anxiety, panic attacks, and de-
pression, although mania or hypomanias, a side effect,
may occur in 25–50% of patients. Mood instability Evaluation & Treatment
may be severe, although it usually responds to a mood Children with autism are often not diagnosed until age
stabilizer, such as valproate, or carbamazepine. One 3 to 4 years, when their disturbances in reciprocal social
should be cautious with lithium because kidney dys- interaction and communication become more appar-
function, secondary to malformations or hypoplasia, ent. However, impairments in communication and be-
occasionally occurs. Psychotic features should be havior can sometimes be recognized in the first 12 to
treated with an atypical antipsychotic such as risperi- 18 months of life. Behaviors noted during this period
done. Consultation with a psychiatrist is helpful be- include a lack of motor imitation, a lack of joint atten-
cause the mental health problems associated with these tion and social referencing, a lack of affect sharing, poor
syndromes are complex. eye contact, and a lack of symbolic play. The three
A speech and language evaluation and an occupa- most striking characteristics during the first year are a
tional therapy evaluation in childhood usually lead to consistent failure to orient to one’s name, failure to re-
documentation of problems, and ongoing therapy is gard people directly, and failure to develop speech. Be-
usually helpful. The most significant problem in alco- cause of evidence that early intervention is particularly
hol-related syndromes is the high rate of legal problems, important for children with autism, great interest has
incarceration, and alcohol or drug abuse in adolescence arisen in developing a screening instrument that can be
and adulthood. An intensive treatment program must used in very young children. The Checklist for Autism
be mobilized to improve the outcome of this disorder. in Toddlers (CHAT) is administered at 18 months and
Long-term counseling and advocacy, along with inten- includes a short parent questionnaire and direct obser-
sive job training, usually keeps these adolescents out of vation. It evaluates pretend play and joint attention
trouble, but the failure rate is high. (which includes pointing for interest and following
gaze). This instrument is quick and easy to administer
and has good specificity and positive predictive value
Hagerman RJ: Fetal Alcohol Syndrome in Neurodevelopmental Disor-
ders: Diagnosis and Treatment. Oxford University Press, 1999.
(83%). Unfortunately, its sensitivity is poor (18%).
Hagerman RJ, Cronister AC (eds): Fragile X Syndrome: Diagnosis,
Work is being done to modify this test or develop oth-
Treatment, and Research, 2nd ed. Johns Hopkins University ers with greater sensitivity. When behaviors consistent
Press, 1996. with autism are noted, the child should be referred to a
Stratton KR et al: Fetal Alcohol Syndrome: Diagnosis, Epidemiology, team of specialists experienced in the assessment of
Prevention, and Treatment. National Academy Press, 1996. autistic spectrum disorders as soon as possible.
 CHILD DEVELOPMENT & BEHAVIOR / 101

All children with autism should have a formal audi- Cohen DJ, Volkman FR (eds): Handbook of Autism and Pervasive
ology evaluation because of their language disorder. For Developmental Disorders, 2nd ed. John Wiley & Sons, Inc.
1997.
children with autism and mental retardation, tests for
high-resolution chromosomes, DNA for fragile X syn- Dawson G, Osterling J: Early intervention in autism: Effectiveness
and common elements of current approaches. In Guralnick
drome, FISH for 15q duplication, as well as metabolic MJ (ed): The Effectiveness of Early Intervention: Second Gener-
screening, lead level, and thyroid studies should be con- ation Research. Brookes/Cole, 1997.
sidered. A Woods lamp test for tuberous sclerosis may Filipek PA et al: Practice parameter: Screening and diagnosis of
also be done. Other tests should be considered as indi- autism: Report of the Quality Standards Subcommittee of the
cated by findings in the history and physical examina- American Academy of Neurology and Child Neurology Soci-
tion. Neuroimaging is not routinely indicated even in ety. Neurology 2000;55:468 [PMID: 10953176].
the presence of macrocephaly since children with Gabriels RL, Hill DE (eds): Autism: From Research to Individual-
autism often have relatively large heads. Approximately ized Practice. Jessica Kingsley Publishers, 2002.
15–30% of children with autism demonstrate plateau- Gilberg C, Coleman M (eds): The Biology of the Autistic Syndromes.
ing or loss of skills (usually language and social skills MacKeith Press, 2000.
only) between 12 and 24 months of age. This usually Lord C, McGee JP (eds): Educating Children with Autism. National
Academy of Sciences Press, 2001.
occurs before attaining 10 words. Children who have a
Ozonoff S et al (eds): Autism Spectrum Disorders: A Research Review
history of regression should have a sleep-deprived EEG, for Practioners. American Psychiatric Publishing, 2003.
or an overnight EEG, with adequate sampling of slow-
Rapin I: Autism. N Engl J Med 1997;337:97 [PMID: 9211680].
wave sleep to rule out epileptiform discharges during
Rogers SJ: Empirically supported comprehensive treatments for
slow-wave sleep. It should be noted that the recommen- young children with autism. J Clin Child Psychol
dations for treatment of that type of EEG abnormality 1998;27:168 [PMID: 9648034].
are still being debated. http://www.autism-society.org
Much controversy surrounds the appropriate treat- http://teacch.com
ment and educational approaches for children with http://firstsigns.org
autistic spectrum disorders. As with any child, treat-
ment should be based on the individual needs of the
child. It is clear, however, that intervention must begin
early and must be comprehensive and intensive. Some Web Resources
advocate 25 hours or more per week of treatment that
[Title V Program Information: Institute for Child Health Policy]
targets development of social attention, peer interac-
www.ichp.edu
tions, functional language, and appropriate play. It
should be noted that psychotropic medications have [Parent Training and Information Centers: Alliance Coordinating
Office]
been helpful in some children with autism. However,
www.taalliance.org
these medications should not take the place of behav-
[Advocacy: The Arc of the United States]
ioral interventions.
www.TheArc.org
Baird G et al: A screening instrument for autism at 18 months of [American with Disabilities Act Information: National Access for
age: A 6-year follow-up study. J Am Acad Child Adolesc Psy- Public Schools Project]
chiatr 2000;39:694 [PMID: 108946303]. www.adaptenv.org
Baird G et al: Current topic: Screening and surveillance for autism [General: NADDC-National Association of Developmental Dis-
and pervasive developmental disorders. Arch Dis Child abilities Councils]
2001;84:468 [PMID: 11369559]. www.naddc.org
 Adolescence 3
David W. Kaplan, MD, MPH, & Kathryn Love-Osborne, MD

Adolescence is a period of rapid physical, emotional, decade, alcohol use remains the underlying cause of
cognitive, and social growth and development. Gener- most teenage motor vehicle deaths. Almost two thirds
ally, adolescence begins at age 11–12 years and ends be- of motor vehicle deaths involving young drinking dri-
tween ages 18 and 21. Most teenagers complete pu- vers occur on Friday, Saturday, or Sunday, and 70%
berty by age 16–18 years; in western society, however, occur between 8:00 PM and 4:00 AM.
for educational and cultural reasons, the adolescent pe- There is continued concern in the United States
riod is prolonged to allow for further psychosocial de- with the problem of youth violence. This concern is
velopment before the individual assumes adult respon- rooted in the high rate of homicides involving hand-
sibilities. guns among young males, the number of firearm-re-
The developmental passage from childhood to lated suicides, and school shootings. Youths ages 12 to
adulthood encompasses the following steps: (1) com- 17 are twice as likely as adults to be victims of serious
pleting puberty and somatic growth; (2) developing so- violent crimes, which include aggravated assault, rape,
cially, emotionally, and cognitively, moving from con- robbery, and homicide. Violent crimes committed by
crete to abstract thinking; (3) establishing an juveniles constitute about 1 in 4 of all violent crimes.
independent identity and separating from the family; Nationally, 17.4% of high-school students reported
and (4) preparing for a career or vocation. carrying a weapon at least once in the preceding
30 days. However, since the peak rate of serious violent
crime involving juvenile offenders in 1993, the rate has
DEMOGRAPHY decreased. The rate of serious violent crimes among
In the United States in 2003, there were 20.3 million youth victims decreased from 37.6 in 1980 to 16.0 in
adolescents between ages 15 and 19 years and 19.8 mil- 2000.
lion between ages 20 and 24 years. Adolescents and
young adults (ages 15–24 years) constitute 14% of the
US population. Over the next several decades, the pro- MORBIDITY DATA
portion of racial and ethnic minority adolescents is ex- Demographic and economic changes in the American
pected to increase. It is projected that by 2040 the per- family since the mid-1970s have had a profound effect
centage of non-Hispanic whites will drop below 50%. on children and adolescents. Between 1955 and 1990,
Hispanics are becoming the second most populous the divorce rate rose from about 400,000 to nearly
racial/ethnic group. 1.2 million a year. Between 1960 and 1990, the num-
ber of children involved in divorce each year increased
from 460,000 to 1.1 million. The percentage of chil-
MORTALITY DATA dren and adolescents living in two-parent households
For the adolescent population, cultural and environ- has decreased significantly, from 79% in 1980 to 69%
mental rather than organic factors pose the greatest in 2001. Sixty-five percent of Hispanic and 38% of
threats to life. The three leading causes of death in the black children and adolescents younger than age
adolescent population (ages 15–19 years) in 2000 were 18 lived in a two-parent household in 2001. In 2002,
unintentional injury (49.8%), homicides (14.1%), and 16.7% of children and adolescents younger than age
suicides (12.0%). These three causes of violent death 18 years in the United States were living below the
accounted for 76.0% of all adolescent deaths. Deaths poverty level, compared with 12% in 1970. Forty per-
resulting from homicide among black 15- to 19-year- cent of children in mother-only families were living in
olds increased 328% between 1983 and 1993. Al- poverty.
though the homicide rate has decreased significantly The major causes of morbidity during adolescence
since the high in 1993, homicide is still the leading are psychosocial: unintended pregnancy, sexually trans-
cause of death for black adolescents age 15–19 years, mitted infections (STIs), substance abuse, smoking,
accounting for 38.0% of all deaths. Although deaths dropping out of school, depression, running away from
from automobile crashes have decreased over the last home, physical violence, and juvenile delinquency.
102
Copyright © 2005, 2001, by The McGraw-Hill Companies, Inc. Click here for terms of use.
 ADOLESCENCE / 103

High-risk behavior in one area is often associated with 9. Conflict with parents.
problems in another (Figure 3–1). For example, 10. Sexual acting-out.
teenagers who live in a dysfunctional family (eg, prob- 11. Conflicts with the law.
lems related to drinking or physical or sexual abuse) are
much more likely than other teenagers to be depressed. 12. Suicidal thoughts or preoccupation with themes
A depressed teenager is at greater risk for drug and alco- of death.
hol abuse, academic failure, inappropriate sexual activ- 13. Drug and alcohol abuse.
ity, STIs, pregnancy, and suicide. 14. Running away from home.
Early identification of the teenager at risk for these
problems is important in preventing immediate com-
plications and future associated problems. Early indica- American Academy of Pediatrics Committee on Injury and Poison
tors for problems related to depression include the fol- Prevention: Firearm-related injuries affecting the pediatric
lowing: population. Pediatrics 2000;105:888 [PMID: 10742344].
Anderson RN: Deaths: Leading causes for 2000. Natl Vital Stat
1. Decline in school performance. Rep 2002;50(16):1 [PMID: 12355905].
2. Excessive school absences or cutting class. Emery RE, Laumann-Billings L: Practical and emotional conse-
3. Frequent or persistent psychosomatic complaints. quences of parental divorce. Adolesc Med: State of the Art
Reviews 1998;9:271 [PMID: 10961235].
4. Changes in sleeping or eating habits.
Grunbaum JA et al: Youth risk behavior surveillance—United
5. Difficulty in concentrating or persistent boredom. States, 2001. MMWR Surveill Summ 2002;51(4):1 [PMID:
6. Signs or symptoms of depression, extreme stress, 12102329].
or anxiety. O’Malley PM, Johnston LD: Drinking and driving among US high
7. Withdrawal from friends or family, or change to a school seniors, 1984–1997. Am J Public Health
1999;89:678 [PMID: 10224978].
new group of friends.
Resnick MD et al: Protecting adolescents from harm: Findings
8. Unusually severe violent or rebellious behavior, or from the national longitudinal study on adolescent health.
radical personality change. JAMA 1997;278:823 [PMID: 9293990].

Physical health:
Acute illness
Chronic disease
Somatic complaints

School and social Family dysfunction:

dysfunction: Parent-parent conflict
Drop out Parent-child conflict
Bad grades Divorce/separation
No friends Alcoholism
Learning disability Parental indifference
Physical/sexual abuse

Emotional dysfunction: HIGH-RISK Juvenile justice:

Depression BEHAVIOR Delinquency
Suicide Detention
Stress/anxiety Institutionalization
Low self-esteem Runaway
Poor self-image

Sexual problems:
Pregnancy
Drug and STD
alcohol abuse Prostitution
Figure 3–1. Interrelation of high-
risk adolescent behavior.
104 / CHAPTER 3

Steinberg L: Gallagher lecture. The family at adolescence: Transi- RELATING TO THE ADOLESCENT
tion and transformation. J Adolesc Health
2000;27(3):170 [PMID: 10960215]. PATIENT
Suicide and suicide attempts in adolescents. Committee on Adoles- Adolescence is one of the physically healthiest periods
cents. American Academy of Pediatrics. Pediatrics 2000;105 in life. The challenge of caring for adolescents lies not
(4 Pt 1):871 [PMID: 10742340].
in managing complex organic disease but in accommo-
dating to the cognitive, emotional, and psychosocial
growth that influences health behavior.
DELIVERY OF HEALTH SERVICES How the physician initially approaches the adoles-
How, where, why, and when adolescents seek health cent may determine the success or failure of the visit.
care depends on ability to pay, distance to health care The physician should behave simply and honestly,
facilities, availability of transportation, accessibility of without an authoritarian or excessively professional
services, time away from school, and privacy. Many manner. Because the self-esteem of many young adoles-
common teenage health problems, such as unintended cents is fragile, the physician must be careful not to
pregnancy and the need for contraception; STIs; and overpower and intimidate the patient. To establish a
substance abuse, depression, and other emotional prob- comfortable and trusting relationship, the physician
lems, have moral, ethical, and legal implications. should strive to present the image of an ordinary person
Teenagers are often reluctant to confide in their parents who has special training and skills.
for fear of punishment or disapproval. Recognizing this Because individuals vary greatly in the onset and ter-
reality, health care providers have established many spe- mination of puberty, chronologic age may be a poor in-
cialized programs such as teenage family planning clin- dicator of physical, physiologic, and emotional develop-
ics, drop-in centers, STI clinics, hotlines, and adoles- ment. In communicating with an adolescent, the
cent clinics. For the physician, establishing a trusting physician must be sensitive to the patient’s develop-
and confidential relationship is basic to meeting an mental level, recognizing that outward appearance and
adolescent patient’s health care needs. A patient who chronologic age may not give an accurate assessment of
senses that the physician will inform the parents about cognitive development.
a confidential problem may lie or fail to disclose infor- Working with teenagers can be emotionally drain-
mation essential for proper diagnosis and treatment. ing. Adolescents have a unique ability to identify hid-
den emotional vulnerabilities. The physician who has a
personal need to control patients or foster dependency
may be disappointed in caring for teenagers. Because
teenagers are consumed with their own emotional
GUIDELINES FOR ADOLESCENT needs, they rarely provide the physician with the ego re-
PREVENTIVE SERVICES wards that younger or older patients do.
The physician should be sensitive to the issue of
countertransference, the emotional reaction elicited in
The American Medical Association guidelines for ado- the physician by the adolescent. How the physician re-
lescent preventive services (GAPS) and the National lates to the adolescent patient often depends on the
Center for Education in Maternal and Child Health physician’s personal characteristics. This is especially
Bright Futures cover health screening and guidance, im- true of physicians who treat families that are experienc-
munization, and health care delivery. The goals of these ing parent–adolescent conflicts. It is common for
guidelines are (1) to deter adolescents from participat- young physicians to overidentify with the teenage pa-
ing in behaviors that jeopardize health; (2) to detect tient and for older physicians to see the conflict from
physical, emotional, and behavioral problems early and the parents’ perspective.
intervene promptly; (3) to reinforce and encourage be- Overidentification with the parents is readily sensed
haviors that promote healthful living; and (4) to pro- by the teenager, who is likely to view the physician as
vide immunization against infectious diseases. The just another authority figure who cannot understand
guidelines recommend that adolescents between ages the problems of being a teenager. Assuming a parental-
11 and 21 years have annual routine health visits. authoritarian role may jeopardize the establishment of a
Health services should be developmentally appropriate working relationship with the patient. In the case of the
and culturally sensitive, and confidentiality between pa- young physician, overidentification with the teenager
tient and physician should be ensured. A complete may cause the parents to become defensive about their
schedule of the recommended guidelines is shown in parenting role and discount the physician’s experience
Figure 3–2A. and ability.
 Preventive Health Services by Age and Procedure
Adolescents and young adults have a unique set of health care needs. The recommendations for Guidelines for
Adolescent Preventive Services (GAPS) emphasize annual clinical preventive services visits that address both the
developmental and psychosocial aspects of health, in addition to traditional biomedical conditions. These
recommendations were developed by the American Medical Association with contributions from a Scientific Advisory
Panel, comprised of national experts, as well as representatives of primary care medical organizations and the health
insurance industry. The body of scientific evidence indicates that the periodicity and content of preventive services
can be important in promoting the health and well-being of adolescents.

Procedure Age of Adolescent

Early Middle Late
11 12 13 14 15 16 17 18 19 20 21
Health Guidance
Parenting*
Development
Diet and Physical Activity
Healthy Lifestyle**
Injury Prevention

Screening
History
Eating Disorders
Sexual Activity***
Alcohol and Other Drug Use
Tobacco Use
Abuse
School Performance
Depression
Risk for Suicide
Physical Assessment
Blood Pressure
BMI
Comprehensive Exam
Tests
Cholesterol 1 1 1
TB 2 2 2
GC, Chlamydia, Syphilis, & HPV 3 3 3
HIV 4 4 4
Pap Smear 5 5 5

Immunizations
MMR
Td
HepB 6 6
Hep A 7 7 7
Varicella 8 8 8

1. Screening test performed once if family history is positive for 7. Vaccinate if at risk for hepatitis A infection.
early cardiovascular disease or hyperlipidemia. 8. Offer vaccine if no reliable history of chickenpox or
2. Screen if positive for exposure to active TB or lives/works in previous immunization.
high-risk situation, eg homeless shelter, jail, health care facility. * A parent health guidance visit is recommended during
3. Screen at least annually if sexually active. early and middle adolescence.
4. Screen if high risk for infection. ** Includes counseling regarding sexual behavior and
5. Screen annually if sexually active or if 18 years or older. avoidance of tobacco, alcohol, and other drug use.
6. Vaccinate any adolescent not previously vaccinated. *** Includes history of unintended pregnancy and STD.
Do not give if administered in last five years.

Figure 3–2. A: Guidelines for preventive health services. (Reproduced, with permission, from AMA Guidelines for Ado-
lescent Preventive Services: Recommendations and Rationale. American Medical Association, 1995.)
105
 TEEN HEALTH HISTORY

This information is strictly confidential. Its purpose is to help your caregiver give you better
care. We request that you fill out the form completely, but you may skip any question that you
do not wish to answer.

NAME DATE
FIRST MIDDLE INITIAL LAST

BIRTHDATE AGE GRADE Name that you like to be called

1. Why did you come to the clinic today?

STRICTLY CONFIDENTIAL
Medical History
2. Are you allergic to any medicines? ........................... YES NO
Name of medicines
3. Are you taking any medicines now? . . . . . . . . . . . . . . . . . . . . . . . . . . . YES NO
Name of medicines
4. Do you have any long-term health conditions? . . . . . . . . . . . . . . . . . . . . . YES NO
Conditions
5. Date or age at your last tetanus (or dT) shot

School Information
6. What grade do you usually make in English?
(Example: A, B, C, D, E, F)
7. What grade do you usually make in Math?
8. How many days were you absent from school last semester?
9. How many days were you absent last semester because of illness?
10. How do you get along at school?

1 2 3 4 5 6 7
TERRIBLE GREAT

11. Have you ever been suspended? ............................. YES NO

12. Have you ever dropped out of school? .......................... YES NO
13. Do you plan to graduate from high school? ...................... YES NO
Job/Career Information
14. Are you working? ...................................... YES NO
If YES, What is your job?
How many hours do you work per week?
15. What are your future plans or career goals?

Family Information
16. Who do you live with? (Check all that apply.)
Both natural parents Stepmother Brother(s)-ages:
Mother Stepfather Sister(s)-ages:
Father Guardian Other:Explain
Adoptive parents Alone
17. Have there been any changes in your family? Check all that apply.
a. Marriage d. Serious illness g. Births
b. Separation e. Loss of job h. Deaths
c. Divorce f. Move to new home i. Other
18. Father's/stepfather's occupation or job:
Mother's/stepmother's occupation or job:

Figure 3–2. B: Adolescent medical history questionnaire.

106
 STRICTLY CONFIDENTIAL
19. How do you get along at home?
1 2 3 4 5 6 7
TERRIBLE GREAT
20. Have you ever run away from home? ........................... YES NO
21. Have you ever lived in foster care or an institution? . . . . . . . . . . . . . . . . . YES NO
Self Information
22. On the whole, how do you like yourself?
1 2 3 4 5 6 7
NOT VERY MUCH A LOT
23. What do you do best?
24. If you could, what would you like to change about yourself?

25. List any habits you would like to break.

26. Do you feel people expect too much from you? . . . . . . . . . . . . . . . . . . . . . YES NO
27. How do you get along with your friends/peers?
1 2 3 4 5 6 7
TERRIBLE GREAT

28. Do you feel you have friends you can count on? .................... YES NO
29. Have you ever felt really sad or depressed for more than 3 days in a row? . . YES NO
30. Have you ever thought of suicide as a solution to your problems? . . . . . . . . . YES NO
31. Have you gotten into any trouble because of your anger/temper? . . . . . . . . . YES NO
Health Concern
32. On a scale of 1–7, how would you rate your general health?
1 2 3 4 5 6 7
TERRIBLE GREAT

33. Do you have any questions or concerns about any of the following? (Check those that apply.)
Height/weight Skin rash Family violence/physical
Blood pressure abuse
Arms, legs/muscle or
Head/headaches joint pain Feeling down or depressed
Dizziness/passing out Dating
Frequent or painful
Eyes/vision urination Sex
Ears/hearing/earaches Wetting the bed Worried about VD/STD
Nose/frequent colds Sexual organs/genitals Masturbation
Mouth/teeth Trouble sleeping Sexual abuse/rape
Neck/back Tiredness Having children/parenting/
adoption
Chest/breathing/coughing Diet food/appetite
Cancer/or dying
Breasts Eating disorder
Other (explain)
Heart Smoking/drugs/alcohol
Stomach/pain/vomiting Future plans/jobs
Diarrhea/constipation Worried about parents

Health Behavior Information

34. Have you lost or gained any weight in the last year? . . . . . . . . . . . . . . . . . . . YES NO
Gained ( ) How much?
Lost ( ) How much?
35. In the past year, have you tried to lose weight or control your weight by vomiting,
taking diet pills or laxatives, or starving yourself? . . . . . . . . . . . . . . . . . . . . . . YES NO
36. Do you ever drive after drinking or when high? . . . . . . . . . . . . . . . . . . . . . . . . YES NO
37. Do you ever smoke cigarettes or use snuff or chewing tobacco? . . . . . . . . . . YES NO
38. Do you ever smoke marijuana? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . YES NO
39. Do you ever drink alcoholic beverages? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . YES NO
40. Do you ever use street drugs (speed, cocaine, acid, crack, etc.)? . . . . . . . . . YES NO
41. Does anyone in your household smoke? . . . . . . . . . . . . . . . . . . . . . . . . . . . . YES NO
42. Does anyone in your family have a problem with drugs or alcohol? . . . . . . . . YES NO

Figure 3–2. Continued

107
 STRICTLY CONFIDENTIAL

43. Have you ever been in trouble with the police or the law? . . . . . . . . . . . . . . . YES NO
44. Have you begun dating? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . YES NO
45. Do you currently have a boyfriend or girlfriend? . . . . . . . . . . . . . . . . . . . . . . . YES NO
If YES, how old is he/she?
46. Do you think you might be gay/lesbian/homosexual? . . . . . . . . . . . . . . . . . . . . . YES NO
47. Have you ever had sex (sexual intercourse)? . . . . . . . . . . . . . . . . . . . . . . . . . YES NO
48. Are you interested in receiving information on preventing pregnancy? . . . . . . YES NO
49. If you have had sex, are you (or your partner) using any kind of birth control? YES NO
50. If you have had sex, have you ever been treated for gonorrhea or chlamydia
or any other sexually transmitted disease? . . . . . . . . . . . . . . . . . . . . . . . . . . YES NO

For males only

51. Have you been taught how to use a condom correctly? . . . . . . . . . . . . . . . . . YES NO
52. If you have had sex, do you use a condom every time or almost every time? YES NO
53. Have you ever fathered a child? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . YES NO
For females only
54. How old were you when your periods began? . . . . . . . . . . . . . . . . . . . . . . .
55. What date did your last period start? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
56. Are your periods regular (once a month)?. . . . . . . . . .. . . . . . . . . . . . . . . . . YES NO
57. Do you have painful or excessively heavy periods? . . . . . . . . . . . . . . . . . . . . . . . . YES NO
58. Have you ever had a vaginal infection or been treated for a female disorder? YES NO
59. Do you think you might be pregnant? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . YES NO
60. Have you ever been pregnant? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . YES NO
Everyone
61. Do you have any other problems you would like to discuss with the caregiver? YES NO
Past Medical History
62. Were you born prematurely or did you have any serious problems as an infant? YES NO
63. Are you allergic to any medicines? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . YES NO
If YES, what?

64. List any medications that you are taking and the problems for which the
medication was given:
MEDICATION REASON HOW LONG

65. Have you ever been hospitalized? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . YES NO

If YES, describe your problem and your age at the time.
AGE PROBLEM

66. Have you had any injuries? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . YES NO

If YES, describe the injury and your age when it occurred.
AGE KIND OF INJURY

67. Have you had any serious illnesses? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . YES NO

If YES, state the kind of illness and your age when it started.
AGE ILLNESS

Figure 3–2. Continued

108
 STRICTLY CONFIDENTIAL
Family History
Have any members of your family, alive or dead (parents, grandparents, uncles, aunts, brothers
or sisters), had any of the following problems? If YES, please state the age of the person when
the condition occurred and the person's relationship to you.

PROBLEM YES NO DON'T KNOW AGE RELATIONSHIP

A. Seizure disorder
Epilepsy

B. Mental retardation
Birth defects

C. Migraine headaches

D. High blood pressure

High cholesterol

E. Heart attack or stroke at less

than age 60

F. Lung disease
Tuberculosis

G. Liver or intestinal disease

H. Kidney disease

I. Allergies
Asthma
Eczema

J. Arthritis

K. Diabetes

L. Endocrine problems
Other glandular problems

M. Obesity
Eating disorder

N. Cancer

O. Blood disorders
Sickle cell anemia

P. Emotional problems
Suicide

Q. Alcoholism
Drug problems

Figure 3–2. Continued

109
110 / CHAPTER 3

THE SETTING and parent together to obtain the history. In the case of
angry adolescents, brought in against their will, it is
Adolescents respond positively to a setting and to ser- useful to meet with the parents and patient just long
vices that communicate a sensitivity to their age. A pe- enough to have the parents describe the conflict and
diatrician’s waiting room with toddlers’ toys and exami- voice their concerns. This meeting should last no longer
nation tables too short for a young adult make than 3–5 minutes, and the adolescent should then be
adolescent patients feel they have outgrown the prac- seen alone. This approach conveys that the physician is
tice. Similarly, a waiting room filled with geriatric or primarily interested in the adolescent patient, yet gives
pregnant patients can make a teenager feel out of place. the physician an opportunity to acknowledge the par-
It is not uncommon to see a teenage patient who has ents’ concerns.
been brought to the office against his or her wishes, es-
pecially for evaluations of drug and alcohol use, par-
ent–child conflict, school failure, depression, or a sus- The Interview
pected eating disorder. Even in cases of acute physical The first few minutes may dictate the success of the
illness, the adolescent may feel anxiety about having a visit, whether or not a trusting relationship can be es-
physical examination. If future visits are to be success- tablished. A few minutes just getting to know the pa-
ful, the physician must spend time on the first visit to tient is time well spent. For example, immediately ask-
foster a sense of trust and an opportunity to feel com- ing, “Do you smoke marijuana?” when a teenager is
fortable. brought in for suspected marijuana use confirms the
adolescent’s negative preconceptions about the physi-
cian and the purpose of the visit.
CONFIDENTIALITY It is preferable to spend a few minutes asking non-
It is helpful at the beginning of the visit to talk with the threatening questions. “Tell me a little bit about your-
adolescent and the parents about what to expect. The self so I can get to know you.” “What do you like to do
physician should address the issue of confidentiality, most?” “Least?” “What are your friends like?” Neutral
telling the parents that two meetings, one with the questions help defuse some of the patient’s anger and
teenager alone and one with only the parents, will take anxiety. Toward the end of the interview, the physician
place. Adequate time must be spent with both the pa- can ask more directed questions about psychosocial
tient and the parents, or important information may be concerns.
missed. At the beginning of the interview with the pa- Medical history questionnaires for the patient and
tient, it is useful to say, “I am likely to ask you some the parents are useful in collecting historical data (Fig-
personal questions. This is not because I am trying to ure 3–2B).
pry into your personal affairs but because these ques- The history should include an assessment of
tions may be important to your health. I want to assure progress with psychodevelopmental tasks and of behav-
you that what we talk about is confidential, just be- iors potentially detrimental to health. The review of
tween the two of us. If there is something I feel we systems should include questions about the following:
should discuss with your parents, I will ask your per- 1. Nutrition: Number and balance of meals; cal-
mission first unless I feel it is life-threatening.” cium, iron, cholesterol intake, body image.
2. Sleep: Number of hours, problems with insomnia
THE STRUCTURE OF THE VISIT or frequent waking.
Caring for adolescents is a time-intensive process. In 3. Seat belt or helmet: Regularity of use.
many adolescent practices, a 40–50% no-show rate is 4. Self-care: Knowledge of testicular or breast self-
not unusual. The stated chief complaint may conceal examination, dental hygiene, and exercise.
the patient’s real concern. For example, a 15-year-old 5. Family relationships: Parents, siblings, relatives.
girl may say she has a sore throat but actually may be 6. Peers: Best friend, involvement in group activities,
worried about being pregnant. gangs, boyfriends, girlfriends.
By age 11 or 12 years, patients should be seen alone. 7. School: Attendance, grades, activities.
This gives them an opportunity to ask questions they
may be embarrassed to ask in front of a parent. Because 8. Educational and vocational interests: College, ca-
of the physical changes that take place in early puberty, reer, short-term and long-term vocational plans.
some adolescents are too self-conscious to undress in 9. Tobacco: Use of cigarettes, snuff, chewing to-
front of a parent. If an adolescent comes in willingly, ei- bacco.
ther for an acute illness or for a routine physical exami- 10. Substance abuse: Frequency, extent, and history
nation, it may be helpful to meet with the adolescent of alcohol and drug use.
 ADOLESCENCE / 111

11. Sexuality: Sexual activity, contraceptive use, preg- for a couple of reasons. First, I want to make sure that
nancies, history of sexually transmitted disease, there aren’t any physical problems, and second, it helps
number of sexual partners, risk for HIV infection. me determine if your development is proceeding nor-
12. Emotional health: Signs of depression and exces- mally.” This also introduces the subject of sexual devel-
sive stress. opment for discussion.
A pictorial chart of sexual development is useful in
The physician’s personal attention and interest is showing the patient how development is proceeding
likely to be a new experience for the teenager, who has and what changes to expect. Figure 3–3 shows the rela-
probably received medical care only through a parent. tionship between height, penis and testes development,
The teenager should leave the visit with a sense of hav- and pubic hair growth in the male, and Figure
ing a personal physician. 3–4 shows the relationship between height, breast de-
velopment, menstruation, and pubic hair growth in the
female. Many teenagers do not openly admit that they
Physical Examination are interested in this subject, but they are usually atten-
During early adolescence, many teenagers may be shy tive when it is raised. This discussion is particularly use-
and modest, especially with a physician of the opposite ful in counseling teenagers who lag behind their peers
sex. The examiner should address this concern directly, in physical development.
because it can be allayed by acknowledging the uneasi- Because teenagers are sensitive about their changing
ness verbally and by explaining the purpose of the ex- bodies, it is useful to comment during the examination:
amination, for example, “Many boys that I see who are “Your heart sounds fine. I feel a small lump under your
your age are embarrassed to have their penis and testes right breast. This is very common during puberty in
examined. This is an important part of the examination boys. It is called gynecomastia and should disappear in

BOYS
APEX STRENGTH SPURT
Height Spurt 10–12 in (25-30 cm)
HEIGHT SPURT PEAK Weight 44 lb (20 kg)
Height 4 in/y
Weight 20 lb/y

GROWTH RATE AGE RANGE

Height 2 in/y 13–17.5 y
Weight 6.5 lb/y

PENIS
TESTES
Testes increase in size Penis grows in Penis grows in Development is
and skin of scrotum length. width. complete.
reddens. AGE RANGE
AGE RANGE 14.5–18 years
10–13.5 years

SEXUAL MATURITY 2 3 4 5
RATING
PUBIC HAIR

Straight hair Hair becomes Hair is full, Full development.

appears at curly, coarse, limited in area.
penis base. and dark.
AGE RANGE AGE RANGE
10–15 years 14.5–18 years

AGE 11 years 12 years 13 years 14 years 15 years 16 years 17 years

Figure 3–3. Adolescent male sexual maturation and growth. (Adapted and reproduced, with permission, from Tan-
ner JM: Growth at Adolescence. Blackwell Scientific, 1962.)
112 / CHAPTER 3

GIRLS
HEIGHT SPURT
PEAK
Height 3 in/y
Weight 17.5 lb/y
GROWTH RATE AGE RANGE
Height 2 in/y 11.5–16.5 y
Weight 6 lb/y
MENARCHE Age Range 10–16.5 y
Average Height 62.5 in (158.5 cm)
Average Weight 106 lb (48 kg)

BREAST

Breast buds Breast and Nipple and Areola rejoins

begin. areola grow. areola form breast contour
AGE RANGE separate and development
8–13 years mound, pro- is complete.
truding from AGE RANGE
breast. 12.5–18.5 years

SEXUAL MATURITY 2 3 4 5
RATING
PUBIC HAIR

Initial hair is Pubic hair Hair looks like Inverted triangular

straight and fine. coarsens, adults but limited pattern is established
AGE RANGE darkens and in area. AGE RANGE
8–14 years spreads. 12.5–16.5 years
AGE 11 years 12 years 13 years 14 years 15 years

Figure 3–4. Adolescent female sexual maturation and growth. (Adapted and reproduced, with permission, from Tan-
ner JM: Growth at Adolescence. Blackwell Scientific, 1962.)

6 months to a year. Don’t worry, you are not turning 4. Suspicion of anatomic abnormalities, such as im-
into a girl.” perforate hymen.
If a teenage girl has not been sexually active and has 5. Pelvic pain.
no gynecologic complaints or abnormalities, a pelvic 6. Patient request for an examination.
examination is usually not necessary until about age
18 years. The following are indications for a pelvic ex-
amination in a younger teenage girl: Green M (ed): Bright Futures: Guidelines for Health Supervision of
Infants, Children, and Adolescents. National Center for Educa-
tion in Maternal and Child Health, 1994.
1. A history of sexual intercourse. (The pelvic exami- Metzl JD: Preparticipation examination of the adolescent athlete:
nation should be done for purposes of contracep- Part 1. Pediatr Rev 2001;22:199 [PMID: 11389307].
tive counseling and to rule out sexually transmit- Metzl JD: Preparticipation examination of the adolescent athlete:
ted disease.) Part 2. Pediatr Rev 2001;22:227 [PMID: 11435624].
Sigman G et al: Confidential health care for adolescents: Position
2. Abnormal vaginal discharge. paper of the Society for Adolescent Medicine. J Adolesc
3. Menstrual irregularities. Health 1997;21:408 [PMID: 9401860].
 ADOLESCENCE / 113

1.2 cm for girls. Pubertal growth usually takes

GROWTH & DEVELOPMENT 2–4 years and continues longer in boys than in girls. By
age 11 years in girls and age 12 years in boys, 83–89%
of ultimate height has been attained. An additional
PUBERTY 18–23 cm in females and 25–30 cm in males will be
achieved during further pubertal growth. Following
Pubertal growth and physical development are a result menarche, growth is rarely more than 5–7.5 cm.
of activation of the hypothalamic–pituitary–gonadal In boys, the quantity of body fat increases before
axis in late childhood. Before the onset of puberty, pi- onset of the height spurt. They then lose fat until the
tuitary and gonadal hormone levels are low. With the growth spurt has finished and gradually again increase
onset of puberty, the inhibition of gonadotropin-releas- in fat. Muscle mass doubles between ages 10 and
ing hormone (GnRH) in the hypothalamus is removed, 17 years. Girls, by contrast, gradually store fat from
allowing pulsatile production and release of the go- about age 6 years and do not decrease the quantity of
nadotropins: luteinizing hormone (LH) and follicle- fat, although its location changes, with an increase of
stimulating hormone (FSH). In early to middle adoles- subcutaneous fat in the region of the pelvis, breasts, and
cence, pulse frequency and amplitude of LH and FSH upper back.
secretion increase, which stimulates the gonads to pro-
duce sex steroids (estrogen or testosterone). In the fe-
male, FSH stimulates ovarian maturation, granulosa SEXUAL MATURATION
cell function, and estradiol secretion. LH is important Sexual maturity rating (SMR) is useful clinically for
in ovulation and is involved also in corpus luteum for- categorizing genital development. SMR staging in-
mation and progesterone secretion. Initially, estradiol cludes age ranges of normal development and specific
has an inhibitory effect on the release of LH and FSH. descriptions for each stage of pubic hair growth, penis
Eventually, estradiol becomes stimulatory, and the se- and testis development in boys, and breast maturation
cretions of LH and FSH become cyclic. Estradiol levels in girls. Figures 3–3 and 3–4 graphically represent this
progressively increase, resulting in maturation of the fe- chronologic development with reference to each sexual
male genital tract and breast development. maturity stage. SMR 1 is prepuberty; SMR 5, adult ma-
In the male, LH stimulates the interstitial cells of the turity. In SMR 2 is the pubic hair is sparse, fine, non-
testes, which produce testosterone. FSH stimulates the pigmented, and downy; in SMR 3, the hair becomes
production of spermatocytes in the presence of testos- pigmented and curly and increases in amount; and in
terone. The testes also produce inhibin, a Sertoli cell pro- SMR 4, the hair is adult in texture but limited in area.
tein that also inhibits the secretion of FSH. During pu- The appearance of pubic hair precedes that of axillary
berty, circulating testosterone levels increase more than hair by more than 1 year. Male genital development be-
20-fold. Levels of testosterone correlate with the physical gins with SMR 2, in which the testes become larger and
stages of puberty and the degree of skeletal maturation. the scrotal skin reddens and coarsens. In SMR 3, the
penis lengthens; and in SMR 4, the penis enlarges in
overall size and the scrotal skin becomes pigmented.
PHYSICAL GROWTH Female breast development follows a predictable se-
During adolescence, a teenager’s weight almost dou- quence. Small, raised breast buds appear in SMR 2. In
bles, and height increases by 15–20%. During puberty, SMR 3, the breast and areolar tissue generally enlarge and
major organs double in size, with the exception of lym- become elevated. The areola and papilla (nipple) form a
phoid tissue, which decreases in mass. Before puberty, separate mound from the breast in SMR 4, and in SMR
there is little difference in the muscular strength of boys 5 the areola assumes the same contour as the breast.
and girls. The body’s musculature increases both in size Great variability exists in the timing and onset of
and in strength during puberty, with maximal strength puberty and growth, and psychosocial development
lagging behind the increase in size by many months. does not necessarily parallel physical changes. Because
Boys attain greater strength and mass, and strength of this variability, chronologic age may be a poor indi-
continues to increase into late puberty. Although motor cation of physiologic and psychosocial development.
coordination lags behind growth in stature and muscu- Skeletal maturation correlates well with growth and pu-
lature, it continues to improve as strength increases. bertal development.
The pubertal growth spurt begins nearly 2 years ear- Teenagers have been entering puberty at increas-
lier in girls than in boys. Girls reach their peak height ingly earlier ages during the last century because of bet-
velocity (PHV) between ages 111⁄2 and 12 years; boys, ter nutrition and improved socioeconomic conditions.
between ages 131⁄2 and 14 years. Linear growth at peak In the United States, the average age at menarche is
velocity is 9.5 cm/y ± 1.5 cm for boys and 8.3 cm/y ± 12.16 years in African American girls and 12.88 in
114 / CHAPTER 3

white girls. Among girls reaching menarche, the average Molgaard C et al: Influence of weight, age and puberty on bone
weight is 48 kg, and the average height is 158.5 cm. size and bone mineral content in healthy children and adoles-
cents. Acta Paediatr 1998;87:494 [PMID: 9641728].
However, menarche may be delayed until age 16 years
or may begin as early as age 10. Although the first mea- Tanner JM, Davies PW: Clinical longitudinal standards for height
and height velocity for North American children. J Pediatr
surable sign of puberty in girls is the beginning of the 1985;107:317 [PMID: 3875704].
height spurt, the first conspicuous sign usually is devel-
opment of breast buds between ages 8 and 11 years. Al-
though breast development usually precedes the growth PSYCHOSOCIAL DEVELOPMENT
of pubic hair, in some girls the sequence may be re- Adolescents are struggling to find out who they are,
versed. A common concern for girls at this time is what they want to do in the future, and, in relation to
whether the breasts will be of the right size and shape, that goal, what their personal strengths and weaknesses
especially because it is not unusual for one breast to are. These questions arise primarily because teenagers
grow faster than the other. Among girls, the growth are in the process of establishing their own identity.
spurt starts at about age 9 years and reaches a peak at Adolescence is a period of progressive individuation
age 111⁄2, usually at SMR 3–4 breast development and and separation from the family. Because of the rapid
stage 3 pubic hair development. The spurt usually ends physical, emotional, cognitive, and social growth occur-
by age 14 years. Girls who mature early will reach their ring during adolescence, it is useful to divide the period
PHV sooner and attain their final height earlier. Girls into three sequential phases of development. Early ado-
who mature late will attain a greater ultimate height be- lescence occurs roughly between ages 10 and 13 years;
cause of the longer period of growth before the growth middle adolescence, between ages 14 and 16 years; and
spurt. Final height is related to skeletal age at onset of late adolescence, at age 17 years and later.
puberty as well as genetic factors. The height spurt cor-
relates more closely with breast developmental stages
than with pubic hair stages. Early Adolescence
The first sign of puberty in the male, usually between Early adolescence (ages 10–13 years) is characterized by
ages 10 and 12 years, is scrotal and testicular growth. rapid growth and development of secondary sex charac-
Pubic hair usually appears early in puberty but may do so teristics. Because of the rapid physical changes during
any time between ages 10 and 15 years. The penis begins this period, body image, self-concept, and self-esteem
to grow significantly a year or so after the onset of testicu- fluctuate dramatically. Concerns about how personal
lar and pubic hair development, usually between ages growth and development deviate from that of peers
10 and 131⁄2. The first ejaculation usually occurs about may be a great worry, especially short stature in boys
1 year after initiation of testicular growth, but its timing is and delayed breast development or delayed menarche
highly variable. About 90% of boys have this experience in girls. Although there is a certain curiosity about sexu-
between ages 11 and 15 years. Gynecomastia, a hard nod- ality, young adolescents tend to feel more comfortable
ule under the nipple, occurs in a majority of boys, with a with members of the same sex. Peer relationships be-
peak incidence between ages 14 and 15 years. Gyneco- come increasingly important. Young teenagers still
mastia usually disappears within 6 months to 2 years. The think concretely and cannot easily conceptualize about
height spurt begins at age 11 years but increases rapidly the future. They may have vague and unrealistic profes-
between ages 12 and 13, with the PHV reached at age sional goals, such as becoming a movie star or a lead
131⁄2 years. The period of pubertal development lasts singer in a rock group.
much longer in boys and may not be completed until age
18 years. The height velocity is higher in males
(8–11 cm/y) than in females (6.5–9.5 cm/y). The devel-
Middle Adolescence
opment of axillary hair, deepening of the voice, and the During middle adolescence (ages 14–16 years), as the
development of chest hair in boys usually occur in mid- rapid pubertal growth rate subsides, teenagers become
puberty, about 2 years after onset of growth of pubic hair. more comfortable with their new bodies. Intense emo-
Facial and body hair begin to increase at age 16–17 years. tions and wide swings in mood are typical. Although
some teenagers go through this experience relatively
peacefully, others struggle desperately. Cognitively,
Herman-Giddens ME et al: Secondary sexual characteristics and teenagers move from concrete thinking to formal oper-
menses in young girls seen in office practice: A study from the
Pediatric Research in Office Settings Network. Pediatrics
ations and develop the ability to think abstractly. With
1997;99:505 [PMID: 9093289]. this new mental power comes a sense of omnipotence
Kaplowitz PB et al: Earlier onset of puberty in girls: Relation to in- and a belief that the world can be changed by merely
creased body mass index and race. Pediatrics thinking about it. Sexually active teenagers may believe
2001;108:347 [PMID: 11483799]. they do not need to worry about using contraception
 ADOLESCENCE / 115

because they can’t get pregnant, “it won’t happen to The development of homosexual identity in adoles-
me.” Sixteen-year-old drivers believe they are the best cence commonly progresses through two stages. The
drivers in the world and think the insurance industry is adolescent feels different, develops a crush on a person
conspiring against them by charging such high rates for of the same sex without clear self-awareness of a gay
automobile insurance. With the onset of the ability to identity, and then goes through a coming-out phase in
think abstractly, teenagers begin to see themselves as which the homosexual identity is defined for the indi-
others see them and may become extremely self-cen- vidual and revealed to others. The coming-out phase
tered. Because they are establishing their own identities, may be a very difficult period for the young person and
relationships with other people, including peers, are the family. The young adolescent is afraid of society’s
primarily narcissistic, and experimenting with different bias and seeks to reject homosexual feelings. This strug-
images is quite common. Peers determine the standards gle with identity may include episodes of both homo-
for identification, behavior, activities, and fashion and sexual and heterosexual promiscuity, STIs, depression,
provide emotional support, intimacy, empathy, and the substance abuse, attempted suicide, school avoidance
sharing of guilt and anxiety during the struggle for au- and failure, running away from home, and other crises.
tonomy. The struggle for independence and autonomy In a clinical setting, the issue of homosexual identity
is often a difficult and stressful period for both the most often surfaces as a result of a teenager being seen
teenager and the parents. for an STI, family conflict, school problem, attempted
As sexuality increases in importance during this suicide, or substance abuse rather than as a result of a
time, adolescents may begin dating and experimenting consultation about sexual orientation. Pediatricians
with sex. Relationships usually tend to be one-sided should be aware of the psychosocial and medical impli-
and narcissistic. cations of homosexual identity and be sensitive to the
possibility of these problems in gay adolescents. Suc-
cessful management depends on the physician’s ability
Late Adolescence to gain the trust of the gay adolescent and on the physi-
cian’s knowledge of the wide range of medical and psy-
During late adolescence (age 17 years and older), the
chological problems for which gay adolescents may be
young person generally becomes less self-centered and
at risk. Pediatricians must be nonjudgmental in posing
begins caring more about others. Social relationships
sexual questions if they are to be effective in encourag-
shift from the peer group to the individual. Dating be-
ing the teenager to share concerns. Physicians who for
comes much more intimate. By age 18 years, nearly half
religious or other personal reasons cannot be objective
of American girls and two-thirds of boys have had sex-
must refer the homosexual patient to another profes-
ual intercourse. The older adolescent becomes more in-
sional for treatment and counseling.
dependent from the family. The ability to think ab-
stractly allows older adolescents to think more
realistically in terms of future plans, actions, and ca- American Academy of Pediatrics Committee on Adolescence: Ho-
mosexuality and adolescence. Pediatrics 1993;92:631
reers. Older adolescents have rigid concepts of what is [PMID: 8414844].
right or wrong. This is a period of idealism. Friedman RC, Downey JI: Homosexuality. N Engl J Med
1994;331:923 [PMID: 8078554].
Garofalo R et al: Sexual orientation and risk of suicide attempts
Sexual Orientation among a representative sample of youth. Arch Pediatr Adolesc
Med 1999;153:487 [PMID: 10323629].
Sexual orientation develops during early childhood.
One’s gender identity is established by age 2 years, and Ghai K, Rosenfeld RL: Disorders of pubertal development: Too
early, too much, too late, or too little. Adolesc Med
a sense of masculinity or femininity usually solidifies by 1994;5:19 [PMID: 10358258].
age 5 or 6 years. Homosexual adults describe homosex- Russell ST, Joyner K: Adolescent sexual orientation and suicide
ual feelings during late childhood and early adoles- risk: Evidence from a national study. Am J Public Health
cence, years before engaging in overt homosexual acts. 2001;91:1276 [PMID: 11499118].
Although only 5–10% of American young people
acknowledge having had homosexual experiences and
only 5% feel that they are or could be gay, homosexual
experimentation is common, especially during early and BEHAVIOR & PSYCHOLOGICAL
middle adolescence. Experimentation may include mu- HEALTH
tual masturbation and fondling the genitals and does
not by itself cause or lead to adult homosexuality. The-
ories about the causes of homosexuality include genetic, It is not unusual for adolescents to seek medical atten-
hormonal, environmental, and psychological models. tion for seemingly minor complaints. During early ado-
116 / CHAPTER 3

lescence, teenagers may worry about normal develop- may vary with the sophistication and cognitive level of
mental changes such as gynecomastia. They may pre- the patient.
sent with vague symptoms, whereas the hidden agenda
may be concerns about pregnancy or an STI. Adoles-
cents with emotional disorders often present with so-
Differential Diagnosis
matic symptoms, for example, abdominal pain, The history and physical findings are usually inconsis-
headaches, dizziness or syncope, fatigue, sleep problems, tent with anatomic and physiologic concepts. Conver-
and chest pain, that appear to have no biologic cause. sion symptoms are exhibited most frequently at times
The emotional basis of such complaints may be varied: of stress and in the presence of individuals meaningful
somatoform disorder, depression, or stress and anxiety. to the patient. The patient often exhibits a characteris-
tic personality pattern, including egocentricity, emo-
tional lability, and dramatic and attention-seeking be-
PSYCHOPHYSIOLOGIC SYMPTOMS haviors.
& CONVERSION REACTIONS Conversion reactions must be differentiated from
hypochondriasis, which is a preoccupation with devel-
The most common somatoform disorders during ado- oping or having a serious illness despite medical reas-
lescence are conversion disorders or conversion reac- surance that there is no evidence of disease. Over time,
tions. (A conversion reaction is a psychophysiologic the fear of one disease may give way to concern about
process in which unpleasant feelings, especially anxiety, another. In contrast to patients with conversion symp-
depression, and guilt, are communicated through a toms, who seem relieved if an organic cause is consid-
physical symptom.) Psychophysiologic symptoms result ered, patients with hypochondriasis become more anx-
when anxiety activates the autonomic nervous system, ious when such a cause is considered.
resulting in tachycardia, hyperventilation, and vasocon- Malingering is uncommon during adolescence. The
striction. The emotional feeling may be threatening or malingering patient consciously and intentionally pro-
unacceptable to the individual, who expresses it as a duces false or exaggerated physical or psychological
physical symptom rather than verbally. This process is symptoms. Such patients are motivated by external in-
unconscious, and the anxiety or unpleasant feeling is centives such as avoiding work, evading criminal prose-
dissipated by the somatic symptom. The degree to cution, obtaining drugs, or obtaining financial compen-
which the conversion symptom lessens anxiety, depres- sation. These patients may be hostile and aloof. Parents
sion, or the unpleasant feeling is referred to as primary of patients with conversion disorders and malingering
gain. Conversion symptoms not only diminish unpleas- have a similar reaction to illness. They have an uncon-
ant feelings but also release the adolescent from conflict scious psychological need to have sick children and re-
or an uncomfortable situation. This is referred to as sec- inforce their child’s behavior.
ondary gain. Secondary gain may intensify the symp- Somatic delusions are physical symptoms, often
toms, especially with increased attention from con- bizarre, that accompany other signs of mental illness.
cerned parents and friends. Adolescents with Examples are visual or auditory hallucinations, delu-
conversion symptoms tend to have overprotective par- sions, incoherence or loosening of associations, rapid
ents and become increasingly dependent on their par- shifts of affect, and confusion.
ents as the symptom becomes the major focus concern
in the family.
Treatment
The physician must emphasize from the onset that both
Clinical Findings physical and emotional causes of the symptom need to
The symptom may appear at times of stress. Nervous, be considered. The relationship between physical causes
gastrointestinal, and cardiovascular symptoms are com- of emotional pain and emotional causes of physical
mon and include paresthesias, anesthesia, paralysis, pain should be described to the family, using examples
dizziness, syncope, hyperventilation, abdominal pain, such as stress causing an ulcer or making a severe
nausea, and vomiting. Specific symptoms may reflect headache worse. The patient should be encouraged to
existing or previous illness (eg, pseudoseizures in ado- understand that the symptom may persist and that at
lescents with epilepsy) or modeling of a close relative’s least a short-term goal is to continue normal daily activ-
symptom (eg, chest pain in a boy whose grandfather ities. Medication is rarely helpful. If the family will ac-
died of a heart attack). cept it, psychological referral is often the best initial
Conversion symptoms are more common in girls step toward psychotherapy. If the family resists psychi-
than boys. They occur in patients from all socioeco- atric or psychological referral, the pediatrician may
nomic levels; however, the complexity of the symptom need to begin to deal with some of the emotional fac-
 ADOLESCENCE / 117

tors responsible for the symptom while building rap- discouragement, irritability, a sense of emptiness and
port with the patient and family. Regular appointments meaninglessness, negative expectations of oneself and
should be scheduled. During the sessions, the teenager the environment, low self-esteem, isolation, a feeling of
should be seen first and encouraged to talk about helplessness, diminished interest or pleasure in activi-
school, friends, the relationship with the parents, and ties, weight loss or weight gain, insomnia or hypersom-
the stresses of life. Discussion of the symptom itself nia, fatigue or loss of energy, feelings of worthlessness,
should be minimized; however, the physician should be and diminished ability to think or concentrate. How-
supportive and must never suggest that the pain is not ever, it is not unusual for a serious depression to be
real. As the parents gain further insight into the cause masked because the teenager cannot tolerate the severe
of the symptom, they will become less indulgent of the feelings of sadness. Such a teenager may present with
complaints, facilitating the resumption of normal activ- recurrent or persistent psychosomatic complaints, such
ities. If management is successful, the adolescent will as abdominal pain, chest pain, headache, lethargy,
increase coping skills and become more independent, weight loss, dizziness and syncope, or other nonspecific
while decreasing secondary gain. symptoms. Other behavioral manifestations of masked
If the symptom continues to interfere with daily ac- depression include truancy, running away from home,
tivities and if the patient and parents feel that no defiance of authorities, self-destructive behavior, van-
progress is being made, psychological referral is indi- dalism, drug and alcohol abuse, sexual acting out, and
cated. A psychotherapist experienced in treating adoles- delinquency.
cents with conversion reactions is in the best position to
establish a strong therapeutic relationship with the pa-
tient and family. After referral is made, the pediatrician
Differential Diagnosis
should continue to follow the patient to ensure compli- A complete history and physical examination, including
ance with psychotherapy. a careful review of the patient’s medical and psychoso-
cial history, should be performed. The family history
American Psychiatric Association: Diagnostic and Statistical Manual should be explored for psychiatric problems.
of Mental Disorders, 4th ed. American Psychiatric Press, 1994. The teenager should be questioned about the previ-
Gold MA, Friedman SB: Conversion reactions in adolescents. Pedi- ously listed symptoms of depression, and specifically
atr Ann 1995;24:296 [PMID: 7659461]. about suicidal ideation or preoccupation with thoughts
Silber TJ, Pao M: Somatization disorders in children and adoles- of death. The history should include an assessment of
cents. Pediatr Rev 2003;24(8):255 [PMID: 12897265]. school performance, looking for signs of academic dete-
Wood BL: Physically manifested illness in children and adolescents: rioration, excessive absence or cutting class, changes in
A biobehavioral family approach. Child Adolesc Psychiatr
Clin North Am 2001;10:543 [PMID: 11449811].
work or other outside activities, and changes in the
family (eg, separation, divorce, serious illness, loss of
employment by a parent, a recent move to a new
DEPRESSION (See also Chapter 6.) school, increasing quarrels or fights with parents, the
Symptoms of clinical depression (lethargy, loss of inter- death of a close relative). The teenager may have with-
est, sleep disturbances, decreased energy, feelings of drawn from friends or family or switched allegiance to a
worthlessness, and difficulty concentrating) are com- new group of friends. The physician should seek to de-
mon during adolescence. The intensity of feelings, velop a history of drug and alcohol abuse, conflicts with
often in response to seemingly trivial events such as a the police, sexual acting out, running away from home,
poor grade on an examination or not being invited to a unusually violent or rebellious behavior, or radical per-
party, makes it difficult to differentiate severe depres- sonality changes. Patients with vague somatic com-
sion from normal sadness or dejection. In less severe de- plaints or concerns about having a fatal illness may have
pression, sadness or unhappiness associated with prob- an underlying affective disorder.
lems of everyday life is generally short-lived. The Adolescents presenting with symptoms of depres-
symptoms usually result in only minor impairment in sion require a thorough medical evaluation to rule out
school performance, social activities, and relationships any contributing or underlying medical illness. Among
with others. Symptoms respond to support and reassur- the medical conditions associated with affective disor-
ance. ders are eating disorders, organic central nervous system
(CNS) disorders (tumors, vascular lesions, closed head
trauma, and subdural hematomas), metabolic and en-
Clinical Findings docrinologic disorders (systemic lupus erythematosus,
The presentation of serious depression in adolescence hypothyroidism, hyperthyroidism, Wilson disease, hy-
may be similar to that in adults, with vegetative signs perparathyroidism, Cushing syndrome, Addison dis-
such as depressed mood, crying spells or inability to cry, ease, premenstrual syndrome), infections (infectious
118 / CHAPTER 3

mononucleosis, syphilis), and mitral valve prolapse. Brent DA, Birmaher B: Clinical practice. Adolescent depression.
Marijuana use, phencyclidine abuse, amphetamine N Engl J Med 2002;347(9):667 [PMID: 12200555].
withdrawal, and excessive caffeine intake can cause Jellinek MS, Snyder JB: Depression and suicide in children and
symptoms of depression. Common prescription and adolescents. Pediatr Rev 1998;19:255 [PMID: 9707715].
over-the-counter medications, including birth control Labellarte MJ et al: The new antidepressants: Selective serotonin re-
uptake inhibitors. Pediatr Clin North Am 1998;45:1137
pills, anticonvulsants, and β-blockers, may cause de- [PMID: 9884679].
pressive symptoms. Whooley MA, Simon GE: Managing depression in medical outpa-
Some routine laboratory studies are indicated in the tients. N Engl J Med 2000;343:1942 [PMID: 11136266].
depressed patient to rule out organic disease: a com-
plete blood count (CBC) and erythrocyte sedimenta-
tion rate (ESR), urinalysis, serum electrolytes, blood ADOLESCENT SUICIDE
urea nitrogen (BUN), serum calcium, thyroxine and (See also Chapter 6.)
thyroid-stimulating hormone (TSH), Venereal Disease In 2000, 3994 people age 15–24 years committed sui-
Research Laboratory (VDRL) or rapid plasma rea- cide, 1621 suicides among those age 15–19 years and
gin (RPR), and liver enzymes. Although metabolic 2378 among those age 20–24 years. In the younger
markers such as abnormal secretion of cortisol, growth group, males had a suicide rate 5 times higher than fe-
hormone, and thyrotropin-releasing hormone have males, and white males had the highest rate, 15.5 per
been useful in confirming major depression in adults, 100,000. The incidence of unsuccessful suicide at-
these neurobiologic markers are less reliable in adoles- tempts is three times higher in females than in males.
cents. The estimated ratio of attempted suicides to actual sui-
The risk of depression appears to be greatest in cides is estimated to be 100:1–50:1. Firearms account
families with a history of early onset and chronic de- for 67% of suicide deaths in both males and females.
pression. Depression of early onset and bipolar illness With the normal mood swings of adolescence, short
are more likely to occur in families with a strong multi- periods of depression are common, and a teenager may
generational history of depression. The lifetime risk of have thoughts of suicide. Normal mood swings during
depressive illness in first-degree relatives of adult de- this period rarely interfere with sleeping, eating, or par-
pressed patients has been estimated to be between 18% ticipating in normal activities. Acute depressive reac-
and 30%. tions (transient grief responses) to the loss of a family
member or friend may result in depression lasting for
Treatment weeks or even months. An adolescent who is unable to
work through this grief can become increasingly de-
The primary care physician may be able to counsel ado- pressed. A teenager who is unable to keep up with
lescents and parents if depression is mild or is the result schoolwork, does not participate in normal social activi-
of an acute personal loss or frustration and if the patient ties, withdraws socially, has sleep and appetite distur-
is not contemplating suicide or other life-threatening bances, and has feelings of hopelessness and helpless-
behaviors. If, however, there is evidence of a long- ness should be considered to be at increased risk for
standing depressive disorder, suicidal thoughts, or psy- suicide.
chotic thinking, or if the physician does not feel com- Another group of suicidal adolescents is composed
petent or has no interest in counseling the patient, of angry teenagers attempting to influence others by
psychological referral should be made. their actions. They may be only mildly depressed and
Counseling involves establishing and maintaining a may not have a long-standing wish to die. Teenagers in
positive supportive relationship; following the patient this group, usually females, may attempt suicide or
at least weekly; remaining accessible to the patient at all make a suicidal gesture as a way of getting back at
times; encouraging the patient to express emotions someone or gaining attention by frightening another
openly, defining the problem and clarifying negative person.
feelings, thoughts, and expectations; setting realistic The last group at risk for suicide are adolescents
goals; helping to negotiate interpersonal crises; teaching with a serious psychiatric problem such as acute schizo-
assertiveness and social skills; reassessing the depression phrenia or a true psychotic depressive disorder.
as it is expressed; and staying alert to the possibility of
suicide. Risk Assessment
Patients with a clinical course consistent with bipo-
lar disease or those who have a significant depression The physician must determine the extent of the
that is unresponsive to supportive counseling should be teenager’s depression and assess the risk of inflicting
referred to a psychiatrist for evaluation of antidepres- self-harm. The evaluation should include interviews
sant medication. with both the teenager and the family. The history
 ADOLESCENCE / 119

should include the medical, social, emotional, and aca- American Academy of Child and Adolescent Psychiatry: Summary
demic background (see Table 6–16). The physician of the practice parameters for the assessment and treatment of
children and adolescents with suicidal behavior. J Am Acad
should inquire about Child Adolesc Psychiatry 2001;40:495 [PMID: 11314578].
American Academy of Pediatrics Committee on Adolescence: Sui-
1. Common signs of depression cide and suicide attempts in adolescents. Pediatrics
2. Recent events that could be the cause of an under- 2000;105:871 [PMID: 10742349].
lying depression Blumenthal SJ: Youth suicide: The physician’s role in suicide pre-
3. Evidence of long-standing problems in the home, vention. JAMA 1990;264:3194 [PMID: 2255029].
at school, or with peers Grossman DC et al: Self-inflicted and unintentional firearm in-
juries among children and adolescents: The source of the
4. Drug or substance use and abuse firearm. Arch Pediatr Adolesc Med 1999;153:875 [PMID:
5. Signs of psychotic thinking, such as delusions or 10437764].
hallucinations The Committee on Adolescence: Adolescent Suicide. American Psy-
6. Evidence of masked depression, such as rebellious chiatric Press, 1996.
behavior, running away from home, reckless dri- Zametkin AJ et al: Suicide in teenagers: Assessment, management,
ving, or other acting-out behavior. and prevention. JAMA 2001;286(24):3120 [PMID:
11754678].
When seeing depressed patients, the physician should
always inquire about thoughts of suicide, for example,
by asking, “Are things ever so bad that life doesn’t seem SUBSTANCE ABUSE
worth living?” If the response is affirmative, a more spe- Substance abuse is a complex problem for adolescents
cific question should be asked, for example, “Have you and the broader society. See Chapter 4 for an in-depth
thought of taking your life?” If the patient has thoughts look at this issue.
of suicide, the immediacy of risk can be assessed by de-
termining if the patient has a concrete, feasible plan.
Although patients who are at greatest risk have a con- EATING DISORDERS (See Chapter 5.)
crete plan that can be carried out in the near future, es-
pecially if they have rehearsed the plan, the physician EXOGENOUS OBESITY
should not dismiss the potential risk of suicide in the (See Chapter 10: Normal Childhood
adolescent who does not describe a specific plan. The Nutrition & Its Disorders)
physician should pay attention to his or her gut feel-
ings. Subtle nonverbal signs may indicate that the pa- Overweight, or at risk for obesity, is defined as body
tient is at greater risk than may be apparent. mass index (BMI) greater than the 85th percentile for
age (Figures 3–5 and 3–6). It is important to note that
mean BMI changes dramatically with age. For a
Treatment 13-year-old, a BMI greater than 25 constitutes obesity,
The primary care physician is often in a unique posi- whereas in adolescents older than 18, the adult stan-
tion to identify an adolescent at risk for suicide, because dard of BMI greater than 30 accurately defines obesity
many teenagers who attempt suicide seek medical at- (Figure 3–7).
tention in the weeks preceding the attempt. These visits
are often for vague somatic complaints. If is the patient Background
shows evidence of depression, the physician must assess
the severity of the depression and suicidal risk. The pe- Recent data from the National Health and Nutrition
diatrician should always seek emergency psychological Examination Survey (NHANES)-IV showed an in-
consultation for any teenager who is severely depressed, crease in obesity in adolescents ages 12–19 from 5% in
psychotic, or acutely suicidal. It is the psychologist’s or 1966–1970 to 14% in 1999. The changes in BMI dur-
psychiatrist’s responsibility to assess the seriousness of ing and after adolescence have been shown to be impor-
suicidal ideation and decide whether hospitalization or tant predictors of adult adiposity. In general, the longer
out-patient treatment is most appropriate. Adolescents a child remains obese, the more likely obesity will per-
with mild depression and at low risk for suicide should sist into adulthood. The medical risks associated with
be followed closely, and the extent of the depression obesity are discussed in Chapter 10. The psychosocial
should be assessed on an ongoing basis. If at any point hazards of obesity tend to be the greatest consequence
it appears that the patient is worsening or the teenager for adolescents, who may experience alienation, dis-
is not responding to supportive counseling, referral torted peer relations, poor self-esteem, guilt, depression,
should be made. or altered body image.
120 / CHAPTER 3

Figure 3–5. Percentile values for BMI (kg/m2) in girls. (Centers for Disease Control and Prevention.)
 ADOLESCENCE / 121

Figure 3–6. Percentile values for BMI (kg/m2) in boys. (Centers for Disease Control and Prevention.)
122 / CHAPTER 3

Weight Height lected: height; weight; BMI; blood pressure; condition

kg cm of the skin, thyroid, heart, and abdomen; hematocrit;
Body and urinalysis. Acanthosis nigricans is a cutaneous find-
150 Mass ing characterized by velvety hyperpigmentation, most
125
140 Index prominent behind the neck, in the axilla, and in the
[weight/(height)2]
130
130
groin. Acanthosis is more commonly seen in dark-
120 70 skinned persons and is a marker for insulin resistance.
110 60 135 Endocrine causes of obesity, such as hypothyroidism
and Cushing disease, can generally be excluded on the
100
95
50 140 basis of the history and physical examination. If an ado-
90 lescent is healthy and has no delay of growth or sexual
85 40 145 maturation, an underlying endocrinologic, neurologic,
80 or genetic cause is unlikely.
75 150

70 30
155
65 Treatment
60 160
Poorly motivated adolescents may be alienated by an
55 20 165 aggressive discussion of weight loss. Instead, providers
50
may give basic information about healthy diet and reg-
170
ular exercise and be available for future visits if patients
45 175 become interested in weight loss. For the highly moti-
vated patient, treatment should be appropriate to age
40 180
and developmental level. The adolescent should be
185 taught appropriate eating and exercise habits to main-
35 10
190 tain weight reduction yet meet nutritional needs for
growth and development. You may be more likely to
195
30 engage the average adolescent by helping him or her to
200 choose concrete, obtainable goals (eg, decreasing soda
205 from three to two per day, or walking with a friend
25
210
3 days a week instead of watching television). Appetite-
suppressing drugs, fasting, and bypass surgery have no
role in the management of obese adolescents unless se-
Figure 3–7. Nomogram for determining body mass vere comorbidities of obesity are present. An age-appro-
index (BMI) from height and weight. A straight-edge priate behavior modification program incorporating
connecting weight and height allows one to read BMI good dietary counseling and exercise is optimal. Studies
(weight in kg ÷ [height in m2]). The three dots on the indicate that increased activity may be more important
left side of the BMI line represent 50th percentile values than dietary changes in long-term weight management.
for females age 20 years (top), 15 years (middle), and Lifestyle activity recommendations, such as walking
10 years (bottom). The dots on the right side are for and taking the stairs, may be more effective in the long
similar-aged males. (Reproduced, with permission, from run than regimented exercise programs. Avoiding label-
Forbes GR: Nutrition and growth. In: McAnarney ER et al ing any food as “forbidden” may improve long-term
[eds]: Textbook of Adolescent Medicine. WB Saunders, 1992.) success with healthy eating behaviors. Behavioral treat-
ment involving parents has been shown to improve
long-term maintenance of weight loss in children;
parental involvement in adolescent weight loss pro-
Diagnosis grams has shown mixed results. In general, the most
important factor in successful weight loss and weight
An adolescent with a BMI above the 85th percentile is maintenance is motivation of the adolescent. Monthly
considered at risk for obesity; BMI above the 95th per- follow-up visits may help to maintain motivation, espe-
centile is considered obese. Patients can be identified as cially initially. Unfortunately, no program has been
at risk for obesity based on current weight relative to proven effective for long-term weight reduction.
height, growth and weight trend, and weight of family
members. In addition, the provider needs to assess a pa-
tient’s readiness to make lifestyle changes. When obe- Styne D: Childhood and adolescent obesity. Pediatr Clin North
sity is diagnosed, the following database can be col- Am 2001;48:823 [PMID 11494639].
 ADOLESCENCE / 123

Yanovski JA: Intensive therapies for pediatric obesity. Pediatr Clin tions, homework, and papers. The pediatrician should
North Am 2001;48:1041 [PMID 11494637]. speak directly with teachers who are punitive. The ob-
jective is to make the transition back to school as easy as
SCHOOL AVOIDANCE possible. The longer adolescents stay out of school, the
more anxious they may become about returning and the
Any teenager who has missed more than 1 week of school more difficult the return becomes. If an illness or symp-
for a physical illness or symptom, and whose clinical pic- tom becomes so severe that an adolescent cannot go to
ture is inconsistent with a serious illness, should be sus- school, the patient and the parents must be informed
pected of harboring primary or secondary emotional fac- that a visit to a medical office is necessary. The physician
tors that contribute to the absence. Investigation of focuses visits on the parents as much as on the adoles-
absences may show a pattern, such as missing morning cent to alleviate any parental guilt about sending the
classes or missing the same days at the beginning or end child to school. If the adolescent cannot stay in school,
of the week. Emotional factors for school absenteeism are hospitalization should be recommended for an in-depth
usually attributed to physical symptoms in this age group. medical and psychiatric evaluation. Parents should be
School avoidance should be suspected in children cautioned about the possibility of relapse after school
who are consistently absent in spite of parents’ and pro- holidays, summer vacation, or an acute illness.
fessionals’ attempts to encourage school attendance.
Adolescents with school avoidance problems often have Klerman LV: School absence: A health perspective. Pediatr Clin
a history of excessive absences or separation difficulties North Am 1988;35:1253 [PMID: 3059298].
as a younger child. They may also have a record of re-
current somatic complaints. Parents of a school avoider SCHOOL FAILURE
often feel helpless to compel their adolescent to attend
school, may lack the sophistication to distinguish ma- When children graduate from grade school to middle
lingering from illness, or may have an underlying need school or junior high school, the amount and complex-
to keep the teenager at home. ity of course work increase significantly. This occurs at
A complete history and physical examination should about the same time as the rapid physical, social, and
be performed, reviewing the patient’s medical, educa- emotional changes of puberty. To perform well acade-
tional, and psychiatric history. Signs of emotional prob- mically, young adolescents must have the necessary cog-
lems should be explored. After obtaining permission nitive capacity, study habits, concentration, motivation,
from the patient and parents, the physician may find it interest, and emotional focus. Academic failure present-
helpful to speak directly with school officials and some ing at adolescence has a broad differential:
key teachers. The adolescent may be having problems 1. Limited intellectual abilities
with particular teachers or subjects or experiencing ad-
2. Specific learning disabilities
versity at school (eg, schoolyard bullying, an intimidat-
ing instructor). Some students get so far behind acade- 3. Depression or emotional problems
mically that they see no way of catching up and feel 4. Physical causes such as visual or hearing problems
overwhelmed. Separation anxiety, sometimes of long 5. Excessive school absenteeism secondary to chronic
duration, may be manifested in subconscious worries disease such as asthma or neurologic dysfunction
that something may happen to the mother while the 6. Lack of ability to concentrate
teenager is at school. 7. Attention-deficit/hyperactivity disorder
The school nurse may give useful information, in-
cluding the number of visits to the nurse during the last 8. Lack of motivation
school year. An important part of the history is how the 9. Drug and alcohol problems.
parents respond to the absences and somatic com- Each of these possible causes must be explored in depth
plaints. The parent(s) may be making a subconscious (Table 3–1). Evaluation of this differential requires a
attempt to keep the adolescent at home, which may be careful history, physical examination, and appropriate
coupled with secondary gains for the patient, such as laboratory tests as well as standardized educational and
increased parental attention. psychological testing.

Treatment Treatment
The importance of returning to school quickly after a Treatment depends on the cause. Management must be
period of school avoidance needs to be emphasized. The individualized to address specific needs, foster strengths,
pediatrician should facilitate this process by offering to and implement a feasible program. For children with
speak with school officials to excuse missed examina- specific learning disabilities, an individual prescription
124 / CHAPTER 3

Table 3–1. A classification of common developmental dysfunctions in adolescence.

Dysfunction Subtypes Frequent Manifestationsa

1. Attention a. Primary Weak attention to detail; distractibility; impulsivity,
deficits b. Secondary (to anxiety or poor information restlessness; task impersistence; performance
processing) inconsistency; organizational problems; reduced
c. Situational (only evident in certain settings) working capacity
2. Memory impair- a. Generalized retrieval problems Deficient, undependable, or slow recall of data from
ments b. Modality-specific retrieval problems long- or short-term memory
c. Attention-retention deficiencies Problems with revisualization or auditory, motor, or
sequential recall
Poor recall associated with superficial initial registration
3. Language a. Receptive Poor verbal and reading comprehension; poor listening;
disorders b. Expressive trouble following directions and explanations
Problems with word finding, sentence formulation
Difficulty with written expression
4. Higher-order a. Inferential weakness Problems understanding and assimilating new concepts;
cognitive dis- b. Poor verbal reasoning tendency to think “concretely,” delays in mathematics,
abilities c. Poor nonverbal reasoning reading comprehension, science, social studies
d. Difficulty with abstraction, symbolization
e. Weak generalization and rule application
5. Fine motor a. Eye:hand coordination problems Slow, labored, sometimes illegible writing; awkward
incoordination b. Impaired propriokinesthetic feedback pencil grip; dyssynchrony between cognitive tempo
c. Dyspraxia and writing speed; output failure—reduced produc-
d. Motor memory impairment tivity
6. Organizational a. Temporal-sequential disorientation Problems with time allocation, schedules, planning,
deficiencies b. Material disarray arranging ideas in writing
c. Integrative dysfunction Tendency to lose, misplace, forget books, papers;
d. Resynthesis problems trouble organizing notebook
e. Attentional disorganization Varying inability to integrate data from multiple
sources or sensory modalities
Trouble extracting most salient details, retelling and
adapting data to current demands
Impulsivity, erratic tempo, poor self-monitoring, care-
less errors
7. Socialization a. Wide range of subtypes, including conduct Antisocial behaviors; delinquency; withdrawal; exces-
disabilities disorder, social impulsivity, impaired social sive dependency on peer support
cognition or feedback, egocentricity
a
Manifestations are likely to vary somewhat depending on compensatory strengths, quality of educational experience, and motivation.
Modified and reproduced, with permission, from Levine MD, Zallen BG: Learning disorders of adolescence. Pediatr Clin North Am 1984;31:2.

for regular and special education courses, teachers, and Brown FR et al: AD/HD: A neurodevelopmental perspective. Con-
extracurricular activities is important. Counseling temp Pediatr 1996;13:25.
helps these adolescents gain coping skills, raise self-es- Goldman LS et al: Diagnosis and treatment of attention-deficit/hy-
teem, and develop socialization skills. If the patient has a peractivity disorder in children and adolescents. JAMA
1998;279:1100 [PMID: 9546570].
history of hyperactivity or attention deficit disorder
Kube DA, Shapiro BK: Persistent school dysfunction: Unrecog-
along with poor ability to concentrate, a trial of stimu- nized comorbidity and suboptimal therapy. Clin Pediatr
lant medication (eg, methylphenidate, dextroampheta- (Phila) 1996;45:571 [PMID: 8953132].
mine) may be useful. If the teenager appears to be de- Reiff MI: Adolescent school failure. Failure to thrive in adoles-
pressed or if other serious emotional problems are cence. Pediatr Rev 1998;19:199 [PMID: 9613171].
uncovered, further psychological evaluation should be Shaywitz BA et al: Attention-deficit/hyperactivity disorder. Adv Pe-
recommended. diatr 1997;44:331 [PMID: 9265975].
 ADOLESCENCE / 125

Shaywitz SE: Dyslexia. N Engl J Med 1998;338:307 [PMID: Table 3–2. Breast masses in adolescent females.
9445412].

Common
Fibroadenoma
BREAST DISORDERS Fibrocystic changes
Breast cysts
Breast abscess/mastitis
The breast examination should become part of the rou- Less common or rare (benign)
tine physical examination in girls as soon as breast bud- Lymphangioma
ding occurs. The preadolescent thus comes to accept Hemangioma
breast examination as a routine part of health care, and Giant fibroadenoma
the procedure serves as an opportunity to offer reassur- Neurofibromatosis
ance about any concerns she may have. The breast ex- Nipple adenoma/keratoma
amination begins with inspection of the breasts for Mammary duct actasia
Lipoma
symmetry and Tanner or sexual maturity rating (SMR)
Hematoma
stage. Asymmetrical breast development is common, es- Rare (malignant potential)
pecially in young adolescents, and is generally transient, Adenocarcinoma
although 25% of women may continue to have some Cystosarcoma phyllodes
degree of asymmetry into adulthood. Unusual causes of Intraductal papilloma
breast asymmetry include unilateral breast hypoplasia, Rhabdomyosarcoma
amastia, absence of the pectoralis major muscle, and Lymphosarcoma
unilateral virginal hypertrophy (massive enlargement of Hemangiosarcoma
the breast during puberty). Metastatic cancer
Palpation of the breasts can be performed with the
patient in the supine position and the patient’s ipsilat-
eral arm placed behind her head. The examiner palpates
the breast tissue with the flat of the fingers in concen-
tric circles from the sternum, clavicle, and axilla in to mass that may occur in any quadrant, but is most com-
the areola. The areola should be compressed gently to monly found in the upper outer quadrant. The average
check for discharge. size is 2–3 cm in diameter. In 10–25% of cases, multi-
Instructions for breast self-examination and its pur- ple or recurrent lesions occur. Quiescence can be ex-
pose can be given to older adolescents approaching age pected after the teenage years.
18 years during this portion of the physical examina-
tion, and the patient should be encouraged to begin
monthly self-examination after each menstrual flow Cysts
after age 18 years. Because the vast majority of breast le-
sions in teens are benign, teaching young adolescents Breast cysts are generally tender and spongy, with exac-
breast self-examination may lead to unnecessary anxiety erbation of symptoms premenstrually and improve-
and overconcern with normal variants. ment after menses. Often they are multiple. Sponta-
neous regression occurs over two or three menstrual
cycles in about 50% of cases.
BREAST MASSES It is reasonable to follow breast masses that are consis-
Most breast masses in adolescents are benign (Table tent with fibroadenoma or cyst in adolescents for two or
3–2); however, cancer does occasionally occur in ado- three menstrual cycles. Approximately 25% of fibroade-
lescents. A large study in Greece of 684 females ages nomas become smaller, and approximately 50% of cysts
14–20 with breast masses showed only 2.5% to be ma- resolve. If a presumed fibroadenoma does not change
lignant. The malignant cases included hemangiosar- after this time, ultrasound will differentiate a solid tumor
coma, rhabdomyosarcoma, ductal carcinoma, cystosar- from a cyst. Patients with solid tumors larger than 2.5 cm
coma phyllodes, and metastatic tumor. in diameter should be referred for fine-needle aspiration
or excisional biopsy. Those with tumors less than 2.5 cm
in diameter may be followed every 3–6 months, because
Fibroadenoma many of these tumors will shrink or remain the same. Per-
Fibroadenoma (which accounts for approximately two- sistent cystic lesions may be drained by needle aspiration.
thirds of all breast masses in adolescents) presents as a Patients with suspicious lesions should be referred imme-
rubbery, well-demarcated, slowly growing, nontender diately to a breast surgeon (Table 3–3).
126 / CHAPTER 3

Table 3–3. Breast lesions. matic relief. Oral contraceptives (OCPs) often improve
symptoms. Studies have shown no association between
Fibroadenoma Rubbery, well demarcated, nontender, methylxanthines and fibrocystic breasts; however, some
slowly growing; most commonly found in women report reduced symptoms when they discon-
the upper outer quadrant of the breast. tinue caffeine intake. The efficacy of vitamins E, B1,
Usually < 5 cm. and A is unknown. Evening primrose oil has been ben-
eficial in 44% of patients. A trial of 1000 mg three
Adenocarcinoma Hard, nonmobile, well-circumscribed,
times a day for 3 months may be helpful.
painless mass; generally indolent clinical
course; occurs also in males but less fre-
quently. Breast Abscess
Cystosarcoma Firm, rubbery mass that may suddenly The female with a breast abscess usually complains of
phyllodes enlarge; associated with skin necrosis; unilateral breast pain, and examination reveals overly-
most often benign. ing inflammatory changes. Often the examination is
Giant juvenile Remarkable large fibroadenoma with misleading in that the infection may extend much
fibroadenoma overlying dilated superficial veins; deeper than suspected. A palpable mass is found only
accounts for 5–10% of fibroadenomas in late in the course. Although breast feeding is the most
adolescents; benign but requires excision common cause of mastitis, trauma and eczema involv-
to prevent breast atrophy and for cosmetic ing the areola are frequent factors in teenagers. Staphy-
reasons. lococcus aureus is the most common pathogen, but other
Intraductal A cylindric tumor arising from the ductal aerobic and anaerobic organisms have also been impli-
papilloma epithelium; often subareolar but may be cated.
in the periphery of the breast in adoles- Cyclic mastodynia, fibrocystic disease, or chest wall
cents, with associated nipple discharge. pain may also be causes of breast pain, but no associ-
Most are benign but require excision for ated inflammatory signs should be present.
cytologic diagnosis. Fluctuant abscesses should be surgically incised and
drained. Oral antibiotics with appropriate coverage (di-
Fat necrosis Localized inflammatory process in one cloxacillin or a cephalosporin) should be given for
breast; follows trauma in about half of
2–4 weeks. Ice packs for the first 24 hours and heat
cases. Subsequent scarring may be con-
fused with cancer.
thereafter may relieve symptoms.
Virginal or Massive enlargement of both breasts or,
juvenile less often, one breast; attributed to end- GALACTORRHEA
hypertrophy organ hypersensitivity to normal hor- In teenagers, galactorrhea is most often benign; how-
monal levels just before or within a few ever, a careful history and work-up are necessary. Pro-
years after menarche. lactinomas are the most common pathologic cause of
Miscellaneous Fibroma, galactocele, hemangioma, in- galactorrhea in adolescents of both sexes and generally
traductal granuloma, interstitial fibrosis, present as amenorrhea or failure of sexual maturation.
keratoma, lipoma, granular cell Hypothyroidism is the second most common cause in
myoblastoma, papilloma, sclerosing ad- the adolescent years but has been reported only in girls,
enosis. usually prepubertally.
Galactorrhea may be present after spontaneous or
induced abortions as well as postpartum. Numerous
prescribed and illicit drugs are associated with galactor-
Fibrocystic Breasts rhea (Table 3–4). In addition, stimulation of the inter-
costal nerves (following surgery or due to herpes zoster
Fibrocystic breast disease sometimes occurs in older infection), stimulation of the nipples, CNS disorders
adolescents and becomes more common with age. It is (hypothalamic injury), or significant emotional distress
characterized by cyclic tenderness and nodularity bilat- may produce galactorrhea.
erally and is believed to be influenced by the estro-
gen–progesterone balance. Clinical Findings
Reassuring the young woman about the benign na-
ture of the process and emphasizing the importance of If the teenager has no history of pregnancy or drug use,
breast self-examination as she becomes an adult may be TSH and serum prolactin levels should be determined.
all that is needed. Support bras may provide sympto- An elevated TSH confirms the diagnosis of hypothy-
 ADOLESCENCE / 127

Table 3–4. Medications and herbs associated Treatment

with galactorrhea. Treatment depends on the underlying cause. Prolactin-
omas may be removed surgically or suppressed with
Antidepressants and anxiolytics Other drugs bromocriptine. Bromocriptine may also be beneficial to
Alprazolam (Xanax) Amphetamines some amenorrheic females with normal serum prolactin
Buspirone (BuSpar) Anesthetics levels. The female with a negative work-up and persis-
Monoamine oxidase inhibitors Arginine tent galactorrhea may be followed with menstrual his-
Moclobemide (Manerix; Cannabis tory and serum prolactin level every 6–12 months. In
available in Canada) Cisapride (Propulsid) many cases, symptoms resolve spontaneously and no di-
Selective serotonin reuptake Cyclobenzaprine (Flex-
agnosis is made. The female with an elevated serum
inhibitors eril)
Citalopram (Celexa) Danazol (Danocrine)
prolactin concentration but negative prolactinoma
Fluoxetine (Prozac) Dihydroergotamine work-up may be treated with bromocriptine if her
Paroxetine (Paxil) (DHE 45) symptoms are bothersome or may be observed with
Sertraline (Zoloft) Domperidone (Motil- MRI scan every 1–2 years for several years.
Tricyclic antidepressants ium; available in Can-
Antihypertensives ada and Mexico) GYNECOMASTIA
Atenolol (Tenormin) Isoniazid (INH)
Methyldopa (Aldomet) Metoclopramide Gynecomastia is a common concern of male adoles-
Reserpine (Serpasil) (Reglan) cents, most of whom (60–70%) develop transient sub-
Verapamil (Calan) Octreotide (Sandostatin) areolar breast tissue during SMR stages 2 and 3. Pro-
Antipsychotics Opiates posed causes include testosterone–estrogen imbalance,
Histamine H2-receptor blockers Rimantadine (Fluma- increased serum prolactin level, and abnormal serum
Cimetidine (Tagamet) dine) protein binding levels.
Famotidine (Pepcid) Sumatriptan (Imitrex)
Ranitidine (Zantac) Valproic acid (Depa- Clinical Findings
Hormones kene)
Conjugated estrogen and Herbs In type I idiopathic gynecomastia, the adolescent pre-
medroxyprogesterone Anise sents with a unilateral (20% bilateral) tender, firm mass
(Premphase, Prempro) Blessed thistle beneath the areola. More generalized breast enlargement
Medroxyprogesterone contra- Fennel is classified as type II. Pseudogynecomastia is the term
ceptive injections (Depo- Fenugreek seed for excessive fat tissue or prominent pectoralis muscles.
Provera) Marshmallow
Oral contraceptive formula- Nettle Differential Diagnosis
tions Red clover
Phenothiazines Red raspberry Gynecomastia may be drug-induced (Table 3–5). Tes-
Chlorpromazine (Thorazine) ticular, adrenal, or pituitary tumors, Klinefelter syn-
Prochlorperazine (Compazine) drome, primary hypogonadism, thyroid or hepatic dys-
Others function, or malnutrition may also be associated with
gynecomastia (Table 3–6). Onset of gynecomastia in
Reprinted, with permission, from American Family Physician.
late (rather than early or middle) adolescence is more
likely indicative of pathology.

Treatment
roidism. An elevated prolactin and normal TSH, often If gynecomastia is idiopathic, reassurance about the
accompanied by amenorrhea, suggest a hypothalamic common and benign nature of the process can be given.
or pituitary tumor, and magnetic resonance imaging Resolution may take up to 2 years. Medical reduction
(MRI) scan is indicated. When the prolactin level is has been achieved with pharmacotherapeutic agents,
normal, uncommon causes such as adrenal, renal, or such as dihydrotestosterone, danazol, clomiphene, and
ovarian tumors should be considered. Males with a neg- tamoxifen, but these agents should be reserved for pa-
ative work-up and normal puberty need to be followed tients in whom no decrease in breast size occurs after
intensively. Males with elevated prolactin levels require 2 years. Surgery is reserved for those with significant
an MRI scan every 12–18 months even if the galactor- psychological trauma or severe breast enlargement.
rhea resolves, because of the significant risk of a small
pituitary adenoma that may become apparent with ser- Lazala C, Saenger P: Pubertal gynecomastia. J Pediatr Endocrinol
ial examinations. Metab 2002;15(5):553 [PMID: 12014513].
128 / CHAPTER 3

Table 3–5. Drugs associated with gynecomastia. Table 3–6. Disorders associated
with gynecomastia.
Antibiotics Drugs and substances of abuse
Isoniazid Alcohol Klinefelter syndrome
Ketoconazole Amphetamines Traumatic paraplegia
Metronidazole Marijuana Male pseudohermaphroditism
Anti-ulcer drugs Opiates Testicular feminization syndrome
Cimetidine Hormones or related agents Reifenstein syndrome
Omeprazole Anabolic steroids 17-Ketosteroid reductase deficiency
Ranitidine Estrogens Endocrine tumors (seminoma, Leydig cell tumor, teratoma,
Cardiovascular drugs Chorionic gonadotropin feminizing adrenal tumor, hepatoma, leukemia, hemo-
Captopril Psychoactive medications philia, bronchogenic carcinoma, leprosy, etc)
Digoxin Tricyclic antidepressants, eg, Hypothyroidism
Enalapril amitriptyline Hyperthyroidism
Methyldopa Antipsychotics, eg, Cirrhosis
Reserpine chlorpromazine, fluphena- Herpes zoster
Verapamil zine, haloperidol Friedreich ataxia
Chemotherapeutic drugs Anxiolytics, eg, chlordiaze-
Busulfan poxide, diazepam
Vincristine

Pena K, Rosenfeld J: Evaluation and treatment of galactorrhea. Am During the luteal phase, LH and FSH gradually de-
Fam Physician 2001;63:1763 [PMID: 11352287]. cline. The corpus luteum secretes progesterones. The
Templeman C, Hertweck S: Breast disorders in the pediatric and endometrium enters the secretory phase in response to
adolescent patient. Obstet Gynecol Clin North Am rising levels of estrogen and progesterone, with matura-
2000;27:19 [PMID: 10693180].
tion 8–9 days after ovulation. If no pregnancy occurs or
placental human chorionic gonadotropin (HCG) is re-
leased, luteolysis begins; estrogen and progesterone lev-
els decline; and the endometrial lining is shed as men-
GYNECOLOGIC DISORDERS strual flow approximately 14 days after ovulation
(Figure 3–8).
IN ADOLESCENCE During the first 2 years after menarche, the majority
of cycles are anovulatory (50–80%). Between 10% and
PHYSIOLOGY OF MENSTRUATION 20% of cycles remain anovulatory for up to 5 years
after menarche.
The ovulatory menstrual cycle is divided into three
consecutive phases: follicular (the first 14 days), ovula-
tory (midcycle), and luteal (days 16–28). During the
PELVIC EXAMINATION
follicular phase, pulsatile GnRH from the hypothala- A pelvic examination may be indicated to evaluate ab-
mus stimulates anterior pituitary secretion of FSH and dominal pain or menstrual disorders or to detect a sus-
LH. Under the influence of FSH and LH, a dominant pected STI in the adolescent. It has previously been rec-
ovarian follicle emerges by days 5–7 of the menstrual ommended that a routine pelvic examination be done
cycle, and the other follicles become atretic. Rising at age 18 years to obtain the first Papanicolaou (Pap)
estradiol levels produced by the maturing follicle cause smear and to evaluate reproductive anatomy. Recently
proliferation of the endometrium. By the midfollicular recommendations have changed to delay the first Pap
phase, FSH is beginning to decline secondary to estra- smear until age 21 years in the absence of menstrual
diol-mediated negative feedback, whereas LH continues problems in patients who have never had intercourse.
to rise as a result of estradiol-mediated positive feed- The first Pap smear should be performed within 3 years
back. of the initiation of sexual activity. Pap smears should be
The rising LH initiates progesterone secretion and performed earlier in adolescents with a history of sexual
luteinization of the granulosa cells of the follicle. Prog- abuse with penile penetration. The adolescent may be
esterone in turn further stimulates LH and FSH. This apprehensive about the first examination. It should not
leads to the LH surge, which causes the follicle to rup- be rushed, and an explanation of the procedure and its
ture and expel the oocyte. purpose should precede it. The patient can be encour-
 ADOLESCENCE / 129

60
aged to relax by slow, deep breathing and by relaxation
LH (mIU/mL)
of her lower abdominal and inner thigh muscles. A
FSH (mIU/mL)
50 young adolescent may wish to have her mother present
during the examination, but the history should be
40 taken privately. A female chaperone should be present
with male examiners.
30 The pelvic examination begins by placing the pa-
tient in the dorsal lithotomy position after equipment
20 and supplies are ready (Table 3–7). The examiner in-
spects the external genitalia, noting the pubic hair ma-
10
turity rating, the size of the clitoris (2–5 mm is nor-
0 mal), Skene glands just inside the urethral meatus, and
Gonadotropins Bartholin glands at 4 o’clock and 8 o’clock outside the
hymenal ring. In cases of alleged sexual abuse or assault,
Estradiol Progesterone
(ng/mL)
the horizontal measurement of the relaxed prepubertal
(pg/mL)
hymenal opening should be recorded and the presence
200 10
of any lacerations, bruises, scarring, or synechiae about
the hymen, vulva, or anus should be noted.
100 5 A vaginal speculum is then inserted at a 45-degree
twist and angled 45 degrees downward. (A medium
0 0 Pedersen speculum is most often used in sexually expe-
1 14 28 rienced patients; a narrow Huffman is used for virginal
Ovarian hormones patients.) The vaginal walls are inspected for estrogen
effects, inflammation, or lesions. The cervix should be
dull pink. Cervical ectropion is commonly observed in
adolescents; the columnar epithelium extends outside
the cervical os onto the face of the cervix until later
Growing follicle Ovulation Corpus luteum adolescence, when it recedes.
Ovarian follicle Specimens are obtained, including a wet preparation
for leukocytes, trichomonads, and clue cells (vaginal ep-
ithelial cells stippled with adherent bacteria); potassium
hydroxide (KOH) preparation for yeast and whiff test;
cervical swab for gonorrhea and Chlamydia; and endo-
cervical and cervical samples for Pap smear. A cervical
brush provides a higher yield of cells for the endocervi-

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29

Endometrium Days
Table 3–7. Items for pelvic exam tray.

Medium and virginal speculums (warm)

Gloves
Figure 3–8. Physiology of the normal ovulatory men- Applicator sticks, sterile
strual cycle; gonadotropin secretion, ovarian hormone Large swabs to remove excess discharge
production, follicular maturation, and endometrial Cervical spatulas, cervical brushes
changes during one cycle. FSH = follicle-stimulating Microscope slides and cover slips (frosted and labeled)
hormone, LH = luteinizing hormone. (Reproduced, with Centrifuge tube or test tube (if swab is to be placed in drop of
permission, from Emans SJH et al: Pediatric and Adolescent saline and slide prepared later)
NaCl dropper bottle
Gynecology, 4th ed. Little, Brown, 1998.)
KOH dropper bottle
Slide container to send to lab
Gonorrhea test media
Chlamydia test media
Lubricant
Kleenex
130 / CHAPTER 3

cal Pap slide. Pap smears should be interpreted by a cy- Table 3–8. Causes of amenorrhea.
topathologist at a laboratory using the Bethesda system
of classification. Hypothalamic–pituitary axis
The speculum is then removed, and bimanual exam- Hypothalamic repression
ination is performed to assess uterine size and position, Emotional stress
adnexal enlargement or tenderness, or cervical motion Depression
tenderness. Bimanual examination may reveal beading Chronic disease
in the adnexa secondary to endometriosis. Weight loss
Obesity
Severe dieting
MENSTRUAL DISORDERS Strenuous athletics
Drugs (post–birth control pills, phenothiazines)
1. Amenorrhea CNS lesion
Amenorrhea is the lack of onset of menses when nor- Pituitary lesion: adenoma, prolactinoma
mally anticipated. Primary amenorrhea is no menstrual Craniopharyngioma, brainstem, or parasellar tumors
periods or secondary sex characteristics by age 14 years Head injury with hypothalamic contusion
or no menses in the presence of secondary sex charac- Infiltrative process (sarcoidosis)
teristics by age 15 years. Constitutional delay is normal Vascular disease (hypothalamic vasculitis)
pubertal progression at a delayed onset or rate. Sec- Congenital conditionsa
Kallmann syndrome
ondary amenorrhea is defined as the absence of menses
Ovaries
for at least three cycles after regular cycles have been Gonadal dysgenesisa
present. In some instances, evaluation should begin im- Turner syndrome (XO)
mediately, without waiting for the specified age or du- Mosaic (XX/XO)
ration of lapsed periods, such as in patients with sus- Injury to ovary
pected pregnancy, short stature with the stigmata of Autoimmune disease
Turner syndrome, or an anatomic defect. Infection (mumps, oophoritis)
Toxins (alkylating chemotherapeutic agents)
Irradiation
Evaluation for Primary Amenorrhea Trauma, torsion (rare)
Primary amenorrhea may be the result of anatomic ab- Polycystic ovary syndrome
normalities, chromosomal deviations, or physiologic Ovarian failure
delay (Table 3–8). Premature menopause
The history should include whether puberty has Resistant ovary
commenced, level of exercise, nutritional intake, pres- Uterovaginal outflow tract
ence of stressors, and the age at menarche for female Müllerian dysgenesisa
relatives. Adrenal androgens are largely responsible for Congenital deformity or absence of uterus, uterine
axillary and pubic hair; estrogen is responsible for breast tubes, or vagina
Imperforate hymen, transverse vaginal septum, vaginal
development, maturation of the external genitalia,
agenesis, agenesis of the cervixa
vagina, and uterus, and menstruation. Testicular feminization (absent uterus)a
A careful physical examination should be done, noting Uterine lining defect
the percentage of ideal body weight for height and age, Asherman syndrome (intrauterine synechiae postcuret-
SMR stage, vaginal patency, presence of the uterus (as- tage or endometritis)
sessed through rectoabdominal examination or ultra- Tuberculosis, brucellosis
sonography if pelvic examination is not appropriate), Defect in hormone synthesis or action (virilization may
signs of virilization (acne, clitoromegaly of > 5 mm, hir- be present)
sutism), or stigmata of Turner syndrome (< 152 cm tall, Adrenal hyperplasiaa
shield-like chest, widely spaced nipples, increased carrying Cushing disease
angle of the arms, webbed neck). If pelvic examination re- Adrenal tumor
veals normal female external genitalia and pelvic organs, Ovarian tumor (rare)
the patient should be given a challenge of medroxyproges- Drugs (steroids, ACTH)
terone, 10 mg orally bid for 5 days (or 10 mg/d for a
Indicates condition that usually presents as primary amenorrhea.
7–10 days) (Figure 3–9). If withdrawal bleeding occurs ACTH = adrenocorticotropic hormone.
within 7 days after administration of medroxyproges-
terone, normal anatomy and adequate estrogen effect are
implied. If physical examination reveals an absent uterus
 ADOLESCENCE / 131

Primary amenorrhea
History and family history
Physical examination:
Tanner stage, percent IBW
Pelvic exam– normal female, uterus present, hymen
patent (if uterus absent, see Figure 3–10)
No virilization (if present, see Figure 3–10)
Identify:
Pregnancy by urine or serum hCG (not by history)
Turner syndrome
Anatomic abnormality (imperforate hymen, transverse vaginal septum)

No puberty Puberty has begun, but no Late-onset puberty but

(breast buds) by menarche by age 15 progressing
age 14

Constitutional delay
Test for estrogen
Confirm:
Medroxyprogesterone acetate
10 mg PO bid x 5 d Family history
Rule out:
Anatomic defect
Rx:
Reassurance
Wait

Low estrogen Normal estrogen

(no bleeding) (withdrawal bleed)

FSH, LH LH

HIGH LOW LOW HIGH

or NORMAL

Karyotype

ABNORMAL NORMAL

Gonadal dysgenesis Ovarian failure Severe hypothalamic Mild hypothalamic Polycystic ovary
repression repression syndrome
Rx: Rx: Rule out: Rx: Rx:
Hormone replacement Hormone replacement Anorexia nervosa Reassurance Birth control pills
Sexuality counseling Sexuality counseling Chronic disease Wait with low androgenic
Gyn consult Gyn consult CNS tumor Correct any profile (Ortho Tri-
Mixed gonadal underlying factors Cyclen, Demulen)
dysgenesis
Do:
Gyn-Endo consult

Figure 3–9. Evaluation of primary amenorrhea in a normal female. FSH = follicle-stimulating hormone, IBW = ideal
body weight, LH = luteinizing hormone.
132 / CHAPTER 3

Primary amenorrhea
Physical examination:
Pelvic exam

Absent uterus Virilized female

(will have breast Normal female Hirsutism
development) See Figure 3–9 Acne
Clitoromegaly >
_ 5 mm

KARYOTYPE TESTOSTERONE (T)

ULTRASOUND OR LAPAROSCOPY DHEAS

XY XX T < 200 ng/dL T > 200 ng/dL

DHEAS < 700 ng/dL DHEAS > 700 ng/dL
but both may be elevated

Testicular feminization Müllerian duct defect Polycystic ovary Adrenal or ovarian

syndrome tumor
Adrenal hyperplasia
Cushing's syndrome or
disease
Lab confirmation: Rx: Rx: Do:
High LH Sexual counseling Cycle with progesterone Gyn-Endo consult
Normal FSH IVP to rule out renal or birth control pills with 17-Ketosteroids
High testosterone anomaly low androgenic profile Dexamethasone
Endocrinology consultation Gynecology consultation Electrolysis after 6 months suppression test
of birth control pills ACTH stimulation test
consider metformin

Figure 3–10. Evaluation of primary amenorrhea in a female without a uterus or with virilization. ACTH = adreno-
corticotropic hormone, DHEAS = dehydroepiandrosterone sulfate, FSH = follicle-stimulating hormone, IVP = intra-
venous pyelogram, LH = luteinizing hormone.

(Figure 3–10), karyotyping should be performed to dif- the proliferative phase. The most common causes are
ferentiate testicular feminization from müllerian duct de- pregnancy, stress, and polycystic ovary syndrome
fect, because these two entities are managed differently. (PCOS). Ovarian failure can also present as secondary
Laboratory studies should include CBC, ESR, and amenorrhea, caused by mosaic Turner syndrome or au-
TSH. If systemic illness is suspected, a urinalysis and a toimmune oophoritis.
chemistry panel including renal and liver function tests The history should focus on issues of stress, chronic
should be obtained. If short stature is present, a bone illness, drugs, weight change, strenuous exercise, sexual
age should be done. If the diagnosis remains unclear activity, and contraceptive use. A review of systems
after preliminary evaluation, or if no withdrawal bleed should include questions about headaches, visual
occurs after a medroxyprogesterone challenge, FSH, changes, hirsutism, constipation, cold intolerance, and
LH, and prolactin levels should be obtained. Low levels galactorrhea.
of gonadotropins indicate a more severe hypothalamic Physical examination should include ophthalmo-
suppression, caused by anorexia nervosa, chronic dis- scopic and visual field examination, palpation of the
ease, or a CNS tumor. Involvement of a gynecologist or thyroid, determination of blood pressure and heart rate,
endocrinologist is helpful at this point. If gonadotropin compression of the areola to check for galactorrhea, and
levels are high, ovarian failure or gonadal dysgenesis is a search for signs of androgen excess (eg, hirsutism, cli-
implied, and karyotype should be obtained. toromegaly, severe acne, ovarian enlargement).
The first laboratory study obtained is a pregnancy test,
Evaluation & Treatment even if the patient denies sexual activity. If the teenager is
not pregnant, a progesterone challenge (medroxyproges-
of Secondary Amenorrhea terone, 10 mg orally bid for 5 days or 10 mg/d for
Secondary amenorrhea results when estrogen stimula- 7–10 days) should be done to determine whether the
tion is unopposed, maintaining the endometrium in uterus is primed with estrogen (Figure 3–11).
 ADOLESCENCE / 133

Patient with SECONDARY AMENORRHEA

A History Pregnancy Test

Identify:
Pregnancy
B Physical examination
Drugs
Chronic disease

C Progesterone challenge

Positive (withdrawal bleed) Negative (no withdrawal bleed)

Nonhirsute Hirsute G Assess:

Estradiol
FSH
D Mild hypothalamic Androgen excess LH
dysfunction (anovulatory) Prolactin

CBC, urinalysis, Obtain LH, FSH ratio, Normal estrogen Low estrogen
erythrocyte sedimentation and free testosterone,
rate, T4, thyroid-stimulating consider DHEAS,
hormone (as indicated) 17-OH-P, androstenedione Interfering
hormones Low FSH High FSH

Correct Polycystic
underlying E ovaries Severe I Ovarian failure
factors H hypothalamic
Androgen or dysfunction
cortisol excess
F Adrenal problem
or Obtain
Repeat
progesterone Prolactin excess chromosomes
every 3 months
(after ruling out Birth control
pregnancy) pills CT scan
Gynecology or endocrinology
or MRI
consultation
Endocrinology
If oligomenorrhea consultation
Consider Pituitary
persists, consider
metformin microadenoma Hormone
LH, FSH, prolactin,
or hyperplasia replacement
thyroid function
therapy
tests
Check:
T4
Thyroid-stimulating hormone
Erythrocyte sedimentation rate

Neurologic
examination

Figure 3–11. Evaluation of secondary amenorrhea. CBC = complete blood count, DHEAS = dehydroepiandro-
sterone sulfate, FSH = follicle-stimulating hormone, LH = luteinizing hormone, T4 = thyroxine.

Most patients who have withdrawal flow after prog- FSH, LH, and prolactin should be checked. An ele-
esterone challenge have mild hypothalamic suppression vated FSH level accompanied by a low estrogen level
due to weight change, athletics, stress, or illness; how- implies ovarian failure, in which case blood for kary-
ever, disorders such as PCOS, adrenal disorders, ovar- otype and antiovarian antibodies (if the karyotype is
ian tumors, thyroid disease, and diabetes mellitus normal) should be obtained and laparoscopy consid-
should be excluded by history and physical examination ered. If gonadotropin levels are low or normal and the
and appropriate laboratory studies. (See section on Pri- estradiol level is low, hypothalamic amenorrhea is
mary Amenorrhea and Figure 3–11.) likely; however, one must consider the possibilities of a
If withdrawal flow occurs after the progesterone CNS tumor (prolactinoma or craniopharyngioma), pi-
challenge (see Figure 3–11), serum levels of estradiol, tuitary infarction from postpartum hemorrhage or
134 / CHAPTER 3

sickle cell anemia, uterine synechiae, or chronic disease. orrhea accounts for 80% of cases of adolescent dysmen-
Further evaluation may be necessary. orrhea and most often affects women younger than age
If signs of virilization are present (see Figure 3–10), 25 years.
determining levels of free testosterone, 17-hydroxy- Pelvic examination is normal in females with pri-
progesterone, and dehydroepiandrosterone sulfate mary dysmenorrhea. The pelvic examination has diag-
(DHEAS) will help to distinguish PCOS from adrenal nostic benefits and provides an opportunity to educate
causes of virilization and amenorrhea. Although eleva- and reassure the patient about her normal reproductive
tion of testosterone and DHEAS may occur in patients function. However, if the patient has never been sexu-
with PCOS, the elevation is not as dramatic as with an- ally active and the history is consistent with primary
drogen-producing adrenal or ovarian tumors, adrenal dysmenorrhea, a trial of a nonsteroidal anti-inflamma-
hyperplasia, or Cushing syndrome. Endocrinologic tory drug (NSAID) is justified. Patients should be in-
consultation will assist in differentiating the cause of structed to begin NSAIDs at the first sign of menses or
significantly elevated androgens. dysmenorrhea and continue them for 2–3 days. Rec-
PCOS is a spectrum of disorders accompanied by ommended doses are ibuprofen 400–800 mg every
symptoms of obesity, insulin resistance, hirsutism, 6 hours or naproxen (220–550 mg) twice a day. If the
acne, oligomenorrhea, and infertility. PCOS is very patient does not respond to NSAIDs, oral contraceptive
common, with a prevalence estimated at 5–10%. Al- pills are an effective treatment for primary dysmenor-
though a classic LH:FSH ratio of greater than 2.5:1 is rhea. If patients do not respond to either of these treat-
described in PCOS, up to 40% of patients do not have ments, secondary dysmenorrhea is more likely and a
elevated LH levels. Because of insufficient FSH, an- pelvic examination is indicated.
drostenedione cannot be converted to estradiol in the Secondary dysmenorrhea is menstrual pain due to
ovarian follicle, and anovulation and production of ex- an underlying pelvic lesion (see Table 3–9). Although
cess androgens result. Thus another term for PCOS is uncommon in adolescents, when present it is most
functional hyperandrogenic anovulation. often due to infection or endometriosis. In one study of
Oral contraceptive pills containing a low androgenic adolescent females with chronic pelvic pain, more than
progestin (desogestrel or norgestimate) such as Desogen 40% who had not received a definitive diagnosis by the
or Ortho Tri-Cyclen help to regulate menses and im- third visit were found to have endometriosis.
prove acne and hirsutism. Patients who do not wish to The clinician evaluating a patient with secondary
take an oral contraceptive pill can be given proges- dysmenorrhea should take a sexual history and conduct
terone, 10 mg daily, for the first 10 days of each month a pelvic examination even if the patient is not sexually
to allow withdrawal flow; however, this treatment does active. Testing for gonorrhea and Chlamydia, a CBC
not suppress ovarian androgen production. Hirsute pa- and ESR, and a pregnancy test should be done. Gyne-
tients should have a lipid profile checked, because cologic consultation is indicated to look for en-
PCOS patients have an increased risk of dyslipidemias. dometriosis or congenital problems by ultrasonography
OCPs may reduce terminal hair growth, but antiandro- or laparoscopy. Treatment depends on the cause (see
gens such as spironolactone reduce the growth and di- Table 3–9).
ameter of terminal hair and may be useful for more se-
vere hirsutism. Weight loss in obese patients helps to
suppress ovarian androgen production. Insulin sensitiz- 3. Dysfunctional Uterine Bleeding
ing medications, such as metformin, have been shown Dysfunctional uterine bleeding may consist of menor-
in recent studies to improve menstrual regularities in rhagia (normal intervals with excessive flow) or metror-
adolescents with PCOS. rhagia (irregular intervals with excessive flow). It results
when an endometrium that has proliferated under un-
2. Dysmenorrhea opposed estrogen stimulation finally begins to slough,
but does so incompletely, causing irregular, painless
Dysmenorrhea is the most common gynecologic com- bleeding. The unopposed estrogen stimulation occurs
plaint of adolescent girls, with an incidence of about during anovulatory cycles, common in younger adoles-
80% by age 18 years. Yet many teenage girls do not cents who have not been menstruating for long. Anovu-
seek help from a physician, relying instead on female lation may also occur in older adolescents during times
relatives, friends, and the media for advice. Therefore, of stress or illness (Figure 3–12).
the physician should ask about menstrual cramps when
taking a review of systems. Clinical Findings
Dysmenorrhea can be divided into primary and sec-
ondary dysmenorrhea on the basis of whether underly- Typically, the adolescent has had several years of regular
ing pelvic disease exists (Table 3–9). Primary dysmen- cycles and then begins to have menses every 2 weeks, or
Table 3–9. Dysmenorrhea in the adolescent.

Primary Dysmenorrhea—no pelvic pathology

Etiology Onset and Duration Symptoms Pelvic Exam Treatment
Primary Excessive amount of Begins with onset of Lower abdominal Normal. May wait to Mild—heating
prostaglandin F2α, flow or just prior cramps radiating examine if never pad, warm
which attaches to and lasts 1–2 d. to lower back and sexually active baths, nonpre-
myometrium, Does not start until thighs. Associated and history is scription
causing uterine 6–18 mos after nausea, vomiting, consistent with analgesics.
contractions, hy- menarche, when diarrhea, and primary dys- Moderate to
poxia, and ischemia. cycles become urinary frequency menorrhea. severe—prosta-
Also, directly ovulatory. also due to excess glandin inhibi-
sensitizes pain prostaglandins. tors at onset
receptors. of flow or
pain. Consider
oral contra-
ceptives.
Secondary Dysmenorrhea—underlying pathology present. (Always perform pelvic exam if secondary dysmenorrhea suspected or patient is
sexually active. Tests for Chlamydia and gonorrhea, CBC, and ESR should be obtained.)
Infection Most often due to a Recent onset of Pelvic cramps, Mucopurulent or Appropriate
sexually trans- pelvic cramps. excessive bleed- purulent dis- antibiotics.
mitted disease ing, intermenstrual charge from cer-
such as chlamydia spotting or vag- vical os, cervical
or gonorrhea. inal discharge. friability, cervical
motion tenderness,
adnexal tender-
ness, positive
test for STI.
Endometriosis Aberrant implants of Generally starts Pelvic pain, may Two thirds are Hormonal sup-
endometrial tissue more than occur intermen- tender on exam, pression by
in pelvis or 2 y after strually. especially during oral contracep-
abdomen; may menarche. late luteal phase. tives or dana-
result from reflux. zol. Surgery
may be neces-
sary for exten-
sive disease.
Complication Spontaneous Acute onset. Pelvic cramps Positive HCG, Immediate
of pregnancy abortion, ectopic associated with a enlarged uterus gynecologic
pregnancy. delay in menses. or adnexal mass. consult.
Congenital Transverse vaginal Onset at menarche. Pelvic cramps. Underlying congen- Gynecologic con-
anomalies septum, septate ital anomaly may sult for ultra-
uterus, or cervi- be apparent. May sound, hyster-
cal stenosis. require exam oscopy, or
under anesthesia. laparoscopy.
IUD Increased uterine Onset after place- Pelvic cramps, Normal, or see Prostaglandin
contractions, or ment of IUD or heavy menstrual infection earlier. inhibitors of
increased risk for acutely if due to bleeding, may mefenamic
pelvic infection. infection. have vaginal dis- acid may be
charge. drug of choice
because they
also reduce
flow. Appro-
priate antibiot-
ics and consi-
der removal of
IUD if infection
is present.
Pelvic Previous abdominal Delayed onset after Abdominal pain, Variable. Surgery. Con-
adhesions surgery or pelvic surgery or PID. may or may not sider a trial of
inflammatory be associated with tricyclic anti-
disease. menstrual cycles; depressants.
possible alteration
in bowel pattern.
CBC = complete blood count; ESR = erythrocyte sedimentation rate; HCG = human chorionic gonadotropin; STI = sexually transmitted infection;
IUD = intrauterine device; PID = pelvic inflammatory disease.
135
136 / CHAPTER 3

Patient with DYSFUNCTIONAL UTERINE BLEEDING

A History CBC with differential and platelets

Reticulocyte count
B Physical Examination Consider:
Prothrombin time, partial
thromboplastin time,
Identify: von Willebrand’s studies
Coagulation disorder Testing (wet prep,
Thyroid disorder Gonorrhea and
Ectopic pregnancy Chlamydia)
Threatened abortion Thyroid function tests
Cervicitis Pregnancy test
Ultrasonography

C Assess degree of illness

Mild (Hgb > 12) Moderate (Hgb 9–12) Severe (Hgb < 9)

Give iron E Iron supplement Hospitalize if hemodynamically

supplement unstable
D (OCPs if Stabilize circulation
sexually active) Consider:
Blood transfusion

Follow in 2 months
Gynecology consultation
Consider:
F Premarin IV with
Give reassurance
high-dose combination OCP

Good response Poor response

If not currently bleeding If currently bleeding

Ultrasonography
Monophasic Monophasic Taper high-dose OCP,
Consider:
low-dose OCP low-dose OCP bid— and continue one cycle
Dilatation and
one/day x 3–6 months qid, taper over 21 days Start iron supplement
curettage

Repeat Hgb 6 weeks Switch to low-dose

OCP after 1 month x
3–6 months

Follow monthly

Continue iron supplement for

D 6–8 weeks after anemia resolves

Figure 3–12. Evaluation of dysfunctional uterine bleeding. CBC = complete blood count, Hgb = hemoglobin, OCP
= oral contraceptive pills.
 ADOLESCENCE / 137

complains of bleeding for 2–3 weeks after 2–3 months 4. Mittelschmerz

of amenorrhea. A history of painless, irregular periods
at intervals of less than 3 weeks may also be elicited. Mittelschmerz is midcycle pain caused by irritation of
Bleeding for more than 10 days should be considered the peritoneum due to spillage of fluid from the rup-
abnormal. Dysfunctional uterine bleeding must be con- tured follicular cyst at the time of ovulation. The pa-
sidered a diagnosis of exclusion (Table 3–10). tient presents with a history of midcycle, unilateral dull
or aching abdominal pain lasting a few minutes to as
long as 8 hours. This pain rarely mimics the abdominal
Management findings of acute appendicitis, torsion or rupture of an
A pregnancy test and pelvic examination with appropri- ovarian cyst, or ectopic pregnancy. The patient should
ate tests for sexually transmitted infections should be be reassured and treated symptomatically. If the find-
performed in sexually active patients. A CBC, including ings are severe enough to warrant consideration of the
a platelet count, should be obtained. The history and previously mentioned diagnoses, laparoscopy may be
physical findings may suggest the need for additional done.
coagulation or hormonal studies. Coagulation studies
should be done if the patient presents with severe ane- 5. Premenstrual Syndrome
mia, especially within 1 year after menarche. Manage-
ment depends on the severity of the problem (Table Premenstrual syndrome (PMS) refers to a cluster of
3–11). It is important to treat for a minimum of physical and psychological symptoms that are tempo-
3–4 months to progressively reduce the endometrium rally related to the luteal phase of the menstrual cycle
to baseline thickness. and are alleviated by the onset of menses. PMS should
be distinguished from major depression, idiopathic
cyclic edema, fibromyalgia, chronic fatigue syndrome,
and psychosomatic disorders. This may be difficult be-
cause of the diversity of symptoms ascribed to PMS and
the variability from month to month in the same pa-
Table 3–10. Differential diagnosis of tient. Premenstrual behavioral symptoms most com-
dysfunctional uterine bleeding in adolescents. monly cited include emotional lability, anxiety, depres-
sion, irritability, impulsivity, hostility, and impaired
Anovulation social function. Physical symptoms include bloating,
Sexually transmitted infections breast tenderness, fatigue, and appetite changes. Previ-
Cervicitis ously thought to be a disorder limited to adult women,
Pelvic inflammatory disease studies indicate that adolescents also experience pre-
Pregnancy complications menstrual symptoms. Although a number of causes
Ectopic pregnancy have been proposed (progesterone deficiency, hyper-
Spontaneous abortion prolactinemia, estrogen excess or imbalance of the es-
Bleeding disorders trogen–progesterone ratio, vitamin B12 deficiency, fluid
von Willebrand disease retention, low levels of endorphins and prostaglandins,
Thrombocytopenia
hypoglycemia, psychosomatic factors), none has been
Coagulopathy
Endocrine disorders
proven. Hormones may play a role; women who have
Hypothyroidism undergone hysterectomy but not oophorectomy may
Hyperprolactinemia have cyclic symptoms resembling PMS, whereas post-
Adrenal hyperplasia menopausal women have no such symptoms.
Polycystic ovary syndrome Several treatments have been advocated but are
Anatomical abnormalities without consistent benefits. OCPs or NSAIDs may be
Uterine fibroids beneficial for some women. Sertraline (50–100 mg) has
Trauma been shown to be significantly better than placebo for
Foreign body treatment of premenstrual dysphoria.
Chronic illness
Malignancy
Leukemia 6. Ovarian Cysts
Carcinoma Functional cysts account for 20–50% of ovarian tu-
Drugs mors in adolescents and are a result of the normal phys-
Birth control pills iologic process of ovulation. They may be asympto-
Depo-Provera
matic or may cause menstrual irregularity, constipation,
138 / CHAPTER 3

Table 3–11. Management of dysfunctional uterine bleeding.a

Mild Moderate Severe

Hgb > 12 g/dL Hgb 9–12 g/dL Hgb < 9 g/dL (or dropping); orthostatic
symptoms and signs
Acute treatment Menstrual calendar Monophasic oral contracep- Fluids, blood transfusion as needed,
Iron supplementation tive pills up to four pills per admit to hospital if Hgb < 7 or
NSAID with menses may day and taper over 2–3 patient is hemodynamically unstable
help reduce flow wk; may need antiemetic. For hemostasis, consider: conju-
Consider oral contracep- Bleeding should stop gated estrogens (Premarin), 25 mg
tive pills if patient is in a few days. Begin ta- IV every 4–6 h for 24 h or until
sexually active and pering dose 2–3 d after bleeding stops. Provide antiemetic
desires contraception bleeding stops. Expect medication.
withdrawal flow a few Then: oral contraceptive pills (1/50)
days after last dose. cycle:
4 pills/d for 4 d
3 pills/d for 4 d
2 pills/d for 17 d
withdrawal bleeding for 7 db
Long-term management Monitor menstrual calendar Cycle with either: Next: Oral contraceptive pills cycle
and Hgb (1) Medroxyprogesterone (using 28-d packs) for 3 mos
Follow-up in 2–3 mos acetate, 10 mg PO daily Begin the Sunday after withdrawal
for 10 d starting on day bleeding begins. Length of use
14 of each cycle for dependent on resolution of
3–6 mos, or anemia.
(2) Oral contraceptive pills Monitor hemoglobin
for 3–6 mos begin- Follow-up within 2–3 wks and
ning the Sunday after every 3 mos
withdrawal bleeding
starts.
Provide iron supplementation.
Monitor Hgb
Follow-up within 2–3 wk
and every 3 mos
a
Diagnosis: Prolonged (> 8 d) painless menses; heavy flow (> 6 tampons/pads per day); short cycles (< 21 d); no cause found.
b
This schedule will use three 21-d packages.
Hgb = hemoglobin; PO = by mouth; NSAID = nonsteroidal anti-inflammatory drug.
Modified from Blythe M: Common menstrual problems. Part 3. Abnormal uterine bleeding. Adolescent Health Update 1992;4:1.

or urinary frequency. Functional cysts, unless large, commonly and may be 5–10 cm in diameter. The pa-
rarely cause abdominal pain; however, torsion or hem- tient may have associated amenorrhea or, as the cyst be-
orrhage of an ovarian cyst may present as an acute ab- comes atretic, heavy vaginal bleeding. The patient may
domen. Follicular cysts account for the majority of be monitored for 3 months but should have a la-
ovarian cysts. They are produced every cycle but occa- paroscopy if the cyst is larger than 5 cm, does not re-
sionally are not resorbed. Follicular cysts are unilateral, solve within 2 months, or if there is pain or bleeding
usually not larger than 4 cm in diameter, and resolve from the cyst.
spontaneously. If the patient is asymptomatic, she can
be reexamined monthly. The patient should be referred
to a gynecologist for laparoscopy if she is premenar-
cheal, if the cyst has a solid component or is larger than Dickerson LM et al: Premenstrual syndrome. Am Fam Physician
5 cm by ultrasonography, if she has symptoms or signs 2003;67(8):1743 [PMID: 12725453].
suggestive of hemorrhage or torsion, or if the cyst Slap GB: Menstrual disorders in adolescence. Best Pract Res Clin
fails to regress within 2 months. Luteal cysts occur less Obstet Gynaecol 2003;17(1):75 [PMID: 12758227].
 ADOLESCENCE / 139

CONTRACEPTION Table 3–12. Emergency postcoital

contraception regimens.
According to the Youth Risk Behavior Survey, by 12th
grade 60.5% of adolescents in 2001 had had sexual in-
tercourse. This percentage had decreased from 66.7 in Each Dose
1991. For female adolescents, reported use of a condom Pill Dosage Achieves:
at last intercourse increased from 38% in 1991 to Plan Ba Two tablets orally Levonorgestrel 1.5 mg
51.3% in 2001. For male adolescents, this percentage b
increased from 54.5% to 65.1%. However, the percent- Preven Two tablets orally, Levonorgestrel 0.5 mg
repeat in 12 h
age of adolescents reporting use of alcohol or drugs be-
fore last intercourse increased 18% between 1991 and Nordetteb Four tablets orally and Levonorgestrel 0.6 mg
2001. repeat in 12 h
Lo-Ovralb Four tablets orally and Norgestrel 1.2 mg
Abstinence & Decision Making repeat in 12 h
Alesseb Five pink pills orally Levonorgestrel 0.5 mg
Many adolescents have given little thought to how they
and repeat in 12 h
feel about their developing sexuality or how they will
handle sexual situations. By talking with teenagers Triphasilb Four yellow pills orally Levonorgestrel 0.5 mg
about sexual intercourse and its implications, and alter- and repeat in 12 h
natives to intercourse, providers can help teens make a
Both doses can be given at the same time.
informed decisions before they find themselves with an b
An antiemetic drug taken 30 minutes before the dose may help
unplanned pregnancy or a sexually transmitted infec- reduce nausea.
tion.
If an adolescent chooses to remain abstinent, the
clinician should reinforce that decision. Encouraging
adolescents to use contraception when they do engage combined estrogen/progesterone product marketed
in sexual intercourse does not lead to higher rates of specifically for EC. If these methods are not available,
sexual activity. Another approach to decreasing teen certain combined OCPs can be used for EC. It is im-
pregnancy is to educate adolescent males on the impor- portant to note that the newer progestin-containing
tance of hormonal contraception and emergency con- contraceptives are not approved for EC. A follow-up
traception for their partners, in addition to condom appointment should be held in 2–3 weeks, to test for
use. The teen pregnancy, birth, and abortion rates are pregnancy if menses have not occurred, to screen for
higher in the United States than in any other developed STI if indicated, and to counsel regarding contraceptive
country, despite similar rates of sexual experience. use.

Emergency Contraception Condoms & Spermicides

A discussion of emergency contraception (EC), which The use of condoms has gained popularity as a result of
could potentially prevent 50–90% of unintended preg- the educational and marketing efforts driven by the ac-
nancies and elective abortions, should be part of antici- quired immunodeficiency syndrome (AIDS) epidemic.
patory guidance given to both female and male Condom use has increased over the past several
teenagers. Indications for EC include unprotected in- decades. Regardless of whether another method is used,
tercourse within the past 120 hours (5 days), condom all sexually active adolescents should be counseled to
breakage, more than two missed oral contraceptive use condoms. Condoms offer protection against STIs
pills, and greater than 14 weeks since the last Depo- by decreasing the transmission of gonorrhea, Chlamy-
Provera injection. The pregnancy rate after EC is 1.8%, dia, syphilis, herpes simplex, hepatitis, and human im-
compared with 6.8% without such intervention. (See munodeficiency virus (HIV). Spermicides containing
Table 3–12 for dosages.) EC works best within nonoxynol-9 are no longer recommended, as recent evi-
24 hours of intercourse but can be taken up to dence has suggested that repeated use of spermicide
120 hours afterward. It should be verified that other in- may increase transmission of HIV. Aside from the di-
stances of unprotected intercourse beyond 120 hours aphragm and cervical cap, barrier methods do not re-
have not occurred. The only contraindication to the use quire a medical visit or prescription and are widely
of EC is pregnancy. Plan B is a progestin-only method available. The polyurethane vaginal pouch, or female
that causes significantly less nausea and vomiting than condom, is also available. Although it has pregnancy
combined estrogen/progesterone methods. Preven is a and STI prevention properties similar to those of the
140 / CHAPTER 3

male condom, its higher cost and greater difficulty of membering to take a pill every day, as compliance is in-
insertion make it less appealing to adolescents. creased. The failure rate for the patch is reported to be
1%.
Oral Contraceptives B. PROGESTIN-ONLY PILLS
OCPs have a three-pronged mechanism of action: Progestin-only pills contain no estrogen. Their chief
(1) suppression of ovulation; (2) thickening of the cer- use is in women who experience unacceptable estrogen-
vical mucus, thereby making sperm penetration more related side effects with combination OCPs or who
difficult; and (3) atrophy of the endometrium, which have a contraindication to estrogen-containing pills.
diminishes the chance of implantation. The latter two Their lack of estrogen, however, is also responsible for
actions are progestin effects. the main side effect, less predictable menstrual patterns.
For this reason, progestin-only pills are not often ap-
A. COMBINATION ORAL AND CUTANEOUS propriate for adolescents. Their mechanism of action
CONTRACEPTIVES relies on the progestin-mediated actions, and ovulation
Combination OCPs contain both estrogen and prog- is suppressed in only 15–40% of cycles.
estin. Ethinyl estradiol is the estrogen currently used in
nearly all OCPs in the United States. A number of C. INDICATIONS AND CONTRAINDICATIONS
progestins are used in OCPs and differ in their estro- Combined OCPs may be the method of choice for sex-
genic, antiestrogenic, and androgenic effects. As estro- ually active adolescents who frequently have unplanned
gen doses decreased in OCPs, the androgenic side ef- intercourse; however, the patient must be able to com-
fects of progestins became more apparent, leading to ply with a daily dosing regimen. Most states allow
the development of two progestins (desogestrel and OCPs to be prescribed to minors confidentially. Ide-
norgestimate) with lower androgenic potential. Ortho ally, it is best to wait until 6–12 regular menstrual cy-
Tri-Cyclen is being advertised as a treatment for acne. cles have occurred before beginning hormonal contra-
All of the lower androgenic pills improve acne and may ception; however, if the teenager is already sexually
especially benefit patients with polycystic ovary syn- active, the medical and social risks of pregnancy out-
drome. Reports of increased risk of thromboembolism weigh the risks of hormonal contraception.
associated with the newer progestins are likely related to OCPs or the contraceptive patch may also be used
an excess of first-time users among desogestrel patients. to treat dysmenorrhea, menorrhagia, dysfunctional
Factor V Leiden has been identified as a risk factor for uterine bleeding, and acne (see previous discussion).
venous thrombosis; 5% of patients of European ances- Contraindications to combined OCPs or the contra-
try are carriers of factor V Leiden. Carriers have a 30- to ceptive patch can be categorized as absolute and relative
50-fold increased risk for thrombosis. Testing family (Table 3–13). When use of estrogenic agents is con-
members with a history of venous thrombosis for factor traindicated, progestin-only pills and Depo-Provera are
V Leiden and other conditions such as the prothrombin alternatives.
gene mutation, protein C and S, and antithrombin III
before prescribing estrogen-containing OCPs to the D. BEGINNING BIRTH CONTROL PILLS OR THE
adolescent may prevent these complications. OCPs CONTRACEPTIVE PATCH AND FOLLOW-UP
have many noncontraceptive benefits, including im- Before a patient begins taking OCPs or the patch, a
provement of dysmenorrhea, acne, and PMS; suppres- careful menstrual history, medical history, and family
sion of ovarian and breast cysts; and lower risk of ane- medical history should be taken. In addition, baseline
mia, pelvic inflammatory disease, and ectopic weight and blood pressure should be established; breast
pregnancy. A pill containing 30–35 mg of ethinyl estra- and pelvic examination should be performed; and spec-
diol with norgestimate, desogestrel, or 0.5 mg norethin- imens for urinalysis, Pap smear, and gonorrhea and
drone is recommended for adolescents beginning Chlamydia testing should be obtained. If patients have
OCPs. not yet initiated intercourse, pelvic examination can be
Ortho Evra is a newly released combined estrogen/ deferred until after intercourse is initiated. If time con-
progesterone patch, which is worn 3 weeks out of every straints are present and a patient has no symptoms sug-
4. It releases 150 µg of norelgestromin and 20 µg of gesting an STI, OCPs or the patch may be started and a
ethinyl estradiol per day. Side effects are similar to pelvic exam scheduled as soon as possible.
those of combined OCPs. Five percent of patients re- If the teen has no contraindications (see Table
port having a patch come off. Two percent report skin 3–13), she may begin her first pack of pills or the patch
irritation. Efficacy may be reduced in patients weighing with her next menstrual period (either the first Sunday
more than 200 pounds. The patch is an attractive alter- after flow begins or the first day of flow, depending on
native to OCPs for adolescents who have difficulty re- the brand). A low-dose monophasic combined oral
 ADOLESCENCE / 141

Table 3–13. Contraindications to combined birth Table 3–14. Noncontraceptive health benefits
control pills. of oral contraceptive pills.

Absolute contraindications Protection against life-threatening conditions

Pregnancy Ovarian cancer
Lactation (wait 6 wk postpartum) Endometrial cancer
History of thrombophlebitis, thromboembolic disorder, Pelvic inflammatory disease
cerebrovascular disease, or ischemic heart disease Ectopic pregnancy
Structural heart disease complicated by endocarditis, atrial Morbidity and mortality due to unintended pregnancies
fibrillation, or pulmonary hypertension
Breast cancer Alleviate conditions affecting quality of life
Severe migraine headaches with neurologic changes Iron deficiency anemia
(numbness, weakness) Benign breast disease
History of benign or malignant liver tumor, active hepatitis Dysmenorrhea
or severe cirrhosis Irregular cycles
Severe hypertension SBP > 160 mmHg or DBP > 100 mmHg Functional ovarian cysts
Major surgery with prolonged immobilization or surgery on Premenstrual syndrome
legs or pelvis Improved acne

Relative contraindications Mounting evidence

Recent pregnancy (wait 3 wk postpartum) Improved bone density
Lactation (6 wk–6 mos) OCPs may decrease milk supply
Undiagnosed vaginal bleeding
Active gallbladder disease
Use of drugs that affect liver enzymes (rifampin, griseoful-
vin, phenytoin, carbamazepine, barbiturates) 3–15). Changes are most often made for persistent
breakthrough bleeding not related to missed pills.
SBP = systolic blood pressure; DBP = diastolic blood pressure;
OCPs = oral contraceptives.
Reprinted with permission from Hatcher RA et al: Contraceptive Injectable and Implantable Hormonal
Technology, 17th ed. Ardent Media, 1998. Contraceptives
The depot form of medroxyprogesterone acetate
(DMPA), or Depo-Provera, is a long-acting injectable
contraceptive or a triphasic pill of low androgenic pro- progestational contraceptive. It is given as a deep intra-
file is used for those without contraindications to use of muscular injection of 150 mg into the gluteal or deltoid
estrogen. With adolescents, it is wise to use 28-day muscle every 12 weeks. The first injection should be
packs rather than 21-day packs to reduce the chance of given within the first 5 days of the menstrual cycle to
missing pills. The patient should be instructed on the ensure immediate contraceptive protection. Patients
use of her pills and on the possible risks and side effects more than 1 week late for their injection should have
and their warning signs. To ensure protection, she two pregnancy tests 2 weeks apart before restarting
should use a back-up method, such as condoms, for the DMPA, unless they have not been sexually active since
first 2 weeks. In addition, the patient should be advised missing the DMPA injection. DMPA works chiefly by
to use condoms at every intercourse to prevent STIs. A blocking the LH surge, thereby suppressing ovulation,
follow-up visit every 3 months for the first year may but it also thickens cervical mucus and alters the en-
improve compliance, because teenagers often discon- dometrium to inhibit implantation. With a failure rate
tinue birth control pills because of nonmedical reasons of less than 0.3%, minimal compliance issues, long-act-
or minor side effects. Teenagers may need reassurance ing nature, reversibility, lack of interference with inter-
about the safety of birth control pills and their added course, and lack of estrogen-related side effects, it may
benefits (Table 3–14). be an attractive contraceptive for many adolescents. Pa-
tients should be warned about unpredictable menstrual
patterns, the possibility of weight gain or mood
E. MANAGEMENT OF SIDE EFFECTS changes, and the potential for decreased bone density,
A different type of combined oral contraceptive should which remains under investigation. DMPA may reduce
be tried if a patient has a persistent minor side effect for intravascular sickling and increase hemoglobin and red
more than the first 2–3 months. Adjustments should be cell survival in patients with sickle cell disease. More-
made on the basis of hormonal effects desired (Table over, DMPA may be the preferred method for patients
142 / CHAPTER 3

Table 3–15. Estrogenic, progestogenic, and androgenic effects of oral contraceptive pills.

Estrogenic Effects Progestogenic Effects Androgenic Effects

Nausea Both the estrogenic and the progestational All low-dose combined pills suppress a woman’s
Increased breast size (duc- components of oral contraceptives may production of testosterone, which has a bene-
tal and fatty tissue) contribute to the development of the ficial effect on acne, oily skin, and hirsutism.
Cyclic weight gain due to following adverse effects: The progestin component may have andro-
fluid retention Breast tenderness genic as well as progestational effects:
Leukorrhea Headaches Increased appetite and weight gain
Cervical eversion or ectopy Hypertension Depression, fatigue
Hypertension Myocardial infarction Decreased libido and/or enjoyment of inter-
Rise in cholesterol concen- (rare) course
tration in gallbladder bile Acne, oily skin
Growth of leiomyoma Increased breast tenderness or breast size
Telangiectasia Increased LDL cholesterol levels
Hepatocellular adenomas Decreased HDL cholesterol levels
or hepatocellular carcinoma Decreased carbohydrate tolerance; increased
(rare) insulin resistance
Cerebrovascular accidents Pruritus
(rare)
Thromboembolic compli-
cations including pul-
monary emboli (rare)
Stimulation of breast neo-
plasia (exceedingly rare)
(Most pills with less than
50 µg of ethinyl estradiol
do not produce troublesome
estrogen-mediated side
effects or complications.)
LDL = low-density lipoprotein; HDL = high density lipoprotein.
Reproduced with permission from Hatcher RA et al: Contraceptive Technology, 17th ed. Ardent Media, 1998.

with seizure disorders, because it has been found to re- bleeding, breast pain, menorrhagia, and dysmenorrhea.
duce the number of seizures in some patients. DMPA Efficacy is excellent, with a reported failure rate of
may also be helpful for adolescents with von Wille- 0.2%. Monthly injections may make this method less
brand disease, since amenorrhea (which decreases blood attractive for adolescents.
loss) is a common effect of DMPA. Studies have shown The levonorgestrel-containing nonbiodegradable
no increased risk of liver cancer, breast cancer, or inva- subdermal implant (Norplant System), which is in-
sive squamous cell cervical cancer among users of serted under the skin of the upper arm using a trocar, is
DMPA, and the risk of endometrial and ovarian can- effective for 5 years, with pregnancy rates ranging from
cers is reduced. 0.04 per 100 woman-years in the first year of use to
Lunelle is a monthly combined estrogen/proges- 1.1 per 100 woman-years in the fifth year. It acts
terone injectable contraceptive that was approved in the through ovulation inhibition and thickening of the cer-
United States in 2000; however, the manufacturer re- vical mucus. Menstrual irregularities (including pro-
cently discontinued production of Lunelle. There is po- longed bleeding, intermenstrual spotting, and amenor-
tential for another company to produce this contracep- rhea) are the most common side effects, although
tive in the future. Lunelle contains 5 mg of estradiol headache, acne, weight gain or loss, and depression may
cypionate and 25 mg of medroxyprogesterone acetate. occur. Its ease of use, lack of compliance issues, high ef-
Its advantages over progestin-only injectable contracep- ficacy, and long-term protection make the subdermal
tives include faster return to fertility and less amenor- implant an ideal contraceptive for adolescents who can
rhea, which theoretically should lower the risk of osteo- tolerate the menstrual irregularities. In 2000, Norplant
porosis. Side effects include weight gain, irregular was removed from the market because of concern over
 ADOLESCENCE / 143

decreased efficacy in the fifth year in some lots. No im- Petitti DB: Clinical practice: Combination estrogen–progestin oral
plantable contraceptive methods are currently marketed contraceptives. N Engl J Med 2003;349(15):1443 [PMID:
14534338].
in the United States.
MMWR: Trends in sexual risk behaviors among high school stu-
dents—United States, 1991–2001. MMWR 2002;51(38):
Implantable Contraceptive Methods 856 [PMID: 12363337].
Meirik O et al: Implantable contraceptives for women. Hum Re-
Available Outside of the United States prod Update 2003;9(1):49 [PMID: 12638781].
Implanon is a single implant, effective for 3 years. It
contains etonogestrel. It has been used in Europe and
has a failure rate approaching 0%. Side effects include PREGNANCY
irregular bleeding, headache, nausea, breast pain, and The teen birth rate in the United States has been
depression. Return to fertility is rapid following re- steadily decreasing since the early 1990s, with a historic
moval. Insertion and removal are reportedly signifi- low in 2001. From 1991 to 2001, the birth rate for
cantly easier than Norplant. Other implantable proges- adolescents age 15–19 years decreased from 61.8 to
terones used in other countries include Norplant II and 45.3/1000. Abortions have also decreased over the past
Jadelle (levonorgestrel) and Uniplant and Surplant decade. In 1997, 16.3% of pregnancies in 15- to
(nomegestrol acetate). 17-year-olds ended in abortion, as did 37.5% of preg-
nancies in 18- to 19-year-olds. Despite decreasing rates,
the United States still has the highest adolescent preg-
Contraceptive Vaginal Ring nancy rate of any developed country. Over
The Nuva Ring is a vaginal ring that releases 15 µg of 800,000 adolescents younger than age 19 become preg-
ethinyl estradiol and 120 µg of etonogestrel per day. nant every year. Young maternal age and associated ma-
The ring is placed inside the vagina for 3 weeks, fol- ternal risk factors have been linked to adverse neonatal
lowed by 1 week without the ring to allow for with- outcome, including higher rates of low-birth-weight ba-
drawal bleeding. A new ring is inserted each month. bies (< 2500 g) and neonatal mortality. The psychoso-
Failure rate is 1%. Side effects include vaginitis in 5%, cial consequences for the teenage mother and her infant
headache in 6%, and foreign body sensation in 2.5%. are listed in Table 3–16. Teenagers who are pregnant
The vaginal ring is easier to insert correctly than the di- require additional support from their caregivers. Clinics
aphragm. However, like the diaphragm, adolescents are for young mothers may be the best providers.
often reluctant to use contraception requiring insertion
into the vagina.
Presentation
Adolescents may present with delayed or missed menses
Contraceptive Methods Not Usually or may even request a pregnancy test, but often they
Recommended for Teenagers present with an unrelated concern or have a hidden
Adolescents should understand the menstrual cycle and agenda. Because of the high level of denial, they may
be taught that ovulation typically occurs 2 weeks before come in with complaints of abdominal pain, urinary
the next menstrual period and may be difficult to pre- frequency, dizziness, or other nonspecific symptoms
dict. Because teenagers frequently have irregular cycles, and have no concern about pregnancy. A history of
the rhythm, or calendar, method is not effective. Ado- symptoms such as weight gain, engorged breasts, an un-
lescents also need to be taught that withdrawal is not a usually light or mistimed period, and urinary frequency
reliable method of contraception. Diaphragms and cer- may be present. Denial contributes to the delay in seek-
vical caps require professional fitting and skill with in- ing prenatal care. Clinicians need to have a low thresh-
sertion and are not popular among teenagers. Adoles- old for suspicion of pregnancy. If any suspicion exists, a
cents who have never been pregnant or who engage in urine pregnancy test should be obtained.
behaviors that carry a risk of STIs should not use an in-
trauterine device. Sterilization is rarely appropriate for
adolescents. Diagnosis
The history and physical examination may assist in
Gallo MF et al: Skin patch and vaginal ring versus combined oral
making the diagnosis. Bluish coloring and softening of
contraceptives for contraception. Cochrane Database Syst the cervix may be noted on speculum examination. The
Rev 2003;(1):CD003552 [PMID: 12535478]. uterine fundus may be palpable on abdominal examina-
Greydanus DE et al: Contraception in the adolescent: An update. tion if sufficient time has elapsed. If uterine size on bi-
Pediatrics. 2001;107(3):562 [PMID: 11230601]. manual examination does not correspond to dates, one
144 / CHAPTER 3

Table 3–16. Psychosocial consequences accurate by the expected date of the missed period in al-
of pregnancy for the adolescent mother most 100% of patients. Serum radioimmunoassay is
and her infant. also specific for the β subunit, is accurate within 7 days
after conception, and is helpful in ruling out ectopic
pregnancy or threatened abortion.
Mother Infant
The timing of pregnancy tests is important, because
Increased morbidity related Greater health risks HCG levels rise initially after conception, peak at about
to pregnancy Increased chance of low 60–70 days, then drop to levels not detected by routine
Greater risk of toxemia, birth weight or prema- office slide tests after 16–20 weeks.
anemia, prolonged turity
labor, premature labor Increased risk of infant
Increased chance of mis- death Special Issues in Management
carriages, stillbirths Increased risk of injury When an adolescent presents for pregnancy testing, it is
Increased change of ma- and hospitalization by helpful, before performing the test, to find out what she
ternal mortality age 5 hopes the result will be and what she thinks she will do
Decreased educational Decreased academic
if the test is positive. If she wants to be pregnant and
attainment achievement
Less likely to get high Lower cognitive scores
the test is negative, further counseling about the impli-
school diploma, go to Decreased development cations of teen pregnancy should be offered. Prenatal
college, or graduate Greater chance of being vitamins should be prescribed. For those who do not
Lower occupational attain- behind grade or need- wish to be pregnant, contraception should be discussed,
ment and prestige ing remedial help because teens with a negative pregnancy test have a
Less chance of stable em- Lower chance of ad- high risk of pregnancy within the next 2 years.
ployment (some resolu- vanced academics If the adolescent is pregnant, the physician must dis-
tion over time) Lower academic cuss her support systems and her options with her
Lower job satisfaction aptitude as a teenager (abortion, adoption, raising the baby). Many teenagers
Lower income/wages and perhaps a higher need help in telling and involving their parents. It is
Greater dependence on probability of dropping important to remain available for further assistance
public assistance out of school with decision making. Patients should be informed of
Less stable marital relation- Psychosocial conse- the gestational age and time frames required for the dif-
ships quences ferent options. If the patient knows what she wants to
Higher rates of single Greater risk of behavior do, she should be referred to the appropriate resources.
parenthood problems Because teenagers are often ambivalent about their
Earlier marriage (though Poverty plans and may have a high level of denial, it is prudent
less common than in the Higher probability of to follow up in 1 week to be certain that a decision has
past) living in a nonintact been made. Avoiding a decision reduces the adoles-
Accelerated pace of mar- home while in high
cent’s options and may result in poor pregnancy out-
riage, separation, school
divorce, and remarriage Greater risk of adoles-
comes. Providers can help ensure that the patient ob-
Faster pace of subsequent cent pregnancy tains prenatal care if she has chosen to continue the
childbearing pregnancy. In addition, brief counseling about healthy
High rate of repeat unin- diet; folic acid supplementation (400 µg/d); and avoid-
tended pregnancy ing alcohol, tobacco, and other drugs is helpful.
More births out of mar- Young maternal age, low maternal prepregnancy
riage weight, poor weight gain, delay in prenatal care, and
Closer spacing of births low socioeconomic status contribute to low birth
Larger families weight and poor fetal outcome. The poor nutritional
status of some teenagers; their erratic diets, smoking,
drinking, or substance abuse; and their high incidence
of STIs also play a role. Teenagers are also at greater
must consider ectopic pregnancy, incomplete or missed risk than adult women for pre-eclampsia, eclampsia,
abortion, twin gestation, or inaccurate dates. iron deficiency anemia, cephalopelvic disproportion,
Enzyme-linked immunoassay test kits specific for prolonged labor, premature labor, and maternal death.
the β-HCG subunit and sensitive to less than Early prenatal care and good nutrition can make a dif-
50 mIU/mL of HCG can be performed on urine ference with a number of these problems.
(preferably the first morning-voided specimen, because Because of the high risk of a second unintended
it is more concentrated) in less than 5 minutes and are pregnancy within the next 2 years, postpartum contra-
 ADOLESCENCE / 145

ceptive counseling and follow-up are imperative. Com- 1. Physiologic Leukorrhea

bined OCPs or the contraceptive patch can be started
3 weeks after delivery in adolescents who are not breast Leukorrhea is the normal vaginal discharge that begins
feeding; progestin-only methods can be started imme- around the time of menarche. The discharge is typically
diately postpartum, even in breastfeeding adolescents. clear or whitish, and its consistency may vary according
Pregnancy prevention is the most cost-effective means to cyclic hormonal influences. There should be no
of reducing the consequences of teenage pregnancy. odor. Girls in early adolescence may have concerns
Sexual decision making, contraceptive counseling, and about such a discharge and need reassurance that it is
close follow-up of sexually active adolescents of both normal. This may be a good time to tell girls that there
sexes can make a difference. Adolescents who receive is no need for douching. If a vaginal wet preparation is
sexuality and contraceptive education are not more examined, a few squamous epithelial cells may be re-
likely to have intercourse but are less likely to become vealed, but there should be fewer than five polymor-
pregnant than their counterparts who do not receive phonuclear cells per high-power field.
such instruction.
2. Candidal Vulvovaginitis
Ectopic Pregnancy Candidal vulvovaginitis is caused by yeast (Candida al-
In the United States, 100,000 ectopic pregnancies bicans). It typically occurs after a course of antibiotics,
occur each year, accounting for 2% of pregnancies. after which the normal perineal flora are altered and
Adolescents have the highest mortality rate from ec- yeast is allowed to proliferate. Diabetic patients, those
topic pregnancy, most likely related to delayed entry with compromised immune systems, and those who are
into health care. Risk factors include history of pelvic pregnant or receiving OCPs are more prone to develop
inflammatory disease or chlamydial infection. Concep- candidal infections.
tion while on progestin-only methods of contraceptives
also increases risk of ectopic pregnancy, because of the Clinical Findings
progestin-mediated decrease in tubal motility.
Providers should keep a high level of suspicion with any The patient usually complains of vulvar pruritus or dys-
adolescent presenting with vaginal bleeding and ab- pareunia and a thick vaginal discharge, frequently be-
dominal pain. ginning the week before menses. Examination of the
vulva reveals erythematous mucosa, sometimes with ex-
coriation, and a thick, white, cheesy discharge. The dis-
Abma JC, Sonenstein FL: Sexual activity and contraceptive prac-
tices among teenagers in the United States, 1988 and 1995.
charge may be adherent to the walls of the vagina.
Vital Health Stat 2001;21:1 [PMID: 11478202]. Leukocytes may be seen on a wet preparation, and a
Elfenbein DS et al: Adolescent pregnancy. Pediatr Clin North Am KOH preparation may reveal budding yeast or mycelia.
2003;50(4):781-800, viii [PMID: 12964694]. The vaginal preparations are often not helpful, and the
Hamilton BE et al: Revised birth and fertility rates for the 1990s patient should be treated on the basis of the clinical ex-
and new rates for Hispanic populations, 2000 and 2001: amination. Vaginal culture for yeast is usually unneces-
United States. Natl Vital Stat Rep 2003;51(12):1 [PMID: sary.
12918931].
Treatment
VULVOVAGINITIS
Butoconazole, clotrimazole, miconazole, terconazole, or
Vaginitis may be due to pathogens or to indigenous tioconazole vaginal creams or suppositories designed for
flora after a change in milieu of the vagina. Candidal seven nightly doses are effective in most patients. Flu-
vulvovaginitis and bacterial vaginosis (formerly called conazole (150 mg once orally) is also effective and may
Gardnerella, Haemophilus, or nonspecific vaginitis) may be beneficial on a monthly prophylactic basis for
occur in patients who are not sexually active. These are women with recurring infections. Patients with recur-
examples of indigenous flora that may cause symptoms. rent episodes should be given prophylactic treatment
Bacterial vaginosis, however, is more prevalent in those whenever they take antibiotics. It may be helpful to si-
who are sexually active. In sexually active patients, Tri- multaneously treat the partners of sexually active pa-
chomonas infection or cervicitis due to sexually trans- tients with recurrent candidal infections.
mitted pathogens must be considered (see Chapter 40).
For this reason, appropriate specimens should be taken
from sexually active patients or suspected victims of
3. Bacterial Vaginosis
sexual abuse in order to detect STIs, even if yeast forms Bacterial vaginosis may be caused by any of the indige-
are present or bacterial vaginosis is identified. nous vaginal flora, such as Gardnerella, Bacteroides, Pep-
146 / CHAPTER 3

tococcus, Mycoplasma hominis, lactobacilli, or other testing should be done whenever a sexually active ado-
anaerobes. lescent complains of vaginal discharge even when the
cervix appears normal.
Clinical Findings
Foreign Body Vaginitis
The patient generally complains of a malodorous dis-
charge. On examination, a thin, homogeneous, grayish Foreign bodies (most commonly retained tampons or
white discharge is found adhering to the vaginal wall. A condoms) cause extremely malodorous vaginal dis-
whiff test, in which a drop of KOH is added to a smear charges. Treatment consists of removal, for which ring
of the discharge on a slide, results in the release of forceps may be useful. Further treatment is generally
amines, causing a fishy odor. Wet preparation reveals not necessary.
an abundance of clue cells and small pleomorphic rods.
Allergic or Contact Vaginitis
Treatment
Bubble baths, feminine hygiene sprays, or vaginal con-
Treatment for bacterial vaginosis is with metronidazole traceptive foams or suppositories may cause chemical
(500 mg orally bid for 7 days) or clindamycin (300 mg irritation of the vaginal mucosa. Discontinuing use of
orally bid for 7 days). Topical metronidazole or clin- the offending agent is indicated.
damycin may also be effective. Ampicillin (500 mg
orally four times a day for 7 days) is the alternative for REFERENCES
pregnant patients.
Brook I: Microbiology and management of polymicrobial female
genital tract infections in adolescents. J Pediatr Adolesc Gy-
4. Other Causes Of Vulvovaginitis necol 2002;15(4):217 [PMID: 12459228].
Sexually Transmitted Infections
STIs are a common cause of vaginal discharge in ado-
lescents (see Chapter 40). Chlamydia and gonorrhea
 Substance Abuse 4
Paritosh Kaul, MD, & Catherine Stevens-Simon, MD

The use and abuse of mood-altering substances— for the major classes of substances are presented in Ta-
alcohol, marijuana, opioids, cocaine, amphetamines, bles 4–2 and 4–3.
sedative-hypnotics, hallucinogens, inhalants, nicotine,
anabolic steroids, γ-hydroxybutyrate (GHB), and American Psychiatric Association: Diagnostic and Statistical Manual
3,4-methylenedioxymethamphetamine (ecstasy)—con- of Mental Disorders, 4th ed. Text Revised. American Psychi-
tinues to be a serious public health problem. The short- atric Association, 2000.
and long-term health, social, emotional, legal, and be- Comerci GD, Schwebel R: Substance abuse: An overview. Adoles-
havioral consequences of substance abuse are particu- cent Medicine: State of the Art Reviews 2000;11(1):
larly damaging during childhood and adolescence. Not 79 [PMID: 10640340].
only does early substance use portend chronic, severe DuRant RH et al: The relationship between early age of onset of
polysubstance abuse later in life, but substance use may initial substance use and engaging in multiple health risk be-
haviors among young adolescents. Arch Pediatr Adolesc Med
also compromise physical, cognitive, and psychosocial 1999;153:286 [PMID: 10086407].
aspects of adolescent development if this maladaptive US Department of Health and Human Services. Healthy People
behavior becomes the preferred response to environ- 2010, 2nd ed. With Understanding and Improving Health
mental stressors. and Objectives for Improving Health (2 vols). Washington,
Substance abuse tends to be a chronic, progressive DC: U.S. Government Printing Office, 2000.
disease. The first or initiation stage—from nonuser to
user—is such a common feature of becoming an Amer-
ican adult that many authorities call it normative be- SCOPE OF THE PROBLEM
havior. At this stage, substance use is typically limited The best source of information about the prevalence of
to experimentation with tobacco or alcohol (so-called substance abuse among American children and adoles-
gateway substances). During adolescence, young people cents is the annual Monitoring the Future Study, which
are expected to establish an independent, autonomous tracks health-related behaviors in a sample of 44,000 8th,
identity. They try out a variety of behaviors within the 10th, and 12th graders in about 400 public and private
safety of their family circles and peer groups. This schools across the United States. This study probably un-
process often involves experimentation with psychoac- derstates the magnitude of the problem of substance
tive substances, usually in culturally acceptable circum- abuse because it excludes two of the most abuse-prone
stances. Progression to the second or continuation stage groups of young people—school dropouts and runaways.
of substance abuse is a nonnormative risk behavior with Although the exclusion of these youngsters may mini-
the potential to compromise adolescent development. mize prevalence estimates only moderately for the entire
The American Psychiatric Association criteria listed in population, errors in estimating drug use among sub-
Table 4–1 can be used to judge the severity of sub- groups with high rates of school dropout (eg, urban mi-
stance use that progresses beyond the experimentation nority youths) are thought to be substantial. Data from
stage to substance abuse or substance dependency. this survey and others show that alcohol is the most fre-
Maintenance and progression within a class of sub- quently abused substance in our society. Experimenta-
stances (eg, from beer to liquor) and progression across tion with alcohol typically begins in or before middle
classes of substances (eg, from alcohol to marijuana) school; is more common among boys than girls; and is
represent the third and fourth stages of substance abuse. most common among whites, less common among His-
Individuals at these stages are polysubstance abusers, panics and Native Americans, and least common among
and most manifest one or more of the symptoms of de- blacks and Asians. Over 50% of children consume alco-
pendency listed in Table 4–1. The transition from one hol before high school, and over 90% do so before grad-
stage to the next is typically a cyclic process of regres- uation. Over 25% of eighth graders and over 50% of
sion, cessation, and relapse. Common symptoms and high-school students seen in an average American pedi-
physiologic effects of intoxication (which can occur at atric practice have used alcohol within the last 30 days,
any stage) and withdrawal (a symptom of dependency) and half have consumed five or more drinks on at least
147
Copyright © 2005, 2001, by The McGraw-Hill Companies, Inc. Click here for terms of use.
148 / CHAPTER 4

Table 4–1. Substance abuse and substance dependency.

Diagnostic criteria for substance abuse

A. A maladaptive pattern of substance use leading to clinically significant impairment or distress, as manifested by one or
more of the following occurring within a 12-month period:
1. Recurrent substance use resulting in a failure to fulfill major role obligations at work, school, or home (eg, repeated ab-
sences or poor work performance related to substance use; substance-related absences, suspensions, or expulsions
from school; neglect of children or household).
2. Recurrent substance use in situations in which it is physically hazardous (eg, driving an automobile or operating a ma-
chine when impaired by substance use).
3. Recurrent substance-related legal problems (arrests for substance-related disorderly conduct).
4. Continued substance use despite having persistent or recurrent social or interpersonal problems caused or exacerbated
by the effects of the substance (eg, arguments with spouse about consequences of intoxication, physical fights).
B. The symptoms have never met criteria for substance dependence for this class of substance.
Diagnostic criteria for substance dependency
A maladaptive pattern of substance use, leading to clinically significant impairment or distress, as manifested by three
or more of the following, occurring at any time in the same 12-month period:
1. Tolerance, as defined by either of the following:
a. Need for markedly increased amounts of the substance to achieve intoxication or desired effect.
b. Markedly diminished effect with continued use of the same amount of the substance.
2. Withdrawal, as manifested by either of the following:
a. The characteristic withdrawal syndrome for the substance (criteria A and B of the criteria for withdrawal from the specific
substance).
b. The same (or closely related) substance taken to relieve or avoid withdrawal symptoms.
3. The substance often taken in larger amounts or over a longer period than was intended.
4. There is a persistent desire or unsuccessful efforts to cut down or control substance use.
5. A great deal of time spent in activities necessary to obtain the substance (eg, visiting multiple doctors, driving long dis-
tances), use the substance (chain-smoking), or recover from its effects.
6. Important social, occupational, or recreational activities given up or reduced because of substance use.
7. The substance use is continued despite knowledge of having a persistent or recurrent physical or psychological problem
that is likely to have been caused or exacerbated by the substance (eg, current cocaine use despite recognition of cocaine-
induced depression, or continued drinking despite recognition that an ulcer was made worse by alcohol consumption).
Reprinted, with permission, from the Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Text Revision. Copyright 2000. Ameri-
can Psychiatric Association.

one occasion. Use of tobacco, marijuana, and other 2000. However, use of both drugs showed a decline in
mood-altering substances is less common (Table 4–4). 2002. Overall drug and alcohol use also decreased
Marijuana is the most commonly used illicit drug in the in 2002. Studies indicate that the rise and fall in use of
United States. First experiences with marijuana and the a substance is heralded by changes in the perceived risks
substances listed in Table 4–4 typically occur during and benefits of using the substance. Increased availabil-
middle school and early high school. Initiation of sub- ity has been a major factor in the rising use of anabolic
stance abuse is rare after age 20 years. steroids and ecstasy. The age at initiation of alcohol and
The level of substance abuse among American youth other substance abuse dropped significantly in the early
rose in the 1960s and 1970s, declined in the 1980s, 1990s. Currently, most first-time users are between
reached a nadir in 1990, and rose again in the early and 12 and 14 years of age. Inhalants such as glue and gaso-
mid-1990s, peaking among eighth graders in 1996 (see line are predominantly a choice of younger adolescents.
Table 4–4). Use declined slightly in the late 1990s and This statistic is particularly worrisome because early-
was stable in 2000. Marijuana accounted for most of onset substance use is one of the best predictors of per-
the increased drug use during the 1990s. Table sistent abuse later in life.
4–4 shows that marijuana use is still widespread among
American youth. Use of most other drugs, including
Bachman JG et al: Explaining recent increases in students’ mari-
crack cocaine, declined during the 1990s. The major juana use: Impacts of perceived risks and disapproval,
exception to this encouraging trend has been the in- 1976–1996. Am J Public Health 1998;88:887 [PMID:
creased use of ecstasy and anabolic steroids in 1999 and 9618614].
 SUBSTANCE ABUSE / 149

Table 4–2. Physiologic effects of commonly abused mood-altering substances.1

EYES/PUPILS
Mydriasis Amphetamines, MDMA, or other stimulants, cocaine, glutethimide, jimsonweed, LSD
Withdrawal from alcohol and opioids
Miosis Alcohol, barbiturates, benzodiazepines, opioids, PCP
Nystagmus Alcohol, barbiturates, benzodiazepines, inhalants, PCP
Conjunctival injection LSD, marijuana
Lacrimation Inhalants, LSD. Withdrawal from opioids.
CARDIOVASCULAR
Tachycardia Amphetamines, MDMA, or other stimulants, cocaine, LSD, marijuana, PCP. Withdrawal from alcohol,
barbiturates, benzodiazepines.
Hypertension Amphetamines, MDMA, or other stimulants, cocaine, LSD, marijuana, PCP. Withdrawal from alcohol,
barbiturates, benzodiazepines.
Hypotension Barbiturates, opioids. Orthostatic: marijuana. Withdrawal from depressants.
Arrhythmia Amphetamines, MDMA, or other stimulants, cocaine, inhalants, opioids, PCP
RESPIRATORY
Depression Opioids, depressants, GHB
Pulmonary edema Opioids, stimulants
CORE BODY TEMPERATURE
Elevated Amphetamines, MDMA, or other stimulants, cocaine, PCP. Withdrawal from alcohol, barbiturates,
benzodiazepines, opioids.
Decreased Alcohol, barbiturates, benzodiazepines, opioids, GHB
PERIPHERAL NERVOUS SYSTEM RESPONSE
Hyperreflexia Amphetamines, MDMA, or other stimulants, cocaine, LSD, marijuana, methaqualone, PCP
Withdrawal from alcohol, barbiturates, benzodiazepines
Hyporeflexia Alcohol, barbiturates, benzodiazepines, inhalants, opioids
Tremor Amphetamines or other stimulants, cocaine, LSD
Withdrawal from alcohol, barbiturates, benzodiazepines, cocaine
Ataxia Alcohol, amphetamines, MDMA, or other stimulants, barbiturates, benzodiazepines, inhalants, LSD,
PCP, GHB
CENTRAL NERVOUS SYSTEM RESPONSE
Hyperalertness Amphetamines, MDMA, or other stimulants, cocaine
Sedation, somnolence Alcohol, barbiturates, benzodiazepines, inhalants, marijuana, opioids, GHB
Seizures Alcohol, amphetamines, MDMA, or other stimulants, cocaine, inhalants, methaqualone, opioids
(particularly meperidine, propoxyphene)
Withdrawal from alcohol, barbiturates, benzodiazepines
Hallucinations Amphetamines, MDMA, or other stimulants, cocaine, inhalants, LSD, marijuana, PCP
Withdrawal from alcohol, barbiturates, benzodiazepines
GASTROINTESTINAL
Nausea, vomiting Alcohol, amphetamines or other stimulants, cocaine, inhalants, LSD, opioids, peyote, GHB
Withdrawal from alcohol, barbiturates, benzodiazepines, cocaine, opioids
1
GHB = gamma hydroxybutyrate, LSD = lysergic acid diethylamide, MDMA = methylenedioxymethamphetamine (ecstasy), PCP = phency-
clidine hydrochloride.
Adapted with permission from: Schwartz B, Alderman EM: Substance abuse. Pediatr Rev 1997;18:215.

Dyer JE, Roth B, Hyman BA: Gamma-hydroxybutyrate with- Overview of Key Findings, 2002 (NIH Publication No.
drawal syndrome. Ann Emerg Med 2001;37(2):147 [PMID: 03-5375). Bethesda, MD: National Institute on Drug Abuse.
11174231]. www.monitoringthefuture.org
Gilpin EA, Choi WS, Berry C, et al: How many adolescents start Kurtzman TL, Otsuka KN, Wahl RA: Inhalant abuse by adoles-
smoking each day in the United States? J Adolesc Health cents. J Adolesc Health 2001;28:1616 [PMID: 11226839].
1999;25:248 [PMID: 10505842]. O’Malley PM, Johnston LD: Drinking and driving among US high
Johnston LD, O’Malley PM, Bachman JG: (2003). The Monitoring school seniors, 1984–1997. Am J Public Health
the Future National Survey Results on Adolescent Drug Use: 1999;89:678 [PMID: 10224978].
150 / CHAPTER 4

Table 4–3. Effects of commonly abused mood-altering substances.

Substance Pharmacology Intoxication Withdrawal Chronic Use

Alcohol (ethanol) Depressant; 10 g/drink Legal: 0.05–0.1 g/dL Mild: headache, tremors, Hepatitis, cirrhosis, car-
Drink: 12 oz beer, (varies by state) nausea and vomiting diac disease, Wer-
4 oz wine, 11⁄2 oz Mild: < 0.1 g/dL; disinhibi- (“hangover”) nicke encephalop-
liquor; one drink tion, euphoria, mild Severe: fever, sweaty, athy, Korsakoff
increases blood sedation and impaired seizure, agitation, syndrome
level by approxi- coordination hallucination, hyper-
mately 0.025 g/dL Moderate: 0.1–0.2 g/dL; tension, tachycardia
(varies by weight) impaired mentation Delirium tremens
and judgment, slurred (chronic use)
speech ataxia
Severe: > 0.3 g/dL; con-
fusion, stupor; > 0.4
g/dL; coma, depressed
respiration
Marijuana (cannabis) Delta-9-tetrahydro- Low: euphoria, relaxation, Irritability, disturbed Cough, gynecomastia,
cannabinol (THC); impaired thinking sleep, tremor, nystag- low sperm count, in-
4–6% in marijuana; High: mood changes, mus, anorexia, fertility, amotivational
20–30% in hashish depersonalization, diarrhea, vomiting syndrome, apathy
hallucinations
Toxic: panic, delusions,
paranoia, psychosis
Cocaine Stimulant; releases Hyperalert, increased Drug craving, depres- Nasal septum ulceration,
biogenic amines; energy, confident, in- sion, dysphoria, irrita- epistaxis, lung
concentration varies somnia, anxiety, para- bility, lethargy, trem- damage, intravenous
with preparation noia, dilated pupils, ors, nausea, hunger drug use
and route of admin- tremors, seizures, hy-
istration pertension, arrhythmia,
tachycardia, fever,
dry mouth
Toxic: coma, psychosis,
seizure, myocardial in-
farction, stroke, hyper-
thermia, rhabdomy-
olysis
Opioids (heroin, Depressant; binds Euphoria, sedation, im- Only after > 3 weeks of Intravenous drug use:
morphine, co- central opioid recep- paired thinking, low regular use: drug crav- cellulitis, endocarditis,
deine, metha- tor; variable con- blood pressure, pin- ing, rhinorrhea, lac- embolisms, HIV
done, opium, fen- centrations with sub- point pupil, urinary re- rimation, muscle
tanyl, meperidine, stance tention aches, diarrhea, anx-
propoxyphene) Toxic: hypotension, ar- iety, tremors, hyper-
rhythmia, depressed tension, tachycardia.
respiration, stupor,
coma, seizure, death
Amphetamines Stimulant; sympatho- Euphoria, hyperalert Lethargy, fatigue, de- Paranoia, psychosis
mimetic state, hyperactive, hy- pression, anxiety,
pertension, arrhythmia, nightmares, muscle
fever, flushing, dilated cramps, abdominal
pupils, tremor, ataxia, pain, hunger
dry mouth
(continued)
 SUBSTANCE ABUSE / 151

Table 4–3. Effects of commonly abused mood-altering substances. (continued)

Substance Pharmacology Intoxication Withdrawal Chronic Use

Toxic: coma, circulatory
collapse, hypertensive
crisis, cerebral
hemorrhage
MDMA (ecstasy) Stimulant, psychedelic; Enhanced empathy, None Paranoid pyschosis
releases serotonin, euphoria, increased
dopamine, and nor- energy and self-esteem,
epinephrine; inhibits tachycardia, hyperten-
reuptake of neuro- tion, increased pyscho-
transmitters; in- motor drive, sensory
creases dopamine enhancement, illusions,
synthesis; inhibits difficulty concentrating
MAO and retaining informa-
tion, headaches, palpi-
tations, flushing, hyper-
thermia
Toxic: frank psychosis,
coma, seizures, intra-
cranial hemorrhage,
cerebral infarction,
asystole, pulmonary
edema, multisystem
organ failure, acute re-
nal or heptic failure,
ARDS, DIC, SIADH,
death
GHB (liquid ecstasy) Depressant, endogen- 10 mg/kg: sleep Only after chronic use Wernicke–Korsakoff
ous CNS transmitter; 30 mg/kg: memory loss with dosing every 3 hrs
influences dopamin- 50 mg/kg: general anes- Early: mild tremor, tachy-
ergic activity, higher thesia cardia, hypertension,
levels of GABA-B ac- Toxic: CNS and respiratory diaphoresis, moderate
tivity depression, aggressive- anxiety, insomnia, nau-
ness, seizures, brady- sea, vomiting
cardia, apnea Progressive: confusion,
delirium, hallucinations
autonomic instability,
death
Sedative-hypnotics Depressant Sedation, lethargy, Only after weeks of use: Paranoia
(barbiturates, ben- slurred speech, pin- agitation, delirium,
zodiazepines, point pupils, hypoten- psychosis, hallucina-
methaqualone) sion, psychosis, sei- tions, fever, flushing,
zures hyper- or hypotension,
Toxic: stupor, coma, death
cardiac arrest, seizure,
pulmonary edema,
death
(continued)
152 / CHAPTER 4

Table 4–3. Effects of commonly abused mood-altering substances. (continued)

Substance Pharmacology Intoxication Withdrawal Chronic Use

Hallucinogens (LSD, Inhibition of serotonin Illusions, depersonaliza- None Flashbacks
peyote, mesca- release tion, hallucination, anx-
line, mushrooms, iety, paranoia, ataxia,
nutmeg, dilated pupils, hyper-
jimsonweed) tension, dry mouth
Toxic: coma, terror,
panic, “crazy feeling”
Phencyclidine Dissociative Low dose (< 5 mg): illu- None Flashbacks
anesthetic sions, hallucinations,
ataxia, hypertension,
flushing
Moderate dose (5–10 mg):
hyperthermia, saliva-
tion, myoclonus
High dose: (> 10 mg):
rigidity, seizure, ar-
rhythmia, coma, death
Inhalants (toluene, Stimulation progress- Euphoria, giddiness, im- None Permanent damage to
benzene, hydro- ing to depression paired judgment, nerves, liver, heart,
carbons and ataxia, rhinorrhea, kidney, brain
fluorocarbons) salivation, hallucination
Toxic: respiratory de-
pression, arrhythmia,
coma, stupor, delirium,
sudden death
Nicotine Releases dopamine, Relaxation, tachycardia, Drug craving, irritability, Permanent damage to
1 mg nicotine per vertigo, anorexia anxiety, hunger, im- lung, heart, cardiovas-
cigarette paired concentration cular system
Anabolic steroidsa Bind steroid receptor Increased muscle bulk, Drug craving, dyspho- Tendon rupture, cardio-
Stacking: use many strength, endurance, ria, irritability, depres- myopathy, atheroscle-
types simulta- increased drive, hypo- sion rosis, peliosis hepatis
neously; pyramiding: gonadism, low sperm (orally active C17 de-
increase dosage count, gynecomastia, rivatives of testoste-
decreased libido, rone are especially
virilization, irregular hepatotoxic)
menses, hepatitis,
early epiphysial clo-
sure, aggressiveness
a
Despite conventional assumptions, scientific studies show that anabolic steroids do not improve aerobic athletic performance and im-
prove strength only in athletes trained in weight lifting before they begin using steroids who continue to train and take a high-protein
diet.

Swaim R et al: The effect of school dropout rates on estimates of MORBIDITY ASSOCIATED WITH
adolescent substance use among three racial/ethnic groups.
Am J Public Health 1997;87:51 [PMID: 9065226]. SUBSTANCE ABUSE
Tomar SL, Giovino GA: Incidence and predictors of smokeless to- Use and abuse of alcohol or other mood-altering sub-
bacco use among US youth. Am J Public Health stances is associated with the leading causes of adoles-
1998;88:20 [PMID: 9584028].
cent and young adult deaths and injuries in the United
States (ie, motor vehicle accidents, other unintentional
injuries, homicide, and suicide), which are typically
 SUBSTANCE ABUSE / 153

Table 4–4. Prevalence of pediatric substance use and abusers by year.

Lifetime Annual 30-day

1991 1996 2000 2001 2002 1991 1996 2000 2001 2002 1991 1996 2000 2001 2002
Any Illicit Drug
8th grade 18.7 31.2 26.8 26.8 24.5 11.3 23.6 19.5 19.5 17.7 5.7 14.6 11.9 11.7 10.4
10th grade 30.6 45.4 45.6 45.6 44.6 21.4 37.5 36.4 37.2 34.8 11.6 23.2 22.5 22.7 20.8
12th grade 44.1 50.8 54.0 53.9 53.0 29.4 40.2 40.9 41.4 41.0 16.4 24.6 24.9 25.7 25.4
Marijuana/Hashish
8th grade 10.2 23.1 20.3 20.4 19.2 6.2 18.3 15.6 15.4 14.6 3.2 11.3 9.1 9.2 8.3
10th grade 23.4 39.8 40.3 40.1 38.7 16.5 33.6 32.2 32.7 30.3 8.7 20.4 19.7 19.8 17.8
12th grade 36.7 44.9 48.8 49.0 47.8 23.9 35.8 36.5 37.0 36.2 13.8 21.9 21.6 22.4 21.5
Inhalants
8th grade 17.6 21.2 17.9 17.1 15.2 9.0 12.2 9.4 9.1 7.7 4.4 5.8 4.5 4.0 3.8
10th grade 15.7 19.3 16.6 15.2 13.5 7.1 9.5 7.3 6.6 5.8 2.7 3.3 2.6 2.4 2.4
12th grade 17.6 16.6 14.2 13.0 11.7 6.6 7.6 5.9 4.5 4.5 2.4 2.5 2.2 1.7 1.5
MDMA (Ecstasy)
8th Grade — 3.4 4.3 5.2 4.3 — 2.3 3.1 3.5 2.9 — 1.0 1.4 1.8 1.4
10th Grade — 5.6 7.3 8.0 6.6 — 4.6 5.4 6.2 4.9 — 1.8 2.6 2.6 1.8
12th Grade — 6.1 11.0 11.7 10.5 — 4.6 8.2 9.2 7.4 — 2.0 3.6 2.8 2.4
Reprinted, with permission, from Monitoring the Future Study, 2003 (www.monitoringthefuture.org).

outcomes of high-risk or violent behaviors combined ijuana has shown a three- to five-fold increase in the
with impaired judgment. Substance abuse is also associ- concentration of THC since the 1970s and 1980s.
ated with physical and sexual abuse. Up to two thirds of Ecstasy, which is gaining in popularity with teens
sexual assaults and acquaintance or date rapes are linked and becoming more accessible, can cause permanent
to alcohol or other drug use. Drug use and abuse also brain damage. Chronic use destroys the serotonin sys-
contribute to other high-risk behaviors, such as unsafe tem of the brain and has been associated with progres-
and increased sexual activity, leading to unintended sive decline of immediate and delayed memory and
pregnancy and sexually transmitted diseases. The use of with alterations in mood, sleep, and appetite. Even
drugs during periods of low self-esteem and depression first-time users may develop frank psychosis indistin-
increases the risk of suicide. guishable from schizophrenia. Irreversible cardiomy-
The well-known long- and short-term risks associ- opathy, noncardiogenic pulmonary edema, and pul-
ated with tobacco, alcohol, and cocaine are listed in monary hypertension may occur with long-term use.
Table 4–3. Less well known are the long- and short- Overdose can cause hyperthermia and multiorgan sys-
term morbidities connected with the currently most tem failure.
popular illicit drugs among adolescents (eg, marijuana Environmental and prenatal exposure to abused
and ecstasy). The active ingredient in marijuana, δ- substances carry significant health risks. Parental to-
9-tetrahydrocannabinol (THC), transiently causes bacco smoking has been associated with low birth
tachycardia, mild hypertension, and bronchodilation. weight in newborns, sudden infant death syndrome,
Regular use can cause lung changes similar to those bronchiolitis, asthma, otitis media, and fire-related in-
seen in tobacco smokers. Heavy use decreases fertility in juries. Paternal use of marijuana during pregnancy is as-
both sexes, leads to immunosuppression, and can cause sociated with an increase the risk of sudden infant
the destruction of hippocampal and basal ganglia nu- death syndrome. In utero exposure to cocaine and alco-
clei, resulting in disruption in cognition, learning, coor- hol can result in fetal malformations, intrauterine
dination, and memory. This may explain the develop- growth retardation, and brain injury.
ment of so-called amotivational syndrome in heavy
users, characterized by decreased attention to environ-
mental stimuli and impaired goal-directed thinking and American Academy of Pediatrics Committee on Substance Abuse:
behavior. Also of concern is the increasing potency of Tobacco’s Toll: Implications for the pediatrician. Pediatrics
available marijuana. Recent analysis of confiscated mar- 2001:794 [PMID: 11335763].
154 / CHAPTER 4

Gouzoulis-Mayfrank et al: Impaired cognitive performance in drug dione. Sold as dietary supplements, these precursors to
free use of recreational Ecstasy. J Neurol Neurosurg Psychiatr testosterone and other sex hormones are sold without
2000;68:719 [PMID: 10811694].
federal regulation. Endogenous DHEA is produced in
Graeme K: New drugs of abuse. Emerg Med Clin North Am the adrenal cortex as a precursor of gonadal hormones.
2000;18:625 [PMID: 11130930].
Putative benefits of DHEA include increased fat catab-
Heyman RB et al, American Academy of Pediatrics Committee on
Substance Abuse: Marijuana: A continuing concern for pedia-
olism; increased muscle mass; increased libido; “im-
tricians. Pediatrics 1999;104:982 [PMID: 10506247]. proved” immune function; and decreased memory loss,
Klonoff-Cohen H, Lam-Kruglick P: Maternal and paternal recre- heart disease, cancer, type II diabetes mellitus,
ational drug use and sudden infant death syndrome. Arch Pe- Alzheimer, and Parkinson disease. Although its effects
diatr Adolesc Med 2001;155:765 [PMID:11434841]. on strength and performance in athletes remain un-
Ownby DR, Johnson CC, Peterson EL: Passive cigarette smoke ex- studied and unproven, the advertised benefits are at-
posure in infants. Arch Pediatr Adolesc Med 2000;154: tractive to many athletes. Its effect on young, healthy
1237 [PMID: 11115309]. individuals (ie, those with higher baseline DHEA lev-
Tapert SF et al: Adolescent substance use and sexual risk-taking be- els) has not been studied. In adults, two studies have
havior. J Adolesc Health 2001;28:181 [PMID: 11226840]. shown that usage at 50 mg/d and 100 mg/d increases
androgenic steroid plasma levels and improves subjec-
tive perception of physical and psychological well-
SUPPLEMENT USE AND ABUSE being. Users of DHEA report few adverse effects.
Use of supplements or special diets to enhance athletic Androstenedione, which is banned by the Interna-
performance dates back to antiquity, when warriors and tional Olympic Committee, National Collegiate Ath-
athletes ate certain animals to acquire their characteris- letic Association, and National Football League, is con-
tics. Today, many elite and casual athletes use ergogenic verted to testosterone by the liver. A recent study of
supplements in an attempt to improve performance. young athletes concluded that oral androstenedione
The most popular products among the pediatric popu- does not increase plasma testosterone concentrations
lation are protein supplements, creatine, and the pro- and, in young eugonadal men, has no anabolic effect on
hormones. Strength athletes (ie, weight lifters) use pro- muscle protein metabolism. Other studies have shown
tein powders and shakes to enhance muscle repair and increased biologically active estrogen levels. No long-
mass. The typical amount of protein consumed by ath- term studies of androstenedione have been conducted.
letes far exceeds the recommended daily allowance for Its side effects are believed to be similar to those of
resistance-training athletes (1.6–1.7 g/kg/d). Excess con- other anabolic and androgenic agents. Most side effects
sumption of protein provides no added strength or are secondary to androgen excess—hyperlipidemia, hy-
muscle mass and can provoke renal failure in teens with pertension, insulin resistance, hyperinsulinism, depres-
underlying renal dysfunction. sion, aggression, paranoia, acne, male pattern baldness,
Creatine is the most popular nutritional supple- alopecia, priapism, and others. Most effects are re-
ment, with annual sales of $400 million. It is a combi- versible with cessation of the product’s use. Irreversible
nation of glycine, arginine, and methionine. Creatine is side effects include virilization in females (hair loss, cli-
produced naturally in the liver, kidneys, and pancreas. toromegaly, hirsutism, voice-deepening) and gyneco-
It facilitates the production of adenosine triphosphate mastia in males.
and increases free energy for muscle contraction. It As the use of supplements and herbs increases, it will
maximizes power during short-duration, intense exer- be increasingly important for pediatric care providers to
cise, and improves baseline strength in adults. In con- be familiar with their common side effects. The Inter-
trast, creatine does not improve performance in longer net has become a source of information and sales of
duration, aerobic exercise; nor has its effectiveness been these products, which could lead to their increased use.
analyzed in children. Although the American College of The easy accessibility, perceived low risk, and low cost
Sports Medicine discourages use of the synthetic prod- of these products significantly increase the likelihood
uct by people under 18 years of age, recent studies show that they will become significant substances of abuse by
that creatine is extensively used by athletes in grades the pediatric population.
6–12. Use by high-school juniors and seniors mirrors
that of collegiate athletes. Side effects include weight
gain, headache, abdominal pain, diarrhea, and in- Ahrendt DM: Ergogenic aids: Counseling the athlete. Am Fam
creased muscle strain. There are conflicting reports Physician 2001;63:913 [PMID: 11261867].
about the risk of renal damage. Metzl JD et al: Creatine use among young athletes. Pediatr
Most disturbing for health care providers is the 2001;108:421 [PMID: 11483809].
growing availability and use of prohormones, specifi- Morris CA, Avorn J: Internet marketing of herbal products. JAMA
cally dehydroepiandrosterone (DHEA) and androstene- 2003;290:1505 [PMID: 13129992].
 SUBSTANCE ABUSE / 155

Rasmussen BB: Androstenedione does not stimulate muscle protein 4–5 and the frequency of substance abuse, a combina-
anabolism in young healthy men. J Clin Endocrinol Metab tion of risk factors is the best indicator of risk. Even so,
2000;85:55 [PMID: 10634363].
most teenagers who exhibit multiple risk characteristics
Sturmi JE: Anabolic agents. Clin Sports Med 1998;17:261 [PMID: never develop a substance abuse problem, presumably
9580841].
because the protective factors listed in Table 4–5 give
Volek JS, Kraemer WJ: Creatine supplementation: Its role in
human performance. Clin Sports Med 1999;18:651 [PMID:
them enough resiliency to cope with stress in more so-
10410847]. cially adaptive ways.
Being aware of the risk domains listed in Table
4–5 will help physicians identify youngsters most apt to
RESPONSE TO THE PROBLEM need counseling about substance abuse. Theories con-
Federal, state, and local governments attempt to control cerning the mechanisms responsible for the association
the damage caused by substance abuse by prohibiting between the risk factors listed in Table 4–5 and sub-
use and by legislating against associated high-risk behav- stance abuse are listed in Table 4–6. These theories pro-
iors (eg, enacting drunk-driving laws and nighttime cur- vide a framework for understanding why individual pa-
fews). However, neither these legal actions nor the large tients may be at risk for progressing from occasional to
sums of money spent on school- and community-based established or compulsive substance abuse. Most theo-
drug abuse prevention and treatment programs have ries emphasize social influences as the most reliable pre-
curbed the problem. Hence, the American Academy of dictors of both the onset and the progression of sub-
Pediatrics (AAP) recommends that pediatricians become stance abuse. For example, most teenage smokers report
knowledgeable about the extent and nature of drugs smoking at home and cite smoking parents or relatives
used in their community, provide anticipatory guidance as a reason to continue smoking.
to parents starting with the first prenatal visit, and be Problem behavior theory is one of the most fre-
aware of community referral and treatment resources for quently cited concepts in the substance abuse literature.
adolescents. The Internet makes this task more difficult. Its main argument is that socially disapproved behav-
For example, poor methods for age verification make it iors tend to cluster and to resist intervention because
easy for minors to purchase tobacco products online. they have both negative and positive consequences for
the individual. Expectancy theory, which takes up
where problem behavior theory leaves off, proposes a
American Academy of Pediatrics Committee on Substance Abuse:
Tobacco, alcohol, and other drugs: The role of the pediatri- potentially modifiable mechanism by which learning
cian in prevention and management of substance abuse. Pedi- experiences influence substance abuse. Measuring alco-
atrics 1998;101:125 [PMID: 11345974]. hol- and drug-related expectations has been found to
Hogan MJ: Diagnosis and treatment of teen drug use. Med Clin provide a more accurate assessment of risk than any of
North Am 2000;84:927 [PMID: 10928196]. the factors listed in Table 4–5. Expectations about the
Ribisl KM et al: Internet sales of cigarettes to minors. JAMA effects of substances are important determinants of so-
2003;290:1356 [PMID: 12966128]. cial and psychological reactions to them. Furthermore,
Siegel M: The effect of local tobacco sales laws on adolescent smok- these expectations are longitudinally related to different
ing initiation. Prev Med 1999;29:334 [PMID: 10564624]. patterns of substance abuse. For example, within ho-
mogeneous groups of nondrinkers, low-risk drinkers,
PREDICTING THE PROGRESSION and high-risk drinkers, expectations about outcomes
differ significantly both at entry into college and 3 years
FROM USE TO ABUSE later. At each level alcohol abusers who progress to the
Most adolescents who use mood-altering substances do next level of drinking expect more positive outcomes
so only intermittently or experimentally. The challenge from the drinking. Conversely, evidence that negative
to pediatric health care providers is to recognize the experiences with alcohol transform some high-risk
warning signs, identify potential abusers early, and in- freshmen drinkers into nondrinking seniors suggests
tervene in an effective and timely fashion before acute that it may be possible to influence indulgence patterns
or chronic use results in morbidity. The best predictors by altering expectancies. Here intervention is critical.
of ethanol and drug abuse are male sex, young age at Without guidance, most youngsters do not draw sober-
first use, and associating with drug-using peers. It is still ing conclusions from their negative experiences with
unclear why only a minority of the young people ex- drugs and alcohol. Despite serious accidents and so-
hibiting the high-risk characteristics listed in Table cially unrewarding experiences, positive expectancies
4–5 go on to abuse substances. Substance abuse is a about the effects of alcohol tend to increase rather than
symptom of personal and social maladjustment as often decrease during the first 3 years of college. Similarly the
as it is a cause. Because a direct relationship exists be- expectation of weight loss and improved mood leads to
tween the number of risk factors listed in Table initiation of smoking or reluctance to quit.
156 / CHAPTER 4

Table 4–5. Factors that influence the progression from substance use to substance abuse.

Enabling Risk Factors Potentially Protective Factors

SOCIETAL AND COMMUNITY
Experimentation encouraged by media Regular involvement in church activities
Illicit substances available Support for norms and values of society
Extreme economic deprivation Strict enforcement of laws prohibiting substance
Neighborhood disorganization, crowding use among minors and abuse among adults
Tolerance of licit and illicit substance use Neighborhood resources, supportive adults
SCHOOL
Lack of commitment to school or education Strong commitment to school or education
Truancy Future-oriented goals
Academic failure Achievement oriented
Early, persistent behavior problems
FAMILY
Models of substance abuse and other unconventional behavior Models of conventional behavior
Dysfunctional parenting styles; excessive authority or permissiveness Attachment to parents
High family conflict; low bonding Cohesive family
Nurturing parenting styles
PEERS
Peer rejection in elementary grades Popular with peers
Substance use prevalent among peers Abstinent friends
Peer attitudes favorable to substance abuse and unconventional behavior Peer attitudes favor conventional behavior
INDIVIDUAL
Genetic predisposition Positive self-concept, good self-esteem
Psychological diagnoses (attention-deficit/hyperactivity disorder; Intolerance of deviance
antisocial personality)
Depression and low self-esteem Internally motivated, takes charge of problems
Alienation and rebelliousness
Sexual or physical abuse
Early onset of deviant behavior or delinquency
Early onset of sexual behavior
Aggressive

Belcher H, Shinitzky H: Substance abuse in children: Prediction, Office Screening

protection, and prevention. Arch Pediatr Adolesc Med
1998;152:952 [PMID: 9790604]. Given the high incidence of substance abuse and the
Comerci GD, Schwebel R: Substance abuse: An overview. Adolesc subtlety of its early signs and symptoms, a general psy-
Med 2000;11:79 [PMID: 10640340]. chosocial assessment is the best way to screen for sub-
Patton GC et al: Depression, anxiety and smoking initiation: A stance abuse. Interviewing and counseling techniques
prospective study over 3 years. Am J Public Health and methods for taking a psychosocial history are dis-
1998;88:1518 [PMID: 9772855]. cussed in Chapter 3. In an atmosphere of trust and con-
fidentiality, physicians must ask routine screening ques-
tions of all patients and be alert for addictive diseases,
MANAGEMENT OF SUBSTANCE ABUSE especially in light of the high level of denial often pre-
sent in addicted patients. The universal screening ap-
It is critical that pediatric care providers have the proach outlined in the American Medical Association
knowledge and skill to diagnose, treat, and advocate for guidelines for adolescent preventive services (GAPS) is a
their substance-using and abusing patients. The AAP good guide for routine screening and diagnosis. Clues to
Committee on Substance Abuse recommends that pe- possible substance abuse include truancy, failing grades,
diatricians include discussions of substance abuse as problems with interpersonal relationships, delinquency,
part of their anticipatory care, starting with parents at depressive affect, chronic fatigue, recurrent abdominal
the prenatal visit. pains, chest pains or palpitations, headache, chronic
 SUBSTANCE ABUSE / 157

Table 4–6. Theories accounting for the progression from substance use to substance abuse.a

Theory Key Constructs and Assumptions Major Protagonist

b
Problem Behavior Socially problematic behaviors occur together and reflect a common Jessor R, Jessor R: Problem
underlying cause. The common antecedent is the reflection of the in- Behavior and Psychosocial
teraction among individual personality traits (eg, unconventionality), Development. Academic Press, 1977.
the perceived environment (eg, models of deviance), and a nondom-
inant pattern of socialization (eg, low value on education).
Social Learning Problem behavior theory plus a scheme to explain reinforcement of Bandura A: Social Learning Theory.
these behaviors. The risk of problem behavior increases when Prentice-Hall, 1977.
youngsters have the opportunity to become skillful in unconven-
tional settings and are rewarded for doing so.
Reasoned Action Behavior is determined by the interaction between perceived con- Ajzen I, Fishbein M: Understanding
sequences and attitudes toward those consequences. The risk of Attitudes and Predicting Behavior.
problem behavior increases when the perceived costs are low or the Prentice-Hall, 1980.
perceived benefits high.
Health Belief Health behaviors reflect assessments of perceived risk or harm, po- Becker MH: The health belief model
tential to avoid that harm through alternative behaviors, and ability and personal health behavior. Health
to access requisite resources. The risk of unhealthy behavior in- Education Monograph 1974;2:324.
creases when the perceived health risk is low or the ability to avoid
that risk is perceived to be low or unrelated to the behavior.
Social Control Behavior is determined by the bonds an individual establishes with Hirschi T: Causes of Delinquency.
society. The risk of problem behavior increases when attachment to Univ California Press; 1969.
those who express conventional values is weak, commitment to
participation in conventional activities is low, little time is spent in
these activities, and the central value system of society is not fully
accepted.
Peer Cluster The socialization process that accompanies adolescent development Oetting ER, Beauvais F: Peer cluster
results in the formation of peer clusters. Family sanctions, religious theory. Counseling Psychol 1987;
identifications, and school adjustment affect behavior indirectly 34:205.
through their effects on peer clusters.
Expectancy Problem behavior and reasoned action theories plus a mechanism Werner MJ: Relation of alcohol ex-
by which learning experiences exert an influence on future behavior. pectancies to change in problem
The risk of problem behavior increases when experiences reinforce drinking among college students.
preexisting positive expectancies about the effects of deviant Arch Pediatr Adolesc Med 1995;149:
behavior. 733.
Self-Medication Individuals are predisposed to addiction when they experience Khantzian EJ: The self-medication
painful affective states or psychiatric disorders; symptom relief per- hypothesis. Am J Psychiatry
petuates the use of specific substances. 1985;142:1259.
a
Ordered by frequency of citation in the literature.
b
A problem behavior is defined as any behavior compromising the accomplishment of normal developmental tasks of adolescence; most
are hard to change because they also serve functions central to the psychosocial development of adolescents who lack conventional al-
ternatives.

cough, persistent nasal discharge, and recurrent com- suspicion. A family history of drug addiction or abuse
plaints of sore throat. Substance abuse should be in- should raise the level of concern about drug abuse in the
cluded in the differential diagnosis of all behavioral, pediatric patient. Possession of promotional products
family, psychosocial, and medical problems. Pediatri- such as T-shirts and caps with cigarette or alcohol logos
cians seeing patients in emergency departments, trauma should also be a red flag as teenagers who own these
units, or prison must have an especially high index of items are more likely to use the products they advertise.
158 / CHAPTER 4

Albers AB, Biener L: Adolescent participation in tobacco promo- tion or maintenance phase of substance abuse. The
tions: Role of psychosocial factors. Pediatrics 2003;111: cause may be different at different periods of develop-
402 [PMID: 12563070].
ment. Although peer group characteristics are one of
Altman DG et al: Tobacco promotion and susceptibility to tobacco the best predictors of substance use among early and
use among adolescents aged 12 through 17 years in a nation-
ally representative sample. Am J Public Health 1996;86: middle adolescents, this is not so among older adoles-
1590 [PMID: 8916525]. cents and young adults.
Brief questionnaires can be used if time does not
Diagnosis allow for more detailed investigation. Two instruments
evaluated rigorously in primary care settings are the
Although few children and adolescents will have been CAGE questionnaire and the Perceived Benefits of
abusing substances long enough to have developed Drinking Scale. CAGE is a mnemonic derived from the
overt signs and symptoms, it is important to look for first four questions listed in Table 4–8. A score of 2 or
them on physical examination. Positive physical find- more is highly suggestive of substance abuse. The Per-
ings can be a tool to penetrate a patient’s denial and ceived-Benefits-of-Drinking Scale consists of the next
convince him or her of the significant extent of the al- five statements listed in Table 4–8. Patients who en-
cohol or drug use. dorse more than three statements deserve further evalu-
When the psychosocial history suggests the possibil- ation. Because CAGE is more predictive of substance
ity of substance use, the primary tasks of the diagnostic use problems among males and the Perceived-Benefits-
interview are the same as the evaluation of other med- of-Drinking Scale is more predictive among females,
ical problems (Table 4–7). many clinicians combine the two scales. Including an
First, specific information about the extent of the additional question about use of tobacco and a question
problem must be gathered. Eliciting multiple-choice about the patient’s best friend’s use of mood-altering
answers is a useful technique. For example, “Has any-
thing really good ever happened to you when you are
high?” or “Some of my patients like to get high because
they feel good; others find it helps them relax and be
sociable with friends; and some find it helps them for- Table 4–8. Substance abuse
get their problems. Are any of these things true for screening questionnaires.
you?”
Second, the provider needs to determine why the CAGE Questionnaire
patient has progressed from initiation to the continua-
CUT DOWN: Have you ever felt you ought to cut down on
your drinking (drug use)?
ANNOYED: Have people annoyed you by criticizing your
Table 4–7. Diagnostic interview for drinking (drug use)?
substance abuse. GUILTY: Have you ever felt bad about your drinking (drug
use)?
I. Define the extent of the problem by determining: EYE OPENER: Have you ever had a drink (used drugs) to
Age at onset of substance use steady your nerves in the morning?
Which substances are being used (Score 1 point for each positive answer; refer if total
Circumstances of use points ≥ 2)
Where?
When? Used, with permission, from Ewing JE: Detecting alcoholism: The
CAGE questionnaire. JAMA 1984;252:1905.
With whom?
To what extent substances are being used Perceived Benefits Scales
How frequently?
1. Drinking (drug use) helps me forget my problems.
How much (quantity)?
2. Drinking (drug use) helps me be friendly.
With what associated symptoms (eg, tolerance,
3. Drinking (drug use) helps me feel good about myself.
withdrawal)?
4. Drinking (drug use) helps me relax.
With what result?
5. Drinking (drug use) helps me be friends with others who
What does the patient gain from becoming high?
drink (use drugs).
Does the patient get into risky situations while high?
Does the patient engage in behaviors while high that (Score 1 point for each positive answer; refer if total
are later regretted? points ≥ 3)
II. Define the cause of the problem by developing a dif-
Used, with permission, from Petchers MK, Singer MI: Perceived-
ferential diagnosis Benefit-of-Drinking Scale. J Pediatr 1987;110:977.
 SUBSTANCE ABUSE / 159

substances further enhances the diagnostic accuracy of abusing substances. Alcohol and substance abusers are
these screening tools. more likely than are their nonabusing counterparts to
Although constructed as screening tools for alcohol have another psychiatric disorder. Affective disorders,
abuse in adults, the questions in Table 4–8 can be anxiety disorders, and mania rank among the disorders
adapted to elicit similar information about use of other most strongly associated with alcohol and drug depen-
mood-altering substances by pediatric patients and by dence. Adolescents with depression are likely to use
their close contacts (eg, parents and older siblings). Fi- drugs in an attempt to feel pleasure, but this type of
nally, clinicians may find it helpful to use these ques- self-medication may exacerbate their condition. In ad-
tionnaires to stimulate discussion of the patient’s self- dition to identifying psychiatric comorbidities, it is im-
perception of his or her substance use. For example, if perative that providers look for medical conditions that
an adolescent admits to a previous attempt to cut down can mimic symptoms of drug withdrawal or intoxica-
on drinking, this provides an opportunity to inquire tion. Patients with significant primary medical condi-
about events that may have led to the attempt. tions may use illicit substances to relieve symptoms (se-
Additional screening instruments include the fol- vere pain, chemotherapeutic side effects). Although it is
lowing: often difficult to determine which diagnosis is primary,
it is important for pediatric health care providers to rec-
1. The Simple Screening Instrument for Alcohol ognize the possibility of a comorbid condition and pro-
and Other Drug Abuse (SSI-AOD), from the vide appropriate treatment.
Center for Treatment of Substance Abuse, is a
quick, 16-item screen that has proven reliable
among adolescent medical patients. Bucholz KK: Nosology and epidemiology of addictive disorders
and their comorbidity. Psychiatr Clin North Am 1999;22:
2. The Personal Experience Inventory is a compre- 221 [PMID: 10385930].
hensive, standardized 260-item self-report mea- Comerci GD, Schwebel R: Substance abuse: An overview. Adolesc
sure of chemical involvement and the psychoso- Med 2000;11(1):79 [PMID: 10640340].
cial aspect of substance use. Jellinek MS: Depression and suicide in children and adolescents.
3. The Personal Experience Screening Questionnaire Pediatr Rev 1998;19:255 [PMID: 9797715].
is a quick, 38-item screen that evaluates the sever-
ity of the problem and associated psychosocial Pharmacologic Screening
risks.
4. The Adolescent Diagnostic Interview is a struc- The use of urine and blood testing for detecting sub-
tured interview based on the American Psychiatric stance abuse is controversial. The consensus is that
Association’s diagnostic criteria for substance pharmacologic screening should be reserved for situa-
abuse (see Table 4–1). tions where behavioral dysfunction is of sufficient con-
cern to outweigh the practical and ethical drawbacks of
Although these instruments may be too time-con- testing. The AAP recommends screening under certain
suming for routine office use, they may prove helpful in circumstances (eg, an inexplicably obtunded patient in
the evaluation of patients who pose diagnostic or thera- the emergency department) but discourages routine
peutic dilemmas. screening for the following reasons: (1) Voluntary
screening programs are rarely truly voluntary owing to
Fuller PG Jr, Cavanaugh RM Jr: Basic assessment and screening for the negative consequences for those who decline to par-
substance abuse in the pediatrician’s office. Pediatr Clin ticipate. (2) Infrequent users or individuals who have
North Am 1995;42(2):295 [PMID: 7724260]. not used substances recently may be missed. (3) Con-
Knight JR et al: Reliabilities of short substance abuse screening tests fronting substance-abusing individuals with objective
among adolescent medical patients. Pediatrics 2000;105(4 Pt evidence of their use has little or no effect on their be-
2):948 [PMID: 10742352].
havior. (4) The AAP reminds providers that their role is
Miller NS: The role of the physician in addiction prevention and counseling and treatment, not law enforcement, so that
treatment. Psychiatr Clin North Am 1999:22:489 [PMID:
10385946]. drug testing should not be done for the purpose of de-
Werner MJ: Screening, early identification, and office-based inter-
tecting illegal use. If testing is to be performed, the
vention with children and youth living in substance-abusing provider should discuss the plan for screening with the
families. Pediatrics 1999;103:1099 [PMID: 10224197]. patient, explain the reasons for it, and obtain informed
consent. The AAP does not consider parental request
and permission sufficient justification for involuntary
Comorbidity screening of mentally competent minors.
It is important for pediatric care providers to recognize Beyond the ethical concerns, there are also practical
the possibility of multiple diagnoses in patients who are concerns. If testing is to be performed, it is imperative
160 / CHAPTER 4

that it be done accurately and that the limitations of Table 4–10. Duration of urine positivity for
testing be understood by all parties. Tests range from selected drugs.
simple, inexpensive, chromatographic spot tests, which
can be performed in the office, to gas chromatography Drug Class Detection Time
and mass spectrometry, which require specialized labo-
ratory equipment and are usually reserved for forensic Amphetamines < 48 hours
investigations. Most commercial medical laboratories Barbiturates Short-acting: 1 d
use the enzyme multiplication immunoassay technique, Long-acting: 2–3 wk
in which a sample of the fluid to be tested is added to a
test reagent consisting of a known quantity of the radi- Benzodiazepines Single dose: 3 d
olabeled index drug (ie, the drug being tested for). If Habitual use: 4–6 wk
the index drug is also present in the patient’s urine or Cocaine metabolites Acute use: 2–4 d
serum, it competes with the radiolabeled drug for bind- Habitual use: 2 wk
ing sites on the test kit antibody. The unbound or ex- Ethanol 2–14 h
cess drug can then be quantified with a spectropho-
tometer. Most of the commonly abused mood-altering Methadone Up to 3 d
substances, with the exception of solvents and in- Opioids Up to 2 d
halants, can be detected by this method.
Caution is necessary in interpreting results because Propoxyphene 6–48 h
false-positives may be obtained as a result of antibody Cannabinoids Moderate use: 5 d
cross-reactions with the medications and substances Habitual use: 10–20 d
listed in Table 4–9 or from passive exposure to illicit
Methaqualone 2 wk
substances. The most common cause of false-negative
tests is infrequent use. Table 4–10 shows the duration Phencyclidine Acute use: 1 wk
of detectability in the urine after last use by class of sub- Habitual use: 3 wk
stance and duration of use. Detectability ranges from a Anabolic steroids Days to weeks
few hours for alcohol to several weeks for regular mari-
juana use. False-negative results can occur if the patient Reprinted, with permission, from Woolf A, Shannon M: Clinical
alters or adulterates the specimen, either by drinking a toxicology for the pediatrician. Pediatr Clin North Am
1995;42:317.
large volume of fluid or adding such substances as
bleach, vinegar, or golden seal powder to the specimen.
(Teenagers should be advised that despite street lore,
ingesting these compounds is an ineffective and poten-
tially dangerous way to prevent drug detection in the
urine.) Close observation during collection and pretest-
Table 4–9. Causes of false-positive drug screens. ing the temperature, specific gravity, and pH of urine
samples may detect attempts at deception.
Opioids
Poppy seeds American Academy of Pediatrics Committee on Substance Abuse:
Dextromethorphan Testing for drugs of abuse in children and adolescents. Pedi-
Chlorpromazine atrics 1996;98:305 [PMID: 8692638].
Diphenoxylate Perrone J: Drug screening versus history in detection of substance
Amphetamines use in ED psychiatric patients. Am J Emerg Med 2001;19:
Ephedrine 49 [PMID: 11146019].
Phenylephrine Woolf A, Shannon M: Clinical toxicology for the pediatrician. Pe-
Pseudophedrine diatr Clin North Am 1995;42:317 [PMID: 7724261].
N-Acetylprocainamide
Chloroquine
Procainamide TREATMENT & REFERRAL
Phencyclidines
Dextromethorphan Office-Based Treatment
Diphenhydramine The AMA and the AAP recommend that all children
Chlorpromazine and adolescents receive counseling about the dangers of
Doxylamine substance use and abuse from their primary health care
Thioridazine providers. By offering confidential health care services
 SUBSTANCE ABUSE / 161

and routinely counseling about the risks associated with Table 4–11. Stages of change and
drug abuse, pediatricians can help most of their patients intervention tasks.
avoid the adverse consequences of experimentation
with mood-altering substances. However, more inter- Patient Stage Motivation Tasks
vention is required for youngsters in environments
where substance abuse is regarded as acceptable recre- Precontemplation Create doubt, increase the patient’s
ational behavior. Because substance use is often deeply awareness of risks and problems with cur-
embedded in the fabric of these young peoples’ lives, rent patterns of substance use
most have little interest in prevention or treatment. Contemplation Help the patient weigh the relative risks
Counseling strategies appropriate for patients who wish and benefits of changing substance use;
to change their behavior may be ineffective for a patient evoke reasons to change and risks of not
who does not consider use of mood-altering substances changing; strengthen the patient’s self-
to be a problem. It may therefore be preferable to begin efficacy for changing current use
discussions about treatment by helping youngsters con- Determination Help the patient determine the best
sider alternative ways of meeting the needs that sub- course of action to change substance use
stance use is currently providing. The clinician may in from among available alternatives
this way help the patient devise alternatives that are
more attractive than substance use. Realistically, few Action Help the patient establish a clear plan of
substance-abusing teenagers will choose to quit because action toward changing substance use
of a single conversation with even a highly respected Maintenance Help the patient identify and use strate-
health care provider. The message is most effective gies to prevent relapse
when offered repeatedly from a variety of sources—
Relapse Help the patient renew the process of
family, peers, guidance counselors, and teachers. change starting at contemplation
Because an assessment of the patient’s readiness to
change is the critical first step in office-based interven- Reprinted from Werner MJ: Principles of brief intervention for
tion, clinicians should consider the construct presented adolescent alcohol, tobacco, and other drug use. Pediatr Clin
in Table 4–11. In theory, individuals pass through this North Am 1995;42:341. With permission of the publisher.
series of stages in the course of changing problem be-
haviors. Thus, to be maximally effective, providers
should tailor their counseling messages to the patient’s
stage of readiness to change. miliar with approaches to smoking cessation may feel
Once it has been established that a patient is pre- that smoking cessation interventions are time-consum-
pared to act on information about treatment, the next ing, nonreimbursable, and impractical in a busy office.
step is to select the program that best fits his or her in- In reality, studies conducted by the National Cancer
dividual needs. Most drug treatment programs are not Institute indicate that health care providers can help
designed to recognize and act on the individual vulner- their patients stop smoking with short office interven-
abilities that have predisposed the patient to substance tions. Some of the most effective smoking cessation in-
abuse. When programs are individualized, even brief terventions are self-help programs consisting of a series
(5- to 10-minute) counseling sessions may promote re- of short (typically under 5 minutes) physician interven-
ductions in cigarette smoking and drinking. This strat- tions reinforced by the entire office staff using the sim-
egy appears to be most effective when the health care ple protocol outlined in Table 4–12.
provider’s message is part of an office-wide program so The first step is motivational. Provide patients with
that the entire staff reinforces the cessation message a list of reasons for quitting. Suggest that they call
with every patient. Specific steps to help youngsters 1-800-4CANCER to obtain the National Cancer Insti-
quit smoking are discussed in the next section and sum- tute’s “Quit for Good” or “Why Do You Smoke?”
marized in Table 4–12. These same strategies and prin- pamphlets and materials.
ciples can be applied to the treatment of drug and alco- However, motivation alone is not enough. Learning
hol use. to use coping skills to prevent relapse and to avoid dis-
couragement at the time of relapse appear to be impor-
Smoking Cessation in Pediatrics tant to ultimate success. Smoking cessation is a process
that takes time. Relapse must be regarded as a normal
Although more than half of adolescents who smoke reg- part of quitting rather than evidence of personal failure
ularly say they want to quit and have tried to quit, only or a reason to forgo further attempts. Patients can actu-
a minority report that they have been advised or helped ally benefit from relapses if they are helped to identify
to do so by a health care provider. Practitioners unfa- the circumstances that led to the relapse and to devise
162 / CHAPTER 4

Table 4–12. How to help your patients strategies to prevent subsequent relapses or respond to
stop smoking. them in a different manner. Because nicotine is a physi-
cally and psychologically addictive substance, replace-
Ask about smoking at every opportunity. ment therapy may relieve withdrawal symptoms. Three
1. Do you smoke? How old were you when you started? types of nicotine replacement therapies (NRT) are
2. How much? available. Nicotine gum and transdermal nicotine
3. How soon after waking do you have your first cigarette? patches are recommended for teens. NRT improves
4. Do you have friends who smoke? family members? rela- smoking cessation rates and provides relief from with-
tives? role models? drawal symptoms. Providers should be aware that ado-
5. Are you interested in stopping smoking? lescents may not exhibit the same symptoms of nicotine
6. Have you ever tried to stop before? If so, what hap- dependence as adults, that symptoms may occur
pened? rapidly, with autonomy lost within as little as 4 weeks.
Advise all smokers to stop. Those who are not comfortable prescribing and moni-
1. State your advice clearly, for example: “As your physi- toring NRT should limit their involvement with pa-
cian, I must advise you to stop smoking now.” tients who smoke to those who do not exhibit signs of
2. Personalize the message to quit. Refer to the patient’s nicotine dependency (eg, patients who smoke less than
clinical condition, smoking history, family history, per- a pack of cigarettes a day or do not feel a craving to
sonal interests, or social roles (see Table 4–13). smoke their first cigarette within 30 minutes after wak-
Assist the patient in stopping. ing). In addition to NRT, sustained-release forms of
1. Set a quit date. Help the patient pick a date within the the antidepressants bupropion, clonidine, and nor-
next 4 weeks, acknowledging that no time is ideal. triptyline have been shown in randomized trials to help
2. Provide self-help materials. The smoking cessation coor-
smokers quit and to decrease relapse rates fivefold.
dinator or support staff member can review the materi-
als with the patient.
Two tobacco-use prevention curricula have been se-
3. Discuss the importance of a smoke-free environment. lected by The Division of Adolescent and School
4. Rehearse through role-playing how to respond to social Health (DASH) of the CDC for adoption by schools—
situations where others are smoking. Botvin’s Life Skills Training Program and Project To-
5. Elicit support of parents and relatives; encourage them ward No Tobacco (TNT). The first is the more com-
to stop smoking with their teen. prehensive of the two curricula. It is designed to target
6. Encourage participation in activities that are incompati- the primary causes of substance use, including tobacco,
ble with smoking. alcohol, and other drugs, by teaching a combination of
7. Consider prescribing replacement therapy (patch or health information, general life skills, and skills in re-
gum) for highly addicted patients (those who smoke a sisting tobacco and other drugs. Program effectiveness
pack or more daily or who smoke their first cigarette has been demonstrated among white, African-Ameri-
within 30 minutes after waking). can, and Hispanic youth.
8. Consider signing a stop-smoking contract with the Project TNT, the second curriculum and the more
patient. effective of the two, was designed to target the primary
9. If the patient is not willing to quit now, provide motivat- causes of cigarette smoking, smokeless tobacco use, and
ing literature and flag the chart and do remember to ask cigar and pipe smoking among teens. Compared with
again at the next visit. the subjects who received the standard school health
Arrange follow-up visits. education, subjects in Project TNT were less likely to
1. Set a follow-up visit within 1–2 weeks after the quit date. start using smokeless tobacco or cigarettes, and less
2. Have a member of the office staff call or write the pa-
likely to use them regularly. The program was equally
tient within 7 days after the initial visit, reinforcing the
decision to stop and reminding the patient of the quit
effective in boys and girls, and was effective during the
date. transitional period from junior to senior high school.
3. At the first follow-up visit, ask about the patient’s smok-
ing status to provide support and help prevent relapse.
4. Set a second follow-up visit in 1 month.
American Academy of Pediatrics Committee on Substance Abuse:
5. Remind the teen that relapse is common—indeed the
Tobacco’s toll: Implications for the pediatrician. Pediatrics
norm. When it happens, discuss the circumstances and 2001;107:794 [PMID: 11335763].
encourage the patient to think of alternative responses
DiFranza JR et al: Initial symptoms of nicotine dependence in ado-
and to try again. lescents. Tobacco Control 2000;9:313 [PMID: 10982576].
Adapted, with permission, from Glynn T, Manley M: How to Help DiFranza JR et al: Measuring the loss of autonomy over nicotine
Your Patients Stop Smoking: A National Cancer Institute Manual for use in adolescents: The DANDY (development and assess-
Physicians. National Institutes of Health, 1989. ment of nicotine dependence in youth) Study. Arch Pediatr
Adolesc Med. 2002;156:397 [PMID: 11929376].
 SUBSTANCE ABUSE / 163

DuRant RH: Adolescent tobacco use and cessation. Prim Care integral component of most adult-oriented programs.
1999;26:553 [PMID: 10436287]. This invariably frustrates counselors who misinterpret
Moolchan ET: A review of tobacco smoking in adolescents: Treat- lack of comprehension as resistance to therapy, and
ment implications. J Am Acad Child Adolesc Psychiatry concrete responses as evidence of deceit.
2000 Jun;39:682 [PMID: 10846302].
Treatment programs range from low-intensity, out-
patient, school-based student assistance programs,
Referral which rely heavily on peers and nonprofessionals, to
residential, hospital-based programs staffed by psychia-
There is no consensus about which substance-abusing trists and other professionals. Outpatient counseling
patients can be adequately treated in the office, which programs are most appropriate for motivated patients
require referral, and which require hospitalization. Fac- who do not have significant mental health or behavioral
tors to be considered are summarized in Table 4–13. problems and are not at risk for withdrawal. Some in-
When doubt exists about the seriousness of the prob- vestigators have raised the concern that in pediatric set-
lem or the advisability of office management, consulta- tings, low-problem users may actually experience a
tion with a specialist should be sought. strengthening of the drug subculture by associating
Although most primary pediatric providers will not with high-problem users in group therapy. More inten-
assume responsibility for the treatment of substance- sive day treatment programs are available for those who
abusing youngsters, clinicians can be instrumental in require a structured environment. Inpatient treatment
motivating their patients to seek treatment and in guid- should be considered for patients who need medical
ing them to appropriate treatment resources. Sub- care and detoxification in addition to counseling, edu-
stance-abusing teenagers must be treated in teen-ori- cation, and family therapy.
ented treatment facilities. Despite the similarities Finally, special dual-diagnosis facilities are available
between adult and adolescent substance abuse, adult for substance-abusing patients who also have other psy-
programs are usually developmentally inappropriate chological conditions. These patients are difficult to di-
and ineffective for adolescents. As discussed in Chapter agnose and treat because it is often unclear whether
3, many adolescents are concrete thinkers. Their inabil- their symptoms are a consequence of substance use or a
ity to reason deductively, especially about emotionally symptom of a comorbid psychological disorder. Recog-
charged issues, makes it difficult for them to under- nition of such disorders is critical because they must be
stand the abstract concepts (such as denial) that are an treated in programs that include psychiatric expertise.
Approaches to the treatment of substance abuse in
children and adolescents are typically modeled after
adult treatment programs. Most notable are the 12-step
Table 4–13. Factors to consider prior to referral programs modeled after Alcoholics Anonymous. These
for substance abuse. programs are attractive because they demand total ab-
stinence and acknowledge that substance abuse is a
Duration and frequency of substance use chronic disease requiring a lifelong commitment to ab-
The type of substances being used stinence and long-term support from family, peers, and
Presence of other psychological disorders community. Although treatment is usually effective, re-
Attention-deficit/hyperactivity disorder lapse is common. Because efficacy research has lagged
Depression behind practice and implementation (especially among
Antisocial personality disorder low-intensity programs), there is little empirical evi-
Presence of other social morbidities dence on which to base recommendations for one pro-
School failure gram or another. Various forms of treatment appear to
Delinquency have the potential to be effective. Thus, in practice, re-
Homelessness ferral recommendations should be based on the signifi-
Ongoing or past physical or sexual abuse cance of the problem for the individual and the avail-
Program Evaluation ability of affordable programs in the community.
View on substance abuse as primary disorder vs symptom
Offers comprehensive evaluation of patient and can man-
age associated problems identified in initial assessment Fleming M et al: Brief physician advice for problem alcohol
(eg, comorbid conditions) drinkers. JAMA 1997;277:1039 [PMID: 9091691].
Adherence to abstinence philosophy Garbutt JC et al: Pharmacological treatment of alcohol depen-
Patient-to-staff ratios dence: A review of the evidence. JAMA 1999;281:1318
[PMID: 10208148].
Separate adolescent and adult treatment programs
Follow-up and continuing care Heyman RB: Turning the tide: Tobacco and the 21st. Adolesc
Med 2000;11:69 [PMID: 10640339].
164 / CHAPTER 4

Hughes JR et al: Recent advances in the pharmacotherapy of smok- program, a same-sex, peer-educator program designed
ing. JAMA 1999;281:72 [PMID: 9892454]. to simultaneously reduce the use of steroids and im-
Hurt RD et al: A comparison of sustained-release bupropion and prove dietary and exercise habits of teen athletes has
placebo for smoking cessation. N Engl J Med 1997; proven effective in randomized controlled trials. Pedi-
337:1195 [PMID: 9337378].
atric health care providers should promote develop-
Swift RM: Drug therapy for alcohol dependence. N Engl J Med
1999;340:1482 [PMID: 10320388].
mentally appropriate prevention programs like this one
that address the social and psychological problems pre-
disposing youngsters to substance abuse and which pro-
vide realistic alternative solutions.
PREVENTION OF SUBSTANCE ABUSE Parents and others should understand that most
Prevention of substance abuse has been a public health adolescents who abuse alcohol and drugs do not do so
priority since the 1980s. Pediatric health care providers just for the high. Rather, these behaviors are often pur-
are important as advocates and educators of the com- poseful, developmentally appropriate coping strategies.
munity and government on developmentally appropri- To the extent that these behaviors meet young peoples’
ate programs. Primary level programs focus on prevent- developmental needs, they are not apt to be abandoned
ing the initiation of substance use. The Drug Awareness unless equally attractive alternatives are available. For
and Resistance Education (DARE) program is a famil- example, even though many teenagers cite stress and
iar example of a primary prevention program that at- anxiety as reasons for smoking, teen-oriented smoking
tempts to educate elementary and middle school stu- cessation programs rarely address the young smoker’s
dents about the adverse consequences of substance need for alternative coping strategies by offering stress
abuse and enable them to resist peer pressures. management training. Similarly, for the youngster
Secondary level programs target populations at in- growing up in an impoverished urban environment, the
creased risk for substance use. The aim is to prevent real costs of substance abuse may be too low and the re-
progression from initiation to continuance and mainte- wards too high to be influenced by talk and knowledge
nance, relying on individualized intervention to reduce alone. It is unreasonable to expect a talk-based interven-
the risk and enhance the protective factors listed in tion to change attitudes and behaviors in a direction
Table 4–5. This approach enables the provider to focus that is opposite to that of the child’s own social milieu.
scarce resources on those who are most likely to benefit The efficacy of the most promising prevention models
from them. Alateen, which supports the children of al- and interventions is apt to decay over time unless
coholic parents typifies secondary level prevention. changes in the social environment provide substance-
Tertiary level prevention programs target young peo- abusing children and adolescents with realistic alterna-
ple who have been identified as substance abusers. The tive ways to meet their developmental needs.
aim is to prevent the morbid consequences of substance
use. One example is identifying adolescents who misuse
alcohol and drugs at parties and providing them with a Ennett S et al: How effective is drug abuse resistance education? A
safe ride home. Because prevention is more effective meta-analysis of project DARE outcome evaluations. Am
when targeted at reducing the initiation of substance J Public Health 1994;84:1394 [PMID: 8092361].
use than at decreasing use, tertiary prevention is the Goldberg L et al: The adolescents’ training and learning to avoid
steroids program: Preventing drug use and promoting health
least effective approach. behaviors. Arch Adolesc Med 2000:154(4):332 [PMID:
Very few population-based programs undergo rigor- 10768668].
ous scientific evaluation. It is the consensus among Goldman LK, Glantz SA: Evaluation of antismoking advertising
drug educators that primary prevention programs, such campaigns. JAMA 1998;279:722 [PMID: 9508154].
as DARE, have minimal effect in decreasing the use of
illicit substances. During the 1990s, when these pro-
grams were most popular, a smaller proportion of mid- Web Resources
dle- and high-school students perceived illicit drug and
alcohol use as dangerous, and substance use actually in- [Monitoring the future Study detailed information and longitudi-
creased. Even when knowledge- and resistance-based nal data] www.monitoringthefuture.org
programs do increase student understanding of adverse [Information on trends from National Institute on Drug Abuse]
www.nida.nih.gov
consequences, there is no evidence that they change at-
[National Clearinghouse Drug and Alcohol Abuse Gives informa-
titudes or abuse rates. tion and resources including free publications for providers,
The failure of resistance education programs has fos- parents, and adolescents] www.health.org
tered interest in a potentially more effective type of pro- [Substance use and mental health services administration resources
gram, exemplified by the Adolescents Training and for both substance use and mental health services]
Learning to Avoid Steroids (ATLAS) program. This www.samhsa.org
 Eating Disorders 5
Eric J. Sigel, MD

Teenagers and younger children continue to develop tends to equilibrate satiety regulation. More research is
eating disorders at an alarming rate. The spectrum of needed to determine which factors are causative and
eating disorders includes anorexia nervosa, bulimia ner- which are results of the eating disorder.
vosa, eating disorders not otherwise specified, and Traditional psychological theory has suggested many
binge-eating disorder. The relationship between biol- factors that might lead to the development of eating
ogy and environment in the development of eating dis- disorders. Enmeshment of mother with daughter to the
orders is complex, so these disorders are best defined in point that the teenager cannot develop her own identity
a biopsychosocial context. (a key developmental marker of adolescence) may be a
predisposing factor. The teenager may cope by asserting
control over food, as she senses her lack of control in
ETIOLOGY the developmental realm. A second theory involves fa-
ther–daughter distancing. As puberty progresses and a
Some evidence supports a genetic predisposition for eat- girl’s sexuality blossoms, a father may experience diffi-
ing disorders. There is a 7% incidence of anorexia ner- culty in dealing with his daughter as a sexual being and
vosa in first-degree relatives of anorexic patients com- may respond by withdrawing both emotionally and
pared with a 1–2% incidence in the general population. physically. The teenage girl may intuitively recognize
Twin studies have shown a 55% concordance rate in this and subconsciously decrease her food intake in
monozygotic twins, compared with 7% in dizygotic order to become prepubertal again. A third theory is re-
twins. A study of males with anorexia nervosa showed a lated to puberty itself. Some teenagers may fear or dis-
relative risk of 20 for first-degree female relatives. Most like their changing bodies. By restricting food intake
studies have found a higher incidence of eating disorders they lose weight, stop menstruating, and effectively re-
among first-degree relatives of bulimic patients as well. verse pubertal development.
Several genetic markers have been associated with an in- In addition, society has provided the message that
creased susceptibility to anorexia nervosa, though no being thin or muscular is necessary for attractiveness
clinically relevant genetic test is available to date. Genet- and success. The ease of access to diet products—foods
ics and eating disorders continue to be an active area of and diet pills—as well as Internet instructions
investigation, with a national study underway that will (proanorexia sites) makes it simple for adolescents to
define the genetic aspect more specifically. embark on a quest for thinness or muscularity.
Leptin, a hormone produced in adipocytes and in- Genetic predisposition, psychological factors, and
volved with satiety signaling, may play a role in the evo- environmental factors combine to create a milieu that
lution of eating disorders. Anorexic patients have a de- promotes adolescent eating disorders.
creased amount of leptin initially, which increases to
excessive levels as they regain weight. One hypothesis is
that there may be an abnormality in leptin receptors, Bailer UF, Kaye WH: A review of neuropeptide and neuroen-
with satiety indicators not responding normally. Other docrine dysregulation in anorexia and bulimia nervosa. Curr
neurotransmitters, such as serotonin and neuropeptide Drug Target CNS Neurol Disord 2003;2(1):53 [PMID:
Y, which are involved in satiety, are abnormal in some 12769812].
anorexic patients. An alteration in dopamine has also Brambilla F et al: Central dopaminergic function in anorexia and
been recognized, though its significance has not been bulimia nervosa: A psychoneuroendocrine approach. Psy-
elucidated. Grehlin, a gut peptide, has been shown to choneuroendocrinology 2001;26(4):393 [PMID:11259859].
be elevated in patients with anorexia nervosa and is also Strober M et al: Males with anorexia nervosa: A controlled study of
eating disorders in first-degree relatives. Int J Eat Disord
hypothesized to play a role in the pathophysiology of 2001;29(3)263 [PMID 11262504].
anorexia. Patients with bulimia nervosa or binge-eating Tolle V et al: Balance in ghrelin and leptin plasma levels in anorexia
disorder appear to have a blunted serotonin response to nervosa patients and constitutionally thin women. J Clin En-
eating and satiety. With a decreased satiety response, docrinol Metab 2003;88(1):109 [PMID: 12519838].
patients continue to eat, leading to a binge. Treatment Urwin RE et al: Anorexia nervosa (restrictive subtype) is associated
with selective serotonin reuptake inhibitors (SSRIs) with a polymorphism in the novel norepinephrine transporter
165
Copyright © 2005, 2001, by The McGraw-Hill Companies, Inc. Click here for terms of use.
166 / CHAPTER 5

gene promoter polymorphic region Mol Psychiatry 2002; image. Sudden changes in dietary habits, such as be-
7(6):652 [PMID: 12140790]. coming vegetarian, may be a first sign of anorexia, espe-
Woodside DB: Specificity of eating disorders diagnoses in families cially if the change is abrupt and without good reason.
of probands with anorexia nervosa and bulimia nervosa. The typical bulimic patient is more impulsive, tend-
Compr Psychiatry 1998;39;261 [PMID: 9777277].
ing to engage in risk-taking behavior such as alcohol
use, drug use, and sexual experimentation. Bulimic pa-
INCIDENCE tients are often an appropriate weight for height or
Among teenage girls in the United States, anorexia ner- slightly overweight, and they get average grades. Some
vosa is the third most common chronic illness. The in- studies have found that 50% of bulimic patients have
cidence in the United States has been increasing been sexually abused. In males, wrestling and homosex-
steadily since the 1930s. Ascertaining exact incidence is ual orientation predispose to bulimia nervosa.
difficult. It is thought that 1–2% of teenagers have
anorexia nervosa and 2–4% have bulimia nervosa. Ado- DIAGNOSIS
lescents outnumber adults 5 to 1, although the number
of adults with eating disorders is rising. The incidence 1. Anorexia Nervosa
is also increasing among younger children. Often pre- Table 5–1 lists the diagnostic criteria for anorexia ner-
pubertal patients have significant associated psychiatric vosa, according to the Diagnostic and Statistical Manual
diagnoses. Females outnumber males 8 to 1. The num- of Mental Disorders, 4th edition (DSM-IV). There are
ber of males diagnosed with eating disorders has also in- two forms of anorexia nervosa. In the restricting type,
creased, which correlates with the increased media em- patients do not regularly engage in binge eating or
phasis on muscular, chiseled appearance as the male purging. In the purging type, classic anorexia nervosa is
ideal. In the recent Youth Risk Behavior Survey (2001) combined with binge eating or purging behavior (or
of US teenagers, 62% of females and 29% of males both). Differentiating the two is important because of
were attempting to lose weight, a 3% increase com- differing implications for prognosis and treatment.
pared with 1999. Fourteen percent of youth did not eat
for more than 24 hours to lose weight. Overall, 9.2% of
youth had used diet pills as a weight loss method in the
Clinical Findings
previous 30 days—12.6% of girls and 5.5% of boys. A. SYMPTOMS AND SIGNS
Self-induced vomiting or laxative use (or both) was also Clinicians should recognize the early symptoms and
common; 7.8% of females and 2.9% of males were signs of anorexia nervosa because intervention may pre-
using one or the other to lose weight. Concern about
weight, and harmful attempts to lose weight all in-
creased from 1999 to 2001. Binge-eating disorder has a
1.1% incidence in the teenage population. Forty-six Table 5–1. Diagnostic criteria for
percent of females and 30% of males report at least one anorexia nervosa.
bingeing episode during their lifetime.
A. Refusal to maintain body weight at or above a minimally
Centers for Disease Control and Prevention. Youth Risk Behavior normal weight for age and height (eg, weight loss leading
Surveillance System 2001. to maintenance of body weight less than 85% of that ex-
http://www.cdc.gov/mmwr/pdf/ss/ss5104.pdf. pected; or failure to make expected weight gain during
Pawluck D: Secular trends in the incidence of anorexia nervosa: In- period of growth, leading to body weight less than 85% of
tegrative review of population-based studies. Int J Eat Disord that expected).
1998;23:347 [PMID: 9561424]. B. Intense fear of gaining weight or becoming fat, even
though underweight.
PREDISPOSING FACTORS C. Disturbance in the way in which one’s body weight or
shape is experienced, undue influence of body weight or
In the past, the typical anorexic patient was described as shape on self-evaluation, or denial of the seriousness of
a high-achieving, athletic, straight-A student from a the current low body weight.
middle class socioeconomic background. Demograph- D. In postmenarchal females, amenorrhea, ie, the absence of
ics have changed somewhat, and anorexia nervosa now at least three menstrual cycles. (A woman is considered to
occurs in all races and socioeconomic classes. Children have amenorrhea if her periods occur only following hor-
involved in gymnastics, figure skating, and ballet—ac- mone, eg, estrogen, administration.)
tivities that emphasize (and in which coaches often re- Reprinted, with permission, from the Diagnostic and Stastistical
quire) thin bodies—are at higher risk for anorexia than Manual of Mental Disorders, 4th ed. Text Revision. Copyright 2000.
are children in sports that do not emphasize body American Psychiatric Association.
 EATING DISORDERS / 167

vent the full-blown syndrome from developing. Pa- ensue, as orthostasis and hypotension secondary to im-
tients may show some of the behaviors and psychology paired cardiac function occur. Left ventricular mass is
of anorexia nervosa, such as reduction in dietary fat and decreased, (as all striated muscle throughout the body
intense concern with body image, even before weight loses mass), stroke volume is compromised, and periph-
loss or amenorrhea occurs. eral resistance is increased. Patients can develop pro-
Making the diagnosis of anorexia nervosa can be longed QT syndrome, putting them at risk for cardiac
challenging because adolescents may try to conceal their arrhythmias. Peripheral circulation is reduced. Hands
illness. Assessing the patient’s body image is essential to and feet may be blue and cool. Hair thins, nails become
determining the diagnosis. Table 5–2 lists screening brittle, and the skin is dry. Lanugo develops as a primi-
questions that help to tease out a teenager’s perceptions tive response to starvation. The gastrointestinal tract
of body image. Additional diagnostic screening tools may be affected. Inability to take in normal quantities
include the Eating Attitudes Test (EAT) or other ques- of food, early satiety, and gastroesophageal reflux can
tionnaires that assess a range of eating and dieting be- develop as the body adapts to reduced intake. The nor-
haviors. Parental observations are critical in determin- mal gastrocolic reflex may be temporarily lost due to
ing whether a patient has expressed dissatisfaction over lack of stimuli, leading to delayed gastric emptying and
body habitus as well as revealing what weight loss tech- constipation.
niques the child has attempted. In the teenager who is Neurologically, patients may experience decreased
not ready to share his or her concerns about body cognition, inability to concentrate, increased irritabil-
image, the clinician may find clues to the diagnosis by ity, and depression, which may be related to structural
carefully considering other presenting symptoms. brain changes and decreased cerebral blood flow.
Weight loss from a baseline of normal body weight is A combination of malnutrition and stress causes hy-
an obvious red flag and should raise the clinical suspi- pothalamic hypogonadism. The hypothalamic–pitu-
cion of an eating disorder. Additionally, anorexia ner- itary–gonadal axis shuts down as the body struggles to
vosa should be considered in any girl with secondary survive, directing finite energy resources to support
amenorrhea who has lost weight. more vital functions. Both males and females experi-
Physical symptoms are usually secondary to weight ence decreased libido and interruption of pubertal de-
loss and proportional to the degree of malnutrition. velopment, depending on the timing of the illness.
The body effectively goes into hibernation, becoming Skeletal growth may be interrupted as well.
functionally hypothyroid (euthyroid sick) to save as Nutritional assessment is vital. Often patients elimi-
much energy as possible. Body temperature decreases, nate fat from their diets and may eat as little as
and patients report being colder than normal. Patients 100–200 kcal/d. A gown-only weight after urination is
become bradycardic, especially in the supine position. the most accurate way to assess weight. Patients tend to
Dizziness, lightheadedness, and occasional syncope may wear bulky clothes and may hide weights in their pock-
ets or drink excessive amounts of fluid (water-loading)
to trick the practitioner. Calculating body mass index
(BMI)—weight in kilograms divided by height in me-
Table 5–2. Screening questions to help diagnose ters squared—is an efficient way to interpret degree of
anorexia and bulimia nervosa. malnutrition. A BMI less than the fifth percentile
(using the new BMI growth curves) indicates signifi-
How do you feel about your body? cant malnutrition. Additionally, ideal body weight
Are there parts of your body you might change? (IBW) for height should be calculated. A weight less
When you look at yourself in the mirror, do you see yourself than 85% IBW is one of the diagnostic criteria for
as overweight, underweight, or satisfactory? anorexia nervosa. Ideal body weight should be calcu-
If overweight, how much do you want to weigh? lated using the 50th percentile of BMI for age.
If your weight is satisfactory, has there been a time that you A hallmark physical feature of anorexia nervosa in
were worried about being overweight? girls is amenorrhea, which occurs for two reasons. The
If overweight/underweight, what would you change? hypothalamic–pituitary–ovarian axis shuts down under
Have you ever been on a diet? stress, causing hypothalamic amenorrhea. Additionally,
What have you done to help yourself lose weight? adipose tissue is needed to convert estrogen to its acti-
Do you count calories or fat grams? vated form. When weight loss is significant, adipose tis-
Do you keep your intake to a certain number of calories? sue is lost and there is not enough substrate to activate
Have you ever used nutritional supplements, diet pills, or lax- estrogen. Resuming normal menses depends on increas-
atives to help you lose weight? ing both body weight and body fat. Approximately
Have you ever made yourself vomit to get rid of food or lose 73% of postmenarcheal girls will resume menstruating
weight? if they reach 90% of their IBW. An adolescent female
168 / CHAPTER 5

needs, on average, 17% body fat to restart menses and disease. The history and physical examination should
22% body fat if she has primary amenorrhea. direct laboratory and radiologic evaluation.

B. LABORATORY FINDINGS 2. Bulimia Nervosa

Most organ systems can potentially suffer some degree
of damage in the anorexic patient, related both to sever- Table 5–4 lists the diagnostic criteria for bulimia ner-
ity and duration of illness (Table 5–3). Initial screening vosa. Binge eating is either eating excessive amounts of
should include complete blood count with differential, food during a normal mealtime or having a meal (or
and serum levels of electrolytes, blood urea nitrogen/ other eating episode) last longer than usual, consuming
creatinine, phosphorus, calcium, magnesium, and thy- food throughout. Bulimic individuals feel out of con-
roid-stimulating hormone, as well as liver function tests trol while eating, unable or unwilling to recognize sati-
and urinalysis. An electrocardiogram should be per- ety signals. Any type of food may be included in a
formed, because significant electrocardiographic abnor- binge, though typically it is either carbohydrates or
malities may be present, most importantly prolonged junk food. Extreme guilt is often associated with the
QT syndrome. Bone densitometry should be done if episode. At some point, either prior to or during a
amenorrhea has persisted for 6 months, as patients binge, bulimic individuals often decide to purge. The
begin to accumulate risk for osteoporosis. amount of food consumed feels overwhelming, and they
do not want to gain weight. The most common ways to
purge are self-induced vomiting, exercise, and laxative
Differential Diagnosis use. Some individuals will vomit multiple times during
If the diagnosis is unclear (ie, the patient has lost a sig- a purge episode, after using large amounts of water to
nificant amount of weight but does not have typical cleanse their system. This can induce significant elec-
body image distortion or fat phobia), then the clinician trolyte abnormalities such as hyponatremia and hy-
must consider the differential diagnosis for weight loss pokalemia, which may put the patient at acute risk for
in adolescents. This includes inflammatory bowel dis- arrhythmia or seizure. Other methods of purging in-
ease, diabetes, hyperthyroidism, malignancy, and de- clude diuretics, diet pills, cathartics, and nutritional
pression. Less common diagnoses include adrenal insuf- supplements, including Metabolife.
ficiency and malabsorption syndromes such as celiac

Table 5–4. Diagnostic criteria for

bulimia nervosa.
Table 5–3. Laboratory findings: anorexia nervosa.
A. Recurrent episodes of binge eating. An episode of binge
Increased blood urea nitrogen/creatinine secondary to renal eating is characterized by both of the following:
insufficiency (1) eating, in a discrete period of time (eg, within any
Decreased white blood cells, platelets, and less commonly red 2-hour period), an amount of food that is definitely
blood cells/hematocrit secondary to bone marrow suppres- larger than most people would eat during a similar pe-
sion or fat atrophy of the bone marrow riod of time and under similar circumstances.
Increased AST and ALT secondary to malnutrition. (2) a sense of lack of control over eating during the
Increased cholesterol, thought to be related to fatty acid me- episodes (eg, a feeling that one cannot stop eating or
tabolism control what or how much one is eating)
Decreased alkaline phosphatase secondary to zinc deficiency B. Recurrent inappropriate compensatory behavior in order
Low to low-normal thyroid-stimulating hormone and thyrox- to prevent weight gain, such as self-induced vomiting;
ine misuse of laxatives, diuretics, enemas, or other medica-
Decreased follicle-stimulating hormone, luteinizing hormone, tions; fasting; or excessive exercise.
estradiol, and testosterone secondary to shutdown of hy- C. The binge eating and inappropriate compensatory behav-
pothalamic–pituitary–gonadal axis iors both occur, on average, at least twice a week for 3
Abnormal electrolytes related to hydrational status months.
Decreased phosphorus D. Self-evaluation is unduly influenced by body shape and
Decreased insulin-like growth factor weight.
Increased cortisol E. The disturbance does not occur exclusively during
Decreased urine specific gravity in cases of intentional water episodes of anorexia nervosa.
intoxication Reprinted, with permission, from the Diagnostic and Statistical
ALT = alanine aminotransferase; AST = aspartate aminotrans- Manual of Mental Disorders, 4th ed. Text Revision. Copyright 2000.
ferase. American Psychiatric Association.
 EATING DISORDERS / 169

Diagnosing bulimia nervosa can be difficult unless Abrasion of the proximal interphalangeal joints may
the teenager is forthcoming or parents or caregivers can occur secondary to scraping the fingers against teeth
supply direct observations. Often bulimic patients are while inducing vomiting. Rarely a heart murmur is
average or slightly above average in body weight, with- heard. An irreversible cardiomyopathy can develop sec-
out any physical abnormalities. Screening all teenagers ondary to ipecac use. Tachycardia and hypertension
for body image concerns is crucial. If the teenager ex- may occur secondary to caffeine and diet pill use.
presses concern about being overweight, then the clini-
cian needs to screen the patient about dieting methods. B. LABORATORY FINDINGS
Asking whether patients have binged, feel out of con- Electrolyte disturbances are characteristic of bulimic pa-
trol while eating, or whether they cannot stop eating tients. The method of purging results in specific abnor-
can clarify the diagnosis. Parents may report that signif- malities. Vomiting causes metabolic alkalosis, hy-
icant amounts of food are missing or disappearing more pokalemia, and hypochloremia. If laxatives are used,
quickly than normal. If the physician is suspicious, di- then a metabolic acidosis develops with hypokalemia
rect questioning about all the ways to purge should fol- and hypochloremia. Amylase may be increased sec-
low. Indicating first that the behavior in question is not ondary to chronic parotid stimulation.
unusual can make the questioning less threatening and
more likely to elicit a truthful response. For example, American Psychiatric Association: Diagnostic and Statistical Manual
the clinician might say, “Some teenagers who try to lose of Mental Disorders, 4th ed. Text Revision. American Psychi-
weight make themselves vomit after eating. Have you atric Association, 2000.
ever considered or done that yourself?” Kreipe RE, Birndorf SA: Eating disorders in adolescents and young
adults. Med Clin North Am Jul 2000;84(4):1027 [PMID:
10928200].
Clinical Findings Panagiotopoulos C et al: Electrocardiographic findings in adoles-
cents with eating disorders. Pediatrics 2000;105(5):1100
A. SYMPTOMS AND SIGNS [PMID: 10790469].
Symptoms are related to the mechanism of purging.
Gastrointestinal problems are most prominent. Ab- 3. Binge-Eating Disorder
dominal pain is a frequent complaint. This can be due
to gastroesophageal reflux, because frequent vomiting The diagnostic category of binge-eating disorder was
may result in esophagitis. Early satiety, involuntary created in DSM-IV. Officially, it is still considered a re-
vomiting, and complaints of food “coming up” on its search diagnosis. Studies show that most adults who
own are frequent. Less common but more serious is he- have binge-eating disorder (a prevalence of 2–4%) de-
matemesis or esophageal rupture. Patients may report velop symptoms during adolescence Table 5–5 lists the
bowel problems—diarrhea or constipation—if laxatives diagnostic criteria.
have been used. Sialadenosis—parotid pain and en-
largement—may occur secondary to frequent vomiting. Clinical Findings
Erosion of dental enamel may result from increased ex-
posure to acidity during vomiting. Because comorbid A. SYMPTOMS AND SIGNS
depression is common in bulimia nervosa, patients may Binge-eating disorder is a new eating disorder category.
report difficulty sleeping, decreased energy, decreased It occurs most often in patients who are overweight or
motivation, and headaches. Lightheadedness or syn- obese. Eighteen percent of such patients report binge-
cope may develop secondary to dehydration. ing at least once in the past year. Patients with binge-
It is important to note that most purging methods eating disorder have an increased incidence of depres-
are ineffective. When patients binge, they may con- sion and substance abuse. Using the DSM-IV
sume thousands of calories. Digestion begins rapidly. diagnostic criteria as a guide for evaluation, the suspi-
Although the patient may be able to vomit some of the cion of binge-eating disorder should be raised for any
food, much is actually digested and absorbed. Laxatives significantly overweight patient. Specific questionnaires
work on the large intestine, leading to fluid and elec- are available for evaluating patients suspected of having
trolyte loss. Consumed calories are still absorbed from binge-eating disorder.
the small intestine. Use of diuretics may result in de-
creased fluid weight and electrolyte imbalance. B. LABORATORY FINDINGS
On physical examination, bulimic patients may be The clinician should assess causes and complications of
dehydrated and have orthostatic hypotension. obesity, and laboratory evaluation should include thy-
Sialadenosis, tooth enamel loss, dental caries, and ab- roid function tests and measurement of cholesterol and
dominal tenderness are the most common findings. triglyceride levels.
170 / CHAPTER 5

Table 5–5. Diagnostic criteria for Table 5–6. Diagnostic criteria for eating disorder
binge-eating disorder. not otherwise specified.

A. Recurrent episodes of binge eating. An episode of binge The eating disorder not otherwise specified category is for
eating is characterized by both of the following: disorders of eating that do not meet the criteria for any spe-
(1) eating, in a discrete period of time (eg, within any cific eating disorder. Examples include
2-hour period), an amount of food that is definitely 1. For females, all of the criteria for anorexia nervosa are
larger than most people would eat in a similar period met except that the individual has regular menses.
of time under similar circumstances. 2. All of the criteria for anorexia nervosa are met except
(2) a sense of lack of control over eating during the that, despite significant weight loss, the individual’s cur-
episode (eg, a feeling that one cannot stop eating or rent weight is in the normal range.
control what or how much one is eating) 3. All of the criteria for bulimia nervosa are met except that
B. The binge-eating episodes are associated with three (or the binge eating and inappropriate compensatory
more) of the following: mechanisms occur at a frequency of less than twice a
(1) eating much more rapidly than normal week or for a duration of less than 3 months.
(2) eating until feeling uncomfortably full 4. The regular use of inappropriate compensatory behav-
(3) eating large amounts of food when not feeling physi- ior by an individual of normal body weight after eating
cally hungry small amounts of food (eg, self-induced vomiting after
(4) eating alone because of being embarrassed by how the consumption of two cookies).
much one is eating 5. Repeatedly chewing and spitting out, but not swallow-
(5) feeling disgusted with oneself, depressed, or very ing, large amounts of food.
guilty after overeating
Reprinted with permission from the Diagnostic and Statistical
C. Marked distress regarding binge eating at present. Manual of Mental Disorders, 4th ed. Text Revision. Copyright 2000.
D. The binge eating occurs, on average, at least 2 days a week American Psychiatric Association.
for 6 months.
E. The binge eating is not associated with regular use of in-
appropriate compensatory behaviors (eg, purging, fasting,
excessive exercise) and does not occur exclusively during
the course of anorexia nervosa or bulimia nervosa. COMPLICATIONS (Table 5–7)
Reprinted, with permission, from the Diagnostic and Statistical 1. Anorexia Nervosa
Manual of Mental Disorders, 4th ed. Text revised. Copyright 2000.
American Psychiatric Association. Short-Term Complications
A. EARLY SATIETY
Patients may have significant difficulty digesting mod-
est quantities as their bodies adapt to increased caloric
Fairburn CG et al: The natural course of bulimia nervosa and binge
eating disorder in young women. Arch Gen Psych 2000;57:
intake. Patients may benefit from a gastric-emptying
659. [PMID: 10891036]. agent such as metoclopramide. This complication usu-
Johnson WG et al: Measuring binge eating in adolescents: Adoles- ally resolves after a patient has become used to larger
cent and parent versions of the questionnaire of eating and meals.
weight patterns. Int J Eat Disord 1999;26:301 [PMID
10441246]. B. SUPERIOR MESENTERIC ARTERY SYNDROME
Schneider M: Bulimia nervosa and binge eating disorder in adoles- As patients become malnourished, the fat pad between
cents. Adolesc Med State of the Art Reviews 2003;14(1): the superior mesenteric artery and the duodenum may
119 [PMID: 12529196]. shrink, compressing the transverse duodenum and
causing vomiting and intolerance of oral intake, espe-
4. Eating Disorder Not Otherwise cially solids. Diagnosis is made by an upper GI series,
Specified which shows to and fro movement of barium in the de-
scending and transverse duodenum proximal to the ob-
An additional diagnostic category found in DSM-IV is struction. Treatment involves a liquid diet or nasoduo-
eating disorder not otherwise specified. Patients do not denal feedings until restoration of the fat pad has
meet all the criteria for either anorexia nervosa or bu- occurred, coincident with weight gain.
limia nervosa, but have features of either or both. Table
5–6 lists the diagnostic criteria. Individuals require sim- C. CONSTIPATION
ilar treatment intervention depending on the clinical Patients may have prolonged constipation, often not
features. having a bowel movement for a week or longer. Two
 EATING DISORDERS / 171

Table 5–7. Complications of anorexia and D. REFEEDING SYNDROME

bulimia nervosa. Described in the Treatment section.

Cardiovascular Hematologic
Bradycardia Leukopenia Long-Term Complications
Postural hypotension Anemia
Arrhythmia, sudden death Thrombocytopenia A. OSTEOPOROSIS
Congestive heart failure ↓ESR Approximately 90% of females with anorexia nervosa
(during refeeding) Impaired cell-mediated have reduced bone mass at one or more sites. The de-
Pericardial effusion immunity velopment of osteopenia and osteoporosis is multifacto-
Mitral valve prolapse Metabolic rial. Estrogen and testosterone are essential to potenti-
ECG abnormalities Dehydration ate bone development. Teenagers are particularly at risk
(prolonged QT, low volt- Acidosis as they accrue 40% of their bone mineral during ado-
age, T-wave abnormali- Hypokalemia lescence. Low body weight is most predictive of bone
ties, conduction defects) Hyponatremia loss. Amenorrhea, an indicator of estrogen deficiency, is
Endocrine Hypochloremia also highly correlated with osteoporosis. Bone minerals
↓LH, FSH Hypochloremic alkalosis
begin to resorb without estrogen. Elevated cortisol lev-
↓T3, ↑rT3; ↓ T4, TSH Hypocalcemia
Irregular menses Hypophosphatemia
els and decreased insulin-like growth factor-1 (IGF-1)
Amenorrhea Hypomagnesemia also contribute to bone resorption. Studies show that as
Hypercortisolism Hypercarotenemia little as 6 months of amenorrhea can lead to osteopenia
Growth retardation Neurologic or osteoporosis. In one study, 44% of adolescents with
Delayed puberty Cortical atrophy anorexia had osteopenia of the lumbar spine. Males also
Gastrointestinal Peripheral neuropathy can develop osteoporosis due to decreased testosterone.
Dental erosion Seizures The only proven treatment for osteoporosis in
Parotid swelling Thermoregulatory anorexia nervosa in girls is regaining sufficient weight
Esophagitis, esophageal abnormalities and body fat to restart the menstrual cycle. Controversy
tears ↓REM and slow-wave exists regarding the use of hormone replacement ther-
Delayed gastric emptying sleep apy (HRT). Most studies do not support use of HRT
Gastric dilatation (rarely Renal to improve bone recovery; however, some evidence in-
rupture) Hematuria dicates that use of HRT may stop further bone loss and
Pancreatitis Proteinuria may be of particular benefit for patients with extremely
Constipation ↓Renal concentrating low body weight (less than 70% IBW). Some practi-
Diarrhea (laxative abuse) ability tioners use HRT if amenorrhea is prolonged (> 1 year)
Superior mesenteric artery Skeletal and the patient is not able to achieve normal body
syndrome Osteopenia weight. The bisphosphonates used to treat post-
Hypercholesterolemia Fractures menopausal osteoporosis are currently being studied in
↑Liver function tests (fatty
adolescents. Newer treatments in research trials have
infiltration of the liver)
shown some promise, including recombinant IGF-1 in-
LH = luteinizing hormone; ECG = electrocardiogram; FSH = jection and use of dehydroepiandrosterone, though
follicle-stimulating hormone; T3 = triiodothyronine; rT3 = resin tri- they are both still under investigation.
iodothyronine uptake; T4 = tetraiodothyronine; TSH = thyroid-
stimulating hormone; ESR = erythrocyte sedimentation rate;
REM = rapid eye movement. B. BRAIN CHANGES
As malnutrition becomes more pronounced, brain tis-
sue—both white and gray matter—is lost and a con-
comitant increase in cerebrospinal fluid occurs in the
sulci and ventricles. Follow-up studies of weight-recov-
mechanisms contribute to this symptom: loss of gastro- ered anorexic patients show a persistent loss of gray
colic reflex and loss of colonic muscle tone. Typically matter, although white matter returns to normal. Func-
stool softeners do not help because the colon has de- tionally there does not seem to be a specific relationship
creased peristaltic amplitude. Agents that induce peri- between cognition and brain tissue loss, though studies
stalsis, such as bisacodyl and polyethylene glycol-elec- have shown a decrease in cognitive ability, as well as de-
trolyte solution (Miralax), are helpful. Constipation can creased cerebral blood flow in more severe malnour-
persist for up to 6–8 weeks after refeeding. Occasionally ished states. Communicating to the patient and the
patients need enemas. family that brain tissue can be lost can have a signifi-
172 / CHAPTER 5

cant effect on the perception of the seriousness of this Mortality

disorder.
The mortality rate in bulimic patients is similar to that
in anorexic patients. Death usually results from suicide
Castro J et al: Bone mineral density in male adolescents with or electrolyte derangements.
anorexia nervosa. J Am Acad Child Adolesc Psychiatry 2002;
41(5) 613 [PMID: 12014794].
Golden NH: Osteopenia and osteoporosis in anorexia nervosa.
Adolesc Med State of the Art Reviews. 2003;14(1):97 TREATMENT
[PMID::12529194].
Karlsson MK: Bone size and volumetric density in women with Many treatment modalities are available. Factors that
anorexia nervosa receiving estrogen replacement therapy and determine treatment interventions are severity of ill-
in women recovered from anorexia nervosa. J Clin En- ness, length of illness, specific manifestations of disease,
docrinol Metab 2000;85:3177 [PMID: 10999805]. previous treatment approaches and outcomes, program
Kerem NC, Katzman DK: Brain structure and function in adoles- availability, financial resources, and insurance coverage.
cents with anorexia nervosa. Adolesc Med State of the Art Re- Treatment options include outpatient management,
views. 2003;14(1):109 [PMID: 12529195]. day treatment hospitalization, and inpatient hospital-
ization of either a medical or psychiatric nature. Resi-
dential treatment is most often used when outpatient
Mortality management or short-term hospitalization fails and the
Patients with eating disorders are at a higher risk of eating disorder becomes chronic. Residential treatment
dying than the general population. Meta-analysis has usually lasts 2–6 months. Day treatment programs are a
shown the risk of dying to be 5.9% in such patients. good intervention for patients who do not yet need in-
Mortality estimates vary between 0% and 18%, de- patient care but who are not improving with outpatient
pending on the patient population studied and the management. Treatment is costly. Many patients do
length of the study. One study showed the risk of dying not have insurance benefits that adequately cover the
to be 0.56% per year. Death in anorexic patients is due cost of treatment, leaving parents and practitioners with
to suicide, abnormal electrolytes, and resultant cardiac profound dilemmas as to how to best provide treatment
arrhythmias. in the face of financial constraints.
Regardless of type of treatment program, a multidis-
ciplinary approach is most effective. Treatment should
Herzog DB et al: Mortality in eating disorders: A descriptive study. include medical monitoring, nutrition therapy, and in-
Int J Eat Dis 2000;28(1):20 [PMID: 10800010]. dividual and family psychotherapy by practitioners ex-
perienced with eating disorder patients. Family therapy
is especially helpful with younger teenagers, whereas
2. Bulimia Nervosa older teenagers tend to benefit more from individual
Short-Term & Long-Term Complications therapy, although both should be encouraged. Family
therapy is an important means by which to help fami-
Complications for normal-weight bulimic patients are lies understand the development of the disease and ad-
related to their mechanisms of purging, and many of dress the issues that may be barriers to recovery. Both
these complications were listed earlier in the Symptoms types of therapy are encouraged in most treatment pro-
and Signs section. If the bulimic patient is significantly grams, and recovery without psychotherapy is unusual.
malnourished, the complications may be the same as The average length of therapy is roughly 6–9 months,
those encountered in the anorexic patient. Other com- although some individuals continue therapy for ex-
plications of bulimia include esophageal rupture, acute tended periods. Adjunctive modalities include art and
or chronic esophagitis, and, rarely, Barrett syndrome. horticulture therapy, therapeutic recreation, and mas-
Chronic vomiting can lead to metabolic alkalosis, and sage therapy.
laxative abuse may cause metabolic acidosis. Patients Careful instruction in nutrition is important in
may develop aspiration pneumonia from vomiting. helping the teenager dispel misconceptions about nutri-
Diet pill use can cause insomnia, hypertension, tachy- tion, identify realistic nutritional goals, and normalize
cardia, palpitations, seizures, and sudden death. eating. Initially, nutrition education may be the most
Patients who stop taking laxatives can have trouble important intervention as the teenager slowly works
with bowel function, most often constipation. Treating through his or her fears of fat-containing foods and
constipation can be difficult psychologically, because weight gain. The teenager begins to trust the nutrition
the practitioner may need to prescribe agents similar to therapist and begins to restore body weight, by eventu-
the drugs of abuse used during the eating disorder. ally eating in a well-balanced, healthy manner.
 EATING DISORDERS / 173

1. Anorexia Nervosa serum phosphate (as the body finally starts making
adenosine triphosphate), decreased serum potassium (as
The key to determining level of intervention depends increased insulin causes shifting of K+ from extracellular
on the degree of malnutrition, the rapidity of weight fluid into K+-depleted cells), and edema related to fluid
loss, the degree of medical compromise, and presence of shifts as well as from congestive heart failure.
life-threatening electrolyte abnormalities. No absolute Caloric intake can be increased 250 kcal/d as long as
criteria determine level of intervention. The practi- refeeding syndrome does not occur. Weight goals vary
tioner must examine the degree of medical compro- depending on programmatic approach. Typically intake
mise, consider immediate risks, and the potential for an is adjusted to reach a goal of 0.1–0.25 kg/d weight gain.
individual to reverse the situation on his or her own. Overnight monitoring for bradycardia is helpful in
A. INPATIENT TREATMENT assessing degree of metabolic compromise. Usually the
more rapid and severe the weight loss, the worse the
Table 5–8 lists the criteria for hospital admission gener- bradycardia. Improving bradycardia correlates with
ally used in the medical community. It is usually quite weight recovery. Orthostatic hypotension is most severe
difficult for a patient who is losing weight rapidly (> around hospital day 4, improving steadily and correct-
2 lb/wk) to reverse the weight loss because the body is ing by the third week of nutritional rehabilitation. An
in a catabolic state. electrocardiogram should be obtained because the pa-
If a patient is hospitalized the initial goal is to stop tient is at risk for prolonged QT syndrome and junc-
weight loss. The clinician can begin a meal plan con- tional arrhythmias related to the severity of bradycardia.
taining approximately 250 kcal more than the patient It usually takes 2–3 weeks to reach the initial goals
has been routinely eating. Depending on the sophistica- of hospitalization—steady weight gain, toleration of
tion of the program and support staff, this can usually oral diet without signs of refeeding syndrome, corrected
be accomplished orally. Ideally, with the help of a nu- bradycardia (heart rate > 45/min for three consecutive
tritionist, patients should start with a well-balanced nights), and orthostasis. Specific weight criteria are used
meal plan, with appropriately divided carbohydrates, by many programs when considering discharge. This
proteins, and fats. Usually patients tolerate oral meals. depends partly on admission weight. Ideally a patient
If the patient resists, a nasogastric tube or intravenous gains at least 5% of his or her ideal weight. Some pro-
alimentation can be used for a short time. Aside from grams set discharge at 80%, 85%, or 90% IBW. Patient
caloric needs, the clinician needs to pay attention to the outcomes are improved with discharge at a higher body
patient’s hydration status, including the appropriate weight. One study has shown that patients do better if
amount of fluid with the meal plan. Dehydration discharged at 95% IBW. Frequently, insurance compa-
should be corrected slowly. The oral route is usually ad- nies do not cooperate and will not pay beyond strict
equate. Aggressive intravenous fluid administration medical stabilization (normal vital signs and normal
should be avoided because left ventricular mass is com- electrolytes). In many practitioners’ experience, relapse
promised and rapid increase in volume may not be tol- rate is high if patients are discharged at less than 75%
erated. Regulating fluid intake is important, because IBW.
water intoxication can contribute to abnormal elec- Extremely malnourished patients may not benefit
trolytes and falsified weights. from individual psychotherapy or nutritional instruc-
During the initial introduction of food, the clinician tion initially because they may be cognitively impaired.
needs to monitor the patient for refeeding syndrome, a Beginning family psychotherapy at first, with the addi-
phenomenon that occurs if caloric intake is increased tion of individual psychotherapy after the first week of
too rapidly. Signs of refeeding syndrome are decreased refeeding, may prove more effective.
Medications (specifically SSRIs) are not helpful in
treating anorexia nervosa independently. Once the pa-
Table 5–8. Criteria for inpatient treatment tient has achieved approximately 85% IBW, then
SSRIs (fluoxetine, citalopram, or sertraline) help prevent
of anorexia nervosa. relapse.
Several open label trials support the use of atypical
Body weight < 75% of ideal body weight antipsychotics (risperidone, olanzapine), which target
Supine heart rate < 45/min specifically the body image distortion that these pa-
Symptomatic hypotension or syncope tients experience.
Hypokalemia: K+ < 2.5 mEq/L To help address the malnourished state, a multivita-
Rapid weight loss that cannot be interrupted as outpatient min with iron and zinc supplementation may be bene-
Failure of outpatient management ficial. Zinc has been found to be depleted in anorexia
Acute food refusal nervosa. Supplementation helps restore appetite as well
174 / CHAPTER 5

as improve depressive moods. Symptomatic treatment complication of initial therapy to help maintain their
for disturbances in the gastrointestinal system should be confidence in the care plan.
used appropriately until symptoms resolve. Another reason to hospitalize bulimic patients is
failure of outpatient management. The binge–purge
B. OUTPATIENT TREATMENT cycle is addictive and can be difficult for patients to in-
Not all patients diagnosed with anorexia nervosa need terrupt on their own. Hospitalization can offer a forced
inpatient treatment, especially if parents and clinicians break from the cycle, allowing patients to normalize
recognize the warning signs early. These patients can their eating, interrupt the addictive behavior, and re-
receive treatment in the outpatient setting, employing gain ability to recognize satiety signals.
the same multidisciplinary team approach. Appropriate Outpatient management can be pursued if patients
nutrition counseling is vital in guiding a patient and are medically stable. Cognitive-behavioral therapy is
family through the initial stages of recovery. As the nu- crucial to help bulimic patients understand their disease
trition therapist is working at increasing the patient’s and to offer suggestions for decreasing bingeing and
caloric intake, a practitioner needs to monitor the pa- purging. Nutrition therapy offers patients ways to regu-
tient’s weight and vital signs. Often activity level needs late eating patterns so that they can avoid the need to
to be decreased to help reverse the catabolic state. A rea- binge. Medical monitoring should be done to check
sonable weight gain goal may be 0.2–0.5 kg/wk. If electrolytes periodically, depending on the purging
weight loss persists, careful monitoring of vital signs, method used.
including supine heart rate, is important in deter- SSRIs are generally quite helpful in treating the
mining whether an increased level of care is needed. binge–purge cycle. Fluoxetine has been studied most
Concomitantly, the patient should be referred to a psy- extensively; a dose of 60 mg/day is most efficacious in
chotherapist, and, if indicated, assessed by a psychia- teenagers. Other SSRIs are thought to work similarly
trist. and are worth trying if the patient experiences side ef-
fects while taking fluoxetine. Treatment for gastro-
esophageal reflux and gastritis should be used when ap-
2. Bulimia Nervosa propriate. The pain and swelling of enlarged parotid
Treatment of bulimia nervosa depends on the fre- glands can be helped by sucking on tart candy and by
quency of bingeing and purging and the severity of bio- the application of heat.
chemical and psychiatric derangement. If K+ is less than
3.0 mEq/L, then inpatient medical admission is war- Bacaltchuk J et al: Antidepressant versus placebo for the treatment
ranted. Typically extracellular K+ is spared at the ex- of bulimia nervosa: A systematic review. Aust NZ J Psychiatry
pense of intracellular K+, so that a patient may become 2000;34:310 [PMID: 10789536].
hypokalemic several days after the serum K+ concentra- Kaye W et al: Double blind placebo-controlled administration of
tion appears to be corrected. Usually cessation of purg- fluoxetine in restricting- and restricting–purging-type
anorexia nervosa. Biol Psychiatry 2001;49(7):644 [PMID:
ing is sufficient to correct K+ concentration and is the 11297722].
recommended intervention for K+ greater than
Mehler P: Bulimia nervosa. N Engl J Med 2003;349:875 [PMID:
3.0 mEq/L; if K+ is 2.5–2.9 mEq/L, oral supplementa- 12944574].
tion is suggested; if K+ is less than 2.5 mEq/L, then in- Newman-Toker J: Risperidone in anorexia nervosa. J Am Acad
travenous therapy is recommended. Supplements can Child Adolesc Psychiatry 2000;39(8):941 [PMID: 10939220].
be stopped once K+ levels are greater than 3.5 mEq/L.
Once serum K+ corrects and remains normal 2 days
after supplements are stopped, the clinician can be con- 3. Binge-Eating Disorder
fident that total body K+ has returned to normal. Con- A combination of cognitive-behavioral therapy and an-
tinued hospitalization depends on the patient’s psycho- tidepressant medication has been helpful in treating
logical status. binge-eating disorder in adults. Use of SSRIs for binge-
Many of these patients abuse laxatives and may be eating disorder in adolescents has not been studied, but
chronically dehydrated. The renin–angiotensin–aldos- in adults, fluoxetine and citalopram help decrease binge
terone axis, as well as the antidiuretic hormone level, episodes, improve depression, and the decreased ap-
may be elevated to compensate. These systems do not petite that contributes to weight loss. This evidence
shut down automatically when laxatives are stopped, suggests that SSRIs in adolescents with binge eating dis-
and fluid retention of up to 10 kg/wk may result. This order may be helpful as well.
puts patients at risk for congestive heart failure and can
scare them as their weight increases dramatically. A di- McElroy SL et al: Citalopram in the treatment of binge-eating dis-
uresis often occurs after approximately 7–10 days. Par- order: A placebo-controlled trial J Clin Psychiatry 2003;
ents and patients should be advised of this possible 64(7):807 [PMID: 12934982].
 EATING DISORDERS / 175

PROGNOSIS comes have been found with brief medical hospitaliza-

tion and long psychiatric or residential hospitalization.
Outcome in eating disorders, especially anorexia ner- Higher discharge weight seems to improve the initial
vosa, has been studied extensively. Unfortunately, most outcome. It is difficult to compare treatment regimens,
studies have focused on specific inpatient treatment because the numbers are small and the type of patient
programs, and few have evaluated the less ill patients and illness varies between studies. No existing studies
who do not need hospitalization. About 40–50% of pa- compare outpatient to inpatient treatment or the effects
tients receiving treatment recover; 20–30% have inter- of day treatment on recovery.
mittent relapses; and 20% have chronic, unremitting Binge-eating disorder has been recognized only re-
illness. As time from initial onset lengthens, the recov- cently, and outcomes have not been studied. Interven-
ery rate decreases and mortality associated with tion with an SSRI appears to help the bingeing, but lit-
anorexia nervosa and bulimia nervosa increase. tle is known regarding long-term prognosis.
The course of anorexia nervosa often includes signif-
icant weight fluctuations over time, and it may be a
matter of years until recovery is certain. The course of Fisher M: The course and outcome of eating disorders in adults and
bulimia nervosa often includes relapse episodes of in adolescents: A review. Adolesc Med State of the Art Re-
bingeing and purging, although bulimic patients ini- views 2003;14(1):149 [PMID: 12529198].
tially recover faster than do anorexic patients. Up to Herzog D et al: Recovery and relapse in anorexia and bulimia ner-
50% of anorexic patients may develop bulimia, as well vosa: A 7.5 year follow-up study. J Am Acad Child Adolesc
as major psychological sequelae, including depression, Psychiatry 1999;38:829 [PMID: 10405500].
anxiety, and substance abuse disorders. Bulimic pa-
tients also develop similar psychological illness but
rarely develop anorexia. Long-term medical sequelae, REFERENCES
aside from low body weight and amenorrhea, have not
been studied in an outcome format, although anorexia Kreipe RE, Birndorf SA: Eating disorders in adolescents and young
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 Child & Adolescent Psychiatric
Disorders & Psychosocial Aspects 6
of Pediatrics
Jennifer Hagman, MD, & Donald W. Bechtold, MD

The task of the primary care provider is often to discern emotional and physical needs of other, more dependent
when symptoms are indicative of a problem versus a family members while defining the norms of behavior
normal variant of development. When the symptoms that will lead to independent adaptive functioning in
include changes in behavior, thoughts, and emotions, the future. The ways in which parents function in their
the task becomes one of determining if a psychiatric roles within the family determines in large part the
disorder is present and what the contributing role of ge- health or impairment of the family and its individual
netic and biologic factors, family and peer relationships, members.
and environment may be. Support systems, which include relatives, friends,
and caregivers, serve an important function to help par-
ents through life transitions from birth to the young
adult years and beyond. In the case of a two-parent
PSYCHOSOCIAL ASPECTS unit, the partners in a healthy relationship can provide
OF CHILD DEVELOPMENT the necessary emotional support, respite, and adult
companionship for each other. The women’s move-
AND FAMILY LIFE ment has helped men expand their parental roles and
personal identities to include more nurturing activities.
Because single parents often have no in-house source of
FAMILY LIFE adult support, relatives, friends, and other external sup-
The structure of families has changed significantly over port systems such as church, school, and childcare
the past two decades, with an increase in the number of providers are critical. In single-parent families or fami-
single-parent homes, mothers who work outside the lies in which the parents are not able to meet each
home, blended families, alternative lifestyles including other’s needs, the child is at risk of becoming a
gay and lesbian parents, and a decline in extended fami- pseudoadult companion, thus completing the parental
lies living in close proximity. The family serves the fol- unit.
lowing functions: (1) rearing children to become au- The lack of a solid parental partnership or effective
tonomous adults and eventually competent parents and support system for the family can be an important
(2) meeting the needs of family members for nurturing, factor in virtually any child-centered problem. To
protection, feedback, recognition (mirroring), promot- function successfully as a couple, both partners must
ing adaptive behaviors, and emotional closeness and find the relationship satisfying through mutual nurtur-
support. Evidence suggests that the lifestyle preferences ing and affirmation, trust and respect, conflict recogni-
of the parent figures are less important to healthy devel- tion and resolution, and intimacy and sexual satisfac-
opment than is the parents’ ability to serve parental tion.
functions consistently. When the parental unit is weakened by dissatisfac-
tion or by persistent conflict, children are at risk of be-
coming the focus of heightened parental attention and
THE PARENTAL UNIT concern, thus displacing the conflict from within the
The cornerstone of family functioning is the parental relationship onto the child. Concern about the child
unit, which optimally serves as the primary source of distracts the parents from their own problems, and the
stability, consistency, and authority during childhood child may function as a buffer between the adults.
and adolescence. Effective parents (or adults in the Questions designed to screen the quality of the marital
parental role) should be aware of and responsive to the and parental relationship are outlined in Table 6–6.
176
Copyright © 2005, 2001, by The McGraw-Hill Companies, Inc. Click here for terms of use.
 CHILD & ADOLESCENT PSYCHIATRIC DISORDERS / 177

Beeber LS, Miles MS: Maternal mental health and parenting in marriage and depend largely on the parents’ ability to
poverty. Annu Rev Nurs Res 2003;21:303 [PMID: maintain a working relationship with respect to parent-
12858701].
ing and financial issues related to the children. Few
Hunfeld JA, Fauser BC, deBeaufort ID, Passchier JP: Child devel- children experience the dissolution of even turbulent
opment and quality of parenting in lesbian families: No psy-
chosocial indications for a-priori withholding of infertility marriages as a relief, because the breakup of the nuclear
treatment: A systematic review. Hum Reprod Update family is perceived as a loss of the structure that pro-
2002;8(6):579 [PMID: 12498426]. vides for their safety and support. Children would
Leinonen JA, Solantaus TS, Punamaki RL: Parental mental health rarely choose divorce as a solution for their parents’
and children’s adjustment: The quality of marital interaction problems.
and parenting as mediating factors. J Child Psychology Psy- The effects of divorce on a child vary with the
chiatry 2003;44(2)227 [PMID: 12587859]. child’s age and developmental level. Preschoolers may
Schor EL: American Academy of Pediatrics Task Force on the Fam- display symptoms of behavioral regression, expressing
ily: Family Pediatrics, report of the Task Force on the Family.
Pediatrics 2003;111(6 Pt 2):1541 [PMID: 12777595].
fears of separation at night and when they are with
babysitters, sleep disturbances, and irritability. Children
Wamboldt MZ, Wamboldt FS: Role of the family in the onset and
outcome of childhood disorders: Selected research findings. age 5–8 years may express their grief with sadness and
J Am Acad Child Adolesc Psychiatry 2000;39(10):1212 weeping. Children often wish for reconciliation of the
[PMID: 11026173]. parents and may develop symptoms or behaviors that
serve a secondary purpose of causing the parents to
EFFECTS OF MARITAL communicate or be together.
Approximately 50% experience a decrease in school
SEPARATION AND DIVORCE performance, and some may become aggressive. Chil-
Currently, about 40% of marriages will end in divorce. dren age 9–12 years often respond with anger and
Seventy-five percent of divorced parents remarry, and blame and are at greatest risk of becoming a surrogate
another 50% divorce a second time. Approximately companion. In adolescence, anger often is accompanied
90% of single parents are mothers, and in about half of by depression. Teenagers rely heavily on their peers
such cases the children have little or no contact with the during this time and can become pessimistic about
father. their own future involvement in intimate relationships.

Clinical Effects of Separation and Divorce Outcome

The adverse emotional effects of divorce can be far- The most favorable outcome is for the parents to avoid
reaching for both adults and children. Many women discussion of their personal conflicts in the presence of
who have been through a divorce report that it takes a the child and resume caregiving relationships with their
minimum of 3 years for a sense of order and stability to children in a collaborative manner. Children do not
return. cope well in a setting of unremitting marital strife, and
Effects on the parent–child relationship include a overall development can be significantly affected. It is
decrease in parenting capacity manifested by irregular- important that parents develop predictable routines for
ity of schedules, flares of temper, lessening of emotional the children despite the challenges of separation and di-
sensitivity and support of the child, inconsistent disci- vorce. Younger children fare best, particularly when
pline, and decreased pleasure in the parent–child rela- they have a support network (eg, siblings, grandpar-
tionship. A tendency exists for the divorced parent to ents) while the parents are preoccupied with their own
look to the child as a source of emotional support or problems. A brief course of psychotherapy should be
even as a surrogate spouse. In the course of separation considered for all parents and children who are going
and divorce one parent may not be able to contain their through separation and divorce. Therapy will assist
angry thoughts about the other, and the child is sub- with coping and communication during this difficult
jected to a litany of complaints and negative statements, time and give the parents and children a place to dis-
which can be confusing and painful for the child and cuss their fears and emotions with someone who is not
significantly affect his or her ability to cope with the di- directly involved in the situation.
vorce. Some children may become inappropriately close Children of divorced parents experience increased
to their parents by acting as little helpers and parental rates of depression and anxiety, especially if the parents
advisors. Adolescents, in contrast, may rebel in order to are not able to maintain a nonhostile working relation-
distance themselves from the emotional needs of their ship regarding visitation and decisions related to the
distressed parents. children’s needs. At 10-year follow-up, 40% of such
The effects of divorce on children are seen most dra- children report worry, underachievement, self-depreca-
matically in the 2 years following dissolution of the tion, and lingering anger. The effect of divorce on chil-
178 / CHAPTER 6

dren may be far-reaching in scope and long-term in du- another generation of children who may themselves dis-
ration. play caregiver dysfunction as parents.
On reaching adulthood, children often fear repeat- These individuals frequently have difficult psy-
ing their parents’ unhappy marriages and may struggle chosocial histories, find themselves without emotional
with issues of commitment and trust in intimate rela- or physical support, and have unmet personal needs
tionships. (Table 6–2). Characteristics of the child may also con-
tribute to the parent’s failure to nurture and meet the
Braver SL, Ellman IM, Fabricius WV: Relocation of children after child’s needs. Risk factors from the child include pre-
divorce and children’s best interests: New evidence and legal maturity, perinatal complications, birth defects, multi-
considerations. J Fam Psychol 2003;17(2):206 [PMID: ple births, chronic medical or mental illness, and a dif-
12828017]. ficult temperament. These characteristics frequently
Cohen GJ: American Academy of Pediatrics. Committee on Psy- define the child as different, defective, or disappointing
chosocial Aspects of Child and Family Health: Helping chil- in the parent’s eyes.
dren and families deal with divorce and separation. Pediatrics
2002;110(5):1019 [PMID: 12415046]. Caregiver dysfunction is identified by interviewing
Kelly JB: Children’s adjustment in conflicted marriage and divorce:
the parents and observing the interaction between par-
A decade review of research. J Am Acad Child Adolesc Psy- ent and child. The child should be evaluated for or-
chiatry 2000,39(8):963 [PMID: 10939225]. ganic disorders that could explain the presenting symp-
Pruett MK, Williams TY, Insabella G, Little TD: Family and legal toms. A history aimed at identifying specific parental
indicators of child adjustment to divorce among families with risk factors should be obtained directly from the parent
young children. J Fam Psychol 2003;17(2):169 [PMID: (see Table 6–2), with emphasis on feelings of stress or
12828014]. of being overwhelmed by the needs of the child or the
Wallerstein JS: The long-term effects of divorce on children: A re- demands of daily life. Attention should be paid to the
view. J Am Acad Child Adolesc Psychiatry 1991;30:349. parent’s description of the child and to parental symp-
Wolchik SA et al: Six-year follow-up of preventive interventions for toms of anxiety or depression manifested by tension, ir-
children of divorce: A randomized controlled trial. JAMA
2002;288(15):1874 [PMID: 12377086].
ritability, fatigability, tearfulness, sleep disturbance, and
a wish to avoid or withdraw from daily activities.
In observing the parent–child interaction, the physi-
CAREGIVER DYSFUNCTION cian should look for reciprocity, mutual enthusiasm,
and enjoyment in the relationship, as opposed to
Primary Caregiver Dysfunction pathologic signs of tension, irritability, or apathy on ei-
Primary caregiver dysfunction can be defined as a fail- ther side of the relationship. Physical disorders that may
ure to provide parenting functions (usually, but not explain the presenting symptoms must be ruled out,
necessarily, by the mother) because of parental vulnera- but it should also be noted that caregiver dysfunction
bility or disability. Caregiver dysfunction can result and organic disease often coexist.
from domestic violence, mental illness, and substance Interventions are focused primarily on supporting
abuse. Caregivers can experience significant impair- and educating the parents and arranging referrals for as-
ment because of anxiety, depression, exhaustion, anger,
or indifference in relation to the demands of child care.
Caregiver dysfunction can lead to a number of symp-
toms in the child (Table 6–1) and includes the risk of Table 6–2. Parental risk factors contributing to
primary caregiver dysfunction.

Table 6–1. Signs and symptoms suggesting History of inadequate relations with own mother
Isolation from an adult support system (eg, single parent)
primary caregiver dysfunction. Psychiatric disorders (particularly acute or chronic depression)
Chronic psychosocial or cognitive dysfunctions (eg, unstable
Failure to thrive relationships, school problems, legal problems, employ-
Feeding problems ment problems)
Delays in development Unresolved grief over past losses
Signs of abuse Marital discord
Frequent physician visits, especially for nonspecific concerns Poverty or financial problems
Excessive parental worry about illness in the child Personal or family illnesses
Inadequate physical care Unwanted or difficult pregnancy
Child perceived as “difficult to deal with” Current life stresses (eg, loss of a relationship, recent illness,
Sleep problems job loss)
 CHILD & ADOLESCENT PSYCHIATRIC DISORDERS / 179

sessment and treatment of physical or mental illness responses and by memories of their own positive expe-
when appropriate. The physician should empathize, ex- riences as children. Children who are developmentally
plaining that being a parent is difficult and tiring work disabled or temperamentally difficult may be more un-
and that it requires health, energy, and emotional sup- predictable and challenging for the parent to respond
port. The task is to help the parent feel well physically to, and difficulty in the parent–child relationship may
and emotionally and then to facilitate the development result. A mild consequence may be a state of tension in
of appropriate childcare skills. A social support system the family. In extreme situations, child abuse and ne-
should be sought through friends, family, and commu- glect may result. Some parents have unrealistic fantasies
nity resources. Parenting skills can be taught and posi- about the children that may reflect their own unmet
tively reinforced over time. Referrals can be made to needs. Children with illnesses, disabilities, or tempera-
parenting classes in the community or through mental mental difficulties call for modified expectations so that
health centers. Reports are necessary to the department the parents can meet the special needs of the child.
of social services in cases where neglect or abuse is sus- Developmental disturbances are variations in nor-
pected. mal child development that cause distress or concern.
The prognosis depends on the parent’s receptiveness Parents frequently contact their physicians with ques-
to professional interventions, support, and education. tions about the terrible twos, childhood fears and anxi-
Follow-up by the physician’s office regarding recom- eties, and adolescent rebellion. The health care provider
mendations will increase the chance that interventions is faced with making the correct diagnosis, educating
to support optimal family functioning will be success- the parents about normal developmental variations, and
ful. developing strategies to facilitate optimal parent–child
interactions.
American Academy of Child and Adolescent Psychiatry: Practice Each new phase of child development presents
parameters for the psychiatric assessment of infants and tod- unique challenges. The infancy years are a time of irreg-
dlers (0–36 months). J Am Acad Child Adolesc Psychiatry ular sleep–wake cycles and a need for almost constant
1997;36 supplement:21S. care and attendance. During the toddler years, the
Benjet C, Azar ST, Kuersten-Hogan R: Evaluating the parental fit- child’s strivings for autonomy and independence
ness of psychiatrically diagnosed individuals: Advocating a should be supported and encouraged within appropri-
functional-contextual analysis of parenting. J Fam Psychol ate limits and without letting the child become the
2003;17(2):238 [PMID: 12828020].
family tyrant. In the subsequent years, parents are faced
Keren M et al: Assessment of caregiver-child interaction in the con-
text of a preschool psychiatric evaluation. Child Adolesc Psy-
with competitive challenges, requiring a balanced re-
chiatr Clin N Am 1999;8:281. spect for the child’s evolving wishes to be independent
Langrock AM et al: Coping with the stress of parental depression: while still setting limits that maintain safety and respect
Parents’ reports of children’s coping, emotional and behav- for others.
ioral problems. J Clin Child Adolesc Psychol 2002;31(3):
312 [PMID: 12149969].
Mayes LC: Addressing mental health needs of infants and young
THE PUSHY PRESCHOOLER
children. Child Adolesc Psychiatr Clin N Am 1999;8:209. The push for independence and autonomy that begins
Zeanah CH, Boris NW, Larrieu JA: Infant development and devel- in the second year of life can pose problems for parents
opmental risk: A review of the past 10 years. J Am Acad who are insecure in the parental role. Preschool chil-
Child Adolesc Psychiatry 1997;36:165.
dren typically want to have their way even when it
poses a danger or is not in their best interest. Children
may try to decide when and what the family eats, what
time is bedtime, and who sleeps in which bed, all as
CHALLENGES IN PARENTING part of their rudimentary push to become independent.
RELATED TO CHILD AND The parents’ task is to respect the child’s wish for self-
ADOLESCENT DEVELOPMENT determination while setting limits and providing guid-
ance so that the child does not become tyrannical or
out of control.
Parenting is challenging, rewarding, and frustrating. Parents who are having difficulty placing limits on
Physical and emotional exhaustion as well as unfulfilled behavior will come in with one of the following types of
expectations about parenting and family life can be complaints:
avoided or mitigated if both partners share the parent-
ing responsibilities, or if there is a strong support sys- 1. Discipline won’t work with this child.
tem available to the parents. Primary caregivers are also 2. I can’t get her to do what I ask without getting
partly replenished emotionally by the child’s positive mad.
180 / CHAPTER 6

3. He says, “ I don’t have to do it if I don’t want to.” Table 6–3. Sequence of developmental anxieties.
4. She won’t sleep in her own bed.
5. Other children his age don’t like him. He always Age at First
wants his own way. Appearance Source of Anxieties
Early infancy Sudden loud noises, unpredictable stimuli,
Parents who have difficulty saying no may be emo- loss of postural support, heights.
tionally drained or may believe that confrontation must
1 year Stranger, unfamiliar situations and objects.
be avoided. In the former case, parental depression or Beginning of separation distress.
emotional exhaustion from working and single parent-
hood is common. In the latter case, the parent typically 2–6 years Animals, darkness, imaginary creatures
overidentifies with the frustrated child’s distress and is (ghosts and monsters).
then reminded of painful conflicts or unhappiness in School age Bodily injury, physical danger. Fear of loss
his or her own life. Keeping the child happy (ie, avoid- of loved one.
ing conflict) keeps the parent from feeling distressed
and unhappy, but inevitably leads to more power strug- Teens and adult- Fear of failure (eg, test anxiety), concerns
gles and defiant behavior. hood about social acceptance, loss of a loved
one, physical danger, natural disasters.
In planning interventions, the physician must edu-
cate the parents about the sometimes pushy nature of
preschool children within a healthy developmental con-
text. With that explanation comes the need for external opmental sequence (Table 6–3) and, overall, tend to
limits, because a child’s judgment and self-control are decrease in frequency and intensity with age.
as yet underdeveloped. Parents need to know that a Although the manifestations of many developmental
child’s disappointment and frustration with limits are a anxieties, such as separation distress and fear of the
necessary component of growth and development. dark, may wax and wane over months or years, most
Parents who are emotionally depleted or depressed specific childhood fears are transient (days to weeks in
need to be cared for themselves, either through rest, duration) and not associated with substantial interfer-
emotional support, and assistance with parenting or ence with daily life. In most cases, all that is needed is
through referrals for therapy. In the case of a parent to reassure the parents about the developmental nature
who avoids conflict, the physician should suggest ad- of fears; the parents can then reassure their children
dressing one or two discipline problems. For example, that they will be fine even though they feel frightened
if toys are not picked up after a reminder, they are put at times. Fears become a source of greater concern to
away out of the child’s reach for some specific period of health care providers when they appear outside the nor-
time. As the parent begins to feel more comfortable mal developmental sequence of fears, when they are
with providing limits and appropriate consequences, persistent, when they cause severe distress, or when they
the child’s behavior typically becomes less oppositional; interfere with adaptive functioning such as poor atten-
at this point, the parent should use positive reinforce- dance at school or avoidance of peer relationships. Ap-
ment, such as, “I like the way you picked up your toys; proximately 2–3% of preschool age children have fears
let’s read a story together.” troublesome enough to require specific mental health
interventions such as referral to a child and adolescent
psychiatrist.
CHILDHOOD FEARS & ANXIETIES
During the elementary school years, parents must begin
to let their children experience the challenges that await
them outside the home. Parental support of develop- Fraiberg SH: The Magic Years: Understanding and Handling the
ment of these social and emotional skills must be bal- Problems of Early Childhood. Scribner, 1959.
anced with realistic definitions of success. Persistent Gilliam WS: Developmental assessment: Its role in comprehensive
separation anxiety on the part of parents and unrealistic psychiatric assessment of young children. Child Adolesc Psy-
chiatr Clin North Am 1999;8:225 [PMID: 10202587].
standards of performance can contribute to problems
Hack S, Jellinek MS: Historical clues to the diagnosis of the dys-
for the child in regulating anxiety and developing self- functional child and other psychiatric disorders in children.
esteem during these years. Pediatr Clin North Am 1998;45(1):25 [PMID: 9491085].
The vast majority of childhood fears are not associ- Shapiro T, Hertig ME: Normal child and adolescent development.
ated with psychological disorders; in fact, the fearful In Hales RE, Yudofsky SC (eds): Essentials of Clinical Psychia-
stimuli tend to evolve and change with age in a devel- try. American Psychiatric Press, 1999.
 CHILD & ADOLESCENT PSYCHIATRIC DISORDERS / 181

ADOLESCENT REBELLION & TURMOIL home should be explored regularly with all adoles-
cents as part of their routine medical care.
Adolescence is a time of considerable physical and emo-
tional change. General theoretic impressions and sam- • Although violence toward others remains difficult to
pling bias at one time tended to exaggerate the turmoil predict, its association with suicidal impulses should
of normal adolescence. A longitudinal study of normal not be overlooked. In general, the suicidal youth is
suburban middle-class boys through their high-school somewhat easier to identify than the homicidal
years identified only 21% as experiencing tumultuous youth, and in many cases may be one and the same
unrest. On closer examination, this segment was distin- (see the section on Suicide in Children & Adoles-
guished from the remainder of the sample by lower so- cents). Any comment about wishes to be dead or
cioeconomic status, more overt marital conflicts in the hopelessness should be taken seriously and help
family, and a higher than normal incidence of mental sought.
illness in the family. Overall, approximately 20% of • Parents and guardians should be aware of their
adolescents have a stormy course; another 20% progress child’s school attendance and performance and peer
continuously and smoothly through adolescence; and groups. They should know their children’s friends
the remainder show normal overall adjustment but and be aware of who they are going out with, where
have transient difficulties during times of stress. they will be, what they will be doing, and when they
The early adolescent has unpredictable changes of will be home. Any concerns should be discussed with
mood, intense attachment to peers, and a self-centered the teen and interventions sought if necessary.
point of view, all of which can diminish positive aspects • Most students involved in school violence could have
of the parent–child relationship and lead to increased benefited from earlier interventions to address prob-
tension between the parent and the adolescent. Not lems in social and educational functioning in the
since infancy and the toddler years have parents re- school environment. Many communities and school
ceived so little gratitude for their efforts. Like parents of districts have increased their efforts to identify and
toddlers, the parents of young adolescents need to sup- intervene with students whom teachers, peers, or par-
port autonomy while providing the structure and limits ents recognize as having difficulty.
necessary to maintain safety and promote good decision
making on the part of the adolescent.
Anderson M et al: School-associated violent deaths in the United
The sexual interests of the middle adolescent can States, 1994–1999. JAMA 2001;286(21):2695 [PMID:
elicit parental reactions related to the parent’s own 11730445].
comfort or concerns about sexuality and can range from Birnbaum AS et al: School functioning and violent behavior among
pride to fear to envy or even confusion about sexual young adolescents: A contextual analysis. Health Educ Res
boundaries with the adolescent. The parents’ own past 2003;18(3):389 [PMID: 12828239].
experience may influence their reactions and ability to D’Angelo SL, Omar HA: Parenting adolescents. Int J Adolesc Med
negotiate this developmental phase in a manner that fa- Health 2003;15(1):11 [PMID: 12723444].
cilitates communication while helping the teen make Denninghoff KR et al: Emergency medicine: Competencies for
responsible decisions. youth violence prevention and control. Acad Emerg Med
Finally, as the late adolescent prepares to leave home 2002;9(9):947 [PMID: 12208685].
for college or other independent living, parents face, in Grant KE et al: Stressors and child and adolescent psychopathol-
ogy: Moving from markers to mechanisms of risk. Psychol
addition to anxiety and excitement, the sense of loss Bull 2003;129(3)447 [PMID: 12784938].
and grief associated with their child going out into the Group for the Advancement of Psychiatry, Committee on Preven-
world. tive Psychiatry: Violent behavior in children and youth: Pre-
Of particular concern to physicians today, as well as ventive intervention from a psychiatric perspective. J Am Acad
to society at large, is the tragic increase in teen violence, Child Adolesc Psychiatry 1999;38:235 [PMID: 10087683].
including school shootings. Although the prediction of Kruesi MJP et al: Suicide and violence prevention: Parent educa-
violent behavior remains a difficult and imprecise en- tion in the emergency department. J Am Acad Child Adolesc
deavor, physicians can support and encourage several Psychiatry 1999;38:250 [PMID: 10087685].
important prevention efforts. Monasterio EB: Enhancing resilience in the adolescent. Nurs Clin
North Am 2002;37(3):373 [PMID: 12448999].
Olsson CA et al: Adolescent resilience: A concept analysis. J Ado-
• The vast majority of the increase in youth violence lesc 2003;26(1):1 [PMID 12550818].
including suicides and homicides involves the use of Pontin LE: The Romance of Risk, Why Teenagers Do the Things They
firearms. Thus the presence of firearms within the Do. Basic Books, 1997.
home, the method of storage and safety measures Twemlow SW, Fonagy P, Sacco FC: An innovative psychodynami-
when present, and access to firearms outside the cally influenced approach to reduce school violence. J Am
182 / CHAPTER 6

Acad Child Adolesc Psychiatry 2001;49(3):377 [PMID: prognosis. At the same time, their primary concerns are
11288781]. the effects of the illness on everyday life, feeling sick,
and limitations on normal activities. Children are also
keenly aware of the family’s reactions and may be reluc-
tant to bring up issues they know are upsetting to their
THE CHRONICALLY ILL CHILD parents. Whenever possible, parents should be encour-
aged to discuss the child’s illness and to answer ques-
Reactions to Chronic Physical tions openly and honestly, including exploration of the
child’s fears and fantasies. Such interactions promote
or Mental Illness and Disability closeness and relieve the child’s sense of isolation. Even
Between 5% and 10% of individuals experience a pro- with these active attempts to promote effective sharing
longed period of medical illness or disability during between the child and the family, ill children frequently
childhood, and another 5–10% experience the onset of experience fear, anxiety, irritability, and anger over
mental illness in childhood. The psychosocial effects for their illness and guilt over causing family distress. Sleep
the child and the family are often profound. Although disturbances, tears, and clinging, dependent behavior
the specific effect of illness on children and their fami- are not infrequent or abnormal.
lies depends on the characteristics of the illness, the age
of the child, and premorbid functioning, it can be ex- THE TERMINALLY ILL CHILD
pected that both the child and the parents will go
through predictable stages toward eventual acceptance The diagnosis of fatal illness in a child is a severe blow
of the disease state. Shock and disbelief at the time of even to families who have reason to suspect that out-
diagnosis give way in time to anger and to mourning come. The discussion with parents (and the child)
the loss of the normal, healthy child. It may take about terminal illness is one of the most difficult tasks
months for a family to accept the disease, to cope with for a physician working with children and adolescents.
the stresses, and to resume normal life to the extent Although parents want and need to know the truth,
possible. These stages resemble those that follow the they are best told in stepwise fashion beginning with
loss of a loved one. If anxiety and guilt remain promi- temporizing phrases such as, “The news is not good”
nent within the family, a pattern of overprotection can and “This is a life-threatening illness.” The parent’s re-
evolve. Likewise, when the illness is not accepted as a actions and questions can then be observed for clues to
reality to be dealt with, a pattern of denial may become how much they want to be told at any one time. The
prominent. The clinical manifestations of these pat- physician must also attempt to gauge how much of the
terns of behavior are presented in Table 6–4. information the parents are able to comprehend during
Children are very observant and intuitive when it the initial discussion and consider involvement of ap-
comes to understanding their illness and its general propriate support services. Parent’s reactions may pro-
ceed in a grief sequence including initial shock and dis-
belief lasting days to weeks, followed by anger, despair,
and guilt over weeks to months, and ending in accep-
Table 6–4. Patterns of coping with tance of the reality of the situation. These responses
chronic illness. vary in intensity, duration, and sequence within the
family.
Overprotection Although children probably do not fully understand
Persistent anxiety or guilt the permanency of death until about age 8, most ill
Few friends and peer activities children experience a sense of danger and doom that is
Poor school attendance associated with death before that age. Even so, the
Overconcern with somatic symptoms question of whether to tell a child about the fatal nature
Secondary gain from the illness of a disease should in most cases be answered in the af-
Effective coping firmative unless the parents object. When the parents
Realistic acceptance of limits imposed by illness object, this should alert the physician to involve the
Normalization of daily activities with peers, play, and school unit social worker, who can work with the family to en-
Denial sure their decision is in the best interest of the child.
Lack of acceptance of the illness Refusal of the adults to tell the child, especially when
Poor medical compliance the adults themselves are very sad, leads to a conspiracy
Risk-taking behaviors of silence that increases fear of the unknown in the
Lack of parental follow-through with medical instructions child and leads to feelings of loneliness and isolation at
General pattern of acting-out behavior the time of greatest need. In fact, children who are able
 CHILD & ADOLESCENT PSYCHIATRIC DISORDERS / 183

to discuss their illness with family members are less de- B. PREPARE THE CHILD FOR CHANGES
pressed, have fewer behavior problems, have higher self- AND PROCEDURES
esteem, feel closer to their families, and adapt better to The physician should explain, in an age-appropriate
the challenges of their disease and its treatment. manner, what could be expected with a new turn in the
The siblings of dying children are also significantly illness or with upcoming medical procedures. This ex-
affected. They may feel neglected and deprived because planation enables the child to anticipate and in turn to
of the time their parents must spend with the sick master the new development and promotes trust be-
child. Anger and jealousy may then give rise to feelings tween the patient and the health care providers.
of guilt over having such feelings about their sick sib-
ling. Awareness of the emotional responses, coping abil- C. ENCOURAGE NORMAL ACTIVITIES
ities, and available resources for support of other family The child should attend school and play with peers as
members can diminish these feelings and make a signif- much as the illness allows. Individual education plans
icant difference in the family’s overall ability to cope (IEP) should be requested from the school if accommo-
with the illness. dation beyond the regular classroom is necessary. At the
After the child dies, the period of bereavement may same time, parents should be encouraged to apply the
last for years. Family members may need outside help same rules of discipline and behavior to the ill child as
in dealing with their grief through supportive counsel- are applied to well siblings.
ing services or peer-support groups. Bereavement usu-
ally does not substantially interfere with overall life D. ENCOURAGE COMPENSATORY ACTIVITIES,
functioning for more than 2–3 months. Most parents INTERESTS, AND SKILL DEVELOPMENT
and siblings are able to return to work and school
within a month, although their emotional state and For example, a child whose athletic development has
thoughts may continue to be dominated by the loss for been interrupted by the disability might pursue the ac-
some time. When the individual is unable to function quisition of computer skills.
in his or her societal and family role beyond this time E. PROMOTE SELF-RELIANCE
frame, a diagnosis of complicated bereavement, major
depression, posttraumatic stress disorder (PTSD), or The health care provider should guide and encourage
adjustment disorder should be considered and appro- parents in helping ill children assume responsibility for
priate interventions recommended, such as referral for some aspects of their medical care.
counseling or psychotherapy and possibly antidepres- F. PERIODICALLY REVIEW FAMILY COPING
sant medication.
From time to time, the physician should ask, “How is
everyone doing with this?” The feelings of the patient,
Long-Term Coping the parents, and other children in the family are ex-
The process of coping with a chronic or terminal illness plored, as well as concerns about finances and the status
is complex and varies with the dynamics of each indi- of the marriage. Feelings of fear, guilt, anger, and grief
vidual child and family. Each change in the course of should be watched for and accepted as normal reactions
the illness and each new developmental stage for the to difficult circumstances.
child present different challenges. It is important for
health care providers to continually assess the family G. RECOMMEND SUPPORT GROUPS
and child’s needs and coping abilities over time and to Appropriate lay support groups for the patient and fam-
provide appropriate support, information, and access to ily should be recommended. Many hospitals have such
interventions. groups, and hospital social workers can facilitate partic-
ipation for the patient and family.
Assistance from Health Care Providers
Browning D: To show our humanness—Relational and commu-
A. EDUCATE THE PATIENT AND FAMILY nicative competence in pediatric palliative care. Bioethics
Children and their families should be given informa- Forum 2002;18(3-4):23 [PMID: 12744267].
tion about the illness, including its course and treat- Christian B: Growing up with chronic illness: Psychosocial adjust-
ment of children and adolescents with cystic fibrosis. Annu
ment, at frequent intervals. Factual, open discussions Rev Nurs Res 2003;21:151 [PMID: 12858696].
minimize anxieties. The explanation should be compre- Geist R, Grdisa V, Otley A: Psychosocial issues in the child with
hensible to all, and time should be set aside for ques- chronic conditions. Best Pract Res Clin Gastroenterol
tions and answers. The setting can be created with an 2003;17(2):141 [PMID: 12676111].
invitation such as, “Let’s take some time together to re- Kubler-Ross E: On Children and Death. Collier Books, Macmillan
view the situation again.” Publishing, 1983.
184 / CHAPTER 6

Meyer EC et al: Parental perspective on end-of-life care in the pedi- ture for the discussion of problems that often or some-
atric intensive care unit. Crit Care Med 2002;30(1):226 times occur; and second, as a general screening device,
[PMID: 11902266].
with a total score of 28 or higher indicating a need for
Oliver RC et al: Beneficial effects of a hospital bereavement inter- in-depth psychosocial evaluation of the child.
vention program after traumatic childhood death. J Trauma
2001;50(3):440 [PMID: 11265051]. Five questions forming the mnemonic PSYCH can
Stewart JL: Children living with chronic illness; An examination of
be addressed to parents as a means of uncovering areas
their stressors, coping responses and health outcomes. Annu of concern. The questions can be rephrased slightly and
Rev Nurs Res 2003;21:203 [PMID: 12858698]. then directed to children as well.
Suris JC: Chronic conditions and adolescence. J Pediatr Endocrinol
Metab 2003;16 (Suppl) 2:247 [PMID: 12729399]. 1. Parent–child interaction: How are things going
Van Riper M: The sibling experience of living with childhood with you and your child?
chronic illness and disability. Annu Rev Nurs Res 2. School: How are things going in school? (Acade-
2003;21:279 [PMID: 12858700]. mically and behaviorally.)
Waugh S: Parental views on disclosure of diagnosis to their
HIV-positive children. AIDS Care 2003;15(2):169 [PMID 3. Youth: How are things going with peer relation-
12856338]. ships?
4. Casa: How are things going at home? (Including
siblings, the marriage, and parents as individuals.)
5. Happiness: How would you describe your child’s
SCREENING FOR mood? (Comfortable and happy versus tense and
PSYCHOSOCIAL PROBLEMS & unhappy.)
PSYCHIATRIC DISORDERS Direct questions regarding age-appropriate behavior
WITHIN THE CONTEXT OF norms can then be reviewed. Concerns about infant at-
tachment, the terrible twos, childhood fears, school
HEALTH MAINTENANCE VISITS problems, and adolescent behavioral problems can in
this way be brought into the open for further discus-
Between 5% and 15% of children in the United States sion.
have psychiatric disorders, and nearly 50% of pediatric
office visits are related to psychosocial or developmental ASSESSMENT OF BEHAVIORAL AND
problems. These statistics underscore the importance of
screening for mental illness and psychosocial problems
EMOTIONAL SIGNS AND SYMPTOMS
in children and their families. When an emotional or behavioral sign or symptom is
Most families seek help from their primary care present, a thorough evaluation is indicated. Informa-
providers when they are concerned about a child’s tion must be collected from caregivers, the child, and
health, growth, or development. It is thus critical that sometimes school personnel and others acquainted with
primary care providers be able to identify the need for, the child’s functioning. At least 30 minutes should be
and initiate the evaluation of, mental health problems scheduled, and additional appointments may be neces-
in children and adolescents. sary. Screening questions and guidelines for observation
The most efficient indicator in screening for psy- are given in Table 6–6.
chosocial problems is the history provided by care- It is useful to see both parents and the child first to-
givers. Psychosocial information can be obtained from gether, then the parents alone, and then the child alone.
checklists, general questioning, and direct questioning. This sequence enables the physician to observe interac-
The most effective method is a combination of these tions among family members and gives the parents and
three information-gathering techniques. Questions can the child an opportunity to talk confidentially about
be incorporated into the general pediatric office screen- their concerns. Parents and children often feel shame
ing forms, or specific questionnaires can be used. The and guilt about some personal inadequacy they perceive
34-item pediatric symptom checklist (Table 6–5) to be causing the problem. The physician can ease that
screens children age 6–12 years for psychosocial dys- burden and facilitate the assessment by acknowledging
function. The checklist is to be completed in the wait- that the family is trying to cope and that the ultimate
ing room by a parent or other caregiver. Each item is task of assessment is to seek solutions and not to assign
rated by the parents as often present (2 points), some- blame. An attitude of nonjudgmental inquiry can be
times present (1 point), or never present (0 points). communicated with supportive statements such as,
The information can be used in two ways: first, as a “Let’s see if we can figure out what might be happening
psychosocial review of symptoms and point of depar- here and find some ways to make things better.”
Table 6–5. Pediatric symptom checklist.a

Never Sometimes Often

1. Complains of aches or pains
2. Spends more time alone
3. Tires easily, little energy
4. Fidgets, is unable to sit still
5. Has trouble with a teacher
6. Is less interested in school
7. Acts as if driven by a motor
8. Daydreams too much
9. Is distracted easily
10. Is afraid of new situations
11. Feels sad, unhappy
12. Is irritable, angry
13. Feels hopeless
14. Has trouble concentrating
15. Has less interest in friends
16. Fights with other children
17. Is absent from school
18. Experiences a drop in school grades
19. Is down on himself or herself
20. Visits doctor, with doctor finding nothing wrong
21. Has trouble with sleeping
22. Worries a lot
23. Wants to be with you more than before
24. Feels he or she is bad
25. Takes unnecessary risks
26. Gets hurt frequently
27. Seems to be having less fun
28. Acts younger than children the same age
29. Does not listen to rules
30. Does not show feelings
31. Does not understand other people’s feelings
32. Teases others
33. Blames others for his or her troubles
34. Takes things that belong to others
a
Parents are asked to indicate which category—Never, Sometimes, or Often—best fits their child, with 0, 1, or 2 points assigned to each
answer, respectively. For interpretation of scores, see text.
Modified and reproduced, with permission, from Murphy JM, Jellinek M: Screening for psychosocial dysfunction in economically disad-
vantaged and minority children: Further validation of the pediatric symptom checklist. Am J Orthopsychiatry 1988;58:450. Copyright ©
1988 by the American Orthopsychiatric Association.

185
186 / CHAPTER 6

Table 6–6. Screening for psychosocial problems.

Developmental history Observation of the parents

1. Review the landmarks of psychosocial development 1. Do they agree on the existence of the problem or concern?
2. Summarize the child’s temperamental traits 2. Are they uncooperative or antagonistic about the evaluation?
3. Review stressful life events and the child’s reactions 3. Do the parents appear depressed or overwhelmed?
to them 4. Can the parents present a coherent picture of the problem
a. Separations and their family life?
b. Losses 5. Do the parents accept some responsibility for the child’s
c. Marital conflict problems, or do they blame forces outside the family and
d. Illnesses, injuries, and hospitalizations beyond their control?
4. Obtain details of past mental health problems and their 6. Do they appear burdened with guilt about the child’s prob-
treatment lem?
Family history Observation of the child
1. Marital history 1. Does the child acknowledge the existence of a problem or
a. Overall satisfaction with the marriage concern?
b. Conflicts or disagreements within the relationship 2. Does the child want help?
c. Quantity and quality of time together away from 3. Is the child uncooperative or antagonistic about the assess-
children ment?
d. Whether the child comes between or is a source of 4. What is the child’s predominant mood or attitude?
conflict between the parents 5. What does the child wish could be different (eg, “three
e. Marital history prior to having children wishes”)?
2. Parenting history 6. Does the child display unusual behavior (activity level, man-
a. Feelings about parenthood nerisms, fearfulness)?
b. Whether parents feel united in dealing with the child 7. What is the child’s apparent cognitive level?
c. “Division of labor” in parenting Observation of parent–child interaction
d. Parental energy or stress level 1. Do the parents show concern about the child’s feelings?
e. Sleeping arrangements 2. Does the child control or disrupt the joint interview?
f. Privacy 3. Does the child respond to parental limits and control?
g. Attitudes about discipline 4. Do the parents inappropriately answer questions addressed
h. Interference with discipline from outside the family to the child?
(eg, ex-spouses, grandparents) 5. Is there obvious tension between family members?
3. Stresses on the family Data from other sources
a. Problems with employment 1. Waiting room observations by office staff
b. Financial problems 2. School (teacher, nurse, social worker, counselor)
c. Changes of residence 3. Department of social services
d. Illness, injuries, and deaths
4. Family history of mental health problems
a. Depression? Who?
b. Suicide attempts? Who?
c. Psychiatric hospitalizations? Who?
d. “Nervous breakdowns”? Who?
e. Substance abuse or problems? Who?
f. Nervousness or anxiety? Who?

History of the Presenting Problem • What attempts have been made to alleviate the prob-
lem?
First, obtain a detailed description of the problem.
• Do the parents have any opinions about the cause of
the problem?
• When did it start?
• Were there unusual stresses at that time?
• How are the child’s life and the family’s functioning Questions to screen for other psychosocial prob-
affected? lems, listed in Table 6–6, can be asked when additional
• What does the child say about the problem? information is sought.
 CHILD & ADOLESCENT PSYCHIATRIC DISORDERS / 187

Interviewing the Preschool Child agrees that a problem exists (eg, unhappiness, anxiety,
sleep disturbance).
Preschool children should be interviewed with their
parents. As the parents discuss their concerns, the • The physician should ask the child to describe the
physician can look for the following behaviors: problem in his or her own words, or ask what he or
1. Does the child use the parents as a source of secu- she thinks is causing the problem.
rity and support? • It is important to ask the child how the problem af-
2. Does the 2- to 5-year-old child warm up to the fects the child and the family.
strange environment and begin to explore the • Asking directly about how mom and dad get along
room and even interact with the physician from a can yield information about parental conflicts.
distance? • Questions about school can yield information about
3. How does the child relate to toys that are offered? life outside the home and with peers.
4. What is the child’s activity level? • Questions about worries, unhappy feelings, and what
5. Does the child display unusual mannerisms (eg, makes the child angry can elicit clues to the child’s
intense clinging, stereotypical motor behaviors)? emotional life.
6. Does the child disrupt or attempt to control the • Asking a child to make three wishes can uncover im-
interview? portant concerns that may not have been apparent
from the history: Let’s pretend you could have any-
7. Do the parents attempt to place appropriate limits thing or change anything. What would you wish for
on behavior? How does the child respond? and why?
It is helpful to have toy human figures, animals, or
puppets, and crayons and paper available that the child At the end of the interview with the child, it is im-
can use to portray emotional states and interpersonal portant to share or reiterate the central points derived
interactions. After hearing the history from the parents from the interview and to state that the next step is to
and after observing the child, the physician may ques- talk with the parents about ways to make things better
tion the 3- to 5-year-old child about toy figures who for the child. At that time, it is good to discuss any con-
appear to be feeling sad, worried, angry, or bossy. Chil- cerns or misgivings the child might have about sharing
dren age 3–5 years are frequently able to confirm im- information with parents so that the child’s right to pri-
portant interpersonal relationships and attitudes in vacy is not arbitrarily violated. Most children want to
such symbolic play activities. make things better and thus will allow the physician to
share appropriate concerns with the parents.
Interviewing the School-Age Child
Interviewing the Adolescent
Most school-age children have mastered separation anx-
iety sufficiently to tolerate at least a brief interview Because the central developmental task of adolescence
alone with the physician. In addition, they may have is to create an identity separate from that of the parents,
important information to share about their own wor- the physician must show respect for the teen’s point of
ries. The child should be told beforehand by the par- view. That process usually begins with the physician
ents or physician (or both) that the doctor will want to meeting briefly with the parents and adolescent to-
talk to the child about his or her feelings. School-age gether to define the concerns. The physician should
children understand and even appreciate parental con- then meet alone with the adolescent. After the physi-
cern about unhappiness, worries, and difficulty in get- cian has interviewed the adolescent and talked further
ting along with people. At the outset, it is useful to con- with the parents, he or she should formulate thoughts
firm that the purpose of the interview is to explore the and recommendations. Whenever possible, it is helpful
child’s own opinions about certain issues raised by the to discuss these with the adolescent before presenting
parents. Rapport can be enhanced by asking if the child them to the parents and teen together. The issue of
has ever talked with anyone else about how he or she confidentiality must be approached during the first in-
feels. If the answer is affirmative, the child may explain terview. A good policy is to say, “What we talk about
more about what he or she liked or did not like about today is between you and me unless we decide someone
that discussion. If the child has never before talked should know or unless it appears to me that you might
about personal feelings with a professional, the physi- be in a potentially dangerous situation.”
cian can acknowledge that it is often not easy to talk The interview with the adolescent alone might then
with a stranger about some kinds of problems. The start with a restatement of the parents’ concern. The
physician should then ascertain whether the child patient is then encouraged to describe the situation in
188 / CHAPTER 6

his or her own words. The physician should then ask The physician’s first task is to decide whether a
questions about: problem exists. For example, how hyperactive must a
5-year-old child be before he or she is too hyperactive?
1. Predominant mood state Functional impairment may be the single best marker
2. Nature of relationships with family members of the difference between symptomatology and normal
3. Level of satisfaction with school and peer relation- variation. When a child’s function is impaired in major
ships domains of life, such as learning, peer relationships,
4. Plans for the future family relationships, authority relationships, and recre-
ation, or when a substantial deviation from the trajec-
5. Drug and alcohol use
tory of normal developmental tasks occurs, a differen-
6. Sexual activity tial diagnosis should be sought based on the symptom
7. Worries or concerns profile. The physician’s interpretation is then presented
8. What the adolescent would like to be different to the family. The interpretive process includes the fol-
lowing components:
In concluding the interview, the physician should
summarize his or her thoughts and develop a plan with 1. An explanation of how the presenting problem or
the teenager to present to the parents. If teenagers par- symptom is a reflection of a suspected cause
ticipate in the solution, they are more likely to work 2. A suggested plan of intervention based on the pre-
with the family in improving the situation. This should sumed cause
include a plan either for further investigation or for 3. A discussion of any further evaluation necessary to
ways of dealing with the problem and arranging subse- confirm or refine a diagnosis
quent appointments with the physician or an appropri-
ate referral to a mental health provider. A joint plan involving the physician, parents, and
child is then negotiated to address the child’s symptoms
and developmental needs in light of the family struc-
DIAGNOSTIC FORMULATION AND ture and stresses. If an appropriate plan cannot be de-
INTERPRETATION OF FINDINGS veloped, or if the physician feels that further diagnostic
Diagnosis starts with a description of the presenting assessment is required, referral to a mental health prac-
problem, which is then evaluated within the context of titioner should be recommended.
the child’s age, developmental needs and tasks, and
temperament; the stresses and strains on the child and Cassidy SJ, Jellinek M: Approaches to recognition and manage-
ment of childhood psychiatric disorders in pediatric primary
the family; and the functioning of the family system care. Pediatr Clin North Am 1998;45(5):1037 [PMID:
and family history of mental illness. The physician then 9884674].
develops an etiologic hypothesis based on the informa- Fritz G: Promoting effective collaboration between pediatricians
tion gathered: and child and adolescent psychiatrists. Pediatr Ann 2003;
32(6):387 [PMID: 12846016].
1. The behavior falls within the range of normal Gardner W et al: Primary care clinicians’ use of standardized tools
given the child’s developmental level. to asses child psychosocial problems. Ambul Pediatr 2003;
2. The behavior is a temperamental variation. 3(4):191 [PMID: 12882596].
3. The behavior is related to central nervous system Hack S, Jellenik M: Early identification of emotional and behav-
impairment (eg, prematurity, exposure to toxins ioral problems in a primary care setting. Adolesc Med: State
of the Art Reviews 1998,9(2):335 [PMID: 10961240].
in utero, seizure disorder, genetic disorders).
Murphy JM et al: Screening for psychosocial dysfunction in pedi-
4. The behavior is a normal reaction to stressful cir- atric practice. Clin Pediatr 1992;31:660 [PMID: 10961240].
cumstances (eg, medical illness, change in family Weist MD, Ginsburg, Shafer M: Progress in adolescent mental
structure, loss of a loved one). health. Adolesc Med: State of the Art Reviews 1999;10(1):
5. The problem is primarily a reflection of family 165 [PMID: 10086173].
dysfunction (eg, the child is the symptom bearer,
or scapegoat, or the identified patient for the fam-
ily).
PSYCHIATRIC DISORDERS OF
6. The problem indicates a possible psychiatric dis-
order. CHILDHOOD & ADOLESCENCE
7. The problem is complicated by an underlying
medical condition. A psychiatric disorder is defined as a characteristic clus-
8. Some combination of the preceding. ter of signs and symptoms (eg, emotions, behaviors,
 CHILD & ADOLESCENT PSYCHIATRIC DISORDERS / 189

thought patterns, and mood states) that are associated Table 6–7. When to consider consultation or
with subjective distress or maladaptive behavior. This referral to a child and adolescent psychiatrist.
definition presumes that the individual’s symptoms are
of such intensity, persistence, and duration that the Diagnosis is not clear
ability to adapt to life’s challenges is compromised. Pediatrician feels further assessment is needed
Psychiatric disorders have their origins in neurobiol- Pediatrician believes medication may be needed, but will not
ogy, genetics, psychological (life experience), or envi- be prescribing
ronmental sources. The neurobiology of childhood dis- Pediatrician has started medications and needs further psy-
orders is today one of the most active areas of chopharmacologic consultation
investigation in child and adolescent psychiatry. Al- Individual, family, and/or group psychotherapy is needed.
though much remains to be clarified, data from genetic Psychotic symptoms (hallucinations, paranoia) are present
studies point to heritable transmission of attention- Bipolar affective disorder is suspected.
deficit/hyperactivity disorder (ADHD), schizophrenia,
mood and anxiety disorders, pervasive developmental
disorders, learning disorders, and tic disorders, among
others. About 3–5% of children and 10–15% of adoles- of clinical differences and family histories. The term
cents are personally affected by psychiatric disorders PDD denotes a group of disorders with the common
and will benefit from psychiatric treatment. findings of impairment of socialization skills and char-
The Diagnostic and Statistical Manual IV—text re- acteristic behavioral abnormalities. Speech and lan-
vision (DSM-IV-TR) is the formal reference text for guage deficits are common as well.
psychiatric disorders and includes the criteria for each
of the mental illnesses, including those that begin in
childhood and adolescence. Psychiatric diagnoses are 1. Autistic Disorder
given on five axes to allow the physician to address the
developmental, medical, psychosocial, and overall adap-
tive issues that contribute to the primary diagnosis on ESSENTIALS OF DIAGNOSIS
axis I or II. & TYPICAL FEATURES
Axis I: Clinical disorders and other conditions that • Severe deficits in social responsiveness and inter-
may be a focus of clinical attention personal relationships.
Axis II: Personality disorders, mental retardation, • Abnormal speech and language development.
learning disabilities
• Behavioral peculiarities such as ritualized, repeti-
Axis III: General medical conditions tive, or stereotyped behaviors; rigidity; and
Axis IV: Psychosocial and environmental problems poverty of age-typical interests and activities.
Axis V: Global assessment of functioning (on a • Onset in infancy or early childhood (before age
scale of 0–100, with 100% being the highest level 3 years).
of functioning)
Primary care physicians often are the first to identify
and recommend treatment for mental illness in chil-
dren and adolescents. Criteria for referral to a child and
adolescent psychiatrist are listed in Table 6–7.
General Considerations
Autistic disorder is uncommon, with an incidence of
American Psychiatric Association: Diagnostic and Statistical Manual approximately 4 cases per 10,000 school-age children.
of Mental Disorders—Text Revision. American Academy of Pe- More boys than girls are affected (3:1). Although the
diatrics, 2000. cause of autistic disorder is unknown, central nervous
system dysfunction is suggested by its higher incidence
PERVASIVE DEVELOPMENTAL in populations affected by perinatal disorders: rubella,
phenylketonuria, tuberous sclerosis, infantile spasms,
DISORDERS & AUTISM encephalitis, and fragile X syndrome. Studies of twins
Pervasive developmental disorders (PDD) and child- reveal over 90% concordance for autistic disorder in
hood autism are early-onset, severe neuropsychiatric monozygotic twins compared with 24% in dizygotic
disorders that were once referred to as childhood psy- twins. Twenty-five percent of families with an autistic
choses. PDD (including autistic disorder) are now dis- child have other family members with language-related
tinguished from childhood schizophrenia on the basis disorders. (See also Chapter 2.)
190 / CHAPTER 6

Clinical Findings Behaviorally oriented special education classes or

day treatment programs are vital in helping the autistic
Severe deficits in reciprocal social interaction (eg, de- child acquire more appropriate social, linguistic, self-
layed or absent social smile, failure to anticipate interac- care, and cognitive skills.
tion with caregivers, and a lack of attention to a pri- No specific medications are available to treat autistic
mary caregiver’s face) are often evident even in the first disorder. Pharmacotherapy is aimed at reducing specific
year of life. In toddlers, findings include deficiencies in target symptoms and must be continually assessed and
imitative play and a relative lack of interest in interac- reevaluated for efficacy and side effects. Coexisting di-
tions with others. Language development is often quite agnoses must be carefully considered. Neuroleptic med-
delayed. In fact, children are often first referred for au- ications (eg, risperidone, olanzapine, and haloperidol)
diologic evaluation because of failure to respond as ex- may modify a variety of disruptive symptoms, includ-
pected to sounds. When speech does begin to develop, ing hyperactivity, aggressiveness, and negativism. Fen-
it may be echolalic or nonsensical. Autistic children fluramine may help the subset of autistic children with
often display peculiar interests; bizarre responses to sen- low serotonin levels (although serotonin levels are very
sory stimuli; repetitive, stereotypical motor behaviors difficult to measure). Psychostimulants may benefit
(eg, twirling, hand-flapping); odd posturing; self-injuri- concurrent ADHD symptoms but can sometimes
ous behavior; abnormal patterns of eating and sleeping; worsen behavior or mood. Antidepressants—especially
and unpredictable mood changes. Thematic pretend the selective serotonin reuptake inhibitors (SSRIs)—
play is often impaired. An intense preoccupation with may benefit both mood symptoms and symptoms of
an age-unusual interest (eg, power poles) may replace excessive rigidity or obsessive behavior. Mood stabiliz-
the usual broad range of interests of the child’s age- ers may diminish irritability, lability, or episodic
mates. About 70% of autistic children have intelligence dyscontrol. Naltrexone may help control severe self-in-
quotients under 70. jurious behavior or stereotypes. Controlled studies do
not support the use of secretin for autism.
Differential Diagnosis Parents and families need strong support as well as
Although most autistic children function at the men- education in caring for a child with autism. Early inter-
tally retarded level, the vast majority of mentally re- ventions to facilitate the development of reciprocal in-
tarded children do not show the essential characteristics teractions, language, and social skills are critical. Occu-
of autistic disorder. A hearing or visual impairment pational therapy for sensory integration is also an
must be ruled out with appropriate screening. Children integral component of the comprehensive assessment.
with developmental speech and language disorders typi- Sensory integration interventions help the autistic child
cally show better interpersonal interactions than autistic and help the family better support the child and adapt
children. Evaluation should include investigations for the environment to their specific needs.
metabolic disorders and fragile X syndrome.
Prognosis
Complications Autism is a lifelong disorder. The best prognosis is for
Approximately 25% of autistic individuals eventually children who have normal intelligence and have devel-
develop a seizure disorder. Comorbid psychiatric disor- oped symbolic language skills by age 5 years. Most indi-
ders such as mood disorders should be screened for if viduals with autism will not be able to live independently
significant changes in behavior occur. Some autistic and will require significant support and supervision
adolescents who have higher cognitive skills become de- throughout their lives. Approximately one sixth of autis-
pressed as they become partially aware of their deficits. tic children become gainfully employed as adults, and
another one sixth are able to function in sheltered work-
Treatment shops or special work and school environments. The re-
mainder need ongoing supervision and support, often in
Parents and families need strong support as well as a milieu-based therapeutic environment to provide a
education in caring for a child with autism. Early inter- structured day. Placement in specialized residential
ventions to facilitate the development of reciprocal in- homes or programs may be necessary for some individu-
teractions, language, and social skills are critical. Occu- als whose guardians are unable to meet their special
pational therapy for sensory integration is also an needs or provide a secure and safe home environment.
integral component of the comprehensive assessment.
Sensory integration interventions help the autistic child Chakrabarti S, Fombonne E: Pervasive developmental disorders in
and help the family better support the child and adapt preschool children. JAMA 2002;285(24):3093 [PMID:
the environment to their specific needs. 11427137].
 CHILD & ADOLESCENT PSYCHIATRIC DISORDERS / 191

Dunn-Geier J, Ho H, Auersperg E, et al: Effect of secretin on chil- General Considerations

dren with autism: A randomized controlled trial. Dev Med
Child Neurol 2000;42:796 [PMID: 11132252]. Children with nonautistic PDDs display a wide range
McDougle CJ et al: Research Units on pediatric psychopharmacol- of deficits in social, language, and behavioral skills that
ogy (RUPP) Autism Network: Background and rationale for are similar to those in children with autistic disorder.
an initial controlled study of risperidone. Child Adolesc Psy- However, these children deviate from the clinical pro-
chiatr Clin North Am 2000;9(1):201 [PMID: 10674197].
file for autistic disorder by failing to meet all the neces-
Practice parameters for the assessment and treatment of children, sary diagnostic criteria, by failing to fulfill severity
adolescents and adults with autism and other pervasive devel-
opmental disorders. J Am Acad Child Adolesc Psychiatry threshold (ie, milder functional impairment), by mani-
1999;38(12, Suppl):32S [PMID: 10624084]. festing atypical symptomatology (eg, the characteristic
Prater CD, Zylstra RG: Autism: A medical primer. Am Fam Physi- hand-wringing or gender distribution in Rett syn-
cian 2002;66(9):1667 [PMID 12449265]. drome), or by experiencing onset at a later age. In the
Santosh PJ, Baird G: Pharmacotherapy of target symptoms in autis- past, many of these children would have been classified
tic spectrum disorders. Indian J Pediatr 2002;68(5):427 in the group manifesting so-called atypical develop-
[PMID: 11407159]. ment. Children with nonautistic PDDs probably out-
number autistic children by as much as 2–3:1.

2. Nonautistic Pervasive Developmental Differential Diagnosis

Disorders Specific developmental speech and language disorders
should be distinguished. Hearing impairment should
Asperger syndrome, childhood disintegrative disorder, be ruled out with appropriate screening.
pervasive developmental disorder not otherwise speci-
fied (PDD-NOS), and Rett syndrome (Table 6–8).
Treatment
The backbone of treatment for Asperger syndrome and
ESSENTIALS OF DIAGNOSIS PDD-NOS is an adaptive behavioral approach aimed at
& TYPICAL FEATURES teaching and reinforcing more appropriate social and
language skills and behaviors. Rett syndrome and child-
• Substantial social impairment, either primary or hood disintegrative disorder have much worse prog-
representing a loss of previously acquired social noses and call for multidisciplinary, often milieu-based
skills. interventions (as for autistic disorder). Occupational
• Abnormalities in speech and language develop- therapy for sensory integration interventions may be
ment or behavior resembling autistic disorder. helpful. In all cases, family education and support are
important.
• Onset by early childhood (may be as late as age Children should be screened for the presence of
9 years in childhood disintegrative disorder). other psychiatric conditions, including mood disorders,
obsessive–compulsive disorder (OCD), ADHD, and

Table 6–8. Characteristics of nonautistic pervasive developmental disorders.

Disorder Age at Onset Clinical Features

Asperger’s syndrome Early childhood “Odd” individuals (probably more common in males) with normal intelli-
gence, motor clumsiness, eccentric interests, and a limited ability to appre-
ciate social nuances
Childhood disintegrative disorder 3–4 years Profound deterioration to severe autistic disorder
Pervasive developmental disorder Early childhood Two to three times more common than autistic disorder, with similar but
less severe symptoms
Rett syndrome 5 months to Females with reduced head circumference and loss of social relatedness
4 years old who develop stereotyped hand movements and have impaired language
and mental functioning
192 / CHAPTER 6

anxiety disorders, and appropriate interventions should Clinical Findings

be initiated. Psychoactive medications may be helpful
for treating specific target symptoms as described for Clinical depression can be defined as a persistent state
autistic disorder. of unhappiness or misery that interferes with pleasure
or productivity. The signs and symptoms of depression
are surprisingly constant from early childhood to ado-
Prognosis lescence and adulthood (Table 6–9). The dysphoria of
depression in children and adolescents is as likely to be
These are lifelong disorders. The prognosis is variable an irritable mood state accompanied by tantrums or
depending on the severity of social and language verbal outbursts, as it is to be a sad mood. Typically, a
deficits and response to treatment interventions. child or adolescent with depression begins to look un-
happy and may make comments such as “I have no
friends,” “Life is boring,” “There is nothing I can do to
Starr E et al: Stability and change among high-functioning children make things better,” or “I wish I were dead.” A change
with pervasive developmental disorders: A 2-year outcome
study. J Autism Dev Disord 2003;33(1):15 [PMID:
in behavior patterns usually takes place that includes so-
12708576]. cial isolation, deterioration in schoolwork, loss of inter-
Tanguay P: Pervasive developmental disorders: A 10 year review. est in usual activities, and flashes of anger and irritabil-
J Am Acad Child Adolesc Psychiatry 2000;39(9):1079 ity. Sleep and appetite patterns commonly change, and
[PMID: 10986804]. the child may complain of tiredness and nonspecific
Volkmar FR et al: Nonautistic pervasive developmental disorders. pain such as headaches or stomachaches.
In Coffey CE, Brombach RA (eds): Textbook of Pediatric
Neuropsychiatry. American Psychiatric Press, 1998.
Differential Diagnosis
Clinical depression can be identified by asking about
MOOD DISORDERS the symptoms. Children are often more accurate than
their caregivers in assessing their own mood state.
1. Depression in Children & Adolescents When several depressive symptoms cluster together
over time and are persistent (2 weeks or more) and se-
ESSENTIALS OF DIAGNOSIS vere, a diagnosis of major depressive disorder is appro-
priate. When symptoms are fewer and of lesser severity
& TYPICAL FEATURES
• Dysphoric mood, mood lability, irritability or de-
pressed appearance, persisting for days to Table 6–9. Clinical manifestations of depression
months at a time. in children and adolescents.
• Characteristic neurovegetative signs and symp-
toms (changes in sleep, appetite, concentration, Depressive
and activity levels). Symptom Clinical Manifestations
• Suicidal ideation, feeling of hopelessness
Anhedonia Loss of interest and enthusiasm in play,
socializing, school, and usual activities;
boredom; loss of pleasure
Dysphoric mood Tearfulness; sad, downturned expres-
sion; unhappiness; slumped posture;
General Considerations quick temper; irritability; anger
The incidence of depression in children increases with Fatigability Lethargy and tiredness; no play after
age, from 1–3% before puberty to around 8% for ado- school
lescents. The rate of depression in females approaches
Morbid ideation Self-deprecating thoughts, statements;
adult levels by age 15. The lifetime risk of depression thoughts of disaster, abandonment,
ranges from 10–25% for women and 5–12% for men. death, suicide, or hopelessness
The incidence of depression in children is higher when
other family members have been affected by depressive Somatic symptoms Changes in sleep or appetite patterns;
disorders. The sex incidence is equal in childhood, but difficulty in concentrating; bodily com-
with the onset of puberty the rates of depression for fe- plaints, particularly headache and stom-
males begin to exceed those for males by 5:1. achache
 CHILD & ADOLESCENT PSYCHIATRIC DISORDERS / 193

but have persisted for months or years, a diagnosis of also helps the young person to identify, label, and ver-
dysthymic disorder is justified. Milder symptoms of balize feelings and misperceptions.
short duration in response to some stressful life event Antidepressant medications should be considered
warrant a diagnosis of adjustment disorder with de- for all patients with a depressive diagnosis (Table
pressed mood (See Table 6–9). 6–10). When the symptoms of depression are moderate
Rating scales of mood can be helpful in assessing to severe and persistent and have begun to interfere
child and adolescent patients. The Child Depression with relationships and school performance, antidepres-
Inventory (CDI), the BECK Depression Rating Scale, sant medications may be indicated. Mild depressive
and the Reynolds Adolescent Depression Scale are eas- symptoms often do not require antidepressant medica-
ily used in primary care. tions and may improve with psychotherapy alone. A
Substantial rates of comorbidity of depression are as- positive family history of depression increases the risk
sociated with ADHD, conduct disorders, anxiety disor- of early-onset depression in children and adolescents
ders, eating disorders, and substance abuse disorders. and chances of a positive response to antidepressant
Medically ill patients also have an increased incidence medication.
of depression. Every child and adolescent with a de-
pressed mood state should be asked directly about suici-
dal ideation and physical and sexual abuse. Depressed Prognosis
adolescents should also be screened for hypothyroidism A comprehensive treatment intervention, including
and substance abuse. psychotherapy, medication assessment, and evaluation
of school and home environments, often leads to com-
plete remission of depressive symptoms over a 1- to
Complications 2-month period. If medications are started and prove
Because the emotional pain associated with depression effective, they must be continued for 6–9 months after
can be intensely distressing, the child or adolescent may remission of symptoms to prevent relapse. Early-onset
consider suicide (see section on Suicide in Children & depression (before age 15) is associated with increased
Adolescents). In addition, adolescents have a propensity risk of recurrent episodes and the potential need for
to avoid the pain of depression through substance abuse longer term treatment with antidepressants. Education
or excitement-seeking behaviors (eg, partying, nega- of the family and child (or adolescent) will help them
tivism and defiance, reckless behavior). School perfor- identify depressive symptoms sooner and limit the
mance usually suffers during a depressive episode as severity of future episodes with earlier interventions.
children are unable to concentrate or motivate them- Some studies suggest that up to 30% of preadolescents
selves to complete homework or projects. The irritabil- with major depression manifest bipolar disorder at
ity, isolation, and withdrawal that often result from the 2-year follow-up. It is important to reassess the child or
depressive episode can lead to loss of peer relationships adolescent with depressive symptoms regularly for at
and tense dynamics within the family. least 6 months and to maintain awareness of the depres-
sive episode in the course of well-child care.

Treatment American Academy of Child and Adolescent Psychiatry: Practice

parameters for the assessment and treatment of children and
Treatment includes identifying the symptoms of de-
pression and developing a comprehensive plan to treat
the depressive episode and help the caregivers to re-
spond more effectively to the patient’s emotional needs.
Referrals should be made for individual and family Table 6–10. Interventions for the treatment
therapy. In therapy, efforts are made to resolve conflicts of depression.
between family members, improve communication
skills within the family, and increase the opportunity Adjustment disorder Refer for psycho- Medications usually
for enjoyable time spent together. Attitudes, expecta- therapy not needed
tions, and disciplinary methods are evaluated. The Mild depression Refer for psycho- Medications may
child is encouraged to become involved in activities and therapy not be needed
to pursue opportunities for maximizing skills and tal- Moderate depression Refer for psycho- Consider antidepres-
ents. Individual psychotherapy aimed at identifying therapy sant medication
pervasively negative thoughts and correcting negativis- Severe depression Refer for psycho- Strongly encourage
tic cognitive distortions can increase the patient’s therapy antidepressant
awareness of care and concern on the part of adults. It medication
194 / CHAPTER 6

adolescents with depressive disorders. J Am Acad Child Ado- 20 years. Onset of bipolar disorder before puberty is
lesc Psychiatry 1998;37(10, Suppl:63S [PMID: 9785729]. thought to be uncommon, whereas the lifetime preva-
Asarnow JR, Jaycox LH, Tompson MC: Depression in youth: Psy- lence of bipolar disorder in middle to late adolescence
chosocial interventions. J Clin Child Psychol 2001;30(1): approaches 1%.
33 [PMID: 11294076].
Birmaher B, Arbalaez C, Brent D: Course and outcome of child
and adolescent major depressive disorder. Child Adolesc Psy- Clinical Findings
chiatr Clin North Am 2002;11(3):619 [PMID: 12222086].
Emslie GJ et al: Fluoxetine for acute treatment of depression in In about 70% of patients, the first symptoms are pri-
children and adolescents: A placebo-controlled randomized marily those of depression; in the remainder, manic,
clinical trial. J Am Acad Child Adolesc Psychiatry hypomanic, or mixed states dominate the presentation.
2002;41(10):1205 [PMID: 12364842]. Manic patients display a variable pattern of elevated,
Olsen AL et al: Primary care pediatrician’s roles and perceived re- expansive, or irritable mood along with more rapid
sponsibility in the identification and management of depres- speech, higher energy levels, some difficulty in sustain-
sion in children and adolescents. Ambulatory Pediatr 2001; ing concentration, and a decreased need for sleep. Pa-
1(2):91 [PMID: 11888379].
tients often do not acknowledge any problem with their
Practice parameters for the assessment and treatment of children
and adolescents with depressive disorders. J Am Acad Child
mood or behavior. The clinical picture can be quite
Adolesc Psychiatry 1998;31(10, supp):63S. dramatic, with florid psychotic symptoms of delusions
Ryan ND: Diagnosing pediatric depression. Biol Psychiatry and hallucinations (a full-blown manic psychosis),
2001;49(12):1050 [PMID: 11430846]. more subtle changes and lability in mood or behavior
Ryan ND: Medication treatment for depression in children and (cyclothymia), or milder symptoms of psychomotor ac-
adolescents. CNS Spectr 2003;8(4):283 [PMID 1267943]. tivation (hypomania).
Stingard RJ: The neuroscience of depression in adolescence. J Af-
fect Disord 2000;61 (Suppl 1):15 [PMID: 11155964].
Strober M et al: The course of major depressive disorder in adoles-
Differential Diagnosis
cents: I. Recovery and risk of manic switching in a follow-up ADHD is thought to be highly comorbid with bipolar
of psychotic and non-psychotic subtypes. J Am Acad Child disorder in prepubertal children. Physical or sexual
Adolesc Psychiatry 1993;32:34.
abuse and exposure to domestic violence can often
cause children to appear mood labile, hyperactive, and
2. Bipolar Affective Disorder aggressive, and PTSD should be considered by review-
ing the history for traumatic life events in children with
these symptoms. Diagnostic considerations should also
ESSENTIALS OF DIAGNOSIS include an acute organic process, particularly substance
& TYPICAL FEATURES abuse disorder. Individuals with manic psychosis may
resemble those with schizophrenia. Psychotic symp-
• Periods of abnormally and persistently elevated, toms associated with bipolar disorder should clear with
expansive, or irritable mood, and heightened lev- resolution of the mood symptoms, which should also
els of energy and activity. be prominent. Hyperthyroidism should be ruled out.
• Not caused by prescribed or illicit drugs. In prepubescent children, mania may be difficult to dif-
ferentiate from ADHD and other disruptive behavior
• Associated symptoms: grandiosity, diminished disorders. Preoccupation with violence, decreased need
need for sleep, pressured speech, racing thoughts, for sleep, intense and prolonged rages or dysphoria, and
impaired judgment. some periodicity of symptom activity suggest bipolar
disorder. Table 6–11 further defines points of differen-
tiation between ADHD, conduct disorder, and bipolar
disorder.
General Considerations
Complications
Bipolar affective disorder (previously referred to as
manic–depressive disorder) is an episodic mood disor- Children and adolescents with bipolar disorder are
der manifested by alternating periods of mania or hypo- more likely to be aggressive or assaultive toward peers
mania and depressive episodes or, less commonly, and family members. This may also result in significant
manic episodes alone. Children and adolescents often interference with academic learning and peer relation-
exhibit a variable course of mood instability combined ships. The poor judgment associated with manic
with misconduct and impulsivity. At least 20% of bipo- episodes predisposes to dangerous, impulsive, and
lar adults experience onset of symptoms before age sometimes criminal activity. Legal difficulties can arise
 CHILD & ADOLESCENT PSYCHIATRIC DISORDERS / 195

Table 6–11. Differentiating behavior disorders.

ADHD Conduct Disorder Bipolar Disorder

School problems Yes Yes Yes
Behavior problems Yes Yes Yes
Defiant attitude Occasional Constant Episodic
Motor restlessness Constant May be present May wax and wane
Impulsivity Constant May be present May wax and wane
Distractibility Constant May be present May wax and wane
Anger expression Short-lived (minutes) Plans revenge Intense rages (minutes to hours)
Thought content May be immature Blames others Morbid or grandiose ideas
Sleep disturbance May be present No May wax and wane
Self-deprecation Briefly, with criticism No Prolonged, with or without suicidal ideation
Obsessed with ideas No No Yes
Hallucinations No No Diagnostic, if present
Family history May be a history of school May be a history of antisocial May be a history of mood disorders
problems behavior
ADHD = attention-deficit/hyperactivity disorder.

from impulsive acts, such as excessive spending, acts of disorder is an illness with a remitting course of alternat-
vandalism, theft, or aggression, associated with ing depressive and manic episodes. The time span be-
grandiose thoughts. Affective disorders are associated tween episodes can be years or months depending on
with a 30-fold greater incidence of successful suicide. the severity of illness and ability to comply with medica-
Substance abuse may be a further complication, often tion interventions. In childhood, the symptoms may be
representing an attempt at self-medication for the more pervasive and not fall into the intermittent
mood problem. episodic pattern until after puberty.

Treatment & Prognosis American Academy of Child and Adolescent Psychiatry: Practice
Most patients with bipolar disorder respond to pharma- parameters for the assessment and treatment of children with
bipolar disorder. J Am Acad Child Adolesc Psychiatry
cotherapy with mood stabilizers such as lithium, carba- 1997;36 (Suppl):157S [PMID: 9432516].
mazepine, or valproate, either alone or in combination. Emslie GJ et al: Predictors of response to treatment in children and
The atypical neuroleptic, olanzapine, has been approved adolescents with mood disorders. Psychiatr Clin North Am
by the Food and Drug Administration (FDA) for the 2003;26(2):435 [PMID: 12778842].
treatment of bipolar affective disorder. Neuroleptic James AD, Javaloyes AM: The treatment of bipolar disorder in chil-
medications may be necessary in addition to a mood sta- dren and adolescents. J Child Psychol Psychiatry 2001;42(4):
bilizer if psychotic symptoms or significant aggression is 439 [PMID: 11383960].
present. In cases of severe impairment, hospitalization is Kent L, Craddock N: Is there a relationship between attention
required to maintain safety and initiate treatment. Al- deficit hyperactivity disorder and bipolar disorder? J Affect
though it is often possible to discontinue the neuroleptic Disord 2003;73(3):211 [PMID: 12547289].
medication after remission of symptoms, it is usually Kowatch RA, Delbello MP: The use of mood stabilizers and atypi-
cal antipsychotics in children and adolescents with bipolar
necessary to continue the mood stabilizer for at least a disorders. CNS Spectr 2003;8(4):273 [PMID: 12679742].
year, and longer if the individual has had recurrent Leibenluft E et al: Defining clinical phenotypes of juvenile mania.
episodes. It is not uncommon for the patient to need Am J Psychiatry 2003;160(3):430 [PMID: 12611821].
lifelong medication. Supportive psychotherapy for the Weller EB, Danielyan AK, Weller RA: Somatic treatment of bipo-
patient and family and education about the recurrent lar disorder in children and adolescents. Child Adolesc Psy-
nature of the illness are critical. In its adult form, bipolar chiatr Clin North Am 2002;11(3):595 [PMID: 12222085].
196 / CHAPTER 6

SUICIDE IN CHILDREN & ADOLESCENTS perienced a crisis event such as a loss (eg, rejection by
girlfriend or boyfriend), a failure, or an arrest prior to
The suicide rate in young people has remained high for completed suicide.
several decades. In 1997, suicide was the third leading
cause of death among children and adolescents age
10–24 years in the United States. The suicide rate Assessment of Suicide Risk
among adolescents age 15–19 years quadrupled from Any clinical assessment for depression must include
approximately 2.7 to 11.3 per 100,000 since the 1960s. questions about suicidal ideation. If a child or adoles-
It is estimated that each year, approximately 2 million cent expresses suicidal thinking, the physician must ask
US adolescents attempt suicide, yet only 700,000 re- if he or she has an active plan. Suicidal ideation accom-
ceive medical attention for their attempt. Suicide and panied by any plan warrants immediate referral for a
homicide rates for children in the United States are two psychiatric crisis assessment. This can usually be ac-
to five times higher than those for the other 25 indus- complished at the nearest emergency room.
trialized countries combined, primarily due to the Assessment of suicide risk calls for a high index of
prevalence of firearms in the United States. For chil- suspicion and a direct interview with the patient and
dren younger than 10 years old, the rate of completed significant others such as family members, peers, and
suicide is low, but from 1980 to 1992 it increased by teachers. A format for the interview is provided in
120%, from 0.8 to 1.7 per 100,000. Table 6–12. The highest risk of suicide is among older
Adolescent girls make three to four times as many white adolescent boys. High-risk factors include previ-
suicide attempts as boys of the same age, but the num- ous suicide attempts, a suicide note, and a viable plan
ber of completed suicides is three to four times greater for suicide with the availability of lethal means, close
in boys. Firearms are the most commonly used method personal exposure to suicide, conduct disorder, and
in successful suicides, accounting for 40–60% of cases; substance abuse. Other risk factors are signs and symp-
hanging, carbon monoxide poisoning, and drug over- toms of major depression or dysthymia, a family history
doses each account for approximately 10–15% of cases. of suicide, a recent death in the family, and a view of
Suicide is almost always associated with a psychiatric death as a relief from the pain in their lives. Persons
disorder and should not be viewed as a philosophic who have little or no family support, those who are fac-
choice about life or death or as a predictable response to ing a crisis in their lives at work or school, and those
overwhelming stress. Most commonly it is associated who refuse to agree not to commit suicide are also at
with a mood disorder and the hopelessness that accom- high risk.
panies a severe depressive episode. Suicide attempts are
often an angry, impulsive, and retaliatory act of aggres-
sion in an individual who is unable to exercise better in- Principles of Intervention
sight and judgment because of an impaired state due to Any suicide attempt must be considered a serious mat-
either mental illness or substance abuse. Although sui- ter. The patient should not be left alone, and one
cide attempts are more common in individuals with a should show understanding of the young person’s pain
history of behavior problems and academic difficulties, and convey a desire to help. The physician should meet
other suicide victims are high achievers who are tem- with the patient and the family, both alone and to-
peramentally anxious and perfectionistic and who com- gether, and listen carefully to their problems and per-
mit suicide impulsively after a failure or rejection, ei- ceptions. It should be made clear that with the assis-
ther real or perceived. Mood disorders (in both sexes, tance of mental health professionals, solutions can be
but especially in females), substance abuse disorders (es- found.
pecially in males), and conduct disorders are commonly These patients should be referred for psychiatric
diagnosed at psychological autopsy in adolescent sui- evaluation and possible hospitalization if there appears
cide victims. Some adolescent suicides reflect an under- to be a high potential for suicide, if they are severely de-
lying psychotic disorder, with the young person usually pressed or intoxicated, if the family does not appear ap-
committing suicide in response to auditory hallucina- propriately concerned, or if there are practical limita-
tions or psychotic delusions. tions on providing supervision and support to ensure
The vast majority of young people who attempt sui- safety. Any decision to send the patient home without
cide give some clue to their distress or their tentative hospitalization should be made only after consultation
plans to commit suicide. Most show signs of dysphoric with a mental health expert. The decision should rest
mood (anger, irritability, anxiety, or depression). Over on a perceived lessening of the risk of suicide and assur-
60% make comments such as “I wish I were dead” or “I ance of the family’s ability to follow through with out-
just can’t deal with this any longer” within the 24 hours patient therapy and provide appropriate support and
prior to death. In one study, nearly 70% of subjects ex- supervision. Guns, pills, knives, and razor blades must
 CHILD & ADOLESCENT PSYCHIATRIC DISORDERS / 197

Table 6–12. Clinical interview to assess firearms are responsible for 85% of deaths due to sui-
suicide risk. cide or homicide in youth in the United States.
Finally, the physician should be aware of his or her
1. An observation or change has been noted. own emotional reactions to dealing with potentially
2. How have you been feeling (inside, emotionally)? suicidal adolescents and their families. Because the as-
3. Have you had periods of feeling down or discouraged? sessment takes considerable time and energy, the physi-
a. How often? cian should be on guard against becoming tired, irrita-
b. How long? ble, or angry. The physician need not be afraid of
c. How severe? precipitating suicide by direct and frank discussions of
4. Do they interfere with your life? suicidal risk.
a. Daily activities?
b. School or work? Borowsky IW: The role of the pediatrician in preventing suicidal
c. Sleep or appetite? Both? behavior. Minerva Pediatr 2002;54(1):41 [PMID: 11862165].
d. Family life? Borowsky IW, Ireland M, Resnick MD: Adolescent suicide at-
5. Do you have feelings of— tempts: Risks and protectors. Pediatrics 2001;107(3):
a. Self-criticism or worthlessness? 485 [PMID: 11230587].
b. Helplessness? Gould MS et al: Youth suicide risk and prevention interventions: A
c. Hopelessness? review of the past 10 years. J Am Acad Child Adolesc Psychi-
d. Wanting to give up? atry 2003;42(4):386 [PMID: 12649626].
6. Are the feelings ever so strong that life does not seem Practice Parameters for the assessment and treatment of children
worth living? Have you had thoughts of suicide? and adolescents with suicidal behavior. J Am Acad Child Ado-
lesc Psychiatry 2001;40(7 Suppl):24S [PMID: 11314578].
a. Are you having thoughts of suicide now?
b. How persistent are they? Schmidt P et al: Suicide in children, adolescents, and young adults.
Forensic Sci Int 2002;127(3):161 [PMID: 12175945].
c. How much effort does it take to resist?
d. Can you tolerate the pain you are feeling? Weller EB et al: Overview and assessment of the suicidal child. De-
press Anxiety 2001;14(3):157 [PMID: 11747125]
7. Have you made any plans to carry out suicide?
a. What are the plans?
b. Have you taken any tentative action (eg, obtaining a ADJUSTMENT DISORDERS
gun or rope, stockpiling pills)?
c. As you have thought about suicide, how have you The most frequent and most disturbing stresses for chil-
viewed the idea of death? dren and adolescents are marital discord, separation and
8. What deters you from trying suicide? divorce, family illness, the loss of a loved one, a change
9. If the suicidal feelings are subsiding, could you resist the of residence, and, for adolescents, peer relationship
feelings if they returned? problems. When faced with stress, children can experi-
10. Is there someone you can turn to for help at those times? ence many different symptoms, including changes in
Who? mood, changes in behavior, anxiety symptoms, and
11. Has the idea of suicide come up in the past? physical complaints. Key findings include the following:
a. How often?
• The precipitating event or circumstance is identifi-
b. When and under what circumstances?
c. What has happened at those times?
able.
12. Can you tolerate the pain that you are feeling right now? • The symptoms have appeared within 3 months after
the occurrence of the stressful event.
• Although the child experiences distress or some func-
tional impairment, the reaction is not severe or dis-
be removed from the home entirely, and, as much as abling.
possible, access to them outside the home must be de- • The reaction does not persist more than 6 months
nied. The patient should be restricted from driving for after the stressor has terminated.
at least the first 24 hours to lessen the chance of impul- The range of symptoms associated with adjustment
sive motor vehicle accidents. Instructions and phone disorders is listed in Table 6–13.
numbers for crisis services should be given, and the
family must be committed to a plan for mental health Differential Diagnosis
treatment.
Suicide prevention should be a community- and When symptoms are a reaction to an identifiable stres-
school-based effort to increase awareness and provide sor but are severe, persistent, or disabling, depressive
access to services, including hotlines. Restricting young disorder, anxiety disorder, and conduct disorders must
people’s access to firearms is also a critical factor, as be considered.
198 / CHAPTER 6

Table 6–13. Signs and symptoms of tial diagnosis when psychotic symptoms are present, but
adjustment reactions. the cluster of symptoms is not consistent with a schizo-
phrenia diagnosis.
Irritable, angry mood
Anxious, worried mood
Unhappy, depressed mood
ESSENTIALS OF DIAGNOSIS
Angry resistance to authority & TYPICAL FEATURES
Fatigue
Aches and pains • Delusional thoughts.
Decreased school performance • Disorganized speech (rambling or illogical speech
Social withdrawal
patterns).
Any combination of the above
• Disorganized or bizarre behavior.
• Hallucinations (auditory, visual, tactile, olfactory),
negative symptoms (ie, flat affect, avolition, alo-
Treatment gia).
The mainstay of treatment is the doctor’s assurance that
the emotional or behavioral change is a predictable con-
sequence of the stressful event. This validates the child’s
reaction and encourages the child to talk about the
stressful occurrence and its aftermath. Parents are asked Clinical Findings
to understand the child’s reaction and encourage appro-
priate verbal expression of feelings, while defining Children and adolescents display many of the symptoms
boundaries for behavior that prevent the child from of adult schizophrenia. Hallucinations or delusions,
feeling out of control. bizarre and morbid thought content, and rambling and
illogical speech are typical. Affected individuals tend to
withdraw into an internal world of fantasy and may
Prognosis then equate fantasy with external reality. They generally
have difficulty with schoolwork and with peer relation-
The duration of symptoms in adjustment reactions de-
ships. Adolescents may have a prodromal period of de-
pends on the severity of the stress; the child’s personal
pression prior to the onset of psychotic symptoms. The
sensitivity to stress and vulnerability to anxiety, depres-
majority of patients with childhood-onset schizophrenia
sion, and other psychiatric disorders; and the available
have had nonspecific psychiatric symptoms or symp-
support system.
toms of delayed development for months or years prior
to the onset of their overtly psychotic symptoms.
SCHIZOPHRENIA
The incidence of schizophrenia is about 1 per 10,000 per Differential Diagnosis
year. The onset of schizophrenia is typically between the
mid- to late teens and early 30s, with onset before pu- Obtaining the family history of mental illness is critical
berty being relatively rare. Symptoms usually begin after when assessing children and adolescents with psychotic
puberty, although a full “psychotic break” may not occur symptoms. Psychological testing is often helpful in
until the young adult years. Childhood onset (before pu- identifying or ruling out psychotic thought processes.
berty) of psychotic symptoms due to schizophrenia is un- Psychotic symptoms in children younger than age
common and usually indicates a more severe form of the 8 years must be differentiated from manifestations of
spectrum of schizophrenic disorders. It affects only one normal vivid fantasy life or abuse-related symptoms.
or two children in every 10,000 of the population Children with psychotic disorders often have learning
younger than age 15 years, and boys outnumber girls by disabilities and attention difficulties in addition to dis-
approximately 2:1. Childhood schizophrenia appears to organized thoughts, delusions, and hallucinations. In
be genetically related to the adult type of schizophrenia. psychotic adolescents, mania is differentiated by high
Schizophrenia is a biologically based disease with a strong levels of energy, excitement, and irritability. Any child
genetic component. Other psychotic disorders that may or adolescent exhibiting new psychotic symptoms re-
be encountered in childhood or adolescence include quires a medical evaluation that includes physical and
schizoaffective disorder and psychosis not otherwise spec- neurologic examinations (including consideration of
ified (NOS). Psychosis NOS may be used as a differen- magnetic resonance imaging and electroencephalo-
 CHILD & ADOLESCENT PSYCHIATRIC DISORDERS / 199

gram), drug screening, and metabolic screening for en- • Violating the rights of others or society’s norms.
docrinopathies, Wilson disease, and delirium. • Aggressive behavior toward persons, animals, or
property.
Treatment
The treatment of childhood and adolescent schizophre-
nia focuses on four main areas: (1) decreasing active
psychotic symptoms, (2) supporting development of General Considerations
social and cognitive skills, (3) reducing the risk of re-
lapse of psychotic symptoms, and (4) providing support Disorders of conduct affect approximately 9% of males
and education to parents and family members. Antipsy- and 2% of females younger than 18 years. This is a very
chotic medications (eg, risperidone, olanzapine, heterogeneous population, and overlap occurs with
haloperidol) are the primary psychopharmacologic in- ADHD, learning and other neuropsychiatric disorders,
tervention. In addition, a supportive, reality-oriented mood disorders, and family dysfunction. Many of these
focus in relationships can help to reduce hallucinations, individuals come from homes where domestic violence,
delusions, and frightening thoughts. A special school or child abuse, drug abuse, shifting parental figures, and
day treatment environment may be necessary depend- poverty are environmental risk factors. Although social
ing on the child’s or adolescent’s ability to tolerate the learning partly explains this correlation, the genetic her-
school day and classroom activities. Support for the itability of aggressive conduct and antisocial behaviors
family emphasizes the importance of clear, focused is currently under investigation.
communication and an emotionally calm climate in
preventing recurrences of overtly psychotic symptoms. Clinical Findings
The typical child with conduct disorder is a boy with a
Prognosis turbulent home life and academic difficulties. Defiance
Schizophrenia is a chronic disorder with exacerbations of authority, fighting, tantrums, running away, school
and remissions of psychotic symptoms. It is generally failure, and destruction of property are common symp-
believed that earlier onset (prior to age 13 years) and toms. With increasing age, fire-setting and theft may
poor premorbid functioning (oddness or eccentricity) occur, followed in adolescence by truancy, vandalism,
generally predict a poorer outcome. and substance abuse. Sexual promiscuity, sexual perpe-
tration, and other criminal behaviors may develop. Hy-
Calderoni D et al: Differentiating childhood-onset schizophrenia
peractive, aggressive, and uncooperative behavior pat-
from psychotic mood disorders. J Am Acad Child Adolesc terns in the preschool and early school years tend to
Psychiatry 2001;40(10):1190 [PMID: 11589532]. predict conduct disorder in adolescence with a high de-
Jacobsen LK, Rapoport JL: Research update: Childhood-onset gree of accuracy, especially when ADHD goes un-
schizophrenia: Implications of clinical and neurobiological re- treated. A history of reactive attachment disorder is an
search. J Child Psychol Psychiatr 1998;39:101 [PMID: additional childhood risk factor. The risk for conduct
9534088]. disorder increases with inconsistent and severe parental
Kumra S et al: Childhood-onset schizophrenia: Research update. disciplinary techniques, parental alcoholism, and
Can J Psychiatry 2001;46(10):923 [PMID: 11816313]. parental antisocial behavior.
Practice parameters for the assessment and treatment of children
and adolescents with schizophrenia. J Am Acad Child Ado-
lesc Psychiatry 2001;40(7 Suppl):4S [PMID: 11434484]. Differential Diagnosis
Shaeffer JL, Ross RG: Childhood onset schizophrenia: Premorbid Young people with conduct disorders, especially those
and prodromal diagnostic and treatment histories. J Am Acad
Child Adolesc Psychiatry 2002;41:538 [PMID: 12014786].
with more violent histories, have an increased incidence
of neurologic signs and symptoms, psychomotor
seizures, psychotic symptoms, mood disorders, ADHD,
CONDUCT DISORDERS and learning disabilities. Efforts should be made to
identify these associated disorders (see Table 6–11) be-
cause they may suggest specific therapeutic interven-
ESSENTIALS OF DIAGNOSIS tions. Conduct disorder is best conceptualized as a final
& TYPICAL FEATURES common pathway emerging from a variety of underly-
ing psychosocial, genetic, environmental, and neu-
A persistent pattern of behavior that includes the ropsychiatric conditions. Other diagnoses that may be
following: present or should be differentiated include intermittent
• Defiance of authority. explosive disorder and oppositional defiant disorder.
200 / CHAPTER 6

Treatment • Loses temper, argues with adults, defies rules.

Effective treatment can be complicated by the problem- • Blames others for own mistakes and misbehavior.
atic psychosocial problems often found in the lives of • Angry, easily annoyed, vindictive.
children and adolescents with conduct disorders and • Does not meet criteria for conduct disorder.
difficulty achieving compliance with treatment recom-
mendations. Efforts should be made to stabilize the en-
vironment and improve functioning within the home,
particularly as it relates to parental functioning and dis- Oppositional defiant disorder (ODD) usually is evident
ciplinary techniques. Identification of learning disabili- before 8 years of age and may be an antecedent to the
ties and placement in an optimal school environment is development of conduct disorder. The symptoms usu-
also critical. Any associated neurologic and psychiatric ally first emerge at home, but then extend to school and
disorders should be addressed. In severe cases, residen- peer relationships. The disruptive behaviors of ODD
tial treatment may be needed, often through the juve- are generally less severe than those associated with con-
nile justice system. Medications such as mood stabiliz- duct disorder and do not include hurting other individ-
ers, neuroleptics, stimulants, and antidepressants have uals or animals, destruction of property, or theft.
all been studied in youth with conduct disorders, yet ODD is more common in families where caregiver
none has been found to be consistently effective in this dysfunction is present, and in children with a history of
population. Early involvement in programs such as Big multiple changes in caregivers; inconsistent, harsh, or
Brothers and Sisters, Scouts, and team sports in which neglectful parenting; or serious marital discord.
consistent adult mentors and role models interact with Interventions include careful assessment of the psy-
youth decreases the chances that the youth with con- chosocial situation and recommendations to support
duct disorders will develop antisocial personality disor- parenting skills and optimal caregiver functioning. As-
der. Multisystemic therapy (MST) is being used in- sessment for comorbid psychiatric diagnoses such as
creasingly as an intervention for youth with conduct learning disabilities, depression, and ADHD should be
disorders and involvement with the legal system. MST pursued and appropriate interventions recommended.
is an intensive home-based model of care that seeks to
stabilize and improve the home environment and to American Academy of Child and Adolescent Psychiatry: Practice
strengthen the support system and coping skills of the parameters for the assessment and treatment of children and
individual and family. adolescents with conduct disorder. J Am Acad Child Adolesc
Psychiatry 1997;36 (Suppl):122S [PMID: 9334568].
Burke JH, Loeber R, Birmaher B: Oppositional defiant disorder
Prognosis and conduct disorder: Review of the past 10 years, part II.
J Am Acad Child Adolesc Psychiatry 2002; 41(11):1275
The prognosis is based on the ability of the child’s sup- [PMID: 12410070].
port system to mount an effective treatment interven- Cunningham CE, Boyle MH: Preschoolers at risk for ADHD and
tion consistently over time. The prognosis is generally ODD: Family, parenting and behavioral correlates. J Abnorm
worse for children in whom the disorder presents before Child Psychol 2002;30(6):555 [PMID: 12481971].
age 10 years; those who display a diversity of antisocial Farmer EM et al: Review of the evidence base for treatment of
behaviors across multiple settings; and those who are childhood psychopathology: Externalizing disorders. J Con-
raised in an environment characterized by parental anti- sult Clin Psychol 2002;70(6):1267 [PMID: 12472301].
social behavior, alcoholism or other substance abuse, Flory K et al: Relation between childhood disruptive behavior dis-
and conflict. Nearly half of such children become anti- orders and substance use and dependence in young adult-
hood. Psychol Addictive Behav 2003;17(2):151 [PMID:
social as adults. Persistent antisocial behavior in child- 12814279].
hood or adolescence tends to predict a diagnosable psy-
Greene RW et al: Psychiatric comorbidity, family dysfunction and
chiatric disorder in adulthood. social impairment in referred youth with oppositional defiant
disorder. Am J Psychiatry 2002;159(7):1214 [PMID:
12091202].
1. Oppositional Defiant Disorder Kazdin AE: Treatments for aggressive and antisocial children.
Child Adolesc Psychiatr Clin North Am 2000;9(4):841
[PMID: 11005009].
ESSENTIALS OF DIAGNOSIS Loeber R et al: Findings on disruptive behavior disorders from the
first decade of the developmental trends study. Clin Child
& TYPICAL FEATURES Fam Psychol Rev 2000;3(1):37 [PMID: 11228766].
Loeber R et al: Oppositional defiant and conduct disorder: A re-
• A pattern of negativistic, hostile, and defiant be- view of the past 10 years Part 1. J Am Acad Child Adolesc
havior lasting at least 6 months. Psychiatry 2000;39(12):1468 [PMID: 11128323].
 CHILD & ADOLESCENT PSYCHIATRIC DISORDERS / 201

Waschbusch DA et al: Reactive aggression in boys with disruptive sociated with social withdrawal and depression. The in-
behavior disorders; behavior, physiology and affect. J Abnorm cidence of anxiety and mood disorders is increased in
Child Psychol 2002;30(6):641 [PMID: 12481977].
these families.

ANXIETY DISORDERS
Differential Diagnosis
1. Anxiety-Based School Refusal
(School Avoidance) The differential diagnosis of school nonattendance is
presented in Table 6–14. Medical disorders that may be
causing the somatic symptoms must be ruled out. Chil-
ESSENTIALS OF DIAGNOSIS dren with learning disorders may wish to stay home to
& TYPICAL FEATURES avoid the sense of failure they experience at school.
Children may also have transient episodes of wanting to
• A persistent pattern of school avoidance related stay at home during times of significant family stress or
to symptoms of anxiety. loss. The onset of school avoidance in middle or late
adolescence may herald the onset of schizophrenia or
• Somatic symptoms on school mornings, with other psychotic disorder. Children who are avoiding
symptoms resolving if the child is allowed to re- school for reasons related to ODD or conduct disorder
main at home. can be differentiated on the basis of their chronic non-
• No organic medical disorder that accounts for the compliance with adult authority and their preference
symptoms. for being with peers rather than at home.
• High levels of parental anxiety are commonly ob-
served.
Table 6–14. Differential diagnosis of
school nonattendance.a

General Considerations I. Emotional or anxiety-based refusalb

Anxiety-based school refusal is a persistent behavioral A. Separation anxiety disorder (50–80% of anxious re-
symptom rather than a diagnostic entity. It refers to a fusers)
pattern of school nonattendance resulting from anxiety, B. Generalized anxiety disorder
which may be related to a dread of leaving home (sepa- C. Mood/depressive disorder (with or without com-
ration anxiety), a fear of some aspect of school, or a fear bined anxiety)
D. Social phobia
of feeling exposed or embarrassed at school (social pho-
E. Specific phobia
bia). In all cases, a realistic cause of the fear (eg, an in- F. Panic disorder
timidating teacher or a playground bully) should be G. Psychosis (“voices” say not to attend)
ruled out. In most cases, anxiety-based school refusal is II. Truancyc behavior disorders
related to developmentally inappropriate separation A. Oppositional defiant disorder, conduct disorder
anxiety. The incidence between males and females is B. Substance abuse disorders
about equal, and there appear to be peaks of incidence III. “Realistic” school refusal
at ages 6–7 years, again at ages 10–11 years, and in A. Learning disability, unaddressed or undetected
early adolescence. B. Marauding students (including gangs)
C. Psychologically abusive teacher
Clinical Findings D. Family-sanctioned nonattendance
1. For companionship
In the preadolescent years, school refusal often begins 2. For child care
after some precipitating stress in the family. The child’s 3. To care for the parent (role-reversal)
anxiety is then manifested either as somatic symptoms 4. To supplement family income
or in displacement of anxiety onto some aspect of the E. Socioculturally sanctioned nonattendance (school is
school environment. The somatic manifestations of not valued)
anxiety include dizziness, nausea, and stomach distress. F. Homosexual attraction, gender concerns
Characteristically, the symptoms become more severe as IV. Undiagnosed medical condition (including pregnancy)
the time to leave for school approaches and then remit a
Medically unexplained absence of more than 2 weeks.
if the child is allowed to remain at home for the day. In b
Subjectively distressed child who generally stays at home.
older children, the onset is more insidious and often as- c
Nonsubjectively distressed and not at home.
202 / CHAPTER 6

Complications Egger HL, Coatello EJ, Angold A: School refusal and psychiatric
disorders: A community study. J Am Acad Child Adolesc
The longer a child remains out of school, the more dif- Psychiatry 2003;42(7):797 [PMID: 12819439].
ficult it is to return and the more strained the relation- King NJ, Bernstein GA: School refusal in children and adolescents:
ship between child and parent becomes. Many parents A review of the past 10 years. J Am Acad Child Adolesc Psy-
of nonattending children feel tyrannized by their defi- chiatry 2001;40(2):197 [PMID: 11211368].
ant, clinging child. Children often feel accused of mak- Masi G, Mucci M, Millepiedi S: Separation anxiety disorder in
ing up their symptoms, leading to further antagonism children and adolescents: Epidemiology, diagnosis, and man-
agement. CNS Drugs 2001;15(2):93 [PMID: 11460893].
between the child, parents, and medical caregivers.

2. Generalized Anxiety Disorder

Treatment
& Panic Disorder
The goal of treatment is to help the child confront anx-
iety and overcome it by returning to school. This re- Transient developmental fears are common in early
quires a strong alliance between the parents and the childhood. Therefore, the person evaluating the clinical
health care provider. The parent must understand that significance of anxiety symptoms in children must con-
no underlying medical disorder exists, that the child’s sider the age of the child, the developmental fears that
symptoms are a manifestation of anxiety, and that the can normally be expected at that age, the form of the
basic problem is anxiety that must be faced to be over- symptoms and their duration, and the degree to which
come. Parents must be reminded that being good par- the symptoms disrupt the child’s life.
ents in this case means helping a child cope with a dis- Anxiety can be manifested either directly or indi-
tressing experience. Children must be reassured that rectly, as shown in Table 6–15. The characteristics of
their symptoms are caused by worry and that they will anxiety in childhood are listed in Table 6–16. Commu-
be overcome on return to school. nity-based studies of school-age children and adoles-
A plan for returning the child to school is then devel- cents suggest that nearly 10% of children have some
oped with parents and school personnel. Firm insistence type of anxiety disorder. The differential diagnosis of
on full compliance with this plan is essential. The child is symptoms of anxiety is presented in Table 6–17.
brought to school by someone not likely to give in, such The child’s family and school environment should
as the father or an older sibling. If symptoms develop at be evaluated for marital discord, family violence, harsh
school, the child should be checked by the school nurse or inappropriate disciplinary methods, sexual abuse, ne-
and then returned to class after a brief rest. The parents
must be reassured that school staff will handle the situa- Table 6–15. Signs and symptoms of anxiety
tion at school and that school personnel can reach the
in children.
primary health care provider if any questions arise.
If these interventions are ineffective, increased in-
volvement of a therapist and consideration of a day Psychological
treatment program may be necessary. For children with Fears and worries
persistent symptoms of separation that do not improve Increased dependence on home and parents
with behavioral interventions, medications such as Avoidance of anxiety-producing stimuli
SSRIs should be considered. Comorbid diagnoses of Decreased school performance
Increased self-doubt and irritability
panic disorder, generalized anxiety, or major depression
Frightening themes in play and fantasy
should be carefully screened for and, if identified, Psychomotor
treated appropriately. Motoric restlessness and hyperactivity
Sleep disturbances
Prognosis Decreased concentration
Ritualistic behaviors (eg, washing, counting)
The vast majority of preadolescent children improve Psychophysiologic
significantly with behavioral interventions and return Autonomic hyperarousal
to school. The prognosis is worsened by the length of Dizziness and lightheadedness
time the child remains out of school. Long-term out- Palpitations
comes are influenced by comorbid diagnoses and re- Shortness of breath
sponsiveness to behavioral or medication interventions. Flushing, sweating, dry mouth
A history of school refusal is more common in adults Nausea and vomiting
with panic and anxiety disorders and agoraphobia than Panic
in the general population. Headaches and stomachaches
 CHILD & ADOLESCENT PSYCHIATRIC DISORDERS / 203

Table 6–16. Anxiety disorders in children Table 6–17. Differential diagnosis of symptoms
and adolescents. of anxiety.

Disorder Major Clinical Manifestations I. Normal developmental anxiety

A. Stranger anxiety (5 months to 21⁄2 years, with a peak
Generalized anxiety Intense, disproportionate or irrational
at 6–12 months)
disorder worry, often about future events
B. Separation anxiety (7 months to 4 years, with a peak
Panic disorder Unprovoked, intense fear with sympa- at 18–36 months)
thetic hyperarousal, and often palpita- C. The child is fearful or even phobic of the dark and
tions or hyperventilation monsters (3–6 years)
II. “Appropriate” anxiety
Posttraumatic stress Fear of a recurrence of an intense, anx-
A. Anticipating a painful or frightening experience
disorder iety-provoking traumatic experience,
B. Avoidance of a reminder of a painful or frightening
causing sympathetic hyperarousal,
experience
avoidance of reminders, and the re-
C. Child abuse
experiencing of aspects of the trau-
III. Anxiety disorder (see Table 6–16), with or without
matic event
other comorbid psychiatric disorders
Separation anxiety Developmentally inappropriate wish IV. Substance abuse
disorder to maintain proximity with caregivers; V. Medications and recreational drugs
morbid worry of threats to family in- A. Caffeinism (including colas and chocolate)
tegrity or integrity of self upon separa- B. Sympathomimetic agents
tion; intense homesickness C. Idiosyncratic drug reactions
VI. Hypermetabolic or hyperarousal states
Social phobia Painful shyness or self-consciousness;
A. Hyperthyroidism
fear of humiliation with public scrutiny
B. Pheochromocytoma
Specific phobia Avoidance of specific feared stimuli C. Anemia
D. Hypoglycemia
E. Hypoxemia
VII. Cardiac abnormality
glect, and emotional overstimulation. The child’s expe- A. Dysrhythmia
rience of anxiety and its relationship to life events B. High-output state
should be explored, and therapy to incorporate specific C. Mitral valve prolapse
cognitive and behavioral techniques to diminish the
anxiety should be recommended. Finally, when panic
attacks or anxiety symptoms do not remit with cogni-
Gullone E, King NJ, Ollendick TH: Self-reported anxiety in chil-
tive, behavioral, and environmental interventions, and dren and adolescents: A three-year follow-up study. J Genet
they significantly affect life functioning, psychophar- Psychol 2001;162(1):5 [PMID: 11338440].
macologic agents may be helpful. SSRIs may be effec- Rynn MA, Siqueland L, Rickels K: Placebo-controlled trial of ser-
tive across a broad spectrum of anxiety symptoms. traline in the treatment of children with generalized anxiety
disorder. Am J Psychiatry 2001;158(12):2008 [PMID:
11729017].
Prognosis
Velosa JF, Riddle MA: Pharmacologic treatment of anxiety disor-
There appears to be continuity between high levels of ders in children and adolescents. Child Adolesc Psychiatr
childhood anxiety and anxiety disorders in adulthood. Clin North Am 2000;9(1):119 [PMID: 10674193].
Anxiety disorders are thus likely to be lifelong condi- Wagner KD: Generalized anxiety disorder in children and adoles-
tions, yet with effective interventions, individuals can cents. Psychiatr Clin North Am 2001;24(1):139 [PMID:
11225504].
minimize their influence on overall life functioning.

American Academy of Child and Adolescent Psychiatry: Practice OBSESSIVE–COMPULSIVE DISORDER

parameters for the assessment and treatment of children and
adolescents with anxiety disorders. J Am Acad Child Adolesc
Psychiatry 1997;36 (Suppl):69S [PMID: 9334566].
ESSENTIALS OF DIAGNOSIS
Blanco C, Antia SX, Lebowitz MR: Pharmacotherapy of social anx-
iety disorder. Biol Psychiatry 2002;51(1):1098 [PMID: & TYPICAL FEATURES
11801236].
Diler RS: Panic disorder in children and adolescents. Yonsei Med • Recurrent obsessive thoughts, impulses, or im-
J 2003;44(1):174 [PMID: 12619196]. ages that cause marked anxiety or distress and
204 / CHAPTER 6

are not simply excessive worries about real-life Cook EH et al: Long-term sertraline treatment of children and ado-
problems. lescents with obsessive–compulsive disorder. J Am Acad
Child Adolesc Psychiatry 2001;40(10):1175 [PMID:
• The individual attempts to ignore or suppress the 11589530].
thoughts or impulses. Geller DA et al: Fluoxetine treatment for OCD in children and
• Repetitive compulsive behaviors or mental acts adolescents: A placebo controlled trial. J Am Acad Child
that the person feels driven to perform in re- Adolesc Psychiatry 2001;40(7):773 [PMID: 11437015].
sponse to the obsessive thought aimed at pre- Grados MA, Riddle MA: Pharmacological treatment of childhood
obsessive compulsive disorder: From theory to practice. J Clin
venting or reducing distress. Child Psychol 2001;30(1):67 [PMID: 11294079].
• The obsessions and compulsions cause marked Kaplan A, Hollander D: A review of pharmacologic treatment for
distress, are time-consuming, and interfere with obsessive-compulsive disorder. Psychiatric Serv 2003;54:
normal routines. 1111 [PMID: 12883138].
March JS: Cognitive-behavioral psychotherapy for children and
adolescents with OCD: A review and recommendations for
treatment. J Am Acad Child Adolesc Psychiatry 1995;
Obsessive–compulsive disorder (OCD) is an anxiety dis- 34(1):7.
order that often begins in early childhood, but may not March JS et al: Cognitive-behavioral psychotherapy for pediatric
be diagnosed until the teen or even young adult years. obsessive–compulsive disorder. J Clin Child Psychol 2001;
30(1):8 [PMID: 11294080].
The essential features of OCD are recurrent obsessions
Riddle MA et al: Fluvoxamine for children and adolescents with
or compulsions that are severe enough to be time-con- OCD: A randomized, controlled, multicenter trial. J Am
suming or cause marked distress and functional impair- Acad Child Adolesc Psychiatry 2001;40(2):222 [PMID:
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pulses that are intrusive and often inappropriate. Thomsen PH: Obsessions: The impact and treatment of obses-
Children may have obsessions about contamination or sive–compulsive disorder in children and adolescents. J Psy-
cleanliness; ordering and compulsive behaviors will fol- chopharmacol 2000;14(2 Suppl 1):S31 [PMID: 10888029].
low, such as frequent hand-washing, counting, or order- Waters TL et al: Cognitive-behavioral family treatment of child-
ing objects. The goal of the compulsive behavior for the hood obsessive–compulsive disorder: Preliminary findings.
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There may be significant avoidance of situations due to
obsessive thoughts or fears of contamination. OCD is POSTTRAUMATIC STRESS DISORDER
often associated with major depressive disorder. The
prevalence of OCD is estimated to be around 2%, and
the rates are equal between males and females. ESSENTIALS OF DIAGNOSIS
& TYPICAL FEATURES
Treatment
• Signs and symptoms of autonomic hyperarousal
OCD is best treated with a combination of cognitive– such as easy startle, increased heart rate, and hy-
behavioral therapy (CBT) specific to OCD and med- pervigilance.
ications in more severe cases. SSRIs are effective in di-
• Avoidant behaviors and numbing of responsive-
minishing OCD symptoms. Fluvoxamine and sertra-
line have FDA approval for the treatment of pediatric ness.
OCD. The tricyclic antidepressant (TCA) clomipramine • Flashbacks to a traumatic event, such as night-
has FDA approval for the treatment of OCD in adults. mares, and intrusive thoughts.
• All of the preceding following the experience of
Prognosis traumatic events such as exposure to violence,
physical or sexual abuse, natural disasters, car ac-
Although OCD is usually a lifelong condition, most in- cidents, dog bites, and unexpected personal
dividuals can achieve significant remission of symptoms tragedies.
with the combination of CBT and medications. A mi-
nority of individuals with OCD are completely dis-
abled by their symptoms.

American Academy of Child and Adolescent Psychiatry: Practice General Considerations

parameters for the assessment and treatment of children and
adolescents with OCD. J Am Acad Child Adolesc Psychiatry Factors that predispose individuals to the development
1998;37(10 Supp):27S [PMID: 9785727]. of posttraumatic stress disorder (PTSD) include proxim-
 CHILD & ADOLESCENT PSYCHIATRIC DISORDERS / 205

ity to the traumatic event or loss, a history of exposure For children with more severe and persistent symp-
to trauma, preexisting depression or anxiety disorder, toms, assessment for treatment with medication is indi-
and lack of an adequate support system. PTSD can de- cated. Sertraline has approval for the treatment of
velop in response to natural disasters, terrorism, motor PTSD in adults. Target symptoms (eg, anxiety, depres-
vehicle accidents, and significant personal injury in ad- sion, nightmares, aggression) should be clearly identi-
dition to physical, sexual, and emotional abuse. Long- fied and appropriate medications trials initiated with
overdue attention is now being paid to the substantial close monitoring. Some of the medications used to treat
effects of family and community violence on the psy- children with PTSD include clonidine or guanfacine
chological development of children and adolescents. (Tenex), mood stabilizers, and antidepressants and neu-
Abused children are most likely to develop PTSD and to roleptics. Children who have lived for an extended time
suffer wide-ranging symptoms and impaired function- in abusive environments or who have been exposed to
ing. Heightened concern about terrorism in the United multiple traumas are more likely to require treatment
States has created increased awareness of PTSD and with medications. Occupational therapy for sensory in-
community-based interventions to decrease the risk of tegration can also be effective in decreasing reactivity to
PTSD. Studies after the terrorist attacks of September stimuli and helping the child and caregivers develop
11, 2001, and Oklahoma City reported up to 40% of and implement self-soothing skills. Individuals who
children and adolescents experienced PTSD symptoms. have suffered single-episode traumas usually benefit sig-
As many as 25% of young people exposed to violence nificantly from psychotherapy and may require limited
develop symptoms of posttraumatic stress disorder. Fac- treatment with medication to address symptoms of anx-
tors that predispose to development of PTSD when a iety, nightmares, and sleep disturbance. Psychotherapy
person is exposed to a traumatic event include a history that includes eye movement desensitization and repro-
of exposure to trauma, preexisting depression or anxiety cessing (EMDR) may also be useful.
disorder, and lack of an adequate support system.

Clinical Findings Prognosis

Children who have been traumatized show persistent At 4- to 5-year follow-up investigations, many children
evidence of fear and anxiety and are hypervigilant to the who have been through a traumatic life experience con-
possibility of repetition. They may regress developmen- tinue to have vivid and frightening memories and
tally and experience fears of strangers, of the dark, and dreams and a pessimistic view of the future. The effects
of being alone, and avoid reminders of the traumatic of traumatic experiences can be far-reaching. The abil-
event. Children also frequently reexperience elements ity of caregivers to provide a safe, supportive, stable,
of the events in dreams and flashbacks. In their sym- empathic environment enhances the prognosis for indi-
bolic play, one can often notice a monotonous repeti- viduals with PTSD. Timely access to therapy and use of
tion of some aspect of the traumatic event. Children therapy over time to work through symptoms also en-
with a history of traumatic experiences or neglect in in- hance prognosis. Evidence is growing to support a con-
fancy and early childhood are likely to show signs of re- nection between victimization in childhood and unsta-
active attachment disorder and have difficulty forming ble personality and mood disorders in later life.
relationships with caregivers.
American Academy of Child and Adolescent Psychiatry: Practice
Treatment parameters for the assessment and treatment of children and
adolescents with posttraumatic stress disorder. J Am
The cornerstone of treatment for PTSD is education of Acad Child Adolesc Psychiatry 1998;37(Suppl):4S [PMID:
the child and family regarding the nature of the disorder 9785726].
so that the child’s emotional reactions and regressive be- Grant KE et al: Stressors and child and adolescent psychopathol-
havior are not mistakenly viewed as crazy or manipula- ogy: Moving from markers to mechanisms of risk. Psychol
tive. Support, reassurance, and repeated explanations and Bull 2002;129(3):447 [PMID: 12784938].
understanding are needed. It is critical that the child be Martin SG: Children exposed to domestic violence: Psychological
living in a safe environment, and if caregivers have been considerations for health care practitioners. Holistic Nurs
Pract 2002;16(3):7 [PMID: 11913229].
abusive, concerns must be reported to social services. In-
Meiser-Stedman R: Towards a cognitive-behavioral model of
terventions to maintain safety of the child are imperative. PTSD in children and adolescents. Clin Child Fam Psychol
Individual and family psychotherapy are central features Rev 2002;5(4):217 [PMID: 12495267].
of treatment interventions. Specific fears usually wane Pine DS: Developmental psychobiology and response to threats:
with time, and behavioral desensitization may help. A Relevance to trauma in children and adolescents. Biol Psychi-
supportive relationship with a caregiving adult is essential. atry 2003;53(9):796 [PMID: 12725972].
206 / CHAPTER 6

Pine DS, Cohen JA: Trauma in children and adolescents: Risk and Table 6–18. Somatoform disorders in children
treatment of psychiatric sequelae. Biol Psychiatry 2002;51(7):
519 [PMID: 11950454].
and adolescents.
Scheeringa MS et al: New findings on alternative criteria for PTSD
in preschool children. J Am Acad Child Adolesc Psychiatry Disorder Major Clinical Manifestations
2003;42(5):561 [PMID: 12707560].
Body dysmorphic Preoccupation with an imagined defect
Teicher MH et al: Developmental neurobiology of childhood stress
disorder in personal appearance
and trauma. Psychiatr Clin North Am 2002;25(2):
397 [PMID: 12136508]. Conversion Symptom onset follows psychologically
disorder stressful event; symptoms express uncon-
scious feelings and result in secondary
SOMATOFORM DISORDERS gain
Hypochondriasis Preoccupation with worry that physical
symptoms manifest unrecognized and
ESSENTIALS OF DIAGNOSIS threatening condition; medical assurance
& TYPICAL FEATURES does not provide relief from worry
Somatization Long-standing preoccupation with mul-
• A symptom suggesting physical dysfunction. disorder tiple somatic symptoms
• No physical disorder accounting for the symptom. Somatoform pain Preoccupation with pain that results in
• Symptoms causing distress, dysfunction, or both. disorder distress or impairment beyond what
• Symptoms not voluntarily created or maintained, would be expected from physical findings
as in malingering.

In the classic case of conversion disorder, the child’s

symptoms and examination findings are not consistent
Clinical Findings with the clinical manifestations of any organic disease
process. The physical symptoms often begin within the
Somatoform disorders are defined by the presence of context of a family experiencing stress, such as serious
physical illness or disability for which no organic cause illness, a death, or family discord. On closer examina-
can be identified, although neither the patient nor the tion, the child’s symptoms are often found to resemble
caregiver is consciously fabricating the symptoms. The symptoms present in other family members. Children
category includes body dysmorphic disorder, conver- with conversion disorder may have some secondary
sion disorder, hypochondriasis, somatization disorder, gain associated with their symptoms. A number of re-
and somatoform pain disorder (Table 6–18). ports have pointed to the increased association of con-
Conversion symptoms most often occur in school- version disorder with sexual overstimulation or sexual
age children and adolescents. The exact incidence is un- abuse. As with other emotional and behavioral prob-
clear, but in pediatric practice they are probably seen lems, health care providers should always screen for
more often as transient symptoms than as chronic dis- physical and sexual abuse.
orders requiring help from mental health practitioners.
A conversion symptom is thought to be an expression
of underlying psychological conflict. The specific symp- Differential Diagnosis
tom may be symbolically determined by the underlying It is sometimes not possible to rule out medical disease
conflict. Furthermore, the symptom may resolve the as a source of the symptoms. Medical follow-up is re-
dilemma created by the underlying wish or fear (eg, a quired to monitor for changes in symptoms and re-
seemingly paralyzed child need not fear expressing his sponse to recommended interventions.
underlying rage or aggressive retaliatory impulses). Al- Somatic symptoms are often associated with anxiety
though children can present with a variety of symp- and depressive disorders (see Table 6–15). Occasion-
toms, the most common include neurologic and gas- ally, psychotic children have somatic preoccupations
trointestinal (GI) complaints. Children with conversion and even somatic delusions.
disorder may be surprisingly unconcerned about the
substantial disability deriving from their symptoms. Treatment & Prognosis
Symptoms include unusual sensory phenomena, paraly-
sis, vomiting, abdominal pain, intractable headaches, In most cases, conversion symptoms resolve quickly
and movement or seizure-like disorders. when the child and family are reassured that the symp-
 CHILD & ADOLESCENT PSYCHIATRIC DISORDERS / 207

tom is a way of reacting to stress. The child is encour- General Considerations

aged to continue with normal daily activities, knowing
that the symptom will abate when the stress is resolved. Enuresis is the passage of urine into bedclothes or un-
Treatment of conversion disorders includes ac- dergarments, whether involuntary or intentional. At
knowledging the symptom rather than telling the child least 90% of enuretic children have primary nocturnal
that the symptom is not medically justified and re- enuresis—that is, they wet only at night during sleep
sponding with noninvasive interventions such as physi- and have never had a sustained period of dryness. Diur-
cal therapy while continuing to encourage normaliza- nal enuresis (daytime wetting) is much less common, as
tion of the symptoms. If the symptom does not resolve is secondary enuresis, which develops after a child has
with reassurance, further investigation by a mental had a sustained period of bladder control. The latter
health professional is indicated. Comorbid diagnoses two varieties are much more commonly associated with
such as depression and anxiety disorders should be ad- emotional stress, anxiety, and psychiatric disorders. Pri-
dressed, and treatment with psychopharmacologic mary nocturnal enuresis is most often a parasomnia, a
agents may be helpful. deep-sleep (stage 3 or stage 4) event. Etiologically, it is
generally viewed as a developmental disorder or matu-
rational lag that children will outgrow. Only infre-
quently is it associated with a serious psychopathologic
Campo JV, Fritz G: A management model for pediatric somatiza- disorder.
tion. Psychosomatics 2001;42(6):467 [PMID: 11815681].
Campo JV et al: Somatization in pediatric primary care: Associa-
tion with psychopathology, functional impairment, and use
Clinical Findings
of services. J Am Acad Child Adolesc Psychiatry 1999;38: Primary nocturnal enuresis is common (Table 6–19).
1093 [PMID: 10504807]. The incidence is three times higher in boys than in
Dhossche D et al: Somatoform disorders in children and adoles- girls. Most children with enuresis become continent by
cents: A comparison with other internalizing disorders. Ann
Clin Psychiatry 2002;14(1):23 [PMID: 12046637].
adolescence or earlier. The family history in such cases
Fritz GK et al: Somatoform disorders in children and adolescents:
frequently reveals other members, especially fathers,
A review of the past 10 years. J Am Acad Child Adolesc Psy- who have had prolonged nighttime bed-wetting prob-
chiatry 1997;36:1329 [PMID: 9334545]. lems. Although the cause of primary nocturnal enuresis
is not established, it appears to be related to matura-
tional delay of sleep and arousal mechanisms or to delay
in development of increased bladder capacity.
ELIMINATION DISORDERS Daytime wetting most often occurs in timid and shy
children or in children with ADHD. It occurs with
1. Enuresis about equal frequency in boys and girls, and 60–80%
It is important for the primary care provider to carefully of daytime wetters also wet at night. Secondary enuresis
assess the developmental age of the child, the situation typically follows a stressful event, such as the birth of a
in which enuresis is occurring, and to screen for med- sibling, a loss, or discord within the family. The symp-
ical concerns before deciding that the enuresis or enco- tom can be seen as the result of regression in response
presis is attributable to a behavioral or emotional disor-
der. It is not uncommon for parents to have unrealistic
expectations about toilet training for young children. In
many cases of enuresis, the child is simply not develop- Table 6–19. Incidence of enuresis in children.
mentally ready or sometimes is unable to remain dry at
night. Most children with enuresis are able to remain Age Primary Nocturnal Occasional Daytime
dry by age 9. (years) Enuresis (%) Enuresis (%)a
5 15 8
ESSENTIALS OF DIAGNOSIS 7–8 7 —
& TYPICAL FEATURES 10 3–5 —
• Urinary incontinence in a child age 5 years (or de- 12 2–3 1
velopmental equivalent) or older. 14 1 —
• No medication or general medical condition a
Diurnal (daytime) enuresis tends to resolve by developmental
causing the urinary incontinence. age 6 years, with a slight recurrence around age 12 years in early
adolescence.
208 / CHAPTER 6

to stress or as a more symbolic expression of the child’s symptom and behavioral interventions to work toward
feelings. dryness and cope with episodes of wetting.

Differential Diagnosis 2. Encopresis

The differential diagnosis includes urinary tract infec-
tions, neurologic diseases, seizure disorders, diabetes ESSENTIALS OF DIAGNOSIS
mellitus, and structural abnormalities of the urinary & TYPICAL FEATURES
tract. Urinalysis and urine culture and observing the
child’s urinary stream can rule out the majority of or- • Fecal incontinence in a child age 4 years (or devel-
ganic causes of enuresis. opmental equivalent) or older.
• Not due to medication or medical disorder.
Complications
The most common complication of enuresis is low self-
esteem in response to criticism from caregivers and em-
barrassment if peers are aware of the problem. Older General Considerations
children with enuresis may be reluctant to attend sleep- Functional encopresis is defined as the repeated passage
overs and be self-conscious with peers. of feces in inappropriate places by a child of at least the
developmental equivalent of age 4 years. It may be ei-
Treatment ther involuntary or intentional, although most often it
is involuntary. It affects approximately 1–1.5% of
Treatment should emphasize that the symptom of noc- school-age children; boys four times more often than
turnal enuresis is a developmental lag and often will be girls. Functional fecal incontinence is rare in adoles-
outgrown even without treatment. Even with these in- cence.
terventions, many children will have difficulty remain-
ing dry. If the child chooses to pursue treatment, a pro- Clinical Findings
gram of bladder exercises can be prescribed: fluids
should be limited after dinner; the child should attempt Functional encopresis can be divided into four types:
to hold urine as long as possible during the day and retentive, continuous, discontinuous, and toilet phobia.
then start and stop the stream at the toilet bowl; the
child is instructed to practice getting up from bed and A. RETENTIVE ENCOPRESIS
going to the bathroom at bedtime before sleep. These In retentive encopresis, also called psychogenic mega-
procedures are helpful in perhaps 30–40% of children colon, the child withholds bowel movements, leading
with nighttime wetting. Another option is a “potty to the development of constipation, fecal impaction,
pager.” This is a beeper-like object that attaches to the and the seepage of soft or liquid feces around the mar-
child’s underwear and vibrates when the child is wet in gins of the impaction into the underclothing. Marked
an attempt to rouse the child into a wakeful state and constipation and painful defecation often contribute to
increase awareness of the need to urinate. a vicious cycle of withholding, thus creating larger im-
Desmopressin acetate (DDAVP), administered in- paction and further seepage. These children often have
tranasally at bedtime, can result in complete remission a history of crossing their legs to resist the urge to defe-
of nocturnal enuresis in 50% of children as long as they cate and of infrequent bowel movements large enough
continue the treatment. DDAVP is expensive, but can to stop up the toilet, and they are found on examina-
be useful until the child develops the ability to hold tion to have large fecal masses in their rectal vaults. The
urine through the night or awaken to use the bath- soiling that occurs distresses most of these children.
room. For others, a trial of the TCA imipramine is
worthwhile, at dosages of 25–50 mg at bedtime for B. CONTINUOUS ENCOPRESIS
children under age 12 years and 50–75 mg for older Children with continuous encopresis have never gained
children. Because many patients relapse once the drug primary control of bowel function. The bowel move-
is stopped, its primary use is for camp attendance or ment is usually randomly deposited in underclothing
overnight visits. Mental health treatment is more often without regard to social norms. Typically, the family
needed for children with daytime wetting or secondary structure does not encourage organization and skill
enuresis. The focus is on the verbal expression of feel- training, and for that reason the child has never had ad-
ings that may be associated with perpetuation of the equate bowel training. These children and their parents
 CHILD & ADOLESCENT PSYCHIATRIC DISORDERS / 209

are more apt to be socially or intellectually disadvan- clothes. The responsibility for rinsing soiled clothing
taged. and depositing it in the appropriate receptacle rests
with the child. In the case of continuous encopresis, the
C. DISCONTINUOUS ENCOPRESIS family is taught to train the child. For toilet phobia, a
Children with discontinuous encopresis have a history progressive series of rewarded desensitization steps is
of normal bowel control for an extended period. Loss of necessary. Children with discontinuous encopresis that
control often occurs in response to a stressful event, persists over a number of weeks often need psychother-
such as the birth of a sibling, a separation, family ill- apy to help them recognize and verbally express their
ness, or marital disharmony. These children may soil anger and wish to be dependent, rather than express
their pants or on occasion defecate on the floor or themselves through fecal soiling.
smear feces as an expression of anger or of a wish to be
perceived as younger. They typically display relative in- Prognosis
difference to the symptom.
Although the ultimate prognosis is excellent, parental
D. TOILET PHOBIA distress and parent–child conflict may be substantial
In the infrequent case of toilet phobia, a young child prior to the cessation of symptoms. The natural history
views the toilet as a frightening structure to be avoided. of soiling is that it resolves by adolescence in all but the
These children may view the bowel movement as an ex- most severely disturbed teenagers.
tension of themselves, which is then swept away in a
frightening manner. They may think that they, too, Bonner L, Dobson P: Children who soil: Guidelines for good prac-
may be swept away, down the toilet. tice. J Fam Health Care 2003;13(2):32 [PMID: 12793299].
Borowitz SM et al: Treatment of childhood encopresis: A random-
ized trial comparing three treatment protocols. J Pediatr Gas-
Differential Diagnosis troenterol Nutr 2002;34(4):378 [PMID: 11930093].
Differential diagnosis includes the medical causes of Cedron M: Removing the stigma: Helping reduce the psychosocial
constipation and retentive encopresis. Hirschsprung impact of bedwetting. Urol Nurs 2002;22(4):286 [PMID:
12242905].
disease can be ruled out with reasonable certainty by
Cox DF et al: Psychological differences between children with and
the history of passing large-caliber bowel movements in without chronic encopresis. J Pediatr Psychol 2002;27(7):
the past and by the presence of palpable stool in the 585 [PMID: 12228330].
rectal vault. Neurologic disorders, hypothyroidism, hy- Fishman L et al: Trends in referral to a single encopresis clinic over
percalcemia, and diseases of smooth muscle must be 20 years. Pediatrics 2003;111(5 pt 1):e604 [PMID: 12728118].
considered as well. The child should be examined for Fritz G, Rockney R: Summary of the practice parameter for the as-
anal fissures, which tend to encourage the withholding sessment and treatment of children and adolescents with
of bowel movements. In addition, fecal soiling can be a enuresis. J Am Acad Child Adolesc Psychiatry 2004;43(1):
presenting symptom in childhood depression and is 123 [PMID: 14691370].
sometimes a concomitant finding in children with Gottsegen DN: Curing bedwetting on the spot: A review of one-
ADHD. If the child engages in fecal smearing, an un- session cures. Clin Pediatr 2003;42(3):273 [PMID: 12739927].
derlying psychotic disorder should be considered. Loening-Baucke V: Encopresis. Curr Opin Pediatr 2002;14(5):
570 [PMID: 12352250].
Mercer R: Dry at night. Treating nocturnal enuresis. Adv Nurs
Treatment Pract 2003;11(2):26 [PMID: 12640815].
Identifying the type of encopresis is important in treat- Mikkelson EJ: Enuresis and encopresis: Ten years of progress. Am
J Child Adolesc Psychiatr 2001;40(10):1146 [PMID:
ment planning. Another important variable is the 11589527].
child’s own concern about the symptom. Encopresis in Thiedke CC: Nocturnal enuresis. Am Fam Physician 2003;67(7):
children who display denial or indifference is much 1499 [PMID: 12722850].
harder to treat. Children with coexisting depression or Van Ginkel R et al: Childhood constipation: Longitudinal follow-
ADHD need to receive treatment for those conditions up beyond puberty. Gastroenterology 2003;125(2):357
before focusing treatment on soiling. [PMID: 12891536].
With the most common type of encopresis, the re-
tentive type, efforts are made to soften stool so that Other psychiatric conditions not covered in this chap-
constipation and painful defecation do not perpetuate ter:
the behavior. These children are then taught to adopt a
regular schedule of sitting on the toilet after meals. A Attention-Deficit/Hyperactivity Disorder (ADHD),
system of positive reinforcement can be added in which See Chapter 2
the child is rewarded for each day with no soiled under- Eating Disorders, See Chapter 5
210 / CHAPTER 6

Mental Retardation, See Chapter 2 minish most or all of the target symptoms before con-
Substance Abuse, See Chapter 4 sidering the simultaneous administration of two or
Tourette Syndrome, See Chapter 23 more agents.
Table 6–20 presents an overview of the clinical con-
ditions for which psychopharmacologic agents should
be considered and medication categories for which
studies have been completed or published case reports
OVERVIEW OF PEDIATRIC have suggested some therapeutic efficacy. Only the
PSYCHOPHARMACOLOGY stimulants for ADHD and fluvoxamine and sertraline
for OCD have FDA approval for specific use in chil-
dren and adolescents.
Pediatric psychopharmacology has improved signifi- In the text that follows, the major classes of psy-
cantly over the past decade with increasing study of the chopharmacologic agents with clinical indications in
effect of psychoactive medications on mental illness in child and adolescent psychiatry are represented. The
childhood and adolescence. Although relatively few more commonly prescribed drugs from each class are
medications are approved for use in children, many of reviewed with reference to indications, relative con-
the same psychopharmacologic agents used in adults are traindications, initial medical screening procedures (in
now used in children and adolescents. addition to a general pediatric examination), dosage,
As with any medication, the risks as well as the ben- adverse effects, drug interactions, and medical follow-
efits of administering psychoactive medications must be up recommendations. This is meant to be a brief refer-
discussed with the child’s parent or guardian and with ence guide, and the physician should consult a child
the child and adolescent, as is age-appropriate. A rec- and adolescent psychopharmacology textbook for addi-
ommendation for medication is warranted if the disor- tional information on specific medications.
der is interfering with psychosocial development, inter-
personal relationships, daily functioning, or the
patient’s sense of personal well-being, and if there is sig-
nificant potential for benefit with the medication and
relatively low risk of harm. Informed consent should be Table 6–20. Clinical conditions and
given by the parent or guardian and noted in the appropriate medications
record. Adolescents should also provide informed con-
sent for treatment. In some states adolescents age Possible Classes
15 and older must give informed consent. Informed of Medications
consent includes a discussion of the diagnosis, target Diagnosis to Target Symptoms
symptoms, possible common side effects, any side ef-
fects that should be closely monitored, potential bene- ADHD Stimulants, bupropion,

-agonists
fits associated with the medication, and documentation
Anorexia nervosa SSRIs, atypical neuroleptics
of informed consent in the medical record. Psychophar- Autism SSRIs, atypical neuroleptics,
macologic agents are seldom the only treatment for a clomipramine, naltrexone
psychiatric disorder. Most often they are best used ad- Bipolar affective disorder Mood stabilizers, neurolep-
junctively along with other therapeutic interventions tics
such as individual and family psychotherapy and psy- Bulimia nervosa SSRIs
chosocial interventions, including assessment of school Major depression and Antidepressants
functioning and special needs. dysthymic disorder
A good rule when considering the use of psychoac- Anxiety disorders Antidepressants, benzodi-
tive medications in children and adolescents is, first, to azepines
identify target symptoms that can be followed to evalu- Posttraumatic stress disorder Antidepressants, α-ago-
ate the efficacy of treatment. When initiating treat- nists, mood stabilizers,
ment, start with low doses and increase slowly (in di- atypical neuroleptics
vided doses, if indicated) monitoring for side effects Obsessive compulsive disorder SSRIs, clomipramine
along with therapeutic effects. When drugs are discon- Schizophrenia and psychotic Neuroleptics
tinued, dosages should be tapered over 2–4 weeks to disorders
minimize withdrawal effects. When multiple choices Conduct disorder and Mood stabilizers, neurolep-
exist, one should select the medication with the fewest severe aggressive behavior tics,
-agonists, stim-
and least ominous risks and side effects. Polypharmacy ulants,  blockers
should be avoided by choosing one drug that might di- SSRIs = selective serotonin reuptake inhibitors.
 CHILD & ADOLESCENT PSYCHIATRIC DISORDERS / 211

MEDICATIONS FOR ATTENTION- periods of discontinuation. Ultimate height is not usu-

DEFICIT/HYPERACTIVITY DISORDER ally noticeably compromised. Treatment with stimu-
lant medications does not predispose to future sub-
(ADHD) stance abuse.
Methylphenidate (Concerta, Metadate, Methylin,
Ritalin) E. DRUG INTERACTIONS
Dextroamphetamine (Dexedrine) Additive stimulant effects are seen with sympath-
Pemoline (Cylert) omimetic amines (ephedrine, pseudoephedrine).
Adderall
Atomoxetine (Strattera) F. MEDICAL FOLLOW-UP
A. INDICATIONS Pulse, blood pressure, height, and weight should be
Approximately 75% of children with ADHD experi- recorded every 3–4 months and at times of dosage in-
ence improved attention span, decreased hyperactivity, creases. Assess for abnormal movements such as motor
and decreased impulsivity when given stimulant med- tics at each visit.
ications. Children with ADHD who do not respond fa-
vorably to one stimulant may respond well to another. G. DOSAGE
Children and adolescents with ADHD without promi-
1. Methylphenidate—The usual starting dose is 5 mg
nent hyperactivity (ADHD, predominantly inattentive
once or twice a day (before school and at noon), gradu-
type) are also likely to be responsive to stimulant med-
ally increasing to 5–10 mg/wk. Maximum daily dose
ications. Atomoxetine (Strattera) and bupropion (Well-
should not exceed 60 mg, and a single dose should not
butrin) are nonstimulant medications used to treat
exceed 0.7 mg/kg. Administration on weekends and
ADHD. Strattera has FDA approval for the treatment
during vacations is determined by the need at those
of ADHD and is a selective noradnergic reuptake in-
times. The duration of action is approximately
hibitor. Bupropion (Wellbutrin) is primarily used as an
3–4 hours. Several extended-release forms can prevent
antidepressant, and blocks both serotonin and norepi-
the need for taking medication at school.
nephrine reuptake.
B. CONTRAINDICATIONS 2. Dextroamphetamine sulfate—The dosage is
Use stimulants cautiously in individuals with a personal 2.5–10 mg twice daily, before school and at noon, with
or family history of motor tics or Tourette syndrome, or without another dose at 4 PM. A sustained-release
or if there is a personal or family history of substance preparation may have clinical effects for up to 8 hours.
abuse, addictive disorders, or psychotic disorders. There is also an extended-release form.
C. INITIAL MEDICAL SCREENING
3. Pemoline—The longer half-life of pemoline allows
The initial interview should include screening for per- for the administration of a single dose each morning.
sonal or family history of motor tics or Tourette syn- The usual starting dose of 37.5 mg is increased weekly
drome. The child should be observed for involuntary by 18.75 mg until the desired clinical effect is achieved
movements. Height, weight, pulse, and blood pressure or until a maximum daily dose of 112.5 mg is reached.
should be recorded. Liver enzymes should be tested if The onset of clinical effect may be delayed for
pemoline is considered. 3–4 weeks. Liver enzymes must be monitored during
D. ADVERSE EFFECTS treatment. Pemoline is contraindicated in individuals
with hepatic disease.
Often dose-related and time-limited. Longer acting stimulants (see a psychopharmacology
1. Common adverse effects—Anorexia, weight loss, reference source for pharmacologic properties and
abdominal distress, headache, insomnia, dysphoria and dosage information): Adderall (dextroamphetamine
tearfulness, irritability, lethargy, mild tachycardia, mild and amphetamine)
elevation in blood pressure. Methylphenidate hydrochloride extended-release
2. Less common effects—Interdose rebound of tablets (Concerta, Metadate)
ADHD symptoms, emergence of motor tics or
Tourette syndrome, behavioral stereotypy, tachycardia 4. Atomoxetine Hydrochloride—The starting dose
or hypertension, depression, mania, and psychotic for children and adolescents up to 70 kg is 0.5 mg/kg,
symptoms. Reduced growth velocity occurs only during with titration to a maximum dose of 1.2 mg/kg, in sin-
active administration. Growth rebound occurs during gle or divided dosing.
212 / CHAPTER 6

ANTIDEPRESSANTS weight loss, insomnia, sedation (10%), sexual dysfunc-

tion (25%). Irritability, social disinhibition, restless-
1. Selective Serotonin Reuptake ness, and emotional excitability can occur in approxi-
Inhibitors mately 20% of children taking SSRIs.
Citalopram, escitalopram (Celexa, Lexapro) E. DRUG INTERACTIONS
Fluoxetine (Prozac, Sarafem) All SSRIs inhibit the efficiency of the hepatic microso-
Fluvoxamine (Luvox) mal enzyme system. The order of inhibition is: fluoxe-
Paroxetine (Paxil) tine > fluvoxamine > paroxetine > sertraline > citalo-
pram. This can lead to higher than expected blood
Sertraline (Zoloft)
levels of other drugs, including antidepressants, antiar-
A. INDICATIONS rhythmics, antipsychotics, β-blockers, opioids, and an-
The SSRIs have become the agents of first choice for tihistamines. Taking tryptophan while on an SSRI may
the treatment of depression and anxiety. Fluvoxamine result in a serotonergic syndrome of psychomotor agita-
and sertraline both have approval from the FDA for tion and GI distress. A potentially fatal interaction that
treatment of pediatric OCD. Although no other SSRIs clinically resembles neuroleptic malignant syndrome
have FDA approval for pediatric indications, some pub- may occur when the SSRIs are administered concomi-
lished studies support the efficacy of SSRIs for the tantly with the monoamine oxidase inhibitors
treatment of depression, anxiety, and OCD in pediatric (MAOIs). Fluoxetine has the longest half-life of the
populations. Each SSRI has different FDA indications. SSRIs and should not be initiated within 14 days of the
However, once an indication is obtained for one SSRI, discontinuation of an MAOI, or an MAOI initiated
it is widely believed that other SSRIs are likely to be ef- within at least 5 weeks of the discontinuation of fluoxe-
fective as well for the same indication. The FDA-ap- tine.
proved indications are the following: F. DOSAGE (TABLE 6–21)
Major depression (> 18 years of age): fluoxetine, The SSRIs are usually given once a day, in the morning
paroxetine, citalopram, sertraline with breakfast. One in 10 individuals may experience
Panic disorder (> 18 years): paroxetine, sertraline sedation and prefer to take the medication at bedtime.
OCD (> 6 years): sertraline, fluvoxamine The alternative antidepressants and fluvoxamine are
usually given in twice daily dosing. Bupropion and ven-
Bulimia (> 18 years): fluoxetine lafaxine are now available in a sustained- and extended-
Posttraumatic stress disorder (> 18 years): sertraline release form. Therapeutic response should be expected
Premenstrual dysphoric disorder (> 18 years): fluox- 4–6 weeks after a therapeutic dose has been reached.
etine The starting dose for a child younger than 12 years old
is generally half the starting dose for an adolescent.
B. CONTRAINDICATIONS
Concern about paroxetine causing a slightly increased 2. Other Antidepressants
incidence of suicidal ideation in children and adoles-
cents in Great Britain led to a 2003 FDA statement re- Bupropion (Wellbutrin), bupropion SR (sustained
garding caution in prescribing this medication for chil- release)
dren and adolescents. Caution should be used in cases Venlafaxine (Effexor), venlafaxine XR (extended re-
of known liver disease, because all SSRIs are metabo- lease)
lized in the liver. Caution should be used when pre-
scribing for an individual with a family history of bipo- Mirtazapine (Remeron)
lar disorder, or when the differential diagnosis includes Nefazodone (Serzone)
bipolar disorder, because antidepressants can induce
manic or hypomanic symptoms. Bupropion
C. INITIAL MEDICAL SCREENING A. INDICATIONS
General medical examination only. Bupropion is an antidepressant that inhibits reuptake of
primarily serotonin, but also norepinephrine and
D. ADVERSE EFFECTS dopamine. It is approved for treatment of major de-
Often dose-related and time-limited: GI distress and pression in adults, but is receiving favorable attention
nausea (can be minimized by taking medication with for its therapeutic effects with major depressive disorder
food), headache, tremulousness, decreased appetite, in adolescents and with ADHD in children and adoles-
 CHILD & ADOLESCENT PSYCHIATRIC DISORDERS / 213

Table 6–21. Medications used to treat depression in adolescents

Adolescent Target Dose (Average

Generic Trade Name Starting Dose Effective Dose) Maximum Dose
SSRIs
Citalopram Celexa 20 mg qAM 20 mg qAM 40–60 mg qAM
Escitalopram Lexapro 10 mg 10 mg 30 mg
Fluoxetine Prozac 10 mg qAM 20 mg qAM 60 mg qAM
Fluvoxamine Luvox 50 mg qhs 100–150 mg qd 100 mg bid
Paroxetine Paxil 10 mg qAM 20 mg qAM 60 mg qAM
Paroxetine CR Paxil CR 25 mg 25 mg 50 mg
Sertraline Zoloft 25 mg qAM 50 mg qAM 150 mg qAM
Alternative Antidepressants
Bupropion Wellbutrin 75 mg qAM 150 mg bid 200 mg bid
Bupropion SR Wellbutrin SR 100 mg qAM 100 mg bid 150 mg bid
Mirtazapine Remeron 7.5 mg qhs 15 mg qhs 30 mg qhs
Nefazodone Serzone 50 mg qhs 100 mg bid 300 mg bid
Venlafaxine Effexor 37.5 mg qAM 75 mg bid 150 mg bid
Venlafaxine XR Effexor XR 37.5 mg qAM 150 mg qd 225 mg qd
qAM = every morning; qhs = every night at bedtime; qd = every day; bid = twice a day.

cents. Like the SSRIs, bupropion has very few anti- D. ADVERSE EFFECTS
cholinergic or cardiotoxic effects. The most common adverse effects are nausea, nervous-
ness, and sweating. Hypertension is likely with doses
B. CONTRAINDICATIONS over 300 mg or over 225 mg of the extended release
History of seizure disorder or bulimia nervosa. version. Venlafaxine must be discontinued slowly to
minimize withdrawal symptoms: severe headaches,
C. INITIAL MEDICAL SCREENING AND FOLLOW-UP dizziness and significant flu-like symptoms. It is also
General medical examination. available in an extended-release form.

D. ADVERSE EFFECTS Mirtazapine

Psychomotor activation (agitation or restlessness), Mirtazapine is an α2-antagonist that enhances central
headache, GI distress, nausea, anorexia with weight noradreneregic and serotonergic activity.
loss, insomnia, tremulousness, precipitation of mania,
and induction of seizures with doses above 450 mg/d. A. INDICATIONS
It is approved for the treatment of major depression in
Venlafaxine adults.
Venlafaxine is an antidepressant that primarily inhibits B. CONTRAINDICATIONS
reuptake of serotonin and norepinephrine.
Mirtazapine should not be given in combination with
A. INDICATIONS MAOIs. Very rare side effects are acute liver failure
(1 case per 250–300,000), neutropenia, and agranulo-
It is approved for the treatment of major depression in cytosis.
adults.
C. INITIAL MEDICAL SCREENING AND FOLLOW-UP
B. CONTRAINDICATIONS General medical examination.
Hypertension.
D. ADVERSE EFFECTS
C. INITIAL MEDICAL SCREENING AND FOLLOW-UP Dry mouth, increased appetite, constipation, weight
General medical examination. gain.
214 / CHAPTER 6

3. Tricyclic Antidepressants increase, and obtain an ECG to monitor for arteriove-

nous block with each dosage increase; after reaching
Imipramine steady state, record pulse, blood pressure, and ECG
Desipramine (Norpramin) every 3–4 months.
Clomipramine (Anafranil) E. ADVERSE EFFECTS
Nortriptyline
1. Cardiotoxic effects—The cardiotoxic effects of
Amitryptyline (Elavil) TCAs appear to be more common in children and ado-
With the introduction of the SSRIs and alternative an- lescents than in adults. In addition to anticholinergic
tidepressants, use of the TCAs has become uncommon effects, TCAs have quinidine-like effects that result in
for the treatment of depression and anxiety disorders. slowing of cardiac conduction. Increased plasma levels
The TCAs have more significant side-effect profiles, re- appear to be weakly associated with an increased risk
quire more substantial medical monitoring, and are of cardiac conduction abnormalities. Steady-state
quite cardiotoxic in overdose. For these reasons, in gen- plasma levels of desipramine or of desipramine plus
eral, SSRIs or alternative antidepressants should be con- imipramine should therefore not exceed 300 ng/mL. In
sidered before recommending a TCA. addition, each dosage increase above 3 mg/kg/d must
be carefully monitored with pulse, blood pressure, and
A. INDICATIONS repeated ECGs to monitor for arteriovenous block.
TCAs have been prescribed for chronic pain syn- Upper limits for cardiovascular parameters when ad-
dromes, migraines, headache, depression, anxiety, ministering TCAs to children and adolescents are listed
enuresis, bulimia nervosa, OCD, and PTSD in children in Table 6–22.
and adolescents. Imipramine and desipramine have 2. Anticholinergic effects—Tachycardia, dry mouth,
FDA approval for the treatment of major depression in stuffy nose, blurred vision, constipation, sweating, vaso-
adults and enuresis for children older than 6 years of motor instability, withdrawal syndrome (GI distress
age. Some published studies have demonstrated clinical and psychomotor activation).
efficacy in the treatment of ADHD, panic disorder,
anxiety-based school refusal, separation anxiety disor- 3. Other effects—Orthostatic hypotension and dizzi-
der, bulimia, night terrors, and sleepwalking. But, as ness, lowered seizure threshold, increased appetite and
yet, the FDA has not approved their use for these indi- weight gain, sedation, irritability and psychomotor agi-
cations. Studies have not supported efficacy in major tation, rash (often associated with yellow dye No. 5),
depression in children and adolescents. Nortriptyline headache, abdominal complaints, sleep disturbance and
has FDA approval for the treatment of major depres- nightmares, mania.
sion in adults. Clomipramine has FDA approval for the F. DRUG INTERACTIONS
treatment of depression and OCD in adults and may be
TCAs may potentiate the effects of CNS depressants
helpful for obsessive symptoms in autism.
and stimulants; barbiturates and cigarette smoking may
B. CONTRAINDICATIONS decrease plasma levels; phenothiazines, methylpheni-
date, and oral contraceptives may increase plasma lev-
Known cardiac disease or arrhythmia, undiagnosed syn-
els; SSRIs given in combination with TCAs will result
cope, known seizure disorder, family history of sudden
in higher TCA blood levels due to inhibition of the
cardiac death or cardiomyopathy, known electrolyte ab-
normality (with bingeing and purging).
C. INITIAL MEDICAL SCREENING Table 6–22. Upper limits of cardiovascular
The family history should be examined for sudden car- parameters with tricyclic antidepressants.
diac death; the patient’s history for cardiac disease, ar-
rhythmias, syncope, seizure disorder, or congenital
Heart rate 130/min
hearing loss (associated with prolonged QT interval).
Other screening procedures include serum electrolytes Systolic blood pressure 130 mm Hg
and blood urea nitrogen (BUN) in patients who have Diastolic blood pressure 85 mm Hg
eating disorders, cardiac examination, and a baseline
electrocardiogram (ECG). PR interval 0.2 s
QRS interval 0.12 s, or no more than 30%
D. MEDICAL FOLLOW-UP over baseline
Measure pulse and blood pressure (monitor for tachy-
cardia and orthostatic hypotension) with each dosage QT corrected 0.45 s
 CHILD & ADOLESCENT PSYCHIATRIC DISORDERS / 215

TCA metabolism by liver enzymes (eg, cytochrome information.) Oral doses of lithium should be titrated
p450 isoenzyme). to maintain therapeutic blood levels of 0.8–1.2 mEq/L.
The drug is generally given in two doses. Blood samples
G. DOSAGE should be drawn 12 hours after the last dose.
Refer to a pediatric psychopharmacology text for
dosages. Daily dosage requirements vary considerably E. ADVERSE EFFECTS
with different clinical disorders. 1. Lithium toxicity—Lithium has a narrow therapeu-
tic index. Blood levels required for therapeutic effect are
MOOD STABILIZERS close to those associated with toxic symptoms. Mild
toxicity may be indicated by increased tremor, GI dis-
Lithium carbonate (Eskalith, Eskalith CR, Lithobid, tress, neuromuscular irritability, and altered mental sta-
Lithotabs) tus (confusion), and can occur when blood levels ex-
Valproic acid (Depakote, Depakote ER) ceed 1.5 mEq/L. Moderate to severe symptoms of
Carbamazepine (Tegretol) lithium toxicity are associated with blood levels above
2 mEq/L. Acute renal failure can occur at levels over
Olanzapine (Zyprexa, atypical neuroleptic)
2.5–3 mEq/L.
Lithium, valproic acid, and olanzapine (neuroleptic) are 2. Side effects—Lithium side effects include intention
FDA approved for the treatment of bipolar disorder. tremor, GI distress (including nausea and vomiting and
Carbamazepine and oxycarbamazepine, although not sometimes diarrhea), hypothyroidism, polyuria and
FDA approved for treatment of bipolar disorder, may polydipsia, drowsiness, malaise, weight gain, acne, and
also be effective and carry less risk of weight gain. Lam- granulocytosis.
otrigine (Lamictal) was recently approved for the treat-
ment of bipolar depression in adults. Other antiepilep- F. DRUG INTERACTIONS
tic medications, such as gabapentin and topiramate,
Excessive salt intake and salt restriction should be
have also been used with varying efficacy. Medications
avoided. Thiazide diuretics and nonsteroidal anti-in-
that are effective as mood stabilizers may be helpful also
flammatory agents (except aspirin and acetaminophen)
in the treatment of severe aggressive symptoms.
can lead to increased lithium levels. Ibuprofen should
be avoided by individuals on lithium due to combined
Lithium renal toxicity. Precautions against dehydration are re-
A. INDICATIONS quired in hot weather and during vigorous exercise.
Lithium remains a frontline drug in the treatment of G. MEDICAL FOLLOW-UP
bipolar disorder and has been shown to have an aug- Serum lithium levels should be measured 5–7 days fol-
menting effect when combined with SSRIs for treat- lowing a change in dosage and then quarterly at steady
ment-resistant depression and OCD. state; serum creatinine and thyroid-stimulating hor-
B. CONTRAINDICATIONS mone concentrations should be determined every
Lithium is contraindicated in patients with known 3–4 months.
renal, thyroid, or cardiac disease; those at high risk for
dehydration and electrolyte imbalance (eg, vomiting Valproic Acid
and purging); and those who may become pregnant
(teratogenic effects).
A. INDICATIONS
Valproate has FDA approval for the treatment of bipo-
C. INITIAL MEDICAL SCREENING lar disorder in adults. Its efficacy in acute mania equals
General medical screening with pulse, blood pressure, that of lithium, but it is generally better tolerated. Val-
height, and weight; complete blood cell count (CBC); proate is more effective than lithium in patients with
serum electrolytes, BUN, and creatinine; and thyroid rapid-cycling bipolar disorder (more than four cycles
function tests including thyroid-stimulating hormone per year) and in patients with mixed states (coexisting
levels. symptoms of depression and mania). Valproate may be
more effective than lithium in adolescents with bipolar
D. DOSAGE disorder because they often have rapid cycling and
For children the starting dose is usually 150 mg once or mixed states.
twice a day, with titration in 150–300-mg increments.
(Dose may vary with the brand of lithium used, consult B. CONTRAINDICATIONS
a psychopharmacology textbook for medication specific Liver dysfunction.
216 / CHAPTER 6

C. INITIAL MEDICAL SCREENING D. DOSAGE

CBC and LFTs. Usually start at 10–20 mg/kg/d, in two divided doses,
in children younger than age 6 years; 100 mg twice
D. DOSAGE daily in children ages 6–12 years; and 200 mg twice
Usually starts at 15 mg/kg/d and is increased in incre- daily in children over age 12 years. Doses may be in-
ments of 5 to 10 mg/kg/d every 1–2 weeks to a range of creased weekly until there is effective symptom control.
500–1500 mg/d in two or three divided doses. Trough Total daily doses should not exceed 35 mg/kg/d in chil-
levels in the range of 80–120 mg/mL are thought to be dren younger than age 6 years; 1000 mg/d in children
therapeutic. ages 6–15 years; and 1200 mg/d in adolescents older
than age 15 years. Plasma levels in the range of
4–12 mg/mL are thought to be therapeutic.
E. ADVERSE EFFECTS
Between 10% and 20% of patients experience sedation E. ADVERSE EFFECTS
or anorexia, especially early in treatment or if the dose Nausea, dizziness, sedation, headache, dry mouth,
is increased too rapidly. GI upset occurs in 25% of pa- diplopia, and constipation reflect the drug’s mild anti-
tients and, when severe, can usually be treated with ci- cholinergic properties. Rashes are more common with
metidine. Increased appetite and weight gain can be carbamazepine than with other mood stabilizers. Aplas-
troublesome for children and adolescents. Blurred vi- tic anemia and agranulocytosis are rare. Leukopenia
sion, headache, hair loss, and tremor occur occasion- and thrombocytopenia are more common and, if pre-
ally. Slight elevations in aminotransferases are frequent. sent, should be monitored closely for evidence of bone
Severe idiosyncratic hepatitis, pancreatitis, thrombocy- marrow depression. These effects usually occur early
topenia, and agranulocytosis occur only rarely. and transiently and then spontaneously revert toward
normal. Liver enzyme induction may significantly
F. MEDICAL FOLLOW-UP change the efficacy of medications given concurrently.
LFTs should be checked monthly for 3–4 months; sub- F. MEDICAL FOLLOW-UP
sequently, LFTs, a CBC, and trough valproate levels
should be obtained every 3–4 months. Conservative management suggests that hematologic,
hepatic, and renal parameters should be followed at
least every 3 months for the first year. White blood cell
Carbamazepine counts below 3000/mL and absolute neutrophil counts
below 1000/mL call for discontinuation of the drug
A. INDICATIONS and referral for hematology consultation.
Similar to lithium and valproate, carbamazepine may
be effective for treating bipolar disorder or for the target Gabapentin
symptoms of mood instability, irritability, or behavioral
dyscontrol. Some data suggest that it is more effective Like valproate and carbamazepine, gabapentin is an an-
than valproate for the depressive phases of a bipolar dis- ticonvulsant that has been used as a mood stabilizer in
order. This may relate to its similarities with the TCAs. some adult populations. It may be used along with ei-
A new form of carbamazepine—oxycarbamazepine ther valproate or carbamazepine in individuals with
(Trileptal)—is also being used for pediatric mood dis- treatment-resistant disorders. The usual adult dose
orders; however, without established efficacy. Report- range for seizure disorders is 900–1800 mg/d in three
edly, it does not have the worrisome side effects of bone divided doses and may need to be adjusted downward
marrow suppression and liver enzyme induction. Blood in individuals with renal impairment. Although its use
levels cannot be monitored, and the dose range is simi- among adolescents and even children is increasing, it is
lar to that with carbamazepine. not approved for this indication, and reports of its effi-
cacy remain largely anecdotal. Some reports suggest it
B. CONTRAINDICATIONS may worsen behavioral parameters in children with un-
derlying ADHD.
History of previous bone marrow depression or history
of adverse hematologic reaction to another drug; his-
tory of sensitivity to a TCA. NEUROLEPTICS
1. Atypical (Newer) Neuroleptics
C. INITIAL MEDICAL SCREENING
Obtain a CBC with platelets, reticulocytes, serum iron, Aripiprazole (Abilify)
and BUN; LFTs; urinalysis. Clozapine (Clozaril)
 CHILD & ADOLESCENT PSYCHIATRIC DISORDERS / 217

Olanzapine (Zyprexa) Olanzapine (Zyprexa)

Risperidone (Risperdal) The FDA has approved this agent for the treatment of
Quetiapine (Seroquel) schizophrenia and bipolar disorder in adults. Olanzap-
Ziprasidone (Geodon) ine has greater affinity for type-2 serotonin receptors
than dopamine-2 receptors and also has an effect on
muscarinic, histaminic, and α-adrenergic receptors. As
2. Conventional Neuroleptics with the other atypical neuroleptics, it may be more
helpful for treating the negative symptoms of schizo-
Chlorpromazine phrenia (flat affect, isolation and withdrawal, apathy)
Thioridazine than conventional neuroleptics. Anecdotal and case re-
Haloperidol port data support its utility in child and adolescent psy-
chotic disorders. The adult dose range of 5–15 mg/d
Thiothixene administered in a single, bedtime dose is probably ap-
Molindone plicable to adolescents as well. Weight gain can be a sig-
Trifluoperazine nificant side effect. The starting dose for children is
Perphenazine usually 1.25 mg.

The neuroleptics, also known as antipsychotics, are in- Quetiapine (Seroquel)

dicated for psychotic symptoms in patients with schizo- Quetiapine is an antagonist at multiple receptor sites,
phrenia. They are also used for acute mania and as ad- including serotonin (5-HT1A, 5-HT2), dopamine (D1,
juncts to antidepressants in the treatment of psychotic D2), histamine, and adrenergic receptors. Quetiapine is
depression (with delusions or hallucinations). The neu- given in 25- to 50-mg increments up to 800 mg for the
roleptics may be used cautiously in refractory PTSD, in treatment of psychotic symptoms. It is thought to be a
refractory OCD, and in individuals with markedly ag- “weight-neutral” medication, and the primary side ef-
gressive behavioral problems unresponsive to other in- fect is sedation.
terventions. They may also be useful for the body image
distortion associated with anorexia nervosa. Risperidone (Risperdal)
The “atypical neuroleptics” differ from conventional
neuroleptics in their receptor specificity and effect on Risperidone blocks type-2 dopamine receptors (similar
serotonin receptors. Conventional neuroleptics are as- to haloperidol) and type-2 serotonin receptors. Adult
sociated with a higher incidence of movement disorders schizophrenic patients given 2–8 mg/d of risperidone
and extrapyramidal symptoms (EPS) due to their wider had better symptom relief and fewer side effects than
effect on dopamine receptors. The introduction of the those treated with conventional neuroleptics. Anecdotal
atypical neuroleptics has significantly changed neu- reports suggest that similar results may be obtained in
roleptic prescribing patterns. The atypical neuroleptics adolescents with schizophrenia. Risperidone has also
have a better side effect profile for most individuals and demonstrated good clinical efficacy in the treatment of
comparable efficacy for the treatment of psychotic Tourette syndrome. The initial dose is 1–2 mg/d in
symptoms and aggression. Atypical neuroleptics have a two divided doses. Side effects include weight gain and
decreased incidence of EPS and tardive dyskinesias sedation.
(TD). Significant side effects can include substantial
weight gain and sedation. Because of their increased use Ziprasidone (Geodon)
over conventional neuroleptics, this section will focus
primarily on the atypical neuroleptics. Ziprasidone has affinity for multiple serotonin recep-
tors (5-HT2, 5-HT1a, 5-HT1D, and 5-HT2C) and
dopamine-2 receptors, and it moderately inhibits nor-
Aripiprazole (Abilify) epinephrine and 5-HT reuptake. It also has moderate
affinity for H1 and α1 receptors. Ziprasidone has a
Aripiprazole is the newest atypical neuroleptic and is in- greater effect on cardiac QT intervals and requires a
dicated for the treatment of schizophrenia. It is a partial baseline ECG and ECG monitoring when a dose of
dopamine blocker and a serotonin agonist. Side effects 80 mg is reached and with each dose change above
include nausea and vomiting and fatigue. It is not asso- 80 mg to monitor for QT prolongation. Ziprasidone is
ciated with weight gain. Doses over 30 mg are more reported to cause minimal weight gain. The initial dose
likely to be associated with EPS. The dose range is of ziprasidone is 20 mg, with dose changes 20-mg in-
10 mg–30 mg, and pills can be split. crements to a total daily dose of 140 mg for the treat-
218 / CHAPTER 6

ment of psychotic symptoms in adults. There are no increased incidence of EPS and TD. Sedation, cogni-
studies of ziprasidone in children and adolescents at tive slowing, and EPS all tend to be dose-related. Be-
this time. cause of the risk of side effects, neuroleptic medications
should be used with caution and monitored regularly.
Clozapine (Clozaril) The risk–benefit ratio of the medication for the identi-
fied target symptom should be carefully considered and
Clozapine is usually reserved for individuals with treat- reviewed with the parent or guardian.
ment who have not responded to multiple other neu-
1. Extrapyramidal side effects—EPS and acute dys-
roleptics due to the side effect of agranulocytosis.
tonic reactions are tonic muscle spasms, often of the
Clozapine blocks type-2 dopamine receptors weakly
tongue, jaw, or neck. EPS symptoms can be mildly un-
and is virtually free of EPS, apparently including TD. It
comfortable or may result in such dramatically distress-
was very effective in about 40% of adult patients with
ing symptoms as oculogyric crisis, torticollis, and even
chronic schizophrenia who did not respond to conven-
opisthotonos. The onset usually occurs within days
tional neuroleptics.
after a dosage change and may occur in up to 25% of
Non–dose-related agranulocytosis occurs in 0.5–2%
children treated with conventional neuroleptics. Acute
of subjects. Some case reports note benefit from clozap-
neuroleptic-induced dystonias are quickly relieved by
ine in child and adolescent schizophrenic patients who
anticholinergics such as benztropine (Cogentin) and
were resistant to other treatment. Contraindications are
diphenhydramine.
concurrent treatment with carbamazepine and any his-
tory of leukopenia. Initial medical screening should in- 2. Tardive dyskinesias—TDs are involuntary move-
clude CBC and LFTs. The daily dose is 200–600 mg in ment disorders that are often irreversible and may ap-
two divided doses. Because of the risk of neutropenia, pear after long-term use of neuroleptic medications.
patients taking clozapine must be registered with the Choreoathetoid movements of the tongue and mouth
Clozapine Registry and a white blood cell count must be are most common, but the extremities and trunk may
obtained biweekly before a 2-week supply of the drug is also be involved. The risk of TD is small in patients on
dispensed. If the white count falls below 3000/mL, cloza- atypical neuroleptics, and those on conventional neu-
pine is usually discontinued. Other side effects include roleptics for less than 6 months. There is no universally
sedation, weight gain, and increased salivation. The inci- effective treatment.
dence of seizures increases with doses above 600 mg/d. 3. Pseudoparkinsonism—Pseudoparkinsonism is usu-
ally manifested 1–4 weeks after the start of treatment. It
3. General Neuroleptic Information presents as muscle stiffness, cogwheel rigidity, mask-
like facial expression, bradykinesia, drooling, and occa-
The following adverse effects of neuroleptics apply to sionally pill-rolling tremor. Anticholinergic medica-
both typical and atypical neuroleptics, but are thought tions or dosage reductions are helpful.
to have a significantly lower incidence with the atypical
neuroleptics. 4. Akathisia—Akathisia is usually manifested after
1–6 weeks of treatment. It presents as a unpleasant feel-
A. INITIAL MEDICAL SCREENING ing of driven motor restlessness that ranges from vague
One should observe and examine for abnormal move- muscular discomfort to a markedly dysphoric agitation
ments and establish baseline values for CBC and LFTs. with frantic pacing. Anticholinergic agents or β-block-
An ECG should be taken if there is a history of cardiac ers are sometimes helpful.
disease or arrhythmia, and to establish a baseline QT 5. Neuroleptic malignant syndrome—Neuroleptic
interval (cardiac repolarization) prior to initiation of malignant syndrome (NMS) is a very rare medical
the neuroleptics that have a greater effect on QT (eg, emergency associated primarily with the conventional
ziprasidone and thioridazine). Neuroleptics can cause neuroleptics, although it has been reported also with
QT prolongation leading to ventricular arrhythmias, atypical neuroleptics. It is manifested by severe muscu-
such as torsades de pointes. Medications that affect the lar rigidity, altered sensorium, hyperpyrexia, autonomic
cytochrome p450 isoenzyme pathway (including lability, and myoglobinemia. NMS can present without
SSRIs) may increase the neuroleptic plasma concentra- muscle rigidity with atypical neuroleptics and should be
tion and increase risk of QTc prolongation. considered in the differential diagnosis of any patient
on neuroleptics who presents with high fever and al-
B. ADVERSE EFFECTS tered mental status. Mortality as high as 30% has been
The most troublesome adverse effects of the atypical reported. Treatment includes immediate medical assess-
neuroleptics are cognitive slowing, sedation, orthostasis, ment, withdrawal of the neuroleptic, and may require
and weight gain. The conventional neuroleptics have transfer to an ICU.
 CHILD & ADOLESCENT PSYCHIATRIC DISORDERS / 219

6. Withdrawal dyskinesias—Withdrawal dyskinesias giving 0.05 mg also in the morning. Further dosage in-
are reversible movement disorders that appear following creases are made by adding 0.05 mg first in the morn-
withdrawal of neuroleptic medications. Dyskinetic ing, then at noon, and then in the evening every
movements develop within 1–4 weeks after withdrawal 3–5 days to a maximum total daily dose of 0.3 mg in
of the drug and may persist for months. three or four divided doses per day. The half-life of
7. Other adverse effects—These include cardiac ar- clonidine is in the range of 3–4 hours. Although a clini-
rhythmias, irregular menses, gynecomastia and galact- cal response generally becomes apparent by about
orrhea due to increased prolactin, sexual dysfunction, 4 weeks, treatment effects may increase over
photosensitivity, rashes, lowered seizure threshold, he- 2–3 months. Therapeutic doses of methylphenidate can
patic dysfunction, and blood dyscrasias. frequently be decreased by 30–50% when used in con-
junction with clonidine. Transdermal administration of
C. DRUG INTERACTIONS clonidine using a skin patch can be quite effective but
Potentiation of CNS depressant effects or the anti- may result in skin irritation in 40% of patients. Patches
cholinergic effects of other drugs may occur, as well as are generally changed every 5 days.
increased plasma levels of antidepressants. The starting dosage of guanfacine is usually
0.5–1 mg once a day, increasing as clinically indicated
D. MEDICAL FOLLOW-UP after 3–5 days to 2–4 mg/d in two or three divided
One should examine the patient at least every 3 months doses per day. Adverse effects include transient
for signs of the side effects listed. An Abnormal Invol- headaches and stomachaches in 25% of patients. Seda-
untary Movement Scale (AIMS) can be used to moni- tion and hypertension are mild. For medical follow-up,
tor for TD for patients taking neuroleptics. pulse and blood pressure should be checked every
1–2 weeks for 2 months and then at 3-month intervals.
ADRENERGIC AGONISTS E. ADVERSE EFFECTS
Clonidine and Guanfacine (Tenex) Sedation can be prominent. Side effects include fatiga-
A. INDICATIONS bility, dizziness associated with hypotension, increased
appetite and weight gain, headache, sleep disturbance,
Clonidine is a nonselective α-adrenergic agonist that is GI distress, skin irritation with transdermal clonidine
clinically useful in decreasing states of hyperarousal administration, and rebound hypertension with abrupt
seen in children and adolescents with PTSD and withdrawal. Bradycardia can occasionally be marked.
ADHD. Guanfacine is a selective agonist for α2-adren-
ergic receptors with advantages over the nonselective F. DRUG INTERACTIONS
agonist clonidine. Guanfacine is less sedating and less
hypotensive and has a longer half-life, allowing for Increased sedation with CNS depressants; possible in-
twice-daily dosing. Case reports find guanfacine effec- creased anticholinergic toxicity. Several case reports
tive in ADHD and Tourette syndrome with comorbid have mentioned cardiac toxicity with clonidine when
ADHD. Bedtime doses of adrenergic agonists can be combined with methylphenidate, although other med-
helpful for the delayed onset of sleep and nightmares ications and clinical factors were present in each case.
that can occur with PTSD, for the difficulty settling for
sleep seen in ADHD, or for ameliorating the side ef- G. MEDICAL FOLLOW-UP
fects of stimulant medications. They are also effective Pulse and blood pressure should be recorded every
in the treatment of tics in Tourette syndrome 2 weeks for 2 months and then every 3 months. The
discontinuation of clonidine or guanfacine should
B. CONTRAINDICATIONS occur gradually, with step-wise dosage decreases every
Adrenergic agonists are contraindicated for patients 3–5 days to avoid rebound hypertension. Blood pres-
with known renal or cardiovascular disease and for sure should be monitored during withdrawal.
those with a family or personal history of depression.
C. INITIAL MEDICAL SCREENING REFERENCES
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 Child Abuse & Neglect 7
Andrew P. Sirotnak, MD, & Richard D. Krugman, MD

The problem of child abuse and neglect, barely recog- gender and age of child. Each of the following condi-
nized as a significant problem in the early editions of tions may exist as separate or concurrent diagnoses.
this textbook, has grown to a problem of such serious
proportions that in 1990 the US Advisory Board on Physical Abuse
Child Abuse and Neglect called the present state of the
nation’s ability to protect children a “national emer- Physical abuse of children is most often inflicted by a
gency.” Over a decade later, the emergency is still with us. caregiver or family member but occasionally by a
What Dr. Henry Kempe and his colleagues first called stranger. The most common manifestations include
battered child syndrome was thought to affect 749 chil- bruises, burns, fractures, head trauma, and abdominal
dren in the United States in 1960. The best data now injuries. A small but significant number of unexpected
available suggest that 1–1.5% of American children are pediatric deaths, particularly in infants and very young
abused or neglected annually. In 2002 an estimated children (eg, sudden infant death syndrome), are re-
3 million children were reported to child protective ser- lated to physical abuse.
vice agencies as alleged victims of child abuse and ne-
glect, which translates to an approximate national mal- Sexual Abuse
treatment rate of 37 victims per 1000 children. Just
under one million of these cases were substantiated by Sexual abuse is defined as the engaging of dependent,
child protective services in 2001, yielding an abuse sub- developmentally immature children in sexual activities
stantiation rate of 12.3 per 1000 American children. At that they do not fully comprehend and to which they
least 2000 children are victims of fatal child abuse each cannot give consent or activities that violate the laws
year. This dramatic increase in cases has resulted from and taboos of a society. It includes all forms of incest,
increased recognition of the problem by professionals, sexual assault or rape, and pedophilia. This includes
partly in response to statutory reporting mandates; a fondling, oral–genital–anal contact, all forms of inter-
broadening of the definitions of abuse and neglect from course or penetration, exhibitionism, voyeurism, ex-
the original battered child concept; and changes in the ploitation or prostitution, and the involvement of chil-
demography and social structure of families and neigh- dren in the production of pornography.
borhoods over the past several decades. Substance
abuse, poverty and economic strains, parental capacity Emotional Abuse
and skills, and domestic violence are cited as the most
common presenting problems in abusive families. Emotional or psychological abuse has been defined as
Abuse and neglect of children are best considered in the rejection, ignoring, criticizing, isolation, or terroriz-
an ecologic perspective, which recognizes the individ- ing of children, all of which have the effect of eroding
ual, family, social, and psychological influences that their self-esteem. The most common form is verbal
come together to contribute to the problem. For most abuse or denigration. Children who witness domestic
pediatric health care professionals, however, their in- violence should be considered emotionally abused.
volvement will be limited to individual cases. This
chapter focuses on the knowledge necessary for the Physical Neglect
recognition, intervention, and follow-up of the more
common forms of child maltreatment and highlights Physical neglect is the failure to provide the necessary
the role of pediatric professionals in prevention. food, clothing, and shelter and a safe environment in
which children can grow and develop. Although often
associated with poverty or ignorance, physical neglect
involves a more serious problem than just lack of re-
FORMS OF CHILD MALTREATMENT sources. There is often a component of emotional ne-
Child maltreatment may occur either within or outside glect and either a failure or an inability, intentionally or
the family. The proportion of intrafamilial to extrafa- otherwise, to recognize and respond to the needs of the
milial cases varies with the type of abuse as well as the child.
221
Copyright © 2005, 2001, by The McGraw-Hill Companies, Inc. Click here for terms of use.
222 / CHAPTER 7

Emotional Neglect Table 7–2. Presentations of sexual abuse.

The most common feature of emotional neglect is the
absence of normal parent–child attachment and a sub- General or direct statements about sexual abuse
sequent inability to recognize and respond to an in- Sexualized play or behavior in developmentally immature
fant’s or child’s needs. A common manifestation of children
Sexual abuse of other children by the victim
emotional neglect in infancy is nutritional (nonorganic)
Behavioral changes
failure to thrive. Sleep disturbances (eg, nightmares and night terrors)
Appetite disturbances (eg, anorexia, bulimia)
Medical Care Neglect Depression, social withdrawal, anxiety
Aggression, temper tantrums, impulsiveness
Medical care neglect is failure to provide the needed Neurotic or conduct disorders, phobias or avoidant
treatment to infants or children with life-threatening behaviors
illness or other serious or chronic medical conditions. Guilt, low self-esteem, mistrust, feelings of helplessness
Hysterical or conversion reactions
Munchausen Syndrome by Proxy Suicidal, runaway threats or behavior
Excessive masturbation
Munchausen syndrome by proxy is a relatively unusual Medical conditions
disorder in which a caregiver, usually the mother, either Recurrent abdominal pain or frequent somatic complaints
simulates or creates the symptoms or signs of illness in a Genital, anal, or urethral trauma
child. The child can present with a long list of medical Recurrent complaints of genital or anal pain, discharge,
problems or often bizarre recurrent complaints. Fatal bleeding
cases have been reported. Enuresis or encopresis
Sexually transmitted diseases
RECOGNITION OF ABUSE & NEGLECT Pregnancy
Promiscuity or prostitution, sexual dysfunction, fear of
The most common features suggesting a diagnosis of intimacy
child abuse are summarized in Tables 7–1 and 7–2. School problems or truancy
Obvious signs of injury, sexual abuse, or neglect may be Substance abuse
present. Classic radiographic and laboratory findings
are discussed later in this chapter. Psychosocial factors
may indicate risk for or confirm child maltreatment.
Recognition of any form of abuse and neglect of of child abuse incidents occur in extrafamilial settings.
children can occur only if child abuse is entertained in Nevertheless, the assumption that the caregiver is
the differential diagnosis of the child’s presenting med- “nice,” combined with the failure to consider the possi-
ical condition. The approach to the family should be bility of abuse, can be costly and even fatal. Raising the
supportive, nonaccusatory, and empathetic. The indi- possibility that a child has been abused is not the same
vidual who brings the child in for care may not have as accusing the caregiver of being the abuser. The
any involvement in the abuse. Approximately one third health professional who is examining the child can ex-
plain to the family that several possibilities might ex-
plain the child’s injuries or abuse-related symptoms. If
the family or presenting caregiver is not involved in the
Table 7–1. Common historical features in child child’s maltreatment, they may actually welcome the
abuse cases. necessary report and investigation.

Discrepant, evolving, or absent history History

Delay in seeking care
Event or behavior by child that triggers a loss of control of A. PHYSICAL ABUSE
caregiver The medical diagnosis of physical abuse is based on the
History of abuse in the caregiver’s childhood presence of a discrepant history, in which the history
Inappropriate affect of the caregiver offered by the caregiver is not consistent with the clini-
Pattern of increasing severity or number of injuries if no cal findings. The discrepancy may exist because the his-
intervention tory is absent, partial, changing over time, or simply il-
Social or physical isolation of the child or the caregiver logical or improbable. The presence of a discrepant
Stress or crisis in the family or the caregiver history should prompt a request for consultation with a
Unrealistic expectations of caregiver for the child multidisciplinary child protection team or a report to
 CHILD ABUSE & NEGLECT / 223

the child protective services agency. This agency is incorrectly as an expression of anger. This misinterpre-
mandated by state law to investigate reports of sus- tation leads to inadequate nutrition and failure to
pected child abuse and neglect. Investigation by social thrive. The clinician must evaluate the psychosocial his-
services and possibly law enforcement officers, as well as tory and family dynamics when neglect is a considera-
a home visit, may be required to sort out the circum- tion, and a careful social services investigation may be
stances of the child’s injuries. Other common historical required.
features in child abuse cases are listed in Table 7–1.
E. FAILURE TO THRIVE
B. SEXUAL ABUSE The history offered in cases of failure to thrive is often
Sexual abuse may come to the clinician’s attention in at odds with the physical findings. Infants who have ex-
different ways: (1) The child may be brought in for perienced a significant deceleration in growth are prob-
routine care or for an acute problem, and sexual abuse ably not receiving adequate amounts or appropriate
may be suspected by the medical professional as a result types of food despite the dietary history provided. Med-
of the history or the physical examination. (2) The par- ical conditions causing poor growth in infancy and
ent or caregiver, suspecting that the child may have early childhood can be ruled out with a detailed history
been sexually abused, may bring the child to the health and minimal laboratory tests. A psychosocial history
care provider and request an examination to “rule in or may reveal maternal depression, family chaos or dys-
rule out” abuse. (3) The child may be referred by child function, or other previously unknown social risk fac-
protective services or the police for an evidentiary ex- tors (eg, substance abuse, violence, poverty, psychiatric
amination following either disclosure of sexual abuse by illness). Placement of the child with another caregiver
the child or an allegation of abuse by a parent or third or hospitalization of the severely malnourished patient
party. Table 7–2 lists the presentations of child sexual is usually followed by a dramatic weight gain.
abuse. It should be emphasized that with the exception
of acute trauma, certain sexually transmitted infections Physical Findings
(STIs), or forensic laboratory evidence, none of these
presentations is specific. The presentations listed should A. PHYSICAL ABUSE
arouse suspicion of the possibility of sexual abuse and The findings on examination of physically abused chil-
lead the practitioner to ask the appropriate questions— dren may include abrasions, alopecia, bites, bruises,
again, in a compassionate and nonaccusatory manner. burns, dental trauma, fractures, lacerations, ligature
The American Academy of Pediatrics has published marks, or scars. Injuries may be in multiple stages of
guidelines for the evaluation of child sexual abuse as healing. Bruises in physically abused children are some-
well as other guidelines relating to child maltreatment. times patterned (eg, belt marks, looped cord marks,
grab or pinch marks) and are typically found over the
C. EMOTIONAL ABUSE soft tissue areas of the body. Toddlers or older children
Emotional abuse may cause nonspecific symptoms in typically sustain accidental bruises over bony promi-
children. Loss of self-esteem or self-confidence, sleep nences such as shins and elbows. Any bruise in an in-
disturbances, somatic symptoms (eg, headaches, stom- fant not developmentally mobile should be viewed with
achaches), hypervigilance, or avoidant or phobic behav- concern. (Other child abuse emergencies are listed in
iors (eg, school refusal, running away) may be present- Table 7–3). Lacerations of the frenulum or tongue and
ing complaints. These complaints may also be seen in bruising of the lips may be associated with force feed-
children who experience domestic violence. Emotional ing. Pathognomonic burn patterns include stocking or
abuse can occur in the home or day care, school, sports glove distribution; immersion burns of the buttocks,
team, or other settings. sometimes with a “doughnut hole” area of sparing; and
branding burns such as with cigarettes or hot objects
D. NEGLECT (eg, grill, curling iron, or lighter). The absence of splash
Even though in 2002 there were three times as many marks or a pattern consistent with spillage may be help-
reports of neglect of children as of physical abuse, ne- ful in differentiating accidental from nonaccidental
glect is not easily documented on history. Physical ne- scald burns.
glect—which must be differentiated from the depriva- Head and abdominal trauma may present with signs
tions of poverty—will be present even after adequate and symptoms consistent with those injuries. Inflicted
social services have been provided to families in need. head trauma (eg, shaken baby syndrome) and ab-
Emotionally neglectful parents appear to have an in- dominal injuries may have no visible findings on
ability to recognize the physical or emotional states of examination. The finding of retinal hemorrhages in an
their children. For example, an emotionally neglectful infant without an appropriate medical condition (eg,
parent may ignore an infant’s cry if the cry is perceived leukemia, congenital infection, clotting disorder) should
224 / CHAPTER 7

Table 7–3. Potential child abuse the diagnosis of human immunodeficiency virus (HIV)
medical emergencies. infection when other modes of transmission (eg, trans-
fusion, perinatal acquisition) have been ruled out. The
Any infant with bruises (especially head, facial, or abdominal), Centers for Disease Control and Prevention and sexual
burns, or fractures abuse atlases list guidelines for the screening of STIs in
Any infant or child under age 2 years with a history of sus- sexually abused children and adolescents.
pected “shaken baby” head trauma or other inflicted head C. NEGLECT AND NONORGANIC FAILURE TO THRIVE
injury
Any child who has sustained suspicious or known inflicted Infants and children with nonorganic failure to thrive
abdominal trauma have a relative absence of subcutaneous fat in the
Any child with burns in stocking or glove distribution or in cheeks, buttocks, and extremities. Other conditions as-
other unusual patterns, burns to the genitalia, and any sociated with poor nutrient and vitamin intake may be
unexplained burn injury present. If the condition has persisted for some time,
Any child with disclosure or sign of sexual assault within these patients may also appear and act depressed. Older
48–72 hours after alleged event if the possibility of acute children who have been chronically emotionally ne-
injury is present or if forensic evidence exists glected may also have short stature (ie, deprivation
dwarfism). The head circumference is usually normal in
cases of nonorganic failure to thrive. Microcephaly may
signify a prenatal condition, congenital disease, or
arouse concern about possible inflicted head trauma. chronic nutritional deprivation and increases the likeli-
Retinal hemorrhages are not commonly seen after car- hood of more serious and possibly permanent develop-
diopulmonary resuscitation in either infants or chil- mental delay.
dren.
D. MUNCHAUSEN SYNDROME BY PROXY
B. SEXUAL ABUSE Children with Munchausen syndrome by proxy may
The genital and anal findings of sexually abused chil- present with the signs and symptoms of whatever illness
dren, as well as the normal developmental changes and is factitiously produced or simulated. They may be ac-
variations in prepubertal female hymens, have been de- tually ill or reported to be ill and have a normal clinical
scribed in journal articles and visual diagnosis guides. appearance. Among the most common reported presen-
The majority of victims of sexual abuse exhibit no tations are recurrent apnea, dehydration from induced
physical findings. The reasons for this include delay in vomiting or diarrhea, sepsis when contaminants are in-
disclosure by the child, abuse that may cause no physi- jected into a child, change in mental status, fever, gas-
cal trauma (eg, fondling, oral–genital contact, exploita- trointestinal bleeding, and seizures.
tion by pornographic photography), or rapid healing of
minor injuries such as labial, hymenal, or anal abra- Radiologic & Laboratory Findings
sions, contusions, or lacerations. Nonspecific abnor-
malities of the genital and rectal regions such as ery- A. PHYSICAL ABUSE
thema, rashes, and irritation may not suggest sexual Certain radiologic findings are strong indicators of
abuse in the absence of a corroborating history, disclo- physical abuse. Examples are metaphyseal “corner” or
sure, or behavioral changes. Finally, some medical con- “bucket handle” fractures of the long bones in infants,
ditions may be misdiagnosed as sexual abuse (eg, lichen spiral fracture of the extremities in nonambulatory in-
sclerosis, dermatitis, labial adhesions, congenital ure- fants, rib fractures, spinous process fractures, and frac-
thral or vulvar disorders, Crohn disease, and accidental tures in multiple stages of healing. Skeletal surveys in
straddle injuries to the labia) and can be ruled out by children age 3 years or younger should be performed
careful history and examination. when a suspicious fracture is diagnosed. Computed to-
Certain STIs should strongly suggest sexual abuse. mography or magnetic resonance imaging findings of
Neisseria gonorrhoeae infection or syphilis beyond the subdural hemorrhage in infants—in the absence of a
perinatal period are diagnostic of sexual abuse. Chlamy- clear accidental history—are highly correlated with
dia trachomatis, herpes simplex virus, trichomoniasis, abusive head trauma, especially after the advent of in-
and human papillomavirus (HPV) are all sexually trans- fant seat restraint laws that have reduced the incidence
mitted, although the course of these perinatally ac- of head trauma in infants. Abdominal CT is the pre-
quired infections may be protracted. In the case of ferred test in suspected abdominal trauma. Any infant
HPV, an initial appearance of venereal warts beyond or very young child with suspected abuse-related head
the toddler age should raise concerns about sexual or abdominal trauma should be evaluated immediately
abuse. Finally, sexual abuse must be considered with by an emergency physician or trauma surgeon.
 CHILD ABUSE & NEGLECT / 225

Coagulation studies and a complete blood count skeletal survey may be helpful if concurrent physical
with platelets are useful in children who present with abuse is suspected. The best screening method, how-
multiple or severe bruising in different stages of heal- ever, is placement in a setting in which the child can be
ing. Coagulopathy conditions may confuse the diagnos- fed and monitored. Hospital or foster care placement
tic picture but can be excluded with a careful history, may be required. Weight gain may not occur for several
examination, laboratory screens, and hematologic con- days to a week in severe cases.
sultation if necessary. Any child with recurrent polymicrobial sepsis (espe-
The differential diagnosis of all forms of physical cially in children with indwelling catheters), recurrent
abuse can be considered in the context of a detailed apnea, chronic dehydration of unknown cause, or other
trauma history, family medical history, radiographic highly unusual, unexplained laboratory findings should
findings, and laboratory testing. The diagnosis of osteo- raise the suspicion of Munchausen syndrome by proxy.
genesis imperfecta or other collagen disorders, for ex-
ample, may be considered in the child with skin and MANAGEMENT & REPORTING
joint findings or multiple fractures with or without the
classic radiographic presentation and is best made in
OF CHILD ABUSE & NEGLECT
consultation with a geneticist, an orthopedic surgeon, Physical abuse injuries, STIs, and medical sequelae of
and a radiologist. Trauma—accidental or inflicted— neglect should be treated immediately. Children with
leads the differential diagnosis list for subdural failure to thrive related to emotional and physical ne-
hematomas. Coagulopathy, disorders of copper metab- glect need to be placed in a setting in which they can be
olism, amino acid or organic acid metabolism (eg, fed and cared for. Likewise, the child in danger of re-
Menkes syndrome, glutaric acidemia type 1), chronic current abuse or neglect needs to placed in a safe envi-
or previous central nervous system infection, birth ronment.
trauma, or congenital central nervous system malforma- In the United States, clinicians and many other pro-
tion (eg, arteriovenous malformations, cerebrospinal fessionals who come in contact with or care for children
fluid collections) may need to be ruled out in some are mandated reporters. If abuse or neglect is suspected,
cases. It should be recognized, however, that children a report must be made to the local or state agency des-
with these rare disorders can also be abuse victims. ignated to investigate such matters. In most cases, this
will be the child protective services agency. Law en-
B. SEXUAL ABUSE forcement agencies may also receive such reports. The
The forensic evaluation of sexually abused children purpose of the report is to permit professionals to
should be performed in a setting that prevents further gather the information needed to determine whether
emotional distress. If the history indicates that the child the child’s environment (eg, home, school, day care set-
may have had contact with the ejaculate of a perpetra- ting, foster home) is safe. Many hospitals and commu-
tor within 72 hours, an examination looking for semen nities make child protection teams or consultants avail-
or its markers (eg, acid phosphatase) should be per- able when there are questions about the diagnosis and
formed according to established protocols. More im- management in a child abuse case. A listing of pediatric
portant, if there is a history of possible sexual abuse consultants in child abuse is available from the Ameri-
within the past 48–72 hours, and the child reports a can Academy of Pediatrics.
physical complaint or a sign is observed (eg, genital or Except in extreme cases, the reporting of emotional
anal bleeding or discharge), the child should be exam- abuse is not likely to generate a response from child
ined for signs of trauma. The most experienced exam- protection agencies. This should not deter reporting,
iner (pediatrician, nurse examiner, child advocacy cen- especially if the concern is in the context of domestic
ter) is preferable. The laboratory and serologic violence or other forms of abuse or neglect. Practition-
evaluation of STIs should be guided by the type of con- ers can encourage parents to get involved with parent
tact reported and the epidemiology of these infections effectiveness training programs (eg, Parents as First
in the community. Teachers or Parents Anonymous) or to seek mental
health consultation. Support for the child may also in-
C. NEGLECT AND GROWTH FAILURE clude mental health counseling or age-appropriate peer
Children with failure to thrive or malnutrition may not activities in school or the community.
require an extensive work-up. Complete blood count,
urinalysis, electrolyte panel, and liver function tests are PREVENTION OF CHILD ABUSE
sufficient screening. Newborn screening should be doc-
umented as normal. Other tests should be guided by
& NEGLECT
any clinical history that points to a previously undiag- Physical abuse is preventable in many cases. Extensive
nosed condition (eg, thyroid, metabolic studies). A experience and evaluation of high-risk families has
226 / CHAPTER 7

shown that the provision of home visitor services to American Academy of Pediatrics: Distinguishing sudden infant
families at risk can prevent abuse and neglect of chil- death syndrome from child abuse fatalities. Pediatrics
2001;107(2):437 [PMID:11158487].
dren. These services can be provided by public health
nurses or trained paraprofessionals, although more data American Academy of Pediatrics: Visual Diagnosis of Child Abuse.
[CD ROM], 2nd ed, 2002.
are available describing public health nurse interven-
American Academy of Pediatrics: Visual Diagnosis of Child Sexual
tion. This makes it as easy for the family to pick up the Abuse. [Slide Set Atlas] American Academy of Pediatrics,
telephone and ask for help before they abuse a child as 2002.
it is for a neighbor or physician to report an episode of American Academy of Pediatrics: Diagnostic imaging of children
abuse after it has occurred. Parent education and antici- abuse. Pediatrics 2000;105(6):1345 [PMID:10835079].
patory guidance may also be helpful, particularly with American Academy of Pediatrics: Rotational cranial injury—technical
respect to handling situations that stress parents (eg, report. Pediatrics 2001;108(1):206 [PMID:11433079].
colic, crying, behaviors, toilet training), age-appropriate American Academy of Pediatrics: Guidelines for the evaluation of
discipline, and general developmental issues. Preven- sexual abuse of children: A subject review. Pediatrics
tion of abusive injuries perpetrated by nonparent care- 1999;103:186 [PMID:9917463].
givers (eg, babysitters, nannies, unrelated adults in the Giardino AP et al (eds): A Practical Guide to the Evaluation of Child
home) may be addressed by education and counseling Abuse and Neglect. Sage, 2001.
of mothers about safe child care arrangements. Heger A et al (eds): Evaluation of the Sexually Abused Child: A Med-
The prevention of sexual abuse is more difficult. ical Textbook and Photographic Atlas, 2nd ed. Oxford Univer-
sity Press, 2000.
Most efforts in this area involve teaching children to
Helfer ME et al (eds): The Battered Child, 5th ed. University of
protect themselves and their “private parts” from harm Chicago Press, 1997.
or interference. These programs are useful but are in Kleinman PK (ed): Diagnostic Imaging of Child Abuse, 2nd ed.
general not as efficacious as they are necessary. The age Williams & Wilkins, 1998.
of toilet training is a good anticipatory guidance time to Olds D et al: Long-term effects of home visitation on maternal life
encourage parents to consider this discussion. The most course and child abuse and neglect fifteen year follow-up of a
rational approach is to place the burden of responsibil- randomized trial. JAMA 1997;278:637.
ity of prevention on the adults who supervise the child Olds DL: Prenatal and infancy home visitation by nurses: From
and the medical providers rather than on the children randomized trials to community replication. Prev Sci
themselves. 2002;3(3):153 [PMID: 12387552].
Efforts to prevent emotional abuse of children have Reece RM, Ludwig S (eds): Child Abuse: Medical Diagnosis and
been undertaken through extensive media campaigns. Management, 2nd ed. Lippincott, Williams & Wilkins.
Philadelphia, 2001.
No data are available to assess the effectiveness of this
approach. Reece RM (ed): Treatment of Child Abuse: Common Ground for
Mental Health, Medical, and Legal Practitioners. Johns Hop-
kins University Press, 2000.
REFERENCES US Department of Health and Human Services: Administration
for Children, Youth, and Families. Child Maltreatment
2002 Guidelines for the treatment of sexually transmitted diseases. 2001. Available at: http//:www.acf.dhhs.gov/programs/cb
MMWR 2002 (RR-6);51. Available at: www.cdc.gov/std/
treatment/rr5106.pdf
 Ambulatory & Community
Pediatrics
8
Robert M. Brayden, MD, Matthew F. Daley, MD, & Jeffrey M. Brown, MD, MPH

Pediatric outpatient services provide a child or adoles- stead of reporting that a child has had a warm, red,
cent with comprehensive longitudinal care and empha- tender, swollen knee for 2 days, the parent may say
size preventive health care. This chapter discusses com- that the child no longer wants to play on the soccer
mon elements of ambulatory visits and offers guidance team.
in the conduct of the health supervision visit, visits for Parents may or may not be able to distinguish
acute and chronic disease management, and consulta- whether symptoms are caused by organic illness or a
tions. Special attention is paid to the pediatric history psychological concern. It is often helpful to ask specifi-
and physical examination, normal developmental cally what problems the parents wish to address in
stages, office telephone management, and community order to determine what really prompted the office
pediatrics. visit. Some visits are occasioned by problems at school,
The development of a physician–patient–parent re- such as low grades or troublesome peer relationships.
lationship is of crucial importance if the patient or par- Understanding the family and its hopes for and con-
ent is to effectively confide his or her concerns. The re- cerns about the child can help in the process of distin-
lationship develops over time and with increasing guishing organic illness from emotional or behavioral
numbers of visits. It is facilitated by the continuity of conditions, thus minimizing unnecessary testing and
clinicians and other pediatric staff members. The trust intervention.
that supports this relationship comes as a result of sev- Although the parents’ concerns need to be under-
eral experiences in the context of the office visit. Per- stood, it is essential also to obtain as much of the his-
haps the greatest factor to facilitate the relationship is tory as possible directly from the patient. Direct histo-
for patients or parents to experience advice as valid and ries not only provide firsthand information but also
effective. Skills such as choosing vocabulary that com- give the child a degree of control over a potentially
municates understanding and competence, commit- threatening situation and may reveal important infor-
ment of time and attention to the concern, and respect mation about the family.
for areas that the patient or parent does not wish to ad- Obtaining a comprehensive pediatric history is
dress (assuming the lack of abuse or neglect concerns) time-consuming. Many offices provide questionnaires
are important. Parents and patients often seek evidence for parents to complete before the clinician sees the
that their concerns will be managed confidentially and child. Data from questionnaires can make an outpa-
that the clinician both understands and sympathizes tient visit more productive, allowing the physician to
with those concerns. The effective physician–patient– address problems in detail while more quickly review-
parent relationship is one of the true joys of ambulatory ing areas that are not of concern. Questionnaires may
pediatrics. be more productive than face-to-face interviews in re-
vealing sensitive parts of the history. However, failure
to review and assimilate this information prior to the
interview may cause a parent or patient to feel that the
PEDIATRIC HISTORY time and effort have been wasted.
Elements of the history that will be useful over time
should be readily accessible in the medical record.
Pediatrics is unique in that patients seldom provide Such information can be accumulated on a summary
their own history. Instead, the parent usually describes sheet, as illustrated in Figure 8–1. Demographic data; a
the child’s complaints and behavior to the physician. problem list; information about chronic medications,
As with any history, this information may be detailed allergies, and previous hospitalizations; and the names
and accurate or vague and unreliable. A vague exposi- of other physicians providing care for the patient are
tion of complaints offered by a parent may be a state- commonly included. Documentation of immuniza-
ment of the parent’s own concerns. For example, in- tions, including all data required by the National
227
Copyright © 2005, 2001, by The McGraw-Hill Companies, Inc. Click here for terms of use.
228 / CHAPTER 8

Name Nickname D.O.B.

Mother Father Sibs
S.S. # Insurance

Problems Chronic Medications

Date of Description Date Start Stop

onset resolved date date

Allergies (Center)

Date

Date Hospitalizations/Injuries/Procedures Date Consultants

Figure 8–1. Use of a summary sheet such as this at the front of the record facilitates reorienting the caregiver and
his or her partners to the patient. Some practices keep track of health supervision visits on this sheet to tell the
physician whether the child is likely to have received the appropriate preventive services. A second page document-
ing immunizations should record data required by the National Childhood Vaccine Injury Act. When an allergy with
potential for anaphylaxis is identified, the patient should wear a medical alert bracelet and obtain an epinephrine
kit, if appropriate.

Childhood Vaccine Injury Act, should be kept on a sec-

ond page. PEDIATRIC PHYSICAL
The components of a comprehensive pediatric his-
tory are listed in Table 8–1. The information should, EXAMINATION
ideally, be obtained at the first office visit. The first
seven items are included on the summary pages. Items
8 and 9 are dealt with during each visit. The entire list In approaching the child, time must be taken to allow
should be reviewed and augmented with relevant up- the patient to become familiar with the examiner. In-
dates at each health supervision visit. teractions and instructions help the child understand
 AMBULATORY & COMMUNITY PEDIATRICS / 229

Table 8–1. Components of the pediatric historical database.a

1. Demographic data Patient’s name and nickname, date of birth, social security number, sex, race, parents’ names (first
and last), siblings’ names, and payment mechanism.
2. Problem list Major or significant problems, including dates of onset and resolution.
3. Allergies “Triggering allergen,” nature of the reaction, treatment needed, and date allergy diagnosed.
4. Chronic medications Name, concentration, dose, and frequency of chronically used medications.
5. Birth history Maternal health during pregnancy, medications, street drugs used, complications of pregnancy;
duration and ease of labor; form of delivery; analgesics and anesthetics used; need for monitor-
ing; and labor complications. Infant’s birth weight, gestational age, Apgar scores, and problems
in the neonatal period.
6. Screening procedures Results of newborn screening, vision and hearing screening, any health screen, or screening labo-
ratory tests. (Developmental screening results are maintained in the development section; see
item 14, below.)
7. Immunizations Date of each immunization administered, vaccine manufacturer and lot number, and name and
title of the person administering the vaccine; previous reaction and contraindication to immuniza-
tion (eg, immunodeficiency or an evolving neurologic problem).
8. Reasons for visit The patient’s or parents’ concerns, stated in their own words, serve as the focus for the visit.
9. Present illness A concise chronologic summary of the problems necessitating a visit, including the duration, pro-
gression, exacerbating factors, ameliorating interventions, and associations.
10. Medical history A statement regarding the child’s functionality and general well-being, including a summary
record of significant illnesses, injuries, hospitalizations, and procedures.
11. Diet Eating patterns, likes and dislikes, use of vitamins, and relative amounts of carbohydrates, fat, and
protein in the diet.
12. Family history Information about the illnesses of relatives, preferably in the form of a family tree.
13. Social history Family constellation, relationships, parents’ educational background, religious preference, and
the role of the child in the family; socioeconomic profile of the family to identify resources avail-
able to the child, access to services that may be needed, and anticipated stressors.
14. Development (1) Attainment of developmental milestones (including developmental testing results); (2) social
habits and milestones (toilet habits, play, major activities, sleep patterns, discipline, peer relation-
ships); (3) school progress and documentation of specific achievements and grades.
15. Sexual history Family’s sexual attitudes, sex education, sexual development and activity, sexually transmitted
diseases, and birth control measures.
16. Review of systems (ROS) This area tends to be overlooked because of the work required to obtain a complete ROS and inte-
grate data into the patient’s problems list and care plan. A focused ROS is essential if any problem
is to be addressed adequately.
a
The components of this table should be included in a child’s medical record and structured to allow easy review and modification. The
practice name and address should appear on all pages.

what is occurring and what is expected. A gentle, tion. Whether or not the physician can establish rap-
friendly manner and a quiet voice help establish a set- port with the child, the process should proceed effi-
ting that yields a nonthreatening physical examination. ciently and systematically.
The order in which the child’s organ systems are exam- Because young children may fear the examination
ined should take into consideration the need for a quiet and become fussy, simple inspection is very important.
child, the extent of trust established, and the possibility For example, during an acute-care visit for fever, the ex-
of an emotional response. Painful or unpleasant proce- aminer should observe the child’s work of breathing
dures should be deferred until the end of the examina- prior to beginning the examination. During a health
230 / CHAPTER 8

supervision visit, observation will provide the examiner servation at each visit. Developmental surveillance is fa-
with an opportunity to assess parent–child interactions. cilitated further through the systematic use of parent-
Clothing should be removed slowly and gently to directed questionnaires or screening tests. Growth is
avoid threatening the child. A parent or the child him- carefully recorded, and the growth chart is brought up
self or herself is usually the best person to do this. Mod- to date (see Chapter 2). Vision and hearing should be
esty should always be respected, and gown or drapes assessed subjectively at each visit, with objective assess-
should be provided. Examinations of adolescents ments at intervals beginning after the child is old
should be chaperoned whenever a pelvic examination enough to cooperate with the screening test. A variety
or a stressful or painful procedure is performed. of laboratory screening tests may also be part of the
Examination tables are convenient, but a parent’s visit.
lap is a safe haven for a young child. For most purposes, A major portion of the health supervision visit is an-
an adequate examination can be conducted on a “table” ticipatory guidance. This portion of the visit enables
formed by the parent’s and examiner’s legs as they sit the health care provider to address behavioral, develop-
facing each other. mental, injury prevention, nutritional issues, school
The nature of the physical examination changes as problems, and other age-appropriate issues that will
the child develops. Although a thorough physical exam- arise before the next well child care visit.
ination is important at every age, at some ages the ex-
amination tends to focus on specific issues and con- American Academy of Pediatrics Committee on Practice and Am-
cerns. At any age, an astute clinician can detect signs of bulatory Medicine: Recommendations for Preventive Pedi-
important clinical conditions in an asymptomatic child. atric Health Care. Pediatrics 2000;105:645.
In infancy, for example, physical examination can re-
veal the presence of craniosynostosis, congenital heart DEVELOPMENTAL & BEHAVIORAL
disease, or congenital hip dysplasia. Similarly, examina-
tion of a toddler may reveal pallor (from iron deficiency ASSESSMENT
anemia) or strabismus. The routine examination of an At each visit, the parent should be interviewed about
adolescent may reveal scoliosis or acanthosis nigricans aspects of the child’s development and behavior. Ques-
(a finding associated with insulin resistance). tionnaires or formal screening tests help to document
development objectively. Useful tests include the Den-
ver II, the Parents’ Evaluations of Developmental Sta-
tus (PEDS), the Denver Articulation Screening Exami-
HEALTH SUPERVISION VISITS nation, and the Early Language Milestone Scale.
School-age children’s cognitive functions can be as-
sessed through academic achievement and any educa-
One of several timetables for health supervision visits is tional testing that may have been performed. Emo-
illustrated in Figure 8–2. (Note: A PDF printable for- tional well-being can be screened by interview and
mat of this figure is available at aap.org.) The federal observation. Practices may decide to use screening tools
Maternal and Child Health Bureau has developed com- for adolescent depression.
prehensive health supervision guidelines through their Observation of parent–child interactions (eg, feed-
Bright Futures program (brightfutures.org). In areas ing, compliance tasks) may provide the clinician with
where evidence-based information is lacking, expert information to help shape behavioral counseling. Ob-
opinion has been used as the basis for these plans. For serving the child’s temperament and gathering history
example, immunizations are proven to be effective and about the family’s disciplinary techniques are other im-
necessary (Centers for Disease Control and Prevention, portant considerations before providing guidance.
www.cdc.gov/nip), whereas there is disagreement about The pediatrician must be familiar with normal de-
whether screening for certain metabolic diseases is uni- velopment in order to provide effective patient assess-
versally warranted. Practitioners should remember that ment and counsel. The following sections summarize
guidelines are not meant to be rigid; services should be some important motor, language, and emotional mile-
individualized according to the child’s needs. stones of child development.
During health supervision visits, the practitioner
should review child development and acute and chronic Newborns & Infants
problems, conduct a complete physical examination,
order appropriate screening tests, and anticipate future Infancy is commonly a period of concern about growth
developments. New historical information should be and behavioral and developmental issues, particularly
elicited through an interval history. Development for the first-time parent. Normal motor and language
should be assessed by parental report and clinician ob- development, feeding, sleep, elimination, and self-stim-
 Recommendations for Preventive Pediatric Health Care (RE9939)
Committee on Practice and Ambulatory Medicine

Each child and family is unique;therefore, these Recommendations for Preventive Pediatric Health Care These guidelines represent a consensus by the Committee on Practice and Ambulatory Medicine in
are designed for the care of children who are receiving competent parenting, have no manifestations of any consultation with national committees and sections of the American Academy of Pediatrics.The Committee
important health problems, and are growing and developing in satisfactory fashion. Additional visits may emphasizes the great importance of continuity of care in comprehensive health supervision and the need
become necessary if circumstances suggest variations from normal. to avoid fragmentation of care.

INFANCY4 EARLY CHILDHOOD4 MIDDLE CHILDHOOD4 ADOLESCENCE4

AGE5 PRENATAL1 NEWBORN2 2-4d3 By 1mo 2mo 4mo 6mo 9mo 12mo 15mo 18mo 24mo 3y 4y 5y 6y 8y 10y 11y 12y 13y 14y 15y 16y 17y 18y 19y 20y 21y

HISTORY
Initial/Interval • • • • • • • • • • • • • • • • • • • • • • • • • • • • •
MEASUREMENTS
Height and Weight • • • • • • • • • • • • • • • • • • • • • • • • • • • •
Head Circumference • • • • • • • • • • •
Blood Pressure • • • • • • • • • • • • • • • • •
SENSORY SCREENING
Vision S S S S S S S S S S S O6 O O O O O S O S S O S S O S S S
Hearing O7 S S S S S S S S S S S O O O O O S O S S O S S O S S S
DEVELOPMENTAL/
BEHAVIORAL ASSESSMENT8 • • • • • • • • • • • • • • • • • • • • • • • • • • • •
PHYSICAL EXAMINATION9 • • • • • • • • • • • • • • • • • • • • • • • • • • • •
PROCEDURES-GENERAL10
Hereditary/Metabolic Screening11 •
Immunization12
Hematocrit or Hemoglobin13
• • • • • • • • • • • • • • • • • • • •14
• • • • • • • •
• • • 15
Urinalysis • •
PROCEDURES-PATIENTS AT RISK
Lead Screening16 *
Tuberculin Test17
*
* * * * * * * * * * * * * * * * * * * * *
Cholesterol Screening18 * * * * * * * * * * * * * * * * * *
STD Screening19
231

Pelvic Exam20
* * * * * * * * * 20 * *
* * * * * * * * * * *
ANTICIPATORY GUIDANCE21
Injury Prevention22
• • • • • • • • • • • • • • • • • • • • • • • • • • • • •
Violence Prevention23
• • • • • • • • • • • • • • • • • • • • • • • • • • • • •
Sleep Positioning Counseling24
• • • • • • • • • • • • • • • • • • • • • • • • • • • • •
Nutrition Counseling25
• • • • • • •
• • • • • • • • • • • • • • • • • • • • • • • • • • • • •
DENTAL REFERRAL26 •
1. A prenatal visit is recommended for parents who are at high risk, for first-time parents, and opmental testing. Parenting skills should be fostered at every visit. should be done upon recognition of high-risk factors.
for those who request a conference. The prenatal visit should include anticipatory guid- 9. At each visit, a complete physical examination is essential, with infant totally unclothed, 18. Cholesterol screening for high-risk patients per AAP statement “Cholesterol in Child-
ance, pertinent medical history, and a discussion of benefits of breastfeeding and plan- older child undressed and suitably draped. hood”(1998). If family history cannot be ascertained and other risk factors are present,
ned method of feeding per AAP statement “The Prenatal Visit”(1996). 10. These may be modified, depending upon entry point into schedule and individual need. screening should be at the discretion of the physician.
2. Every infant should have a newborn evaluation after birth. Breastfeeding should be en- 11. Metabolic screening (eg, thyroid, hemoglobinopathies, PKU, galactosemia) should be done 19. All sexually active patients should be screened for sexually transmitted diseases (STDs).
couraged and instruction and support offered. Every breastfeeding infant should have an according to state law. 20. All sexually active females should have a pelvic examination. A pelvic examination and
evaluation 48-72 hours after discharge from the hospital to include weight, formal breast- 12. Schedule(s) per the Committee on Infectious Diseases, published annually in the January routine pap smear should be offered as part of preventive health maintenance between
feeding evaluation, encouragement, and instruction as recommended in the AAP state- edition of Pediatrics. Every visit should be an opportunity to update and complete a the ages of 18 and 21 years.
ment “Breastfeeding and the Use of Human Milk” (1997). child’s immunizations. 21. Age-appropriate discussion and counseling should be an integral part of each visit for
3. For newborns discharged in less than 48 hours after delivery per AAP statement “Hospital 13. See AAP Pediatric Nutrition Handbook (1998) for a discussion of universal and selective care per the AAP Guidelines for Health Supervision III (1998).
Stay for Healthy Term Newborns” (1995). screening options. Consider earlier screening for high-risk infants (eg, premature infants 22. From birth to age 12, refer to the AAP injury prevention program (TIPP®) as described in
4. Developmental, psychosocial, and chronic disease issues for children and adolescents and low birth weight infants). See also “Recommendations to Prevent and Control Iron A Guide to Safety Counseling in Office Practice (1994).
may require frequent counseling and treatment visits separate from preventive care vis- Deficiency in the United States”. MMWR. 1998;47 (RR-3):1-29. 23. Violence prevention and management for all patients per AAP Statement “The Role of the
its. 14. All menstruating adolescents should be screened annually. Pediatrician in Youth Violence Prevention in Clinical Practice and at the Community Lev-
5. If a child comes under care for the first time at any point on the schedule, or if any items 15. Conduct dipstick urinalysis for leukocytes annually for sexually active male and female el” (1999).
are not accomplished at the suggested age, the schedule should be brought up to date adolescents. 24. Parents and caregivers should be advised to place healthy infants on their backs when
at the earliest possible time. 16. For children at risk of lead exposure consult the AAP statement “Screening for Elevated putting them to sleep. Side positioning is a reasonable alternative but carries a slightly
6. If the patient is uncooperative, rescreen within 6 months. Blood Levels”(1998).Additionally, screening should be done in accordance with state law higher risk of SIDS. Consult the AAP statement “Changing Concepts of Sudden Infant
7. All newborns should be screened per the AAP Task Force on Newborn and Infant Hear- where applicable. Death Syndrome: Implications for Infant Sleeping Environment and Sleep Posi-
ing statement, “Newborn and Infant Hearing Loss: Detection and Intervention” (1999). 17. TB testing per recommendations of the Committee on Infectious Diseases, published in tion”(2000).
8. By history and appropriate physical examination: if suspicious, by specific objective devel- the current edition of Red Book: Report of the Committee on Infectious Diseases. Testing 25. Age-appropriate nutrition counseling should be an integral part of each visit per the AAP

NB:Special chemical,immunologic, and endocrine testing is usually carried out upon specific indications. Testing other than newborn (eg,inborn errors of metabolism, sickle
Key:
•S == to be performed
subjective, by history * = to be performed for patients at risk
O = objective, by a standard testing method
disease, etc) is discretionary with the physician.
= the range during which a service may be provided, with the dot The recommendations in this statement do not indicate an exclusive course of treatment or standard of medical care. Variations, taking into account individual
indicating the preferred age. circumstances, may be appropriate. Copyright ©2000 by the American Academy of Pediatrics. No part of this statement may be reproduced in any form or by any means
without prior written permission from the American Academy of Pediatrics except for one copy for personal use. , etc) is discretionary with the physician.

Figure 8–2. Recommendations for preventive health care.

232 / CHAPTER 8

ulating behaviors (thumb sucking, rocking, head bang- cation. Fine motor skills are needed to dress and un-
ing) are frequently of concern. More complete informa- dress and to wash the hands.
tion about developmental milestones and behavioral
concerns of infancy is found in Chapter 2. Early School Years: Ages 5–7 Years
Attachment is the process by which an infant devel-
ops a relationship with a caregiver. Attachment has Separation–individuation is a theme of the early school
both biologic and experiential roots and serves as the years. The child is ready to relate to peers in a more in-
basis for additional interpersonal interactions. It devel- teractive manner than he or she did during preschool
ops over months to years and shifts in focus as the child years. Sensorimotor abilities are maturing and facilitate
develops. Initially the child seeks proximity to the at- pencil-and-paper tasks and participation in sports activ-
tachment figure but then gradually moves away in dis- ities.
tance to meet exploratory needs. The first-grader is generally able to recognize num-
bers, letters, and words; read and write; and understand
the concept of conservation of length and mass. Magi-
The Second Year cal thinking tends to decrease during this time.
Using the first year as a template for secure relation-
ships, normal toddlers have an expanding set of rela- Middle Childhood Years: Ages 8–11 Years
tionships with other individuals. The toddler learns a Academic skills become more sophisticated. Not only
broad set of general and specific behavioral expecta- can a child add and subtract multiple-digit numbers,
tions. The child may be dependent on the caregiving but he or she has a growing ability to perform multipli-
figure(s) and at other times may stubbornly wish to be cation and division. The child should also be able to
independent. However, children begin to understand provide effective verbal descriptions. For example, in
parental expectations and what is not permitted. response to the question “What is an orange?” the child
Children begin to understand feelings of others and may reply, “A sweet-tasting fruit.” Children develop an
develop empathy. They take pleasure in their achieve- awareness of month, day, and year. Peers, organized
ments and express distress when they have misbehaved. clubs, and sports are important activities for preadoles-
Spoken language normally expands rapidly, as do gross cent children.
motor skills.
Adolescence
Preschool Years: Ages 2–4 Years The behavioral and developmental stages of adoles-
cence are outlined in Chapter 3. Familiarity with the
Gross motor development during the preschool years child and family over several years makes the pediatri-
results in children running, jumping, and climbing. cian an excellent professional to screen for the many
Children learn to balance on one foot and hop. Vocab- concerns in this age group.
ulary continues to expand rapidly with the mastery of
hundreds of words. Language development proceeds American Academy of Pediatrics Committee on Children with Dis-
with multiword sentences, the use of pronouns, and the abilities: Developmental Surveillance and Screening of In-
gradual improvement in articulation skills. Children fants and Young Children. Pediatrics 2001;108:192.
normally master the concept of numbers 1, 2, and 3 by http://paeditrics.aappublications.org
31⁄2 years. Four-year-old children should know basic col- Levine MD et al (eds): Developmental-Behavioral Pediatrics, 3rd ed.
ors and clearly articulate most words. WB Saunders, 1999.
The social and emotional development of preschool
children is characterized by the transition from parallel
to group play and the development of magical think-
GROWTH PARAMETERS
ing. Parallel play is the observation of the play of others Pediatric growth charts are based on a broad sampling
and initiation of similar activities individually. By age of the US population, with representation of young in-
4 years, most children will begin to prefer the social as- fants, breastfed infants, and certain ethnic minorities.
pects of group play. The 2- to 18-year growth charts include a chart of body
Toileting skills usually are mastered during these mass index (BMI) for age. The BMI is calculated as the
years. Toilet training requires a variety of developmen- weight (in kilograms) divided by the squared height (in
tal skills. Expressive and receptive language skills are meters). The BMI is useful for determining obesity
needed to express and respond to questions about the (BMI ≥ 95th percentile for age) and underweight status
need to use the toilet. Gross motor skills are needed to (BMI ≤ 5th percentile for age). The BMI is highly cor-
get to the bathroom and to control urination and defe- related with secondary complications of obesity.
 AMBULATORY & COMMUNITY PEDIATRICS / 233

Height, weight, and head circumference are care- Norwood VF: Hypertension. Pediatr Rev 2002;23:197 [PMID:
fully measured and plotted at each visit during the first 12042594].
3 years (see growth charts in Chapter 2). For children Park MK, Menard SW, Yuan C: Comparison of auscultatory and
older than 3 years, height and weight should be mea- oscillometric blood pressures. Arch Pediatr Adolesc Med
2001;155:50 [PMID: 11177062].
sured at each well-child examination. To ensure accu-
rate weight measurements for longitudinal compar-
isons, infants should be undressed completely, and VISION & HEARING
young children should be wearing underpants only. Re- Examination of the eyes and an assessment of vision
cumbent length is plotted on the chart for birth to should be performed at every health supervision visit.
3 years (see Figures 2–1 and 2–2). When the child is Parents should be queried about any concerns regarding
old enough to be measured upright, height should be vision, eye alignment, or any other eye problems. For
plotted on the charts for ages 2–18 years (see Figures example, parental observation of photophobia or exces-
2–3 and 2–4). If circumferential head growth has been sive tearing may be suggestive of glaucoma.
steady for the first 2 years, routine measurements may For children from birth to 3 years of age, the eyes
be suspended. However, if a central nervous system and eyelids should be inspected, the movement and
problem exists or develops, or if the child has growth alignment of the eyes assessed, and the pupils and red
deficiency, this measurement continues to be useful. reflexes examined. The red reflex, performed on each
Tracking the growth velocity for each of these parame- pupil individually and then on both eyes simultane-
ters allows early recognition of deviations from normal. ously, is used to detect eye opacities (eg, cataracts or
corneal clouding) and retinal abnormalities (eg, retinal
detachment or retinoblastoma). In children younger
Kuczmarski RJ et al: CDC Growth Charts: United States. Advance than 3 years of age or in nonverbal children of any age,
Data from Vital and Health Statistics, no. 314. National Cen- vision can be assessed by testing a child’s ability to fix-
ter for Health Statistics, 2000.
ate on and follow an object.
www.cdc.gov/growthcharts/default.htm
For children 3 years and older, in addition to the eye
evaluations, formal testing of visual acuity should be
done. This can be performed in the office with a variety
BLOOD PRESSURE of tests, including the tumbling E chart or picture tests
such as Allen cards. Each eye is tested separately, with
Blood pressure screening at well-child visits should start the nontested eye completely covered. Credit is given
at age 3 years. If the child has a renal or cardiovascular for any line on which the child gets more than 50%
abnormality, a blood pressure reading should be ob- correct. Children 4 years and older who are unable to
tained at each visit regardless of age. Accurate determi- cooperate should be retested, ideally within 1 month,
nation of blood pressure requires proper equipment and those who cannot cooperate with repeated attempts
(stethoscope, manometer and inflation cuff, or an auto- should be referred to an ophthalmologist. Because vi-
mated system) and a cooperative, seated subject. Al- sual acuity improves with age, results of the test are in-
though automated blood pressure instruments are terpreted using the cutoff values in Table 8–2; however,
widely available and easy to use, blood pressure read- any two-line discrepancy between the two eyes should
ings from these devices are typically 5 mm Hg higher be referred to an ophthalmologist. Throughout child-
for diastolic and 10 mm Hg higher for systolic blood hood and adolescence, the clinician should screen for
pressure compared with auscultatory techniques. undetected strabismus (ocular misalignment) and de-
Therefore, the diagnosis of hypertension should not be creased visual acuity. The random dot E test is recom-
made on the basis of automated readings alone. Addi- mended for detecting strabismus. The corneal light re-
tionally, blood pressure varies somewhat by the height
and weight of the individual. Consequently, hyperten-
sion is diagnosed as a systolic or diastolic blood pressure
greater than the 95th percentile based on the age and Table 8–2. Age-appropriate visual acuity.a
height (or weight) percentile of the patient.
The width of the inflatable portion of the cuff Age (years) Minimal Acceptable Acuity
should be 40–50% of the circumference of the limb.
Obese children thus need a larger cuff size to avoid a 3–5 20/40
falsely elevated blood pressure reading. Cuffs that are 6 and older 20/30
too narrow will overestimate and those that are too a
Refer to an ophthalmologist if minimal acuity is not met at a
wide will underestimate the true blood pressure. Blood given age or if there is a difference in scores of two or more lines
pressure norms are provided in Chapter 19. between the eyes.
234 / CHAPTER 8

flex test, the cover test, and visual acuity tests are de- nosed, both diseases result in severe mental retardation.
scribed further in Chapter 15. Early treatment maintains cognitive function in the
Hearing loss, if undetected, can lead to substantial normal range. Also, most states test for galactosemia
impairments in speech, language, and cognitive devel- and sickle cell disease. Additional diseases screened for
opment. Because significant bilateral hearing loss is one in some state programs include congenital adrenal hy-
of the more common major anomalies found at birth, perplasia, homocystinuria, maple syrup urine disease,
and early detection and intervention of hearing loss biotinidase deficiency, tyrosinemia, other metabolic
leads to better outcomes for children, universal hearing conditions, cystic fibrosis, and toxoplasmosis. After
screening of all infants is required in many parts of newborn screening is performed, several additional
the United States. Hearing in infants is assessed using steps are necessary. Infants with a positive screen result
either auditory brainstem responses or evoked oto- should receive close follow-up, with additional confir-
acoustic emissions. Because universal newborn hearing matory studies performed. Screening tests are usually
screening will inevitably be associated with some false- accurate, but the sensitivity and specificity of a particu-
positive test results, confirmatory audiology testing is lar screening test must be carefully considered. If the
required for all abnormal tests. screening test result is reported as positive, a confirma-
In infants and toddlers, hearing can be assessed by tory test must be performed. If symptoms of a disease
asking the parent to provide examples of sounds to are present despite a negative screening test, the infant
which the baby has responded and by using simple should be tested further. Once a diagnosis is confirmed,
techniques such as shaking rattles or snapping the fin- the infant will need further evaluation and treatment.
gers. Pure tone audiometry in the office is feasible be- Advances in science and technology, such as the
ginning at age 3 years. Any evidence of hearing loss Human Genome Project (http://www.nhgri.nih.gov),
should be substantiated by repeated testing, and if still have created the potential to test for myriad additional
abnormal, a referral for formal hearing testing should inherited diseases. Any such screening should directly
be made. A number of inherited or acquired conditions benefit the infant, because not all conditions are worth
increase the risk of hearing loss. Children with any risk looking for in current newborn screening programs. To
factors for hearing loss should be closely followed and justify testing the entire population for a condition,
periodically screened. Additional details are provided in that condition would have to be a serious and prevalent
Chapter 17. health problem; early detection and treatment of the
disease must improve patient outcomes; and testing
American Academy of Pediatrics et al: Eye examination in infants, would have to be simple, safe, and affordable.
children, and young adults by pediatricians. Pediatrics
2003;111:902 [PMID: 12671132].
Cunningham M et al: Hearing assessment in infants and children:
Lead Screening
Recommendations beyond neonatal screening. Pediatrics The developing infant and child are at risk of lead poi-
2003;111:436 [PMID: 12563074]. soning because of their propensity to place objects in
Joint Committee on Infant Hearing et al: Year 2000 statement: the mouth and their efficient absorption of the metal.
Principles and guidelines for early hearing detection and in-
tervention programs. Pediatrics 2000;106;798 [PMID:
High blood levels (> 70 µg/dL) can cause severe health
11015525]. problems such as seizures and coma. Blood lead levels
as low as 10 µg/dL may cause behavioral problems and
learning disabilities, and these effects persist into later
LABORATORY SCREENING life. Blood lead levels below 10 µg/dL have been corre-
lated with lower intelligence quotients. The primary
Newborn Screening source of lead exposure in this country remains lead-
Newborn screening involves population-wide testing based paint, even though most of its uses have been
for metabolic and genetic diseases. Blood samples are banned since 1977. Typically, children are exposed
collected by heelstick from newborns before hospital through chronic ingestion of dust that is contaminated
discharge, and results are usually available within with lead. Environmental controls such as the elimina-
1 week. States vary in the types of diseases for which tion of leaded gasoline and paints as well as public ser-
they screen, and many states repeat blood testing be- vice educational efforts are thought to be the main rea-
tween 7 and 14 days of life. Repeat testing is necessary son blood lead levels have declined nationally from a
to detect such diseases as phenylketonuria (PKU), mean of 16 µg/dL in 1976 to 2 µg/dL in 2001. How-
which may not be discovered if the first newborn blood ever, considerable variation in lead levels exists in differ-
screen is performed before 24 hours of life. ent regions of the United States, and a majority of chil-
All state newborn screening programs include tests dren at risk of lead toxicity are not currently screened.
for PKU and congenital hypothyroidism. If undiag- To eliminate childhood lead poisoning by 2010 (a na-
 AMBULATORY & COMMUNITY PEDIATRICS / 235

tional health objective—http://www.healthypeople.gov), blood levels over 14 µg/dL should be evaluated and at-
health care providers need to be vigilant about this en- tempts made to identify the environmental source. Iron
vironmental health threat. deficiency should be treated if present. Chelation of lead
State public health authorities set policies on child- should be considered for levels above 25 µg/dL, is always
hood lead screening. The Centers for Disease Control indicated for levels over 44 µg/dL, and is urgently re-
and Prevention (www.cdc.gov) recommends universal quired for levels of 70 µg/dL or more. All families should
lead screening for communities with a high percentage receive education to decrease the risk of lead exposure.
of old housing (> 27% of houses built before 1950) or a With any elevated lead level (> 10 µg/dL) rescreening
high percentage of children with elevated blood lead should be performed at recommended intervals.
levels (> 12% of children with levels above 10 µg/dL).
Communities with inadequate data regarding local
blood lead levels should also undergo universal screen-
Iron Deficiency
ing. Medicaid requires that all children (ages 1–5 years) Iron deficiency is the most common nutritional defi-
be screened twice, once at 1 year of age and a second ciency in the United States. Severe iron deficiency
screen at 2 years of age. In communities with newer causes anemia, behavioral problems, and cognitive ef-
housing and a lower percentage of children with ele- fects, but recent evidence suggests that even iron defi-
vated lead levels, blood lead screening is recommended ciency without anemia may cause behavioral and cogni-
only for targeted groups of children. In these areas, tive difficulties. Furthermore, the developmental effects
caregivers of children between ages 6 months and of iron deficiency may be present after 10 years, even if
6 years may be interviewed by questionnaire about en- iron deficiency is corrected in infancy. Risk factors for
vironmental risk factors for lead exposure (Table 8–3), iron deficiency include preterm or low-birth-weight
although the data to support the use of this screening births, multiple pregnancy, iron deficiency in the
are inconclusive. If risk factors are present, a blood lead mother, use of nonfortified formula or cow’s milk be-
level should be obtained. fore age 12 months, and an infant diet that is low in
A venous blood sample is preferred over a capillary iron-containing foods. Infants and toddlers consuming
specimen. An elevated capillary (fingerstick) blood sam- greater than 24 oz of cow’s milk per day are at risk, as
ple should always be confirmed by a venous sample. No are children with chronic illness, restricted diet, or ex-
action is required for blood lead levels below 10 µg/dL. tensive blood loss.
The cognitive development of children with confirmed Primary prevention of iron deficiency should be
achieved through dietary means, including feeding in-
fants iron-containing cereals by age 6 months, avoiding
Table 8–3. Elements of a lead risk questionnnaire. low-iron formula during infancy, and limiting cow’s
milk to 24 oz/d in children age 1–5 years. Selective early
screening for iron deficiency should be considered with
Recommended questions the presence of any of the preceding risk factors. A
1. Does your child live in or regularly visit a house built screening hemoglobin or hematocrit should be obtained
before 1950? This could include a day care center, pre-
for high-risk children between ages 9–12 months and
school, the home of a baby-sitter or relative, and so on.
2. Does your child live in or regularly visit a house built
again at 15–18 months, and it should be considered an-
before 1978 with recent, ongoing, or planned renova- nually through age 5 years. Premature and low-birth-
tion or remodeling? weight infants may need testing before 6 months of age.
3. Does your child have a sister or brother, housemate, or Universal anemia screening at 9 and 15 months of age is
playmate being followed for lead poisoning? appropriate for children in communities or patient pop-
Questions that may be considered by region or locality ulations in which anemia is found in 5% or more of
1. Does your child live with an adult whose job (eg, at a those tested. Biochemical tests of iron deficiency focus-
brass/copper foundry, firing range, automotive or boat ing on ferritin, transferrin saturation, and erythrocyte
repair shop, or furniture refinishing shop) or hobby (eg, protoporphyrin may be useful because they are sensitive
electronics, fishing, stained-glass-making, pottery- measures of iron status. Lead poisoning can cause iron
making) involves exposure to lead? deficiency anemia and should be explored as a cause for
2. Does your child live near a work or industrial site (eg, at-risk infants and children. A screening hematocrit is
smelter, battery recycling plant) that involves the use recommended for pregnant teenagers.
of lead?
3. Does your child use pottery or ingest medications that
are suspected of having a high lead content? Hypercholesterolemia & Hyperlipidemia
4. Does your child have exposure to burning lead-painted The benefits of screening and treatment for hypercho-
wood? lesterolemia and hyperlipidemia in children are not
236 / CHAPTER 8

fully known. However, the American Academy of Pedi- matic, gonococcal and chlamydial cultures and screen-
atrics (www.aap.org) and the American Heart Associa- ing tests for syphilis and trichomoniasis are appropriate
tion (www.americanheart.org) recommend obtaining a at the time of each pelvic examination.
total cholesterol measurement in children older than
2 years who have a parent with elevated cholesterol American Academy of Pediatrics: Tuberculosis. In Pickering LK
(above 240 mg/dL). If there is a family history of car- (ed): 2000 Red Book: Report of the Committee on Infectious
diovascular disease before age 55 years, a complete Diseases, 25th ed. American Academy of Pediatrics 2000, p
lipoprotein analysis (fasting cholesterol, high-density 593.
lipoproteins, low-density lipoproteins, triglycerides) is American Academy of Pediatrics Committee on Nutrition: Choles-
terol in children. Pediatrics 1998;101:141 [PMID:
recommended. For all children, a prudent diet is ad- 11345978].
vised (see Nutrition Counseling section).
American Academy of Pediatrics Committee on Practice and Am-
bulatory Medicine: Recommendations for preventive pedi-
Tuberculosis atric health care. Pediatrics 2000;105:645.
American Academy of Pediatrics Newborn Screening Task Force:
In 2002, 15,075 cases of tuberculosis were reported in Serving the family from birth to the medical home: Newborn
the United States, with 946 of these cases occurring in screening: A blueprint for the future—a call for a national
children younger than age 15 years. Well-child care agenda on state newborn screening programs. Pediatrics
should include assessment of the risk of tuberculosis, 2000;106:389 [PMID: 10947682].
and tuberculosis screening should be based on high-risk Recommendations to prevent and control iron deficiency in the
United States. MMWR Morb Mortal Wkly Rep 1998;
status. High risk is defined as contact with a person 47(RR-3):1 [PMID: 9563847].
with known or suspected tuberculosis; having symp-
Surveillance for elevated blood lead levels among children—United
toms or radiographic findings suggesting tuberculosis; States, 1997–2001. MMWR Morb Mortal Wkly Rep 2003;
birth, residence, or travel to a region with high tubercu- 52(SS-10):1 [PMID: 14532866].
losis prevalence (Asia, Middle East, Africa, Latin Amer-
ica); contact with a person with AIDS or HIV; contact
with a prisoner, migrant farm worker, illicit drug user, ANTICIPATORY GUIDANCE
or a person who is or has been recently homeless. The A major portion of the health supervision visit is antici-
Mantoux test (5 tuberculin units of purified protein de- patory guidance. This time enables the clinician to di-
rivative) is the only recommended screening test. It can rect the parent’s or the older child’s attention to issues
be done as early as 3 months of age and should be re- that may arise in the future. Guidance must be appro-
peated annually if the risk persists. The tine test should priate to age and should focus on, but not be limited to,
not be used. Previous vaccination with bacille Cal- concerns expressed by the parent or patient. Anticipa-
mette–Guérin (BCG) is not a contraindication to tu- tory guidance should focus on issues in depth rather
berculosis skin testing. than run through a number of issues superficially. A
combination of oral and printed presentations may be
Screening of Adolescent Patients used. Handouts are an important supplement to antici-
patory guidance. A routine schedule for preventive
Screening adolescents for blood cholesterol, tuberculo- handouts is shown in Table 8–4. Areas of concern in-
sis, and HIV should be offered based on high-risk crite- clude diet, injury prevention, developmental and be-
ria outlined in this chapter and in Chapter 37. Females havioral issues, and health promotion. Injury preven-
with heavy menses, weight loss, poor nutrition, or ath- tion is discussed in the next section; other topics are
letic activity should have a screening hematocrit. Dur- found in other chapters of this book.
ing routine visits, adolescents should be questioned sen-
sitively about sexually transmitted infection (STI) risk Injury Prevention
factors (eg, multiple partners; early onset of sexual ac-
tivity, including child sexual abuse) and STI symptoms Injuries are the leading cause of death in children and
(eg, genital discharge, infectious lesions, pelvic pain). A adolescents after the first year of life (Figure 8–3). For
dipstick urinalysis for leukocytes is generally recom- young people age 15–24 years, injuries are responsible
mended for sexually active adolescents. Teenage girls for more than 50% of all deaths. Each year, 16 million
who are sexually active and all girls regardless of sexual visits to emergency departments are occasioned by in-
experience age 18 years and older should have a pelvic juries to children and adolescents, and more than
examination with Papanicolaou (Pap) smear. A Pap 500,000 of these patients are hospitalized. In the case of
smear should be performed at least every 3 years there- physical injury to a young child, the physician must
after and more frequently in patients with STI risk fac- recognize that some injuries may be intentional or the
tors. Because females with STIs are often not sympto- result of parental neglect (see Chapter 7).
 AMBULATORY & COMMUNITY PEDIATRICS / 237

Table 8–4. Preventive handouts for health children 15 years old or younger killed in motor vehicle
supervision visits. accidents were unrestrained. Car safety seats for chil-
dren are required in this country, and their proper use
Age Suggested Topics could reduce vehicle-associated fatalities and hospital-
izations by at least 50%. The type of safety seat to be
2 weeks Sleep problems: Prevention used depends on the child’s weight and age: rear-facing
2 months Passive smoking infant seat for a child under 20 lb and 1 year of age; for-
4 months Weaning problems: Prevention ward-facing car seat for a child 20–40 lb and older than
6 months Teething 1 year; a belt-positioning booster seat for a child who
12 months Temper tantrums has outgrown the safety seat. When children have
18 months Toilet training basics grown enough to properly fit the vehicle seat belts (usu-
2 years Time-out technique
ally when 4 feet tall), they should use a combination
3 years Spoiled children: Prevention
4 years Sex education for preschoolers
lap/shoulder belt. A rear-facing car seat should never be
5 years Television: Reducing the negative impact used in a seat with a passenger air bag. A car seat should
6 years School work: Preventing problems never be used if the child has outgrown the seat—for
8 years Siblings’ arguments and quarrels example, ears above the back of the seat or shoulders
10 years R-rated movies above the seat strap slots.
12 years Adolescents: Dealing with normal rebellion Up-to-date information on car seats can be found at
www.aap.org/family/carseatguide.htm.
Adapted and reproduced, with permission, from Contemporary When a child is a passenger in a car crash, the case
Pediatrics. These and other topics relevant to preventive health
services can be purchased in the Pediatric Advisor, a computerized
fatality rate is 1%; for children hit by cars, the risk of
patient handout program. Information about the Pediatric Advisor fatality increases threefold. Pedestrian safety skills
is available by calling Clinical Reference Systems at 1-800-237- should be taught to children early in childhood; how-
8401. The author has a financial interest in this product. ever, parental supervision of children near roadways
continues to be required for many years. A final motor
vehicle risk for health involves the use of portable elec-
Injury prevention counseling should be part of each tronic devices. Using a cellular telephone while driving
health supervision visit and can be reinforced at is associated with a fourfold increase in motor vehicle
episodic visits. Counseling should focus on problems accidents. Parents and teenage drivers should avoid this
that are frequent and age-appropriate. Passive strategies risk.
of prevention should be emphasized, because these are
more effective than active strategies; for example, en- B. BICYCLE INJURIES
couraging the use of childproof cupboard latches to In 2001, over 400,000 Americans sustained a bicycle
prevent poisoning will be more effective than instruct- injury, and two thirds of these injuries involved chil-
ing parents to watch their children closely. dren or adolescents. Head trauma accounts for three
Informational handouts about home safety, such as fourths of all bicycle-related fatalities. More than 85%
The Injury Prevention Program (TIPP; available from of brain injuries can be prevented through the use of bi-
the American Academy of Pediatrics), can be provided cycle helmets, and the rate of fatality to bicyclists is
in the waiting room. Advice can then be tailored to the dropping. Therefore, bike riders should wear a helmet
specific needs of each family, with reinforcement from every time they ride. Unfortunately, 25% or less of
age-specific TIPP handouts. children wear a bike helmet when riding.
The pediatrician’s influence can extend beyond the
office to advocate for safer communities. For example, a C. FIREARM INJURIES AND VIOLENCE PREVENTION
community program in Seattle, Washington, to pro- The United States has a higher rate of firearm-related
mote the use of bicycle helmets has increased helmet use death than any other industrialized country. Injuries
from 2% to nearly 40%. The primary care provider is in from firearms are more frequent for young people age
an ideal position to identify high-risk situations and in- 15–24 years than for any other age group, and black
tervene before injury occurs. If a teenager has emotional males are especially vulnerable. Some gun deaths may
problems (eg, depression) and a history of driving viola- be accidental, but most are the result of homicide or
tions, for example, the clinician should recommend in- suicide. A gun in the home doubles the likelihood of a
terventions that could prevent a motor vehicle accident. lethal suicide attempt. Although handguns are often
kept in homes for protection, a gun is more likely to
A. MOTOR VEHICLE INJURIES kill a family member or a friend than an intruder. The
The primary cause of death of children in the United most effective way to prevent firearm injuries is to re-
States is motor vehicle injuries. In 1998, about 57% of move guns from the home and community. Families
238 / CHAPTER 8

Children 1–4 years

Accidents 11.1

Congenital anomalies 3.6

Malignant neoplasms 2.7

Homicide 2.6

Heart disease 1.4

0 5 10 15

Children 5–14 years

Accidents 6.8

Malignant neoplasms 2.4

Congenital anomalies 0.9

Homicide 0.8

Heart disease 0.7

0 2 4 6 8 10

Young adults 15–24 years

Accidents 34.7

Homicide 12.8

Suicide 9.6

Malignant neoplasms 4.3 Figure 8–3. Leading causes of

death in children at 1–4 years, at
5–14 years, and at 15–24 years (the
Heart disease 2.3 1999 rate per 100,000 population).
(National Center for Health Statistics.
0 10 20 30 40 50 Used with permission.)
 AMBULATORY & COMMUNITY PEDIATRICS / 239

who keep firearms at home should lock them in a cabi- exposure. The safety of sunscreen is not established for
net or drawer and store ammunition in a separate infants younger than 6 months; thus sun avoidance, ap-
locked location. propriate clothing, and hats are recommended for this
A nonviolent environment should be provided to all age group.
children. Secure parent–infant attachments, social and
conflict-resolution skills, and the avoidance of violence American Academy of Pediatrics, Committee on Injury and Poison
(on television or actual) all have a role in promoting Prevention: Bicycle helmets. Pediatrics 2001;108:1030
nonviolence. [PMID: 11581464].
American Academy of Pediatrics, Committee on Injury and Poison
D. DROWNING AND NEAR DROWNING Prevention: Firearm-related injuries affecting the pediatric
Drowning is the second leading cause of injury-related population. Pediatrics 2000;105:888 [PMID: 10742344].
death in children, and those age 1–3 years have the American Academy of Pediatrics, Committee on Injury and Poison
Prevention: Reducing the number of deaths and injuries from
highest rate of drowning. For every death by drowning, residential fires. Pediatrics 2000;105:1355 [PMID:
six children are hospitalized for near drowning, and up 10835082].
to 10% of survivors experience severe brain damage. Brenner RA et al: Where children drown, United States, 1995. Pe-
Children younger than age 1 year are most likely to diatrics 2001;108:85 [PMID: 11433058].
drown in the bathtub. Buckets filled with water also
present a risk of drowning to the older infant or tod-
dler. For children age 1–4 years, drowning or near NUTRITION COUNSELING
drowning occurs most often in home swimming pools; Screening for nutritional problems and guidance for
and for school-age children and teens, drowning occurs age-appropriate dietary choices should be part of every
most often in large bodies of water (eg, swimming health supervision visit. Undernutrition, overnutrition,
pools or open water). After the age of 5 years, the risk and eating disorders can be detected early by the careful
of drowning in a swimming pool is much greater for analysis of food choices and eating behaviors, particu-
black males than white males. School-age children larly when interpreted in the context of the child’s
should be taught to swim, and recreational swimming growth pattern. Clinicians should assess the structure of
should always be supervised. Home pools must be meals (ie, does the family eat three regular meals inter-
fenced securely, and parents should know how to per- spersed with healthy snacks), the type and amounts of
form cardiopulmonary resuscitation. food provided, and the degree to which the child grazes
or watches television while eating. Iron-fortified for-
E. FIRE AND BURN INJURIES mula or breast milk should be used for the first year of
Fires and burns are the leading cause of injury-related life, after which whole cow’s milk can be given. Because
deaths in the home. Categories of burn injury include of continued rapid growth and high energy needs, chil-
smoke inhalation; flame contact; scalding; and electri- dren should continue to drink whole milk until age
cal, chemical, and ultraviolet burns. Scalding is the 2 years. Baby foods are generally introduced around
most common type of burn in children. Most scalds in- ages 4–6 months.
volve foods and beverages, but nearly one fourth of For children 2 years old and older, a prudent diet
scalds are with tap water, and for that reason it is rec- consists of diverse food sources, encourages high-fiber
ommended that hot water heaters be set to less than foods (eg, fruits, vegetables, grain products), and limits
54°C (130°F). The greatest number of fire-related sodium and fat intake. Foods to be avoided or limited
deaths result from smoke inhalation. Smoke detectors include processed foods, soft drinks, and candy. For ad-
can prevent 85% of the injuries and deaths caused by ditional information on nutritional guidelines, see
fires in the home. Families should practice emergency Chapter 10; for eating disorders, see Chapter 5; for
evacuation from the home. obesity, see Chapter 3.
Sunburn is a common thermal injury, perhaps be-
cause symptoms of excessive sun exposure do not begin American Academy of Pediatrics, Committee on Nutrition: Pre-
until after the skin has been damaged. Sunburn and ex- vention of pediatric overweight and obesity. Pediatrics
cessive sun exposure are associated with skin cancers. 2003;112:424 [PMID: 12897303].
Prevention of sunburn is best achieved by sun avoid- Hall RT, Carroll RE: Infant feeding. Pediatr Rev. 2000;21:191
ance, particularly during the midday hours of 10 AM, to [PMID: 10854314].
3 PM. Sunscreen using a sun protection factor (SPF) of
15 or greater extends the duration of time that a child IMMUNIZATIONS
can spend in the sun without sunburn. Hats, sun-
glasses, and special precautions for fair-skinned individ- A child’s immunization status should be assessed at
uals and infants are also important aspects of safe sun every clinic visit. Even though parents may keep an im-
240 / CHAPTER 8

munization record, it is critical that providers also keep ance should be provided. Careful documentation of
an accurate record of a child’s immunizations. This in- these visits is important for medicolegal reasons.
formation may be written in a prominent location in
the chart or kept in a specialized computer database,
called an immunization registry.
Despite high overall national immunization cover-
PRENATAL VISITS
age levels, areas of underimmunization continue to Ideally, a couple’s first trip to a physician’s office should
exist in the United States. Therefore, it is important take place before the birth of the baby. A prenatal visit
that clinicians screen records and administer required goes a long way toward establishing trust and enables
immunizations at all types of visits, and administer all the physician to learn about a family’s expectations,
needed vaccinations simultaneously. Additionally, clini- concerns, and fears regarding the anticipated birth. If
cians should operate reminder/recall systems, in which the infant develops a problem during the newborn pe-
parents of underimmunized children are prompted by riod, the physician who has already met the family is in
mail or telephone to visit the clinic for immunization. a better position to maintain rapport and communica-
The assessment of clinic-wide immunization levels and tion with the new parents. If possible, both parents
feedback of these data to providers has also been shown should be present for this visit.
to increase immunization rates. Finally, clinicians A prenatal visit provides an easy way to acquaint
should emphasize to parents the importance of timely parents with how the practice is conducted, its hours of
immunization. operation, after-hours coverage, appointment schedul-
Immunization schedules and other details of specific ing, and billing. Parents want to know whom they will
vaccines are presented in Chapter 9. A wealth of infor- speak to when they call the office, when they may bring
mation for parents and providers about immunizations in children for acute-care visits, and how their concerns
is also available at the National Immunization Pro- will be managed.
gram’s website (http://www.cdc.gov/nip).

Santoli JM et al: Immunization pockets of need: Science and prac- SPORTS PHYSICALS
tice. Am J Prev Med 2000;19(1S):89 [PMID: 11024333].
Task Force on Community Preventive Services: Recommendations
The purpose of the preparticipation health evaluation is
regarding interventions to improve vaccination coverage in to determine whether a child can safely participate in
children, adolescents, and adults. Am J Prev Med 2000; organized sports activity. Attention should be directed
18(1S):92 [PMID: 10806981]. toward those parts of the body that are most vulnerable
to the stresses of sports. The history and physical exam-
ination should focus on the following systems: cardio-
vascular (stenotic lesions, hypertension, surgery), respi-
OTHER TYPES OF GENERAL ratory (asthma), vision, genitourinary (absence or loss
of function of one testicle), gastrointestinal (he-
PEDIATRIC SERVICES patosplenomegaly, hernia), skin (infection), muscu-
loskeletal (inflammation, dysfunction), and neurologic
(concussions, uncontrolled seizures). The sports physi-
ACUTE-CARE VISITS cal should include counseling about medication usage
Acute-care visits account for 30% or more of the gen- (eg, diuretic, steroid, and β-blocker abuse, changes in
eral pediatrician’s office visits. These visits must be con- insulin requirements), protective equipment, proper su-
ducted in an efficient, structured way. Office personnel pervision and instruction, injury management, and the
should determine the reason for the visit, obtain a brief emotional aspects of competition and teamwork. The
synopsis of the child’s symptoms, carefully document physician should suggest sports that will be compatible
vital signs, and list known drug allergies. The physician with the child’s size, strength, endurance, agility, and
should document the events related to the presenting chronic illness history. The potential for mild men-
problem and note them with the results of the physical strual irregularities should be explained to the adoles-
examination. The record should include supporting cent female athlete. The athlete with moderate to severe
laboratory data and a diagnosis. Treatments and follow- menstrual irregularities should be referred for en-
up instructions must be recorded, including when to docrinologic evaluation. Anticipatory guidance should
return to the office if the problem is not ameliorated. address nutritional needs to maintain growth, cessation
Immunization status should be screened and appropri- of activity when pain occurs, and fluid and electrolyte
ate vaccinations given. As time allows, age-appropriate availability to avoid dehydration. (See Chapter 24 for a
health maintenance screenings and anticipatory guid- more detailed discussion of sports medicine.)
 AMBULATORY & COMMUNITY PEDIATRICS / 241

CHRONIC DISEASE FOLLOW-UP problems often mean chronic use of medications and
the need to monitor their use. Notes should be made in
Chronic disease is defined as illness that has been pre- the chart whenever a prescription is refilled. A medica-
sent for more than 3 months. When both the history tion summary page in the chart allows easy access to the
from the parent and the physical examination are used drug history and is a convenient place to make notes
to define chronic disease, 25% of children and 35% of such as when the anticonvulsant level was last checked
adolescents will meet the definition of chronic illness. and what it was at that time (Figure 8–4). Children
The most common chronic illnesses in pediatric prac- with medical appliances such as gastrostomy tubes and
tice include asthma, otitis media with effusion, skin dis- indwelling intravenous and bladder catheters need ad-
orders, and allergic diseases. vice on their management. Nutritional intake is often
The goal of chronic disease management is to opti- complicated and must be closely and carefully moni-
mize quality of life. The child and family’s emotional tored.
responses to chronic illness should be addressed, and re-
ferrals to counselors should be offered if needed. Spe-
cialty referrals need to be monitored and results Ludder-Jackson P, Vessey JA: Primary Care of the Child with a
recorded in the chart in an organized manner. Chronic Chronic Condition, 3rd ed. Mosby-Year Book, 2000.

Medication:

Date:
Visit (V) Tablet
or Size or Pharmacy
Phone Liquid Number Approved and Phone
Call (PC) Concentration Sig. Disp. of Refills by Called by No.

Notes (eg, levels):

Figure 8–4. Medication summary sheet.

242 / CHAPTER 8

COUNSELING being requested should be clearly determined at the

time of referral of the patient. This understanding
Topics amenable to office counseling include behav- should be clarified with the patient’s insurance com-
ioral issues such as negativism and noncompliance, pany so that appropriate authorization and reimburse-
temper tantrums, oppositional behavior, and biting; ment for the visit can occur.
childhood fears and feeding disorders; school problems;
family upheavals such as separation, divorce, or remar-
riage; attention-deficit/hyperactivity disorder; and Communication with the Referring Source
deaths of family members or close friends. Forty-five Communication is the key to a satisfactory referral
minutes is usually enough time for the therapeutic process. The pediatric consultant frequently sends the
process to evolve, and this time should be protected referral source a brief note acknowledging the referral
from interruption. The young child is usually inter- and requesting additional information. The final con-
viewed with the parent; school-age children and adoles- sultation report should be sent promptly, with content
cents benefit from time alone with the physician. After appropriate for the referring source. School officials
assessing the situation in one or two sessions, the pri- usually want to know only whether the patient is physi-
mary care physician must decide whether the child’s cally healthy or, if not, what their responsibility is. A re-
and family’s needs are within his or her area of expertise ferring physician expects a full report. Recommenda-
or whether referral to another professional such as a tions should be specific (eg, drugs, dosages, other forms
psychologist or an education specialist would be appro- of therapy, duration of therapy, specific laboratory
priate. The pediatrician should know the warning signs tests). A copy of or reference to a recent review article
for childhood depression and bipolar disorder and have on the subject will also be appreciated.
a low threshold for referral of these concerns to the ap- A medical evaluation should contain a factual sum-
propriate mental health professional. mary of the history, physical examination, and labora-
tory and radiologic findings. Families are grateful if a
copy is sent to them for their information and records.
CONSULTATIONSa At the end of the consultation, the parents should be
Referring Source told when the patient should see the primary physi-
cian—usually in 1–2 weeks. Positive comments about
Physicians, other professionals, and parents may initiate the referring physician’s competence and judgment
consultations with a general pediatrician. The general serve to support the primary physician–patient relation-
pediatrician may be called on to evaluate many differ- ship. The parents must feel confident that the primary
ent types of problems both in the hospital and in the physician can provide the necessary follow-up care. If
ambulatory setting. Parents sometimes desire a second the referring physician had tentatively made the correct
opinion regarding a specific concern while maintaining diagnosis prior to referral, the consultant’s corrobora-
a relationship with another clinician for their child’s pri- tion should be made clear to the parents and included
mary care. Subspecialists, family physicians, or profes- in the consultation report.
sionals such as school officials, psychologists, or social
workers may also seek second opinions. Finally, an in- TELEPHONE TRIAGE AND ADVICEb
surance company physician or administrator may want a
second opinion before authorizing a set of services. Providing appropriate, efficient, and timely clinical ad-
Consultations usually require one or two 45- to vice over the telephone is a critical element of patient
60-minute appointments. When the patient is referred care for all primary care providers. In fact, an estimated
to a pediatric consultant, the number of visits and the 20–30% of all clinical care delivered by general pedi-
extent of service should be specified. A screening ques- atric offices is provided by telephone. Telephone calls
tionnaire, completed in advance by a parent, should de- to and from patients occur both during regular office
lineate the patient’s physical, behavioral, and develop- hours and after the office has closed (termed after-
mental (or school) problems and serve as an initial hours), and the personnel and systems in place to han-
database. dle office-hours versus before- and after-hours calls may
The types of consultations the general pediatrician differ. In either circumstance, several principles are im-
may be asked to do include an evaluation only, an eval- portant: (1) advice is given only by clinicians or other
uation and interpretation, or an evaluation and treat- staff with formal medical education (eg, nurse, medical
ment of an isolated problem. The type of consultation assistant), (2) staff is given additional training in pro-

a b
Contributed by Barton D. Schmitt, MD. Contributed by Barton D. Schmitt, MD.
 AMBULATORY & COMMUNITY PEDIATRICS / 243

viding telephone care, (3) documentation is made of all the end of the call, it should be confirmed that parents
pertinent information from calls, (4) standardized pro- understand and feel comfortable with the plan for their
tocols covering the most common pediatric symptoms child.
are used, and (5) a physician is always available to han-
dle urgent or difficult calls.
During routine office hours, approximately 20–25% Kempe A et al: Delivery of pediatric after-hours care by call centers:
of all telephone calls made to pediatric offices are re- A multicenter study of parental perceptions and compliance.
garding clinical matters. Many of these calls, however, Pediatrics 2001;108:e111 [PMID: 11731638].
are routine in nature, and an experienced nurse within Luberti AA: After-hours telephone care: Options for the pediatri-
the office can screen calls and provide appropriate ad- cian. Pediatr Ann 2001;30:249 [PMID: 11383464].
vice by telephone. Calls from inexperienced or anxious Poole SR: Creating an after-hours telephone triage system for office
practice. Pediatr Ann 2001;30:268 [PMID: 11383466].
parents about simple concerns should be answered with
understanding and respect. Certain types of calls re-
ceived during office hours should be promptly trans-
ferred to a physician: (1) true emergencies, (2) calls re- COMMUNITY PEDIATRICS
garding hospitalized patients, (3) calls from other Community pediatrics is by definition “a concern for
medical professionals, and (4) calls from parents who all children in the community, especially children who
demand to speak with a physician. Nurses should also do not get adequate medical care.” Pediatricians have
seek help from a clinician whenever they are uncertain historically been very involved in supporting and devel-
about how to handle a particular call. When in doubt oping services for vulnerable children in their commu-
about the diagnosis or necessary treatment, nurses giv- nities. As a group, pediatricians recognize that commu-
ing telephone advise should err on the side of having nities are integral determinants of a child’s health and
the patient seen in the office. that the synthesis of public health and personal health
Several different options are available for handling principles and practices is important in the practice of
after-hours pediatric telephone care. Clinicians may community pediatrics. As well, pediatricians have a
choose to take all calls from their patients, may rely on long commitment to work with other professionals in
“advice” nurses without specific pediatric protocols or the community and advocate for the needs of all chil-
training, or may use a system specifically designed for dren.
pediatric telephone care, called a pediatric after-hours Pediatricians in practice are frequently instrumental
call center. Pediatric call centers, although not available in referring children and families to valuable services
in all communities and potentially more expensive than and resources. For example, uninsured children can be
other options for after-hours care, have certain benefits. enrolled in either their state Medicaid program or State
Calls are managed using standardized protocols, the call Children’s Health Insurance Program (SCHIP). Chil-
centers are typically staffed by nurses with abundant pe- dren with special health care needs may be eligible for
diatric experience, the calls are well-documented, and services typically funded through state health depart-
call centers often perform ongoing quality assurance. ments and through programs such as those provided
Extensive research on pediatric call centers has revealed based on the Individuals with Disabilities Education
a high degree of appropriate referrals to emergency de- Act (IDEA). A variety of community-based immuniza-
partments, and a high level of parent satisfaction with tion programs can provide access to needed immuniza-
the process. tion for eligible children. Food and nutrition programs
In general, after-hours pediatric telephone calls tend such as the federally funded Women, Infant and Chil-
to be more serious than calls made during regular dren (WIC) program provide sources of free food for
office hours. Deciding which patients need to be seen, eligible families. Finally, subsidized preschool and child
and how urgently, are the most important aspects care services such as the federally funded Head Start
of these after-hours telephone “encounters.” Several program provide needed preschool programs. Pediatri-
factors influence this final patient disposition: (1) the cians are in a unique position to make referrals to these
age of the patient, (2) the duration and type of important services from the ambulatory and hospital-
symptom, (3) the presence of any underlying chronic based practice settings.
condition, (4) whether the child appears “very sick”
to the caller, and (5) the anxiety level of the caller.
Once all the pertinent medical information is gathered, American Academy of Pediatrics, Committee on Child Health Ser-
a decision is made about whether the child should vices: The pediatrician’s role in community pediatrics. Pedi-
be seen immediately (by ambulance versus car), seen atrics 1999;103:1304 [PMID: 10353949].
in the office later (today versus tomorrow), or Haggerty RJ: Community pediatrics. N Engl J Med 1968;278:15
whether the illness can be safely cared for at home. At [PMID: 5634652].
244 / CHAPTER 8

Table 8–5. Guidelines for evaluating children

COMMON GENERAL with fever.
PEDIATRIC ISSUES A. See immediately if:
(1) The child is less than 3 months old.
FEVER (2) The fever is over 40.6°C.
(3) The child is crying inconsolably or whimpering.
Definition and Measurement (4) The child is crying when moved or even touched.
(5) The child is difficult to awaken.
Fever is one of the most common reasons for pediatric (6) The child’s neck is stiff.
office visits, emergency department encounters, and (7) Purple spots or dots are present on the skin.
after-hours telephone calls. Several different definitions (8) The child’s breathing is difficult, and not better
of fever exist, but most experts define fever as a rectal after the nasal passages are cleared.
temperature of 38°C or above. Temperature in pedi- (9) The child is drooling saliva and is unable to swal-
atric patients can be measured in a variety of manners: low anything.
rectal (using a mercury or digital thermometer), oral (10) A convulsion has occurred.
(mercury, digital), axillary (mercury, digital, or liquid (11) The child acts or looks “very sick.”
crystal strip), forehead (liquid crystal strip), or tym- B. See within 24 hours if:
panic (using a device that measures thermal infrared en- (1) The child is 3–6 months old (unless fever occurs
ergy from the tympanic membrane). Tympanic mea- within 48 hours after a diphtheria-tetanus-
surement of temperature, because it is quick, not pertussis vaccination and the infant has no other
particularly uncomfortable, and requires little patient serious symptoms).
cooperation, is rapidly becoming the norm in many set- (2) The fever exceeds 40°C (especially if the child is
tings. However, several cautions apply to the use of this under age 3 years).
technique: tympanic temperatures have been shown to (3) Burning or pain occurs with urination.
be less accurate in infants younger than 3 months old (4) The fever has been present for more than 24
hours without an obvious cause or identified site
and are subject to false readings if the instrument is not
of infection.
positioned properly or the external ear canal is occluded (5) The fever has subsided for more than 24 hours
by wax. and then returned.
(6) The fever has been present for more than 72
Causes of Fever hours.
Fever occurs when there is a rise in the hypothalamic
set-point in response to endogenously produced pyro-
gens. A tremendously broad range of conditions cause heart rate, respiratory rate, and blood pressure should
fever, including infections, malignancies, autoimmune be documented, as well as an oxygen saturation if the
diseases, metabolic diseases, chronic inflammatory con- child has any increased work of breathing. A complete
ditions, medications (including immunizations), central physical examination, including a neurologic exam,
nervous system abnormalities, and exposure to excessive should then be performed, with particular attention
environmental heat. In most settings, however, the ma- paid to the child’s degree of toxicity and hydration sta-
jority of fevers in pediatric patients are caused by self- tus. A well-appearing, well-hydrated child with evi-
limiting viral infections. Teething does not cause fever dence of a routine viral infection can be safely sent
over 38.4°C. home with symptomatic treatment and careful return
precautions. Depending on the age of the patient, pres-
Evaluation ence of underlying conditions, type of infection, and
the provider’s assessment of toxicity and hydration,
A. GENERAL CONSIDERATIONS many focal bacterial infections can also be treated as
When evaluating a child with fever, one should elicit outpatients, with appropriate oral antibiotics as dis-
from the parents information about the duration of cussed in Chapter 38.
fever, the maximum height of fever documented at
home, all associated symptoms, any chronic medical B. FEVER WITHOUT A FOCUS OF INFECTION
conditions, any medications taken, medication aller- Children who present with fever but without any
gies, fluid intake, urine output, exposures and travel, symptoms or signs of a focal infection are often a diag-
and any additional features of the illness that concern nostic and management challenge. Literally hundreds
the parents (Table 8–5). In the office, a temperature, of articles have been published in the medical literature
 AMBULATORY & COMMUNITY PEDIATRICS / 245

about the proper evaluation and treatment of infants bacteremia in febrile 3–36-month-olds with no focus of
and young children with fever. When assessing a child infection. Nevertheless, for children 3–36 months old
with fever but no apparent source of infection on exam- with temperatures ≥ 39°C, urine cultures should be
ination, the provider needs to carefully consider the considered in all male children younger than 6 months
likelihood of a serious but “hidden” or occult bacterial of age and in all females younger than 2 years of age.
infection. With the widespread use of effective vaccines Chest radiographs should be performed in any child
against Haemophilus influenzae type b and Streptococcus with increased work of breathing and should also be
pneumoniae, two of the most common causes of inva- considered in children with high (≥ 20,000/mm3)
sive bacterial infections in unimmunized children, the WBC counts but no respiratory symptoms. Depending
incidence of occult bacterial infections appears to be de- on the child’s appearance, underlying medical condi-
clining. However, vaccines are not 100% effective, and tion, and the height of fever, blood cultures should also
other organisms cause serious occult infections in chil- be obtained. Empiric antibiotic therapy may be consid-
dren; therefore, febrile children will always demand ered, particularly for children with temperature ≥ 39°C
careful evaluation and observation. Appropriate choices and WBC count ≥ 15,000/mm3. However, in previ-
for empiric antibiotic therapy of children with fever ously healthy, well-appearing, fully immunized children
without focus are discussed in Chapter 35. with reassuring laboratory studies, observation without
Febrile infants 28 days old or younger, because of antibiotics is safe and appropriate in many circum-
their likelihood of serious disease including sepsis, stances.
should always be treated conservatively. Hospitalization
and parenteral antibiotics should be strongly considered
in all circumstances. An initial diagnostic evaluation Treatment of Fever
should include complete blood count; blood culture;
urinalysis; urine culture; Gram stain, protein, and glu- Fever phobia is a term that describes parents’ anxious
cose tests of cerebrospinal fluid (CSF); and CSF cul- response to the fevers that all children experience. In a
ture. Consideration should also be given to the possibil- recent study, 91% of caregivers thought that a fever
ity of a perinatal herpes simplex virus infection could cause harmful effects. Seven percent of parents
(neonatal herpes is described in more detail in Chapter thought that if they did not treat the fever, it would
36). A chest radiograph should be obtained for any in- keep going higher. Parents need to be reassured that
fant with increased work of breathing. fevers < 41.7°C cause no brain damage. Parents need to
Infants age 29–90 days are at risk of a variety of in- be counseled that, although fevers can occasionally
vasive bacterial infections, including perinatally ac- (≈4%) cause seizures, in which case their child needs to
quired organisms (eg, group B streptococci) or infec- be seen, febrile seizures are generally harmless and also
tions acquired in the household (eg, pneumococci or cause no brain damage.
meningococci). Febrile infants without a focus of infec- Several safe and effective medications are available
tion can be divided into those who appear toxic versus for the treatment of fever. Acetaminophen is indicated
nontoxic, and those at low risk versus higher risk of in- for children older than 2 months of age for fevers ≥
vasive bacterial disease. As with febrile neonates, toxic 39°C or if the child is uncomfortable. Acetaminophen
children in this age group should be admitted to the is given in a dosage of 15 mg/kg of body weight per
hospital for parental antibiotics and close observation. dose and can be given every 4–6 hours. The other
In nontoxic infants, low risk has been defined as previ- widely used antipyretic in the United States is ibupro-
ously healthy; no focal infection on examination; white fen. Ibuprofen is given in a dosage of 10 mg/kg of body
blood cell (WBC) count between 5000 and weight per dose and can be given every 6–8 hours.
15000/mm3; band cells < 1500/mm3; normal urinaly- Ibuprofen and acetaminophen are similar in safety and
sis; and, when diarrhea is present, < 5 WBCs/hpf. Non- their ability to reduce fever; however, ibuprofen is
toxic low-risk infants in this age group are typically longer lasting. Aspirin should not be used for treating
treated as outpatients with close follow-up. Longstand- fever in any child or adolescent, because of its associa-
ing practice guidelines, published by Baraff and col- tion with the development of Reye syndrome (particu-
leagues in 1993, recommend that nontoxic but high- larly during infections with varicella and influenza).
risk infants be admitted, undergo lumbar puncture, and
receive parental antibiotics. Other experts have more
Crocetti M, Moghbeli N, Serwint J: Fever phobia revisited: Have
recently suggested that in certain circumstances these parental misconceptions about fever changed in 20 years? Pe-
infants can be safely treated as outpatients. diatrics 2001;107:1241 [PMID: 11389237].
In an era of increasing immunization coverage Klein JO: Management of the febrile child without a focus of infec-
against the most commonly invasive pneumococcal tion in the era of universal pneumococcal immunization. Pe-
serotypes, it is difficult to estimate the risk of occult diatr Infect Dis J 2002;21:584 [PMID: 12182394].
246 / CHAPTER 8

McCarthy PL: Fever without apparent source on clinical examina- Table 8–6. Components of initial evaluation.
tion. Curr Opin Pediatr 2002;14:103 [PMID: 11880744].
Rehm KP: Fever in infants and children. Curr Opin Pediatr
2001;13:83 [PMID: 11216593]. Birth history: Newborn screening result. Rule out intrauterine
growth retardation, anoxia, congenital infections.
Feeding and nutrition: Difficulty sucking, chewing, swallow-
ing. Feeding patterns. Intake of formula, milk, juice, solids.
GROWTH DEFICIENCY Stooling and voiding of urine: Diarrhea, constipation, vomit-
ing, poor urine stream.
Growth deficiency—formerly termed failure to Growth pattern: Several points on the growth chart are cru-
thrive—is deceleration of growth velocity resulting in cial.
crossing two major percentile lines on the growth chart. Recurrent infections.
The diagnosis is warranted also if a child younger than Hospitalizations.
age 6 months has not grown for 2 consecutive months HIV risk factors.
or if a child older than age 6 months has not grown for Developmental history.
3 consecutive months. Growth deficiency occurs in Social and family factors: Family composition, financial status,
about 8% of children. supports, stresses. Heritable diseases, heights and weights
Patterns of growth deficiency suggest, but are not of relatives.
specific for, different causes. In type I growth defi- Review of systems.
ciency, the head circumference is preserved and the
weight is depressed more than the height. This most
common type results from inadequate caloric intake,
excessive loss of calories, excessive intake of calories, or B. FURTHER EVALUATION
inability to use calories peripherally. Most such cases re-
sult from inadequate delivery of calories. This may be A prospective 3-day diet record should be a standard
the result of poverty, lack of caregiver understanding, part of the evaluation. This is useful in assessing under-
poor caregiver–child interaction, abnormal feeding pat- nutrition even when organic disease is present. The diet
terns, or a combination of factors. Type II growth defi- history is evaluated by a pediatric dietitian for calories,
ciency, which is associated with genetically determined protein, and micronutrients as well as for the pattern of
short stature, endocrinopathies, constitutional growth eating. Additional laboratory tests should be ordered
delay, heart or renal disease, or various forms of skeletal based on the history and physical examination. For ex-
dysplasias, is characterized by normal head circumfer- ample, stool collection for fat determination is indi-
ence and proportionate diminution of height and cated if a history of diarrhea suggests malabsorption.
weight. In type III growth deficiency, all three parame- Moderate or high amounts of proteinuria should
ters of growth—head circumference, weight, and prompt work-up for nephrotic syndrome. Vomiting
height—are lower than normal. This pattern is associ- should suggest a gastrointestinal, metabolic, neurologic,
ated with central nervous system abnormalities, chro- infectious, or renal cause. The tempo of evaluation
mosomal defects, and in utero or perinatal insults. should be based on the severity of symptoms and the
magnitude of growth failure.

Treatment
Clinical Findings
A successful treatment plan addresses the child’s diet
A. INITIAL EVALUATION and eating patterns, the child’s development, caregiver
The history and physical examination will identify the skills, and any organic disease. High-calorie diets and
cause of growth reduction in the vast majority of cases frequent monitoring (every 1 or 2 weeks initially) are
(Table 8–6). The physical examination should focus on essential. Acceptable weight gain varies by age (Table
signs of organic disease or evidence of abuse or neglect: 8–7).
dysmorphic features, skin lesions, neck masses, adventi- The child with growth deficiency may also be devel-
tial breath sounds, heart murmurs, abdominal masses, opmentally delayed because of living in an environment
and neuromuscular tone and strength. Throughout the that fails to promote development or from the effect on
evaluation, the physician should observe the care- the brain of nutrient deprivation. Restoring nutrition
giver–child interaction and the level of family function- does not fully reverse the deficit but does reduce the
ing. Developmental screening and laboratory screening long-term consequences.
tests (complete blood count, blood urea nitrogen, crea- Education in nutrition, child development, and be-
tinine, electrolytes, urinalysis, and urine culture) com- havioral management as well as psychosocial support of
plete the initial office evaluation. the primary caregiver is essential. If family dysfunction
 AMBULATORY & COMMUNITY PEDIATRICS / 247

Table 8–7. Acceptable weight gain by age. assistance to the family. Rarely, the child may need to
be temporarily or permanently removed from the
Age (months) Weight Gain (g/d) home. Hospitalization is reserved for management of
dehydration, for cases in which home therapy has failed
Birth to 3 20–30 to result in expected growth, for children who show ev-
3–6 15–20 idence of abuse or willful neglect, for management of
6–9 10–15 an illness that compromises a child’s ability to eat, or
9–12 6–11
for care pending foster home placement.
12–18 5–8
18–24 3–7
Weston JA: Growth deficiency. In Berman S (ed): Pediatric Deci-
sion Making, 4th ed. Mosby-Year Book, 2003.
is mild, behavior modification and counseling will be
useful. Day care may benefit the child by providing a
structured environment for all activities, including eat-
ing. If family dysfunction is severe, the local depart-
ment of social services can help provide structure and
 Immunization 9
Matthew F. Daley, MD, Ann-Christine Nyquist, MD, MSPH, & Eric A. F. Simoes, MD, DCH

Immunization is used either to prevent primary infec- diseases. Although 97–98% of these children are vacci-
tion or to prevent the secondary consequences of an in- nated by or shortly after school entry, about a quarter
fection. Any assessment of the benefits of a proposed of the 2-year-olds in this country are not fully immu-
immunization program must take into account the like- nized. Low immunization coverage has been attributed
lihood of occurrence of infection in a defined popula- to difficulties in reaching the urban poor and racial and
tion or specific individual, the consequence of infec- ethnic minorities, and an increasingly mobile society.
tion, and the likelihood that the vaccination will However, deficiencies in the health care delivery system
prevent that infection. The anticipated benefit of im- are also a contributor, as is limited use of recall systems.
munization must be weighed against the risk to the in- Some parents seeking immunization for their children
dividual of adverse consequences. The physician must face significant barriers; not all providers take advantage
present this information to the parents so they can give of opportunities to administer vaccines, and inadequate
informed consent to immunization. The immunization or absent third-party payment for immunizations fur-
recommendations outlined in this chapter are current ther reduces coverage. The AAP recommends the fol-
but will change as technology evolves and our under- lowing specific proven practices to improve this cover-
standing of the epidemiology of vaccine-preventable age: (1) sending caretakers reminder and recall notices,
diseases changes. The most useful sources for current (2) using prompts during all visits, (3) periodic mea-
information about immunization are the following: surement of immunization rates, and (4) having stand-
ing orders for vaccines.
1. Morbidity and Mortality Weekly Report. Published The National Childhood Vaccine Injury Act of
weekly by the Centers for Disease Control and 1986 requires that for each vaccine covered under the
Prevention (CDC), Atlanta, GA 30333. Available Vaccine Injury Compensation Program (VICP) care-
at http://www.cdc.gov/mmwr. takers should be advised about the risks and benefits of
2. The Red Book: Report of the Committee on Infec- vaccination, in a standard manner, using the Vaccine
tious Diseases. Published at 2- to 3-year intervals Information Statements (VIS). In addition the CDC
by the American Academy of Pediatrics (AAP). and AAP have the requirements and recommendations
The 2003 Red Book is available from the AAP. summarized later on. Each time a VICP covered vac-
Updates are published in the journal Pediatrics cine is administered the current version of VIS must be
and can be accessed at http://www.aap.org/. provided to the nonminor patient or legal caretaker.
3. CDC: National Immunization Program Informa- Documentation is required in the medical record, in-
tion Hotline. Provides services to consumers cluding the vaccine manufacturer, lot number, and its
and health care professionals regarding new date of administration and expiration. The name and
vaccines, new schedules, and safety issues. address of the person administering the vaccine, VIS
1-800-232-2522 (Spanish 1-800-232-0233). Op- version and date, and site and route of administration
erates from 8:00 AM to 11:00 PM Monday should also be recorded.
through Friday. Printed information can be ob- The use of disposable syringes and needles or some
tained at http://cdc.gov/nip/. other form of single-dose delivery of vaccine is pre-
ferred to minimize the opportunity for contamination.
4. CDC: Advisory Committee on Immunization prac- A 70% solution of alcohol is appropriate for disinfec-
tice. Available at http://www.cdc.gov/nip/ACIP. tion of the stopper of the vaccine container and of the
skin at the injection site. A 5% topical emulsion of li-
STANDARDS FOR PEDIATRIC docaine–prilocaine (EMLA) cream applied to the site of
vaccination for 30–60 minutes prior to the injection
IMMUNIZATION PRACTICES minimizes the pain, especially when multiple vaccines
An estimated 11,000 children are born each day in the are administered.
United States, each requiring 15–19 doses of vaccine by The manufacturer’s recommendations for route and
age 18 months to be protected against 12 childhood site of administration of injectable vaccines are critical
248
Copyright © 2005, 2001, by The McGraw-Hill Companies, Inc. Click here for terms of use.
 IMMUNIZATION / 249

for safety and efficacy. All vaccines containing an adju- final antibody titers, and thus lapsed schedules do not
vant must be administered intramuscularly to avoid require restarting the series.
granuloma formation or necrosis. Such injections
should be given at a 90-degree angle into the anterolat-
eral thigh (not intragluteally) in infants (< age Atkinson WL et al: Centers for Disease Control and Prevention:
18 months) and may be given in the deltoid or triceps General recommendations on immunization: Recommenda-
tions of the Advisory Committee on Immunization Practices
in older children. A 22-gauge needle 7⁄8–11⁄4 inches long (ACIP) and the American Academy of Family Physicians
is recommended for children, but a 25-gauge 7⁄8–1 inch (AAFP). MMWR Recomm Rep 2002;51(RR-2):1.
needle may be sufficient for young infants. Aspiration Halperin BA et al: Use of lidocaine–prilocaine patch to decrease in-
prior to intramuscular injection is suggested by many tramuscular injection pain does not adversely affect the anti-
experts. Vaccines may be administered intramuscularly, body response to diphtheria–tetanus–acellular pertussis–inac-
subcutaneously, or intradermally. Subcutaneous injec- tivated poliovirus–Haemophilus influenzae type b conjugate
tions should be administered at a 45-degree angle on and hepatitis B vaccines in infants from birth to six months of
age. Pediatr Infect Dis J 2002;21:399 [PMID: 12150176].
the volar surface of the forearm using a 25-gauge 5⁄8-inch
needle. Intradermal injections should be administered Saari TN, American Academy of Pediatrics Committee on Infec-
tious Diseases: Immunization of preterm and low birth
with the bevel facing upward using a 3⁄8- to 3⁄4-inch 25- to weight infants. Pediatrics 2003;112:193 [PMID: 12837889].
27-gauge needle. A 25-gauge 3⁄4- to 5⁄8-inch needle is rec- Wood DL, American Academy of Pediatrics Committee on
ommended. A separate syringe and needle should be Community Health Services, American Academy of
used for each vaccine. Pediatrics Committee on Practice and Ambulatory
It is safe to administer many combinations of vac- Medicine: Increasing immunization coverage. Pediatrics
cines simultaneously without increasing the risk of ad- 2003;112:993 [PMID: 14523201].
verse effects or compromising response. Up to seven in-
jections may be necessary at the 12- to 15-month visit.
(See the following individual preparations for further
discussion.) Inactivated vaccines (with the exception of THE COMPOSITION OF
cholera and yellow fever) can be given simultaneously
or at any time after a different vaccine. Parenteral live- IMMUNIZING AGENTS
virus vaccines, if not administered on the same day,
should be given at least 30 days apart (eg, measles,
mumps, rubella [MMR] and varicella [VAR]). Lapses
ACTIVE IMMUNIZATION
in the immunization schedule do not call for reinstitu- The immune response to immunization varies. A small
tion of the series. Extra doses of hepatitis B (HepB), proportion of children receiving certain antigens simply
Haemophilus influenzae type B (Hib), MMR, or VAR do not mount a response capable of conferring protec-
are not harmful, but repetitive exposure to tetanus vac- tion. For this reason, every vaccine has a definable fail-
cine beyond the recommended intervals can result in ure rate.
hypersensitivity reactions and should be avoided. If an The immunogen is suspended or dissolved in sterile
immunoglobulin (Ig) or blood product has been ad- water or saline, or in more complex media such as tissue
ministered, live-virus vaccination should be delayed culture medium, which may contain constituents from
3–10 months, depending on the product, to avoid in- the biologic system used to produce the immunogen.
terference with the immune response (eg, 3 months for Most vaccines contain preservatives and trace amounts
tetanus Ig, hepatitis A Ig, and hepatitis B Ig, of antibiotics such as neomycin to prevent bacterial
5–6 months for measles Ig or cytomegalovirus Ig overgrowth. Some vaccines contain adjuvants such as
(CMVIg), 9 months for respiratory syncytial virus im- aluminum hydroxide and aluminum phosphate that
munoglobulin, and 11 months for IgIV for Kawasaki also help to retain the immunogen at the site of inocu-
disease). lation for a prolonged time, thus increasing antigenic
With the large number of vaccine preparations avail- stimulation. The theoretical cumulative toxicity of mer-
able, interchangeability of vaccines is an issue. All cury in thimerosal-containing vaccines has led to the
brands of Hib conjugate, hepatitis B, and hepatitis A development of thimerosal-free vaccines. All vaccines
vaccines are interchangeable. For vaccines containing routinely administered to children are now free of
acellular pertussis antigens, it is recommended that the thimerosal.
same brand be used, but when the brand is unknown or Although the prospect is unlikely, vaccine adminis-
the same brand is unavailable, any DTaP (diphtheria, tration could have unforeseen adverse consequences.
tetanus toxoids, and acellular pertussis vaccine) should Thus vaccines should be administered where there is
be used to continue vaccination. Longer than recom- ready access to emergency resuscitative equipment and
mended intervals between vaccinations does not reduce drugs (eg, epinephrine, antihistamines).
250 / CHAPTER 9

PASSIVE IMMUNIZATION Avdicova M et al: Immunogenicity and reactogenicity of a novel

hexavalent DTPa–HBV–IPV/Hib vaccine compared to sepa-
Immune globulin (Ig) is derived from pooled donations rate concomitant injections of DTPa–IPV/Hib and HBV Eur
of large numbers of individuals (more than 1000 per J Pediatr 2002;161:581 [PMID: 12424582].
lot). Ig is prepared by alcohol fractionation, is sterile, Centers for Disease Control and Prevention: Recommended child-
and will not transmit any infectious agents (including hood and adolescent immunization schedule—United States,
June–2004. MMWR 2004;53:1 [PMID: 14733209].
hepatitis B and C viruses and HIV). Ig is a 16.5% solu-
FDA licensure of diphtheria and tetanus toxoids and acellular per-
tion consisting primarily of IgG with very small tussis adsorbed, hepatitis B (recombinant), and poliovirus
amounts of IgA and IgM. vaccine combined, (PEDIARIX) for use in infants. MMWR
Morb Mortal Wkly Rep 2003;52:203.
Halperin SA et al: Simultaneous administration of meningococcal
ROUTINE CHILDHOOD C conjugate vaccine and diphtheria–tetanus–acellular pertus-
& ADOLESCENT IMMUNIZATIONS sis–inactivated poliovirus–Haemophilus influenzae type b con-
jugate vaccine in children: A randomized double-blind study.
Table 9–1 sets forth a schedule of routine immuniza- Clin Invest Med 2002;25:243 [PMID: 12516995].
tions for normal infants and children. Table 9–2 pre-
sents recommended schedules for children who did not
start vaccination at the recommended time during the
first year of life. Variations from these schedules may be SAFETY OF IMMUNIZATION
necessitated by epidemiologic or individual clinical cir-
cumstances. Recommendations for minimum ages and
intervals between doses are shown in Table 9–2. VACCINE FACTORS
To complete the 2004 schedule, 19 separate injec- The safety standards for all vaccines licensed for use in
tions may be required from birth to age 6 years. Com- the United States are established by the Food and Drug
bination vaccines represent a solution to the problem of Administration (FDA) and involve regular examination
large numbers of injections during any single clinic of manufacturing techniques as well as production lots
visit. Currently available combination vaccines include of vaccine. No incidents of bacterial or viral contamina-
MMR and various combinations of Hib, HepB, and tion of vaccines at the factory level have been reported
diphtheria, tetanus, and pertussis vaccines, and more in the United States for decades.
recently a DTaP–HBV–IPV/Hib combination vaccine.
Combination vaccines incorporating hepatitis A,
meningococcal, pneumococcal, and varicella vaccines HOST FACTORS
are being developed, and a pentavalent vaccine combin- The contraindications and precautions relating to im-
ing MMR, HepB, and IPV will soon be available. Sepa- munization presented in Table 9–3 reflect the current
rate vaccines should not be combined into one syringe recommendations of the Advisory Committee on Im-
by the provider, unless approved by the FDA, because munization Practices and the Committee of Infectious
this could decrease the efficacy of each component vac- Diseases of the AAP.
cine.
Healthy Children
Safe Handling of Vaccines Minor acute illnesses, with or without low-grade fever,
The numerous vaccines and other immunologic sub- are not contraindications (see Table 9–3) to vaccina-
stances, such as antibody preparations and immuno- tion, because there is no evidence that vaccination
globulins for routine use by the practitioner, vary in the under these conditions increases the rate of adverse ef-
storage temperatures required. Vaccines that require fects or decreases efficacy. A moderate to severe febrile
routine freezing are VAR and oral poliovirus (OPV). illness may be a reason to postpone vaccination. Rou-
Yellow fever vaccine may also be stored frozen. Product tine physical examination and temperature assessment
package inserts should be consulted for detailed infor- are not necessary before vaccinating healthy infants and
mation on vaccine storage conditions and shelf life. children.

American Academy of Pediatrics: Combination vaccines for child- Children with Chronic Illnesses
hood immunizations: Recommendations of the Advisory Most chronic diseases are not contraindications to vac-
Committee on Immunization Practices (ACIP), the Ameri-
can Academy of Pediatrics (AAP), and the American Acad- cination; in fact, children with chronic diseases may be
emy of Family Physicians (AAFP). Pediatrics 1999;103:1064 at greater risk of complications from vaccine-pre-
[PMID: 10224194]. ventable diseases such as influenza and pneumococcal
 IMMUNIZATION / 251

infections. Premature infants are a good example. They cine rather than to the antigen itself. MMR, IPV, and
should be immunized according to their chronologic, VAR contain microgram quantities of neomycin, and
not gestational, age. Vaccine doses should not be re- IPV also contains trace amounts of streptomycin and
duced for preterm or low-birth-weight infants. The one polymyxin B. Children with known anaphylactic re-
exception to this rule may be children with progressive sponses to these antibiotics should not be given these
central nervous system (CNS) disorders. Vaccination vaccines. Trace quantities of egg antigens may be pre-
may be deferred or avoided entirely for such children, sent in influenza, and yellow fever vaccines and MMR.
whereas children with static CNS diseases are candi- Children who have had anaphylactic reactions to eggs
dates for vaccination. should not be given these vaccines; children with less
serious reactions to eggs may generally be safely immu-
nized. If doubt exists about the nature of a child’s egg
Immunodeficient Children sensitivity, a skin testing procedure is outlined in the
Congenitally immunodeficient children should not be Red Book. Some vaccines (MMR, VAR, and yellow
immunized with live-virus or live-bacteria vaccines. De- fever) contain gelatin, a substance to which persons
pending on the nature of the immunodeficiency, other with known food allergy may develop an anaphylactic
vaccines are safe, but may fail to evoke an immune re- reaction. Skin testing before vaccination may be an op-
sponse. Children with cancer and children receiving tion in such cases.
high-dose corticosteroids or other immunosuppressive
agents should not be vaccinated with live-virus or live-
bacteria vaccines. This contraindication does not apply Special Circumstances
if the malignancy is in remission and chemotherapy has Detailed recommendations for preterm low-birth-
not been administered for at least 90 days. Live-virus weight babies; pediatric transplant recipients; Alaskan
vaccines may also be administered to previously healthy Natives/American Indians; children in residential insti-
children receiving low to moderate doses of corticoster- tutions or military communities; or are refugees, new
oids (defined as up to 2 mg/kg/d of prednisone or pred- immigrants, or travelers are available in the AAP Red
nisone-equivalent, with a 20 mg/d maximum) for less Book.
than 14 days; children receiving low to moderate doses
of alternate-day corticosteroids; children being main-
tained on physiologic corticosteroid therapy without American Academy of Pediatrics: 2003 Red Book: Report of the
Committee on Infectious Diseases, 26th ed. American Academy
other immunodeficiency; and children using only topi- of Pediatrics, 2003.
cal, inhaled, or intraarticular corticosteroids. Bohlke K et al: Vaccine Safety Datalink Team: Risk of anaphylaxis
Contraindication of live-pathogen vaccine also ap- after vaccination of children and adolescents. Pediatrics
plies to children with HIV infection, with the proviso 2003;112:815 [PMID: 14523172].
that MMR is recommended at 12 months of age (after
6 months during an epidemic). The booster dose may
be given as early as 1 month later, but doses given be- DIPHTHERIA
fore 1 year of age should not be considered part of a The risk for exposure to toxigenic strains of Clostridium
complete series. VAR vaccination is recommended for diphtheriae in the United States is low (2 cases in
CDC class N1 or A1 (CD4 ≥ 25%). Severely immuno- 2002); however, diphtheria remains endemic in many
compromised children with HIV infection should not countries. Diphtheria toxoid is prepared by the
receive the measles or VAR vaccines. OPV is con- formaldehyde inactivation of diphtheria toxin. The
traindicated and is no longer recommended in the protective efficacy of diphtheria toxoid has never been
United States. The ACIP recommends routine vaccina- measured on a mass scale, but is estimated to be greater
tion for all children with an all inactivated poliovirus than 85%.
vaccine (IPV) vaccination schedule. Thus immunodefi-
cient children should no longer be exposed to oral po-
liovaccine through household contacts. MMR and Preparations Available
VAR are not contraindicated in household contacts of
immunocompromised children. 1. Diphtheria toxoid is used only when tetanus tox-
oid and pertussis vaccine are both contraindi-
cated.
Allergic or Hypersensitive Children 2. Diphtheria–tetanus vaccine (DT) (pediatric) is
Hypersensitivity reactions are rare following vaccina- used when pertussis vaccine is contraindicated.
tion, occurring in 1.53 cases/million doses. They are DT contains more diphtheria toxoid per dose
generally attributable to a trace component of the vac- than preparations used for adults and should not
252 / CHAPTER 9

Table 9–1. Recommended childhood and adolescent immunization schedulea,j: United States,
January–June 2004.

Range of recommended ages catch-up vaccination Preadolescent assessment

1 2 4 6 12 15 18 24 4–6 11–12 13–18

Vaccine Birth mo mos mos mos mos mos mos mos yrs yrs yrs
HepB #1 only if mother HBsAg (-)
Hepatitis Bb HepB series
HepB #2 HepB #3
Diphtheria, Tetanus,
Pertussisc DTaP DTaP DTaP DTaP DTaP Td Td

Haemophilus
influenzae type bd Hib Hib Hibd Hib

Inactivated Polio IPV IPV IPV IPV

Measles, Mumps, MMR #1 MMR #2 MMR #2

Rubellae

Varicellaf Varicella Varicella

Pneumococcalg PCV PCV PCV PCV PCV PPV

Vaccines below this line are for selected populations

Hepatitis Ah Hepatitis A

Influenzai Influenza (yearly)

a least 16 weeks after the first dose and at least 8 weeks after the
Indicates the recommended ages for routine administration of
currently licensed childhood vaccines, as of December 1, 2003, for second dose. The last dose in the vaccination series (third or
children through age 18 years. Any dose not given at the recom- fourth dose) should not be administered before age 24 weeks. In-
mended age should be given at any subsequent visit when indi- fants born to HBsAg-positive mothers should receive HepB vaccine
cated and feasible. Indicates age groups that warrant spe- and 0.5 mL hepatitis B immune globulin (HBIG) within 12 hours of
cial effort to admister those vaccines not given previously. birth at separate sites. The second dose is recommended at age
Additional vaccines may be licensed and recommended during 1–2 months. The last dose in the vaccination series should not be
the year. Licensed combination vaccines may be used whenever administered before age 24 weeks. These infants should be
any components of the combination are indicated and the vac- tested for HBsAg and anti-HBs at age 9–15 months. Infants born to
cine’s other components are not contraindicated. Providers mothers whose HBsAg status is unknown should receive the first
should consult the manufacturers’ package inserts for detailed dose of the HepB vaccine series within 12 hours of birth. Maternal
recommendations. Clinically significant adverse events that fol- blood should be drawn as soon as possible to determine the
low vaccination should be reported to the Vaccine Adverse Event mother’s HBsAg status; if the HBsAg test is positive, the infant
Reporting System (VAERS). Guidance on how to obtain and com- should receive HBIG as soon as possible (no later than age 1
plete a VAERS form is available at http://www.vaers.org or by tele- week). The second dose is recommended at age 1–2 months. The
phone, 800-822-7967. last dose in the vaccination series should not be administered be-
b fore age 24 weeks.
Hepatitis B vaccine (HepB). All infants should receive the first
c
dose of HepB vaccine soon after birth and before hospital dis- Diphtheria and tetanus toxoids and acellular pertussis vac-
charge; the first dose also may be given by age 2 months if the in- cine (DTaP). The fourth dose of DTaP may be administered at
fant’s mother is HBsAg-negative. Only monovalent HepB vaccine age 12 mo provided 6 mo have elapsed since the third dose and
can be used for the birth dose. Monovalent or combination vac- the child is unlikely to return at age 15–18 mo. The final dose in
cine containing HepB may be used to complete the series; the series should be given at age ≥4 y. Tetanus and diphtheria
4 doses of vaccine may be administered when a birth dose is toxoids (Td) is recommended at age 11–12 y if at least 5 y have
given. The second dose should be given at least 4 weeks after the elapsed since the last dose of tetanus and diphtheria toxoid-con-
first dose except for combination vaccines, which cannot be ad- taining vaccine. Subsequent routine Td boosters are recom-
ministered before age 6 weeks. The third dose should be given at mended every 10 y.
 IMMUNIZATION / 253
d vaccinated against hepatitis A can begin the hepatitis A vaccina-
Haemophilus influenzae type b (Hib) conjugate vaccine.
Three Hib conjugate vaccines are licensed for infant use. If PRP- tion series during any visit. The two doses in the series should be
OMP (PedvaxHIB or ComVax [Merck]) is administered at ages 2 administered at least 6 months apart.
i
and 4 months, a dose at age 6 months is not required. DTaP/Hib Influenza vaccine. Influenza vaccine is recommended annually
combination products should not be used for primary vaccina- for children aged ≥ 6 months with certain risk factors (including
tion in infants at ages 2, 4, or 6 mo but can be used as boosters but not limited to asthma, cardiac disease, sickle cell disease, HIV,
after any Hib vaccine. The final dose in the series should be given and diabetes), and household members of persons in groups at
at age ≥ 12 mo. high risk (see MMWR 2003;52[No. RR-8]:1–36), and can be adminis-
e tered to all others wishing to obtain immunity. In addition, healthy
Measles, mumps, and rubella vaccine (MMR). The second
dose of MMR is recommended routinely at age 4–6 y but may be children aged 6–23 mo are encouraged to receive influenza vac-
administered during any visit provided that at least 4 weeks have cine if feasible because children in this age group are at substan-
elapsed since the first dose and that both doses are administered tially increased risk for influenza-related hospitalizations. For
beginning at or after age 12 months. Those who have not re- healthy persons aged 5–49 y, the intranasally administered live-at-
ceived the second dose previously should complete the schedule tenuated influenza vaccine (LAIV) is an acceptable alternative to
by the visit at age 11–12 years. the intramuscular trivalent inactivated influenza vaccine (TIV). See
f MMWR 2003;52(No. RR-13):1–8. Children receiving TIV should be
Varicella vaccine (VAR). Varicella vaccine is recommended at
any visit at or after age 12 months for susceptible children (i.e., administered a dosage appropriate for thier age (0.25 mL if 6–35
those who lack a reliable history of chickenpox). Susceptible per- mo or 0.5 mL if ≥3 y). Children aged ≤8 y who are receiving in-
sons aged ≥13 years should receive 2 doses given at least 4 weeks fluenza vaccine for the first time should receive 2 doses (separated
apart. by at least 4 weeks for TIV and at least 6 weeks for LAIV).
g j
Pneumococcal vaccine. The heptavalent pneumococcal conju- Additional information about vaccines, including precautions and
gate vaccine (PCV) is recommended for all children aged 2–23 contraindications for vaccination and vaccine shortages, is avail-
mo and for certain children aged 24–59 mo. The final dose in the able at http://www.cdc.gov/nip or from the National Immuniza-
series should be given at age ≥12 mo. Pneumococcal polysac- tion information hotline, telephone 800-232-2522 (English) or 800-
charide vaccine (PPV) is recommended in addition to PCV for 232-0233 (Spanish). Approved by the Advisory Committee on
certain high-risk groups. See MMWR 2000;49(No. RR-9):1–35. Immunization Practices (http://www.cdc.gov/nip/acip), the
h American Academy of Pediatrics (http://www.aap.org), and the
Hepatitis A vaccine. Hepatitis A vaccine is recommended for
children and adolescents in selected states and regions, and for American Academy of Family Physicians (http://www.aafp.org).
certain high-risk groups. Consult local public health authority and Reproduced, with permission, from recommended adulthood
MMWR 1999;48(No. RR-12):1–37. Children and adolescents in and adolescent immunization schedule—United States, Janu-
these states, regions, and high-risk groups who have not been ary–June 2004. MMWR 2004:53; Q1–4 [PMID 14733209].

be used in adults because of potentially severe 7. Diphtheria–tetanus–acellular pertussis–hepatitis

local adverse reactions. B–inactivated poliovirus (DTaP–HepB–IPV) is
3. Tetanus–diphtheria vaccine (Td) (adult) is for use licensed for use in infants ages 2, 4, and 6 months.
in persons age 7 years or older. It is less likely to
produce local reactions while still eliciting a good Dosage & Schedule of Administration
immunogenic response in this population.
4. Diphtheria–tetanus–pertussis vaccine (DTP) was The preceding preparations are given intramuscularly in a
the standard immunizing agent for healthy chil- dose of 0.5 mL. The use of jet injection may be associated
dren prior to availability of DTaP but may still be with more local reactions. See Table 9–1 for the routine
used when DTaP is unavailable. DTP is no longer schedule and Table 9–2 for immunization of children not
manufactured in the United States. appropriately immunized during the first year of life.
5. Diphtheria–tetanus–acellular pertussis vaccine
(DTaP) contains an amount of diphtheria toxins Adverse Effects
similar to DTP and is recommended as the stan- No significant adverse reactions have been associated
dard immunizing agent for healthy children. with diphtheria toxoid alone.
6. Diphtheria–tetanus–acellular pertussis and H in-
fluenzae type b conjugate vaccine (DTaP–Hib) is
licensed only for the fourth dose in the DTP–Hib Antibody Preparations
series (age 15–18 months). Earlier use may result Equine diphtheria antitoxin is available for the treat-
in suboptimal response to the Hib component. ment of diphtheria. Dosage depends on the size and lo-
254 / CHAPTER 9

Table 9–2. Catch-up immunization schedule for children and adolescents who start late or who are
>1 month behind.

Catch-up schedule for children aged 4 months–6 years

Minimum interval between doses
Dose 1
(minimum age) Dose 1 to dose 2 Dose 2 to dose 3 Dose 3 to dose 4 Dose 4 to dose 5
DTaP (6 wk) 4 wk 4 wk 6 mo 6 moa
IPV (6 wk) 4 wk 4 wk 4 wkb
HepBc (birth) 4 wk 8 wk (and 16 wk after
1st dose)
MMR (12 mo) 4 wkd
VAR (12 mo)
Hibe (6 wk) 4 wk: if 1st dose given at 4 wkf: if current ag <12 mo 8 wk (as final dose): this
age <12 mo 8 wk (as final dose)f: if dose only necessary for
8 wk (as final dose): if 1st current age ≥12 mo and children aged 12 mo–5 y
dose given at age 2nd dose given at age who received 3 doses
12–14 mo <15 mo before age 12 mo
No further doses needed: No further doses needed:
if 1st dose given at if previous dose given at
age ≥15 mo age ≥15 mo
PCVg (6 wk) 4 wk: if 1st dose given at 4 wk: if current age <12 mo 8 wk (as final dose): this
age <12 mo and current 8 wk (as final dose): if dose only necessary for
age <24 mo current age ≥12 mo children aged 12 mo–5 y
8 wk (as final dose): if 1st No further doses needed: who received 3 doses
dose given at age ≥12 for healthy children if before age 12 mo
mo or current age previous dose given at
24–59 mo age ≥24 mo
No further doses needed:
for healthy children if
1st dose given at age
≥24 mo
Catch-up schedule for children aged 7–18 years
Minimal interval between doses
Dose 1 to dose 2 Dose 2 to dose 3 Dose 3 to booster dose
Td: 4 wk Td: 6 mo Tdh: 6 mo: if 1st dose given at age <12 mo and current age <11 y
5 y: if 1st dose given at age ≥12 mo and 3rd dose given at age <7 y
and current age ≥11 y
10 y: if 3rd dose given at age ≥7 y
IPVi: 4wk IPVi: 4wk IPVb,i
HepB: 4 wk HepB: 8 wk (and 16 wk after 1st dose)
MMR: 4 wk
VARj: 4 wk
Note: A vaccine series does not require restarting, regardless of the time that has elapsed between doses.
a
Diphtheria and tetanus toxoids and acellular pertussis vaccine (DTaP): The fifth dose is not necessary if the fourth dose was given
after the fourth birthday.
b
Inactivated polio vaccine (IPV): For children who received an all-IPV or all-oral poliovirus (OPV) series, a fourth dose is not necessary if
third dose was given at age ≥4 years. If both OPV and IPV were given as part of a series, a total of 4 doses should be given, regardless of
the child’s current age.
 IMMUNIZATION / 255

cation of the diphtheritic membrane and an estimate of Preparations Available

the patient’s level of intoxication. Before using this
preparation, the presence or absence of equine serum 1. Tetanus toxoid (fluid) is used rarely—only when
sensitivity must be determined using a scratch test of a rapid immunization is desirable.
1:1000 dilution. If the test is positive, desensitization 2. Tetanus toxoid adsorbed on aluminum phosphate
must be undertaken. If negative, the doses shown in is the standard single-antigen booster toxoid.
Table 9–4 are suggested. 3. Tetanus–diphtheria vaccines (pediatric DT and
As of January 1997, diphtheria antitoxin is no adult Td) are the standard dual-antigen booster
longer commercially available in the United States but toxoids and are more often used for prophylaxis
may be obtained from the CDC. in routine wound management over the single-
antigen preparation.
TETANUS 4. DTaP with or without Hib (discussed in the sec-
tion on Hib).
When anaerobic Clostridium tetani colonizes devitalized 5. DTaP–Hep B–IPV.
tissue, the exotoxin tetanospasmin is disseminated to
inhibitory motor neurons, resulting in tetanus. Tetanus
primarily occurs in unvaccinated or inadequately vacci-
nated persons. Despite the existence of a safe and effec-
Dosage & Schedule of Administration
tive vaccine, 22 cases of tetanus were reported in the The preceding preparations are administered intramus-
United States in 2002. Tetanus-prone wounds include cularly in a dose of 0.5 mL. See Table 9–1 for the rou-
(1) puncture wounds, including those acquired due to tine schedule and Table 9–2 for vaccination of children
body piercing, tattooing, and intravenous drug abuse; not appropriately immunized during the first year of
(2) animal bites; (3) lacerations or abrasions; and life. A booster dose of Td should be scheduled at age
(4) wounds resulting from nonsterile delivery and um- 11–12 years or at age 14–16 years and every 10 years
bilical cord care (neonatal tetanus). Intravenous drug thereafter to protect against tetanus and diphtheria.
abusers are an increasing proportion of tetanus patients Table 9–5 summarizes recommendations for the use
in the United States, accounting for up to 20–40% of of tetanus prophylaxis in routine wound management.
cases in some states. Patients with non–tetanus-prone wounds should be
Tetanus toxoid is prepared by inactivating the toxin boosted if more than 10 years have elapsed since their
with formaldehyde. The protective efficacy of tetanus last immunization; those with tetanus-prone wounds
toxoid has never been measured in any large study, but should receive a booster if more than 5 years have
it is believed to be high. elapsed.

c
Hepatits B vaccine (HepB): All children and adolescents who have not been vaccinated against hepatis B should begin the hepatitis B
vaccination series during any visit. Providers should make special efforts to immunize children who were born in, or whose parents were
born in, areas of the world where hepatitis B virus infection is moderately or highly endemic.
d
Measles, mumps, and rubella vaccine (MMR): The second dose of MMR is recommended routinely at age 4–6 years, but may be given
earlier if desired.
e
Haemophilus influenzae type b (Hib) conjugate vaccine: Vaccine generally is not recommended for children aged ≥5 years.
f
Hib: If current age is <12 months and the first 2 doses were PRP-OMP (PedvaxHIB® or ComVax® [Merck]), the third (and final) dose should
be given at age 12–15 months and at least 8 weeks after the second dose.
g
Pneumococcal conjugate vaccine (PCV): Vaccine generally is not recommended for children age ≥5 years.
h
Tetanus and diphtheria toxoids (Td): For children aged 7–10 years, the interval between the third and booster dose is determined by
the age when the first dose was given. For adolescents aged 11–18 years, the interval is determined by the age when the third dose was
given.
i
IPV: Vaccine generally is not recommended for persons aged ≥18 years.
j
Varicella vaccine (VAR): Give 2-dose series to all susceptible adolescents aged ≥13 years.
Reporting adverse reactions. Clinically significant adverse events that follow vaccination should be reported to the Vaccine Adverse
Event Reporting System (VAERS). Guidance on completing a VAERS form is available at http://www.vaers.org or at telephone, 800-822-
7967. Disease reporting. Suspected cases of vaccine-preventable diseases should be reported to state or local health departments. Ad-
ditional information about vaccines, including precautions and contraindications for vaccination and vaccine shortages, is available at
http://www.cdc.gov/nip or at the National Immunization information hotline, telephone 800-232-2552 (English) or 800-232-0233
(Spanish).
Reproduced, with permission, from Recommended childhood and adolescent immunization schedule Unted States, January–June 2004.
MMWR 2004:53; Q1–4 [PMID 14733209].
256 / CHAPTER 9

Table 9–3. Guide to contraindications and precautionsa to commonly used vaccines.

Vaccine True contraindications and precautionsa Untrue (vaccines can be administered)

General for all vaccines, including Contraindications Mild acute illness with or without fever
diphtheria and tetanus toxoids Serious allergic reaction (eg, anaphylaxis) Mild to moderate local reaction (ie, swelling,
and acellular pertussis vaccine after a previous vaccine dose redness, soreness); low-grade or moderate
(DTaP); pediatric diphtheria- Serious allergic reaction (eg. anaphylaxis) fever after previous dose
tetanus toxoid (DT); adult to a vaccine component Lack of previous physical examination in well-
tetanus-diphtheria toxoid (Td); Precautions appearing person
inactivated poliovirus vaccine Moderate or severe acute illness with or Current antimicrobial therapy
(IPV); measles-mumps-rubella without fever Convalescent phase of illness
vaccine (MMR); Haemophilus Premature birth (hepatitis B vaccine is an ex-
influenzae type b vaccine (Hib); ception in certain circumstances)b
hepatitis A vaccine; hepatitis B Recent exposure to an infectious disease
vaccine; varicella vaccine; History of penicillin allergy, other nonvaccine
pneumococcal conjugate allergies, relatives with allergies, receiving
vaccine (PCV); influenza allergen extract immunotherapy
vaccine; and pneumococcal
polysaccharide vaccine (PPV)
DTaP Contraindications Temperature of <40.5°C, fussiness or mild
Severe allergic reaction after a previous drowsiness after a previous dose of
dose or to a vaccine component diphtheria toxoid-tetanus toxoid-pertussis
Encephalopathy (eg, coma, decreased level vaccine (DTP)/DTaP
of consciousness; prolonged seizures) Family history of seizuresc
within 7 days of administration of Family history of sudden infant death
previous dose of DTP or DTaP syndrome
Progressive neurologic disorder, including Family history of an adverse event after DTP or
infantile spasms, uncontrolled epilepsy, DTaP administration
progressive encephalopathy: defer DTaP Stable neurologic conditions (eg, cerebral
until neurologic status clarified and palsy, well-controlled convulsions, develop-
stabilized. mental delay)
Precautions
Fever of >40.5°C ≤48 h after vaccination
with a previous dose of DTP or DTaP
Collapse or shock-like state (ie, hypotonic
hyporesponsive episode) ≤48 h after
receiving a previous dose of DTP/DTaP
Seizure ≤3 d of receiving a previous dose of
DTP/DTaPc
Persistent, inconsolable crying lasting ≥3 h
≤48 hours after receiving a previous
dose of DTP/DTaP
Moderate or severe acute illness with or
without fever
DT, Td Contraindications
Severe allergic reaction after a previous
dose or to a vaccine component
Precautions
Guillain-Barré syndrome ≤6 wk after
previous dose of tetanus toxoid-
containing vaccine
Moderate or severe acute illness with or
without fever
(continued)
 IMMUNIZATION / 257

Table 9–3. Guide to contraindications and precautionsa to commonly used vaccines.

Vaccine True contraindications and precautionsa Untrue (vaccines can be administered)

IPV Contraindications —
Severe allergic reaction to previous dose or
vaccine component
Precautions
Pregnancy
Moderate or severe acute illness with or
without fever
MMRd Contraindications Positive tuberculin skin test
Severe allergic reaction after a previous Simultaneous TB skin testingf
dose or to a vaccine component Breast-feeding
Pregnancy Pregnancy of recipient’s mother or other close
Known severe immunodeficiency (eg, hema- or household contact
tologic and solid tumors; congenital Recipient is child-bearing–age female
immunodeficiency; long-term immuno- Immunodeficient family member or house-
suppressive therapy,e or severely symp- hold contact
tomatic human immunodeficiency virus Asymptomatic or mildly symptomatic HIV
[HIV] infection) infection
Precautions Allergy to eggs
Recent (≤11 mo) receipt of antibody-
containing blood product (specific
interval depends on product)g
History of thrombocytopenia or
thrombocytopenic purpura
Moderate or severe acute illness with or
without fever
Hib Contraindications —
Severe allergic reaction after a previous
dose or to a vaccine component
Age <6 wk
Precaution
Moderate or severe acute illness with or
without fever
Hepatitis B Contraindication Pregnancy
Severe allergic reaction after a previous Autoimmune disease (eg, systemic lupus ery-
dose or to a vaccine component thematosus or rheumatoid arthritis)
Precautions
Infant weighing <2000 gb
Moderate or severe acute illness with or
without fever
Hepatitis A Contraindications —
Severe allergic reaction after a previous
dose or to a vaccine component
Precautions
Pregnancy
Moderate or severe acute illness with or
without fever
(continued)
258 / CHAPTER 9

Table 9–3. Guide to contraindications and precautionsa to commonly used vaccines.

Vaccine True contraindications and precautionsa Untrue (vaccines can be administered)

d
Varicella Contraindications Pregnancy of recipient’s mother or other close
Severe allergic reaction after a previous or household contact
dose or to a vaccine component Immunodeficient family member or household
Substantial suppression of cellular immunity contacth
Pregnancy Asymptomatic or mildly symptomatic HIV
Precautions infection
Recent (≤11 mo) receipt of antibody- Humoral immunodeficiency (eg, agammaglob-
containing blood product (specific ulinemia)
interval depends on product)g
Moderate or severe acute illness with or
without fever
PCV Contraindication —
Severe allergic reaction after a previous
dose or to a vaccine component
Precautions
Moderate or severe acute illness with or
without fever
Influenza Contraindication Nonsevere (eg, contact) allergy to latex or
Severe allergic reaction to previous dose thimerosal
or vaccine component, including egg Concurrent administration of coumadin or
protein aminophylline
Precautions
Moderate or severe acute illness with or
without fever
PPV Contraindication —
Severe allergic reaction after a previous
dose or to a vaccine component
Precaution
Moderate or severe acute illness with or
without fever
a
Events or conditions listed as precautions should be reviewed carefully. Benefits and risks of administering a specific vaccine to a person
under these circumstances should be considered. If the risk from the vaccine is believed to outweigh the benefit, the vaccine should not
be administered. If the benefit of vaccination is believed to outweigh the risk, the vaccine should be administered. Whether and when to
administer DTaP to children with proven or suspected underlying neurologic disorders shoud be decided on a case-by-case basis.
b
Hepatitis B vaccination should be deferred for infants weighing <2000 g if the mother is documented to be hepatitis B surface antigen
(HbsAg)-negative at the time of the infant’s birth. Vaccination can commence at chronological age 1 month. For infants born to HbsAg-
positive women, hepatitis B immunoglobulin and hepatitis B vaccine should be administered at or soon after birth regardless of weight.
See text for details.
c
Acetaminophen or other appropriate antipyretic can be administered to children with a personal or family history of seizures at the time
of DTaP vaccination and every 4–6 h for 24 h thereafter to reduce the possibility of postvaccination fever (Source: American Academy of
Pediatrics. Active immunization. In: Pickering LK, ed. 2000 red book: report of the Committee on Infectious Diseases. 25th ed. Elk Grove
Village, IL: American Academy of Pediatrics, 2000).
d
MMR and varicella vaccines can be administered on the same day. If not administered on the same day, these vaccines should be sepa-
rated by ≥28 d.
e
Substantially immunosuppressive steroid dose is considered to be ≥2 wk of daily receipt of 20 mg or 2 mg/kg body weight of prednisone
or equivalent.
f
Measles vaccination can suppress tuberculin reactivity temporarily. Measles-containing vaccine can be administered on the same day as
tuberculin skin testing. If testing cannot be performed until after the day of MMR vaccination, the test should be postponed for ≥4 weeks
after the vaccination. If an urgent need exists to do skin test, do so with the understanding that reactivity might be reduced by the vaccine.
g
See text for details.
h
If a vaccinee experiences a presumed vaccine-related rash 7–25 d after vaccination, avoid direct contact with immunocompromised per-
sons for the duration of the rash.
Reproduced, with permission, from MMWR Recomm Rep 2002:51(RR-2)1–35 [PMID 11848294].
 IMMUNIZATION / 259

Table 9–4. Suggested dosing for equine 300–600 units (one or two vials) intramuscularly. Part
diphtheria antitoxin.a of the dose may be infiltrated locally.

Duration Dose Tetanus Surveillance—United States, 1998–2000. MMWR

Site of Lesion Toxic (?) (units) 2003;52 (SS-3):1 [PMID: 12825541].

Pharyngeal or ≤ 48 h NA 20,000–40,000
laryngeal PERTUSSIS
Nasopharyngeal NA NA 40,000–60,000 Pertussis is increasingly recognized as a disease affecting
Extensive or brawny ≥ 72 h Yes 80,000–120,000 older children and adults, including fully vaccinated
swelling of the neck persons with waning immunity. Maintaining vaccina-
tion in young infants will protect against severe disease
Cutaneous NA NA 20,000–40,000
in this age group, but because booster vaccination is not
a
NA = Not applicable. approved for children over age 7 years, a reservoir of
disease among those with waning immunity is a contin-
uing problem.
Adverse Effects Pertussis vaccines currently used in the United
States for initial immunization contain purified compo-
Significant reactions to tetanus toxoid, historically an nents of pertussis antigens. The DTaP preparations
extremely safe preparation, are very unusual. Anaphy- have a protective efficacy of about 70–90% after three
laxis, Guillain–Barré syndrome, and brachial neuritis doses, depending on the source. Further epidemiologic
related to tetanus toxoid are extremely rare. evidence of the efficacy of pertussis vaccine is provided
by the observation of a large increase in pertussis cases
Antibody Preparations in Great Britain and Japan after those countries re-
duced or abandoned use of the vaccine.
Tetanus immune globulin (TIg) (human) is indicated
in the management of tetanus-prone wounds in indi-
viduals who have had an uncertain number or fewer Preparations Available
than three tetanus immunizations with tetanus toxoid,
as described earlier. Persons fully immunized with at 1. DTaP
least three doses do not require TIg, regardless of the 2. DTaP–Hib
nature of their wounds (see Table 9–5). The dose is 3. DTaP–HepB–IPV

Table 9–5. Summarized recommendations for the use of tetanus prophylaxis

in routine wound management—Advisory Committee on Immunization Practices
(ACIP), 1991.

Clean, Minor Wounds All Other Woundsa

History of Adsorbed Tetanus Toxoid Tdb or DT TIGc Td or DT TIG
Unknown or < 3 doses Yes No Yes Yes
≥ 3 dosesd Noe No Nof No
a
Such as, but not limited to, wounds contaminated with dirt, feces, soil, or saliva; puncture wounds; avulsions; and
wounds resulting from missiles, crushing, burns, or frostbite.
b
For children over age 7 y the diphtheria and tetanus toxoids and acellular pertussis vaccines (DTaP)—or pediatric
diphtheria and tetanus toxoids (DT), if pertussis vaccine is contraindicated—is preferred to tetanus toxoid (TT)
alone. For persons age 7 y or older, the tetanus and diphtheria toxoids (Td) for adults is preferred to TT alone.
c
TIG-tetanus immune globulin.
d
If only three doses of fluid toxoid have been received, a fourth dose of toxoid—preferably an adsorbed toxoid—
should be administered.
e
Yes, if more than 10 years have elapsed since the last dose.
f
Yes, if more than 5 years have elapsed since the last dose. More frequent boosters are not needed and can accen-
tuate side effects.
From: MMWR Morb Mortal Wkly Rep 1998;47(SS-2):11.
260 / CHAPTER 9

Dosage & Schedule of Administration DIPHTHERIA–TETANUS–PERTUSSIS

Each of the available preparations is administered in a VACCINE
dose of 0.5 mL intramuscularly. See Table 9–1 for the DTP has been used for the vaccination of healthy in-
routine schedule and Table 9–2 for vaccination of those fants against diphtheria, tetanus, and pertussis for more
children not appropriately immunized during the first than 40 years. It has the combined clinical efficacy of
year of life. the three single-dose preparations, and the efficacy of
pertussis vaccine may even be enhanced by the adjuvant
effect of the diphtheria and tetanus toxoids. DTP is no
Adverse Effects longer manufactured in the United States.
A large number of adverse reactions have been attrib- As of 1999, DTaP is the recommended vaccination
uted to pertussis vaccine. These can be divided into against diphtheria, tetanus, and pertussis for all doses in
three categories: local reactions, mild to moderate sys- the routine vaccination series (the DTaP–Hib combi-
temic reactions (that occur in up to half of children), nation vaccine can only be used as the fourth dose).
and severe systemic reactions. The estimated rates of Two basic types of acellular (DTaP) vaccines have
these reactions within the first 48 hours after vaccina- been studied. The T-type vaccines are produced by ex-
tion are shown in the following discussion. The only traction and purification of B pertussis cultures. In con-
absolute contraindications to the further use of pertus- trast, the B-type vaccines contain combinations of per-
sis vaccine are an anaphylactic reaction to the vaccine or tussis toxin (PT), filamentous hemagglutinin (FHA),
a severe acute neurologic illness within 7 days after vac- pertactin (Prn), and fimbriae (Fim). It has been hy-
cination (see Table 9–3). Precaution is urged for the pothesized that immunity against PT alone may be suf-
following associations: a convulsion within 3 days ficient to protect against pertussis, but this view has
(1:1750); persistent, severe, inconsolable screaming or been challenged, and it has been claimed that antibod-
crying for over 3 hours (1:100); a hypotonic–hypore- ies against FHA, Prn, and Fim may be required for op-
sponsive episode within 48 hours (1:1750); and an un- timal protection.
explained temperature rise to 40.5°C within 48 hours Efficacy trials of various acellular pertussis vaccines in
(1:330). Sweden, Germany, Italy, and Senegal have established a
Controversy continues regarding the causation of se- 2- to 10-fold lower frequency of minor adverse events
rious neurologic illness by pertussis vaccine. The only and reduced rates of more serious events (hypotonic–hy-
large-scale case-controlled study with enough statistical poresponsive episodes, persistent crying, temperatures
power to examine this issue—the British National higher than 40°C, and seizures) compared with the
Childhood Encephalopathy Study (NCES)—has mini- whole-cell vaccine, good immunogenicity, and a protec-
mized any potential relationship. tive efficacy ranging from 59% to 89%. Tripedia (Aven-
It was calculated that although the attributable risk tis Pasteur, Inc) is licensed for use as the complete five-
for serious acute neurologic injury ranges from less than dose series. Infanrix (GlaxoSmithKline) and
1:1,000,000 to 1:140,000, the risk for permanent brain DAPTACEL (Aventis Pasteur) are approved for use for
damage is even lower, if indeed there is any risk. This the first four doses of the five-dose series. Licensure of
reassessment, along with new studies, has led the AAP, other DTaP vaccines as a five-dose series is anticipated.
the Canadian National Advisory Committee, and the For children with adverse reactions in the precaution
British Pediatric Association to conclude that pertussis category to DTP, DTaP may be substituted. In those
vaccine has not been proven to cause brain damage and with a true contraindication, neither vaccine should be
to reaffirm the safety and effectiveness of routine per- used. Studies are underway to evaluate the efficacy and
tussis vaccine in immunization programs for infants safety of acellular vaccines containing reduced quantities
and children. of pertussis antigens for use as boosters in adolescents.
The 1991 National Academy of Sciences Institute of
Medicine report concluded that the vaccine was causally
related to only four adverse effects: acute encephalopa- Preparations Available
thy, the range of excess risk being nil to 10.5 per million
immunizations; shock (and an unusual shock-like state), 1. DTaP (Tripedia [Aventis Pasteur]) contains diph-
3.5–291 cases per 100,000 immunizations; anaphylaxis, theria toxoid, tetanus toxoid, PT, and FHA.
2 cases per 100,000 injections of DTP; and protracted, 2. DTaP (Infanrix [GlaxoSmithKline]) contains
inconsolable crying, 0.1–6% of recipients. Thus, al- diphtheria toxoid, tetanus toxoid, PT, FHA, and
though epidemiologic evidence may be consistent with a Prn.
causal relationship, pertussis toxin has no proven role in 3. DTaP (DAPTACEL) contains PT, FHA, per-
severe neurologic reactions to DTP. tactin, and fimbriae types 2 and 3.
 IMMUNIZATION / 261

4. DTaP–Hib (TriHIBit [Aventis Pasteur]) has been than 18,000 in 1954 to 0–10 per year currently. As of
licensed for use as the fourth dose (booster) in the November 2003, 556 polio cases were reported world-
DPT immunization series. wide since the beginning of the year, from the Indian
5. DTaP–Hep B–IPV (Pediarix) contains PT, FHA, subcontinent (India, Pakistan, and Afghanistan), the
and pertactin and is licensed for the first three Middle East (Lebanon and Egypt), and west Africa
doses beginning at 2 months of age. (Burkina Faso, Nigeria, Chad, Togo, Niger, and
Ghana). The World Health Organization (WHO) has
reset the target of 2008 for global eradication of po-
Dosage & Schedule of Administration liomyelitis. The injectable poliovirus vaccine of en-
DTaP is administered in a dose of 0.5 mL intramuscu- hanced potency (IPV-E), which has a higher content of
larly. See Table 9–1 for the routine schedule and Table antigens than the old IPV, is the only vaccine against
9–2 for the procedure in children not immunized during poliomyelitis available in the United States.
the first year. The ACIP/AAP and AAFP recommend a IPV is incapable of causing poliomyelitis by virtue of
series of five vaccinations before age 7 years (at 2, 4, 6, being inactivated, whereas OPV can do so rarely. The rate
and 15–18 months and at 4–6 years). Whenever feasible, of this in the United States was 1 case of paralytic disease
the same brand of DTaP should be used for all doses. per 760,000 first doses of OPV distributed. Ninety-three
percent of recipient cases and 76% of all vaccine-associ-
ated paralytic poliomyelitis (VAPP) occurred after admin-
Adverse Effects istration of the first or second dose of OPV. The risk of
Local reactions, fever, and other mild systemic effects paralysis in the immunodeficient recipient may be as
occur with one fourth to two thirds the frequency noted much as 6800 times that in normal subjects. However,
following whole-cell DTP vaccination. Moderate to se- IPV cannot protect against intestinal infection with wild
vere systemic effects, including fever of 40.5°C, persis- virus, as OPV does. IPV cannot produce so-called sec-
tent inconsolable crying lasting 3 hours or more, and ondary vaccination of close contacts when vaccine-strain
hypotonic–hyporesponsive episodes, are less frequent virus is shed into the environment. IPV, however, pro-
than with whole-cell DTP. These are without sequelae. duces a much higher serologic response than OPV, a
Severe neurologic effects have not been temporally asso- higher booster response at lower prevaccination levels,
ciated with DTaP vaccinations in use in the United and an equivalent mucosal response. IPV has the practical
States. Data are limited regarding differences in reacto- advantage of not requiring freezing for storage, as OPV
genicity among currently licensed acellular pertussis vac- does. On the basis of these data, the ACIP recommends
cines. With all currently licensed DTaP vaccines, reports that all children in the United States receive an all-IPV
of the frequency and magnitude of substantial local re- schedule (four doses of IPV). However, the mass adminis-
actions at injection sites have increased with increasing tration of OPV requires no needles and syringes.
dose number (including swelling of the thigh or entire Completely immunized adult visitors to areas of
upper arm after receipt of fourth and fifth doses). continuing wild-type poliovirus circulation should re-
ceive a booster dose of IPV-E. Unimmunized or incom-
Braun M et al: Infant immunization with acellular pertussis vac- pletely immunized adults and children should have re-
cines in the US: Assessment of the first two years’ data from ceived two (preferably three) doses of the vaccine prior
the Vaccine Adverse Event Reporting System (VAERS). Pedi- to travel to these and other areas with circulation of
atrics 2000;106:e51 [PMID: 20473510]. wild-type or vaccine-type virus.
Pichichero M et al: Safety and immunogenicity of six acellular per-
tussis vaccines and one whole-cell pertussis vaccine given as a
fifth dose in four- to six-year-old children. Pediatrics Preparations Available
2000;105:e11 [PMID: 20085384].
1. Inactivated IPV-E (IPOL) [Aventis Pasteur] con-
Use of Diphtheria Toxoid-Tetanus Toxoid-Acellular Pertussis Vac-
cine as a Five-Dose Series: Supplemental recommendations of
tains antigens of types 1, 2, and 3 poliovirus.
the Advisory Committee on Immunization Practices. 2. DTaP-HepB-IPV (PEDIARIX), [GlaxoSmithKline
MMWR Morb Mortal Wkly Rep 2000;49(RR13):1 [PMID: Biologicals] contains diphtheria and tetanus tox-
11106289]. oids and acellular pertussis adsorbed (DTaP),
hepatitis B (HepB), and inactivated poliovirus
POLIOMYELITIS vaccine (IPV-E)
Vaccines directed against poliovirus infections have Dosage & Schedule of Administration
eliminated the naturally occurring disease in developed
countries. In the United States, the number of reported IPV-E is administered in a dose of 0.5 mL subcuta-
cases of paralytic poliomyelitis has fallen from more neously. The DTaP–HepB–IPV combination vaccine
262 / CHAPTER 9

can be used in the primary series at 2, 4, and 6 months Given the efficacy rate of the current vaccine (>
and can be used to complete the primary series. It can 95%), the elimination of indigenous measles from the
be administered with Hib and pneumococcal conjugate Americas is an attainable public health goal. Only
(PCV) vaccines at separate sites, but is not approved for 116 measles cases (1 death) were reported in the United
the fourth dose of IPV or fourth and fifth doses of States during 2001. It is believed there is no endemic
DTaP. circulation of measles in the Americas. In 2002 only
Venezuela and Columbia had indigenous transmission.
Adverse Effects Recently reports in the medical and lay press have
suggested a possible association between MMR vaccina-
IPV has essentially no adverse effects associated with it tion, autism, and gastrointestinal inflammation. This
other than possible rare hypersensitivity reactions to association, has been refuted because of the limited
trace quantities of antibiotics. The DTaP–HepB–IPV number of patients studied, methods of case and con-
combination has similar rates of local and systemic ad- trol selection, and means of determining developmental
verse responses to three doses administered separately regression. Several large epidemiologic studies subse-
except for fever, which is higher in the combination quently found no association between MMR vaccina-
vaccinated children. tion and either autism or bowel inflammation. Also, no
evidence has been found to support the separate admin-
Aristegui J et al: Comparison of the reactogenicity and immuno- istration of measles, mumps, and rubella vaccines (as
genicity of a combined diphtheria, tetanus, acellular pertussis,
hepatitis B, inactivated polio (DTPa–HBV–IPV) vaccine,
opposed to the MMR combination). However, the in-
mixed with the Haemophilus influenzae type b (Hib) conju- fluence of the lay press is most profound in the United
gate vaccine and administered as a single injection, with the Kingdom, where low vaccination rates with measles
DTPa-IPV/Hib and hepatitis B vaccines administered in two vaccine has lead to a resurgence of measles, with a dis-
simultaneous injections to infants at 2, 4, and 6 months of tinct possibility that it will become an endemic disease
age. Vaccine 2003;21:3593 [PMID: 12922087]. in the United Kingdom.
Centers for Disease Control: FDA licensure of diphtheria and
tetanus toxoids and acellular pertussis adsorbed, hepatitis B
(recombinant), and poliovirus vaccine combined, (PEDI- Preparations Available
ARIX) for use in infants. MMWR Morb Mortal Wkly Rep
2003;52:203. The Moraten strain is a live attenuated vaccine derived
Pichichero ME et al: Impact of a birth dose of hepatitis B vaccine from the Edmonston B strain after multiple passages in
on the reactogenicity and immunogenicity of chick embryo tissue culture. The Moraten strain is
diphtheria–tetanus–acellular pertussis–hepatitis B–inactivated available as a monovalent vaccine or in combination
poliovirus–Haemophilus influenzae type b combination vacci-
nation. Pediatr Infect Dis J 2002;21:854 [PMID: with rubella vaccine (MR) or in the MMR combina-
12352809]. tion.
Schmitt HJ et al: The safety, reactogenicity and immunogenicity of
a 7-valent pneumococcal conjugate vaccine (7VPnC) concur-
rently administered with a combination DTaP-IPV-Hib vac- Dosage & Schedule of Administration
cine. Vaccine 2003;21:3653 [PMID: 12922095].
A. ROUTINE VACCINATION
Measles vaccine should be given as MMR at
MEASLES 12–15 months and again at 4–6 years of age. A dose of
In the 20 years after the 1963 introduction of measles 0.5 mL, whether alone or in combination, should at
vaccination in the United States, the annual number of least be given subcutaneously. The second dose of
reported cases decreased from 500,000 to fewer than MMR is recommended at school entry to help prevent
1500. However, between 1989 and 1991 there was a school-based measles outbreaks. Children not reimmu-
resurgence of measles, with 55,622 cases reported. The nized at school entry should receive their second MMR
major reasons for the increase in cases and the resulting by 11–12 years of age. If an infant receives the vaccine
deaths were failure to provide vaccine to preschool chil- before 12 months of age, two doses are required to
dren aged 15 months or older, the presence in the com- complete the series, the first after at least 12 months of
munity of susceptible children younger than age age and the second at least 1 month later. Ig interferes
15 months, and the growing number of appropriately with the immune response to the attenuated vaccine
vaccinated but nonimmune individuals (primary vac- strains of MMR. Therefore, MMR immunization after
cine failures: 2–10%) in schools and colleges. These Ig administration should be deferred by 3 to
reasons have led to recommendations for a two-dose 11 months, depending on the type of Ig product re-
vaccination schedule at 12–15 months and at 4–6 years ceived. Consult the American Academy of Pediatrics’
of age. 2003 Red Book for specific recommendations.
 IMMUNIZATION / 263

B. VACCINATION OF TRAVELERS 3 months can receive MMR safely. Children with

People traveling abroad should be immune to measles. minor acute illnesses (including febrile illnesses),
In high-risk areas, age at primary vaccination should be nonanaphylactic egg allergy, or a history of tuberculosis
as soon as possible after the first birthday (ie, at should be immunized. Monovalent measles or MMR
12 months). However, younger infants 6–11 months of may be safely administered simultaneously with other
age traveling to high-risk areas should receive the routine pediatric immunizations.
monovalent vaccine followed by two doses at
12–15 months given at least 4 weeks apart, and should Adverse Effects
complete the series at 4–6 years.
Between 5% and 15% of vaccinees become febrile to
C. REVACCINATION UNDER OTHER CIRCUMSTANCES 39.5°C or higher about 6–12 days following vaccina-
tion, lasting approximately 1–2 days, and 5% may de-
Persons entering college and other institutions for edu- velop a transient morbilliform rash. Transient throm-
cation beyond high school, medical personnel begin- bocytopenia occurs in 1:25,000 to 1:100,000 persons.
ning employment, and persons traveling abroad should Encephalitis and other CNS conditions such as aseptic
have documentation of immunity to measles, defined as meningitis and Guillain–Barré syndrome are reported
receipt of two doses of measles vaccine after their first to occur at a frequency of 1 case per 3 million doses in
birthday, birth before 1957, or a documented measles the United States. This rate is lower than the rate of
history or immunity. these conditions in the general unvaccinated popula-
tion, implying that the relationship between them and
D. OUTBREAK CONTROL measles vaccination may not be causal. MMR vaccina-
A community outbreak is defined as a single docu- tion is associated with an increased risk of febrile
mented case of measles. Control depends on immediate seizures 8 to 14 days after vaccination, but no subse-
protection of all susceptible persons (defined as persons quent long-term complications have been seen. A re-
who have no documented immunity to measles in the cent study found an increase in female mortality in
affected community. In the case of unvaccinated indi- Guinea Bissau after receiving the high titered measles
viduals, the following recommendations hold: (1) age vaccine at less than 6 months of age.
6–11 months, monovalent measles vaccine (or MMR)
if cases are occurring in children younger than age Antibody Preparations
1 year, followed by two doses of MMR at age
12–15 months and again at age 4–6 years; and (2) age If a child is seen within 72 hours after exposure, vacci-
12 months or older, MMR followed by revaccination at nation is the preferred method of protection. If vaccine
4–6 years. A child with an unclear or unknown vaccina- is contraindicated, Ig, given intramuscularly at a dose of
tion history should be reimmunized with MMR. Any- 0.25 mL/kg (0.5 mL/kg in immunocompromised pa-
one with a known exposure who is not certain of receiv- tients; maximum dose in either circumstance is 15 mL),
ing two doses of MMR should receive an additional is effective in preventing or modifying measles if it is
dose. Unimmunized persons who are not immunized given within 6 days after exposure. Measles vaccine
within 72 hours of exposure should be excluded from should be given 5 months later to children receiving the
contact with potentially infected persons until at least 0.25 mg/kg dose and 6 months later for the higher
2 weeks after the onset of rash of the last case of dose. For children receiving regular IgIV, a dose of
measles. 100–400 mg/kg should be adequate for measles pro-
Measles vaccination is contraindicated in pregnant phylaxis for exposures occurring within 3 weeks of the
women, women intending to become pregnant within last dose.
the next 28 days, immunocompromised persons (ex-
cept those with asymptomatic HIV or those with HIV Aaby P et al: Differences in female–male mortality after high-titer
infection who are not severely immunocompromised), measles vaccine and association with subsequent vaccination
and persons with anaphylactic egg or neomycin allergy. with diphtheria–tetanus–pertussis and inactivated poliovirus:
It is also contraindicated in children receiving high- Reanalysis of West African studies. Lancet 2003;361:
dose steroid therapy (greater than or equal to 2183 [PMID: 14643138].
2 mg/kg/d, or 20 mg/day total, for longer than 14 days) Jansen VA et al: Measles outbreaks in a population with declining
vaccine uptake. Science 2003;301:804 [PMID: 12907792].
with the exception of those receiving physiologic re-
placement doses. In these patients, an interval of Melvin AJ, Mohan KM: Response to immunization with measles,
tetanus, and Haemophilus influenzae type b vaccines in chil-
1 month between cessation of steroid therapy and vac- dren who have human immunodeficiency virus type 1 infec-
cination is sufficient. Leukemic patients who have been tion and are treated with highly active antiretroviral therapy.
in remission and off chemotherapy for at least Pediatrics 2003;111:e641[PMID: 12777579].
264 / CHAPTER 9

Stein CE et al: The global burden of measles in the year 2000—A Adverse Effects
model that uses country-specific indicators. J Infect Dis
2003;187 (Suppl) 1:S8 [PMID: 12721886]. Reactions after mumps vaccination are rare and include
Stratton K et al (eds): Institute of Medicine, Immunization Safety parotitis, low-grade fever, and orchitis. In 1989, a na-
Review Committee: Immunization Safety Review: Thimerosal- tionwide surveillance of neurologic complications after
Containing Vaccines and Neurodevelopmental Disorders. Na- a mumps vaccine was conducted in Japan. At least
tional Academies Press, 2001.
311 cases of mild aseptic meningitis (96 had vaccine-
Wilson K et al: Association of autistic spectrum disorder and the type mumps virus in the cerebrospinal fluid) occurred
measles, mumps, and rubella vaccine: A systematic review of
current epidemiological evidence. Arch Pediatr Adolesc Med among 630,157 recipients. There were no sequelae.
2003;157:628 [PMID: 12860782]. Aseptic meningitis may be more common than was pre-
viously suspected (1–4 cases per 10,000 vaccinations).
This rate was also found in Brazil but not in Germany,
where different vaccine strains were used.
MUMPS
Mumps vaccine has dramatically reduced this infection
and its complications in the United States, from
Nolan T et al: Reactogenicity and immunogenicity of a live attenu-
185,691 cases in 1967 to 226 cases in 2001. Most re- ated tetravalent measles–mumps–rubella–varicella (MMRV)
ported cases of mumps are in children age 5–14 years. vaccine. Vaccine 2002;21:281 [PMID: 12450703].
Schlipkoter U et al: Surveillance of measles–mumps–rubella vac-
cine-associated aseptic meningitis in Germany. Infection
Preparations Available 2002;30:351 [PMID: 12478324].

The Jeryl Lynn Strain is the only mumps vaccine avail-

able in the United States. It is prepared from virus iso-
lated from a child and passaged in embryonated eggs RUBELLA
and in chick embryo tissue culture. The vaccine is avail-
able as a monovalent vaccine and, in its preferred form, The use of rubella vaccine represents an important
in the MMR combination. deviation from the public health philosophy under-
lying the other vaccines discussed in this chapter. It is
not intended to protect individuals from rubella infec-
Dosage & Schedule of Administration tion but rather to prevent the serious consequences of
rubella infection during pregnancy: miscarriage, fetal
Mumps vaccine is given to children in the combination demise, and congenital rubella syndrome (CRS). CRS
vaccine MMR at age 12–15 months and again at age is a group of birth defects including deafness, cataracts,
4–6 years. Despite the greater than 95% efficacy of the heart defects, and mental retardation. In the United
mumps vaccine, outbreaks have been reported in highly States, the approach has been to vaccinate young
vaccinated populations. Most cases were attributed to children. The intent is to reduce transmission to sus-
primary vaccine failure. It is hoped that the two-dose ceptible women of childbearing age via a herd immu-
schedule (with the second dose given before school nity effect. Immunity lasts for at least 15 years. Other
entry) will prevent school-based outbreaks. As monova- countries, notably the United Kingdom, vaccinate
lent vaccine, it is safe and effective if given after the first pubertal girls (age 11–14 years). The relative efficacy
birthday. The dose of either monovalent or MMR vac- of these two strategies in the prevention of CRS is un-
cine is 0.5 mL subcutaneously. Use of the monovalent clear.
vaccine is limited to susceptible individuals with proven With the use of rubella vaccines since 1970, rubella
immunity to the other constituents of MMR. Revacci- incidence rates have declined more than 99%. Twenty-
nation with mumps vaccine or any of the vaccines three cases were reported during 2001 in the United
in MMR is not harmful; therefore, anyone with an States. However, approximately 10% of young adults
unclear vaccination history should be immunized are now susceptible to rubella. Outbreaks of rubella
with MMR. The same recommendations and con- continue to occur in the United States, despite wide-
traindications apply to mumps vaccine as to measles spread use of MMR, but the epidemiology of rubella
vaccine, except as relates to travel. Because maternal an- transmission has changed in the past decade. Currently
tibody to mumps is present in most infants, and the most cases of rubella are seen in foreign-born adults,
disease is not severe in infancy, infants younger than and outbreaks have occurred in poultry and meat pro-
12 months of age traveling to endemic countries need cessing plants that employ many foreign-born workers.
not routinely be given mumps vaccine (see previous dis- Similarly, 92% of infants with CRS during
cussion). 1997–1999 were born to foreign-born mothers.
 IMMUNIZATION / 265

Preparations Available Centers for Disease Control and Prevention: Control and preven-
tion of rubella: Evaluation and management of suspected out-
The RA 27/3 strain is the only vaccine available in the breaks, rubella in pregnant women, and surveillance for con-
United States. It is grown in human diploid cells. The genital rubella syndrome. MMWR Morb Mortal Wkly Rep
RA 27/3 strain is available as a monovalent vaccine, in 2001;50(RR-12):1 [PMID: 11475320].
combined preparations with measles vaccine, or in Centers for Disease Control and Prevention: Revised ACIP recom-
mendation for avoiding pregnancy after receiving a rubella-
measles and mumps vaccines. In most circumstances, containing vaccine. MMWR Morb Mortal Wkly Rep
MMR vaccination is the recommended means of im- 2001;50:1117.
munizing against rubella. Danovaro-Holliday MC et al: Identifying risk factors for rubella
susceptibility in a population at risk in the United States. Am
Dosage & Schedule of Administration J Public Health 2003;93:289 [PMID: 12554568].
Geier DA, Geier MR: A one-year follow-up of chronic arthritis fol-
Either the monovalent or combined form should be ad- lowing rubella and hepatitis B vaccination based upon analy-
ministered subcutaneously in a dose of 0.5 mL. Current sis of the Vaccine Adverse Events Reporting System (VAERS)
practice is to administer MMR vaccine at age database. Clin Exp Rheumatol 2002;20:767 [PMID:
12–15 months and again at 4–6 years. A person can be 12508767].
considered immune only with documentation of either
serologic immunity to rubella or vaccination with at
least one dose of rubella vaccine after age 1 year, or if
born before 1957. A clinical diagnosis of rubella is un- HAEMOPHILUS INFLUENZAE
acceptable. Susceptible pubertal girls and postpubertal TYPE B INFECTION
women identified by premarital or prenatal screening
should also be immunized. Whenever rubella vaccina- The first vaccine licensed against Haemophilus influen-
tion is offered to a woman of childbearing age, preg- zae type b in the United States, composed of the capsu-
nancy should be ruled out and the woman advised to lar polysaccharide of H influenzae type b polyribosyl
prevent conception for 3 months following vaccination. ribitol phosphate (PRP), was moderately effective in
If a pregnant woman is vaccinated or becomes pregnant preventing H influenzae type b disease in children older
within 3 weeks of vaccination, she should be counseled than 18 months of age. Conjugation of the PRP with
regarding the risk to her fetus. It has been estimated protein carriers confers T-cell–dependent characteristics
that the risk of serious malformations attributable to on the vaccine and enhances the immunologic response
giving the RA 27/3 vaccine to pregnant women is from to PRP in infancy. Since 1993, the incidence of H in-
zero to 1.6%. This is much less than the 20–85% risk fluenzae type b invasive disease in children younger
of CRS after maternal infection in the first trimester of than age 5 years has declined 99% in the United States.
pregnancy. All susceptible adults in institutional set- Three conjugate vaccines are currently available in
tings (including colleges), day care center personnel, the United States (Table 9–6). Studies in infants ages
military personnel, and hospital and health care person- 2–6 months demonstrated the immunogenicity of each
nel should be immunized. of these vaccines except DTaP-Hib, which is approved
only for the fourth (booster) dose. A geometric mean
titer (GMT) of 1 mcg/mL of antipolysaccharide anti-
Adverse Effects body 3 weeks postvaccination has correlated with long-
In children, adverse effects from rubella vaccination are term protection from invasive disease. After three doses
very unusual. Between 5% and 15% of children de- at ages 2, 4, and 6 months, each of the three vaccines
velop rash, fever, or lymphadenopathy 5–12 days after (see Table 9–6) produces protective levels of antibody.
vaccination. Rash also occurs alone or as a mild rubella Regardless of the vaccine used in the primary series,
illness in 2–4% of adults. Arthralgia and arthritis occur booster vaccination of children older than age
in 10–25% of adult vaccinees, as opposed to only 12 months with any licensed vaccine elicits an adequate
0–2% of 6- to 16-year-old vaccinees. Chronic arthritis response. Furthermore, each vaccine is immunogenic as
may be causally related to RA 27/3 vaccinations and oc- a single dose given after age 15 months. Limited infor-
curs more often in women age 45 or older, starting mation on interchangeability of different H influenzae
10–11 days after the vaccination and lasting for up to a type b vaccines suggests that any combination of the H
year. Rare complications include peripheral neuritis and influenzae type b conjugate vaccines will provide ade-
neuropathy, transverse myelitis, and diffuse myelitis. quate protection.
If PRP-OMP is administered as only part of a pri-
Castillo-Solorzano C et al: New horizons in the control of rubella mary series, the recommended number of doses to
and prevention of congenital rubella syndrome in the Ameri- complete the series is determined by the other Hib con-
cas. J Infect Dis 2003;187 (Suppl) 1:S146 [PMID: 12721906]. jugate vaccine.
266 / CHAPTER 9

Table 9–6. Haemophilus influenzae type b conjugate vaccines for children.

Vaccine Trade Name and Manufacturer Polysaccharide Linkage Protein Carrier

HbOC HibTITER (Wyeth-Lederle-Praxis) Small None CRM197 mutant Corynebacterium diphtheriae
toxin protein
PRP-OMP PedvaxHIB (Merck & Co.) Medium Thioether Neisseria meningitidis outer membrane pro-
tein complex
PRP-T ACTHIB (Aventis Pasteur) Large Six-carbon Tetanus toxoid
PRP-T TriHIBit (Aventis Pasteur) Large Six-carbon See above for PRP-T
DTaP
PRP-OMP- Comvax (Merck & Co.) Medium Thioether See above for PRP-OMP
Hepatitis B

Because of the differences in the immunogenic re- responses are comparable to those for HbOC and DTP
sponse and the different regimens used in these trials, or PRP-OMP and HepB administered separately. In
the recommendations for use of HbOC, PRP-T, and addition, PRP-T-DTaP (TriHIBit) has been licensed
PRP-OMP differ and are summarized in Table 9–7. for use as a booster. Use in the primary series may result
Regardless of the regimen implemented, it is crucial to in insufficient titers to Hib. If the exact conjugate vac-
complete the series, because cases of invasive H influen- cine previously administered is unknown, it is recom-
zae type b disease have been described in partially vacci- mended that at least three doses of conjugate vaccine be
nated children. Given the increased risk of disease in administered to children between ages 2 and 6 months.
early infancy among Native American and Alaskan Na- Unvaccinated or partially vaccinated children younger
tive children, the use of PRP-OMP for the first dose in than age 2 years who experience invasive H influenzae
the series is recommended because high antibody re- type b disease should receive a complete series of vacci-
sponses occur after the first dose in this vaccine. nations. Children older than age 2 years mount an ade-
The FDA has licensed PRP-OMP-HepB (Comvax) quate immune response to invasive H influenzae type b
for use in infants as young as 6 weeks of age. Antibody disease and do not require further vaccinations. Unim-

Table 9–7. Schedule for Haemophilus influenzae type b conjugate vaccine administration.

Vaccine Age at First Vaccination Primary Series (Same Vaccine If Possible) Booster (Any Conjugate Vaccine)
a
HbOC or PRP-T 2–6 mo Three doses 2 mo apart 12–15 mo
7–11 mo Two doses 2 mo apart 12–19 mo
12–14 mo One dose 2 mo later
15–59 mo One dose ...
b
PRP-OMP 2–6 mo Two doses 2 mo apart 12–15 mo
7–11 mo Two doses 2 mo apart 12–18 mo
12–14 mo One dose 2 mo later
15–59 mo One dose ...
a
A booster dose of DTP or DTaP should be administered at 4–6 y of age, before kindergarten or elementary school. This booster is not
necessary if the fourth vaccinating dose was administered after the fourth birthday. DTaP-Hib (TriHIBit) is only approved for the fourth
(booster) dose.
b
Comvax may be administered by the same schedule for primary immunization as PRP-OMP. It should only be used in infants of hepatitis
B-negative mothers. If the series is started late, three doses should be given if started in infants (≤ 10 mo), two doses if started at 11–14
mo, and one dose if started at age 15–71 mo. However, three doses of hepatitis B vaccine are required regardless of age of starting immu-
nization.
 IMMUNIZATION / 267

munized children age 5 years or older with a chronic ill- pneumococci in day care centers. Postlicensure, its rou-
ness known to be associated with invasive H influenzae tine implementation in infancy has led not only to a
type b disease, such as sickle cell anemia and asplenia, remarkable 92% reduction in invasive disease in chil-
should be given a single dose of any of the licensed con- dren younger than 2 years, but also a 46% reduction
jugate vaccines. against vaccine type in adults and 47% effectiveness
against disease in the elderly caused by the types in the
Preparations Available vaccine.
Subsequently studies with a heptavalent pneumo-
See Table 9–6. coccal polysaccharide-meningococcal outer membrane
protein complex conjugate vaccine (PnOMPC) in Fin-
Dosage & Schedule of Administration land demonstrated an overall vaccine efficacy of 56%
against acute otitis media (AOM) in children age
The dose for all preparations is 0.5 mL, given intramus- 6–24 months, with vaccine serotype-specific efficacy
cularly. ranging from 37–82%, but a trial in 383 Dutch chil-
dren with recurrent AOM showed no efficacy in this
Adverse Effects population. A trial in South Africa of a nonavalent
Fewer than 5% of those immunized develop systemic pneumococcal polysaccharide vaccine (PnCRM9) re-
reactions (including fever) to the vaccine. About 25% duced invasive disease by 83% in children without HIV
of recipients develop mild transient local reactions. Ad- and 65% in those with HIV. However, it only reduced
verse effects following the second dose of PRP-OMP radiographic pneumonia by 20%
are more frequent than following the first dose and Universal immunization of all infants with PCV7 is
more frequent following the third dose of HbOC than now recommended, with four doses given at 2, 4, 6,
following the first two doses. and 12–15 months of age. Children age 24 to
59 months at high risk of invasive pneumococcal dis-
ease should receive both the conjugate vaccine (PCV7)
Breukels MA et al: Immunological characterization of conjugated
Haemophilus influenzae type b vaccine failure in infants. Clin and the 23-valent polysaccharide vaccine (23PS). Al-
Infect Dis 2001;32:1700 [PMID: 21259605]. though definitive data about using PCV7 and 23PS in
Edwards KM, Decker MD: Combination vaccines. Infect Dis Clin combination are not available for invasive disease, it
North Am 2001;15:209 [PMID: 21197372]. does reduce AOM in one study. It is also known that
immunization with PCV7 induces immunologic mem-
ory that is boosted by some of the serotypes in 23PS.
PNEUMOCOCCAL INFECTIONS Additionally, 23PS provides coverage against a broader
Streptococcus pneumoniae is the most common cause of range of serotypes than does PCV7. Recommendations
invasive bacterial infection in children, with most inva- for using PCV7 and 23PS in high-risk children age
sive disease occurring in children younger than age 24–59 months are found in Table 9–8. Children at
2 years. Prior to the year 2000, the available pneumo- high risk of invasive pneumococcal disease include
coccal polysaccharide vaccine had an overall efficacy of those with chronic cardiovascular, pulmonary (cystic fi-
57%, was not effective in children younger than brosis but not asthma), or liver diseases, and those with
2 years, and therefore was only indicated for certain anatomic and functional asplenia (including sickle cell
high-risk children age 2 years or older. However, the disease), nephrotic syndrome, chronic renal failure, dia-
seven most common serotypes of pneumococcus that betes mellitus, cerebrospinal fluid leak, or immunosup-
cause invasive disease in children in the United States pression (including those with HIV infection, comple-
have now been linked to a nontoxic but immunogenic ment deficiencies, malignancies, prolonged use of
variant of diphtheria toxin. In the largest efficacy and steroids, and organ transplants). Penicillin prophylaxis
safety trial, the heptavalent pneumococcal conjugate of patients with sickle cell disease should be continued
vaccine (PCV7) was 97.4% effective at preventing inva- regardless of vaccination with PCV7 or 23PS. Insuffi-
sive disease by vaccine serotypes. Additionally, the re- cient data are available to provide definitive recommen-
duction in total invasive pneumococcal infections in dations for pneumococcal vaccination for immuno-
children who had received one or more vaccine doses, compromised children 5 years and older. Providers can
regardless of pneumococcal serotype, was 89.1%. consider giving one dose each of PCV7 and 23PS, sepa-
PCV7 was much less effective in preventing acute otitis rated by 6 to 8 weeks, to older children at risk of inva-
media. Although the vaccine’s effect on invasive disease sive pneumococcal disease. An additional 23PS booster
in American Indian children was difficult to demon- should be given 3–5 years later. Additionally, because
strate, PCV7 has been shown to reduce the incidence of otherwise healthy Alaskan Natives and American Indi-
invasive disease and carriage of antibiotic-resistant ans are at moderately increased risk of invasive pneu-
268 / CHAPTER 9

Table 9–8. Recommended pneumococcal (PCV7 and 23PS) immunization of children at high risk of
invasive pneumococcal disease.

Age Previous Doses PCV7 23PS

2–6 mo None 3 doses, 6–8 wk apart 1 dose at 24 moa
1 booster dose at 12–15 mo 2nd dose 3–5 y after the first dose of 23PS
7–11 mo None 2 doses, 6–8 wk apart 1 dose at 24 moa
1 booster dose at 12–15 mo 2nd dose 3–5 y after the first dose of 23PS
12–23 mo None 2 doses, 6–8 wk apart 1 dose at 24 moa
2nd dose 3–5 y after the first dose of 23PS
24–59 mo 4 doses of PCV7 None 1 dose, 6–8 wk after last dose of PCV7
2nd dose 3–5 y after the first dose of 23PS
24–59 mo 1–3 doses of 1 dose, 6–8 wk after the last 1 dose, 6–8 wk after last dose of PCV7
PCV7 dose of PCV7 2nd dose 3–5 y after the first dose of 23PS
24–59 mo 1 dose of 23PS 2 doses, 6–8 wk apart, starting 1 dose 3–5 y after the first dose of 23PS
6–8 wk after 23PS dose
24–59 mo None 2 doses, 6–8 wk apart 1 dose, 6–8 wk after last dose of PCV7
2nd dose 3–5 y after the first dose of 23PS
a
The dose of 23PS should be given at least 8 weeks after the last dose of PCV7.
Modified, with permission, from American Academy of Pediatrics. Pneumococcal infections. In Pickering LK (ed): Red Book 2003 Report of
the Committee on Infectious Diseases, 20th ed. American Academy of Pediatrics, 2003, p 498.

mococcal disease, they also may benefit from receiving 12–15 months. Children who receive their first dose of
both PCV7 and 23PS. PCV7 at 7–11 months of age should receive two doses
separated by 6–8 weeks, followed by a booster dose at
Preparations Available 12–15 months. Children who receive their first dose of
PCV7 at 12–23 months require two doses total, sepa-
Pneumococcal conjugate vaccine (Prevnar) is composed rated by 6–8 weeks. PCV7 may be given concurrently
of seven purified capsular polysaccharides, each coupled with the other routinely recommended childhood im-
to a nontoxic modified diphtheria toxin. Serotypes in- munizations.
cluded in the vaccine and potentially cross-reacting Children older than 23 months at high risk of inva-
serotypes accounted for 86% of bacteremia, 83% of sive pneumococcal disease should receive both
meningitis, and 65% of AOM cases caused by pneumo- PCV7 and 23PS, as outlined in Table 9–8. PCV7 and
coccus during the period 1978–1994. The vaccine is li- 23PS should not be given simultaneously, and when
censed for use in children age 6 weeks to 9 years. both are indicated, they should be given 6–8 weeks
The 23-valent polysaccharide vaccine (Pneumovax) apart. The dose of 23PS is 0.5 mL, given intramuscu-
is only for use in persons 2 years and older. It contains larly. If splenectomy or immunosuppression can be an-
25 µg of each purified capsular polysaccharide antigen ticipated, vaccination should be done at least 2 weeks
of 23 serotypes of S pneumoniae. These 23 types cause beforehand. Revaccination with 23PS may be consid-
88% of cases of pneumococcal bacteremia and menin- ered after 3–5 years in children at high risk of fatal
gitis in adults and nearly 100% of those in children in pneumococcal infection.
the United States. Cross-reactive antibody responses
may protect against an additional 8% of bacteremic Adverse Effects
serotypes in adults.
The most common adverse effects associated with
PCV7 administration are fever, induration, and tender-
Dosage & Schedule of Administration ness at the site of the injection. When it is given simul-
PCV7 is given as a 0.5-mL intramuscular dose. The taneously with DTaP, no increase in febrile seizures has
first dose can be given as early as 6 weeks of life, with a been seen when compared with administration of
recommended vaccination schedule of 2, 4, 6, and DTaP alone. Vaccination with PCV7 is contraindi-
 IMMUNIZATION / 269

cated for individuals with a known hypersensitivity to disease will be sustained, and if the decline is the result
any component of the vaccine. of HepA vaccination strategies.
With 23PS, 50% of all vaccine recipients develop Children are known to be an important source of
pain and redness at the injection site. Fewer than 1% transmission of hepatitis A through a community. Ap-
develop systemic side effects such as fever and myalgia. proximately one third of all reported cases occur in chil-
Anaphylaxis is rare. The vaccine is contraindicated dur- dren younger than 15 years of age. Additionally, the
ing pregnancy. likelihood of being symptomatic from infection varies
inversely with age, with approximately 70% of children
American Academy of Pediatrics, Committee on Infectious Dis- younger than 6 years of age being asymptomatic when
eases: Policy statement: Recommendations for the prevention infected. The predominance of a fecal–oral route of
of pneumococcal infections, including the use of pneumococ- transmission, the less than vigilant hand-washing
cal conjugate vaccine (Prevnar), pneumococcal polysaccharide among young children, and their preponderance of
vaccine, and antibiotic prophylaxis. Pediatrics 2000;106:362
[PMID: 10920170].
asymptomatic infections all combine to create a potent
Black S et al: Efficacy, safety and immunogenicity of heptavalent
mechanism for spread of hepatitis A infection.
pneumococcal conjugate vaccine in children. Pediatr Infect National hepatitis A vaccination recommendations
Dis J 2000;19:187 [PMID: 10749457]. were revised in 1999, with increased emphasis on child-
Centers for Disease Control and Prevention: Preventing pneumo- hood immunization as a means of hepatitis A control.
coccal disease among infants and young children: Recom- Routine vaccination of children 2 years and older is rec-
mendations of the Advisory Committee on Immunization ommended for areas with greater than twice the na-
Practices (ACIP). MMWR Morb Mortal Wkly Rep tional average of hepatitis A infection (primarily the
2000;49(No. RR-9):1. western United States), and vaccination should be con-
Dagan R et al: Effect of a nonavalent conjugate vaccine on carriage sidered in areas with disease rates exceeding (but less
of antibiotic-resistant Streptococcus pneumoniae in day-care
centers. Pediatr Infect Dis J 2003;22:532 [PMID:
than twice) the national average. Although the long-
12799510]. term effect of this strategy is unknown, one community
Kilpi T et al: Finnish Otitis Media Study Group: Protective effi- with recurrent hepatitis A epidemics documented a
cacy of a second pneumococcal conjugate vaccine against 94% reduction in infections after instituting routine
pneumococcal acute otitis media in infants and children: childhood vaccination, and disease incidence declined
Randomized, controlled trial of a 7-valent pneumococcal in both children and adults.
polysaccharide-meningococcal outer membrane protein com- In addition to the routine immunization of children
plex conjugate vaccine in 1666 children. Clin Infect Dis
2003;37:1155 [PMID: 14557958].
in areas of increased disease incidence, HepA is indi-
cated for the following groups: (1) international travelers
Klugman KP et al: A trial of a 9-valent pneumococcal conjugate
vaccine in children with and those without HIV infection. (except to Canada, Western Europe, Japan, Australia,
N Engl J Med 2003;349:1341 [PMID: 14523142]. and New Zealand), (2) children with chronic hepatitis B
O’Brien KL et al: Efficacy and safety of seven-valent conjugate or hepatitis C infections or other chronic liver disease,
pneumococcal vaccine in American Indian children: Group (3) children with clotting factor disorders, (4) homosex-
randomised trial. Lancet 2003;362:355 [PMID: 12907008]. ual or bisexual males, (5) persons with an occupational
Veenhoven R et al: Effect of conjugate pneumococcal vaccine fol- exposure to hepatitis A, and (6) illegal drug users.
lowed by polysaccharide pneumococcal vaccine on recurrent Vaccine efficacy is 94–100% at protecting against
acute otitis media: A randomised study. Lancet 2003;361: clinical hepatitis A. HepA is not approved for use in
2189 [PMID: 12842372].
children younger than 2 years old.
Whitney CG et al: Active bacterial core surveillance of the emerg-
ing infections program network. Decline in invasive pneumo-
coccal disease after the introduction of protein-polysaccharide Preparations Available
conjugate vaccine. N Engl J Med 2003;348:1737 [PMID:
12724479]. Two inactivated hepatitis A vaccines are currently avail-
able for children: Havrix (GlaxoSmithKline) and Vaqta
(Merck). Havrix contains a preservative (2-phe-
HEPATITIS A noxyethanol), but Vaqta does not. A combination vac-
In 2001, approximately 11,000 cases of hepatitis A in- cine against hepatitis A and hepatitis B (Twinrix, Glaxo-
fection were reported in the United States. This repre- SmithKline) is also available, but is only licensed in the
sents a substantial decline from the 32,000 cases re- United States for persons 18 years and older.
ported in 1995, the year hepatitis A vaccine (HepA)
was first licensed. However, because the incidence of Dosage & Schedule of Administration
hepatitis A infection varies from year to year and from
region to region in the United States, continued sur- Havrix is available in two formulations. For individuals
veillance will be needed to determine if the decline in between the ages of 2 and 18 years, 720 ELU (ELISA
270 / CHAPTER 9

units) is administered in two doses of 0.5 mL, separated HEPATITIS B

by 6–12 months. For persons older than 18 years, a
higher dose (1440 ELU) is recommended, also in two Hepatitis B vaccine (HepB), when given with hepatitis
doses. B immune globulin (HBIg), is 95% effective in pre-
Vaqta also has two formulations. For persons venting vertical (perinatal) transmission of hepatitis B
2–17 years of age, two doses of 25 ELU (0.5 mL) are virus. HepB alone is 90–95% effective in preventing
given, separated by 6–18 months. Individuals older horizontal hepatitis B transmission in susceptible chil-
than 17 years old are given 50 ELU (1.0 mL) in a two- dren and adults. Between 1982 and 2002 an estimated
dose schedule. 40 million children and 30 million adults in the United
Both vaccines should be stored and shipped at States received hepatitis B vaccine. The use of HepB is
2–8°C and should not be frozen. HepA is given intra- also increasing internationally, with 126 (66%) of
muscularly, and may be given simultaneously with 191 World Health Organization member countries re-
other vaccines, including hepatitis B vaccine. porting childhood HepB vaccination programs.
All pregnant women should be routinely screened
for hepatitis B surface antigen (HBsAg). Women with
Adverse Effects positive reactions are highly likely to transmit the infec-
Adverse reactions are mild and consist of pain and in- tion to their offspring. Infants born to HBsAg-positive
duration at the injection site, feeding problems, and mothers should receive both HepB and HBIg immedi-
headache. The vaccine should not be administered to ately after birth. Infants for whom the maternal HBsAg
children with hypersensitivity to 2-phenoxyethanol (in status is unknown should receive HepB (but not HBIg)
the case of Havrix) or alum (for both preparations). within 12 hours of birth, and the mother’s HBsAg sta-
tus (and thus the newborn’s need for HBIg) should be
determined as soon as possible.
Antibody Preparations Universal HepB immunization of low-risk new-
For children younger than age 2 years at increased risk borns (those with HBsAg-negative mothers) was tem-
of hepatitis A infection (eg, those traveling to endemic porarily halted in July of 1999 because of concerns
areas or those with clotting factor disorders), Ig should about the amount of thimerosal (a mercury-containing
be used as preexposure prophylaxis. The recommended preservative) that infants were receiving through vacci-
dosages are 0.02 mL/kg in a single intramuscular dose if nation. Once a thimerosal-free vaccine became avail-
the duration of exposure is likely to be less than able, the AAP and ACIP recommended reinstituting
3 months and 0.06 mL/kg if exposure is likely to be HepB vaccination of all infants at birth, using only
more than 3 months. For long-term prophylaxis of per- thimerosal-free vaccine. Despite the updated recom-
sons not eligible for vaccination, prophylactic doses can mendations, some institutions have been slow to restart
be repeated every 5 months. their newborn HepB programs, thereby missing an im-
Postexposure prophylaxis with Ig should be given to portant opportunity to interrupt hepatitis B transmis-
previously unvaccinated persons exposed within the sion.
prior 2 weeks to hepatitis A. Postexposure Ig is recom- Routine immunization with HepB is recommended
mended for household or sexual contacts of persons for all infants and all previously unvaccinated children
with serologically confirmed hepatitis A, and for day 0–18 years of age. A two-dose schedule (as opposed to
care staff and attendees in outbreak situations. Individ- the standard pediatric three doses) is available for ado-
uals given one dose of HepA at least 1 month before ex- lescents (see following discussion). Since initiating uni-
posure do not need Ig. When indicated, a single intra- versal recommendations, the percentage of children age
muscular dose of Ig (0.02 mL/kg) should be given as 19–35 months receiving three doses of HepB increased
soon as possible, but not more than 2 weeks after the from less than 10% in 1991 to 90% in 2002.
last exposure. If HepA is also indicated, it may be given In addition to the universal immunization of chil-
simultaneously with Ig, but at a different anatomic in- dren, older persons in several risk categories have been
jection site. identified as target populations for preexposure vaccina-
tion. Those that are relevant to physicians caring for
children include residents and staff in institutions for
Armstrong GL, Bell BP: Hepatitis A virus infection in the United
States: Model-based estimated and implications for childhood the developmentally delayed, residents and staff of he-
immunization. Pediatrics 2002;109:839 [PMID: 11986444]. modialysis units, recipients of clotting factor concen-
Averhoff F et al: Control of hepatitis A through routine vaccination trates, homosexually active males, users of illicit in-
of children. JAMA 2001;286:2968 [PMID: 11743837]. jectable drugs, household contacts of chronic hepatitis
Bell BP: Hepatitis A vaccine. Semin Pediatr Infect Dis 2002:13: B carriers, incarcerated juveniles, long-term interna-
165 [PMID: 12199612]. tional travelers to endemic areas, and all health care
 IMMUNIZATION / 271

personnel. Screening for markers of past infection be- age. Any single or combination vaccine (except Twin-
fore HepB immunization is generally not indicated for rix) may be used to complete the hepatitis B vaccina-
children and adolescents, but may be considered for tion series. All pediatric formulations contain trace to
high-risk individuals. Because vaccines consist of a puri- no thimerosal.
fied inactive subunit of the virus and are not infectious,
they are not contraindicated in immunosuppressed in- Dosage & Schedule of Administration
dividuals or in pregnant women.
HepB is immunogenic in infants, children, and HepB is administered as part of the primary childhood
young adults. The protective efficacy of HepB corre- immunization schedule for infants and children, as out-
lates well with antibody levels, and virtually all persons lined in Table 9–9. The preferred initial dose is during
with levels of 10 mIU/mL or more are protected in the postpartum period. For children younger than
clinical trials. 11 years of age, three intramuscular doses of HepB are
needed. Adolescents age 11–15 years have two options:
the standard pediatric three-dose schedule or two doses
Preparations Available of adult Recombivax HB (1.0-mL dose), with the sec-
1. HepB (Recombivax HB, Merck) contains recom- ond dose administered 4–6 months after the first dose.
binant hepatitis B vaccine only. Simultaneous administration with other vaccines at dif-
ferent sites is safe and effective. HepB should be given
2. HepB (Engerix-B, GlaxoSmithKline) contains re- intramuscularly in either the anterolateral thigh or del-
combinant hepatitis B vaccine only. toid, depending on the age and size of the patient. Ad-
3. HepB-Hib (Comvax, Merck) contains Recom- ministration intradermally or in the buttocks results in
bivax HB and Haemophilus influenzae type b poor immune responses in some individuals.
(PRP-OMP) vaccine.
4. DTaP-IPV-HepB (Pediarix, GlaxoSmithKline) A. NEONATAL
contains diphtheria and tetanus toxoids and acel- Infants of HBsAg-positive mothers should be cleansed
lular pertussis (DTaP), inactivated poliovirus of blood in the delivery room. Both HepB (see Table
(IPV), and Engerix-B vaccines. 9–9) and HBIg (0.5 mL intramuscularly) should be ad-
5. HepB-HepA (Twinrix, GlaxoSmithKline) con- ministered simultaneously at different sites within
tains Engerix-B and hepatitis A vaccines; only ap- 12 hours of birth. The vaccine should be repeated at
proved for persons 18 years of age or older. 1 month and 6 months. After completion of the HepB
series, at 9 to 15 months of age, immunized infants
Only the single-antigen vaccines (Recombivax HB, should be tested for anti-HBs. If the anti-HBs assay is
Engerix-B) can be given between birth and 6 weeks of positive, vaccination has been effective. If the result is

Table 9–9. Hepatitis B vaccine schedule and dosage.

Recombivax HB Engerix-B Dose Schedule and Ages

a
Infants of HBsAg-negative mothers 0.5 mL 0.5 mL 0–2 d, 1–2 mo, and 6–18 mo
Infants of HBsAg-positive mothersb (HBIG 0.5 mL 0.5 mL 0.5 mL Day 0, 1 mo, and 6 mo
should also be given)
Children and adolescents < 20 y old 0.5 mLc 0.5mL Day 0, 1 mo, and 4 mo
Immunosuppressed persons and dialysis patients 1.0 mLd 2.0 mLe
a
Infants of mothers with unknown HBsAg status should be tested at delivery. The infant should receive hepatitis B vaccine within 12
hours of birth. Preterm and low-birth-weight infants of HBsAg-negative mothers should receive the first vaccine dose at 30 days of
chronologic age if medically stable, or at discharge if before 30 days of age.
b
Preterm and low-birth-weight infants of HBsAg-positive mothers should receive Hepatitis B vaccine and HBIG within 12 hours of birth re-
gardless of birthweight and gestational age; these infants should receive 4 vaccine doses total.
c
A 2-dose schedule (1.0 mL at 0 months and 4–6 months) is also available for adolescents age 11–15 years.
d
Special formulation containing 40 micrograms/mL.
e
Two doses of 1.0 mL at one site in a four-dose schedule at Day 0 and at 1, 2, and 6 months.
HBsAg: hepatitis B surface antigen; HBIG: hepatitis B immune globulin.
Modified from MMWR Vol 40, No RR13;001
272 / CHAPTER 9

negative, HBsAg should be tested for; if that test result should receive HBIg (0.06 mL/kg) and the first dose of
is positive, immunization has failed and the infant is a HepB at a separate anatomic site. For sexual contact or
chronic carrier. If both HBsAg and anti-HBs are nega- household blood exposure with an acute case of hepati-
tive, the series should be repeated at 0, 1, and tis B, HBIg and HepB should be given. Sexual and
6 months, followed by repeat anti-HBs testing 1 month household contacts of someone with chronic infection
after the third dose. should receive immunization (but not HBIg). For indi-
For infants born to mothers of unknown HBsAg viduals with percutaneous or permucosal exposure to
status, the same schedule should be followed, except blood, HepB should be given, and HBIg considered de-
that HBIg should be withheld until the HBsAg status pending on the HBsAg status of the person who was
of the mother is known. If the mother is HBsAg-posi- the source of the blood and on the vaccination response
tive, HBIg should be initiated as soon as possible but status of the exposed person. All previously vaccinated
no later than 7 days after birth. persons exposed to hepatitis B should be retested for
For infants born to HBsAg-negative mothers, the anti-HBs. If levels are adequate (≥ 10 mIU/mL), no
first dose should be administered in the newborn pe- treatment is necessary. If levels are inadequate and the
riod, or, if this is not possible, at least before age exposure was to HBsAg-positive blood, HBIg and vac-
2 months. The doses and the schedule for routine vac- cination are required.
cination of these infants are set forth in Table 9–9. For
preterm infants with birth weights of less than 2 kg Adverse Effects
born to HBsAg-negative mothers, initiation of HepB
should be delayed until 30 days of chronologic age if The overall rate of adverse effects is low and minor, and
the infant is medically stable or prior to hospital dis- effects include fever (1–6%) and pain at the injection
charge if discharged before 30 days of age. site (3–29%). There is no evidence of an association be-
If maternal screening is not possible, the infant tween vaccination and sudden infant death syndrome,
should receive the first dose of HepB within 12 hours multiple sclerosis, autoimmune disease, or chronic fa-
after birth, the second at age 1–2 months, and the third tigue syndrome.
at 6 months. There should be at least 1 month between
first and second doses. The third dose should be ad- Antibody Preparations
ministered at least 4 months after the first dose and at
least 2 months after the second dose, but not before the HBIg is prepared from HIV-negative and hepatitis C
child is 6 months old. virus-negative donors with high titers of hepatitis B sur-
face antibody. The process used to prepare this product
B. OLDER CHILDREN AND ADOLESCENTS inactivates or eliminates HIV and hepatitis C virus.
All children should receive HepB as part of the routine The use of HBIg is described earlier in this section.
schedule. The universal immunization of all adolescents
is recommended, on either a two- or three-dose sched- Biroscak BJ et al: Impact of the thimerosal controversy on hepatitis
ule. (See Table 9–9 for dosages and schedules.) B vaccine coverage of infants born to women of unknown
hepatitis B surface antigen status in Michigan. Pediatrics
C. IMMUNOSUPPRESSED PERSONS 2003;111:e645 [PMID: 12777580].
AND DIALYSIS PATIENTS Centers for Disease Control and Prevention (CDC): Hepatitis B
vaccination—United States, 1982–2002. MMWR Morb
Hemodialysis patients and other immunocompromised Mortal Wkly Rep 2002;51:549 [PMID: 12118536].
persons should be vaccinated with larger doses or an in- Centers for Disease Control and Prevention (CDC): Global
creased number of doses (or both) (see Table 9–9). progress toward universal childhood hepatitis B vaccination,
2003. MMWR Morb Mortal Wkly Rep 2003;52:868
D. LAPSED HEPATITIS B IMMUNIZATION [PMID: 12970620].
The HepB series can be completed regardless of the in-
terval from the last vaccine dose. There is no need to VARICELLA
start the series over or to test routinely for anti-HBs in
healthy children unless the child’s mother is HBsAg- Prior to the availability of vaccine, about 4 million cases
positive. of varicella-zoster virus (VZV) infection occurred annu-
ally in the United States, mostly in children younger
E. POSTEXPOSURE PROPHYLAXIS than 10 years. This resulted in 11,000 hospitalizations
Postexposure prophylaxis is indicated for unvaccinated and 100 deaths per year due to severe complications
persons with perinatal, sexual, household, percuta- such as secondary bacterial infections, pneumonia, en-
neous, or permucosal exposure to hepatitis B. When cephalitis, hepatitis, and Reye syndrome. A live attenu-
prophylaxis is indicated, unvaccinated individuals ated (VAR) vaccine was developed in Japan in the
 IMMUNIZATION / 273

1970s and licensed in the United States by the FDA in immunization, susceptible groups targeted for immu-
1995 for children older than 12 months. As of 2002, nization include: (1) adults or adolescents older than
approximately 81% of children age 19–35 months in 13 years residing in households with susceptible chil-
the United States have received one dose of VAR. In dren; (2) those who work as teachers of young children
three communities participating in an active disease or as day care workers; (3) persons living or working in
surveillance program, reported VZV cases declined environments that facilitate transmission (eg, colleges,
from 71% to 84% from 1995 to 2000. VZV disease correctional facilities); (4) international travelers; and
declined by a similar amount in all age groups, includ- (5) nonpregnant women of childbearing age.
ing infants and susceptible adults, suggesting that dis-
ease transmission has been reduced even among the un-
vaccinated.
Preparations Available
In seven postlicensure studies, vaccine effectiveness A cell-free preparation of OKA strain VZV is produced
ranged from 95% to 100% in preventing moderate and and marketed in the United States (Merck). Each dose
severe disease, and 71% to 100% in preventing any dis- of VAR contains not less than 1350 plaque-forming
ease among vaccinees. However, a more recent investi- units of VZV and trace amounts of neomycin and
gation of a VZV outbreak at a day care center revealed gelatin. Storage in a freezer at a temperature of −15°C
vaccine effectiveness of 86% against serious disease and or colder provides a shelf life of 15 months. VAR may
44% against any disease. Preliminary data suggest that be stored for 72 hours at refrigerator temperature in its
vaccine effectiveness may be somewhat diminished lyophilized state, VAR must be administered within
when (1) vaccine is given nonsimultaneously but within 30 minutes after thawing and reconstitution.
28 days of MMR vaccination or (2) oral steroids have
been used in the preceding 3 months. The administra-
tion of vaccine at younger than 15 months of age has
Dosage & Schedule of Administration
been suggested as a potential risk factor for diminished One dose (0.5 mL) of VAR is recommended for immu-
protection, but this has not been confirmed. Some con- nization for all healthy children age 12 months to
cern has also arisen that vaccine-induced immunity 12 years who lack a history of VZV infection. Children
may wane over time, although no evidence supports 13 years or older require two doses of VAR 1 month
this contention to date. The necessity for and cost-ef- apart. Asymptomatic or mildly symptomatic HIV-in-
fectiveness of changing to a two-dose schedule for chil- fected children (CDC class N1 or A1) should receive
dren has not been determined. two doses of vaccine (with a 3-month interval between
In February 1999, the ACIP expanded its recom- doses). VAR may be given simultaneously with MMR
mendations for VZV vaccine to promote wider usage. at separate sites. If not given simultaneously, the inter-
It is predicted that with 97% coverage rates, transmis- val between administration of VAR and MMR must be
sion of VZV could be ended in 30 years. Updated rec- greater than 28 days. Simultaneous VAR administra-
ommendations include (1) establishing child care and tion does not appear to affect the immune response to
school entry requirements, (2) use of the vaccine fol- other childhood vaccines. VAR should be delayed
lowing exposure and for outbreak control, (3) use for 5 months after intravenous immunoglobulin infusion.
some children with HIV infection, and (4) use in adults
and adolescents at risk for exposure.
Proof of immunity to VZV is recommended as a re-
Adverse Events
quirement for day care and school entry, and is now re- Since the approval of VAR in 1995, more than
quired in 38 states; vaccination, physician diagnosis of 30,000,000 doses have been distributed in the United
VZV infection, and serologic documentation of protec- States. The most commonly recognized adverse reac-
tive antibody meet this requirement. tions, occurring in approximately 20% of vaccinees, are
Data from US and Japanese studies suggest that vac- minor injection site reactions. Additionally, 3–5% of
cine is effective in preventing or modifying VZV sever- patients will develop a localized rash, and an additional
ity in susceptible individuals if used within 3–5 days of 3–5% will develop a sparse generalized varicelliform
exposure, and this is now recommended by the ACIP rash. These rashes typically consist of two to five lesions
and the AAP. A study in the United States suggests that and may appear 5–26 days after immunization. In most
the efficacy of postexposure vaccination is 95% for pre- cases in which rash occurred within the first 2 weeks
vention of any disease and 100% for prevention of after immunization, polymerase chain reaction (PCR)
moderate or severe disease. There is no evidence that analysis of these lesions has demonstrated the presence
postexposure prophylaxis will increase the risk for vac- of wild-type rather than vaccine-strain virus, suggesting
cine-related adverse events or interfere with develop- natural infection sometime immediately prior to vacci-
ment of immunity. In addition to routine childhood nation. Transmission of vaccine virus from healthy pa-
274 / CHAPTER 9

tients to healthy recipients is very rare; has never oc- (whose mother lacks history of chickenpox or is
curred in the absence of a rash in the index case; and seronegative), and hospitalized premature infants less
has only resulted in mild disease. One case involved than 28 weeks gestation (regardless of maternal history
transmission from a vaccinee to a susceptible pregnant or serostatus). Exposure is defined as a household con-
female. The pregnancy was terminated, but PCR analy- tact or playmate contact (over 1 h/d), hospital contact
sis of the fetus showed no evidence of VZV infection. (in the same or contiguous room or ward), intimate
Based on data from the Vaccine Adverse Event Report- contact with a person with zoster deemed contagious,
ing System (VAERS), rates of serious adverse events fol- or a newborn contact. Susceptibility is defined as the
lowing VAR are not increased compared with rates ex- absence of anti-VZV antibody by an appropriate test.
pected after natural infection or the background rates of VZIg should be given as soon as possible after exposure,
similar events in the community. Herpes zoster infec- but should be administered within 96 hours. Newborns
tion has occurred following VAR administration in im- should be given one vial (125 U) intramuscularly. The
munocompetent and immunocompromised persons dose for all others is 125 U/10 kg body weight intra-
within 25–722 days after immunization. Many of these muscularly (maximum dose, 625 U). VZIg should be
cases were due to presumably unappreciated latent readministered following reexposure of susceptible per-
wild-type virus. Furthermore, based on preliminary sons if more than 3 weeks has elapsed since a prior dose
data, the age-specific risk of herpes zoster infection of VZIg.
seems to be lower in immunocompetent children fol-
lowing VAR immunization than after natural infection. American Academy of Pediatrics. Committee on Infectious Dis-
eases: Varicella vaccine update. Pediatrics 2000;105:136
[PMID: 10617719].
Contraindications Galil K et al: Outbreak of varicella at a day-care center despite vac-
Table 9–3 lists contraindications to VZV immuniza- cination. N Engl J Med 2002;347:1909 [PMID: 12477940].
tion, such as known hypersensitivity or allergy to any Seward JF et al: Varicella disease after introduction of varicella vac-
cine in the United States, 1995–2000. JAMA 2002;287:606
VAR component, including neomycin. VAR is also [PMID: 11829699].
contraindicated in children who have cellular immun-
Verstraeten T et al: A retrospective cohort study of the association
odeficiencies, including those with leukemia, lym- of varicella vaccine failure with asthma, steroid use, age at
phoma, other malignancies affecting the bone marrow vaccination, and measles–mumps–rubella vaccination. Pedi-
or lymphatic systems, and congenital T-cell abnormali- atrics 2003;112:e98 [PMID: 12897314].
ties (although vaccine administration to children with
acute lymphocytic leukemia is under investigation).
The exception to this rule is the recommendation that
INFLUENZA
VAR be administered to HIV-infected children in Influenza occurs each winter and early spring, often as-
CDC immunologic class I (CD4+ T-lymphocyte count sociated with significant morbidity and mortality rates
of 25% or more) because the vaccine is safe and im- in certain high-risk persons. Up to 36,000 deaths per
munogenic in this group. Children receiving immuno- year in the United States are attributable to influenza,
suppressive therapy, including high-dose steroids, and global epidemics (pandemics) can occur. Children
should not receive VAR. Household contacts of im- at high risk of influenza-related complications include
munodeficient patients should be immunized. VAR those with hemoglobinopathies and those with chronic
should not be given to pregnant women; however, the cardiac, pulmonary (including asthma), metabolic,
presence of a pregnant mother in the household is not a renal, and immunosuppressive diseases. Children and
contraindication to immunization of a child within that adolescents receiving long-term aspirin therapy are also
household. at risk of substantial morbidity from influenza-related
Reye syndrome. Additionally, healthy children younger
than 2 years of age are at increased risk of hospitaliza-
Antibody Preparations tion during influenza season.
Varicella-zoster immune globulin (VZIg) is prepared Annual influenza vaccination is indicated for all
from plasma harvested from persons known to have children older than 6 months of age who have a chronic
high titers of anti-VZV antibody. It is indicated for health condition that places them at higher risk of com-
high-risk susceptible persons who are exposed to VZV, plications from influenza infection. Members (includ-
for example, immunocompromised individuals without ing other children) of households with persons in high-
a history of chickenpox, susceptible pregnant women, risk groups should also be immunized. The vaccine
newborns whose mothers develop varicella 5 days prior may be administered to healthy children older than age
to delivery or within 48 hours after delivery, hospital- 6 months, and the inactivated vaccine is now routinely
ized premature infants 28 weeks or more gestation recommended for all children ages 6–23 months.
 IMMUNIZATION / 275

Physicians should identify high-risk children in their Dosage & Schedule of Administration
practices and encourage parents to seek influenza vacci-
nation for them each fall. In pandemic years, it may be A. INACTIVATED INFLUENZA VIRUS VACCINE
important to advocate vaccination in all children re- Because influenza can circulate yearly from November
gardless of their usual state of health. Influenza vaccina- through early March in the United States, the key time
tion has a 65–80% efficacy in protecting against dis- to initiate vaccination is between October and early
ease. In high-risk groups, it may be even more effective November of each year. However, providers should
in preventing lower respiratory disease or other sec- continue vaccinating individuals as long as vaccine is
ondary complications, thereby decreasing hospitaliza- available and there is still influenza activity in the com-
tions and deaths. Each year, recommendations are for- munity. Children younger than age 6 months should
mulated in the spring and summer regarding the not be immunized. Two doses are recommended for
constituents of influenza vaccine for the coming season. children younger than age 9 years who are receiving in-
These recommendations are based on the results of sur- fluenza vaccine for the first time; subsequent seasons re-
veillance in Asia and the southern hemisphere during quire single doses. Older children receiving vaccine for
the spring and summer. The vaccine each year is a the first time require only a single dose. The dose for
trivalent inactivated vaccine containing antigens from children ages 6–35 months is 0.25 mL, given intramus-
two strains of influenza A and one strain of influenza B, cularly; for older children, 0.5 mL, given intramuscu-
chosen as those likely to circulate in the United States larly. The recommended site of vaccination is the an-
during the upcoming winter. terolateral aspect of the thigh for younger children and
To eliminate the need for injections, and potentially the deltoid for older children. Because this vaccine is
to enhance mucosal and systemic immune response to inactivated, pregnancy is not a contraindication to its
vaccination, a live attenuated intranasal vaccine has use. The vaccine is recommended for women in the
been developed. This vaccine is trivalent (containing second or third trimester of pregnancy (or those who
two type A strains and one type B strain), cold-adapted, will enter the second or third trimester) during the in-
and temperature-sensitive. These viruses replicate fluenza season. Influenza vaccine has been shown in
poorly in the lower respiratory tract but well in the some but not all studies to transiently increase HIV
nasal mucosa (thereby producing immunity). The vac- replication. Nevertheless, the CDC currently recom-
cine is effective in preventing influenza in healthy chil- mends influenza vaccination for all HIV-infected per-
dren. However, because of questions regarding its pos- sons. Simultaneous administration with other routine
sible association with pneumonia and asthma in vaccinations is acceptable.
vaccines aged 12–60 months, it is currently licensed
only for otherwise healthy children and adults age B. LIVE ATTENUATED INFLUENZA VIRUS VACCINE
5–49 years of age. This vaccine is supplied in a prefilled single-use sprayer
containing 0.5 mL of the vaccine, approximately half of
which is sprayed into each nostril. A dose divider clip is
Preparations Available provided to assist in dividing the dose. If the patient
The inactivated influenza vaccine virus is grown in eggs, sneezes during administration, the dose should not be
formalin-inactivated, and contains trace quantities of repeated. It can be administered to children with minor
thimerosal as a preservative. These whole-virus prepara- illnesses, but should not be given if significant nasal
tions may be further treated with detergents to produce congestion is present. Because it is a live vaccine it
split (subvirion) or purified surface antigen vaccines. should be administered 48 hours after cessation of ther-
Only split-virus or purified surface antigen preparations apy in children receiving antiinfluenza antivirals, and
should be used for children age 12 years and younger. antivirals should not be given for 2 weeks after vaccina-
Several manufacturers produce similar vaccines each tion.
year. Fluzone split-virus (Aventis Pasteur) is approved
for children 6 months and older; Fluvirin (Evans Vac- Adverse Effects
cines) is approved only for children 4 years and older.
The intranasal trivalent live attenuated influenza A. INACTIVATED VACCINE
virus vaccine (Flumist, Medimmune) is also produced The killed vaccine is safe. A small proportion of chil-
in a trivalent formulation using identical virus strains to dren will experience some systemic toxicity, consisting
the killed vaccine. It is also made in eggs and comes in a of fever, malaise, and myalgias. These symptoms gener-
single-use prefilled sprayer. It should be stored at ally begin 6–12 hours after vaccination and may last
–15°C in a frost-free freezer. It may be thawed and 24–48 hours. Cases of Guillain–Barré syndrome fol-
stored in a 4–8°C refrigerator for less than 24 hours lowed the swine influenza vaccination program in
prior to use. It should not be refrozen after thawing. 1976–1977, but careful study by the Institute of Medi-
276 / CHAPTER 9

cine showed no association with that vaccine in chil- Szilagyi PG et al: Potential burden of universal influenza vaccina-
dren and young adults—nor in any age with vaccines tion of young children on visits to primary care practices. Pe-
diatrics 2003;112:821 [PMID: 14523173].
given in subsequent years. For patients with anaphylac-
tic egg allergies in whom influenza vaccination is indi-
cated, a protocol for influenza vaccination is referenced
in later discussion. VACCINATIONS FOR SPECIAL
B. LIVE VACCINE SITUATIONS
In 20 studies of the vaccine where 28,000 doses were
administered to more than 20,000 children, signs and RABIES
symptoms reported more in vaccinees than placebo re-
cipients were runny nose and nasal congestion Human rabies infection is almost universally fatal, even
(20–75%), headache (2–46%), fevers (0–26%), myal- with aggressive treatment. Fortunately, the incidence of
gias (0–21.5%), vomiting (3–13%), and abdominal human rabies in the United States is very low, with
pain (2%). These were reported more frequently with fewer than three cases per year in the 1990s. Of the
the first dose and were all self-limited. However, in a 36 human cases with rabies reported in the United
study of the vaccine in children age 1–17 years of age, States from 1980 to 1996, bat exposure was suspected
significant increases in asthma or reactive airway disease in 21 cases. However, there was a definite history of
occurred in the subset age 11–59 months. Hence, it is bite in only one or two of these cases. Although dogs
not recommended in high-risk patients or in children represent the most important vector for human rabies
younger than 5 years of age. worldwide, in the United States, because of widespread
vaccination of dogs and cats, bats are the most impor-
tant cause of human rabies. Rabies is also common in
Chemoprophylaxis and Treatment skunks, raccoons, and foxes; it is uncommon in ro-
In the United States four influenza antiviral agents are dents.
available: amantadine, rimantidine, zanamivir, and os- Human rabies is preventable with appropriate and
eltamivir. The prophylactic and therapeutic uses of these timely postexposure prophylaxis. Postexposure care
drugs are discussed in Chapter 36. Chemoprophylaxis consists of local wound care, passive immunization, and
is not a substitute for vaccination, and chemoprophy- active immunization. Immediately after an animal bite,
laxis does not interfere with vaccine immunogenicity. all wounds should be flushed and aggressively cleaned
with soap and water. If possible, the wound should not
be sutured. Passive immunization after high-risk expo-
Bernstein DI et al: Cold-Adapted, Trivalent, Influenza Vaccine sure consists of the injection of rabies immune globulin
Study Group: Effect of yearly vaccinations with live, attenu-
ated, cold-adapted, trivalent, intranasal influenza vaccines on
near the wound, as described later. Active immuniza-
antibody responses in children. Pediatr Infect Dis J 2003;22: tion is accomplished by completing a schedule of im-
28 [PMID: 12544405]. munization with one of the three rabies vaccines avail-
Bridges CB et al: Prevention and control of influenza: Recommen- able in the United States. It is important to keep in
dations of the Advisory Committee on Immunization Prac- mind that bites from bats are often unrecognized; pro-
tices (ACIP). MMWR Recomm Rep 2003;52(RR-8):1 phylaxis should be given if a bat is found indoors even
[PMID: 12755288]. if there is no history of contact, especially if found in
Committee on Infectious Diseases, American Academy of Pedi- the same room with a sleeping or unattended child or
atrics: Reduction of the influenza burden in children. Pedi- with an intoxicated or otherwise incapacitated individ-
atrics 2002;110:1246 [PMID: 12456947].
ual.
DeStefano F et al: Vaccine Safety Datalink Research Group, Na-
tional Immunization Program, Centers for Disease Control
Local public health officials should be consulted be-
and Prevention: Vaccinations and risk of central nervous sys- fore postexposure rabies prophylaxis is started to avoid
tem demyelinating diseases in adults. Arch Neurol 2003;60: unnecessary vaccination and to assist in the proper han-
504 [PMID: 12707063]. dling of the animal (if confinement or testing of the an-
Harper SA et al: Using live, attenuated influenza vaccine for pre- imal is appropriate). To facilitate consultation, the
vention and control of influenza: Supplemental recommenda- physician should know the species of animal, its avail-
tions of the Advisory Committee on Immunization Practices ability for testing or confinement, the nature of the at-
(ACIP). MMWR Recomm Rep 2003;52(RR-13):1. [PMID:
14557799].
tack (provoked or unprovoked), and the nature of the
exposure (bite, scratch, lick, aerosol of saliva). Preexpo-
Stratton K et al (eds): Immunization Safety Review: Influenza Vac-
cines and Neurological Complications 2003. Immunization sure prophylaxis is indicated for veterinarians, animal
Safety Review Committee, National Research Council. Na- handlers, and any persons whose work or home envi-
tional Academies Press, 2003. ronment potentially places them in close contact with
 IMMUNIZATION / 277

animal species in which rabies is endemic—bats, tramuscularly at a site distant from vaccine administra-
skunks, raccoons, and foxes. Rabies immunization tion. The first dose of rabies vaccine should be adminis-
should also be considered for children traveling to tered as soon as possible. Vaccine and RIg should never
countries where rabies is endemic; this is particularly be mixed in the same syringe or given at the same ana-
important for travelers who will not have prompt access tomic site. Postexposure failures occurred only when
to medical care should an exposure occur. some deviation from the approved protocol occurred
(eg, less than usual amount of RIg, no RIg at wound
Preparations Available site, no cleansing of wound, vaccination in the gluteal
area). Four subsequent doses of rabies vaccine should be
Rabies vaccines stimulate immunity after 7–10 days, given on days 3, 7, 14, and 28. The WHO recom-
and the immunity persists for 2 years or more postvac- mends an additional dose on day 90, but the ACIP
cination. Three preparations are available: does not concur.
1. Human diploid cell vaccine (HDCV) is grown in 2. In previously vaccinated individuals—RIg is not
human cell culture (Imovax, Aventis Pasteur). necessary, and only two doses of vaccine on days 0 and
2. Rabies vaccine adsorbed (RVA) is prepared in 3, are needed.
fetal rhesus lung cell culture (BioPort Corpora- C. BOOSTER VACCINATION
tion).
Previously vaccinated individuals with potential contin-
3. Purified chick embryo cell vaccine (PCEC) is
ued exposure to rabies should have a serum sample
grown in chick embryo cells (RabAvert, Chiron).
tested for rabies antibody every 2 years. If the titer is
less than 1:5 for complete neutralization by the rapid
Dosage & Schedule of Administration fluorescent focus inhibition test, a booster dose of ra-
The three rabies vaccines available in the United States bies vaccine should be administered.
are equally safe and efficacious for both preexposure
and postexposure prophylaxis. For all three vaccines, Adverse Effects
1.0 mL is given intramuscularly in the deltoid (for
The rabies vaccines are relatively free of side effects. Ap-
adults and older children) or anterolateral thigh (for in-
proximately 15–25% of adults experience pain,
fants and young children). The volume of the dose is
swelling, or erythema at the injection site; 10–20% may
not reduced for children. Vaccine should not be given
have mild systemic reactions such as headache, nausea,
in the gluteal region. In some parts of the world, be-
muscle aches, and dizziness. Three cases of Guillain–
cause of limited resources, a smaller dose of vaccine is
Barré syndrome have been described; all three patients
given intradermally; this is not recommended in the
recovered fully. Children complain of side effects less
United States.
frequently. An immune complex-like reaction occurs in
A. PRIMARY PREEXPOSURE VACCINATION about 6% of persons 2–21 days after receiving booster
Preexposure rabies immunization should be considered doses of HDCV. Travelers to countries where rabies is
for individuals at high risk for exposure to rabies, for endemic may need immediate postexposure prophylaxis
example, veterinarians, animal handlers, spelunkers, and may have to use locally available vaccines and anti-
and people moving to or extensively traveling in areas sera. In many developing countries, the only vaccines
with endemic rabies. Three intramuscular injections in readily available may be nerve tissue vaccines (NTV)
the deltoid area of 1 mL of any vaccine are given on derived from the brains of adult animals or suckling
days 0, 7, and 21 or 28. mice, and the antirabies sera may be of equine origin.
Although adverse reactions to antisera are uncommon
B. POSTEXPOSURE PROPHYLAXIS and typically mild, the NTV may induce neuropara-
Postexposure prophylaxis is a medical urgency, but lytic reactions in 1:2000 to 1:8000 vaccinees; this is a
there is time for consultation with local or state public significant risk and may justify preexposure vaccination
health officials. The incubation period for rabies virus is prior to travel.
usually several weeks but up to one year.
Antibody Preparations
1. In unvaccinated individuals—As soon as possible
after exposure (and up to 7 days after the first dose of RIg is prepared from the plasma of human volunteers
vaccine), human rabies immune globulin (RIg) should hyperimmunized with rabies vaccine. The recom-
be administered (recommended dose 20 IU/kg). The mended dose is 20 IU/kg body weight. The rabies-neu-
full dose of RIg should be infiltrated near the wound, if tralizing antibody content is 150 IU/mL, supplied in
anatomically possible, with the remainder infiltrated in- 2-mL or 10-mL vials. It is very safe.
278 / CHAPTER 9

Centers for Disease Control and Prevention: Human rabies preven- dispensed from a package that has been opened before-
tion–United States, 1999. Recommendations of the Advisory hand. The antimalarial drugs mefloquine and chloro-
Committee on Immunization Practices (ACIP): MMWR
Morbid Mortal Wkly Rep 1999;48(RR-1):1 [PMID:
quine can be given simultaneously with oral typhoid
10077411]. vaccine; however, the antimalarial proguanil, as well as
Chang HG et al: Public health impact of reemergence of rabies, antimicrobials, should not be given simultaneously
New York. Emerg Infect Dis 2002;8:909 [PMID: with Ty21a.
12194765].
Hanlon CA et al: The incurable wound revisited: Progress in Adverse Reactions
human rabies prevention? Vaccine 2001;19:2273 [PMID:
11257347]. The oral and parenteral typhoid vaccines may produce
Plotkin SA: Rabies. Clin Infect Dis 2000;30:4 [PMID: 10619725]. mild adverse reactions such as abdominal complaints
(for oral) and injection site swelling or redness (for par-
enteral). As with all live attenuated vaccines, Ty21a
TYPHOID FEVER should not be given to immunocompromised patients.
Typhoid vaccines have shown variable efficacy in field
trials, typically producing protection in the 50–80% Garmory HS et al: Salmonella vaccines for use in humans: Present
range. Two vaccines are currently available in the and future perspectives. FEMS Microbiol Rev
United States: a parenteral vaccine derived from a viru- 2002;26:339 [PMID: 12413664].
lence (Vi) antigen capsular polysaccharide (ViCPS); Lin FY et al: The efficacy of a Salmonella typhi Vi conjugate vaccine
in 2-to-5-year-old children. N Engl J Med 2001;344:
and a live attenuated oral vaccine (Ty21a). Moderate 1263 [PMID: 11320385].
protection against invasive Salmonella typhi, the Parry CM et al: Typhoid fever. N Engl J Med 2002;347:1770
causative bacterium of typhoid fever, has been demon- [PMID: 12456854].
strated for 2–5 years following vaccination.
Routine typhoid vaccination is recommended only
for children who reside in households with a docu- MENINGOCOCCAL DISEASE
mented typhoid carrier or who are going to live or Infection with Neisseria meningitidis causes significant
travel extensively in an endemic area. The oral vaccine morbidity and mortality, with 120,000 cases worldwide
is most commonly used because of its ease of adminis- per year, including 2400–3000 cases in the United
tration. However, noncompliance with oral vaccine States. Meningococcal disease has a 10% case-fatality
dosing instructions occurs frequently, and correct usage rate in the United States, and up to 19% of survivors
should be stressed or the parenteral ViCPS vaccine are left with serious disabilities, such as neurologic im-
used. Travelers should be advised, however, that be- pairment, loss of limb function, or hearing loss. Infants
cause none of the vaccines offer total protection, careful younger than 1 year of age have the highest rate of dis-
selection of food and drink is imperative. ease, but college freshmen, particularly those living in
dormitories, have a higher incidence than the general
Preparations Available US population. Five serogroups of meningococcus (A,
B, C, W-135, and Y) cause the vast majority of disease.
1. Parenteral ViCPS (Typhim Vi, Aventis Pasteur) is In prior years, meningococcal disease in the United
for intramuscular use. States was caused primarily by serogroup B and C
2. Oral live attenuated Ty21a vaccine (Vivotif Berna strains (45% each), with the remainder of cases due to
Vaccine, Swiss Serum and Vaccine Institute) is W-135 and Y serogroups (10%). Now disease due to
supplied as enteric-coated capsules. serogroup B is decreasing, and disease due to Y is in-
creasing (up to 43% in some areas). The majority of
disease in developing countries is caused by serogroups
Dosage & Schedule of Administration A and C.
ViCPS is administered as a single intramuscular dose A polysaccharide-based vaccine against serogroups
(0.5 mL), with boosters needed every 2 years if exposure A, C, Y, and W-135 is available in the United States.
continues. It is approved for children 2 years and older. The vaccine has 85–100% efficacy in older children
The dose of the oral preparation is one capsule every and adults against groups A and C disease. The vaccine
2 days for a total of four capsules, taken 1 hour before is not recommended for routine immunization because
meals. The capsules should be taken with cool liquids, it is relatively ineffective in children younger than
and should be kept refrigerated. A full course of four 2 years; it is unable to protect against serogroup B dis-
capsules is recommended every 5 years if exposure con- ease; and the immunity it confers appears to be short-
tinues. This vaccine is not approved for children lived, and its repeated use may actually decrease anti-
younger than age 6 years, and capsules should not be body response. However, functionally or anatomically
 IMMUNIZATION / 279

asplenic children should be vaccinated, as well as those Adverse Effects

with terminal complement or properdin deficiencies.
Meningococcal vaccine provides some protection for With more than 6 million doses of vaccine distributed,
travelers to countries with epidemic or endemic disease few serious adverse events have been reported. A recent
(primarily sub-Saharan Africa). The vaccine is also rec- national review of meningococcal vaccine safety found
ommended in outbreaks caused by vaccine-preventable that fever, injection site hypersensitivity, and allergic re-
serogroups. Because of a moderately increased risk actions were the most common associated events.
(three- to fourfold) of meningococcal disease in college Until better vaccines are available, chemoprophy-
freshmen, the ACIP and AAP recommend that care laxis with rifampin, ceftriaxone, or ciprofloxacin
providers discuss meningococcal vaccination with in- (adults) should be used to prevent meningococcal dis-
coming and current freshmen, and administer vaccine ease in exposed individuals (see Chapter 38).
to those who request it.
Ball R et al: Vaccine Adverse Event Reporting System Working
Because of the severe disease caused by the meningo- Group: Safety data on meningococcal polysaccharide vaccine
coccus and the limitations of the currently licensed vac- from the Vaccine Adverse Event Reporting System. Clin In-
cine, intensive effort is going into the development of fect Dis 2001;32:1273 [PMID: 11303261].
new meningococcal vaccines. However, a number of Centers for Disease Control and Prevention: Prevention and con-
barriers still exist. Because of the global variation in the trol of meningococcal disease in college students: Recommen-
incidence of different meningococcal serogroups, a vac- dations of the Advisory Committee on Immunization Prac-
cine designed for use in the United States and western tices (ACIP). MMWR Morb Mortal Wkly Rep 2000;49(No.
Europe may provide little benefit to the developing RR-7):13 [PMID: 10902835].
world. The bacterial capsule proteins of serogroup B, Centers for Disease Control and Prevention: Prevention and con-
trol of meningococcal disease. Recommendations of the Advi-
which causes a substantial proportion of disease in the sory Committee on Immunization Practices (ACIP).
United States, particularly in infants younger than MMWR Morb Mortal Wkly Rep 2000;49(RR-7):1 [PMID:
1 year old, are poorly immunogenic in humans. Anti- 10902834].
bodies to serogroup B capsular proteins cross-react with Lingappa JR et al: Active Bacterial Core surveillance (ABCs) team:
human embryonal neural tissue, and therefore Surveillance for meningococcal disease and strategies for use
serogroup B vaccines carry a theoretical risk of produc- of conjugate meningococcal vaccines in the United States.
ing autoimmunity. Finally, the relatively low incidence Vaccine 2001;19:4566 [PMID: 11483285].
of meningococcal disease makes studying vaccine effi- Soriano-Gabarro M et al: Vaccines for the prevention of meningo-
cacy difficult and costly. coccal disease in children. Semin Pediatr Infect Dis 2002;
13:182 [PMID: 12199614].
Despite these challenges, there are a number of
promising meningococcal vaccine developments.
Serogroup A and C polysaccharide have been linked to CHOLERA
protein carriers and found to be immunogenic in infants. Cholera causes significant morbidity and mortality
In 1999, the United Kingdom began routine childhood worldwide. It may present only as travelers diarrhea.
immunization with a conjugate meningococcal For travelers, the risk of developing cholera per month
serogroup C vaccine. Early results have shown an 80% of stay in a developing country is low, ranging from
reduction in serogroup C disease in targeted age groups. 0.001% to approximately 0.01%. No cholera vaccines
The only vaccine currently available in the United are available in the United States. Because the causative
States is the quadrivalent A, C, W-135, and Y vaccine bacterium Vibrio cholerae is not invasive, and because
(Menomune, Aventis Pasteur). Each dose contains secretory IgA (sIgA) is crucial, newer vaccines available
50 µg of the four purified capsular polysaccharides. It is in other countries are administered orally. Two oral
approved for children 2 years of age and older. vaccines (one consisting solely of live attenuated bacte-
ria and the other in combination with the B subunit of
Dosage & Schedule of Administration cholera toxin) are safe and immunogenic. Cholera vac-
cination is no longer required for international travel or
Quadrivalent meningococcal vaccine is given as a single for entry into any countries.
0.5-mL subcutaneous injection. It can be given simul-
taneously with other vaccines. It should be given to Ryan ET, Calderwood SB: Cholera vaccines. Clin Infect Dis
high-risk individuals and to those affected by vaccine- 2000;31:561 [PMID: 20472098].
preventable outbreaks. Because reimmunization of
young children produces serogroup A but not
serogroup C antibodies, reimmunization is only recom-
TUBERCULOSIS
mended when there is continued risk of serogroup A In 2000, 22 states in the United States had tuberculosis
infection. incidence rates of less than 3.5 cases/100,000 popula-
280 / CHAPTER 9

tion, setting the stage for possible elimination of the screening). Recently, a case-control study from New
disease in these areas. However, of the 11,795 cases re- York identified that contact with an adult with active
ported to the CDC in 2002, nearly 40% of new cases TB, foreign birth, foreign travel, or a relative with a
of TB occur in persons born in other countries. Bacille positive TST predicted latent TB (with use of the
Calmette-Guérin vaccine (BCG) consists of live attenu- TST). This may justify routinely testing children with
ated Mycobacterium bovis. BCG is not currently indi- these risk factors as well. In 2001 a new test (Quanti
cated for mass use in the United States, chiefly because FERON-TB) that measures the release of interferon-γ
of doubts about its efficacy. BCG is the most widely in whole blood in response to stimulation with purified
used vaccine in the world and has been administered to protein derivative (PPD) was approved by the FDA.
over 2.5 billion people (71% of infants worldwide are This test is not recommended for persons with symp-
vaccinated) with a low incidence of serious complica- toms of active TB who are at increased risk for progres-
tions. It is inexpensive, can be given any time after sion to active TB, but may be used instead of TST in
birth, sensitizes the vaccinated individual for those at increased or low risk for latent TB infection,
5–50 years, and stimulates both B-cell and T-cell im- including as a screening of recent immigrants. BCG al-
mune responses. BCG is useful in two circumstances in most invariably causes its recipients to be tuberculin-
the United States: (1) in tuberculin-negative infants or positive (5–7 mm), but the reaction often becomes neg-
older children residing in households with untreated or ative after 3–5 years. However, a positive Mantoux test
poorly treated individuals with active infection with in a child with a history of BCG vaccination who is
isoniazid- and rifampin-resistant Mycobacterium tuber- being investigated for TB as a case contact should be
culosis and (2) in infants or children found to live under interpreted as indicating infection with M tuberculosis.
constant exposure without the possibility of removal
from continuous exposure or access to prophylaxis and Almeida LMD et al: Use of purified protein derivative to assess the
treatment. BCG reduces the risk of tuberculous menin- risk of infection in children in close contact with adults with
gitis and disseminated TB in pediatric populations by tuberculosis in a population with high Calmette-Guérin
50–100%. BCG appears to have had little epidemio- bacillus coverage. Pediatr Infect Dis J 2001;20:1061 [PMID:
logic effect on TB, despite a reported efficacy of 50% in 11734712].
a meta-analysis of 26 vaccine trials, with the greatest Brewer TF: Preventing tuberculosis with bacillus Calmette-Guérin
protection against pulmonary disease. The two cur- vaccine: A meta-analysis of the literature. Clin Infect Dis
2000;31 (Suppl) 3:S64 [PMID: 11010824].
rently licensed BCG vaccines in the United States are
produced by Connaught Laboratories and Organon Mazurek GH, Villarino ME: CDC. Guidelines for using the Quan-
tiFERON-TB test for diagnosing latent Mycobacterium tuber-
Teknika Corporation. They are given intradermally in culosis infection. Centers for Disease Control and Prevention.
a dose of 0.05 mL for newborns and 0.1 mL for all MMWR Recomm Rep 2003;52(RR-2):15 [PMID:
other children. Mantoux testing is advised 2–3 months 12583541].
later, and revaccination is advised if the Mantoux test is Saiman L et al: Risk factors for latent tuberculosis infection among
negative. Adverse effects occur in 1–10% of healthy in- children in New York City. Pediatrics 2001;107:999 [PMID:
dividuals, including local ulceration, regional lymph 11331677].
node enlargement, and lupus vulgaris. The vaccine is
contraindicated in pregnant women and in immuno-
compromised individuals, including those with HIV
YELLOW FEVER
infection, because it has caused disseminated or fatal Immunization against yellow fever is indicated for chil-
infection. dren as young as age 4 months traveling to endemic
Factors associated with increased probability that a areas or to countries that require it for entry, but other-
positive TB skin test (TST) is due to M tuberculosis in- wise immunization should be delayed until age
fection include (1) larger reactions, (2) contact with an 9 months or older. Public health authorities maintain
individual known to be infected, (3) family history of updated information on these requirements and must
TB, (4) longer interval between BCG administration be consulted. Yellow fever vaccine is a live vaccine made
and skin testing, and (5) country of origin with in- from the 17D yellow fever attenuated virus strain
creased incidence of endemic TB. The details and cut- grown in chick embryos. It is contraindicated in infants
off observations for TB skin testing are described in younger than age 4 months due to an increased suscep-
Chapter 38. To ensure that those infected with TB are tibility to vaccine-associated encephalitis, in pregnant
evaluated, a 5-mm or greater cutoff for a positive Man- women, in persons with anaphylactic egg allergy, and in
toux test is used in immunocompromised children. In immunocompromised individuals. It can only be ad-
immunocompetent persons, the cutoff is 10 mm or ministered at licensed yellow fever vaccination locations
above, whereas it is 15 mm or above when no risk fac- (usually public health departments). A single subcuta-
tors are present in the absence of clinical disease (eg, neous injection of 0.5 mL of reconstituted vaccine is
 IMMUNIZATION / 281

administered. The International Health Regulations re- settings in which repeated exposure to aerosolized B an-
quire revaccination at 10-year intervals, but immunity thracis spores might occur. For military personnel, and
may be lifelong. Adverse reactions are generally mild— for other selected populations for which a calculable risk
consisting of fever, mild headache, and myalgia can be assessed, preexposure vaccination has been used.
5–10 days after vaccination occurring in less than 25% The recommended vaccination schedule is subcuta-
of vaccinees. The risk for vaccine-associated encephali- neous injections at 0, 2, and 4 weeks; then at 6 months,
tis within 30 days following vaccination has been esti- 12 months, and 18 months. Postexposure vaccination
mated to be less than 1/8,000,000 persons. Recently, a consists of three injections: as soon as possible after expo-
new serious adverse reaction syndrome was described. sure and again at 2 and 4 weeks after exposure in combi-
This yellow fever vaccine-associated viscerotropic dis- nation with antimicrobial chemoprophylaxis for 60 days.
ease consists of severe multiple organ system failure and The duration of protection in humans is unknown; how-
death within 1–2 two weeks postvaccination, especially ever, annual booster injections are recommended to
in older adults. These reports have caused a reevalua- maintain immunity. The vaccine has not been evaluated
tion of the vaccine’s use. Health care providers should for safety and efficacy in children younger than age
be careful to administer yellow fever vaccine only to 18 years or in adults older than age 60 years.
persons truly at risk for exposure to yellow fever. There
is no contraindication to giving other live-virus vaccines Adverse Events
simultaneously with yellow fever vaccine or at intervals
of a day to a month. No studies have definitively documented occurrence of
chronic diseases (eg, cancer or infertility) following an-
thrax vaccination. Although controversial, analysis of
Centers for Disease Control and Prevention: Yellow fever vaccine:
Recommendations of the Immunization Practices Advisory
VAERS data documents no pattern of serious adverse
Committee (ACIP), 2002. MMWR 2002;51(RR-17):1 events clearly associated with the vaccine, except mild
[PMID: 22324159]. injection site reactions.
Monath TP: Yellow fever: An update. Lancet Infect Dis 2001;1:
11 [PMID: 21860137]. Centers for Disease Control and Prevention: Use of anthrax vaccine
Thompson MJ: Immunizations for international travel. Prim Care: in the United States: Recommendations of the Advisory
Clin Office Pract 2002;29:787 [PMID:22574700]. Committee on Immunization Practices (ACIP). MMWR
2000;49(RR15):1 [PMID: 21017696].
Centers for Disease Control and Prevention: Use of anthrax vaccine
ANTHRAX in response to terrorism: Supplemental recommendations of
the Advisory Committee on Immunization Practices.
Anthrax is an acute infectious disease caused by the MMWR 2002;51:1024 [PMID: 22346733].
spore-forming bacteria Bacillus anthracis. Although it
occurs most frequently as a disease of cattle, goats, and
sheep, humans may become infected through contact
SMALLPOX (VARIOLA)
with, ingestion of, or inhalation of spores from infected Smallpox is a highly contagious infection caused by the
animals or their products. The spore is durable and can variola virus. In 1972, routine smallpox immunization
be delivered as an aerosol, with an incubation of was discontinued in the United States, and in 1980 the
2–30 days. Inhalation causes the most serious form of World Health Organization declared smallpox to be
human anthrax, making it an attractive agent for poten- eradicated worldwide. In recent years, concern that
tial use by bioterrorists (see Chapter 11). In December smallpox virus stocks may be in the hands of bioterror-
2001, the US Department of Health and Human Ser- ists and potentially released within a nonimmune popu-
vices obtained a limited supply of anthrax vaccine for lation has incited a debate about whether a large-scale
potential preexposure civilian vaccination. The only smallpox immunization should be resumed. A smallpox
available anthrax vaccine in the United States is an inac- immunization plan has been implemented in the
tivated, noninfectious, cell-free anthrax vaccine (BioPort United States to develop smallpox response teams
Corporation). It is prepared from a toxigenic, throughout the nation. The only smallpox vaccine li-
nonenecapsulated strain and is aluminum hydroxide-ad- censed in the United States is a lyophilized, live vac-
sorbed. Routine preexposure vaccination with anthrax cinia virus preparation. Vaccinia is related to variola
vaccine adsorbed (AVA) is indicated for persons at risk and is highly effective in preventing smallpox. Vaccine
for repeated exposure to B anthracis spores, such as labo- is administered using a bifurcated needle to deliver vac-
ratory personnel handling environmental specimens for cine into the epidermis. Vaccine “take” is determined
bioterrorism level B and C laboratories, workers making by the development of a papule progressing to vesicle to
repeated entries into known B anthracis spore-contami- pustule to scab that heals after 14–21 days. Fever is
nated areas after a terrorist attack, and workers in other common after primary immunization and less common
282 / CHAPTER 9

after reimmunization. Severe complications of immu- ment of Kawasaki disease, idiopathic thrombocytopenic
nization include death, postvaccinal encephalitis, pro- purpura, Guillain–Barré syndrome, and other autoim-
gressive vaccinia, myocarditis, eczema vaccinatum, and mune diseases, and chronic B-cell lymphocytic
accidental inoculation to other body sites. Transmission leukemia. IVIg may be beneficial in some children with
of vaccine virus from a recently immunized individual HIV infection, toxic shock syndrome, and for anemia
to a susceptible contact can occur. Smallpox vaccine is caused by parvovirus B19. Specific antibody-enriched
not recommended for people younger than 18 years of IVIg preparations have also been developed for the pre-
age. The US government has contracted for develop- vention and treatment of the following viral infections:
ment of 200 million doses of tissue culture-derived vac- cytomegalovirus immune globulin (CMVIg) for pre-
cinia vaccine and has encouraged development of safer vention and treatment of CMV disease and respiratory
effective smallpox vaccines. Vaccinia immune globulin syncytial virus immune globulin (RSVIg) for preven-
(VIg) is recommended only for the treatment of com- tion of RSV illness in high-risk children. Prophylaxis to
plications of vaccination and not for prophylaxis or prevent RSV in infants and children at increased risk
treatment. for severe disease is available in either an intravenous
(RSV-IVIg) or intramuscular (Palivizumab) prepara-
Abramson JS et al: The US smallpox vaccination plan. Pediatrics tion. Both products should be considered for (1) in-
2002;110:841 [PMID: 22662823]. fants and children younger than age 2 years with
Centers for Disease Control and Prevention: Recommendations for chronic lung disease who have required medical therapy
using smallpox vaccine in a preevent vaccination program. (supplemental oxygen, bronchodilator, diuretic, or cor-
Supplemental recommendations of the Advisory Committee ticosteroid therapy) for their disease within 6 months
on Immunization (ACIP) and the Healthcare Infection Con- before the anticipated RSV season, (2) infants born be-
trol Practices Advisory Committee (HICPAC). MMWR
2003;52:1 [PMID: 22596449]. tween 33 and 35 weeks (32 weeks 1 day and 35 weeks
Centers for Disease Control and Prevention: Smallpox vaccination
0 days) gestation or earlier without chronic lung disease
and adverse reactions: Guidance for clinicians. MMWR with two or more risk factors (child care attendance,
2003;52:1 [PMID: 22504376]. school-age siblings, exposure to environmental air pol-
lution, congenital airway abnormalities, or severe neu-
romuscular disease) up to age 6 months, (3) infants
born at 29–32 weeks up to 6 months of age, and (4) up
PASSIVE PROPHYLAXIS to age 12 months for infants born at 28 weeks or ear-
lier.
Palivizumab is approved for use in children who are
Intramuscular Immune Globulin 24 months old or younger with hemodynamically sig-
Ig may prevent or modify infection with hepatitis A nificant cyanotic or acyanotic congenital heart disease.
virus if administered in a dose of 0.02 mL/kg within Those most likely to benefit from prophylaxis are in-
14 days after exposure. Measles infection may be pre- fants (< 1 year of age) who are receiving medication to
vented or modified in a susceptible person if Ig is given control congestive heart disease, with moderate to severe
in a dose of 0.25 mL/kg within 6 days after exposure. pulmonary hypertension and cyanotic heart disease. An
Special forms of Ig include TIg, HBIg, RIg, VIg, and increased number of cyanotic events occurred following
VZIg. These are obtained from donors known to have RSV-IVIg administration in these infants. RSV prophy-
high titers of antibody against the organism in ques- laxis should be initiated at the onset of the RSV season
tion. Their use has been described earlier in this chap- and continued until the end of the season, regardless of
ter. Palivizumab is a humanized monoclonal antibody breakthrough RSV illness during that RSV season.
against respiratory syncytial virus (RSV) and is used to RSV-IVIg (RespiGam [MedImmune]) is derived
prevent RSV in high-risk populations with monthly from human donors screened for high levels of RSV-
doses during RSV season. neutralizing activity. It is administered intravenously in
Ig must be given intramuscularly. The dose varies a dose of 750 mg/kg once a month during the RSV sea-
depending on the clinical indication. Adverse reactions son. RSV intramuscular monoclonal antibody,
include pain at the injection site, headache, chills, dys- palivizumab (Synagis [MedImmune]), is a humanized
pnea, nausea, and anaphylaxis, although all but the first monoclonal antibody directed against the F glycopro-
are rare. tein of RSV, a surface protein that is highly conserved
among RSV isolates. It is administered in a dose of
15 mg/kg once a month and is packaged in 50- and
Intravenous Immune Globulin 100-mg vials.
The primary indications for IVIg are for replacement Although palivizumab has greater ease of adminis-
therapy in antibody-deficient individuals, for the treat- tration and fewer adverse effects, some considerations
 IMMUNIZATION / 283

may favor the use of RSV-IVIg. Specifically, RSV-IVIg pensation Program (NVICP). The purpose was to pro-
provides protection from other non-RSV respiratory in- vide no-fault compensation for persons found to have
fections, including influenza and acute and recurrent been injured by certain vaccines. Under the terms of
otitis media. In contrast, palivizumab avoids the risk of the act, liability claims against those who administer or
transmission of human pathogens, because it is a pure manufacture vaccines must go before a federal compen-
preparation of RSV antibody. Palivizumab does not in- sation board before a civil suit may be filed. Compensa-
terfere with response to routine childhood vaccinations; tion may be sought for certain events following certain
infants receiving RSV-IVIg should have MMR and immunizations within specified time intervals. The
VAR deferred for 9 months after their last dose. compensation system is funded by a continuing sur-
IVIg must only be administered intravenously. Ad- charge levied against the manufacturers for each dose
verse reactions include headache, flushing, diaphoresis, sold of the specified vaccines.
hypotension, fever, nausea, vomiting, and anaphylaxis. Physicians administering the specified vaccines are
Since November 1997, a shortage of IVIg has existed in also obliged by the act to report any of the specified re-
the United States. Distribution and production factors actions to the VAERS (call 1-800-822-7967 for forms).
have contributed to the shortage, but increased off-label Compensation forms from the NVICP may be ob-
use of the product is also a factor. Despite FDA, Na- tained by calling 1-800-338-2382. The act provides no
tional Institutes of Health, and CDC guidelines, over penalty for failure to report.
50% of IVIg is issued for unapproved purposes. Recognizing the need to improve its capability to
study vaccine safety, the CDC participated in pilot
Feltes TF et al: Palivizumab prophylaxis reduces hospitalization due studies using large linked databases of computerized
to respiratory syncytial virus in young children with hemody- vaccination and medical records. The Vaccine Safety
namically significant congenital heart disease. J Pediatr Datalink Project (which is a network of several health
2003;143:532 [PMID: 14571236]. maintenance organizations’ computerized information
Impact-RSV Study Group: Palivizumab, a human respiratory syn- on immunization, medical outcomes, and potential
cytial virus monoclonal antibody, reduces hospitalization
from RSV infection in high-risk infants. Pediatrics
confounders) was initiated in 1989 and has served as a
1998;102:531. useful tool to accumulate and analyze data as new vac-
Meissner HC, Long SS, American Academy of Pediatrics Commit- cines are introduced.
tee on Infectious Diseases and Committee on Fetus and Vaccine information materials are available from the
Newborn: Revised indications for the use of palivizumab and CDC to meet the requirements of the act. Separate
respiratory syncytial virus immune globulin intravenous for short (1500- to 2000-word) forms are used for DTaP,
the prevention of respiratory syncytial virus infections. Pedi- MMR, and poliovirus vaccines. Patients or parents are
atrics 2003;112(6 Pt 1):1447 [PMID: 14654628]. legally required to sign these forms if the vaccine is pur-
Simoes EA: Immunoprophylaxis of respiratory syncytial virus: chased on a federal contract. Informed consent is also
Global experience. Respir Res 2002;3 (Suppl 1):S26 [PMID:
12119055].
needed for physicians who wish to be covered fully by
the vaccine compensation program. Current recom-
mendations of the AAP and CDC for VCIP were dis-
Antitoxins & Antivenins cussed at the start of this chapter and should be fol-
Igs of animal origin are available for use in certain situa- lowed.
tions. These include botulinum antitoxin, tetanus anti-
toxin, diphtheria antitoxin, and snake and spider an- Atkinson WL et al: Centers for Disease Control and Prevention:
tivenins. A variety of adverse reactions, including acute General recommendations on immunization: Recommenda-
tions of the Advisory Committee on Immunization Practices
febrile responses, anaphylaxis, and serum sickness, may (ACIP) and the American Academy of Family Physicians
develop after use of these products. A schedule for hy- (AAFP). MMWR Recomm Rep 2002;51(RR-2):1 [PMID:
persensitivity testing and desensitization for antisera of 11848294].
equine origin can be found in the Red Book. Chen RT et al: The Vaccine Safety Datalink: Immunization re-
search in health maintenance organizations in the USA. Bull
World Health Organ 2000;78:186 [PMID: 10743283].
Chen RT et al: Vaccine Safety Datalink project: A new tool for im-
LEGAL ISSUES IN proving vaccine safety monitoring in the United States: The
Vaccine Safety Datalink Team. Pediatrics 1997;99:765
IMMUNIZATION [PMID: 9164767].

The National Childhood Vaccine Injury Act of

1986 established two programs: the National Vaccine
Program (NVP) and the National Vaccine Injury Com-
 Normal Childhood Nutrition
& Its Disorders
10
Nancy F. Krebs, MD, MS, Laura E. Primak, RD, CNSD, CSP &
K. Michael Hambridge, MD, BChir, ScD

(CNS) especially vulnerable to the effects of malnutri-

NUTRITIONAL REQUIREMENTS tion in early postnatal life.

NUTRITION & GROWTH ENERGY

The nutrient requirements of children are influenced The major determinants of energy expenditure are basal
by their growth rate and body composition and the metabolism, metabolic response to food, physical activ-
composition of new growth. These factors vary with age ity, and growth. The efficiency of energy use may be a
and are especially important during early postnatal life. significant factor, and thermoregulation may contribute
Growth rates are higher in early infancy than at any in extremes of ambient temperature if the body is inad-
other time, including the adolescent growth spurt equately clothed. Because adequate data on require-
(Table 10–1). Growth rates decline rapidly starting in ments for physical activity in infants and children are
the second month of postnatal life (proportionately unavailable and because individual growth require-
later in the premature infant). Because of their more ments vary, recommendations have been based on cal-
rapid growth rate in early infancy, nutrient require- culations of actual intakes by healthy subjects. The re-
ments are slightly higher in males than in females. cent trend toward lower figures for infants reflects a
Nutrient requirements also depend on body compo- move away from hypercaloric and possibly inappropri-
sition. In the adult, the brain, which accounts for only ate feeding practices that were in vogue in past decades.
2% of body weight, contributes 19% to the total basal Suggested guidelines for energy intake of infants and
energy expenditure. In contrast, in a full-term neonate, young children are given in Table 10–2. Also included
the brain accounts for 10% of body weight and for in this table are calculated energy intakes of infants who
44% of total energy needs under basal conditions. are exclusively breast-fed, which have been verified re-
Thus, in the young infant, total basal energy expendi- cently in a number of centers. Growth velocity of
ture and the energy requirement of the brain are rela- breast-fed infants during the first 3 months typically
tively high. equals or exceeds the 50th percentile for the National
Composition of new tissue is a third factor influenc- Center for Health Statistics (NCHS) grids. The recom-
ing nutrient requirements. For example, fat accounts mended dietary allowances (RDAs) of the Food and
for about 40% of weight gain between birth and Nutrition Board, National Academy of Sciences, and
4 months but for only 3% between 24 and 36 months. National Research Council (10th edition) are not syn-
The corresponding figures for protein are 11% and onymous with requirements. The RDAs do not take
21%; for water, 45% and 68%. The high rate of fat de- into account the rapid changes in requirements that
position in early infancy has implications not only for occur during infancy, especially the first 6 months,
energy requirements but also for the optimal composi- RDAs should therefore be used cautiously for calculat-
tion of infant feedings. ing energy requirements of infants.
Because of the high nutrient requirements for After the first 4 years, energy requirements expressed
growth and the body composition, the young infant is on a body weight basis decline progressively. The esti-
especially vulnerable to undernutrition. Slowed physical mated daily energy requirement is about 40 kcal/kg/d
growth rate is an early and prominent sign of undernu- at the end of adolescence. Approximate daily energy re-
trition in the young infant. The limited fat stores of the quirements can be calculated by adding 100 kcal per
very young infant mean that energy reserves are unusu- year to the base of 1000 kcal per day at age 1 year. Ap-
ally restricted. The relatively large size and continued petite and growth are reliable indices of caloric needs in
growth of the brain render the central nervous system most healthy children, but intake also depends to some
284
Copyright © 2005, 2001, by The McGraw-Hill Companies, Inc. Click here for terms of use.
 NORMAL CHILDHOOD NUTRITION & ITS DISORDERS / 285

Table 10–1. Changes in growth rate, energy required for growth, and body
composition in infants and young children.

Growth Rate
(g/d) Body Composition
Energy Requirements
Age (months) Male Both Female for Growth (kcal/kg/d) Water Protein Fat
a
0–0.25 0 75 11.5 11
0.25–1 40 35 50
1–2 35 30 25
2–3 28 25 16
3–6 20 10 60 11.5 26
6–9 15
9–12 12
12–18 8
18–36 6 2 61 16 21
a
Birth weight is regained by 10 d. Weight loss of more than 10% of birth weight indicates dehydration or
malnutrition; this applies to both formula-fed and breast-fed infants.
Data from Fomon SJ (ed): Infant Nutrition, 2nd ed. WB Saunders, 1974. Used with permission.

extent on the energy density of the food offered. Indi- rather than actual weight. Alternatively the extra daily
vidual energy requirements of normal infants and chil- energy requirement for catch-up growth can be calcu-
dren vary considerably, and malnutrition and disease lated as:
increase the variability. Premature infant energy re-
quirements can exceed 120 kcal/kg/d, especially during 5 × Weight (g) deficit below IBW
illness or when catch-up growth is desired. Interval (days) for correction of deficit
One method of calculating requirements for mal-
nourished patients is to base the calculations on the where 5 kcal is the energy cost of each gram of new tis-
ideal body weight (ie, 50th percentile weight for the pa- sue deposited. These calculations should be adjusted ac-
tient’s length age or 50th percentile weight-for-height) cording to the growth response.

Table 10–2. Recommendations for energy and protein intake.

Energy Protein
(kcal/kg/d) (g/kg/d)
Based on
Measurements Intake from Guidelines for Intake from Guidelines for
Age of Energy Expenditure Human Milk Average Requirements Human Milk Average Requirements
10 days to — 105 120 2.05 2.5
1 month
1–2 months 110 110 115 1.75 2.25
2–3 months 95 105 105 1.36 2.25
3–4 months 95 75–85 95 1.20 2.0
4–6 months 95 75–85 95 1.05 1.7
6–12 months 85 70 90 — 1.5
1–2 years 85 — 90 — 1.2
2–3 years 85 — 90 — 1.1
3–5 years — — 90 — 1.1
Compiled from Krebs NF et al: Growth and intakes of energy and zinc in infants fed human milk. J Pediatr 1994;124:32–9; Garza C, Butte
NF: Energy intakes of human milk-fed infants during the first year. J Pediatr 1990;117:(S)124. Data used with permission.
286 / CHAPTER 10

World Health Organization: Report of a Joint FAO/WHO/UNO proximately 0.2 g of protein per gram of new tissue de-
Expert Consultation: Energy and Protein Requirements. posited). Young infants experiencing rapid recovery
WHO Tech Rep Ser No. 724, 1985;724.
may need as much as 1–2 g/kg/d of extra protein. By
age 1 year, the extra protein requirement is unlikely to
be more than 0.5 g/kg/d. Inadequate protein intake
PROTEIN may occur in breast-fed infants fed low-protein supple-
Only amino acids and ammonium compounds are us- ments (eg, fruit juices), in infants with protein malab-
able as sources of nitrogen in humans. Amino acids are sorption (cystic fibrosis), or in infants fed low-protein
provided through the digestion of dietary protein. Ni- weaning food (eg, cassava) as the dietary staple.
trogen is absorbed from the intestine as amino acids The quality of protein depends on its amino acid
and short peptides. Absorption of nitrogen is more effi- composition. Infants require 43% of protein as essen-
cient from synthetic diets that contain peptides in addi- tial amino acids, and children require 36%. Adults can-
tion to amino acids. Some intact proteins are absorbed not synthesize eight essential amino acids: isoleucine,
in early postnatal life, a process that may be important leucine, lysine, methionine, phenylalanine, threonine,
in the development of protein tolerance or allergy. tryptophan, and valine. Histidine may be added to this
The liver plays a central role in amino acid metabo- list. Cysteine and tyrosine are considered partially es-
lism, including regulation of the absorbed amino acids. sential because their rates of synthesis are limited and
Excess amino acids, including essential amino acids, are may be inadequate in certain circumstances. In young
degraded in the liver, except for the branched-chain infants, synthetic rates for cysteine, tyrosine, and per-
amino acids, which pass into the systemic circulation haps taurine are insufficient for needs. Taurine, an
and are taken up primarily by muscle. Insulin stimu- amino acid used to conjugate bile acids, may also be
lates this uptake and suppresses muscle protein catabo- conditionally essential in infancy. Taurine supplemen-
lism. Protein turnover rates far exceed intake, indicat- tation may improve fat absorption in preterm infants
ing a reuse of amino acids. However, some of these and in infants with cystic fibrosis. Taurine supplements
amino acids released from protein turnover are de- may also improve auditory brainstem evoked potentials
graded. After removal of the amino group, the keto in preterm infants. Lack of an essential amino acid leads
acids are either used directly for energy or converted to to weight loss within 1–2 weeks. Wheat and rice are de-
carbohydrate and fat. Nitrogen is excreted primarily via ficient in lysine, and legumes are deficient in methion-
the kidney as urea. ine. Appropriate mixtures of vegetable protein are
Because there are no major stores of body protein, a therefore necessary to achieve high protein quality.
regular dietary supply of protein is essential. In infants Because the mechanisms for removal of excess nitro-
and children, optimal growth depends on an adequate gen are efficient, moderate excesses of protein are not
dietary protein supply. Relatively subtle effects of pro- harmful and may help to ensure an adequate supply of
tein deficiency are now recognized, especially those af- certain micronutrients. Adverse effects of excessive pro-
fecting tissues with rapid protein turnover rates, such as tein intake may include increased calcium losses in
the immune system and the GI mucosa. urine and, over a life span, increased loss of renal mass.
Relative to body weight, rates of protein synthesis Excessive protein intake may also cause elevated blood
and turnover and accretion of body protein are excep- urea nitrogen, acidosis, hyperammonemia, and, in the
tionally high in the infant, especially the premature in- premature infant, failure to thrive, lethargy, and fever.
fant. Eighty percent of the dietary protein requirement
of a premature infant is used for growth, compared
with only 20% in a 1-year-old child. Protein require- Denne SC: Protein and energy requirements of preterm infants.
ments per unit of body weight decline rapidly during Semin Neonatal 2001;6:377 [PMID: 11988027].
infancy as growth velocity decreases. The recommenda- Heird WC: Determination of nutritional requirements in preterm
infants, with special reference to “catch-up” growth. Semin
tions in Table 10–2 are derived chiefly from the Joint Neonatol 2001;6:365 [PMID: 11988026].
FAO/WHO/UNO Expert Committee and are similar
to the RDAs. They deliver a protein intake above the
quantity provided in breast milk. The protein intake re-
quired to achieve protein deposition equivalent to the
LIPIDS
in utero rate in very low birth weight infants is Fats are the main dietary energy source for infants and
3.7–4.0 g/kg/day simultaneous with adequate energy account for up to 50% of the energy in human milk.
intake. Protein requirements increase in the presence of Over 98% of breast milk fat is triglyceride, which has
skin or gut losses, burns, trauma, and infection. Re- an energy density of 9 kcal/g. Fats can be stored effi-
quirements also increase during times of catch-up ciently in adipose tissue with a minimal energy cost of
growth accompanying recovery from malnutrition (ap- storage. This is especially important in the young in-
 NORMAL CHILDHOOD NUTRITION & ITS DISORDERS / 287

fant. Fats are required for the absorption of fat-soluble lumen of the gut. Substantial hydrolysis of triglycerides
vitamins and for myelination of the CNS. Fat also pro- in milk formulas occurs in the stomach by the action of
vides essential fatty acids (EFAs) necessary for brain de- lingual and gastric lipases. Pancreatic lipases and bile
velopment, for phospholipids in cell membranes, and salt levels are relatively low in early postnatal life, but
for the synthesis of prostaglandins and leukotrienes. breast milk contains a bile salt-stimulated lipase that is
The EFAs are polyunsaturated fatty acids, linoleic acid effective in the lumen of the duodenum. Bile salts pro-
(18:2ω6) and linolenic acid (18:3ω3). Arachidonic acid mote the formation of the colipase–lipase complex,
(20:4ω6) is derived from dietary linoleic acid and is which adheres to the triglycerides prior to hydrolysis.
present primarily in membrane phospholipids. Oxy- Bile salts also have a major role in the emulsification of
genation of arachidonic acid through the lipoxygenase fatty acids, allowing their passage through the unstirred
pathway yields leukotrienes, and oxygenation through water layer to the surface of the mucosal cell. After pas-
the cyclooxygenase pathway yields prostaglandins. Im- sage into the enterocyte, long-chain (≥ C12) fatty acids
portant derivatives of linolenic acid are eicosapen- and monoglycerides are reesterified to triglycerides and
taenoic acid (20:6ω3) and docosahexaenoic acid are packaged with phospholipids, cholesterol, and pro-
(22:6ω3) found in human milk and brain lipids. Visual tein into chylomicrons, which are transported in the
attention and possibly psychomotor development of lymphatics to the liver and thence the circulation. At
formula-fed premature infants is improved in formulae the capillary endothelial surface of adipose and muscle
supplemented with 20:6ω3, which is not derived read- tissue, lipoprotein lipase (LPL) hydrolyzes triglycerides
ily from 18:3ω3. from chylomicrons, releasing free fatty acids and glyc-
Clinical features of EFA ω6 deficiency include erol, which are taken up by the adjacent cells. LPL also
growth failure, erythematous and scaly dermatitis, cap- hydrolyzes triglycerides synthesized in the liver and
illary fragility, increased fragility of erythrocytes, transported to peripheral tissues as very low density
thrombocytopenia, poor wound healing, and suscepti- lipoproteins.
bility to infection. The clinical features of deficiency of Beta-oxidation of fatty acids occurs in the mito-
ω3 fatty acids are less well defined, but dermatitis and chondria of muscle and liver. Carnitine is necessary for
neurologic abnormalities including blurred vision, pe- oxidation of the fatty acids, which must cross the mito-
ripheral neuropathy, and weakness have been reported. chondrial membranes as acylcarnitine. Carnitine is syn-
Marine oil-supplemented formula improves visual acu- thesized in the human liver and kidney from lysine and
ity of preterm infants through age 4 months by improv- methionine. Carnitine needs of infants are met by
ing docosahexaenoic acid status. Fatty fish are the best breast milk or formulas, and carnitine is now added
dietary source of ω3 fatty acids. A high intake of fatty routinely to soy-based formulas. In the liver, substantial
fish is associated with decreased platelet adhesiveness quantities of fatty acids are converted to ketone bodies,
and decreased inflammatory response. which are then released into the circulation as an im-
Up to 5–10% of fatty acids in human milk are portant fuel for the brain of the young infant.
polyunsaturated. Most of these are ω6 series with smaller MCTs are sufficiently soluble that micelle formation
amounts of long-chain ω3 fatty acids. About 40% of is not required for transport across the intestinal mu-
breast milk fatty acids are monounsaturates, primarily cosa. They are transported directly to the liver via the
oleic acid (18:1), and up to 10% of total fatty acids are portal circulation. MCTs are rapidly metabolized in the
medium-chain triglycerides (MCTs) (C8 and C10) with a liver, undergoing beta-oxidation or ketogenesis. They
calorie density of 7.6 kcal/g. In general, the percentage of do not require carnitine to enter the mitochondria. Ke-
calories derived from fat is a little lower in infant formu- tones are formed from MCTs even when provided
las than in human milk. Infant formulas usually contain orally. MCTs are useful for patients with luminal phase
a relatively high percentage of linoleic acid but very little defects, absorptive defects, and chronic inflammatory
long-chain ω3 fatty acid. The American Academy of Pe- bowel disease. The potential side effects of MCT ad-
diatrics recommends that infants receive at least 30% of ministration include diarrhea when given in large quan-
calories from fat, with at least 1.7% of total calories from tities; high octanoic acid levels in patients with cirrho-
ω6 fatty acids and 0.5% from ω3 fatty acids. It is appro- sis; and, if they are the only source of lipids, deficiency
priate that 40–50% of energy requirements be provided of EFA.
as fat during the first 2 years of life. Children older than
2 years should be switched gradually to a diet containing
approximately 30% of total calories from fat, with no
more than 10% of calories either from saturated fats or
Auestad N et al: Growth and development in term infants fed long-
polyunsaturated fats. chain polyunsaturated fatty acids: A double-masked, random-
During digestion, triglycerides are hydrolyzed to ized, paralleled, prospective, multivariate study. Pediatrics
monoglycerides, free fatty acids, and glycerol in the 2001;108:372 [PMID: 11483802].
288 / CHAPTER 10

Jensen CL, Heird WC: Lipids with an emphasis on long-chain retic basis for the composition of oral rehydration solu-
polyunsaturated fatty acids. Clin Perinatol 2002;29:261 tions in the management of diarrhea. The glucose en-
[PMID: 12168241].
hances the absorption of sodium (and thus of water)
Willatts P, Forsyth JS: The role of long chain polyunsaturated fatty and also supplies some energy.
acids in infant cognitive development. Prostaglandins Leukot
Essent Fatty Acids 2000;63:95 [PMID: 10970720]. During and immediately following a meal, plasma
glucose levels are maintained by glucose absorption. If
less than 10% of dietary energy is regularly provided by
carbohydrate, ketosis results. Between 2–4 hours after a
CARBOHYDRATES meal, plasma glucose depends increasingly on use of he-
The energy density of carbohydrate is 4 kcal/g. Approx- patic glycogen stores. These provide only 100–150 g glu-
imately 40% of caloric intake in human milk is in the cose in the adult and only 6 g in the neonate. After liver
form of lactose, or milk sugar. Lactose supplies 20% of glycogen is depleted, the body progressively depends on
the total energy in cow’s milk. The percent of total en- gluconeogenesis. Glucose is the principal fuel for the
ergy in infant formulas from carbohydrate is similar to brain and is the main energy source for other tissues, in-
that of human milk. cluding red and white blood cells.
After the first 2 years of life, 55–60% of energy re- Children and adolescents in North America con-
quirements should be derived from carbohydrates, with sume large quantities of sucrose in soft drinks, candy,
no more than 10% from simple sugars. These dietary syrups, and sweetened breakfast cereals. A high sucrose
guidelines are, unfortunately, not reflected in the diets intake may predispose a child to obesity and is a major
of North American children, who typically derive 25% risk factor for dental caries. Sucrase hydrolyzes sucrose
of their energy intake from sucrose and less than 20% to glucose and fructose in the brush border of the small
from complex carbohydrates. intestine. Fructose is absorbed more slowly than and in-
The rate at which lactase hydrolyzes lactose to glu- dependently of glucose by facilitated diffusion. This
cose and galactose in the intestinal brush border deter- characteristic can be an advantage. Neither fructose nor
mines how quickly milk carbohydrates, are absorbed. galactose stimulates insulin secretion. Fructose, how-
Lactase levels are highest in young infants, declining by ever, is easily converted to hepatic triglycerides, which
more than 50% later in the first year. Lactase levels de- may be undesirable in malnourished patients.
cline further with age depending on genetic factors. Dietary fiber can be classified in two major types:
Lactose-intolerant children experience varying degrees nondigested carbohydrate (β1–4 linkages) and noncar-
of symptoms depending on the specific activity of their bohydrate (lignin). Insoluble fibers (cellulose, hemicel-
own intestinal lactase and the amount of lactose con- lulose, and lignin) increase stool bulk and water content
sumed. Lactase is located predominantly at the tip of and decrease gut transit time. They may impair mineral
the intestinal villi, where it is especially vulnerable to absorption. Soluble fibers (pectins, mucilages, oat bran)
the effects of gastroenteritis or malnutrition. Thus, it bind bile acids and reduce lipid and cholesterol absorp-
may be helpful to avoid giving lactose-containing foods tion. Pectins also slow gastric emptying and the rate of
to children recovering from gastroenteritis or malnutri- nutrient absorption. Fiber intakes are low in North
tion, although this is not universally necessary. Galac- America. Few data regarding the fiber needs of children
tose is preferentially converted to glycogen in the liver are available. Federally recognized standards for dietary
prior to conversion to glucose for subsequent oxidation. fiber intake do not yet exist. However, the American
Infants with galactosemia, an inborn metabolic disease Academy of Pediatrics suggests 0.5 g dietary fiber for
caused by deficient galactose-1-phosphate uridyltrans- every kilogram of the child’s weight, up to 35 g/d. The
ferase, require a lactose-free diet starting in the neonatal American Health Foundation recommends that chil-
period. dren older than 2 years consume in grams per day an
Starch is broken down in the lumen of the gut into amount of fiber equal to 5 plus the age in years.
disaccharides and oligosaccharides, which are hy-
drolyzed into glucose by maltase, isomaltase, and glu-
coamylase in the brush border. Glucoamylase, which
MAJOR MINERALS
hydrolyzes oligosaccharides of 4–9 glucose units, is lo- (See Table 10–3 for recommended intakes.)
cated predominantly at the base of the villi, where it
may be protected from partial villus atrophy. Glucose Calcium
polymers of this length are used extensively in infant
formulas and as caloric supplements. Advantages in- The major dietary sources of calcium are milk and other
clude a relatively low osmolality and better hydrolysis dairy products. Although some calcium is available from
by the damaged mucosa. Glucose and galactose are ab- legumes, broccoli, some green leafy vegetables, and forti-
sorbed actively with sodium. This provides the theo- fied cereals, it is difficult to achieve an adequate calcium
 NORMAL CHILDHOOD NUTRITION & ITS DISORDERS / 289

Table 10–3. Summary of dietary reference intakes for selected minerals

and trace elements

14–18 yr 14–18 yr
0–6 mo 7–12 mo 1–3 yr 4–8 yr 9–13 yr male female
Calcium 210a 270a 500a 800a 1300a 1300a 1300a
(mg/d)
Phosphorus 100a 275a 460a 500 1250 1250 1250
(mg/d)
Magnesium 30a 75a 80 130 240 410 360
(mg/d)
Iron 0.27a 11 7 10 8 11 15
(mg/d)
Zinc 2a 3 3 5 8 11 9
(mg/d)
Copper 200a 220a 340 440 700 890 890
(µg/d)
Selenium 15a 20a 20 30 40 55 55
(µg/d)
a
Adequate Intakes (AI). All other values represent the Recommended Dietary Allowances (RDA).
Both the RDA and AI may be used as goals for individual intakes.
National Academy of Sciences, Food and Nutritional Board, Institute of Medicine: Dietary Refer-
ence Intakes, Applications in Dietary Assessment. National Academy Press, Washington, DC 2000:
287–289. http://www.nap.edu.

intake without dietary dairy products or calcium supple- portant implications for achieving peak bone density
mentation. Average calcium absorption, is 20–30%, but and minimizing postmenopausal osteoporosis.
calcium absorption from human milk is 60%. Absorp-
tion is enhanced by lactose, glucose, and protein and is
impaired by phytate, fiber, oxalate, and unabsorbed fat. Phosphorus
Control of calcium absorption is exerted primarily by Phosphorus is abundant in meats, eggs, dairy products,
variations in serum 1,25-dihydroxycholecalciferol (cal- grains, legumes, and nuts. Phosphorus levels are high in
citriol), which increases in response to increases in circu- processed foods and very high in colas and other soft
lating parathyroid hormone (PTH). PTH is secreted in drinks. Approximately 80% of dietary phosphorus is
response to a fall in plasma ionized calcium. It also pro- absorbed; the kidney is responsible for homeostatic
motes the release of calcium from bone. Calcium is ex- control. PTH decreases tubular reabsorption of phos-
creted primarily via the kidney. It is the most abundant phorus. More than 85% of body phosphorus is in
mineral in the body, and more than 99% is in the skele- bone. Phosphorus is also a component of many organic
ton. Many vital cellular processes depend on calcium, compounds with vital metabolic roles, including adeno-
especially changes in cytosolic free calcium levels. sine triphosphate (ATP) and 2,3-diphosphoglycerate.
Changes in these levels also occur in various pathologic Many of the clinical effects of phosphorus depletion are
states and can grossly disturb intracellular metabolism. attributable to cellular energy depletion from lack of
A deficiency in dietary calcium can occur in premature ATP or to cellular anoxia secondary to impaired release
infants and lactating adolescents as a result of restricted of oxygen from hemoglobin. Other key compounds
milk intake and also in patients with steatorrhea. Defi- containing phosphorus include cell membrane phos-
cient calcium intake results in decreased bone density. pholipids and nucleotides.
Bone density increases with increasing calcium intake Nutritional phosphorus deficiency is rare but has
up to a daily intake of more than 1000 mg in adoles- occurred in very premature infants fed human milk, in
cents. Maximizing bone density in adolescence has im- whom it can produce osteoporosis and rickets, and in
290 / CHAPTER 10

patients with severe protein-energy malnutrition. Non- salt added to processed foods during manufacturing.
nutritional phosphorus depletion may result from The 10% derived from unprocessed foods is sufficient
chronic diarrhea, Fanconi tubulopathy, and the inges- to meet normal requirements. Current dietary recom-
tion of phosphorus-binding antacids. Severe hypophos- mendations suggest that North Americans should re-
phatemia results from a deficiency together with an duce sodium intake so as to restore a normal ratio of di-
acute extracellular-to-intracellular shift in phosphorus. etary sodium to potassium. The present ratio is
This shift can be triggered by glucose, by insulin, or approximately 2:1, but in other cultures and in other
during nutritional rehabilitation of the malnourished mammalian species the ratio is 0.25:1. A high sodium-
patient. Phosphorus deficiency affects most organ sys- to-potassium ratio has been implicated in the patho-
tems, including muscle (weakness progressing to rhab- genesis of hypertension, especially if the intake of di-
domyolysis), cellular components of blood (both physi- etary calcium is low.
ologic and functional changes), the GI system, the Excessive sweating or high sweat sodium (as in cystic
CNS, and bone (bone pain, osteomalacia). Respiratory fibrosis) may increase the requirement for dietary
insufficiency may result from weakness of the di- sodium. Sodium deficiency occurs most commonly as a
aphragm. Phosphate depletion in the premature infant result of diarrhea and vomiting. Anorexia, vomiting,
can cause hypercalcemia. Phosphorus depletion can be and mental apathy may result from chronic depletion
treated with phosphorus salts or skim milk. Phosphorus of sodium chloride. Hyponatremic and hypernatremic
excess may cause neonatal tetany due to decreased dehydration are discussed in Chapter 42.
serum calcium. Phosphorus retention in chronic renal Severe malnutrition and severe stress or hypermetab-
disease leads to metabolic bone disease. olism can disturb the ionic gradient across cell mem-
branes and lead to excess intracellular sodium, which
can adversely affect cellular metabolism. Sodium should
Magnesium be administered with great caution in these circum-
stances. Suggested dietary intake of sodium for infants
Two thirds of dietary magnesium is derived from veg-
is 50 mg/kg/d; for children older than 1 year, it is
etables, cereals, and nuts. The kidney controls magne-
250–500 mg/d.
sium homeostasis by minimizing excretion when intake
is low. Magnesium is the second most abundant intra-
cellular cation; 50% is in bone. Levels in the cytosol are
10 times that in the extracellular fluids and are especially Chloride
high in mitochondria. Magnesium activates many en-
The intake and homeostasis of dietary chloride are
zymes, especially phosphorus-hydrolyzing and -transfer-
closely linked with those of sodium. However, chloride
ring enzymes involved in energy metabolism. Magne-
is itself important in the physiologic mechanisms of the
sium also plays major roles in nucleic acid metabolism.
kidney and the gut. Active chloride transport in the as-
Dietary magnesium deficiency is not recognized ex-
cending loop of Henle is necessary for the passive reab-
cept as a component of protein-energy malnutrition,
sorption of sodium. Deficiency of chloride leads to a
but magnesium depletion may occur secondary to renal
decrease in the absorption of sodium in the ascending
disease, intestinal malabsorption, or medications induc-
loop of Henle and an increase in the amount of sodium
ing magnesium loss from the gut or kidney. Hypomag-
presented to the distal tubule. This sodium is ex-
nesemia produces neuromuscular excitability, muscle
changed for H+ and K+, which can result in hy-
fasciculation and tremors, personality changes, neuro-
pokalemic alkalosis.
logic abnormalities, and electrocardiographic changes
Infants fed formulas low in chloride have experi-
(depression of ST segment and T waves). Disturbances
enced a nutritional deficiency of chloride. Other causes
of PTH metabolism can cause secondary hypocalcemia.
of chloride deficiency include cystic fibrosis, pyloric
Acute magnesium depletion can be treated with a 50%
stenosis and other causes of vomiting, familial chloride
solution of MgSO4, providing 0.3–1.0 mEq of magne-
diarrhea, chronic diuretic (furosemide) therapy, and
sium per kilogram given intravenously over a 24-hour
Bartter syndrome. Chloride deficiency has been associ-
period. Magnesium excess can cause respiratory depres-
ated with failure to thrive and may especially affect
sion, lethargy, and coma.
head growth. Other features include anorexia, lethargy,
muscle weakness, vomiting, dehydration, and hypo-
volemia. Laboratory features include hypochloremia,
Sodium hypokalemia, metabolic alkalosis, and hyperreninemia.
In the United States and western Europe, only 10% of Suggested dietary intake of chloride for infants is
sodium intake is derived from unprocessed foods; 15% 70 mg/kg/d; for children older than 1 year, it is
is derived from salt added while cooking and 75% from 700 mg/d.
 NORMAL CHILDHOOD NUTRITION & ITS DISORDERS / 291

Potassium testinal function. The GI tract is the major site of

homeostatic control for iron and zinc; the liver for cop-
Potassium is readily available in unprocessed foods, in- per; the intestinal tract and liver for manganese; and the
cluding nuts, whole grains, meats and fish, beans, ba- kidneys for selenium, chromium, and iodine.
nanas, and orange juice. Relatively high potassium in- Deficiencies of iron, zinc, and possibly copper,
takes are encouraged except in the presence of renal occur in the free-living population. In certain geo-
failure. The kidneys control potassium homeostasis via graphic regions iodine and selenium deficiency is com-
the aldosterone–renin–angiotensin endocrine system. mon because of deficiencies in soil and water. Infants
Potassium is the principal intracellular cation. The exclusively fed cow’s milk are at risk for iron and cop-
amount of total body potassium, therefore, depends on per deficiency. Excessive loss and impaired absorption
lean body mass. Potassium deficiency occurs in protein- can cause iron, zinc, or copper deficiency. Trace ele-
energy malnutrition and can be a cause of sudden death ment deficiencies have been associated with the use of
from cardiac failure if not treated aggressively during synthetic diets and especially intravenous (IV) nutri-
the initial phase of rehabilitation. Because of loss of tion. Protein-energy malnutrition may be complicated
lean body mass, excessive potassium is excreted in the by deficiencies in iron, zinc, copper, selenium, or
urine in any catabolic state. This too requires aggressive chromium. Deficiencies in zinc, copper, iron, and
replenishment during recovery. During acidosis, intra- molybdenum occur as a result of specific genetic dis-
cellular potassium is exchanged for H+. Potassium is eases affecting the absorption or metabolism of these el-
shifted into the extracellular fluid, and large amounts ements (see Chapter 33).
may be lost in the urine (eg, in diabetic ketoacidosis)
despite normal or elevated plasma potassium. Other
causes of potassium deficiency are diarrhea and diuret- Zinc
ics. Potassium deficiency may produce muscle weak- Zinc is a component of many enzymes and plays im-
ness, mental confusion, and sudden death from ar- portant roles in nucleic acid metabolism, protein syn-
rhythmias. Electrocardiographic findings include thesis, and membrane structure and function. Zinc de-
depression of the ST segment and low T waves. Hyper- ficiency is the result of diets low in available zinc (high
kalemia may result from renal insufficiency. Suggested phytate) and synthetic diets (oral or IV) lacking ade-
dietary intake of potassium for infants is 80 mg/kg/d; quate zinc supplements. Diseases associated with im-
for children older than 1 year, it is 800 mg/d. paired absorption (regional enteritis, celiac disease, cys-
tic fibrosis) or excessive loss (chronic diarrhea), and
inborn diseases of zinc metabolism may produce a state
TRACE ELEMENTS of zinc deficiency. Although the zinc in human milk is
Trace elements with a recognized role in human nutri- very efficiently absorbed, the zinc concentration in
tion are iron, iodine, zinc, copper, selenium, man- breast milk steadily declines over time. After 6 months,
ganese, molybdenum, chromium, cobalt (as a compo- the exclusively breast-fed infant is likely to need addi-
nent of vitamin B12), and fluoride. Dietary tional zinc from complementary foods.
requirements of trace elements are summarized in Several recent large trials have shown that zinc sup-
Table 10–3. Iron deficiency is discussed in Chapter 27. plementation in infants and young children is associ-
In general, good dietary sources of trace elements in- ated with a significant reduction in the incidence of
clude human milk, meats, shellfish, legumes, nuts, and pneumonia and of acute and chronic diarrhea. Im-
whole-grain cereals. Fish are a good source of selenium. proved zinc status has also been associated with im-
Absorption of iron, zinc, copper, and probably other proved immunocompetence. Low-birth-weight infants
trace elements from human milk is especially efficient; appear to be particularly vulnerable to zinc deficiency,
healthy full-term breast-fed infants generally do not re- and randomized trials of zinc supplementation in devel-
quire exogenous trace elements, including iron, until oping countries have shown significant improvements
approximately 6 months. Factors affecting trace ele- in growth as well as reduction in the mortality and
ment absorption include the quantity in the diet, the si- morbidity associated with infection. Mild deficiency is
multaneous ingestion of foods promoting the forma- associated with impaired growth and poor appetite. Se-
tion of insoluble complexes (phytate, fiber, phosphate, vere deficiency is characterized by mood changes, irri-
oxalate), the oxidation state of the element (ascorbic tability, and lethargy. Impairment of the immune sys-
acid increases iron absorption and decreases copper ab- tem, especially T-cell function, has been linked to
sorption), its chemical form in the diet (heme versus increased susceptibility to infection. The most severe
nonheme iron), competitive inhibition of mucosal ab- deficiency state is characterized by an acroorificial skin
sorption (interactions of iron, zinc, and copper), and rash, usually accompanied by diarrhea and alopecia.
host factors such as nutritional status, diarrhea, and in- These features occur in patients with acrodermatitis en-
292 / CHAPTER 10

teropathica, an inborn error of zinc metabolism, in sub- cupping and flaring of long-bone metaphyses, and
jects receiving IV feeding without adequate zinc supple- spontaneous rib fractures may occur. The radiologic
ments, and in some breast-fed infants whose mothers findings must be distinguished from child abuse (asym-
have a defect in the secretion of zinc by the mammary metrical fractures), rickets, and scurvy. Neutropenia
gland. Plasma zinc collected before breakfast is below and hypochromic anemia are other early manifesta-
6 µmol/L (40 µg/dL) in patients with severe zinc defi- tions. The anemia is unresponsive to iron therapy. Very
ciency and 6–9 µmol/L (40–60 µg/dL) in patients with severe CNS disease is present in Menkes steely (kinky)
moderate zinc deficiency. In patients with mild zinc de- hair syndrome, in which a profound copper deficiency
ficiency, plasma zinc concentration may be within the state results from an X-linked defect in cellular metabo-
normal range (60–100 µg/dL). lism of copper.
Dietary zinc deficiency can be treated with A low plasma copper or ceruloplasmin level helps
1 mg/kg/d of zinc for 3 months (eg, 4.5 mg of ZnSO4 confirm the diagnosis of copper deficiency. However,
+ 7 H2O/kg/d), preferably administered separately these levels are normally very low in the young infant,
from meals and iron supplements. Sustained clinical re- especially the premature infant, and are higher than
mission in acrodermatitis enteropathica is usually adult values in later infancy and early childhood.
achieved with 30–50 mg Zn2+ per day, but larger quan- Hence, age-matched normal data are necessary for com-
tities may be required. parison. Interleukin-1 grossly elevates both ceruloplas-
min and copper levels; the levels are also high in preg-
Black RE: Zinc deficiency, infectious disease and mortality in the nancy.
developing world. J Nutr 2003;133:1485S [PMID: Copper deficiency can be treated with a 1% copper
12730449]. sulfate solution (2 mg of the salt or 500 mg of elemen-
Gibson RS: Zinc supplementation for infants. Lancet 2000;355: tal copper per day for infants).
2008 [PMID: 10885346].
Krebs NF et al: Abnormalities in zinc homeostasis in young infants
with cystic fibrosis. Pediatr Res 2000;48:256 [PMID: Olivares M et al: Copper homeostasis in infant nutrition: Deficit
10926304]. and excess. J Pediatr Gastroenterol Nutr 2000;31(2):102
[PMID: 10941959].
Sazawal S et al: Zinc supplementation in infants born small for ges-
tational age reduces mortality: A prospective, randomized,
controlled trial. Pediatrics 2001;108:1280 [PMID: Selenium
11731649].
Selenium is an essential component of glutathione per-
oxidase, which catalyzes the reduction of hydrogen per-
Copper oxide to water in the cell cytosol by the addition of re-
Copper is a vital component of several oxidative en- ducing equivalents derived from glutathione. Hence,
zymes: cytochrome c oxidase, the terminal oxidase in selenium plays an important role in protection against
the electron transport chain; cytosolic and mitochondr- free-radical injury.
ial superoxide dismutase, which have key roles in the Selenium deficiency is the major causal factor in Ke-
body defense against free radicals; lysyl oxidase, which shan disease, an often fatal cardiomyopathy primarily
is necessary for the cross-linking of elastin and collagen; affecting infants, children, and young women in a large
and ferroxidases (including ceruloplasmin) necessary for area of China where there is a severe geochemical sele-
the oxidation of ferrous storage iron to ferric iron prior nium deficiency. Similar cases have been identified in
to attachment to transferrin for transport to the red cell the United States in patients maintained on long-term
precursors in the bone marrow. Cu2+ is highly reactive TPN without adequate selenium supplement, in whom
and must be transported in the circulation bound to symptoms also include skeletal muscle pain and tender-
ceruloplasmin so that its oxidative potential can be con- ness. Macrocytosis and loss of hair pigment occur in
tained. milder selenium deficiency. Premature infants have ex-
Copper deficiency occurs in the following circum- ceptionally low serum selenium levels, which decline
stances: in premature infants fed milk preparations low further without supplementation. Blood levels are espe-
in copper; in association with prolonged feeding with cially low in premature infants with bronchopulmonary
unmodified cow’s milk; in association with generalized dysplasia. The minimum recommended selenium con-
malnutrition; in patients maintained on prolonged total tent for full-term infant formulas is 1.5 µg/100 kcal,
parenteral nutrition (TPN) without copper supplemen- and that for preterm infant formulas is 1.8 µg/100 kcal.
tation; and in patients with intestinal malabsorption or A plasma selenium level less than 0.5 µmol/L
prolonged diarrhea. (< 40 µg/L) suggests mild selenium deficiency. A level
Osteoporosis is an early finding of copper defi- less than 0.12 µmol/L (< 10 µg/L) indicates a possible
ciency. Later, enlargement of costochondral cartilages, severe selenium deficiency.
 NORMAL CHILDHOOD NUTRITION & ITS DISORDERS / 293

Iodine Table 10–4. Supplemental fluoride

Endemic goiter resulting from environmental iodine recommendations (mg/d).
deficiency has been eradicated in North America by
prophylactic measures but continues to be a health Concentration of Fluoride
problem in many developing countries. Goiter occurs in Drinking Water
when iodine intake is less than 20 mg/d. Most persons Age < 0.3 ppm 0.3–0.6 ppm > 0.6 ppm
with endemic goiter are clinically euthyroid. Maternal
iodine deficiency causes endemic neonatal hypothy- 6 months to 3 years 0.25 0 0
roidism in about 5–15% of neonates who may have 3–6 years 0.5 0.25 0
goiter at birth.
6–16 years 1 0.5 0
Neurologic endemic cretinism, seen in most parts
of the world, is characterized by severe mental re- Reprinted, with permission, from Centers for Disease Control and
tardation, deaf–mutism, spastic diplegia, and strabis- Prevention: Recommendations for using fluoride to prevent and
mus. Evidence of hypothyroidism is usually absent, control dental caries in the United States. MMWR Morb Mortal
and it is thought that the neurologic damage is due to a Wkly Rep 2001;50(RR-14):8.
direct effect of fetal iodine deficiency or to an imbal-
ance between thyroxine (low) and triiodothyronine
(normal or elevated). Myxedematous endemic cre- VITAMINS
tinism occurs in some central African countries. Signs
of congenital hypothyroidism are present. Milder neu- 1. Fat-Soluble Vitamins
rologic damage occurs in some cases of endemic neona-
tal goiter. Because they are insoluble in water, the fat-soluble vita-
The use of iodized salt has been highly effective in mins require digestion and absorption of dietary fat and
preventing goiter. In areas where endemic goiter occurs, a carrier system for transport in the blood. Deficiencies
intramuscular depot injections of iodized oil have also in these vitamins develop more slowly than deficiencies
been used for prevention. in water-soluble vitamins because the body accumulates
stores of fat-soluble vitamins. Excessive intakes carry a
considerable potential for toxicity (Table 10–5).
Fluoride
Vitamin A
When fluoride is incorporated into the hydroxyapatite
matrix of dentin, it effectively reduces the incidence of Dietary sources of vitamin A include dairy products,
dental caries. Fluoride is most effectively administered fortified margarine, eggs, liver, meats, fish oils, and
as an additive to drinking water, but in infancy and corn. The vitamin A precursor β-carotene is abundant
childhood, fluoride vitamin preparations serve the same in yellow and green vegetables. Dietary retinyl palmi-
purpose. Ready-made formulas contain less than tate requires hydrolysis by pancreatic and intestinal hy-
0.3 ppm of fluoride. The recognized benefits of topical drolases. β-Carotene is cleaved in the intestinal mucosal
fluoride supplementation in preventing caries must be cells by dioxygenase to yield two molecules of retinal
weighed against the increasing incidence of fluorosis in (retinaldehyde), which is then reduced to retinol (vita-
children in the United States. Fluorosis is characterized min A alcohol). Carotene appears to have an important
by an increased porosity (undermineralization) of the role in its own right as an antioxidant.
enamel and is evident clinically as discoloration of the Retinol is reesterified in the intestinal mucosa and
teeth. Recommendations for fluoride supplementation transported in chylomicrons to the liver for storage.
in infants have been revised (Table 10–4). The Ameri- From the liver, vitamin A is exported to the body at-
can Academy of Pediatrics Committee on Nutrition, tached to retinol-binding protein and prealbumin.
recommends withholding fluoride supplementation Retinol-binding protein may be decreased in liver dis-
until age 6 months. ease or in protein-energy malnutrition. Circulating
retinol-binding protein may be increased in chronic
renal failure.
Vitamin A has a critical role in the photochemical
Centers for Disease Control and Prevention: Recommendations for
using fluoride to prevent and control dental caries in the
basis of vision. The photosensitive pigment rhodopsin
United States. MMWR Morb Mortal Wkly Rep 2001;50(no. is formed from retinal and a protein called opsin. Vita-
RR-14):1. min A also modifies differentiation and proliferation of
Klein CJ: Nutrient requirements for preterm infant formulas. epithelial cells, especially in the respiratory tract. Vita-
J Nutr 2002;132:1472S [PMID: 12042465]. min A is necessary for glycoprotein synthesis. Retinol
294 / CHAPTER 10

Table 10–5. Effects of vitamin toxicity. The features of vitamin A deficiency are primarily
related to the eye and vision. Night blindness progresses
Thiamin to xerosis (dryness of cornea and conjunctiva), xeroph-
(Very rare.) Anaphylaxis; respiratory depression thalmia (extreme dryness of the conjunctiva), Bitot
Riboflavin spots, keratomalacia (clouding and softening of the
None cornea), ulceration and perforation of the cornea, pro-
Pyridoxine lapse of the lens and iris, and eventually blindness. Vit-
Sensory neuropathy at doses > 500 mg/d amin A deficiency is the leading cause of blindness in
Niacin children worldwide. Other features of vitamin A defi-
Histamine release → cutaneous vasodilation; cardiac ar- ciency include follicular hyperkeratosis (dry, thickened,
rhythmias; cholestatic jaundice; gastrointestinal distur- rough skin), pruritus, growth retardation, increased
bance; hyperuricemia; glucose intolerance susceptibility to infection, anemia, and hepato-
Pantothenic acid splenomegaly. Vitamin A treatment of children with
Diarrhea rubeola in developing countries has been associated
Biotin with reduction in morbidity and mortality from this
None viral infection.
Folic acid Serum retinol levels below 20 µg/dL are low, and
May mask B12 deficiency, hypersensitivity
levels less than 10 µg/dL indicate deficiency. A ratio of
Cobalamin
None
retinol to retinol-binding protein below 0.7 is also in-
Vitamin C dicative of vitamin A deficiency.
Interference with copper absorption; decreased tolerance Suggested intakes of vitamin A are summarized in
to hypoxia, increased oxalic acid excretion Table 10–6. Therapy of xerophthalmia requires
Carnitine 5000–10,000 international units (IU)/kg/d for 5 days
None recognized orally or intramuscularly. The standard maintenance
Vitamin A dose in fat malabsorption syndromes is 2500–5000 IU
(> 20,000 IU/d): Vomiting, increased intracranial pressure (800–1600 µg). Doses as high as 25,000–50,000 IU/d
(pseudotumor cerebri); irritability; headaches; insomnia; may be needed, but monitoring to avoid toxicity is es-
emotional lability; dry, desquamating skin; myalgia and sential. The effects of vitamin A toxicity are summa-
arthralgia; abdominal pain; hepatosplenomegaly; cortical rized in Table 10–5.
thickening of bones of hands and feet
Vitamin D Villamor E, Fawzi WW: Vitamin A supplementation: Implications
(> 40,000 IU/d): Hypercalcemia; vomiting; constipation; for morbidity and mortality in children. J Infect Dis
nephrocalcinosis 2000;182 (Suppl):S122 [PMID: 10944494].
Vitamin E
(? 25–100 mg/kg/d intravenously): Necrotizing enterocolitis
and liver toxicity (but probably due to polysorbate 80 Vitamin D
used as a solubilizer) Vitamin D requirements are normally met primarily
Vitamin K
from cholecalciferol (vitamin D3) produced by ultravio-
Lipid-soluble vitamin K: Very low order of toxicity.
Water-soluble, synthetic vitamin K: Vomiting, porphyrin-
let radiation of dehydrocholesterol in the skin. Simi-
uria; albuminuria; hemolytic anemia; hemoglobinuria; larly, ergocalciferol (vitamin D2) is derived from UV ir-
hyperbilirubinemia (do not give to neonates) radiation of ergosterol in the skin. Vitamin D is
transported from the skin to the liver attached to a spe-
cific carrier protein. The primary dietary source of vita-
min D is fortified milk and formulas. Egg yolk and
fatty fish contain some vitamin D. Vitamin D absorp-
can be irreversibly oxidized to retinoic acid, which is ef- tion depends on normal fat absorption. Absorbed vita-
fective in glycoprotein synthesis but is ineffective for vi- min D is transported to the liver in chylomicrons. Vita-
sion. mins D2 and D3 undergo 25-hydroxylation in the liver
Vitamin A deficiency occurs in premature infants, in and then 1α-hydroxylation in kidney proximal tubules
association with IV nutrition with inadequate vitamin to yield 1,25-dihydroxycholecalciferol (calcitriol) and
A supplement, and in association with protein-energy calcitriol, respectively. PTH activates the 1α-hydroxy-
malnutrition, when the manifestations are frequently lase enzyme in the kidney. 25-Hydroxycholecalciferol
made more severe by measles. Other causes of vitamin (calcidiol) is the major circulating form of vitamin D.
A deficiency are dietary insufficiency and fat malab- Calcitriol is the biologically active form of vitamin D.
sorption. Calcitriol stimulates the intestinal absorption of cal-
 NORMAL CHILDHOOD NUTRITION & ITS DISORDERS / 295

Table 10–6. Summary of dietary reference intakes for select vitamins.

14–18 yr 14–18 yr
0–6 mo 7–12 mo 1–3 yr 4–8 yr 9–13 ys male female
Thiamin 0.2a 0.3a 0.5 0.6 0.9 1.2 1.0
(mg/d)
Riboflavin 0.3a 0.4a 0.5a 0.6a 0.9a 1.3a 1.0a
(mg/d)
Pyridoxine 0.1a 0.3a 0.5 0.6 1.0 1.3 1.2
(mg/d)
Niacin 2a 4a 6 8 12 16 14
(mg/d)
Pantothenic 1.7a 1.8a 2a 3a 4a 5a 5a
Acid
(mg/d)
Biotin 5a 6a 8a 12a 20a 25a 25a
(µg/d)
Folic Acid 65a 80a 150 200 300 400 400
(µg/d)
Cobalamin 0.4a 0.5a 0.9 1.2 1.8 2.4 2.4
(µg/d)
Vitamin C 40a 50a 15 25 45 75 65
(mg/d)
Vitamin A 400a 500a 300 400 600 900 700
(µg/d)
Vitamin D 200a 200a 200a 200a 200a 200a 200a
(IU/d)
Vitamin E 4a 5a 6 7 11 15 15
(mg/d)
Vitamin K 2a 2.5a 30a 55a 60a 75a 75a
(µg/d)
a
Adequate Intakes (AI). All other values represent the Recommended Dietary Allowances (RDA).
Both the RDA and AI may be used as goals for individual intakes.
Reprinted, with permission, from National Academy of Sciences, Food and Nutritional Board, Insti-
tute of Medicine: Dietary Reference Intakes, Applications in Dietary Assessment. National Academy
Press, Washington, DC 2000: 287–89. http://www.nap.edu.

cium and phosphate, the renal reabsorption of filtered gists advise caution in exposure to sun, even for young
calcium, and the mobilization of calcium and phospho- infants. Vitamin D content of human milk is low. In
rus from bone. the United States, cow’s milk and infant formulas are
Vitamin D deficiency usually results from a combi- routinely supplemented with vitamin D. The American
nation of inadequate sunlight exposure and low dietary Academy of Pediatrics now recommends vitamin D
intake. An infant with light skin pigmentation requires supplementation for all breast-fed infants until they are
only about 30 minutes per week of total body sun ex- receiving at least 500 mL/d of vitamin D in fortified
posure or 2 hours per week of head exposure to main- formula or milk. Supplementation should be initiated
tain adequate vitamin D status. Adequate amounts of during the first 2 months of life.
sun exposure for infants with more darkly pigmented Vitamin D deficiency also occurs in fat malabsorp-
skin are difficult to quantify. Furthermore, dermatolo- tion syndromes. Use of P-450–stimulating drugs may
296 / CHAPTER 10

decrease hydroxylated vitamin D, which can also be de- acids. Vitamin E also functions as a cell membrane sta-
creased by hepatic and renal disease and by inborn er- bilizer, may function in the electron transport chain,
rors of metabolism. End-organ unresponsiveness to cal- and may modulate chromosomal expression.
citriol may also occur. Vitamin E deficiency may occur in the following
The clinical effects of vitamin D deficiency are os- circumstances: prematurity; cholestatic liver disease,
teomalacia (adults) or rickets (children), in which os- pancreatic insufficiency, abetalipoproteinemia, and
teoid (matrix) with reduced calcification accumulates in short bowel syndrome; as an isolated inborn error of vi-
bone. Cartilage fails to mature and calcify. Clinical tamin E metabolism; and perhaps as a result of in-
findings include craniotabes, rachitic rosary, pigeon creased use due to oxidant stress.
breast, bowed legs, delayed eruption of teeth and Vitamin E deficiency shortens red cell half-life and
enamel defects, Harrison groove, scoliosis, kyphosis, may cause hemolytic anemia. Chronic vitamin E defi-
dwarfism, painful bones, fractures, anorexia, and weak- ciency results in a progressive neurologic disorder with
ness. Radiographic findings include cupping, fraying, loss of deep tendon reflexes, loss of coordination, vibra-
and flaring of metaphyses. The loss of sharp definition tory and position sensation, nystagmus, weakness, scol-
of bone trabeculae accounts for the general decrease in iosis, and retinal degeneration. In premature infants, vi-
skeletal radiodensity. The diagnosis is supported by tamin E deficiency may contribute to oxidant injury of
characteristic radiologic abnormalities of the skeleton, the lung, retina, and brain (brain hemorrhage). These
low serum phosphorus, high serum alkaline phos- putative adverse effects in the premature infant require
phatase, and high serum PTH. The diagnosis can be confirmation.
confirmed by a low level of serum 25-hydroxycholecal- Vitamin E nutritional status can be partially assessed
ciferol. by measuring serum vitamin E (normal range for chil-
Rickets is treated with 1600–5000 IU/d of vitamin dren is 3–15 mg/mL). The ratio of serum vitamin E to
D3 (1 IU = 0.025 µg). If this is poorly absorbed, calcidi- total serum lipid is normally more than 0.8 mg/g. Sen-
ol, 25 µg/d (1000 IU), or calcitriol, 0.05–0.2 µg/kg/d, sitivity of erythrocytes to hydrogen peroxide-induced
is given. Renal osteodystrophy is treated with calcitriol. hemolysis is also used as a test of vitamin E status.
Suggested dietary intakes for vitamin D are summa- Suggested dietary intakes of vitamin E are summa-
rized in Table 10–6 and toxic effects in Table 10–5. rized in Table 10–6. Requirements increase if dietary
polyunsaturated fatty acids increase. Between 0.4 mg
and 0.5 mg of vitamin E is needed per gram of polyun-
Gartner LM, Greer FR, Section on Breastfeeding and Committee
on Nutrition, American Academy of Pediatrics: Prevention of saturated fatty acids in the diet (1 IU = 1 mg of DL-α-
rickets and Vitamin D deficiency: New Guidelines for Vita- tocopherol acetate).
min D intake. Pediatrics 2003;111(4):908 [PMID: Large oral doses (up to 100 IU/kg/d) of vitamin E
12671133]. correct the deficiency resulting from most malabsorp-
Kreiter SR et al: Nutritional rickets in African American breastfed tion syndromes. For abetalipoproteinemia, 100–200
infants. J Pediatr 2000;137:153 [PMID: 10931404]. IU/kg/d of vitamin E are needed. Vitamin E therapy in
ischemia-reperfusion injury and in the prevention of in-
tracranial hemorrhage in the preterm infant remains
Vitamin E controversial. Toxic effects of intravenously adminis-
Vegetable oils are the main dietary source of vitamin E. tered vitamin E are summarized in Table 10–5.
Coconut and olive oils, however, are low in vitamin E.
Some vitamin E is present in cereals, dairy products, Vitamin K
and eggs. Vitamin activity may decrease with process-
ing, storage, or heating. Vitamin E is a family of com- Vitamin K1 (phylloquinone) is obtained from leafy veg-
pounds, the tocopherols, with four major forms: alpha, etables, soybean oil, fruits, seeds, and cow’s milk. Vita-
gamma, beta, and delta. α-Tocopherol has the highest min K2 (menaquinone), which has 60% of the activity
biologic activity. Vitamin E can donate an electron to a of K1, is synthesized by intestinal bacteria. K2 may be a
free-radical molecule to stop oxidation reactions. Oxi- major source of vitamin K in infants and young chil-
dized vitamin E is then reduced by ascorbic acid or glu- dren, but less is produced in the intestine of breast-fed
tathione. The reduced tocopherol is able to scavenge infants.
another free radical. The nutrients that participate in Vitamin K is necessary for the posttranslational car-
antioxidant defenses include β-carotene, vitamin C, se- boxylation of glutamic acid residues of the vitamin K-
lenium, copper, manganese, and zinc. Vitamin E is lo- dependent coagulation proteins. Carboxylation allows
cated at specific sites in the cell to protect polyunsatu- these proteins to bind calcium, leading to activation of
rated fatty acids in the membrane lipids from lipid the clotting factors. Thus vitamin K is necessary for the
peroxidation and to protect thiol groups and nucleic maintenance of normal plasma levels of coagulation
 NORMAL CHILDHOOD NUTRITION & ITS DISORDERS / 297

factors II (prothrombin), VII, IX, and X and is also Table 10–7. Summary of biologic roles
necessary for maintenance of normal levels of the anti- of water-soluble vitamins.
coagulation protein C. Vitamin K deficiency occurs in
newborns, especially those who are breast-fed and who B vitamins involved in production of energy
do not receive vitamin K prophylaxis at delivery. The Thiamin (B1)
deficiency may result in hemorrhagic disease of the Thiamin pyrophosphate is coenzyme in oxidative decar-
newborn. Later, vitamin K deficiency may result from boxylation (pyruvate dehydrogenase, α-ketoglutarate
fat malabsorption syndromes and the use of nonab- dehydrogenase, and transketolase).
sorbed antibiotics and anticoagulant drugs (eg, war- Riboflavin (B2)
farin). Clinical features are bruising or bleeding in the Coenzyme of several flavoproteins (eg, flavin mononu-
GI tract, genital urinary tract, gingiva, lungs, joints, cleotide [FMN] and flavin adenine dinucleotide [FAD])
and brain. Vitamin K status can be assessed with involved in oxidative/electron transfer enzyme sys-
plasma levels of protein-induced vitamin K absence or tems.
by prothrombin time. Niacin
Vitamin K requirements are summarized in Table Hydrogen-carrying coenzymes: nicotinamide-adenine
10–6. Newborns require prophylactic intramuscular vi- dinucleotide (NAD), nicotinamide-adenine dinucleo-
tamin K (0.5–1 mg). For older children with acute tide phosphate (NADP); decisive role in intermedi-
bleeding, 3–10 mg of vitamin K is given intramuscu- ary metabolism.
larly or intravenously. For chronic malabsorption syn- Pantothenic acid
dromes, 2.5 mg twice weekly to 5 mg/d is given orally. Major component of coenzyme A.
To reverse warfarin effect, 25–50 mg of IV vitamin K is Biotin
Component of several carboxylase enzymes involved
given. Toxic effects of vitamin K are summarized in
in fat and carbohydrate metabolism.
Table 10–5. Hematopoietic B vitamins
Folic acid
Greer FR: Do breastfed infants need supplemental vitamins? Pedi- Tetrahydrofolate has essential role in one-carbon trans-
atr Clin North Am 2001;48(2):415 [PMID: 11339161]. fers. Essential role in purine and pyramidine synthesis;
Miller CA, Committee on Fetus and Newborn, American Academy deficiency → arrest of cell division (especially bone
of Pediatrics: Controversies concerning vitamin K and the marrow and intestine).
newborn. Pediatrics 2003;112(1):191 [PMID: 12837888]. Cobalamin (B12)
Methyl cobalamin (cytoplasm): synthesis of methionine
2. Water-Soluble Vitamins with simultaneous synthesis of tetrahydrofolate
(reason for megaloblastic anemia in B12 deficiency).
Deficiencies of water-soluble vitamins are uncommon Adenosyl cobalamin (mitochondria) is coenzyme for
in the United States because of the abundant food sup- mutases and dehydratases.
ply and fortification of prepared foods. Most bread and Other B vitamins
wheat products are routinely fortified with B vitamins, Pyridoxine (B6)
including the mandatory addition of folic acid to en- Prosthetic group of transaminases, etc, involved in
riched grain products since January 1998. There is con- amino acid interconversions; prostaglandin and heme
clusive evidence that folic acid supplements (400 µg/d) synthesis; central nervous system function; carbohy-
during the periconceptional period protect against drate metabolism; immune development.
neural tube defects. Dietary intakes of folic acid from Other water-soluble vitamins
L-Ascorbic acid (C)
natural foods and enriched products also result in pro-
Strong reducing agent—probably involved in all hydrox-
tection. Recommended intakes of folic acid during the ylations. Roles include collagen synthesis; phenylal-
periconceptional period may also afford protection later anine → tyrosine; tryptophan → 5-hydroxytrypto-
against neuroectodermal brain tumors in young chil- phan; dopamine → norepinephrine; Fe3+; folic acid →
dren. folinic acid; cholesterol → bile acids; leukocyte func-
The risk of toxicity from water-soluble vitamins is tion; interferon production; carnitine synthesis. Cop-
not as great as that associated with fat-soluble vitamins per metabolism; reduces oxidized vitamin E.
because excesses of the former can be excreted in the Carnitine
urine. However, deficiencies in these vitamins develop Transfer of long-chain fatty acids from cytosol to mito-
more quickly than deficiencies in fat-soluble vitamins chondria (necessary for beta-oxidation).
because of the limited stores.
Additional salient details are summarized in Tables
10–6 to 10–11. Although dietary intake of the water-
soluble vitamins on a daily basis is not necessary, these
298 / CHAPTER 10

Table 10–8. Major dietary sources of water- Table 10–10. Causes of deficiencies
soluble vitamins. in water-soluble vitamins.

Thiamin Thiamin
Whole grains, cereals (including fortification), lean pork, Infantile beriberi; seen in infants breast-fed by mothers
legumes with history of alcoholism or poor diet; has been
Riboflavin described as complication of total parenteral nutrition
Dairy products, meat, poultry, wheat germ, leafy vegeta- (TPN); protein-energy malnutrition; prematurity
bles Riboflavin
Pyridoxine General undernutrition; prematurity; inactivation in total
All foods parenteral nutrition solutions exposed to light
Niacin Pyridoxine
Meats, poultry, fish, legumes, wheat, all foods except fats, Prematurity (these infants may not convert pyridoxine to
synthesized in body from tryptophan pyridoxal-5-P); B6 dependency syndromes; drugs (isoni-
Pantothenic acid azid); heat-treated formulas (historical)
Ubiquitous Niacin
Biotin Maize or millet diets (high leucine and low tryptophan in-
Yeast, liver, kidneys, legumes, nuts, egg yolks (synthesized takes); prematurity
by intestinal bacteria) Pantothenic acid
Folic acid None
Leafy vegetables (lost in cooking), fruits, whole grains, Biotin
wheat germ, orange juice, beans, nuts Suppressed intestinal flora and impaired intestinal ab-
Cobalamin sorption
Eggs, dairy products, liver, meats; none in plants Folic acid
Vitamin C Prematurity; seen in term breast-fed infants whose moth-
Fresh fruits and vegetables ers are folate-deficient and in term infants fed un-
Carnitine supplemented processed cow’s milk or goat’s milk;
Meats, dairy products; none in plants kwashiorkor; chronic overcooking; malabsorption of fo-
late because of a congenital defect; sprue; celiac disease;
drugs (phenytoin)
Increased requirements: chronic hemolytic anemias, diar-
rhea, malignancies, hypermetabolic states, infections,
extensive skin disease, cirrhosis, pregnancy
Cobalamin
Rare; seen in breast-fed infants of mothers with latent per-
Table 10–9. Circumstances in which the nicious anemia or who are on an unsupplemented strict
possibility of vitamin deficiencies merit vegetarian diet; absence of luminal proteases; congeni-
consideration. tal malabsorption of B12
Vitamin C
Prematurity; maternal megadoses during pregnancy → de-
Circumstance Possible Deficiency
ficiency in infants; lack of fresh fruits or vegetables;
Prematurity All vitamins seen in infants fed formula and pasteurized cow’s milk
Protein-energy malnutrition B1, B2, folate, A (historical)
Synthetic diets (including All vitamins Carnitine
total parenteral nutrition) Seen in premature infants fed unsupplemented formula
Inherited disorders Folate, B12, D, carnitine or fed intravenously; dialysis; inherited deficits in
Vitamin–drug interactions B6, biotin, folate, B12, carnitine, carnitine synthesis; organic acidemias; valproic acid
fat-soluble vitamins
Fat malabsorption syndrome Fat-soluble vitamins
Breast-feeding B1,a folate,b B12,c D,d Ke
Periconceptional Folate
a
Alcoholic or malnourished mother.
b
Folate-deficient mother.
c
Vegan mother or maternal pernicious anemia.
d
Infant not exposed to sunlight and mother’s vitamin D status
suboptimal.
e
Maternal status poor; neonatal prophylaxis omitted.
 NORMAL CHILDHOOD NUTRITION & ITS DISORDERS / 299

Table 10–11. Clinical features of deficiencies of neural tube defects. Am J Clin Nutr 2000;71(5):1308S
[PMID: 10799407].
in water-soluble vitamins.

Thiamin
Infantile beriberi (cardiac; aphonic; pseudomeningitic)
Riboflavin
INFANT FEEDING
Cheilosis; angular stomatitis; glossitis; soreness and burn-
ing of lips and mouth; dermatitis of nasolabial fold and BREAST FEEDING
genitals; ± ocular signs (photophobia → indistinct vi-
sion) Breast feeding, one of the most important influences on
Pyridoxine children’s health worldwide, provides optimal nutrition
Listlessness; irritability; seizures; gastrointestinal distur- for the normal infant during the early months of life.
bance; anemia; cheilosis; glossitis Numerous immunologic factors in breast milk (includ-
Niacin ing secretory IgA, lysozyme, lactoferrin, bifidus factor,
Pellagra (weakness; lassitude; dermatitis of exposed areas; and macrophages) provide protection against GI and
diarrhea; dementia) upper respiratory infections. In developing countries,
Pantothenic acid lack of refrigeration and contaminated water supplies
Weakness; gastrointestinal disturbance; burning feet. make formula feeding hazardous. Allergic diseases are
Biotin less common among breast-fed infants. Although for-
Scaly dermatitis; alopecia; irritability; lethargy mulas have improved progressively and are made to re-
Folic acid semble breast milk as closely as possible, it is impossible
Megaloblastic anemia; neutropenia; thrombocytopenia;
to mimic the nutritional or immune composition of
growth retardation; delayed maturation of central ner-
vous system in infants; diarrhea (mucosal ulcerations);
human milk. Additional differences of physiologic im-
glossitis; jaundice; mild splenomegaly; neural tube portance continue to be identified. Furthermore, the
defects relationship developed through breast feeding can be an
Cobalamin important part of early maternal interactions with the
Megaloblastic anemia; neurologic degeneration infant and provides a source of security and comfort to
Vitamin C the infant.
Anorexia, irritability, apathy, pallor; fever; tachycardia; Breast feeding has been reestablished as the predom-
diarrhea; failure to thrive; increased susceptibility to in- inant mode of feeding the young infant in the United
fections; hemorrhages under skin, mucous membranes, States. Unfortunately, breast-feeding rates remain low
into joints and under periosteum; long-bone tenderness; among several subpopulations, including low-income,
costochondral beading minority, and young mothers; many mothers face ob-
Carnitine stacles in maintaining lactation once they return to
Increased serum triglycerides and free fatty acids; de- work. Skilled use of a breast pump, particularly an elec-
creased ketones; fatty liver; hypoglycemia; progres- tric one, may help to maintain lactation in these cir-
sive muscle weakness, cardiomyopathy, hypo- cumstances.
glycemia Absolute contraindications to breast feeding are rare.
They include tuberculosis (in the mother) and galac-
tosemia (in the infant). Breast feeding is associated with
maternal-to-child transmission of HIV, but the risk is
vitamins, with the exception of vitamin B12, are not influenced by duration and pattern of breast feeding
stored in the body. and maternal factors, including immunologic status
Carnitine is synthesized in the liver and kidneys and presence of mastitis. Complete avoidance of breast
from lysine and methionine. In certain circumstances feeding by HIV-infected women is presently the only
(see Table 10–10) synthesis is inadequate, and carnitine mechanism to ensure prevention of maternal–infant
can then be considered a vitamin. A dietary supply of transmission. Current recommendations are that HIV-
other organic compounds, such as inositol, may also be infected mothers in developed countries refrain from
required in certain circumstances. breast feeding if safe alternatives are available. In devel-
oping countries, the benefits of breast feeding, espe-
Honein MA et al: Impact of folic acid fortification of the US food
cially the protection of the child against diarrheal illness
supply on the occurrence of neural tube defects. JAMA and malnutrition outweigh the risk of HIV infection
2001;285:2981 [PMID: 11410096]. via breast milk.
McNulty H et al: Response of red blood cell folate to intervention: The newborn weighing less than 1500 g and receiv-
Implications for folate recommendations for the prevention ing human milk benefits from the addition of a human
300 / CHAPTER 10

milk fortifier designed to increase the protein, calcium, bies. In neonates, a loose stool is often passed with each
phosphorus, and micronutrient content as well as the feeding; later (at age 3–4 months), there may be an in-
caloric density. Breast-fed infants with cystic fibrosis terval of several days between stools. Failure to pass sev-
can be breast-fed successfully if exogenous pancreatic eral stools a day in the early weeks of breast feeding sug-
enzymes are provided. If normal growth rates are not gests inadequate milk intake and supply.
achieved in the breast-fed child with CF, energy or spe- Expressing milk may be indicated if the mother re-
cific macronutrient supplements may be necessary. All turns to work or if the infant is premature, cannot suck
infants should receive supplemental vitamins A, D, E, adequately, or is hospitalized. Modern electric breast
K, and sodium chloride based on standardized nutri- pumps are very effective and can be borrowed or rented.
tion protocols for cystic fibrosis.
Technique of Breast Feeding
Borowitz D et al: Consensus report on nutrition for pediatric pa-
tients with cystic fibrosis. J Pediatr Gastroenterol Nutr Breast feeding can be started after delivery as soon as
2002;35:246-59 [PMID: 12352509]. both mother and baby are stable. Correct positioning
Coutsoudis A, Rollins N: Breast-feeding and HIV transmission: and breast-feeding technique are necessary to ensure ef-
The jury is still out. J Pediatr Gastroenterol Nutr fective nipple stimulation and optimal breast emptying
2003;26(4):434 [PMID: 12658031]. with minimal nipple discomfort.
Ryan AS et al: Breastfeeding continues to increase into the new mil- If the mother wishes to nurse while sitting, the in-
lennium. Pediatrics 2002;110(6):1103 [PMID: 12456906]. fant should be elevated to the height of the breast and
turned completely to face the mother, so that their ab-
domens touch. The mother’s arms supporting the in-
Management of Breast Feeding fant should be held tightly at her side, bringing the
In developed countries, we cannot assume that the art baby’s head in line with her breast. The breast should
of breast feeding is being automatically passed from be supported by the lower fingers of her free hand, with
mother to daughter. Health professionals are now play- the nipple compressed between the thumb and index
ing roles of greater importance in supporting and pro- fingers to make it more protractile. The infant’s initial
moting breast feeding. Organizations such as the La licking and mouthing of the nipple helps make it more
Leche League have been effective in promoting breast erect. When the infant opens its mouth, the mother
feeding and providing education and support for moth- should rapidly insert as much nipple and areola as pos-
ers and health professionals. sible.
Perinatal hospital routines and follow-up pediatric Some breast-fed infants fail to thrive. The most
care have a great influence on the successful initiation common cause of early failure to thrive is poorly man-
of breast feeding. Breast feeding is promoted by prena- aged mammary engorgement, which rapidly decreases
tal and postpartum education, frequent mother–baby milk supply. Unrelieved engorgement can result from
contact after delivery, one-on-one advice about breast- inappropriately long intervals between feeding, im-
feeding technique, demand feeding, rooming-in, avoid- proper infant suckling, a nondemanding infant, sore
ance of bottle supplements, early follow-up after deliv- nipples, maternal or infant illness, nursing from only
ery, maternal confidence, family support, adequate one breast, and latching difficulties. The mother’s igno-
maternity leave, and good advice about common prob- rance of technique, inappropriate feeding routines, and
lems such as sore nipples. Breast feeding is undermined inadequate amounts of fluid and rest all can be factors.
by mother and baby separations, bottle-feeding babies Some infants are too sleepy to do well on an ad libitum
in the nursery at night, routinely offering supplemental regimen and may need waking to feed at night. Primary
bottles, conflicting advice from staff, incorrect infant lactation failure is rare, occurring in less than 5% of
positioning and latch-on, scheduled feedings, lack of women.
maternal confidence or support, delayed follow-up, A sensible guideline for duration of feeding is
early return to employment, and inaccurate advice for 5 minutes per breast at each feeding the first day,
common breast-feeding difficulties. 10 minutes on each side at each feeding the second day,
It is important for mothers to know that very few and approximately 15 minutes per side thereafter. A
women are unable to nurse their babies. The newborn vigorous infant can obtain most of the available milk in
is generally fed ad libitum every 2–3 hours, with longer 5–7 minutes, but additional sucking time ensures
intervals (4–5 hours) at night. Thus a newborn infant breast emptying, promotes milk production, and satis-
nurses at least eight to ten times a day, so that a gener- fies the infant’s sucking urge. The side on which feed-
ous milk supply is stimulated. This frequency is not an ing is commenced should be alternated. The mother
indication of inadequate lactation. Mothers also need may break suction gently after nursing by inserting her
reassurance about the stooling patterns of breast-fed ba- finger between the baby’s gums.
 NORMAL CHILDHOOD NUTRITION & ITS DISORDERS / 301

Follow-Up pounds, antimetabolites, lithium, diazepam, chloram-

phenicol, antithyroid drugs, and tetracycline. For up-
Individualized assessment before discharge should iden- to-date information, a regional drug center should be
tify the mothers and infants needing additional sup- consulted.
port. All mother–infant pairs require early follow-up. Maternal use of illicit or recreational drugs is a con-
The onset of copious milk secretion between the second traindication to breast feeding. Expression of milk for a
and fourth postpartum days is a critical time in the es- feeding or two after use of a drug is not an acceptable
tablishment of lactation. Failure to empty the breasts compromise. The breast-fed infants of mothers taking
during this time can cause engorgement, which quickly methadone (but no alcohol or other drugs) as part of a
leads to diminished milk production. treatment program have generally not experienced ill
effects when the daily maternal methadone dose is
Common Problems under 40 mg.
Nipple tenderness requires attention to proper posi-
tioning of the infant and correct latch-on. Ancillary American Academy of Pediatrics, Committee on Drugs: The trans-
fer of drugs and other chemicals to human milk. Pediatrics
measures include nursing for shorter periods, beginning 2001;108(3):776 [PMID: 11533352].
feedings on the less sore side, air drying the nipples well
Case Western Reserve University:
after nursing, and use of lanolin cream. Severe nipple (http://www.breastfeedingbasics.org).
pain and cracking usually indicate improper infant at- Dr. Hales Breastfeeding Pharmacology Page:
tachment. Temporary pumping, which is well toler- (http://neonatal.ttuhsc.edu/lact/).
ated, may be needed. Lactation Education Resources:
Breast-feeding jaundice is exaggerated physiologic (http://www.leron-line.com/medications.htm).
jaundice associated with inadequate intake of breast Spencer JP et al: Medications in the breast-feeding mother. Am
milk, infrequent stooling, and unsatisfactory weight Fam Physician 2001;64(1):119 [PMID: 11456429].
gain (see Chapter 1). If possible, the jaundice should be
managed by increasing the frequency of nursing and, if Nutrient Composition
necessary, augmenting the infant’s sucking with regular
breast pumping. Supplemental feedings may be neces- The nutrient composition of human milk is summa-
sary, but care should be taken not to decrease breast rized and compared with that of cow’s milk and formu-
milk production further. las in Table 10–12. Outstanding characteristics include
In a small percentage of breast-fed infants, breast (1) relatively low but highly bioavailable protein con-
milk jaundice is caused by an unidentified property of tent, which is adequate for the normal infant; (2) gener-
the milk that inhibits conjugation of bilirubin. In se- ous but not excessive quantity of essential fatty acids;
vere cases, interruption of breast feeding for (3) long-chain unsaturated ω3 fatty acids, of which do-
24–36 hours may be necessary. The mother’s breast cosahexaenoic acid is thought to be especially impor-
should be emptied with an electric breast pump during tant; (4) relatively low sodium and solute load; and
this period. (5) lower concentration of highly bioavailable calcium,
The symptoms of mastitis include flu-like symptoms iron, and zinc, which are adequate for the needs of nor-
with breast tenderness, firmness, and erythema. Antibi- mal breast-fed infants for approximately 6 months. A
otic therapy covering β-lactamase-producing organisms source of iron, from iron-fortified cereal, meat, or a
should be given for 10 days. Analgesics may be neces- supplement, should be introduced by age 6 months.
sary, but breast feeding should be continued. Breast
pumping may be helpful adjunctive therapy. Weaning and Complementary Foods
Neifert MR: Prevention of breastfeeding tragedies. Pediatr Clin
The American Academy of Pediatrics and the World
North Am 2001;48(2):273 [PMID: 11339153]. Health Organization recommend the introduction of
solid foods in normal infants at about 6 months of age.
Gradual introduction of a variety of foods including en-
Maternal Drug Use riched cereals, fruits, vegetables, and meats should
Many factors play a role in determining the transmis- complement the breast milk diet. Although the order of
sion of drugs in breast milk, including the route of ad- introduction is not critical, single-ingredient comple-
ministration, dosage, molecular weight, pH, and pro- mentary foods are introduced one at a time at weekly in-
tein binding. In general, any drug prescribed to tervals before a new food is given. Fruit juice is not an
newborns can be consumed via breast milk without ill essential part of an infant diet. When introduced (ide-
effect. Very few drugs are absolutely contraindicated in ally at > 6 months and with a cup), the amount should
breast-feeding mothers; these include radioactive com- be limited to 4 oz/d. Breast feeding should ideally con-
302 / CHAPTER 10

Table 10–12. The composition of milk (per 100 kcal).

Typical
Minimal Level Mature Commercial Cow’s Milk
Nutrient (unit) Recommendeda Human Milk Formula (mean)
Protein (g) 1.8b 1.3–1.6 2.3 5.1
Fat (g) 3.3c 5 5.3 5.7
Carbohydrate (g) — 10.3 10.8 7.3
Linoleic acid (mg) 300 560 2300 125
Vitamin A (IU) 250 250 300 216
Vitamin D (IU) 40 3 63 3
Vitamin E (IU) 0.7/g linoleic acid 0.3 2 0.1
Vitamin K (µg) 4 2 9 5
Vitamin C (mg) 8 7.8 8.1 2.3
Thiamin (µg) 40 25 80 59
Riboflavin (µg) 60 60 100 252
Niacin (µg) 250 250 1200 131
Vitamin B6 (µg) 15 µg of protein 15 63 66
Folic acid (µg) 4 4 10 8
Pantothenic acid (µg) 300 300 450 489
Vitamin B12 (µg) 0.15 0.15 0.25 0.56
Biotin (µg) 1.5 1 2.5 3.1
Inositol (mg) 4 20 5.5 20
Choline (mg) 7 13 10 23
Calcium (mg) 5 50 75 186
Phosphorus (mg) 25 25 65 145
Magnesium (mg) 6 6 8 20
Iron (mg) 1 0.1 1.5 in 0.08
fortified
Iodine (µg) 5 4–9 10 7
Copper (µg) 60 25–60 80 20
Zinc (mg) 0.5 0.1–0.5 0.65 0.6
Manganese (µg) 5 1.5 5–160 3
Sodium (mEq) 0.9 1 1.7 3.3
Potassium (mEq) 2.1 2.1 2.7 6
Chloride (mEq) 1.6 1.6 2.3 4.6
Osmolarity (mOsm) — 11.3 16–18.4 40
a
Committee on Nutrition, American Academy of Pediatrics.
b
Protein of nutritional quality equal to casein.
c
Includes 300 mg of essential fatty acids.

tinue for at least 12 months, and thereafter for as long as Kleinman RE: American Academy of Pediatrics recommendations
mutually desired. Infants who are not breast-fed should for complementary feeding. Pediatrics 2000;106(5):
1274 [PMID: 11061819].
receive standard iron-fortified infant formula. Whole
cow’s milk can be introduced after the first year of life. Kramer MS et al: Infant growth and health outcomes associated
with 3 compared with 6 mo of exclusive breastfeeding. Am
J Clin Nutr 2003;78:291 [PMID: 12885711].
American Academy of Pediatrics, Committee on Nutrition: The
use and misuse of fruit juice in pediatrics. Pediatrics
2001;107(5):1210 [PMID: 11331711]. SPECIAL DIETARY PRODUCTS
Dewey KG: Nutrition, growth, and complementary feeding of the FOR INFANTS
breastfed infant. Pediatr Clin North Am 2001;48(1):
87 [PMID: 11236735]. Soy Protein Formulas
Gibson RS, Hotz C: The adequacy of micronutrients in comple-
mentary foods. Pediatrics 2000;106(5):1298 [PMID: A common rationale for the use of soy protein formulas
11061842]. is transient lactose intolerance after acute gastroenteri-
 NORMAL CHILDHOOD NUTRITION & ITS DISORDERS / 303

tis. In such cases it is reasonable to recommend a soy Formula Additives

protein formula for a period of 2–4 weeks. These for-
mulas are also useful for infants with galactosemia and Occasionally it may be necessary to increase the caloric
hereditary lactase deficiency. Lactose-free cow’s milk density of an infant feeding to provide greater calories
protein-based formulas are also available. Soy protein or restrict fluid intake. Concentrating formula to
formulas are often used in cases of suspected intoler- 24–26 kcal/oz is usually well tolerated, delivers an ac-
ance to cow’s milk protein. Although infants with true ceptable renal solute load, and increases the density of
cow’s milk protein intolerance may also be intolerant of all the nutrients. Beyond this, individual nutrient addi-
soy protein, those with documented IgE-mediated al- tives (Table 10–13) are usually employed to achieve the
lergy to cow’s milk protein usually do well on soy for- desired caloric density (up to 30 kcal/oz). Adding car-
mula. bohydrates (eg, glucose polymers, maltodextrin) has the
following benefits: they are generally well tolerated, mix
readily with the formula, and are reasonably priced.
Semielemental & Elemental Formulas Microlipid (Mead Johnson), a safflower lipid emulsion,
Semielemental formulas include protein hydrolysate also mixes well but is more expensive. MCT oil doesn’t
formulas. The major nitrogen source of most of these mix well and is expensive, but can be very beneficial for
products is casein hydrolysate, supplemented with se- patients with cholestasis or malabsorptive disorders.
lected amino acids. These formulas contains an abun- The caloric density of breast milk can be increased by
dance of EFA from vegetable oil; certain brands also adding infant formula powder or any of the additives
provide substantial amounts of MCTs. Elemental for- used with infant formula. Human milk fortifiers are
mulas are available with free amino acids and varying generally used only for premature infants because of
levels and types of fat components. their specialized nutrient composition.
Semielemental and elemental formulas are invalu-
able for infants with a wide variety of malabsorption Special Formulas
syndromes. They are also effective in infants who can-
not tolerate cow’s milk and soy protein. For specific Special formulas are those in which one component,
product information, consult standard pediatric refer- often an amino acid, is reduced in concentration or re-
ence texts, formula manufacturers, or a pediatric dieti- moved for the dietary management of a specific inborn
tian. metabolic disease. Also included under this heading are
formulas designed for the management of specific dis-
ease states, such as hepatic failure, pulmonary failure
Hernell O, Lonnerdal B: Nutritional evaluation of protein hy-
drolysate formulas in healthy term infants: Plasma amino with chronic carbon dioxide retention, and renal fail-
acids, hematology, and trace elements. Am J Clin Nutr ure. These condition-specific formulas were made pri-
2003;78:296 [PMID: 12885712]. marily with the critically ill adult in mind and are even

Table 10–13. Common infant formula additives.

Additive Kcal/g Kcal/Tbsp Kcal/mL Comments

Dry rice cereal 3.75 15 — Thickens formula but not breast milk
Polycose (Ross) 3.8 23 2 Glucose polymers
Moducal (Mead Johnson) 3.75 30 — Maltodextrin
MCT oil (Mead Johnson) 8.3 116 7.7 Not a source of essential fatty acids
Microlipid (Mead Johnson) 9 68.5 4.5 Safflower oil emulsion with 0.4 g linoleic acid/mL
Vegetable oil 9 124 8.3 Does not mix well
Promod (Ross) 4.3 16.8 (3 g protein) — Whey protein concentrate
Casec (Mead Johnson) 3.8 16.7 (4 g protein) — Calcium caseinate
Duocal (SHS) 4.9 42 — Protein-free mix of hydrolyzed corn starch
(60% kcal), and fat (35% MCT)
MCT = medium-chain triglyceride.
304 / CHAPTER 10

used sparingly in those populations, thus their use in recommendations are to routinely screen those children
pediatrics should only be undertaken with clear indica- who have a positive family history of premature cardio-
tion and caution. vascular disease, although this approach will identify
Complete information regarding the composition of only about 50% of those with significantly elevated
these special formulas, the standard infant formulas, cholesterol levels. If the result is high (≥ 200 mg/dL), a
specific metabolic disease formulas, and premature in- fasting lipoprotein analysis should be obtained.
fant formulas can be found in standard reference texts
and in the manufacturers’ literature.
Coon KA et al: Relationships between use of television during
PRUDENT DIET meals and children’s food consumption patterns. Pediatrics
2001;107:E7 [PMID: 11134471].
Because of the association of diet with the development Kavey RE et al: American Heart Association guidelines for pri-
of such chronic diseases as diabetes, obesity, and cardio- mary prevention of atherosclerotic cardiovascular disease be-
vascular disease, learning a healthy eating behavior at a ginning in childhood. J Pediatr 2003;142(4):368 [PMID:
young age is an important preventative measure. 12712052].
Salient features of a prudent diet for children older Lauer RM et al: Efficacy and safety of lowering dietary intake of
than 2 years include the following: total fat, saturated fat, and cholesterol in children with ele-
vated LDL cholesterol: The Dietary Intervention Study in
1. Consumption of three regular meals per day, and Children. Am J Clin Nutr 2000;72(Suppl):1332S [PMID:
2 or 3 healthful snacks according to appetite, ac- 11063475].
tivity, and growth needs. Obarzanek E et al: Long-term safety and efficacy of a cholesterol-
lowering diet with elevated low-density lipoprotein choles-
2. Inclusion of a variety of foods. Diet should be nu- terol: Seven-year results of the Dietary Intervention Study in
tritionally complete and promote optimal growth Children (DISC). Pediatrics 2001;107(2):256 [PMID:
and activity. 11158455].
3. Fat less than 30% of total calories (though severe
fat restriction may result in an energy deficit and
growth failure). Saturated fats and polyunsatu-
rated fats each should provide less than 10% of
total calories. Monounsaturated fats should pro- PEDIATRIC UNDERNUTRITION
vide 10% or more of caloric intake.
4. Cholesterol intake less than 100 mg/1000 kcal/d, Failure to thrive is a term used to describe infants and
to a maximum of 300 mg/d. young children whose weight curve has fallen by two
5. Carbohydrates should provide 55–60% or more major percentile channels from a previously established
of daily caloric intake, with no more than 10% in rate of growth (see Chapter 8). The acute loss of
the form of simple sugars. A high-fiber, complex weight, or failure to gain weight at the expected rate,
carbohydrate diet is recommended. produces a condition of reduced weight for height
6. Limitation of grazing behavior, eating while known as wasting. The reduction in height for age, as
watching television, and the consumption of soft is seen with more chronic malnutrition, is termed
drinks and other high-sugar beverages. stunting.
7. Limitation of sodium intake by choosing fresh The typical pattern for mild pediatric undernutri-
over highly processed foods. tion is decreased weight, with normal height and head
circumference. In more chronic malnutrition, height
The consumption of lean cuts of meats, poultry, and and eventually head circumference growth will slow rel-
fish should be encouraged. Skim milk, soft margarine, ative to the standard for age. Significant calorie depriva-
and vegetable oils (especially olive oil) should be used. tion produces severe wasting, called marasmus. Signifi-
Whole-grain bread and cereals and plentiful amounts of cant protein deprivation in the face of adequate energy
fruits and vegetables are recommended. The consump- intake, possibly with additional insults such as infec-
tion of processed foods, soft drinks, desserts, and candy tion, may produce edematous malnutrition called
should be limited. kwashiorkor.
A prudent diet should be only one component of Pediatric undernutrition is usually multifactorial in
counseling on lifestyles for children. Other aspects are origin, and successful treatment depends on accurate
the maintenance of a desirable body weight and body identification and management of those factors. The
mass index (BMI), regular physical activity, avoidance terms “organic” and “nonorganic” failure to thrive,
of smoking, and screening for hypertension. Universal though still used by many medical professionals, are not
screening for total cholesterol is controversial. Current helpful because any systemic illness or chronic condi-
 NORMAL CHILDHOOD NUTRITION & ITS DISORDERS / 305

tion can cause growth impairment and yet may also be with even higher rates among subpopulations of minor-
compounded by psychosocial problems. ity and economically disadvantaged children. The in-
A discussion of the multiple medical conditions that creasing incidence of childhood obesity is related to a
can cause pediatric undernutrition are beyond the scope complex combination of genetic, environmental, psy-
of this chapter. However, the most common cause is in- chosocial, biologic, and socioeconomic factors.
adequate dietary intake. Inappropriate formula mixing Overweight status in the pediatric population is as-
or a family’s food beliefs may lead to hypocaloric or un- sociated with significant comorbidities, which if un-
balanced dietary intakes. Highly restricted diets sec- treated are likely to persist into adulthood. The proba-
ondary to perceived food allergies or intolerances may bility of obesity persisting into adulthood increases
result in inadequate intake of calories, protein, or spe- from 20% at 4 years to 80% by adolescence. Obesity is
cific micronutrients. Iron and zinc are micronutrients associated with cardiovascular and endocrine abnormal-
that are often marginal in many patients with undernu- ities (eg, dyslipidemia, insulin resistance and type II di-
trition. Zinc deficiency can depress appetite and affect abetes), orthopedic problems, pulmonary complications
growth, and can easily be corrected with oral zinc sup- (eg, obstructive sleep apnea), and mental health prob-
plements given over 1–2 months. Cases of severe mal- lems.
nutrition and kwashiorkor have occurred in infants of
well-intentioned parents who substitute “health food”
milk alternatives (eg, rice milk and unfortified soy Definitions
milk) for infant formula.
BMI is the standard measure of obesity in adults. Its
Poor eating is often a learned behavior. Families
use in children provides a consistent measure across age
should be counseled regarding choices of foods that are
groups. BMI is correlated with more accurate measures
appropriate for the age and developmental level of the
of body fatness and is calculated with readily available
child. Children should have structured meal times (eg,
information: weight and height (kg ÷ m2). Routine
three meals and two to three snacks during the day),
plotting of the BMI on age- and gender-appropriate
ideally at the same time other family members eat.
charts (http://www.cdc.gov/growthcharts) can identify
Consultation with a pediatric dietitian can be helpful
those with excess weight gain relative to linear growth.
for educating the families. Estimates of calorie needs
BMI between the 85th and 95th percentile for age and
should be based on the need for catch-up growth rather
sex identifies those at risk of being overweight. Over-
than on the usual RDA for age. Poor feeding may be re-
weight or obese is defined as BMI at or above 95% and
lated to family dysfunction. Children whose households
is associated with increased risk of secondary complica-
are chaotic and children who are abused, neglected, or
tions. An upward change in BMI percentiles in any
exposed to poorly controlled mental illness may be de-
range should prompt an evaluation and possible treat-
scribed as poor eaters, and may fail to gain. Careful as-
ment. Although the degree of change that indicates risk
sessment of the social environment of such children is
has not been defined, an annual increase of 3–4 BMI
critical, and disposition options may include support
units is almost always an indicator of a rapid increase in
services, close medical follow-up visits, family counsel-
body fat. For children younger than 2 years old, weight
ing, and even foster placement while a parent receives
for length greater than 95th percentile indicates over-
therapy.
weight and warrants further assessment, especially of
energy intake.
Carvalho NF et al: Severe nutritional deficiencies in toddlers result-
ing from health food milk alternatives. Pediatrics 2001;
107(4):1 [PMID: 11335767].
Risk Factors
Schwartz ID: Failure to thrive: An old nemesis in the new millen-
nium. Pediatr Rev 2000;21(8):257 [PMID: 10922022]. There are multiple risk factors for developing obesity,
reflecting the complex relationships between genetic
and environmental factors. Family history is a strong
PEDIATRIC OVERWEIGHT/OBESITY risk factor. If one parent is obese, the odds ratio is ap-
(See also Chapter 3 for specifics on proximately 3 for obesity in adulthood, but if both par-
adolescent obesity.) ents are obese, the odds ratio increases to greater than
10.
Background Environmental risk factors offer potential areas to
The prevalence of childhood and adolescent obesity has target for intervention. The absence of family meals, ex-
increased rapidly in the United States and many other cessive consumption of sweetened beverages, large por-
parts of the world. Currently in the United States, ap- tion sizes, frequent consumption of foods prepared out-
proximately 15% of 6- to 19-year-olds are overweight, side the home, excessive television viewing, and
306 / CHAPTER 10

sedentary lifestyle are all associated with a greater preva- Treatment

lence of obesity.
Therapy should be based on risk factors, including age,
severity of obesity, and comorbidities, as well as family
Assessment history and support. For all children with uncompli-
cated obesity, the primary goal is to achieve healthy eat-
Early recognition of high-risk patterns of weight gain or ing and activity patterns, not necessarily to achieve ideal
high-risk behaviors is essential, as it is likely that antici- body weight. For children with a secondary complica-
patory guidance or intervention before weight gain be- tion, improvement of the complication is an important
comes severe will be more successful. Routine evalua- goal. For children 2–7 years old with BMI at 95% or
tion at well-child visits should include: above and without complications, the goal should gen-
erally be maintenance of baseline weight, allowing the
1. Measurement of weight and height, calculation of child to “grow into” his or her height, with a gradual
BMI, and plotting all three parameters on age- normalization of BMI. For children 2–7 years old with
and sex-appropriate growth charts (http://www. BMI at 95% or above and secondary complications,
cdc.gov/growthcharts). Evaluate for upward cross- weight loss is indicated. For children older than 7 years
ing of BMI percentile channels. with BMI between 85th and 95th percentile, without
2. History regarding diet and activity patterns complications, weight maintenance is an appropriate
(Table 10–14) Physical exam: Blood pressure, as- goal. If secondary complications are present, weight loss
sess distribution of adiposity (central vs general- is recommended; an appropriate goal is 1 pound weight
ized); markers of comorbidities, such as acanthosis loss/month until a BMI less than 85% is achieved. Ex-
nigricans, hirsutism, hepatomegaly, orthopedic cessive acute weight loss should be avoided, as this may
abnormalities; physical stigmata of genetic syn- contribute to nutrient deficiencies and linear growth
drome (eg, Prader–Willi syndrome). stunting.
3. Laboratory studies are generally reserved for chil- There are few studies of the long-term effects of
dren with BMI in overweight category (> 95th weight control programs for children. Treatment fo-
percentile) or those who have evidence of comor- cused on behavior changes in the context of the family
bidities; may include fasting lipid profile, insulin has been associated with sustained weight loss and de-
and glucose, liver function tests, thyroid function creases in BMI. Clinicians should assess the family’s
(if evidence of plateau in linear growth). Other readiness to take action (stages-of-change model). Con-
studies should be guided by findings in history current changes in dietary patterns and increasing phys-
and physical. ical activity are most likely to provide success. The
whole family should be encouraged to adopt healthy
eating patterns, with parents modeling healthy food
choices, controlling foods brought into the home, and
guiding appropriate portion sizes. Limiting sedentary
Table 10–14. Suggested areas for assessment of activity has been found to be more effective than specif-
diet and activity patterns. ically promoting increased physical activity. The Amer-
ican Academy of Pediatrics recommends no television
Diet for children younger than 2 years old, and a maximum
Meal and snack pattern: structured vs grazing, skipping of 2 h/d of television and video games for older chil-
meals dren.
Portion sizes: adult portions for young children? Treatment may be considered at three different lev-
Frequency of meals away from home (restaurants or take els depending on the severity of the problem, the age of
out) the child, the ability of the family to implement
Frequency/amounts of caloric beverages (soda, juice, changes, the preferences of the parents and child, and
milk) the skills of the health care provider. (1) General:
Frequency of eating fruits and vegetables Counseling regarding problem areas identified by
Frequency of family meals? screening questions (see Table 10–14); emphasis on
Activity guidelines around healthy eating and physical activity
Time spent in sedentary activity: television, video games patterns. This is especially appropriate for preventing
Time spent in vigorous activity: organized sports, physical further weight gain or for mildly overweight children.
education, free play
(2) Structured: Provide more specific and structured di-
Activities of daily living: walking to school, chores, yard
work
etary pattern, such as meal planning, exercise prescrip-
tion, behavior change goals. This may be done in the
 NORMAL CHILDHOOD NUTRITION & ITS DISORDERS / 307

primary care setting or, if resources are available, re- ings should be attempted. Enteral nutrition, full or par-
ferred to more specialized treatment program. tial, provides multiple physiologic benefits:
(3) Group treatment: Generally best for the older child
or adolescent, with varying level of parental involve- 1. Maintaining gut mucosal integrity
ment depending on age of child. Several published pro- 2. Preserving gut-associated lymphoid tissue
grams are available. The Weight Information Network 3. Stimulation of gut hormones and bile flow
(WIN) is a service available through the National Insti-
tutes of Health, which disseminates information on Most pediatric patients requiring enteral nutrition
weight control programs and is available online: can have their needs met with standard enteral formula-
(http://www.niddk.nih.gosv//NutritionDocs.html). No tions. Specialized formulas are available for patients of
single prescription is effective for all patients. The all ages who have conditions such as severe milk protein
physician will do best to assess the severity of the prob- allergy, single- or multiple-nutrient malabsorption,
lem, treatment needs in context of the family’s prefer- renal failure, and hepatic failure. The decision to use
ences and abilities, and local resources, including avail- such specialized formulas must be made in the context
ability of registered dietitians with expertise in pediatric of the patient’s condition and nutritional needs.
weight management and behaviorists or family thera-
pists. Access Devices
Pharmacotherapy can be an adjunct to dietary, ac-
tivity, and behavioral treatment, but by itself it is un- Nasogastric feeding tubes can be used for supplemental
likely to result in significant or sustained weight loss. nocturnal drip or daytime bolus feedings, but generally
For severe obesity in adolescents, particularly with co- are not used for more than 6 months. Complications
morbidities, bariatric surgery is being performed in such as otitis media and sinusitis may limit the duration
some centers. This is still considered experimental, and of nasogastric tube feedings. Initiation of nasogastric
there is an urgent need for long-term outcome, safety, feeding usually requires a brief hospital stay to ensure
and efficacy data. However, there is limited evidence tolerance to feedings and to allow for parental instruc-
that in carefully selected and closely monitored pa- tion in tube placement and feeding administration.
tients, medications or surgery (or both) can result in If long-term feeding support is anticipated, a more
significant weight loss with a reduction in comorbidi- permanent feeding device, such as a gastrostomy tube,
ties for those who are severely afflicted. may be considered. With either a nasogastric or a gas-
trostomy tube, insurance coverage is important, as
many carriers do not cover the cost of formula for tube
Barlow SE, Dietz WH: Obesity evaluation and treatment: Expert
Committee Recommendations. Pediatrics 1998;102(3):e29
feedings. Referral to a homecare company is necessary
[PMID: 9724677]. for equipment and other services such as nursing visits
Berkowitz RI et al: Behavior Therapy and sibutramine for the treat- and dietitian follow-up.
ment of adolescent obesity. JAMA 2003;289(14): 1805. Table 10–15 suggests appropriate timing for initia-
[PMID: 12684359]. tion and advancement of drip and bolus feedings, ac-
Krebs NF, Jacobson MS, Committee on Nutrition, American cording to a child’s age. Clinical status and tolerance to
Academy of Pediatrics: Prevention of Pediatric Overweight feedings should ultimately guide their advancement.
and Obesity Policy Statement. Pediatrics 2003;112(2):1
[PMID: 12897303].
Ogden CL et al: Prevalence and trends in overweight among US
Monitoring
children and adolescents, 1999–2000. JAMA. 2002;288: Monitoring the adequacy of enteral feeding depends on
1728 [PMID: 12365956].
nutritional goals. Growth should be frequently assessed,
especially for young infants and malnourished children.
NUTRITION SUPPORT Hydration status should be monitored carefully at the
initiation of enteral feeding. Constipation and diarrhea
1. Enteral can be problems, and attention to stool frequency, vol-
ume, and consistency can help guide management.
Indications When diarrhea occurs, factors such as infection, hyper-
Enteral nutrition support is indicated when a patient tonic enteral medications, antibiotic use, and alteration
cannot adequately meet nutritional needs by oral intake in normal gut flora should be addressed before formula
alone and has a functioning GI tract. This method of changes are tried.
support can be used for both short- and long-term de- It is important to determine whether the feeding
livery of nutrition. Even when the gut cannot be used schedule is developmentally appropriate. This will not
to deliver 100% of nutritional needs, some enteral feed- be possible for all patients, especially those who are crit-
308 / CHAPTER 10

Table 10–15. Guidelines for the initiation and advancement of tube

feedings.

Drip Feeds Bolus Feeds

Age Initiation Advancement Initiation Advancement
Preterm 1–2 mL/kg 1 mL as tolerated 5–20 mL 5–10 mL as tolerated
Birth–12 mos. 5–10 mL/h 5–10 mL q 2–8 h 10–60 mL 20–40 mL q 3–4 h
1–6 years 10–15 mL/h 10–15 mL q 2–8 h 30–90 mL 30–60 mL q feed
6–14 years 15–20 mL/h 10–20 mL q 2–8 h 60–120 mL 60–90 mL q feed
> 14 years 20–30 mL/h 20–30 mL q 2–8 h 60–120 mL 60–120 mL q feed

ically ill. However, for children who are more stable, it The primary indication for TPN is the loss of func-
is recommended that tube feeding schedules mimic as tion of the GI tract that prohibits the provision of more
closely as possible an age-appropriate feeding schedule, than a small proportion of required nutrients by the en-
such as six small feedings per day for a toddler. When teral route. Important examples include short bowel
night drip feedings are used in conjunction with day- syndrome, some congenital defects of the GI tract, and
time feeds, it is suggested that less than 50% of goal prematurity.
calories be delivered at night so as to maintain a day-
time sense of hunger and satiety. This will be especially
important once a transition to oral intake begins. Chil- Cather Selection & Position
dren who are satiated by tube feedings will be less likely An indwelling central venous catheter is preferred for
to take significant amounts of food by mouth, thus pos- long-term IV nutrition. For periods of up to
sibly delaying the transition from tube to oral nutrition. 3–4 weeks, a percutaneous central venous catheter
threaded into the superior vena cava from a peripheral
2. Parenteral Nutrition vein can be used. For the infusion of dextrose concen-
trations higher than 12.5%, the tip of the catheter
Indications should be located in the superior vena cava. Catheter
positioning in the right atrium has been associated with
A. PERIPHERAL PARENTERAL NUTRITION complications, including right atrial thrombi forma-
Peripheral parenteral nutrition is indicated when com- tion. After placement, a chest radiograph must be ob-
plete enteral feeding is not possible or desirable (eg, in tained to check this position. If the catheter is to be
the premature infant of very low birth weight during used for nutrition and medications, a double-lumen
the first few days of postnatal life or in the malnour- catheter should be used if possible.
ished surgical patient during the early postoperative pe-
riod). Short-term partial IV feeding via a peripheral
vein is a preferred alternative to dextrose and electrolyte Complications
solutions alone. Because of the osmolality of the solu-
tions required, it is usually impossible to achieve total A. MECHANICAL COMPLICATIONS
calorie and protein needs with parenteral nutrition via a 1. Related to catheter insertion or to erosion of
peripheral vein. catheter through a major blood vessel—Complica-
tions include trauma to adjacent tissues and organs,
B. TOTAL PARENTERAL NUTRITION damage to the brachial plexus, hydrothorax, pneumo-
TPN should be provided only when clearly indicated. thorax, hemothorax, and cerebrospinal fluid penetra-
Apart from the expense, numerous risks are associated tion. The catheter may slip during dressing or tubing
with this method of feeding (see Complications sec- changes, or the patient may manipulate the line.
tion). Even when TPN is indicated, every effort should
be made to provide at least a minimum of nutrients en- Chaturvedi A et al: Catheter malplacement during central venous
terally to help preserve the integrity of the GI mucosa cannulation through arm veins in pediatric patients. J Neuro-
and of GI function. surg Anesthes 2003;15(3):170 [PMID: 12826963].
 NORMAL CHILDHOOD NUTRITION & ITS DISORDERS / 309

2. Clotting of the catheter—Addition of heparin ical risk factors include prematurity, sepsis, hypoxia,
(1000 U/L) to the solution is an effective means of pre- major surgery (especially GI surgery), absence of enteral
venting this complication. If an occluded catheter does feedings, and small bowel bacterial overgrowth. Risk
not respond to heparin flushing, filling the catheter factors related to TPN include amino acid excess or im-
with recombinant tissue plasminogen activator or ster- balance and prolonged duration of TPN. Amino acid
ile 95% ethanol may be effective. solutions with added cysteine decrease cholestasis. Prac-
3. Related to composition of infusate—Calcium tices that may minimize cholestasis include initiating
phosphate precipitation may occur if excess amounts of even minimal enteral feedings as soon as feasible, avoid-
calcium or phosphorus are administered. Factors that ing sepsis by meticulous line care, avoiding overfeeding,
increase the risk of calcium phosphate precipitation in- using cysteine- and taurine-containing amino acid for-
clude increased pH and decreased concentrations of mulations designed for infants, preventing or treating
amino acids. Precipitation of medications incompatible small bowel bacterial overgrowth, protecting TPN solu-
with TPN or lipids can also cause clotting. tions from light, and avoiding hepatotoxic medications.

Freytes CO: Thromboembolic complications related to indwelling Waitzberg DL et al: Access routes for nutritional therapy. World
central venous catheters in children. Curr Opin Oncol J Surg 2000;24(12):1468 [PMID: 11193710].
2003;15:289 [PMID: 12874506].
Hooke C: Recombinant tissue plasminogen activator for central ve-
nous access device occlusion. J Pediatr Oncol Nurs NUTRIENT REQUIREMENTS & DELIVERY
2000;17(3):174 [PMID: 10944865].
Energy
B. SEPTIC COMPLICATIONS When patients are fed intravenously, no fat and carbo-
Septic complications are the most common cause of hydrate intakes are unabsorbed, and no energy is used
nonelective catheter removal, but strict use of aseptic in nutrient absorption. These factors account for at
technique and limiting entry into the catheter can re- least 7% of energy in the diet of the enterally fed pa-
duce the rates of line sepsis. tient. The intravenously fed patient also expends less
Fever over 38–38.5°C in a patient with a central energy in physical activity because of the impediment
catheter should be considered a line infection until to mobility. Average energy requirements are therefore
proved otherwise. Cultures should be obtained and IV at least 7% lower in children fed intravenously, and the
antibiotics empirically initiated. Removing the catheter decrease in activity probably increases this figure to a
may become necessary with certain infections (eg, fun- total reduction of 10–15%. Caloric guidelines for the
gal), with catheter replacement deferred until the infec- IV feeding of infants and young children are as follows:
tion is adequately treated.

Benjamin DK et al: Bacteremia, central catheters, and neonates:

When to pull the line. Pediatrics 2001;107(6):1272 [PMID: Age Requirements
11389242]. (months) (kcal/kg/d)

C. METABOLIC COMPLICATIONS 0–1 100–110

2–4 90–100
A variety of metabolic complications associated with 5–60 70–90
TPN may occur. Many of the complications are related > 5 years 1500 kcal for 1st 20 kg + 25
to deficiencies or excesses of specific nutrients in ad- kcal for each additional kg/d
ministered fluids. These complications are less common
as a result of experience and improvements in nutrient
solutions. However, specific deficiencies still occur, es-
pecially in the premature infant. Avoidance of deficien- These guidelines are averages; individuals vary con-
cies and excesses and of metabolic disorders requires siderably. A multitude of factors can significantly in-
attention to the nutrient balance, electrolyte composi- crease the energy requirement, including exposure to a
tion, and delivery rate of the infusate and careful moni- cold environment, fever, sepsis, burns, trauma, cardiac
toring, especially when the composition or delivery rate or pulmonary disease, and catch-up growth after mal-
is changed. nutrition.
Currently the most challenging metabolic complica- With few exceptions, such as some cases of respira-
tion is cholestasis, particularly common in premature tory insufficiency, at least 50–60% of energy require-
infants of very low birth weight. The cause of cholesta- ments are provided as glucose. Up to 40% of calories
sis associated with TPN is unknown. Patient and med- may be provided by IV fat emulsions.
310 / CHAPTER 10

Dextrose (with osmotic diuresis and dehydration). Possible

causes of unexpected hyperglycemia include the follow-
The energy density of IV dextrose (monohydrate) is ing: (1) inadvertent infusion of higher glucose concen-
3.4 kcal/g. Dextrose is the main exogenous energy trations than ordered, (2) uneven flow rate, (3) sepsis,
source provided by total IV feeding. IV dextrose sup- (4) a stress situation, and (5) pancreatitis. IV insulin re-
presses gluconeogenesis and provides a substrate that duces hyperglycemia but does not increase glucose oxi-
can be oxidized directly, especially by the brain, red and dation rates; it may also decrease the oxidation of fatty
white blood cells, and wounds. Because of the high os- acids, resulting in less energy for metabolism. Hence,
molality of dextrose solutions (D10W yields insulin should be used very cautiously. A standard IV
505 mOsm/kg H2O), concentrations greater than dose is 1 U/4 g of carbohydrate, but much smaller
10–12.5% cannot be delivered via a peripheral vein or quantities may be adequate and, usually, one starts with
improperly positioned central line. 0.2–0.3 U/4 g of carbohydrate.
Dosing guidelines: The standard initial quantity of Hypoglycemia may occur after an abrupt decrease in
dextrose administered will vary by age (Table 10–16). or cessation of IV glucose. When cyclic IV nutrition is
Tolerance to IV dextrose normally increases rapidly, provided, the IV glucose load should be decreased
due primarily to suppression of hepatic production of steadily for 1–2 hours prior to discontinuing the in-
endogenous glucose. Dextrose can be increased by fusate. If the central line must be removed, the IV dex-
2.5 g/kg/d; by 2.5%–5%/day; or by 2–3 mg/kg/min/d trose should be tapered gradually over several hours.
if there is no glucosuria or hyperglycemia. Standard Maximum oxidation rates for infused dextrose de-
final infusates for infants via a properly positioned cen- crease with age. It is important to note that the ranges
tral venous line usually range from 15% to 25% dex- for dextrose administration provided in Table
trose, though concentrations of up to 30% dextrose 10–16 are guidelines and that individual patient toler-
may be used especially at low flow rates. Tolerance to ance and clinical circumstances may warrant adminis-
IV dextrose loads is markedly diminished in the prema- tration of either less or more dextrose. Quantities of ex-
ture neonate and in hypermetabolic states. ogenous dextrose in excess of maximal glucose
Problems associated with IV dextrose administration oxidation rates are used initially to replace depleted
include hyperglycemia, hyperosmolality, and glucosuria glycogen stores; hepatic lipogenesis occurs thereafter.

Table 10–16. Pediatric macronutrient guidelines for total

parenteral nutrition.

Dextrose Amino acids Lipid

Age mg/kg/min g/kg/d g/kg/d g/kg/d
50–60% kcal 10–20% kcal 30–40% kcal
Preterm Initial 5–8 Initial 7–11 Initial 1.5–2 Initial 0.5–1
Max 11–12.5 Max 16–18 Max 3–4 Max 2.5–3.5
Birth–12 mo. Initial 6–8 Initial 9–11 Initial 1.5–2 Initial 1
Max 11–15 Max 16–21.5 Max 3 Max 2.5–3.5
1–6 yr Initial 6–7 Initial 8–10 Initial 1–1.5 Initial 1
Max 10–12 Max 14–17 Max 2–2.5 Max 2.5–3.5
> 6 yr Initial 5–7 Initial 8–10 Initial 1 Initial 1
Max 9 Max 13 Max 1.5–2 Max 3
> 10 yr Initial 4–5 Initial 5–7 Initial 1 Initial 1
Max 6–7 Max 8–10 Max 1.5–2 Max 2–3
Adolescents Initial 2–3 Initial 3–4 Initial 1 Initial 0.5–1
Max 5–6 Max 7–8 Max 1.5–2 Max 2
 NORMAL CHILDHOOD NUTRITION & ITS DISORDERS / 311

Excess hepatic lipogenesis may lead to a fatty liver. Li- 4. The production of CO2 is 40% lower per unit of
pogenesis results in release of carbon dioxide, which energy, an important consideration in cases of
when added to the amount of carbon dioxide produced pulmonary insufficiency.
by glucose oxidation (which is 40% greater than that 5. The energy cost of fat storage is negligible.
produced by lipid oxidation) may elevate the PaCO2 6. The risk of fatty liver is decreased because of de-
and aggravate respiratory insufficiency or impede wean- creased hepatic lipogenesis from dextrose.
ing from a respirator.
Potential disadvantages of fat emulsions include the
following:
Lipids
1. Impairment of function of neutrophils, macro-
The energy density of lipid emulsions (20%) is phages, and the reticuloendothelial system.
10 kcal/g of lipid or 2 kcal/mL of infusate. The lipids 2. Coagulation defects, including thrombocytope-
are derived from either soybean or safflower oil. All nia, elevated prothrombin time, and partial
consist of more than 50% linoleic acid and 4–9% thromboplastin time.
linolenic acid. It is recognized that this high level of
linoleic acid is not ideal, except when small quantities 3. Decrease in pulmonary oxygen diffusion.
of lipid are being given to prevent an EFA deficiency. 4. Competition by free fatty acids with bilirubin and
Ultimately, improved emulsions are anticipated. Be- drugs for albumin-binding sites.
cause 10% and 20% lipid emulsions contain the same 5. Increase in low-density lipoprotein cholesterol.
concentrations of phospholipids, a 10% solution deliv-
ers more phospholipid per gram of lipid than a 20% so- In general, these adverse effects can be avoided by
lution. Twenty percent lipid emulsions are preferred. starting with modest quantities and advancing cau-
The level of LPL activity is the rate-limiting factor tiously in light of results of triglyceride monitoring and
in the metabolism and clearance of fat emulsions from clinical circumstances. In cases of severe sepsis, special
the circulation. LPL activity is inhibited or decreased by caution is required to ensure that the lipid is metabo-
malnutrition, leukotrienes, immaturity, growth hor- lized effectively. Monitoring with long-term use is also
mone, hypercholesterolemia, hyperphospholipidemia, essential.
and theophylline. LPL activity is enhanced by glucose, IV lipid dosing guidelines: Check serum triglyc-
insulin, lipid, catecholamines, and exercise. Heparin re- erides before starting and after increasing the dose.
leases LPL from the endothelium into the circulation Commence with l g/kg/d, given over l2–20 hours or
and enhances the rate of hydrolysis and clearance of 24 hours in small preterm infants. Advance by
triglycerides. In small premature infants, low-dose he- 0.6–l.0 g/kg/d, every 1–2 days, up to goal (Table
parin infusions may increase tolerance to IV lipid emul- 10–16).
sion. As a general rule, do not increase the dose if the
The advantages of using fat emulsions to provide up serum triglyceride level is above 250 mg/dL during in-
to 40% of caloric intake include the following: fusion (150 mg/dL in neonates) or if the level is greater
than 150 mg/dL 6–l2 hours after cessation of the lipid
infusion.
1. The high energy density allows more energy to be Serum triglyceride levels above 400–600 mg/dL
provided when fluid volume is restricted. may precipitate pancreatitis. In patients for whom nor-
2. The low osmolality (280 mOsm/kg H2O) is of mal amounts of IV lipid are contraindicated, 4–8% of
special value when using a peripheral line. calories as IV lipid should be provided (300 mg linoleic
3. EFA deficiencies can be prevented. acid/100 kcal) to prevent essential fatty acid deficiency.

Table 10–17. Electrolyte requirements for parenteral nutrition.

Electrolyte Preterm Infant Full-Term Infant Child Adolescent

Sodium 2–5 mEq/kg 2–3 mEq/kg 2–3 mEq/kg 60–150 mEq/d
Chloride 2–5 mEq/kg 2–3 mEq/kg 2–3 mEq/kg 60–150 mEq/d
Potassium 2–3 mEq/kg 2–3 mEq/kg 2–3 mEq/kg 70–180 mEq/d
312 / CHAPTER 10

Neonates and malnourished pediatric patients receiving 24–48 hours after administration. The dose of added
lipid-free parenteral nutrition are at high risk for EFA cysteine is 40 mg/g of TrophAmine. The relatively low
deficiency because of limited adipose stores. pH of TrophAmine is also advantageous for solubility
of calcium and phosphorus.
Crook MA: Lipid clearance and total parenteral nutrition: The im-
portance of monitoring plasma lipids. Nutrition D. DOSING GUIDELINES
2000;16:774 [PMID: 10978859]. Amino acids can be started at 1.0–2.0 g/kg/d in most
patients (see Table 10–16). In severely malnourished
Nitrogen infants, the initial amount should be 1.0 g/kg/d. Even
One gram of nitrogen is yielded by 6.25 g of protein in very low birth weight infants, there is evidence that
(1 g of protein contains 16% nitrogen). Caloric density higher initial amounts of amino acids are tolerated with
of protein is equal to 4 kcal/g. little indication of protein “toxicity.” Larger quantities
of amino acids in relation to calories can minimize the
A. PROTEIN REQUIREMENTS degree of negative nitrogen balance when the infusate is
Protein requirements for IV feeding are the same as hypocaloric. Amino acid intake can be advanced by
those for normal oral feeding (see Table 10–2). 0.5–1.0 g/kg/d toward the goal. Normally the final in-
fusate will contain 2–3% amino acids, depending on
B. PROTEIN-ENERGY INTERACTIONS the rate of infusion. Concentration should not be ad-
There are important interactions between protein and vanced beyond 2% in peripheral vein infusates due to
energy requirements. A positive nitrogen balance can- osmolality.
not be achieved on a hypocaloric diet, because protein
will be catabolized for energy. When energy intakes are E. MONITORING
low, the administration of some amino acid does, how- Monitoring for tolerance of the IV amino acid solu-
ever, lessen the severity of the negative nitrogen bal- tions should include routine blood urea nitrogen.
ance. Conversely, when nitrogen intake is low, the pro- Serum alkaline phosphatase, γ-glutamyltransferase, and
vision of calories improves nitrogen balance to some bilirubin should be monitored to detect the onset of
extent. In infants, the energy necessary to minimize ni- cholestatic liver disease.
trogen loss associated with an amino acid-free diet is
approximately 70 kcal/kg/d. At this level of energy in- F. SPECIAL AMINO ACID PREPARATIONS
take, positive nitrogen balance depends on the level of Some solutions are designed to provide high concentra-
nitrogen intake and is independent of further increase tions of branched-chain amino acids. These solutions
in energy intake. are expensive and should not be ordered without a spe-
In infants receiving about 50 kcal/kg/d, increasing cific reason, which does not include their routine use in
protein intake up to 3 g/kg/d improves the nitrogen liver disease. They may be indicated in hepatic failure,
balance. In these circumstances, therefore, a ratio of especially in the presence of encephalopathy, and are
grams of nitrogen per kilocalorie as low as 1:100 can be also undergoing experimental use in multisystem organ
advantageous. However, at higher levels of energy in- failure. In this circumstance, the branched-chain amino
take, ratios of 1:250 to 1:150 or more are optimal. Al- acids are given as a source of metabolizable energy, pro-
though these ratios provide a useful crude check, they viding up to 25% of energy intake. Solutions contain-
are not usually the best means of determining protein ing only essential amino acids may have some applica-
requirements. tion in the management of acute renal failure.
C. INTRAVENOUS AMINO ACID SOLUTIONS G. ALBUMIN
Nitrogen requirements can be met by one of the com- Albumin can be added to the infusate when clinically
mercially available amino acid solutions. For older chil- indicated to restore blood volume or oncotic pressure.
dren and adults, none of the standard preparations has If the origin of hypoalbuminemia is considered to be
a clear advantage over the others as a source of amino primarily nutritional, however, the hypoalbuminemia
acids. For infants, however, including premature in- should be managed by careful nutritional rehabilitation
fants, accumulating evidence suggests that the use of rather than by IV administration of albumin. Albumin
TrophAmine (McGaw) is associated with a normal is deficient in isoleucine and tryptophan and has too
plasma amino acid profile, superior nitrogen retention, long a half-life (15–20 days) to be considered a useful
and a lower incidence of cholestasis. TrophAmine con- nutritional source of amino acids. Potential adverse ef-
tains 60% essential amino acids, is relatively high in fects of IV albumin administration include loss of albu-
branched-chain amino acids, contains taurine, and is min from the circulation into interstitial fluid of the
compatible with the addition of cysteine within lungs and elsewhere due to increased capillary perme-
 NORMAL CHILDHOOD NUTRITION & ITS DISORDERS / 313

ability, coagulation defects secondary to volume expan- cause of impaired membrane function and high intracel-
sion and dilution of clotting factors, inhibition of lular sodium levels. Conversely, generous quantities of
platelet aggregation, increases in prothrombin time and potassium are indicated. Replacement electrolytes and
partial thromboplastin time, increased sodium intake in fluids should be delivered via a separate infusate.
the albumin infusate, and increased binding to serum
calcium resulting in decreased ionized calcium. C. TRACE ELEMENTS
Albumin is a poor nutritional marker because of the Recommended IV intakes of trace elements are as fol-
number of nonnutritional factors that contribute to hy- lows: zinc 100 µg/kg, copper 20 µg/kg, manganese
poalbuminemia. 1 µg/kg, chromium 0.2 µg/kg, selenium 2 µg/kg, and
Dosing Guidelines: When clinical circumstances iodide 1 µg/kg. Of note, IV zinc requirements may be
warrant, albumin can be added to parenteral nutrition as high as 400 µg/kg for premature infants and can be
in the amount of 0.5–1.0 g/kg/d. The half-life of IV al- up to 250 µg/kg for infants with short bowel syndrome
bumin in critical illness can be as short as under and significant GI losses of zinc. When IV nutrition is
12 hours. National shortages of albumin are not un- supplemental or limited to fewer than 2 weeks, and pre-
usual. Thus its use must be reserved for patients with existing nutritional deficiencies are absent, only zinc
true therapeutic need who show a clinical response to need routinely be added.
the intervention. IV copper requirements are relatively low in the young
infant because of the presence of hepatic copper stores.
These are significant even in the 28-week fetus. Circulat-
Minerals & Electrolytes ing levels of copper and manganese should be monitored
A. CALCIUM, PHOSPHORUS, AND MAGNESIUM in the presence of cholestatic liver disease. If monitoring is
not feasible, temporary withdrawal of added copper and
Intravenously fed premature and full-term infants
manganese is advisable. Copper and manganese are ex-
should be given relatively high amounts of calcium and
creted primarily in the bile, but selenium, chromium, and
phosphorus. Current recommendations are as follows:
molybdenum are excreted primarily in the urine. These
calcium, 500–600 mg/L; phosphorus, 400–450 mg/L;
trace elements, therefore, should be administered with
and magnesium, 50–70 mg/L. After age 1 year, the rec-
caution in the presence of renal failure.
ommendations are as follows: calcium, 200–400 mg/L;
Although low doses of iron are routinely added in
phosphorus, 150–300 mg/L; and magnesium,
some centers to the IV infusate for infants and children,
20–40 mg/L. The ratio of calcium to phosphorous
no official recommendation has been made because of
should be 1.3:1 by weight or 1:1 by molar ratio. These
the lack of adequate published data regarding compati-
recommendations are deliberately presented as mil-
bility. Iron added to the infusate should be in a diluted
ligrams per liter of infusate to avoid inadvertent admin-
form of iron dextran in a concentration of 1 mg/L.
istration of concentrations of calcium and phosphorus
After age 2 months, maintenance IV iron requirements
that are high enough to precipitate in the tubing. Dur-
for the full-term infant are approximately 100 µg/kg/d.
ing periods of fluid restriction, care must be taken
After the first month, the premature infant requires up
not to inadvertently increase the concentration of
to 200 µg/kg/d intravenously. Although overload is un-
calcium and phosphorus in the infusate. These recom-
likely to occur during short-term parenteral nutrition, a
mendations assume an average fluid intake of
surreptitious accumulation of extra iron could occur if
120–150 mL/kg/d and an infusate of 25 g of amino
parenteral nutrition is prolonged. This risk is enhanced
acid per liter. With lower amino acid concentrations, if the patient has received blood transfusions. A second
the concentrations of calcium and phosphorus should concern is that the potential for free iron is increased in
be decreased. malnourished infants with low transferrin levels. Excess
iron is thought to enhance the risk of gram-negative
B. ELECTROLYTES septicemia. Iron has powerful oxidant properties and
Standard recommendations are given in Table 10–17. can enhance the demand for antioxidants, especially vi-
After chloride requirements are met, the remainder of tamin E. None of these concerns appear to preclude the
the anion required to balance the cation should be given routine use of iron supplements during IV nutrition,
as acetate to avoid the possibility of acidosis resulting but they do emphasize the need for a conservative atti-
from excessive chloride. The required concentrations of tude in determining dosage schedules.
electrolytes depend to some extent on the flow rate of
the infusate and must be modified if flow rates are un- Vitamins
usually low or high and if there are specific indications
in individual patients. IV sodium should be adminis- Two vitamin formulations are available for use in pedi-
tered sparingly in the severely malnourished patient be- atric parenteral nutrition: MVI Pediatric and MVI-
314 / CHAPTER 10

12 (AstraZeneca). MVI Pediatric contains the follow- A. PHYSICAL EXAMINATION

ing: vitamin A, 0.7 mg; vitamin D, 400 IU; vitamin E, Monitor especially for hepatomegaly (differential diag-
7 mg; vitamin K, 200 µg; ascorbic acid, 80 mg; thi- noses include fluid overload, congestive heart failure,
amin, 1.2 mg; riboflavin, 1.4 mg; niacinamide, 17 mg; steatosis, and hepatitis) and edema (differential diag-
pyridoxine, 1 mg; vitamin B12, 1 µg; folic acid, 140 µg; noses include fluid overload, congestive heart failure,
pantothenate, 5 mg; and biotin, 20 µg. This formula- hypoalbuminemia, and thrombosis of superior vena
tion is suboptimal, with too little vitamin A and exces- cava).
sive amounts of water-soluble vitamins, but it is the
best one available. Recommended dosing is as follows: B. INTAKE AND OUTPUT RECORD
5 mL for children weighing more than 3 kg, 3.25 mL Calories and volume delivered should be calculated
for infants 1–3 kg, and 1.5 mL for infants weighing less from previous day’s intake and output records (that
than 1 kg. Children older than 11 years old can receive which was delivered rather than that which was or-
10 mL of the adult formulation, MVI-12, which con- dered). The following entries should be noted on flow
tains the following: vitamin A, 1 mg; vitamin D, sheets: IV, enteral, and total fluid (mL/kg/d); dextrose
200 IU; vitamin E, 10 mg; ascorbic acid, 100 mg; thi- (g/kg/d or mg/kg/min); protein (g/kg/d); lipids (g/kg/d);
amin, 3 mg; riboflavin, 3.6 mg; niacinamide, 40 mg; energy (kcal/kg/d); percent of energy from enteral nu-
pyridoxine, 4 mg; vitamin B12, 5 µg; folic acid, 400 µg; trition.
pantothenate, 15 mg; and biotin, 60 µg. MVI-12 con-
tains no vitamin K. C. GROWTH, URINE, AND BLOOD
IV lipid preparations contain enough tocopherol to Routine monitoring guidelines are given in Table
affect total blood tocopherol levels. The majority of to- 10–18. These are minimum requirements, except in the
copherol in soybean oil emulsion is α-tocopherol, very long-term stable patient. Individual variables
which has substantially less biologic activity than the α- should be monitored more frequently as indicated, as
tocopherol present in safflower oil emulsions. should additional variables or clinical indications. For
A dose of 40 IU/kg/d of vitamin D (maximum example, a blood ammonia analysis should be ordered
400 IU/d) is adequate for both full-term and preterm for an infant with lethargy, pallor, poor growth, acido-
infants. sis, azotemia, or abnormal liver test results.

Greene HL et al: Guidelines for the use of vitamins, trace elements,

calcium, magnesium, and phosphorus in infants and children
Fluid Requirements receiving total parenteral nutrition: Report of the Subcom-
The initial fluid volume and subsequent increments in mittee on Pediatric Parenteral Nutrient Requirements from
flow rate are determined by basic fluid requirements, the Committee on Clinical Practice Issues of the American
Society for Clinical Nutrition. Am J Clin Nutr 1988;48:
the patient’s clinical status, and the extent to which ad- 1324 [PMID: 3142247].
ditional fluid administration can be tolerated and may Shulman RJ, Phillips S: Parenteral nutrition in infants and chil-
be required to achieve adequate nutrient intake. Calcu- dren. J Pediatr Gastroenterol Nutr 2003;36(5):587 [PMID:
lation of initial fluid volumes to be administered should 12717082].
be based on standard pediatric practice. Tolerance of
higher flow rates must be determined on an individual
basis. If replacement fluids are required for ongoing ab-
INTENSIVE CARE NUTRITION
normal losses, these should be administered via a sepa- Severe stress of any kind (eg, large surface area and deep
rate line. burns, major trauma, major surgery, sepsis) results in
common metabolic changes that require special nutri-
tional management. First, several hormones are in-
creased, including thyroid hormone, catecholamines,
Monitoring cortisol, and glucagon. These hormones, acting directly
Vital signs should be checked on each shift. With a cen- on peripheral tissues or indirectly through an increase
tral catheter in situ, a fever of more than 38.5°C re- in peripheral insulin resistance, produce a hypermeta-
quires that peripheral and central-line blood cultures, bolic state accompanied by rapid protein catabolism
urine culture, complete physical examination, and ex- and hyperglycemia. These hormonal changes develop
amination of the IV entry point be made. Instability of in seconds for the catecholamines, within minutes for
vital signs, elevated white blood cell count with left insulin and glucagon, and within hours for thyroid and
shift, and glycosuria suggest sepsis. Removal of the cen- cortisol. Rapid measurements of these hormones and
tral venous catheter should be considered if the patient their metabolic effects are not available for routine clin-
is toxic or unresponsive to antibiotics. ical management, so clinicians anticipate and deal with
 NORMAL CHILDHOOD NUTRITION & ITS DISORDERS / 315

Table 10–18. Routine total parenteral nutrition monitoring summary.

Variables Acute Stage Long-Termb

Growth
Weight Daily Weekly
Length Weekly
Head circumference Weekly
Urine
Glucose (dipstick) With each void With changes in intake or status
Specific gravity Void
Volume Daily
Blood
Glucose 4 hours after changes,a then daily × 2 days Weekly
Na+, K+, Cl−, CO2, blood Daily for 2 days after changes,a then twice weekly Weekly
urea nitrogen
Ca2+, Mg2+, P Initially, then twice weekly Weekly
Total protein, albumin, bilirubin, Initially, then weekly Every other week
aspartate transaminase,
and alkaline phosphatase
Zinc and copper Initially according to clinical indications Monthly
Triglycerides Initially, 1 day after changes,a then weekly Weekly
Compete blood count Initially, then twice weekly; according to clinical indications Twice weekly
(see text)
a
Changes include alterations in concentration or flow rate.
b
Long-term monitoring can be tapered to monthly or less often, depending on age, diagnosis, and clinical status of patient.

them. Early and aggressive IV and enteral nutrition are ture will be adequate for the stressed patient. Ideally,
essential, with the goal of providing adequate nonpro- energy expenditure should be measured in critically ill
tein calories (favoring lipids over glucose) and amino patients. When this is impossible, the patient should be
acids to preserve essential protein structures. The utility monitored for weight gain (fluid vs tissue) and signs of
of insulin infusion, including coinfusion of growth hor- overfeeding.
mone and insulin-like growth factor-1 remains contro- The muscle proteolysis and negative nitrogen bal-
versial. ance characteristic of the hypermetabolic state cannot
be counteracted totally by aggressive nutrition support,
Agnus MSD, Jaksic T: Nutritional support of the critically ill child. but the adverse effects can be attenuated. Negative ni-
Curr Opin Pediatr 2002;14:470 [PMID: 12130914]. trogen balance can be improved by providing
Briassoulis G et al: Energy expenditure in critically ill children. Crit 1.5–2 times the basal protein requirement for the pa-
Care Med 2000;28(4):1166 [PMID: 10809300]. tient’s age. Larger quantities are unlikely to improve ni-
trogen balance, require substantial energy expenditure
Provision of Nutrients in Hypermetabolic for oxidation, and increase CO2 production.
Another metabolic aberration in the stress-induced,
States hypermetabolic state is uncontrolled hepatic gluconeo-
Enteral feeding should be continued whenever possible, genesis, often producing markedly elevated blood glu-
so that the integrity of the enterocytes can be main- cose concentrations. Gluconeogenesis is not switched
tained. The increase in energy requirements varies ac- off, as would normally be expected, by the administra-
cording to the severity of hypermetabolism and its tion of IV dextrose. In fact, dextrose administration
cause. Requirements are highest in burn patients, but may aggravate hyperglycemia and increase hepatic lipo-
major trauma and sepsis may increase energy require- genesis. In some patients (especially those who develop
ments by 20–50% over resting energy needs. Mounting multisystem organ failure), only very modest quantities
evidence suggests that increases in energy needs associ- of dextrose (< 45% of energy requirements) are toler-
ated with acute stress are short-lived, and that in most ated. If severe hyperglycemia and glycosuria occur, in-
cases energy needs equivalent to resting energy expendi- sulin therapy may be necessary. However, the effects of
316 / CHAPTER 10

insulin in hypermetabolic states are complex and not show consistent results. Glutamine is a nonessential
well clarified. Hypermetabolism is characterized by in- amino acid that is an important source of nitrogen for
sulin resistance. Furthermore, insulin requires the si- nucleic acid synthesis. It may become conditionally es-
multaneous administration of greater than normal sential during acute illness and serve as a preferred en-
amounts (≤ 25% of energy needs) of amino acids to ergy source for certain tissues. Most glutamine supple-
limit or partially reverse muscle catabolism and gluco- mentation studies have involved adults and have
neogenesis. Theoretically, insulin administration could yielded conflicting results; thus its therapeutic relevance
decrease lipolysis and thus deprive the hypermetabolic to pediatric populations is unknown. Other factors po-
patient of some of the major sources of usable endoge- tentially useful as immune modulators include arginine,
nous fuel. which has a central role in nitric oxide metabolism; nu-
Although lipolysis is increased in hypermetabolic cleotides, which may be essential nutrients in formula-
states, beta-oxidation of fatty acids also is increased, at fed infants; probiotics, which may shorten the course of
least initially. IV lipids usually can be metabolized well bacterial and viral gastroenteritis; and prebiotics, whose
in early stages, and up to 50% of energy may be pro- fermentation products (short-chain fatty acids) may be
vided as lipid. Metabolically, lipid is the preferred fuel a source of nutrition for the colon. The use of these
in patients with severe sepsis. Lipid tolerance deterio- compounds in pediatric nutrition support is still experi-
rates in advanced multisystem organ failure. mental, and further research is needed to show clear
The metabolic and nutritional advantages of lipid as safety and efficacy.
a fuel must be balanced against potential adverse effects
in the septic child (see preceding discussion of IV
lipids). It is important not to administer fat emulsion in Ball PA, Hardy G: Glutamine in pediatrics: Where next? Nutrition
excess of quantities that can be cleared effectively from 2002;18:451 [PMID: 12044814].
the circulation. Buchman AL: Glutamine: Commercially essential or conditionally
Much interest has focused on the potential benefits essential? A critical appraisal of the human data. Am J Clin
Nutr 2001;74:25 [PMID: 11451714].
of dietary factors in conferring an advantage to the im-
Jackson NC et al: Effects of glutamine supplementation, GH, and
mune system, called “immunonutrition.” Of the factors IGF-I on glutamine metabolism in critically ill patients. Am
studied, glutamine during acute stress has garnered J Physiol Endocrinol Metab 2000;278:E226 [PMID:
much attention, though clinical trials have failed to 10662706].
 Emergencies & Injuries 11
F. Keith Battan, MD, & Marsha S. Anderson, MD

way must be opened (eg, by head positioning and the

I. EMERGENCIES & INJURIES chin lift maneuver) before breathing and then circula-
tion are assessed.

F. Keith Battan, MD
Airway
Look, listen, and feel for upper airway patency:
ADVANCED LIFE SUPPORT (1) Look for signs of obstruction such as inspiratory
work or suprasternal retractions. A patient with signifi-
FOR INFANTS & CHILDREN cant airway obstruction will have an altered level of
A systematic approach to a seriously ill or injured child consciousness, such as agitation or lethargy. (2) Listen
will allow rapid determination of the child’s physiologic for adventitious breath sounds such as stridor, snoring,
status and concurrent initiation of resuscitative mea- or gurgling. (3) Feel for air movement with your face
sures. The goal of rapid assessment and intervention is near the child’s mouth and nose.
not initially to make a specific clinical diagnosis but to The airway is managed initially by noninvasive
correct any physiologic derangement—Is there airway means such as oxygen administration, chin lift, jaw
obstruction or respiratory failure? Is there shock?—and thrust, suctioning, or bag–valve–mask ventilation, then
then to intervene rapidly to ensure adequate oxygena- by invasive maneuvers such as endotracheal intubation,
tion, ventilation, circulation, and thereby cerebral per- laryngeal mask insertion, or, rarely, cricothyroidotomy.
fusion. Once initial resuscitative measures are begun, If neck injury is suspected, the cervical spine must be
consideration of the cause of the arrest begins, with an immobilized and kept from extension or flexion. (See
emphasis on treatable, reversible causes. It is essential to Approach to the Pediatric Trauma Patient section.)
determine whether any directed therapy (eg, glucose The following discussion assumes that basic life support
administration for hypoglycemia) is needed. has been instituted.
When progressive deterioration leads to bradycardia Knowledge of pediatric anatomy is important for
and ultimately to asystole, sufficient hypoxic and is- airway management. Infants are obligate nasal
chemic insult to the brain and other vital organs has oc- breathers; therefore, secretions or blood in the na-
curred to make neurologic recovery extremely unlikely, sopharynx can cause significant distress. Children’s
even in the doubtful event that the child survives the tongues are large relative to their oral cavities, and the
arrest. Children who respond to ventilation and oxy- larynx is high and anteriorly located.
genation alone or to less than 5 minutes of advanced A. Place the head in the sniffing position (Figure
life support are much more likely to survive neurologi- 11–1). The neck should be slightly flexed and the head
cally intact. Therefore, it is essential to recognize the gently extended so as to bring the face forward. This
child who is at risk for progressing to cardiopulmonary position aligns the oral, pharyngeal, and tracheal planes
arrest and to provide aggressive intervention before (Figure 11–2). The head should be repositioned if air-
asystole occurs. way obstruction persists after head tilt and jaw thrust.
Note: Standard precautions must be maintained In an infant, the relatively large occiput puts the head
during resuscitation efforts. in a sniffing position when supine; in an older child,
more head extension is necessary. Avoid hyperextension
of the neck, especially in infants.
THE ABCS OF RESUSCITATION B. Perform the chin lift or jaw thrust maneuver
Severely ill children should be rapidly evaluated in a de- (Figure 11–3). Lift the chin upward while avoiding
liberate sequence of airway patency, breathing ade- pressure on the submental triangle, or lift the jaw by
quacy, and circulation integrity. Derangement at each traction upward on the angle of the jaw. Jaw thrust
point must be corrected before proceeding to the next without head tilt should be done if cervical spine injury
function. Thus, if a child’s airway is obstructed, the air- is possible.
317
Copyright © 2005, 2001, by The McGraw-Hill Companies, Inc. Click here for terms of use.
318 / CHAPTER 11

Figure 11–1. Opening the airway

with the head tilt/chin lift. Gently lift
the chin with one hand and push
down on the forehead with the other
hand. (Reproduced, with permission,
from Textbook of Pediatric Life Support.
American Heart Association, 1997.)

C. Suction the mouth of secretions, blood, and for- accessory muscle use (eg, abdominal muscles), skin
eign material. color, and tracheal deviation. Cyanosis is a late finding
D. Remove visible foreign bodies, using fingers or a in children owing to their relative anemia, making
Magill forceps—visualizing by means of a laryngoscope pulse oximetry determination highly desirable. Again
if necessary. Blind finger sweeps should not be done. note mental status. (2) Listen for adventitious breath
E. Insert an oropharyngeal or, in the conscious pa- sounds such as wheezing. Auscultate for air entry, sym-
tient, a nasopharyngeal airway to relieve upper airway metry of breath sounds, and rales. (3) Feel for subcuta-
obstruction due to prolapse of the tongue into the pos- neous crepitus.
terior pharynx (Figures 11–4 and 11–5). This is the If spontaneous breathing is inadequate, initiate posi-
most common cause of airway obstruction in uncon- tive-pressure ventilation with bag–mask ventilation and
scious children. The correct size for an oropharyngeal 100% oxygen. If some respiratory effort is present but
airway is obtained by measuring from the upper central inadequate, coordinate bagging with the patient’s ef-
gumline to the angle of the jaw. Nasopharyngeal air- forts. Adequacy of ventilation is reflected in adequate
ways should fit snugly but not tightly within the nares rise and fall of the chest and auscultation of good air
and should be equal in length to the distance from the entry bilaterally. If the chest does not rise and fall easily
nares to the tragus. with bagging, reposition the airway and repeat the ma-
neuvers described previously in the Airway section. Per-
form airway foreign body extraction maneuvers if the
Breathing airway remains obstructed, including visualizing the
Assessment of respiratory status is largely accomplished airway with a laryngoscope and using Magill forceps.
by inspection. (1) Look for adequate and symmetrical The presence of asymmetrical breath sounds in a child
chest rise and fall, respiratory rate, increased work of in cardiac arrest or in severe distress suggests pneu-
breathing (including retractions, flaring, and grunting), mothorax and is an indication for needle thoracostomy.
 EMERGENCIES & INJURIES / 319

A In small children, the transmission of breath sounds

throughout the chest may impair the ability to auscul-
tate the presence of a pneumothorax. Bag–mask venti-
lation is effective in the vast majority of cases. Note: Ef-
T fective oxygenation and ventilation are the keys to
successful resuscitation.
Using cricoid pressure (Sellick maneuver) during all
P
O positive-pressure ventilation, intubate the trachea in pa-
tients unresponsive to bag–mask ventilation, those in
coma, those who require airway protection, or those
who will require prolonged ventilation. Advanced air-
way management techniques are described in the refer-
ences accompanying this section. Cricothyroidotomy is
B rarely necessary. (See Approach to the Pediatric Trauma
Patient section.)

Circulation
The diagnosis of shock must be rapid. Diagnosis can
T and should be made by clinical examination. Clinical
O P assessments A–E are often referred to as an assessment
of perfusion:
A. PULSES
Check adequacy of peripheral pulses. Pulses become
weak and thready only with severe hypovolemia. Com-
pare peripheral pulses to central pulses.
C
B. HEART RATE
Compare with age-specific norms. Tachycardia can be a
nonspecific sign of distress, whereas bradycardia for age
is a prearrest sign and necessitates aggressive resuscita-
T tion.
P
C. EXTREMITIES
O
As shock progresses, extremities become cooler, from
distal to proximal. For example, a child whose extremi-
ties are cool distal to the elbows and knees is in severe
shock.
D. CAPILLARY REFILL TIME
Figure 11–2. Correct positioning of the child older This is an important indicator of perfusion. A refill
than 2 years of age for ventilation and tracheal intuba- time longer than 2.0 seconds is abnormal unless the
tion. A: With the patient on a flat surface (eg, bed or child is cold.
table), the oral (O), pharyngeal (P), and tracheal (T) axes
pass through three divergent planes. B: A folded sheet E. MENTAL STATUS
or towel placed under the occiput of the head aligns Hypoxia, hypercapnia, or ischemia will result in altered
the pharyngeal and tracheal axes. C: Extension of the mental status. Remember that other important treat-
atlanto-occipital joint results in alignment of the oral, able conditions may also result in altered mental status,
pharyngeal, and tracheal axes. (Reproduced, with per- such as intracranial hemorrhage, meningitis, and hypo-
mission, from Textbook of Pediatric Life Support. American glycemia.
Heart Association, 1997.) F. SKIN COLOR
Compromised cardiopulmonary status can cause pallor
or gray, mottled, or ashen skin colors.
320 / CHAPTER 11

Figure 11–3. Opening the airway

with the jaw thrust. Lift the angles of
the mandible. This moves the jaw
and tongue forward and opens the
airway without bending the neck.
(Reproduced, with permission, from
Textbook of Pediatric Life Support. Amer-
ican Heart Association, 1997.)

A B

Figure 11–4. A-D: Selection of an

oral airway. An airway of the proper
size will relieve obstruction caused
by the tongue without damaging lar-
yngeal structures. The appropriate
size can be estimated by holding the
airway next to the child’s face (A).
The tip of the airway should end just
cephalad to the angle of the
mandible (dashed line), resulting in
proper alignment with the glottic
opening (B). If the oral airway in-
serted is too large, the tip will align
posterior to the angle of the
C D
mandible (C) and obstruct the glottic
opening by pushing the epiglottis
down (arrow). If the oral airway is too
small, the tip will align well above the
angle of the mandible (D) and exac-
erbate airway obstruction by pushing
the tongue into the hypopharynx (ar-
rows). (Adapted, with permission, from
Cote and Todres in Textbook of Pedi-
atric Life Support. American Heart Asso-
ciation, 1997.)
 EMERGENCIES & INJURIES / 321

A G. BLOOD PRESSURE
Blood pressure determination is not necessary to make
the diagnosis of shock. It is important to remember
that shock or inadequate perfusion of vital organs may
be present before the blood pressure falls below the nor-
mal limits for age. As intravascular volume falls, periph-
eral vascular resistance increases so that blood pressure
is maintained until there is 35–40% depletion of blood
volume, followed by precipitous and often irreversible
deterioration of perfusion (Figure 11–6). Shock that
occurs with signs of decreased perfusion (eg, tachycar-
dia and delayed capillary refill time) but normal blood
Nasopharyngeal pressure is compensated shock. When blood pressure
airways (2), also falls, decompensated shock is present. The appro-
shortened
endotracheal priate-size cuff must be used to obtain an accurate
tube blood pressure. Blood pressure determination should be
done manually, because automated machines can give
erroneous readings in children.
B

MANAGEMENT OF SHOCK
Intravenous (IV) access is essential but can be difficult
to establish in children with shock. Peripheral access,
especially the antecubital veins, should be attempted
first, but central cannulation—depending on individual
expertise—should follow quickly if peripheral access is
unsuccessful. Alternatives are percutaneous cannulation
Nasopharyngeal
airway in place

140 Vascular
C resistance

100
Percent of control

60

20 Cardiac Blood
output pressure
Figure 11–5. A: Nasopharyngeal airways. A short-
ened tracheal tube may be substituted (to reduce resis-
tance). B: Placement of a nasopharyngeal airway. C: 25 50 75
Shortened (cut) tracheal tube used as a nasopharyngeal Percent blood volume deficit
airway. Note that the standard 15-mm adapter must be
firmly reinserted into the tracheal tube. (Reproduced, Figure 11–6. Model for cardiovascular response to
with permission, from Textbook of Pediatric Life Support. hypovolemia from hemorrhage (based on normative
American Heart Association, 1997.) data). (Reproduced, with permission, from Textbook of Pe-
diatric Life Support. American Heart Association, 1997.)
322 / CHAPTER 11

of femoral, subclavian, or internal or external jugular B. DISTRIBUTIVE SHOCK

veins; cutdown at antecubital, femoral, or saphenous Distributive shock represents relative hypovolemia from
sites; or intraosseous (IO) lines (Figure 11–7). Consider increased vascular capacitance of circulating volume. Ex-
IO needle placement in any severely ill child when ve- amples are sepsis, anaphylaxis, and spinal cord injury.
nous access cannot be established rapidly. Use short, Initial therapy is again by limited isotonic volume re-
wide-bore catheters to allow maximal flow rates. Two placement with crystalloid, but pressors may be necessary
IV lines should be started in severely ill children. In if perfusion does not normalize after delivery of two
newborns, the umbilical veins may be cannulated. Con- 20 mL/kg boluses of crystalloid. Children in distributive
sider arterial access if beat-to-beat monitoring or fre- shock must be admitted to a pediatric intensive care unit.
quent laboratory tests will be needed.
C. CARDIOGENIC SHOCK
Differentiation of Shock States Cardiogenic shock can occur as a complication of con-
& Initial Therapy genital heart disease, myocarditis, dysrhythmias, inges-
Therapy for inadequate circulation is determined by tions (eg, clonidine, cyclic antidepressants), or as a se-
the cause of circulatory failure. quela of prolonged shock due to any cause. The
diagnosis is suggested by any of the following signs: ab-
A. HYPOVOLEMIC SHOCK normal cardiac rhythm, distended neck veins, rales, ab-
The most common type of shock in the pediatric popu- normal heart sounds such as an S3 or S4, friction rub,
lation is hypovolemic. Frequent causes include dehy- narrow pulse pressure, or hepatomegaly. Chest radi-
dration, diabetes, or heat illness; hemorrhage; and ographs will show cardiomegaly and pulmonary
burns. Initial therapy is with isotonic crystalloid solu- edema—not seen in shock due to other causes. An ini-
tion, that is, normal saline or lactated Ringer solution. tial bolus of crystalloid may be given, but dopamine or
Give 20 mL/kg body weight, repeated as necessary, other pressors, and possibly agents to reduce afterload,
with frequent reassessments, until perfusion normalizes. are necessary to improve perfusion. Comprehensive car-
Children tolerate large volumes of fluid replacement— diopulmonary monitoring is essential. Children in car-
the full circulating blood volume of 80 mL/kg could diogenic shock must be admitted to a pediatric inten-
potentially be given safely with appropriate monitoring sive care unit.
and reassessment. Typically, in hypovolemic shock, no
more than 50 mL/kg is needed. Packed red blood cell
transfusion is indicated in trauma patients not respond-
Observation & Further Management
ing to two boluses of crystalloid solution. Pressors are Reassess perfusion after each fluid bolus to determine
not required in simple hypovolemic states. additional fluid needs. Serial central venous pressure

Tibial tuberosity

Anterior border

Figure 11–7. IO cannulation tech-

nique. (Reproduced, with permission,
90° to from Textbook of Pediatric Life Support.
medial surface American Heart Association, 1997.)
 EMERGENCIES & INJURIES / 323

determinations or a chest radiograph may aid clinical estimation formulas and helps minimize dosing errors.
assessments to help determine volume status. Place an Selected emergency drugs used in pediatrics are sum-
indwelling urinary catheter to monitor urine output. marized in Table 11–2.
Caution must be exercised with volume replacement
if intracranial pressure is potentially elevated, as in se-
vere head injury, diabetic ketoacidosis, or meningitis.
Even in such situations, however, normal intravascular APPROACH TO THE SERIOUSLY
volume must be restored, as reflected by adequate pe- ILL CHILD
ripheral perfusion and mean arterial pressure, to achieve
adequate cerebral perfusion pressure. An unstable patient may present with a known diagno-
sis, such as a child known to have asthma in status asth-
maticus and respiratory failure, or a child with known
Summary of Cardiopulmonary congenital heart disease. Often a child presents in car-
Resuscitation diorespiratory failure of unknown cause. The initial ap-
Assess the ABCs in sequential fashion and begin inter- proach is designed to rapidly identify and reverse life-
ventions as soon as a derangement is detected—before threatening conditions. Children with chronic disease
assessing the next system. After each intervention, it is may present with an exacerbation in that system or sec-
essential that each system be reassessed to ensure im- ondary to a new, unrelated problem.
provement and to avoid failing to recognize clinical de-
terioration. Preparation for Emergency Management
Resuscitation occurs simultaneously at two levels: rapid
Chameides L et al (eds): Textbook of Pediatric Advanced Life Sup- cardiopulmonary assessment, with indicated stabilizing
port. American Heart Association/American Academy of Pe-
diatrics, 2002.
measures, while venous access (“lifelines”) are gained
Textbook of Advanced Pediatric Life Support, 4th ed. APLS Joint
and cardiopulmonary monitoring initiated. The tech-
Task Force: American College of Emergency Physicians/ nique of accomplishing these concurrent goals is out-
American Academy of Pediatrics, 2003. lined as follows:
http://www.aap.org/apls/aplsmain.htm A. If advance notice of the patient’s arrival has been
received, prepare a resuscitation room and summon ap-
propriate personnel as needed, such as a neurosurgeon
for an unresponsive child after severe head injury or a
EMERGENCY PEDIATRIC DRUGS radiology technician for imaging studies.
B. Assign team responsibilities, including a team
Though careful attention to airway and breathing re-
leader plus others designated to manage the airway, per-
mains the mainstay of pediatric resuscitation, medica-
form chest compressions, achieve access, draw blood for
tions are often needed. Rapid delivery to the central cir-
laboratory studies, place monitors, gather additional
culation, which can be via peripheral IV catheter, is
historical data, and provide family support.
essential. Infuse medications close to the catheter’s hub
C. Age-appropriate equipment should be made
and flush in with saline to achieve the most rapid sys-
ready, including a cardiorespiratory monitor, pulse
temic effects. If no IV or IO access is achievable, some
oximeter, and appropriate blood pressure cuff. Age- and
drugs may be given by endotracheal tube (Table 11–1).
weight-appropriate laryngoscope blades, endotracheal
The use of length-based emergency measuring tapes
tubes, a naso- or orogastric tube, and an indwelling uri-
that contain preprinted drug dosages, equipment sizes,
nary catheter should be assembled for rapid access. Use
and IV fluid amounts (Broselow tapes) or preprinted
a length-based emergency tape if available. See Table
resuscitation drug charts is much more accurate than
11–3 for sizes.

Reception & Assessment

Table 11–1. Emergency drugs that can be given When the patient arrives, the team leader begins a rapid
by endotracheal tube. assessment as team members perform their preassigned
tasks. If the patient is received from prehospital care
providers, careful attention must be paid to their re-
Lidocaine port, because they have information that they alone
Epinephrine have observed. Interventions and medications should
Atropine be ordered only by the team leader to avoid confusion,
Naloxone and the leader should refrain from personally perform-
324 / CHAPTER 11

Table 11–2. Emergency pediatric drugs.

Drug Indications Dosage and Route Comment

Atropine 1. Bradycardia, especially car- 0.01–0.02 mg/kg (minimum, Atropine may be useful in hemodynami-
diac in origin 0.1 mg; maximum, cally significant primary cardiac-based
2. Vagally mediated bradycardia, 2 mg) IV, IO, ET. May bradycardias. Because of paradoxic
eg, during laryngoscopy and repeat every 5 min. bradycardia sometimes seen in infants,
intubation a minimum dose of 0.1 mg is recom-
3. Anticholinesterase poisoning mended by the American Heart Associ-
ation. Epinephrine is the first-line drug
in pediatrics for bradycardia caused by
hypoxia or ischemia.
Bicarbonate 1. Documented metabolic 1 meq/kg IV or IO; by arterial Infuse slowly. Sodium bicarbonate will
acidosis blood gas: 0.3 × kg × base be effective only if the patient is ade-
2. Hyperkalemia deficit. May repeat every quately oxygenated, ventilated, and per-
5 min. fused. Some adverse side effects.
Calcium 1. Documented hypocalcemia 10–30 mg/kg slowly IV, Calcium is no longer indicated for asys-
chloride 10% 2. Calcium channel blocker preferably centrally, or IO tole. Potent tissue necrosis results if in-
overdose with caution. filtration occurs. Use with caution.
3. Hyperkalemia, hypermag-
nesemia
Epinephrine 1. Bradycardia, especially Bradycardia and first dose in Epinephrine is the single most impor-
hypoxic–ischemic arrests: 0.01 mg/kg of tant drug in pediatric resuscitation. Evi-
2. Hypotension (by infusion) 1:10,000 solution IV or IO. dence from animal studies and small
3. Asystole Second and subsequent series of human subjects indicates that
4. Fine ventricular fibrillation doses in arrests: 0.1–0.2 the present recommended dose may
refractory to initial defibrilla- mg/kg of 1:1000 solution be insufficient, and some clinicians use
tion IV or IO. Repeat every 3–5 doses of 0.1–0.3 mg/kg IV. A random-
5. Pulseless electrical activity min. ized controlled trial has not been done.
6. Anaphylaxis ET: 10x intended IV dose
SC: 0.01 mg/kg of 1:1000
solution (= 0.01 mL/kg)
(anaphylactic shock). Max-
imum dose: 0.3–0.5 mL.
Constant infusion by IV drip:
0.1–1 µg/kg/min.
Glucose 1. Hypoglycemia 0.5–1 g/kg IV or, IO. May repeat Neonates: 1 cc/kg D10W. Older children:
2. Altered mental status (em- as necessary. 2–4 cc/kg D25W, 6–10 cc/kg D10W.
pirical)
3. With insulin, for hyperkalemia
Naloxone 1. Opioid overdose 0.1 mg/kg IV, IO, or ET; maxi- Side effects are few. A dose of 2 mg
2. Altered mental status (em- mum dose, 2 mg. May repeat may be given in young children. Repeat as
pirical) as necessary. necessary, or give as constant infusion in
opioid overdoses.
ET = endotracheally, IO = intraosseously, IV = intravenously, SC = subcutaneously.
 EMERGENCIES & INJURIES / 325

Table 11–3. Equipment sizes and estimated weight by age.

Endotracheal
Age Weight Tube Size Laryngoscope Chest Tube Foley
(years) (kg) (mm)a Blade (Size) (Fr) (Fr)
Premature 1–2.5 2.5 uncuffed 0 8 5
Term newborn 3 3.0 0–1 10 8
1 10 3.5–4.0 1 18 8
2 12 4.5 1 18 10
3 14 4.5 1 20 10
4 16 5.0 2 22 10
5 18 5.0–5.5 2 24 10
6 20 5.5 2 26 12
7 22 5.5–6.0 2 26 12
8 24 6.0 cuffed 2 28 14
10 32 6.0–6.5 cuffed 2–3 30 14
Adolescent 50 7.0 cuffed 3 36 14
Adult 70 8.0 cuffed 3 40 14
a
Internal diameter.

ing procedures, which may distract him or her from op- involving terrorism, gang violence, or threats to
timal direction of the resuscitation. A complete timed staff or family.
record should be kept of events, including medications,
interventions, and response to intervention. B. AS APPROPRIATE
A. ALL CASES 1. Immobilize neck.
2. Have chest radiograph taken for line and tube
In addition to cardiac compressions and ventilation, en-
placement.
sure that the following are instituted:
3. Insert central venous pressure and arterial line.
1. 100% high-flow oxygen.
2. Monitoring, including cardiorespiratory, pulse Patterson M: Resuscitation update for the pediatrician. Pediatr
oximetry, and end-tidal CO2 if the patient is intu- Clin North Am 1999;46:1285 [PMID: 10629685].
bated.
3. IV (peripheral, IO, or central) access. Two lines
preferred.
4. Blood drawn and sent. Bedside blood glucose de-
APPROACH TO THE PEDIATRIC
termination is essential. TRAUMA PATIENT
5. Full vital signs obtained. Injuries, including motor vehicle crashes, falls, burns,
6. Clothes removed. and immersions, account for the greatest number of
7. Foley catheter and naso- or orogastric tube in- deaths among children older than age 1 year. All
serted. providers of pediatric care must be cognizant of this
8. Complete history. sobering statistic, become involved, and work with in-
jury prevention specialists, prehospital providers, and
9. Notify needed consultants. emergency, critical care, and rehabilitation physicians
10. Family support. and nurses to reduce this terrible loss.
11. Consider law enforcement or security activation A team approach to the severely injured child, using
and emergency unit lockdown for cases possibly assigned roles as outlined in the preceding section, will
326 / CHAPTER 11

optimize outcomes. A calm atmosphere in the receiving PRIMARY SURVEY

area will contribute to thoughtful care. Conscious chil-
dren are terribly frightened by serious injury; constant The primary survey is designed to identify rapidly and
reassurance can help alleviate anxiety. Analgesia and se- treat immediately all physiologic derangements result-
dation can and should be given to stable patients. It is ing from trauma. It is the resuscitation phase. Priorities
unconscionable in the modern era to let children suffer are still airway, breathing, and circulation, but with im-
pain needlessly. Treat pain expeditiously with oral or portant further considerations in the trauma setting:
parenteral narcotics with appropriate monitoring. Par- Airway, with cervical spine control
ents are often anxious, angry, or guilty and require on-
going support from the services of staff, social workers Breathing
or child life workers (therapists knowledgeable about Circulation, with hemorrhage control
child development). To provide optimal multidiscipli- Disability (neurologic deficit)
nary care, regional pediatric trauma centers provide Exposure (maintain a warm Environment, undress
dedicated teams of pediatric specialists in emergency the patient completely, and Examine)
pediatrics, trauma surgery, orthopedics, neurosurgery,
and critical care. Because most children with severe in- Evaluation and treatment of the ABCs are as dis-
juries are not seen in these centers, however, primary cussed earlier in this chapter. Modifications in the
care providers must be able to provide initial assessment trauma setting are added in the sections that follow.
and stabilization of the child with life-threatening in-
juries before transport to a verified pediatric trauma
center.
Airway
Failure to manage the airway appropriately is the most
common cause of preventable morbidity and death.
Mechanism of Injury Administer 100% high-flow oxygen to all patients.
During assessment and management of the airway, pro-
Document the time of occurrence, the type of energy
vide cervical spine protection, initially by manual in-
transfer to the child (eg, hit by a car, rapid decelera-
line immobilization, not traction. A hard cervical spine
tion), secondary impacts if the child was thrown by the
collar is then applied, and the head and body are se-
initial impact, appearance of the child at the scene, in-
cured to a backboard, surrounded by a lightweight
terventions performed, and clinical condition during
means of cushioning (eg, rolled blankets) to further im-
transport. The report of emergency service personnel is
mobilize the head and body and allow log-rolling of the
invaluable. All information of this type must be for-
child in case of vomiting. Assess the airway for patency
warded with the patient to the referral facility if sec-
as before. Head positioning must avoid flexion or ex-
ondary transport occurs.
tension of the neck. Use jaw thrust rather than chin lift
Trauma in children is predominantly blunt, al-
during intubation. Suction the mouth and pharynx free
though penetrating trauma occurs in 10% of cases.
of blood, foreign material, or secretions, and remove
Head and abdominal injuries are particularly common
loose teeth. Insert an oropharyngeal airway if upper air-
and important in the pediatric age group.
way noises are heard or obstruction from posterior pro-
lapse of the tongue occurs. A child with a depressed
level of consciousness or a need for prolonged ventila-
Initial Assessment & Management tion, hyperventilation, or operative intervention re-
The vast majority of children who reach a hospital alive quires endotracheal intubation after bag–mask preoxy-
survive to discharge. Most deaths from trauma in chil- genation. Orotracheal intubation is the route of choice
dren are due to head injuries. Therefore, cerebral resus- and is possible without cervical spine manipulation.
citation must be the foremost consideration when treat- Nasotracheal intubation may be possible in children
ing children with serious injuries. The ultimate measure age 12 years or older who have spontaneous respira-
of outcome is the child’s eventual level of functioning. tions—if not contraindicated by midfacial injury with
Strict attention to the ABCs ensures optimal oxygena- the possibility of cribriform plate disruption. Rarely, if
tion, ventilation, and perfusion, and ultimately, cere- tracheal intubation cannot be accomplished—particu-
bral perfusion. larly in the setting of massive midfacial trauma—
The primary and secondary survey is a method for cricothyroidotomy may be necessary. Needle cricothy-
evaluating and treating injured patients in a systematic roidotomy using a large-bore catheter through the
way that provides a rapid assessment and stabilization cricothyroid membrane is the procedure of choice in
phase, followed by a head-to-toe examination and de- patients younger than age 12 years. Operative revision
finitive care phase. will be needed for formal controlled tracheostomy.
 EMERGENCIES & INJURIES / 327

Breathing hepatomegaly, or muffled heart sounds are present. Ul-

trasound may be diagnostic if readily available. Diag-
Most ventilatory problems are resolved adequately by nose and treat with pericardiocentesis and rapid volume
the airway maneuvers described earlier in this chapter infusion.
and by positive-pressure ventilation. Breathing assess- Treat signs of poor perfusion vigorously: A tachy-
ment is as described previously: Assess for an adequate cardic child with a capillary refill time of 3 seconds, or
rate and for symmetrical chest rise, increased work of other abnormalities in the perfusion examination, is in
breathing, color, tracheal deviation, crepitus, flail seg- shock and is sustaining vital organ insults. Remember
ments, deformity, or penetrating wounds. Sources of that hypotension is a late finding. Volume replacement
traumatic pulmonary compromise include pneumotho- is initially accomplished by rapid infusion of normal
rax, hemothorax, pulmonary contusion, flail chest, and saline or lactated Ringer solution at 20 mL/kg of body
central nervous system (CNS) depression. Asymmetri- weight, followed by 10 mL/kg of packed red blood cells
cal breath sounds, particularly if tracheal deviation, if perfusion does not normalize after two crystalloid
cyanosis, or bradycardia is present, suggest pneumotho- bolus infusions.
rax, probably under tension. To evacuate the pneu- Reassessment should be done rapidly following each
mothorax, insert a large-bore catheter-over-needle as- bolus. If clinical signs of perfusion have not normalized,
sembly attached to a syringe over the fourth rib in the repeat the bolus. Lack of response or later signs of hy-
anterior axillary line into the pleural cavity and with- povolemia suggest the need for blood transfusion and
draw air. If a pneumothorax or hemothorax is present, possible surgical exploration. For every milliliter of ex-
place a chest tube to water seal. Insertion should be ternal blood loss 3 mL of crystalloid solution should be
over the rib to avoid the neurovascular bundle that runs administered.
below the rib margin. Open pneumothoraces can be A common problem is the brain-injured child who
treated temporarily by taping petrolatum-impregnated is at risk for intracranial hypertension and who is also
gauze on three sides over the wound, creating a flap hypovolemic. In such cases, circulating volume must be
valve. After airway and breathing interventions have restored to ensure adequate cerebral perfusion; there-
begun, hemodynamic status may be addressed. fore, fluid replacement is required until perfusion nor-
malizes. Thereafter provide maintenance fluids with
careful serial reassessments. Do not restrict fluids for
Circulation children with head injuries.
Ongoing hemorrhage, external or internal, gives pedi-
atric trauma some of its anxiety-provoking character. Disability–Neurologic Deficit
During the assessment of circulation, IV access should
be achieved, preferably at two sites. If peripheral access Assess pupillary size and reaction to light and the level
is not readily available, a central line, cutdown, or IO of consciousness. The level of consciousness can be re-
line is established. A cardiorespiratory monitor and producibly characterized by the AVPU system (Table
oximeter should be applied early in the resuscitation. 11–4). Pediatric Glasgow Coma Scale assessments
Peripheral perfusion and blood pressure should be should be done as part of the secondary survey (Table
recorded at frequent intervals. Determine hematocrit, 11–5; see Secondary Survey section).
blood type and cross-match, and serum amylase. Con-
sider blood and urine toxicologic screening. Exposure and Environment
External hemorrhage can be controlled by direct
pressure. To avoid damage to adjoining nerves and ves- Significant injuries can be missed unless the child is
sels, avoid placing hemostats on vessels, except in the completely undressed and examined fully, front and
scalp. back. Cutting away clothing as necessary can minimize
Determination of the site of internal hemorrhage movement. Because of their high ratio of surface area to
can be challenging. Sites include the chest, abdomen,
retroperitoneum, pelvis, and thighs. Bleeding into the
intracranial vault rarely causes shock in children except Table 11–4. AVPU system for evaluation of level
in infants. An experienced pediatric trauma surgeon of consciousness.
and radiologic studies—principally computed tomogra-
phy (CT) and ultrasound—will localize the site of in-
ternal bleeding. A Alert
Suspect cardiac tamponade after penetrating or V Responsive to Voice
blunt injuries to the chest if shock, pulseless electrical P Responsive to Pain
U Unresponsive
activity, narrowed pulse pressure, distended neck veins,
328 / CHAPTER 11

Table 11–5. Glasgow Coma Scale.a SECONDARY SURVEY

After the resuscitation phase, a head-to-toe examination
Eye opening response should be performed to reveal all injuries and deter-
Spontaneous 4 mine priorities for definitive care.
To speech 3
To pain 2
None 1 Skin
Verbal response Search for lacerations, hematomas, swelling, and abra-
Oriented 5 sions. Remove foreign material, and cleanse as neces-
Confused conversation 4 sary. Cutaneous signs may indicate underlying pathol-
Inappropriate words 3
ogy (eg, a flank hematoma overlying a renal contusion)
Incomprehensible sounds 2
None 1
although surface signs may be absent even with signifi-
Best upper limb motor response cant internal injury. Make certain the child’s tetanus
Obeys 6 immunization status is current. Consider tetanus im-
Localizes 5 mune globulin for unimmunized children.
Withdraws 4
Flexion in response to pain 3 Head
Extension in response to pain 2
None 1 Check for hemotympanum and for clear or bloody cer-
a
ebrospinal fluid (CSF) leak from the nares. Battle sign
The appropriate number from each section is added to total be- (hematoma over the mastoid) and raccoon eyes are late
tween 3 and 15. A score less than 8 usually indicates central ner-
vous system depression requiring positive pressure ventilation.
signs of basilar skull fracture. Explore wounds, exclud-
ing foreign bodies and defects in galea or skull. CT scan
of the head is an integral part of evaluation for altered
level of consciousness, seizure after trauma, or focal
body mass, infants and children cool rapidly. Because neurologic findings (see Head Injury section). Pneumo-
hypothermia compromises outcome except with iso- coccal vaccine is indicated for basilar skull fractures.
lated head injuries, it is necessary to continuously mon-
itor the body temperature and to use warming tech- Spine
niques vigorously as necessary. Hyperthermia, Cervical spine injury must be excluded in all children.
conversely, adversely affects outcomes in children with This can be done without radiographs in children with
acute brain injuries, so maintain normal body tempera- normal neurologic findings on examination who are
tures. able to deny midline neck pain or midline tenderness
on palpation of the neck and who have no other painful
Monitoring injuries that might obscure the pain of a cervical spine
injury. Voluntary movement of the extremities must be
Cardiopulmonary monitors with pulse oximetry and observed. If radiographs are indicated, a cross-table lat-
end-tidal CO2 monitors should be put in place imme- eral neck view is obtained initially, followed by
diately. At the completion of the primary phase, addi- anteroposterior and odontoid views. “Normal” studies
tional “tubes” should be placed. do not exclude significant injury, which can be bony or
A. NASOGASTRIC OR OROGASTRIC TUBE ligamentous, or involve the spinal cord itself. There-
fore, an obtunded child should be maintained in cervi-
Children’s stomachs should be assumed to be full, and cal spine immobilization until the child has awakened
gastric distention from positive-pressure ventilation in- and an appropriate neurologic examination can be per-
creases the chance of vomiting and aspiration. formed. The entire thoracolumbar spine must be pal-
pated and areas of pain or tenderness examined by radi-
B. URINARY CATHETER ography.
An indwelling urinary bladder catheter should be
placed to monitor urine output. Contraindications are Chest
based on the risk of urethral transection; signs include
blood at the meatus or in the scrotum or a displaced Pneumothoraces are detected and decompressed during
prostate detected on rectal examination. Urine should the primary survey. Hemothoraces can occur with rib
be tested for blood. Urine output should exceed fractures or with injury to intercostal vessels, large pul-
1 mL/kg/h. monary vessels, or lung parenchyma. Tracheobronchial
 EMERGENCIES & INJURIES / 329

disruption is suggested by large continued air leak de- injury. A full sensorimotor examination should be per-
spite chest tube decompression. Pulmonary contusions formed. Deficits require immediate neurosurgical consul-
may require ventilatory support. Myocardial contusions tation. Extensor or flexor posturing represents intracranial
and aortic injuries are unusual in children. hypertension, not seizure activity, until proved otherwise,
and should be treated with mild hyperventilation (PaCO2
Abdomen in the mid-30s mm Hg), and adequate but not excessive
volume resuscitation. If accompanied by a fixed and unre-
Blunt abdominal injury is common in multisystem in- active pupil a herniation syndrome is present, and hyper-
juries. Significant injury can exist without cutaneous ventilation should be to a PaCO2 in the mid-20s. Diuret-
signs or instability of vital signs. Tenderness, guarding, ics, usually mannitol, should be given if perfusion is
distention, lack of bowel sounds, or poor perfusion normal and signs of herniation are present. Normal pe-
mandates immediate evaluation by a pediatric trauma ripheral perfusion must be ensured to optimize cerebral
surgeon. Injury to solid viscera frequently can be man- perfusion. Level of consciousness by the AVPU system
aged nonoperatively in stable patients; however, in the (see Table 11–4) or Glasgow Coma Scale (see Table
presence of intestinal perforation or hypotension, oper- 11–5) should be assessed serially. Seizure activity warrants
ative treatment is indicated. Serial examinations, ultra- exclusion of significant intracranial injury. In the trauma
sound, and CT scan—or, in unstable patients, diagnos- setting, seizures are frequently treated with fosphenytoin.
tic peritoneal lavage—provide diagnostic help. Elevated Acute spinal cord injury may benefit from high-dose
liver function tests have good specificity but only fair methylprednisolone therapy. Corticosteroids are not indi-
sensitivity for hepatic injury. Serum amylase will rise cated for head trauma.
progressively with pancreatic injury, which may not be
easily visualized by initial CT.
American College of Surgeons, Committee on Trauma: Textbook
of Advanced Trauma Life Support. American College of Sur-
Pelvis geons, 1997.
http://www.facs.org/trauma/atls/information.html
Pelvic fractures are classically manifested by pain, crepi-
Junkins E et al: A prospective evaluation of the clinical presentation
tus, and abnormal motion. Pelvic fracture is a relative of pediatric pelvic fractures. J Trauma 2001;51(1):64
contraindication to urethral catheter insertion. Perform a [PMID: 11468469].
rectal examination, noting tone, tenderness, and prostate Schutzman SA, Greenes DS: Pediatric minor head trauma. Ann
position in boys. Stool should be tested for blood. Emerg Med 2001;37:65 [PMID: 11145776].
Viccellio P et al: A prospective multicenter study of cervical spine
Genitourinary System injury in children. Pediatrics 2001;108(2):E20 [PMID:
11483830].
If urethral transection is suspected (see earlier discus-
sion), perform a urethrogram before catheter place-
ment. Diagnostic imaging of the child with hematuria
includes CT scan, or occasionally IV urograms. Man- HEAD INJURY
agement of kidney injury is largely nonoperative except
for renal pedicle injuries. Closed head injuries range in severity from minor
asymptomatic trauma without sequelae to intracranial
hemorrhage leading to death. Head injury, including
Extremities the shaken-baby syndrome, is common in cases of child
Long bone fractures are common but rarely life-threaten- abuse. Even following minor closed head injury, neu-
ing. Test for pulses, perfusion, and sensation. Neurovas- ropsychiatric sequelae can occur.
cular compromise requires immediate orthopedic consul-
tation. Delayed diagnosis of fracture sometimes occurs Assessment
when children are comatose; reexamination is necessary
to avoid overlooking previously missed fractures. The considerations discussed earlier in the Approach to
the Pediatric Trauma Patient section apply here as well.
The history should include the time and mechanism of
Central Nervous System injury. How far did the child fall and onto what sur-
Most deaths in children with multisystem trauma are face? Was there loss of consciousness? Does the child
from head injuries, so optimal neurointensive care is im- remember events preceding, during, and following the
portant. Significant injuries include diffuse axonal injury; injury? What have been the child’s levels of conscious-
cerebral edema; subdural, subarachnoid, and epidural ness and activity since the injury? Has there been vom-
hematomas; parenchymal hemorrhages; and spinal cord iting, headache, ataxia, seizures, or visual disturbance?
330 / CHAPTER 11

The physical examination should be complete, keep- These patients require CT scan, a period of observa-
ing in mind the mechanism of injury, and should in- tion, and consideration of neurorehabilitation follow-
clude a detailed neurologic examination. Look for asso- up for posttraumatic brain injury sequelae.
ciated injuries such as mandibular fracture, scalp or
skull injury, or cervical spine injury. CSF leak from the
ears or nose or the two later-appearing signs of perior-
DIFFUSE AXONAL INJURY
bital hematomas (raccoon eyes) and Battle sign, imply Diffuse axonal injury is a potentially severe form of
basilar skull fracture. Children with suspected basilar traumatic brain injury characterized by coma without
skull fractures should receive the pneumococcal vac- focal signs on neurologic examination. There may be
cine. Obtain vital signs and assess the child’s level of no external signs of trauma. The initial CT scan is nor-
consciousness by the AVPU system (see Table 11–4) or mal or may demonstrate only scattered small areas of
Glasgow Coma Scale (see Table 11–5), noting irritabil- cerebral contusion and areas of low density. Prolonged
ity or lethargy; pupillary equality, size, and reaction to disability may follow diffuse axonal injury.
light; funduscopic examination; reflexes; body posture;
and rectal tone. Always consider child abuse—the in-
juries observed should be consistent with the history
ACUTE INTRACRANIAL HYPERTENSION
and the child’s developmental level. Close observation will detect early signs and symptoms
Radiographic studies may be indicated. Plain films of intracranial pressure elevation. Early recognition is
are useful only in cases of penetrating head trauma or essential to avoid disastrous outcomes. In addition to
for assessing depressed skull fractures and ruling out traumatic causes, intracranial pressure elevation with or
foreign bodies. Major morbidity does not follow from without herniation syndromes may be seen in sponta-
skull fracture per se but rather from the associated in- neous intracranial hemorrhage, CNS infection, hy-
tracranial injury. The presence of a skull fracture on drocephalus, ruptured arteriovenous malformation,
plain films is associated with an increased likelihood of metabolic derangement (eg, diabetic ketoacidosis), ven-
finding a serious intracranial injury demonstrated by triculoperitoneal shunt obstruction, or tumor. Symp-
CT scanning. CT scan should be performed in the toms include headache, vision changes, vomiting, gait
child with persistent vomiting or an abnormal or later- difficulties, and a progressively decreasing level of con-
alizing neurologic examination, including an abnormal sciousness. Other signs may include stiff neck, cranial
mental status that does not quickly return to normal. In nerve palsies, and progressive hemiparesis. Cushing
infants, a normal neurologic exam does not exclude sig- triad (bradycardia, hypertension, and irregular respira-
nificant intracranial hemorrhage. In the setting of an tions) is a late and prearrest finding. Papilledema is also
appropriate mechanism, and if scalp findings such as a late finding. Consider CT scan before lumbar punc-
large hematomas are found, consider performing CT. ture if there is concern about intracranial pressure ele-
vation because of the risk of precipitating herniation.
CONCUSSION Lumbar puncture should be deferred if coma or shock
is present.
A concussion injury is defined as a brief loss or alter- Therapy for intracranial pressure elevation must be
ation of consciousness followed by a return to normal. swift and aggressive. Strict attention to normal oxy-
Brain tissue is not damaged, and there are no focal find- genation, moderate ventilation, and adequate perfusion
ings on detailed neurologic examination. There may be is paramount. Controlled rapid sequence intubation
pallor, amnesia, or several episodes of vomiting. Dispo- with appropriate sedation, muscle relaxation, and
sition is based on the clinical course and suitability of agents to reduce the intracranial pressure elevation that
follow-up. The patient may be discharged when neuro- accompanies intubation is followed by mild hyperventi-
logically normal after a period of observation. Parents lation (PaCO2 lowered to 35–38 mm Hg) and avoid-
should closely observe the child at home and return if ance of hypoperfusion and hypoxemia. Mannitol
the child exhibits altered level of consciousness, persis- (0.5 g/kg intravenously), an osmotic diuretic, will re-
tent vomiting, gait disturbances, unequal pupils, duce brain water, as will furosemide (0.1–0.2 mg/kg in-
seizures, or increasing headache, or if the parents have travenously). These measures may acutely lower in-
any concerns. tracranial pressure. Fluid infusion and, ultimately,
pressors should be used to maintain normal arterial
blood pressure and peripheral perfusion, if necessary.
CONTUSION Adjunctive measures include elevating the head of the
A bruise of the brain matter is a contusion. The child’s bed 30 degrees, treating hyperpyrexia and pain, and
level of consciousness decreases, and focal findings if maintaining the head in a midline position. Obtain im-
any correspond to the area of the brain that is injured. mediate neurosurgical evaluation. Further details about
 EMERGENCIES & INJURIES / 331

management of intracranial hypertension (cerebral that appear gray and necrotic, with surrounding ery-
edema) are presented in Chapter 13. thema. If an arc is created with passage of current
through the body, the pattern of the thermal injury will
DISPOSITION FOR CHILDREN WITH depend on the path of the current; therefore, search for
an exit wound and internal injuries. Extensive damage
CLOSED HEAD INJURY to deep tissues may occur. Current traversing the heart
Patients with mild head injury may be discharged with may cause nonperfusing arrhythmias. Neurologic ef-
detailed written instructions—after a period of brief fects of electrical burns can be immediate (eg, confu-
observation—if the examination remains normal and sion, disorientation, peripheral nerve injury), delayed
parental supervision and follow-up are appropriate. (eg, nerve damage in the thrombosed limb after com-
Children with persistent deficits require admission or partment syndrome), or late (eg, impaired concentra-
prolonged observation. If the patient responds to voice tion or memory).
commands and mental status is improving gradually
over a period of several hours, observation may be done EVALUATION OF THE BURNED PATIENT
without further radiographic studies. If the mental sta-
tus deteriorates, however, CT scan and neurosurgical Classification
consultations are indicated. If the CT scan is normal Burns are classified clinically according to the nature of
and the physical findings normalize, these children may the burn and the extent and thickness; associated in-
also be discharged after a period of observation. Pa- juries are ascertained in the initial evaluation.
tients with severe head injury require cerebral resuscita- Superficial (first-degree) burns are easily recognized
tion, evaluation by a neurosurgeon, and admission to and treated. They are painful, dry, red, and hypersensi-
hospital. tive. Sunburn is a common example. Healing occurs
with minimal damage to epidermis. At the other end of
Baker C et al: Evaluation of pediatric cervical spine injuries. Am the spectrum are full-thickness (third-degree) burns af-
J Emerg Med 1999;17(3):230 [PMID: 10337876].
fecting all epidermal and dermal elements, leaving avas-
Hendey GW et al: Spinal cord injury without radiologic abnormal- cular skin. The wound is dry, depressed, leathery in ap-
ity: Results of the National Emergency X-radiography Uti-
lization Study in blunt cervical study. J Trauma 2002;53:1 pearance, and without sensation. Unless skin grafting is
[PMID: 12131380]. provided, the scar will be hard, uneven, and fibrotic.
Holmes JF et al: Identification of children with intra-abdominal in- Partial-thickness (second-degree) burns are further clas-
juries after blunt trauma. Ann Emerg Med 2002;39:500 sified as superficial or deep, depending on appearance
[PMID: 11973557]. and healing time, with each subgroup treated differ-
Ponsford J et al: Impact of early intervention on outcome after mild ently. Superficial partial-thickness burns are red and
traumatic brain injury in children. Pediatrics 2001;108:1297 may blister. Deep partial-thickness burns are white and
[PMID: 11731651]. dry, blanch with pressure, and the involved skin has de-
Simon B et al: Pediatric minor head trauma: Indications for com- creased sensitivity to pain.
puted tomographic scanning revisited. J Trauma 2001;51:
231 [PMID: 11493779].
Management
Burn management depends on the depth and extent of
BURNS thermal injury. Burn extent can be classified as major or
minor. Minor burns are less than 10% of the body sur-
Thermal injury is a major cause of accidental death and face area for superficial and partial-thickness burns, or
disfigurement in children. Pain, morbidity, the associa- less than 2% for full-thickness burns. Partial- or full-
tion with child abuse, and the preventable nature of thickness burns of the hands, feet, face, eyes, ears, and
burns constitute an area of major concern in pediatrics. perineum are considered major.
Common causes include hot water or food, appliances,
flames, grills, vehicle-related burns, and curling irons. A. SUPERFICIAL AND PARTIAL-THICKNESS BURNS
Burns occur commonly in toddlers—in boys more fre- These injuries can generally be treated in the outpatient
quently than in girls. setting. It is mandatory that rapid and effective analgesia
be provided, and redosed as indicated by the child.
Oral codeine may occasionally suffice, but often par-
ELECTRICAL BURNS enteral narcotics are indicated. Superficial burns are
Even brief contact with a high-voltage source will result treated with cool compresses and analgesia. Treatment
in a contact burn. When an infant or toddler bites an of partial-thickness burns with blisters consists of anti-
electric cord, burns to the commissure of the lips occur septic cleansing, topical antimicrobial coverage, and ob-
332 / CHAPTER 11

servation for infection. Blisters appear early in deeper Infant Less Than One Year of Age
partial-thickness burns and, if open, may be debrided.
Alternatively, the blister may be used as a protective Name____________ Age_______ Ward__________
flap after cleaning and dressing. After debridement, the 1st-degree erythema
wound should be cleansed with dilute (1–5%) povi- not to be included.
done–iodine solution, thoroughly washed with normal 2nd-degree 3rd-degree
saline, and covered with topical antibiotic, which does 9 1/2 91/2
not need to be silver sulfadiazine. The wound should be
protected with a bulky dressing and reexamined within
24 hours and serially thereafter. Wounds with a poten-
11/2
tial for causing loss of function or scarring—especially 11/2
wounds of the hand or digits—should be referred
promptly to a burn surgeon. Outpatient analgesia 2 2
2 2
should be provided on discharge. 13 13

11/2 11/2 1 1/2 11/2

B. FULL-THICKNESS AND DEEP OR EXTENSIVE PARTIAL-
THICKNESS BURNS 11/4 11/4 11/4 2 2 11/4
Major burns place particular importance on the ABCs 23/4
1
23/4
of trauma management. Early establishment of an arti- 23/4 23/4
ficial airway is critical with oral or nasal burns because
of their association with inhalation injuries and critical
airway narrowing. 21/2 21/2
21/2 21/2
The trauma resuscitation protocol outlined previ-
ously, in the Primary Survey section, should be fol-
lowed. There may be inhalation injury from carbon 13/4 13/4
13/4 13 / 4
monoxide, cyanide, or other toxic products if flames
were present. A nasogastric tube and bladder catheter
Variations From Adults Distribution in
should be placed. The secondary survey should ascer- Infants and Children (in Percent).
tain whether any other injuries are present, including
those suggestive of abuse. New- 1 5 10
Fluid administration is based on several principles. born Year Years Years
Capillary permeability is markedly increased. Fluid
Head 19 17 13 11
needs are based on examination findings, percentage of Both thighs 11 13 16 17
body surface area burned, depth, and age. Maintaining Both lower legs 10 10 11 12
normal intravascular pressure and replacing fluid losses Neck 2
Anterior trunk 13
are essential. Figure 11–8 shows percentages of body Posterior trunk 13
surface area by body part in infants and children. The Both upper arms 8 These percentages
Parkland formula for fluid therapy is 4 mL/kg/% body Both lower arms 6
remain constant at
Both hands 5
surface area burned for the first 24 hours, with half in Both buttocks 6 all ages
the first 8 hours, in addition to maintenance rates. Both feet 7
Acutely, however, fluid resuscitation should be based Genitalia 1
on clinical assessment of volume status as described ear- 100
lier.
Indications for admission include major burns as Figure 11–8. Lund and Browder modification of
previously defined; uncertainty of follow-up; suspicion Berkow scale for estimating extent of burns. (The table
of abuse; presence of upper airway injury; explosion, in- under the illustration is after Berkow.)
halation, electrical, or chemical burns; burns associated
with fractures; or the need for parenteral pain control.
Children with chronic metabolic or connective tissue tings? Consider whether the child needs relief from
diseases and infants deserve hospitalization. anxiety (sedation) or relief from pain (analgesia). Many
agents also have amnestic properties. Parenteral agents
can be effective and safe and produce few side effects if
Sedation and Analgesia used judiciously.
What more important mission can providers have than Conditions such as fracture reduction, laceration re-
relieving pain and anxiety in children in acute care set- pair, burn care, sexual assault examinations, lumbar
 EMERGENCIES & INJURIES / 333

puncture, and diagnostic procedures such as CT and and short half-life. Administration may be oral, rectal,
magnetic resonance imaging may all be performed intranasal, intramuscular, or IV. When given slowly in-
more effectively and with less trauma to the child if ef- tranasally, the drug’s kinetics are nearly the same as
fective sedation or analgesia is used. The clinician when given intravenously. Many children report a
should decide whether procedures will require either se- burning sensation with intranasal administration. Oral
dation or analgesia alone, or both, and then choose or rectal administration results in relatively delayed
agents accordingly. onset, and titration is difficult. Intramuscular injections
Safe and effective sedation requires thorough knowl- can be combined with opioid analgesics if systemic
edge of the selected agent and its side effects; suitable analgesia is desired. IV administration allows optimal
monitoring devices; resuscitative medications, equip- ability to titrate dosing to the desired sedation level.
ment, and personnel; and appropriate informed con- Complicated or prolonged procedures are best facili-
sent from the parents. This process is now called proce- tated by IV placement to facilitate redosing, which also
dural sedation and analgesia (PSA) and should proceed provides IV access if resuscitation becomes necessary.
as follows: Potential side effects of midazolam include cardiorespi-
ratory depression.
1. Choose the right medication or combination of
medications for the procedure. 2. Barbiturates—This class of agents (eg, pentobarbi-
2. Discuss risks and benefits of the proposed PSA and tal [Nembutal]) has the advantage of minimizing move-
obtain verbal informed consent from the parents. ment during procedures, which makes them advanta-
3. Ensure appropriate NPO (nothing-by-mouth) geous for diagnostic studies such as CT or magnetic
status for 4–6 hours. For certain emergency pro- resonance imaging. Rectal administration of thiopental
cedures, suboptimal NPO status may be allowed, is safe and effective. Onset of action with IV adminis-
with attendant risks identified. tration is rapid. Potential side effects, although uncom-
mon, include respiratory and cardiac depression and
4. Establish vascular access as required. laryngospasm.
5. Ensure that resuscitative equipment and person-
nel are readily available. 3. Narcotics—These agents (eg, morphine, meperi-
6. Attach the cardiorespiratory monitor and pulse dine, and fentanyl) have powerful analgesic and seda-
oximeter, as indicated. tive effects. They can be combined with anxiolytics
7. Give the agent selected, with continuous moni- such as benzodiazepines. Desired and adverse effects,
toring for side effects. A dedicated observer, usu- such as respiratory depression, are potentiated when
ally a nurse, should monitor the patient at all benzodiazepines and narcotics or barbiturates are given
times. Respiratory effort, perfusion, and mental together. Therefore, sedative doses should be reduced
status should be assessed and documented serially. when sedatives and analgesics are given together.
8. Titrate the medication to achieve the desired se- 4. Ketamine—Increasingly and now commonly used
dation level. The ideal level is that of “conscious” in emergency departments, this agent has the advantage
or “light” sedation—that is, the patient’s senso- of being a sympathomimetic, that is, increasing heart
rium is slightly dulled, but eyes are generally open rate and blood pressure. It is a potent analgesic and
and airway reflexes are preserved. anxiolytic and has amnestic properties. Side effects in-
9. Continue monitoring the patient after finishing clude salivation (therefore, it is usually given with gly-
the procedure. If a painful stimulus has been copyrrolate as an antisalivation agent), laryngospasm
eliminated (eg, fracture reduction) mental status (occasionally), nystagmus, emergence reactions, and
can decrease. vomiting. With comprehensive knowledge of this med-
10. Criteria for discharge include the child’s ability to ication, its use can be a significant advantage to chil-
sit unassisted, to take oral fluids, and to answer dren.
verbal commands. A PSA discharge handout
should be given, with precautions for close obser- American Academy of Pediatrics, Committee on Drugs: Guidelines
vation and avoidance of potentially dangerous ac- for monitoring and management of pediatric patients during
tivities. and after sedation for diagnostic and therapeutic procedures:
An addendum. Pediatrics 2002;110:836 [PMID: 12359805].
The following are some commonly used sedatives Berde CB, Sethna NF: Analgesics for the treatment of pain in chil-
and analgesics: dren. N Engl J Med 2002;347:1094 [PMID: 12362012].
Singer AJ et al: Parents and practitioners are poor judges of young
1. Midazolam (Versed)—This agent has particular children’s pain severity. Acad Emerg Med 2002;9:609
usefulness in pediatrics due to its safety, rapid onset, [PMID: 12045074].
334 / CHAPTER 11

DISORDERS DUE TO HIGH 4. Place monitors, check rectal temperatures contin-

ENVIRONMENTAL TEMPERATURE uously, and place a Foley catheter and nasogastric
tube.
Disorders due to heat range from mild cramps to life- 5. Obtain laboratory tests: complete blood count;
threatening heat stroke. Heat cramps are characterized electrolytes; glucose; creatinine; prothrombin time
by brief, severe cramping (not rigidity) of skeletal or ab- and partial thromboplastin time; creatine kinase;
dominal muscles following exertion. Core body temper- liver function tests; arterial blood gases; urinalysis;
ature is normal or only slightly elevated. Heat cramps and serum calcium, magnesium, and phosphate.
may be associated with a relative sodium deficiency.
Mild cases can be treated with oral salt-containing solu- 6. Admit to pediatric intensive care unit.
tions; more severe cases require IV infusion of normal
saline solution. Heat exhaustion is manifested by consti- Malignant Hyperthermia
tutional symptoms after exposure to heat and humidity. Malignant hyperthermia is a rare but life-threatening
Patients continue to sweat, and core temperature is nor- syndrome characterized by a hypermetabolic state in-
mal or only slightly increased. Patients with heat exhaus- cluding high fever, diaphoresis, malaise, rhabdomyoly-
tion have varying proportions of salt and water deple- sis, disseminated intravascular coagulation, hyper-
tion. Presenting symptoms and signs include weakness, reflexia, and psychosis. It is most often associated with
fatigue, headache, disorientation, pallor, thirst, nausea anesthetic agents, but can be seen in the outpatient set-
and vomiting, and occasionally muscle cramps. Shock ting in the neuroleptic-malignant syndrome. Drugs
may be present. No major CNS dysfunction should be such as atropine, lidocaine, meperidine, nonsteroidal
present. Treat with IV fluids, modified by measured anti-inflammatory agents, tricyclic antidepressants, co-
electrolyte levels. Both heat cramps and heat exhaustion caine, and antipsychotics can induce a central hyper-
can be avoided with acclimatization and liberal water thermic syndrome. Treatment includes cooling, rectal
and salt intake during exercise. acetaminophen, seizure treatment with a benzodi-
Heat stroke represents failure of thermoregulation azepine, and, in the case of malignant hyperthermia
and is life-threatening. The diagnosis is based on a rec- caused by neuromuscular blockers, dantrolene sodium.
tal temperature of over 40°C with associated neurologic
signs in a patient with an exposure history. Lack of
sweating is not a necessary criterion. Symptoms are
similar to those of heat exhaustion, but CNS dysfunc- HYPOTHERMIA
tion is more prominent. Patients with heat stroke are Seriously ill children should have core temperature
often incoherent and combative. In more severe cases, quickly determined. Hypothermia in children, defined
vomiting, shivering, coma, seizures, nuchal rigidity, and as core body temperature less than 35°C, is frequently
posturing may be present. Patients can have high, low, associated with cold water submersion accidents. Many
or normal cardiac output. Cellular hypoxia, enzyme other disorders cause incidental hypothermia, including
dysfunction, and disrupted cell membranes lead to sepsis, metabolic derangements, ingestions, CNS disor-
global end-organ derangements: rhabdomyolysis, myo- ders, and endocrinopathies. Neonates, trauma victims,
cardial necrosis, electrolyte abnormalities, acute tubular intoxicated patients, and the chronically disabled are
necrosis and renal failure, hepatic degeneration, adult particularly at risk. Mortality rates are high and are re-
respiratory distress syndrome, and disseminated in- lated to the underlying disorder. Conversely, mild ther-
travascular coagulation. Consider sepsis, malignant hy- apeutic hypothermia following hypoxic–ischemic CNS
perthermia, and neuroleptic malignant syndrome in the insult and isolated traumatic brain injury may be a rec-
differential diagnosis. ommendation in the near future.
As core temperature falls, a variety of mechanisms
begin to conserve and produce heat. Peripheral vaso-
Heat Stroke Management constriction allows optimal maintenance of core tem-
1. Immediately cool the patient’s body with cool perature. Heat production can be increased by a hypo-
water mist, ice, fans, or other cooling device. thalamic-mediated increase in muscle tone and
metabolism. When shivering begins, heat production
2. If the patient is unresponsive, manage the airway, increases to two to four times basal levels.
giving 100% oxygen.
3. Administer IV fluids: isotonic crystalloid for hy- Clinical Findings
potension, 5% dextrose normal saline for mainte-
nance. Consider central venous pressure determi- Clinical manifestations of hypothermia depend on the
nation. severity of body temperature depression. Severe cases (≤
 EMERGENCIES & INJURIES / 335

28°C) mimic death: Patients are pale or cyanotic, pupils Table 11–6. Management of hypothermia.
may be fixed and dilated, muscles are rigid, and there
may be no palpable pulses. Heart rates as low as 4–6/min General measures
may provide adequate perfusion, because of the lowered Administer warmed and humidified 100% oxygen.
metabolic needs in severe hypothermia. If these findings Monitor core temperature, heart and respiratory rates,
are a result of primary hypothermia and not postmortem and blood pressure continuously.
changes, the fact of death cannot be ascertained until the Consider central venous pressure determination for severe
patient has been rewarmed and remains unresponsive to hypothermia.
resuscitative efforts. Children with a core temperature as Laboratory studies
low as 19°C have survived neurologically intact. Complete blood count and platelets
Serum electrolytes, glucose, creatinine, amylase
Prothrombin time, partial thromboplastin time
Treatment Arterial blood gases
A. GENERAL SUPPORTIVE MEASURES Consider toxicology screen
Treatment
Management of hypothermia is complex but largely Correct hypoxemia, hypercapnia, pH < 7.2, clotting ab-
supportive. Core body temperature must be docu- normalities, and glucose and electrolyte disturbances.
mented by continuously monitoring with a low-reading Start rewarming techniques: passive, active (core and
indwelling rectal thermometer. Patients must be han- external), depending on degree of hypothermia.
dled gently, because the hypothermic myocardium is Replace intravascular volume with warmed intravenous
exquisitely sensitive and prone to arrhythmias. Ventric- crystalloid infusion at 42°C.
ular fibrillation may occur spontaneously or as a result Treat asystole and ventricular fibrillation per PALS proto-
of minor handling or invasive procedures. If asystole or cols. Cardiac massage should be continued at least
ventricular fibrillation is present on the cardiac moni- until core temperature reaches 30°C, when defibrilla-
tor, perform chest compressions and use standard pedi- tion is more likely to be effective.
atric advanced life support techniques and medications.
Spontaneous reversion to sinus rhythm at 28–30°C
may occur as rewarming proceeds.
B. REWARMING are ubiquitous and include lakes and streams; swim-
ming pools; bathtubs; and even toilets, buckets, and
1. Passive rewarming, such as covering with blan- washing machines. Risk factors include epilepsy, alco-
kets, is appropriate only for mild cases (> 33°C). hol, intentional trauma, and lack of supervision. Males
2. Active rewarming is achieved by external or core predominate in submersion deaths, as in most other
rewarming techniques. External rewarming meth- nonintentional deaths. All pediatric care providers must
ods include warming lights, thermal mattresses or make efforts to prevent these needless tragedies.
electric warming blankets, immersion in warm Major morbidity stems from CNS and pulmonary
baths, and hot water bottles or warmed bags of IV insult. Laryngospasm or breath-holding may lead to
solutions. One must be aware of the potential for loss of consciousness and cardiovascular collapse before
core temperature depression after rewarming is aspiration can occur (so-called dry drowning).
begun, as warmed peripheral acidemic blood is Anoxia from laryngospasm or aspiration leads to ir-
distributed to the core circulation. Core rewarm- reversible CNS damage after only 4–6 minutes. A child
ing techniques are optimal and include the deliv- must fall through ice or directly into icy water for cere-
ery of warmed, humidified oxygen and the use of bral metabolism to be slowed sufficiently by hypother-
warmed (to 40°C) fluids for IV replacement, peri- mia to provide some protection from anoxic damage.
toneal dialysis, bladder irrigation, and mediastinal Cardiovascular changes include myocardial depres-
lavage. Extracorporeal blood rewarming achieves sion and arrhythmias. Electrolyte alterations are gener-
controlled core rewarming, can stabilize volume ally slight. Unless hemolysis occurs, hemoglobin con-
and electrolyte disturbances, and is maximally ef- centrations also change only slightly.
fective (Table 11–6).
Assessment & Management
Depending on the duration of submersion and any pro-
SUBMERSION INJURIES tective hypothermia effects, children may appear clini-
Drowning is the second most common cause of death cally dead or completely normal. Observation over time
by unintentional injury among children. Water hazards assists with prognosis. The child who has been re-
336 / CHAPTER 11

warmed to at least 33°C and is still apneic and pulseless Infected dog bites can be treated with penicillin for P
in the emergency department will probably not survive multocida, and broad-spectrum coverage can be pro-
to discharge or will be left with severe neurologic vided by amoxicillin and clavulanic acid or cephalexin
deficits. Until a determination of brain death can be (see dose for cat bites in next section). Complications of
made, however, aggressive resuscitation should be con- dog bites include scarring, CNS infections, septic
tinued. arthritis, osteomyelitis, endocarditis, and sepsis.
One should keep in mind possible associated in-
juries, such as neck injury from diving into shallow
water. For children who appear well initially, observa- CAT BITES
tion for 8–12 hours will detect late pulmonary compro- Cat-inflicted wounds occur more frequently in girls,
mise or changes in neurologic status. Respiratory dis- and their principal complication is infection. The infec-
tress, an abnormal chest radiograph, abnormal arterial tion risk is higher in cat bites than dog bites because of
blood gases, or hypoxemia by pulse oximetry indicates the puncture character of the wound produced by cat
the need for treatment with supplemental oxygen, car- teeth. Wound management is similar to that for dog
diopulmonary monitoring, and frequent reassessment. bites. Cat wounds should not be sutured except when
Serially assess the degree of respiratory distress and absolutely necessary for cosmetic reasons. P multocida is
mental status. Signs of pulmonary infection may appear the most common pathogen. Cat bites create a punc-
many hours after the submersion event. ture-wound inoculum, and prophylactic antibiotics
Patients who are in coma and who require mechani- (penicillin plus cephalexin, or amoxicillin and clavu-
cal ventilation have a high risk of anoxic encephalopa- lanic acid) are recommended. The dose of amoxicillin
thy. The value of therapy with hyperventilation, corti- trihydrate and clavulanic acid should be on the high
costeroids, intentional hypothermia, and barbiturates side of recommended dosage in order to ensure ade-
remains unproved. quate tissue penetration both in dog and cat bites. The
dosage of the amoxicillin component should be
80 mg/kg/24 h in three divided doses. The maximum
dosage is 2 g/24 h. Scratches or bites from young cats
BITES: ANIMAL & HUMAN may result in cat scratch fever.
Bites account for a large number of visits to the emer-
gency department. Most fatalities are due to dog bites. HUMAN BITES
However, the majority of infected bite wounds are from
human and cat bites. Most human bites occur during fights. P multocida is
not a known pathogen in human bites—cultures most
DOG BITES commonly grow streptococci, anaerobes, staphylococci,
Boys are bitten more frequently than girls, and the dog
is known by the victim in most cases. Younger children
have a higher incidence of head and neck wounds,
whereas school-age children are bitten most often on PEDIATRIC EMERGENCY MEDICINE
the upper extremities.
Dog bites are treated largely the same way as other
wounds: high-pressure, high-volume irrigation with Pediatric emergency medicine is a subspecialty with fellow-
normal saline, scrubbing, debridement of any devital- ship training and subboard certification that provides resus-
ized tissue and removal of foreign matter, and tetanus citation and urgent care of ill or injured infants, children, and
prophylaxis. The risk of rabies from dogs is low in de- adolescents. The body of emergency research literature is
veloped countries, but rabies prophylaxis should be substantial and growing rapidly. EMS-C (Emergency Medical
considered when appropriate. Wounds should be su- Services for Children) programs exist to enhance the spec-
tured only if necessary for cosmetic reasons because clo- trum of care of the severely ill or injured child through, for ex-
sure of the wound increases the risk of infection. Pro- ample, community injury prevention, prehospital care by
phylactic antibiotics have not been shown to decrease emergency medical technicians and paramedics, emergency
rates of infection in low-risk dog bite wounds not in- department-based stabilization and critical care, and rehabili-
volving the hands or feet. If a bite involves a joint, peri- tation. Pediatric emergency medicine physicians are inti-
osteum, or neurovascular bundle, prompt orthopedic mately involved in the care of injured patients, because
surgery consultation should be obtained. trauma is the leading cause of death among children over
Pathogens that infect dog bites include Pasteurella age 1 year.
multocida, streptococci, staphylococci, and anaerobes.
 EMERGENCIES & INJURIES / 337

and Eikenella corrodens. Hand wounds and deep Table 11–7. Potential bioterrorism agents and
wounds should be treated with antibiotic coverage the diseases produced.
against E corrodens and gram-positive pathogens by a
penicillinase-resistant penicillin. Wound management Agent Disease Produced
is the same as for dog bites. Only severe lacerations in-
volving the face should be sutured. Other wounds can Bacillus anthracis Anthrax
be managed by delayed primary closure or healing by Variola virus Smallpox
second intention. Yersinia pestis Plague
A major complication of human bite wounds is in- Botulinum toxin Botulism
fection of the metacarpophalangeal joints. A hand sur- Francisella tularensis Tularemia
geon should evaluate clenched-fist injuries from human Brucella species Brucellosis
Coxiella burnetti Q-fever
bites. Operative debridement is followed in many cases
Filoviradae Ebola, Marburg
by IV antibiotics. Bunyaviridae Rift Valley fever
Salmonella typhi Typhoid fever
Knapp JF: Updates in wound management for the pediatrician. Pe-
diatr Clin North Am 1999 46(6):1201 [PMID: 10629682].

There are many potential biologic agents (Table

11–7). Bacillus anthracis (anthrax), variola virus (small-
II. BIOTERRORISM pox), Yersinia pestis (plague), and botulinum toxin (bot-
ulism) are the most likely attack agents.
Marsha S. Anderson, MD Biologic agents can be delivered via aerosolization,
food or water contamination, parenteral injection, or
Bioterrorism is the intentional use of biological agents direct contact with skin. Aerosolization is thought to be
to produce disease or intoxication in a susceptible pop- the most efficient exposure method for many agents.
ulation. Biologic agents have been used frequently The aim is to create an invisible cloud of infectious par-
throughout history, the most recent instances being the ticles with diameters of 0.5–10 µg. At this particle size,
United States anthrax outbreak in 2001 and the ricin the aerosolized infectious agents reach the alveolar
contamination of the Dierksen Senate Office Building spaces.
in 2004. In the anthrax outbreak inhalational and cuta- Unlike a bomb explosion or a chemical spill, a
neous anthrax disease resulted from exposures to an- bioterrorism event is likely to be covert. A covert attack
thrax spores in envelopes that traveled through the US may not have an immediate effect because of the time
Postal system. Over 32,000 people were treated or re- between exposure and development of disease. Days to
ceived antibiotic prophylaxis, 22 people contracted an- weeks later (depending on the agent and incubation pe-
thrax, and 5 died. Several cases involved postal workers, riod), patients will present to their primary care physi-
and were believed to be related to high-speed mail sort- cians or local emergency departments. Consequently,
ing and stamping equipment and the compressed air first responders to a covert biologic incident will not be
used to clean these machines—all of which were the military or law enforcement officials. Rather, physi-
thought to increase aerosolization of spores in the cians, nurses, or emergency medical technicians will
postal facilities. identify the initial cases. Only after an outbreak has
been recognized will the possibility of a biologic attack
be considered. For this reason, it is imperative that
General Considerations medical first-responders remain vigilant and report any
unusual clustering of disease to their state health de-
Bioterrorism is a concern because at least 17 nations are
partments.
thought capable of producing biologic weapons. In ad-
dition, some cult groups are interested in obtaining
these agents. Biologic weapons are attractive to terror-
ists and rogue states because they are relatively simple
ANTHRAX
and cheap to manufacture, difficult to detect, and capa- Anthrax is caused by the bacterium Bacillus anthracis, a
ble of inflicting mass casualties over a wide area. More- spore-forming gram-positive rod. Anthrax occurs natu-
over, most target populations are susceptible to candi- rally in domesticated and wild herbivores. B anthracis
date disease agents, and mass casualty and medical spores, common in the soil, are ingested by grazing ani-
response systems are unprepared to deal with the effects mals. Three proteins—protective antigen, lethal factor,
of these agents. and edema factor—combine to form two toxins re-
338 / CHAPTER 11

sponsible for the morbidity and mortality associated Table 11–8. Empiric treatment of cutaneous
with the disease. Edema toxin (made by the linkage of anthrax (without systemic involvementa)
protective antigen and edema factor) is an adenylate cy- associated with a bioterrorist attack.b
clase analogue that promotes generation of cyclic
adenosine monophosphate and alters intercellular flux
Initial therapy Course
of water and ions. This is responsible for the edema
characteristically seen around cutaneous lesions. Lethal Children Ciprofloxacin 10–15 mg/kg orally 60 dd
toxin, produced by the interaction of protective antigen (maximum 500 mg/dose)
and lethal factor, is a mitogen-activated protein kinase or
inhibitor that influences cell signaling. Doxycycline
≤ 45 kg: 2.2 mg/kg/dose orally 60 dd
A. CUTANEOUS ANTHRAX > 45 kg: 100 mg orally 60 dd
Ninety-five percent of naturally acquired anthrax cases Adultsc Ciprofloxacin 500 mg orally 60 dd
are acquired by direct skin contact with infected ani- or
mals, animal parts, or spores. Presumably the bacteria Doxycycline 100 mg orally q12h 60 dd
or spores are inoculated through wounds or small a
Cutaneous anthrax with systemic involvement, extensive edema,
breaks in the skin. After an incubation period of or lesions on the head or neck requires a multidrug regimen as in
1–12 days, a small macular or papular and sometimes inhalational anthrax (see Table 11–9).
pruritic lesion appears at the site of inoculation. This b
This table is for initial therapy. Each bioterrorist episode is poten-
develops into a vesicle or group of vesicles that ulti- tially unique, and the orgnaisms may have unique suseptibilities.
mately ulcerates, enlarges, and develops a characteristic Regimens may need to be revised once the susceptibility pattern
black center, or eschar. Marked edema surrounding the of the organism is known.
c
lesion is typical. The ulcer is depressed, painless, and Recommendations for pregnant women are the same as for
may have a heaped border. Systemic symptoms such as adults, since this is a serious and sometimes life-threatening ill-
fever, headache, and myalgias may be present. The dif- ness. Doxycycline’s adverse effects on bones and teeth is dose re-
lated.
ferential diagnosis includes brown recluse spider (Lox- d
At least 60 days is recommended to treat the infection and for
osceles reclusa) bite (where these are endemic), ecthyma prophylaxis for inhalational exposures. Longer prophylaxis (up to
gangrenosum (common in neutropenic hosts), ulcero- 100 days) might be recommended if the patient is judged to be at
glandular tularemia, and routine wound infection high risk for exposure to a large number of spores. Anthrax vac-
(Staphylococcus aureus, group A Streptococcus). Diagnosis cine might also be considered as part of postexposure prophy-
is made by culture and Gram stain of the vesicular fluid laxis (currently available under research protocol, discussion with
or a biopsy specimen. Cultures obtained prior to antibi- the state health department is recommended).
otic treatment usually yield the diagnosis. Polymerase
chain reaction (PCR) and immunohistochemical tests
are available at most state health departments or
through the Centers for Disease Control and Preven- be at risk for inhalational disease. For this reason, dur-
tion (CDC). PCR can be done on formalin-fixed tissue ing the 2001 outbreak, the CDC recommended con-
from a biopsy specimen. All suspected anthrax cases tinuation of antibiotics for 60 days (this was later ex-
should be immediately reported to the state health de- tended to a total of 100 days).
partment. Although person-to-person transmission of
any form of anthrax has not been reported, patients are B. GASTROINTESTINAL
generally placed in contact isolation because they have a Gastrointestinal anthrax, which is typically acquired by
draining wound. the ingestion of poorly cooked contaminated meat, has
Mortality is 10–20% without treatment. Doxycy- an incubation period of 1–7 days. It might be acquired
cline and ciprofloxacin are effective first-line therapy by swallowing aerosolized spores. The oropharyngeal
(Table 11–8). Ciprofloxacin might be preferred ini- form consists of fever, marked cervical adenopathy, ul-
tially, because some investigators have reported geneti- cerations at the base of the tongue, dysphagia, and sub-
cally engineered B anthracis strains resistant to peni- mental swelling. Fever, vomiting, abdominal pain, and
cillin and tetracycline. Once the susceptibilities are bloody diarrhea are characteristics of the abdominal
known, therapy can be tailored (usually penicillin, form. Massive ascites may occur. Blood culture results
ciprofloxacin, or doxycycline). Patients who are not sys- are often positive. Mortality is high, despite antibiotic
temically ill can be treated orally. If intravenous (IV) therapy. Thus antibiotics should be instituted as soon
therapy is initiated, oral therapy can be used once the as the diagnosis is considered. Patients should be
patient improves. Patients who develop cutaneous an- treated with the same regimen as for inhalational an-
thrax as a consequence of a bioterrorist attack may also thrax (Table 11–9).
 EMERGENCIES & INJURIES / 339

Table 11–9. Initial therapy of invasive or C. INHALATIONAL

inhalational anthrax secondary to a Inhalational anthrax, the most lethal form, occurs after
bioterrorist attack.a the inhalation of anthrax spores. It is estimated that
8000–40,000 spores can produce lethal disease in 50%
Empiric therapy of those exposed. Onset of symptoms is typically
1–7 days after exposure, but may be as long as 60 days,
Children Ciprofloxacinb,c 20–30 mg/kg/day, in- depending on inoculum size, host factors, and concur-
travenously, divided in two daily rent antibiotic use (for prophylaxis or other illnesses).
doses (maximum 1 gram/day) Patients initially develop flu-like symptoms of fever,
Plus one or two additional antibi-
headache, malaise, and myalgias. Vomiting and abdom-
otics from this list:d
Vancomycin
inal pain were observed in the 2001 inhalational an-
Rifampin thrax outbreak. Precordial discomfort or chest pain is
Doxycycline also common, sometimes first occurring several days
Penicilline after the onset of symptoms. After 2–3 days transient
Imipenem improvement sometimes occurs, followed by abrupt
Clindamycin onset of respiratory deterioration, which often leads to
respiratory failure, shock, and death. Aggressive antibi-
Adults Ciprofloxacinb 400 mg intravenously otic therapy as well as modern intensive care manage-
every 12 hours ment reduced mortality from 80% to 45% in the
Plus one or two additional antibi-
2001 outbreak. Inhalational anthrax is not transmitted
otics from this list:d
Vancomycin
from one person to another.
Rifampin
Doxycycline Diagnosis
Penicilline
Imipenem The diagnosis may be difficult early in the illness (out-
Clindamycin side of a known outbreak) because the symptoms (ex-
Pregnant Women Same as for adults above (high mor- cept rhinorrhea, which is usually absent) are similar to
tality outweighs the risks of the an- influenza and other acute viral diseases. Almost all pa-
tibiotics to the developing fetus). tients have abnormalities on either chest radiograph or
Immunocompromised Same as for children and adults CT scans. The most common abnormality is a widened
Persons (above) mediastinum caused by mediastinitis (Figure 11–9).
a Pulmonary effusions are present in many patients,
Consult a specialist in infectious disease as well as the state
health department. Therapy may need to be modified once sus- probably due to mechanical obstruction of lymphatic
ceptibility results are known or in specific outbreak situations. vessels (from enlarged nodes) as well as from the effects
These recommendations also apply to patient with cutaneous an- of edema toxin. Pulmonary infiltrates are seen in some
thrax with signs of systemic disease or head/neck lesions, and to patients, contradicting the classical teaching that infil-
patients with gastrointestinal anthrax. trates are not seen in inhalational anthrax.
b
Ciprofloxacin is preferred in a patient with inhalational anthrax Blood cultures obtained prior to antibiotics gener-
secondary to a bioterrorist attack. ally will grow B anthracis within 24–36 hours. Coagula-
c
If unable to give ciprofloxacin due to patient allergy or unavail- tion studies, blood urea nitrogen, creatinine, and liver
ability, doxycycline would be the next preferred agent. Doxycy- function tests should be obtained for severely ill pa-
cline dose for adults and children > 45 kg is 100 mg, given intra-
venously every 12 hours. Doxycycline dose for children ≤ 45 kg is
tients. A chest CT scan could be considered if the chest
2.2 mg/kg/dose, given intravenously every 12 hours. radiograph is normal. Rapid influenza tests can be per-
d
Doxycycline and penicillin have in vivo activity with susceptible formed on nasal wash specimens when influenza is in
organisms. The rest of the list has demonstrated activity in vitro. the differential diagnosis. Patients with signs or symp-
Consider CNS penetration of antibiotics in patients with possible toms suggestive of meningitis should have a lumbar
meningitis. Consult with an infectious disease specialist. puncture. Pleural fluid may contain the organism. The
e
Bacillus anthracis may have inducible or constitutive beta lacta- state health department can arrange specific tests for
mase production. Penicillin should not be used alone. Consult an anthrax, such as PCR or immunohistochemistry tests.
infectious disease specialist.

Treatment
Patients with possible inhalational anthrax should be
started on IV antibiotics when the diagnosis is sus-
pected. Most patients will require intensive care moni-
340 / CHAPTER 11

the patient is improved enough to be discharged from

the hospital. Antibiotics should be continued for at
least 60 days.
Steroids might be considered for meningitis, based
on experience with steroids in other forms of bacterial
meningitis. Steroids have been used for severe edema,
particularly of the head and neck.

Postexposure Prophylaxis
A. ANTIBIOTIC PROPHYLAXIS
Once a bioterrorist attack with anthrax has been identi-
fied, the state health department and CDC will identify
individuals at high risk for exposure. Possible prophy-
laxis regimens include oral ciprofloxacin or doxycycline.
Once susceptibilities of the offending strain are known,
other antibiotics might be recommended. B anthracis
spores are hardy, and rhesus monkey studies have
shown some exposed animals died even after 30 days of
antibiotics. For this reason, long prophylaxis regimens
are recommended. In the 2001 anthrax outbreak, high-
Figure 11–9. Chest radiograph of a patient with in- risk individuals were asked to complete 60 days initially
halational anthrax demonstrates the characteristic and then given the option to extend the prophylaxis
widened mediastinum and the presence of pleural effu- regimen by an additional 40 days (100 days total) with
sions. (CDC, Dr PS Brachman, 1961.) or without receiving three doses of the anthrax vaccine.
B. ANTHRAX VACCINE
Currently, anthrax vaccine is not licensed for postexpo-
toring. The optimal antibiotic regimen for patients sure prophylaxis. Protective antigen is the immuno-
with inhalational anthrax is unknown. There is even genic agent in a cell-free filtrate of an attenuated strain.
less experience with pediatric patients. Table 11–9 lists This vaccine has been routinely given to active US mili-
recommendations for empiric therapy for invasive or tary personnel and reservists to induce protective im-
inhalational anthrax prior to susceptibility results. munity prior to exposures. It is given subcutaneously at
These recommendations are for guidance until consul- 0, 2 weeks, 4 weeks, 6 months, 12 months, and
tations with an infectious disease specialist and the state 18 months. After this series, annual boosters are re-
health department or CDC are available. Once the sus- quired. Animal studies have suggested some protective
ceptibility results are known, therapy may be altered. efficacy of the vaccine in postexposure prophylaxis, but
The specific circumstances of a given bioterrorist event there are no data for humans. However, based on ani-
may prompt the CDC to issue alternative recommen- mal studies and human immunogenicity studies, it has
dations. been suggested that three doses of anthrax vaccine (at 0,
Combination therapy was employed during the 2, and 4 weeks postexposure) might protect against
2001 outbreak and reduced mortality (compared with residual anthrax spores in patients receiving postexpo-
historical cases). If susceptibilities are unknown, sure antibiotics. Antibiotics would be continued until
ciprofloxacin should be used as a first-line agent with about 6 weeks after the first vaccine. Use of vaccine
one or two other recommended drugs (see Table 11–9). with this approach is available under an investigational
Clindamycin inhibits bacterial protein synthesis and new drug protocol (contact Centers for Disease Control
would theoretically inhibit toxin production. Strains of and Prevention, Atlanta, GA).
B anthracis may produce β-lactamases, so penicillin
should not be used alone. If meningitis is suspected,
one or two of the drugs used should be able to cross the
SMALLPOX
blood–brain barrier. (If penicillin is used, be sure to use Smallpox is caused by the variola virus. The disease has
another drug that crosses the blood–brain barrier.) two forms: variola major, the more severe form, with
Once susceptibilities of the strain of B anthracis are mortality rates sometimes exceeding 30% in unvacci-
known, the antibiotic regimen may be altered. Antibi- nated persons (1% if vaccinated); and variola minor, a
otics can be changed from the IV to the oral route once milder form with a mortality rate of less than 1%.
 EMERGENCIES & INJURIES / 341

Smallpox is spread person to person by aerosol or

droplet routes. There are no animal reservoirs or
human “carrier states.” To eliminate smallpox as a
human disease, it was essential to disrupt the human-
to-human chain of transmission. The World Health
Organization (WHO) began a global vaccination cam-
paign in 1967 that eradicated smallpox by 1980. Rou-
tine vaccination in the civilian US population stopped
in 1972, and the US military ceased vaccination in the
late 1980s. In 1999, WHO recommended that all
smallpox virus stocks be destroyed or sent for storage to
two reference laboratories: CDC in Atlanta and the In-
stitute of Virus Preparations in Moscow. The destruc-
tion of these remaining smallpox stores has been post-
poned, citing the need to maintain the strains for
vaccine research.
There is concern that smallpox virus may exist out-
side the two reference laboratories. The world’s popula-
tion is relatively unprotected from this virus, since no
smallpox vaccine has been given worldwide for almost
20 years. Following a single vaccination, neutralizing
antibody declines over a 5- to 10-year period. Few peo-
ple have received more than one vaccine, except as part
of travel or military requirements.
In 2002–2003 the United States began a voluntary
smallpox vaccination program. The goal of the initia-
tive was to increase the nation’s smallpox preparedness
capacity by offering vaccination to public health teams
and health care workers, who would be the individuals
most likely to come in contact with smallpox patients Figure 11–10. Typical smallpox lesions. (CDC, James
in the event of an outbreak of disease. The plan called Hicks, 1973.)
for immunization of 450,000 health care and public
health workers in the first phase. By August 2003,
38,000 health care and public health workers had re-
ceived the vaccine. In large part, the effort was stalled infections at the end of the first week or during the sec-
by concerns about side effects of vaccination, as well as ond week of the illness. By day 8 or 9, crusts form, and
reports of 22 cases of myocarditis and pericarditis that by day 12, scabs are seen. Mortality rates vary with the
occurred in vaccine recipients. virulence of the strain and may approach or exceed
30%. As opposed to varicella, smallpox is a disease that
affects the deep epithelial structures, including the seba-
Clinical Signs and Symptoms ceous glands. Therefore, scarring is extensive. Smallpox
The incubation period is 7–17 days (usually lesions of the cornea can cause scarring and blindness.
12–14 days). Initial symptoms are similar to those of Two forms of smallpox are difficult to recognize
influenza: fever, headache, and myalgias. By day 4–5, a clinically: hemorrhagic smallpox and malignant small-
maculopapular rash develops on the face, then spreads pox. Hemorrhagic smallpox can occur in persons of
to the extremities, and finally to the trunk. By day 6–7, all ages, but pregnant women are particularly vulnera-
the characteristic pustules form, which are quite painful ble. The initial symptoms are typical of smallpox, al-
and deeply embedded in the skin (Figure 11–10). The though more severe, and are followed by a dusky ery-
rash is most concentrated on the extremities and face, thema of the skin and the appearance of petechiae and
in contrast to varicella (Table 11–10). The lesions de- hemorrhages of the mucosal surfaces and gastrointesti-
velop “in phase” (all at the same time) on a given area nal tract. In addition hemorrhage into the skin lesions
of the body. This also contrasts with chickenpox, in occurs. Mortality is very high, and death usually occurs
which lesions are seen in multiple phases of evolution. within several days of the rash developing. Malignant
At the height of the illness, the patient is toxic. Death smallpox also begins with the typical constitutional
occurs from overwhelming viremia or from secondary symptoms. Lesions develop and become confluent, but
342 / CHAPTER 11

Table 11–10. Clinical differences between chickenpox and smallpox.

Chickenpox Smallpox
Rash progression Occurs in crops Does not occur in crops
Rash distribution Concentrated on trunk Concentrated on face and extremities
Rash evolution Lesions are present in Lesions all look the same on a given body part—they evolve in phase.
multiple forms at the
same time: vesicles,
pustules, crusts
Rash presence on palms and soles Uncommon Common. Extensive lesions on the palms and soles frequently seen.

never progress to the vesicular or pustular stage. In- rubber stopper replaced, and the junction of the tube
stead, they are flat and soft to the touch. The skin de- and stopper sealed with adhesive tape. The whole vacu-
velops a crepe paper-like appearance, and petechiae or tainer should then be placed in an additional water-
purpura are sometimes seen. This form of smallpox is proof, sealed container. Smallpox virus isolation and
difficult to diagnose primarily because the typical “pox” examination require BL-4 level containment facilities,
lesions are not seen. Death is common, and the few sur- to which these specimens must often be transported.
vivors often have large epidermal losses. Contact your state health department for specific rec-
Smallpox is highly contagious. All patients requiring ommendations on packaging specimens for transport.
hospitalization need to be isolated in negative-pressure In a bioterrorist event, this specimen might be consid-
rooms with airborne precautions. In large outbreaks, ered evidence, and chain of custody must be observed.
when the number of patients exceeds isolation capacity, For all these reasons, it is imperative to notify the state
patients can be grouped into cohorts. In addition, a re- health department immediately if a case is suspected.
gional “smallpox” hospital or facility might need to be
established. Treatment
No known therapy is effective against human smallpox.
Differential Diagnosis The antiviral agent cidofovir appears to prevent disease
The initial differential diagnosis includes influenza and in mice and monkeys when given in the first 2 days of
other viral diseases and early anthrax (also presenting exposure. However, no studies have been done of its ef-
with influenza-like symptoms). Later, when the skin le- ficacy in humans with smallpox. The drug must be
sions are apparent, smallpox must be distinguished given intravenously and is potentially myelosuppressive
from varicella (see Table 11–10). and nephrotoxic.

Diagnosis Infection Control and Postexposure

The state health department and the CDC must be no-
Prophylaxis
tified immediately for any case of suspected smallpox. Patients who do not need hospitalization should be iso-
Because smallpox is an eradicated disease, a single case lated and cared for at home to minimize spread. Those
constitutes a probable bioterrorist event. The reemer- who require hospitalization should be isolated in nega-
gence of smallpox would be an international medical tive-pressure rooms with aerosol precautions. Anyone
emergency because of its potential for spread and the entering the room should wear a gown, mask, gloves,
vulnerability of the world’s population. and eye protection. All bed linens, laundry, and wastes
If possible, specimens from the patient should be should be bagged and autoclaved prior to being laun-
collected by a person who has been vaccinated within dered or incinerated.
the prior 3 years. In an initial case, however, this may Smallpox vaccination administered within 2–3 days
not be possible. Personal protective equipment should after exposure will prevent the disease in most individu-
be worn (gown, gloves, eye protection, and mask). To als. Vaccination as late as 4–5 days after exposure may
obtain vesicle or pustule fluid for viral culture, exami- attenuate the disease and prevent death. Therefore, all
nation by electron microscopy, or PCR, the lesion will close contacts of the patient must be identified, vacci-
likely need to be opened with a scalpel. The material nated (if within 4–5 days of exposure), and monitored
obtained should be placed in a dry vacutainer tube, the for development of symptoms. If the contacts become
 EMERGENCIES & INJURIES / 343

febrile or experience other symptoms, they should be time as the primary vaccine lesion, thus distinguishing
isolated until a diagnosis is made. The Working Group them from autoinoculation variety. They evolve in the
for Civilian Biodefense (Johns Hopkins University) rec- same manner as the primary lesion.
ommends vaccination of all hospital employees (unless
6. Progressive vaccinia—This occurs in immuno-
contraindicated) at a hospital where a smallpox case is
compromised persons who receive smallpox vaccine. It
admitted. Currently, the CDC has stockpiled smallpox
has been seen in patients with humoral (agammaglobu-
vaccine that could be released in the event of a smallpox
linemia) defects, cell-mediated immunity problems,
outbreak. In addition to stocks of smallpox vaccine, the
and patients receiving immunosuppressive agents. The
CDC maintains control of supplies of vaccinia immune
vaccinial lesion does not heal, and the virus spreads to
globulin (VIG) to be used in the setting where im-
contiguous tissue and systemically to bones and organs.
munocompromised persons are judged to need immu-
Local tissue destruction is seen. Death occurs in over
nization. The following groups of patients should be
one third of patients.
given VIG if smallpox vaccination is required secondary
Patients with progressive vaccinia, eczema vaccina-
to an exposure: (1) patients who are receiving immuno-
tum, severe generalized vaccinia, or corneal autoinocu-
suppressive agents or radiation, (2) persons with an im-
lation of vaccinia may benefit from administration of
munodeficiency syndrome (acquired or congenital,
VIG. The recommended dose is 0.6 mL/kg, adminis-
HIV), (3) persons with eczema or other significant ex-
tered intramuscularly. Due to the large volume of this
foliative skin diseases, and (4) pregnant women. VIG
dose, it can be divided and administered over
should be given intramuscularly at a dose of 0.3 mL/kg
24–36 hours. In addition, a second dose (also divided)
in an extremity other than the one used for the small-
can be administered if no improvement is noted within
pox vaccine at the same visit. This will not significantly
48–72 hours.
affect vaccine efficacy. VIG intended for intramuscular
A new intravenous vaccinia immune globulin (IV-
administration cannot be given intravenously. In addi-
VIG) is currently available from the CDC under an in-
tion, VIG is indicated for some types of vaccine com-
vestigational new drug protocol for treatment of ad-
plications such as severe generalized vaccinia, progres-
verse events related to smallpox vaccination (CDC,
sive vaccinia, and eczema vaccinatum.
1-877-554-4652).
Potential Vaccine Complications 7. Myocarditis/pericarditis—Myocarditis or peri-
carditis (or both) was reported in 22 primary vaccine
The strain of vaccinia used in the currently stockpiled recipients under the pre-event voluntary health care
vaccine has been associated with the lowest complica- and public health worker vaccine program. Five civilian
tion rate, but complications may still be significant. patients had cardiac ischemic events after receiving the
The number and severity of potential complications of smallpox vaccine. Review of the data suggested a causal
smallpox vaccine are reasons (among others) why rou- relationship between myocarditis/pericarditis and the
tine smallpox vaccination is not currently recom- vaccine. However, the rate of cardiac ischemic events in
mended. vaccine recipients was not above the expected back-
1. Encephalopathy—Encephalopathy is most com- ground rate. As a precaution, the Advisory Committee
mon among children younger than 2 years of age, and on Immunization Practices (ACIP) and the CDC rec-
10–25 cases occur per million vaccinees. ommend screening and excluding persons from pre-
event vaccination if there is a history of cardiac disease
2. Encephalitis—This occurs in 2–9 vaccinees per or any of the following risk factors: previous myocardial
million first-time recipients. infarction, angina, congestive heart failure, cardiomy-
3. Autoinoculation—Self-inoculation of the vaccinia opathy, stroke, or transient ischemic attack. In addi-
virus from the vaccine site lesion to other sites of the tion, persons with three or more of the following risk
body is fairly common. factors should not receive vaccine under this program:
hypertension, diabetes, hypercholesterolemia, smoking,
4. Eczema vaccinatum—Persons with active or inac- or an immediate family member who had onset of a
tive eczema or other exfoliative skin diseases may de- heart condition before age 50.
velop vaccinia lesions (sometimes extensive) at sites of
current or previous eczema. This complication can be
serious and even fatal. PLAGUE
5. Generalized vaccinia—Generalized vaccinia occurs Plague is caused by Yersinia pestis, a gram-negative bac-
when lesions develop outside the vaccination site in terium. The clinical manifestations of plague caused by
otherwise healthy persons. It is seen only in first-time a bioterrorist attack would differ from bubonic plague,
vaccine recipients. These lesions develop at the same the type clinicians are most familiar with. A bioterrorist
344 / CHAPTER 11

attack would likely use aerosolized Y pestis. Inhalation use in plague. Antibiotics are usually continued for
of 100–500 bacilli could result in primary pneumonic 10 days or, in late responders, for several days beyond
plague (as opposed to “bubonic plague”). Primary lysis of fever.
pneumonic plague is rare in the United States and has All of the medications useful for plague are poten-
been associated with cats that have acquired pneumonic tially problematic for pregnant women. Pregnant
plague and passed it to their owners. The incubation women should not be treated with streptomycin, if
period for primary pneumonic plague is short: 1–6 days avoidable, as it is associated with fetal deafness. Gen-
(usually 2–4). Symptoms include fever, malaise, short- tamicin is also not generally recommended in preg-
ness of breath, cough, and sometimes hemoptysis or nancy, except for serious illness. Doxycycline has been
bloody sputum. Nausea, vomiting, diarrhea, and ab- associated with fetal bone developmental problems and
dominal pain are common. No buboes usually appear maternal liver toxicity. Gentamicin is recommended as
(as seen in bubonic plague), although occasionally cer- the preferred agent in pregnancy, followed by doxycy-
vical buboes may be seen. Chest radiograph typically cline as an alternative.
shows a bilateral, lobar pneumonia. The white blood
count is typically elevated with leukocytosis. Infection Control
Primary pneumonic plague is transmitted by respira-
Diagnosis tory droplets or aerosols. A 7-day course of doxycycline
No widely accessible, rapid diagnostic tests are available is recommended for plague prophylaxis for individuals
for plague. A presumptive diagnosis may be made from who are asymptomatic household (or close) contacts or
the Gram stain of sputum, lymph node aspirate (if hospital contacts. Close contacts are those who were
bubo present), CSF, or stained blood smear. Gram- within 6 feet an infected person. Contacts who begin
negative bacilli or coccobacilli, sometimes with “safety prophylaxis should also wear a surgical mask and limit
pin” bipolar staining, are characteristic. Blood culture unnecessary contact with others for the first 48 hours of
results are usually positive. CSF and lymph node aspi- therapy. Masks can be discontinued for asymptomatic
rate specimens, if obtained, should be cultured. The contacts that have been on prophylaxis for more than
laboratory should be alerted to take appropriate precau- 48 hours. Contacts who develop fever or other symp-
tions with the samples, and they should be informed toms should be promptly evaluated, isolated, and given
plague is suspected. The health department should be IV antibiotics while awaiting diagnostic evaluation.
notified immediately for suspected plague, as pneu- Hospital personnel attending to patients with pneu-
monic plague has the potential for rapid spread. The monic plague should wear gowns, gloves, masks, and
state health department can also facilitate further test- eye protection.
ing for plague. A direct fluorescent antibody test, as In the event of a bioterrorist incident, postexposure
well as PCR, is available through some state health de- prophylaxis might be recommended by the CDC or
partments and the CDC. state health department to individuals known to be at
high risk for an exposure. Doxycycline and
ciprofloxacin would be the agents most likely recom-
Treatment mended, because they are oral drugs and readily obtain-
Primary pneumonic plague progresses rapidly. There- able.
fore, antibiotics need to be administered immediately if
the diagnosis is suspected. Mortality is quite high if an-
tibiotic therapy is initiated later than 24 hours after
BOTULINUM TOXIN
symptoms start. Streptomycin has been used histori- Clostridium botulinum is a spore-forming, anaerobic
cally for plague and is FDA-approved for this use. bacterium that makes botulinum toxin. This is the
However, lack of availability of this medicine, coupled most potent neurotoxin known. There are actually
with lack of familiarity with its use, has led many ex- seven different botulinum toxins made by C botulinum,
perts to recommend gentamicin. In addition, strepto- designated by the letters A through G. These act by ir-
mycin must be administered intramuscularly. For pa- reversibly binding to the presynaptic cholinergic mem-
tients with sepsis or shock, the intramuscular route may brane and inhibiting release of acetylcholine. Botulism
lead to erratic absorption. All these factors make genta- is classically a food-borne disease seen when humans in-
micin a reasonable choice. Doxycycline has been used gest preformed toxin present in improperly canned
in some cases with successful results. In the event that foods. A bioterrorist release of botulinum toxin would
streptomycin or gentamicin cannot be given, doxycy- likely be aerosolized. Inhalation of the toxin and ab-
cline could be used. Ciprofloxacin has shown efficacy in sorption into the bloodstream carry the toxin
animal studies, but there are no human studies of its throughout the body. The clinical syndrome seen in
 EMERGENCIES & INJURIES / 345

these patients is very similar to food-borne botulism. and prevent clinical botulism. This has been demon-
The incubation period for an inhalational exposure is strated in primate studies. However, botulism antitox-
unknown, but is probably 12–96 hours. ins are scarce in the United States, and providing anti-
toxin for widespread exposures would be impossible.
Signs and Symptoms
Arnon SS et al: Botulinum toxin as a biological weapon: Medical
Patients typically present with diplopia, ptosis, diffi- and public health management. Smallpox as a biological
culty swallowing, and speech abnormalities (see Chap- weapon: Medical and public health management. Working
ter 38). Loss of head control, symmetrical weakness, Group on Civilian Biodefense. JAMA 2001;285:1059
[PMID: 11209178].
and respiratory difficulties may occur as the descending
Fulginiti VA et al: Smallpox vaccination: A review, part I. Back-
paralysis progresses. Patients may need mechanical ven- ground, vaccination technique, normal vaccination and re-
tilation due to loss of gag reflexes and paralysis of respi- vaccination, and expected normal reactions. Clin Infect Dis
ratory musculature. The toxin does not cross the 2003;37(2):241 [PMID: 12856217].
blood–brain barrier, so patients have a clear sensorium. Inglesby T et al: Plague as a biological weapon. JAMA 2000;283:
This may be difficult to establish, however, as these pa- 2281 [PMID: 10807389].
tients may have extreme difficulties communicating be- Inglesby TV et al: Anthrax as a biological weapon, 2002: Updated
cause of bulbar palsies. Patients with botulism are recommendations for management. JAMA 2002;287(17):
afebrile unless they have a secondary infection such as 2236 [PMID: 11980524].
aspiration pneumonia. Deep tendon reflexes are often Jernigan JA et al: Bioterrorism-related inhalational anthrax: The
diminished or absent. first 10 cases reported in the United States. Emerg Infect Dis
2001;7:993 [PMID: 11747719].
Wharton M et al: Recommendations for using smallpox vaccine in
Diagnosis and Treatment (These are a pre-event program. MMWR 2003;52(RR07):1 [PMID:
discussed in Chapter 38.) 12710832].

Postexposure Prophylaxis
Theoretically, neutralizing antibody present prior to ex-
posure or delivered shortly after could bind to toxins
 Poisoning 12
Richard C. Dart, MD, PhD, & Barry H. Rumack, MD

Poisonings result from the complex interaction of the 6. If you are interrupted while using a product, take
agent, the child, and the family environment. The peak it with you—it takes only a few seconds for your
incidence is at age 2 years. Most ingestions occur in child to get into it.
children younger than age 5 years as a result of insecure 7. Know what your child can do physically. For ex-
storage of drugs, household chemicals, and the like. ample, if you have a crawling infant, keep house-
Twenty-five percent of children will have a second hold products stored above floor level, not be-
episode of ingestion within 1 year following the first neath the kitchen sink.
one. Repeated poisonings may require intervention on 8. Keep the phone numbers of your doctor, poison
the child’s behalf. Accidental poisonings are unusual center, hospital, police department, and emer-
after age 5 years. Poisonings in older children and ado- gency medical system near the phone.
lescents usually represent manipulative behavior, chem-
ical or drug abuse, or genuine suicide attempts.
PHARMACOLOGIC PRINCIPLES
OF TOXICOLOGY
Watson WA et al: 2002 annual report of the American Association
of Poison Control Centers Toxic Exposure Surveillance Sys- In the evaluation of the poisoned patient, it is impor-
tem. Am J Emerg Med 2003;21:353 [PMID: 14523881]. tant to compare the anticipated pharmacologic or toxic
effects with the patient’s clinical presentation. If the
history is that the patient ingested a tranquilizer
PREVENTING CHILDHOOD 30 minutes ago, but the clinical examination reveals di-
POISONINGS lated pupils, tachycardia, dry mouth, absent bowel
sounds, and active hallucinations—clearly anticholiner-
Each year, children are accidentally poisoned by medi- gic toxicity—diagnosis and therapy should proceed ac-
cines, polishes, insecticides, drain cleaners, bleaches, cordingly.
household chemicals, and garage products. It is the re-
sponsibility of adults to make sure that children are not
exposed to potentially toxic substances. LD50
Here are some suggestions for parents: Estimates of the LD50 (the amount per kilogram of
body weight of a drug required to kill 50% of a group
1. Insist on packages with safety closures and learn of experimental animals) or median lethal dose are of
how to use them properly. little clinical value in humans. It is usually impossible
2. Keep household cleaning supplies, medicines, to determine with accuracy the amount swallowed or
garage products, and insecticides out of the reach absorbed, the metabolic status of the patient, or in
and sight of your child. Lock them up whenever which patients the response to the agent will be atypi-
possible. cal. Furthermore, these values are often not valid in hu-
mans even if the history is accurate.
3. Never store food and cleaning products together.
Store medicine and chemicals in original contain-
ers and never in food or beverage containers. Half-Life (t1/2)
4. Avoid taking medicine in your child’s presence. The t 1/2 of an agent must be interpreted carefully. Most
Children love to imitate. Never suggest that med- published t 1/2 values are for therapeutic dosages. The t 1/2
icine is candy. may increase as the quantity of the ingested substance
5. Read the label on all products and heed warnings increases for many common intoxicants such as salicy-
and cautions. Never use medicine from an unla- lates and phenytoin. One cannot rely on the published
beled or unreadable container. Never pour medi- t 1/2 for salicylate (2 hours) to assume rapid elimination of
cine in a darkened area where the label cannot be the drug. In an acute salicylate overdose (150 mg/kg),
seen clearly. the apparent t 1/2 is prolonged to 24–30 hours.
346
Copyright © 2005, 2001, by The McGraw-Hill Companies, Inc. Click here for terms of use.
 POISONING / 347

Volume of Distribution be directed first by the clinical signs and symptoms, fol-
lowed by more specific therapy based on laboratory de-
The volume of distribution (Vd) of a drug is deter- terminations. Clinical information may speed the iden-
mined by dividing the amount of drug absorbed by the tification of a toxic agent by the laboratory.
blood level. With theophylline, for example, the Vd is
0.46 L/kg body weight, or 32 L in an adult. In contrast,
digoxin distributes well beyond total body water. Be- GENERAL TREATMENT OF POISONING
cause the calculation produces a volume above body
The telephone is often the first contact in pediatric poi-
weight this figure is frequently referred to as an appar-
soning. Proper telephone management can reduce mor-
ent volume of distribution, a designation shared by
bidity and prevent unwarranted or excessive treatment.
many drugs (Table 12–1).
The decision to refer the patient is based on the identity
The Vd can be useful in predicting which drugs will
and dose of the ingested agent, the age of the child, the
be removed by dialysis, extracorporeal perfusion, or ex-
time of day, the reliability of the parent, and whether
change transfusion. When a drug is differentially con-
child neglect or endangerment is suspected.
centrated in body lipids or is heavily tissue- or protein-
bound and has a high volume of distribution, only a
small proportion of the drug will be in the free form Initial Telephone Contact
and thus accessible to diuresis, dialysis, or exchange
transfusion. A drug that is water-soluble and has a low Basic information that should be written down at the
volume of distribution may cross the dialysis membrane first telephone contact includes the patient’s name, age,
well and also respond to diuresis. In general, methods weight, address and telephone number, the agent and
of extracorporeal elimination are not effective for toxic amount of agent ingested, the patient’s present condi-
agents with a Vd greater than 1 L/kg. tion, and the time elapsed since ingestion or other ex-
posure.
Use the history to evaluate the urgency of the situa-
Metabolism & Excretion tion and decide whether immediate emergency trans-
The route of excretion or detoxification is important portation to a health facility is indicated. An emergency
for planning treatment. Methanol, for example, is me- exists if the ingestant is high risk (caustic solutions, hy-
tabolized to the toxic product, formic acid. This meta- drogen fluoride, drugs of abuse, or medications such as
bolic step may be blocked by the antidote fomepizole or a calcium channel blocker, opioid, hypoglycemic agent,
ethanol. antidepressant) or if the self-poisoning was intentional.
If immediate danger does not exist, obtain more details
Blood Levels about the suspected toxic agent. It may be difficult to
obtain an accurate history. Obtain names of drugs or
Care of the poisoned patient should never be guided ingredients, manufacturers, prescription numbers,
solely by laboratory measurements. Treatment should names and phone numbers of prescribing physician and

Table 12–1. Some examples of pKa and Vd.

Drug pKa Diuresis Dialysis Apparent Vd

Amobarbital 7.9 No No 200–300% body weight
Amphetamine 9.8 No Yes 60% body weight
Aspirin 3.5 Alkaline Yes 15–40% body weight
Chlorpromazine 9.3 No No 40–50 L/kg (2800–3500% body weight)
Codeine 8.2 No No 5–10 L/kg (350–700% body weight)
Desipramine 10.2 No No 30–40 L/kg (2100–2800% body weight)
Ethchlorvynol 8.7 No No 5–10 L/kg (350–700% body weight)
Glutethimide 4.5 No No 10–20 L/kg (700–1400% body weight)
Isoniazid 3.5 Alkaline Yes 61% body weight
Methadone 8.3 No No 5–10 L/kg (350–700% body weight)
Methicillin 2.8 No Yes 60% body weight
Phenobarbital 7.4 Alkaline Yes 75% body weight
Phenytoin 8.3 No No 60–80% body weight
Tetracycline 7.7 No No 200–300% body weight
348 / CHAPTER 12

pharmacy, and so on. Find out whether the substance Bring the Poison to the Hospital
was shared among several children, whether it had been
recently purchased, who had last used it, how full the Everything in the vicinity of the patient that may be a
bottle was, and how much was spilled. If unsure of the cause of poisoning should be brought to the health care
significance of an exposure, consult with a certified Poi- facility.
son Control Center.
OBTAINING INFORMATION
FIRST AID FOR POISONING ABOUT POISONS
(Advice for Parents) Current data on ingredients of commercial products
Syrup of ipecac is used to induce vomiting; the acti- and medications can be obtained from a certified re-
vated charcoal is used to bind poisons. Use them only gional poison center. It is important to have the actual
as instructed by your Poison Control Center or doctor. container at hand when calling. Caution: Antidote in-
Consult your physician to decide if you should keep formation on labels of commercial products or in the
syrup of ipecac and activated charcoal in your home. Physicians’ Desk Reference may be incorrect or inappro-
priate.
Inhaled Poisons
FOLLOW-UP
If smoke, gas, or fumes have been inhaled, immediately
drag or carry the victim to fresh air. Then call 911, the In over 95% of cases of ingestion of potentially toxic
Poison Control Center, or your doctor. Do not enter substances by children, a trip to the hospital is not re-
an area where poisonous fumes are present that have quired. In these cases, it is important to call the parent
caused loss of consciousness. Too often the rescuer be- at 1 and 4 hours after an ingestion. If the child has in-
comes a victim as well. gested an additional unknown agent and develops
symptoms, a change in management may be needed,
including transportation to the hospital. An additional
Poisons on the Skin call should be made 24 hours after the ingestion to
If the poison has been spilled on the skin or clothing, begin the process of poison prevention.
remove the clothing and flood the involved parts with
water. Wash with soapy water and rinse thoroughly. PREVENTION OF POISONING
Then call the Poison Control Center or your doctor.
A major goal of pediatricians is to reduce the number of
accidental ingestions in the high-risk age group (ie,
Swallowed Poisons < age 5 years). A systematic poison education effort
If the substance swallowed is a medicine, give nothing. should be part of the routine care of every patient. Par-
Milk or water should be administered immediately to ents of very young children should be encouraged to
any patient who has ingested a strongly acid or alkaline search the house and identify all hazardous substances
agent. Do not give more than 15 mL/kg (250 mL max- that should be removed from the home or locked up.
imum in a child weighing 16 kg or more). Do not in- Pediatric or medical office staff can help families with
duce vomiting in patients who are comatose, convuls- poison prevention by telephone by asking a few simple
ing, or who have lost the gag reflex. Induce emesis with questions about storage of hazardous substances in the
ipecac or administer charcoal only if advised to do so home. The following is a partial list of potentially poi-
by a health care professional. Caution: Antidote labels sonous substances that must be stored safely if small
on products may be incorrect. Do not give salt, vinegar, children are in the home: drain-cleaning crystals or liq-
or lemon juice. Call before doing anything else. uid, dishwasher soap and cleaning supplies, paints and
paint thinners, garden spray and other insecticide mate-
rials, automobile products (antifreeze, windshield wiper
Poisons in the Eye fluid, gasoline), and all medications.
Rinse out the eye with plain water before the patient ar- The section entitled Preventing Childhood Poison-
rives at the emergency room. Use plain tap water—do ings may be copied from this book and given to parents
not try to neutralize acids or bases. Pour water into the at the 6-month check-up. Although syrup of ipecac is
eye from a drinking glass or pitcher for 15–20 minutes not recommended for all poisonings, it is useful for
or fill a basin with water and have the patient put his or some types, such as plant material, pills too large to be
her face into the water and open the eyes to dilute. lavaged, and decontamination in rural areas where
Then transport the patient to the hospital. health care may be 30 minutes or more away. Rein-
 POISONING / 349

forcement should occur at the 1-year check-up to make some hydrocarbons, or sharp objects. The use of ipecac
certain that adequate poison-proofing measures have has decreased dramatically over the past 10 years and is
been instituted and maintained. reserved for those instances when medications have
been taken within 30–60 minutes prior to contact.
INITIAL EMERGENCY 1. Ipecac method—This may be effective if adminis-
DEPARTMENT CONTACT tered within an hour of ingestion. Adult dose, 30 mL;
pediatric dose, 15 mL. Give orally (PO) and repeat
Make Certain the Patient Is Breathing once in 20 minutes if necessary.
As in all emergencies, the principles of treatment are at- 2. Other emetics—The only approved oral emetic
tention to airway, breathing, and circulation. These are agent is syrup of ipecac. Use of sodium chloride may
sometimes overlooked under the stressful conditions of lead to lethal hypernatremia. Apomorphine, mustard,
a pediatric poisoning. soap, and other emetics should not be used.

Treat Shock B. LAVAGE

If the patient is or is becoming unconscious, is convuls-
Initial therapy of the hypotensive patient should consist ing, or has lost the gag reflex, gastric lavage following
of laying the patient flat and administering intravenous endotracheal or nasotracheal intubation should be per-
isotonic solutions. Vasopressors should be reserved for formed rather than induction of vomiting. Lavage is
poisoned patients in shock who do not respond to these rarely performed in pediatric patients. Emesis and
standard measures. lavage recover an average of about 30% of the stomach
contents if performed soon after ingestion. Although
Treat Burns these procedures may be helpful in reducing the
Burns may occur following exposure to strong acid or amount of material available for absorption, approxi-
strong alkaline agents or petroleum distillates. Burned mately 70% of an ingested dose will remain. Additional
areas should be decontaminated by flooding with sterile measures such as charcoal should be instituted to pre-
saline solution or water. A burn unit should be con- vent further absorption.
sulted if more than minimal burn damage has been sus- C. CHARCOAL
tained. Skin decontamination should be performed in a
patient with cutaneous exposure. Emergency depart- The dose of charcoal is 1–2 g/kg (maximum, 100 g) per
ment personnel in contact with a patient who has been dose. Repeating the dose of activated charcoal may be
contaminated (with an organophosphate insecticide, useful for those agents that slow passage through the
for example) should themselves be decontaminated if gastrointestinal (GI) tract. When multiple doses of acti-
their skin or clothing becomes contaminated. vated charcoal are given, repeated doses of sorbitol or
saline cathartics must not be given. Repeated doses of
cathartics may cause electrolyte imbalances and fluid
Take a Pertinent History loss. Charcoal dosing is repeated every 2–6 hours until
The history should be taken from the parents and all charcoal is passed through the rectum.
individuals present at the scene. It may be crucial to de-
termine all of the kinds of poisons in the home. These D. CATHARSIS
may include drugs used by family members, chemicals Despite their widespread use, cathartics have not been
associated with the hobbies or occupations of family shown to improve outcome. The use of cathartics
members, or the purity of the water supply. Unusual should therefore be avoided.
dietary or medication habits or other clues to the possi-
ble cause of poisoning should also be investigated. E. WHOLE GUT LAVAGE
Whole bowel lavage uses an orally administered, non-
absorbable hypertonic solution such as CoLyte or
DEFINITIVE THERAPY OF POISONING GoLYTELY. The use of this procedure in poisoned pa-
Prevention of Absorption tients remains controversial. Preliminary recommenda-
tions for use of whole bowel irrigation include poison-
A. EMESIS ing with sustained-release preparations, mechanical
Induced vomiting is contraindicated in patients who movement of items through the bowel (eg, cocaine
have ingested a minimally toxic substance (eg, most an- packets, iron tablets), and poisoning with substances
tibiotics), who are comatose or convulsing, or who have poorly absorbed by charcoal (eg, lithium, iron). Under-
lost the gag reflex or ingested strong acids, strong bases, lying bowel pathology and intestinal obstruction are
350 / CHAPTER 12

relative contraindications to its use. Consultation with b. Hypotension threatening renal or hepatic func-
a certified regional poison center is recommended. tion that cannot be corrected by adjusting circulating
volum.
American Academy of Clinical Toxicology, European Association c. Marked hyperosmolality or severe acid–base or
of Poisons Centers and Clinical Toxicologists: Position state- electrolyte disturbances not responding to therapy.
ment and practice guidelines on the use of multidose acti- d. Marked hypothermia or hyperthermia not re-
vated charcoal in the treatment of acute poisoning. J Toxicol
Clin Toxicol 1999;37:731 [PMID: 10584586]. sponding to therapy.
Gielen AC et al: Effects of improved access to safety counseling,
products, and home visits on parents’ safety practices: Results
2. Immediate dialysis—Immediate dialysis should be
of a randomized trial. Arch Pediatr Adolesc Med considered in ethylene glycol and methanol poisoning
2002;156:33 [PMID: 11772188]. only if acidosis is refractory, the patient does not re-
Hoffman RJ, Nelson L: Rational use of toxicology testing in chil- spond to fomepizole treatment, or blood levels of
dren. Curr Opin Pediatr 2001;13:183 [PMID: 11317063]. ethanol of 100 mg/dL are consistently maintained.
Vale JA: Position statement: Gastric lavage. American Academy of
Clinical Toxicology; European Association of Poisons Cen- 3. Dialysis indicated on basis of condition of pa-
tres and Clinical Toxicologists. J Toxicol Clin Toxicol tient—In general, dialyze if the patient is in a coma
1997;35:711 [PMID: 9482426]. deeper than level 3. Peritoneal dialysis or exchange
transfusion may be more useful than hemodialysis in
small children—as much for ease of achieving fluid and
Enhancement of Excretion electrolyte homeostasis as for poison removal. Other
Excretion of certain substances can be hastened by uri- drugs not listed here may be dialyzable. Information
nary alkalinization or dialysis. It is important to make should be verified prior to institution of dialysis.
certain that the patient is not volume-depleted. Vol-
ume-depleted patients should receive a normal saline
bolus of 10–20 mL/kg, followed by sufficient intra-
venous (IV) fluid administration to maintain urine out- MANAGEMENT OF SPECIFIC
put at 2–3 mL/kg/h. COMMON POISONINGS
A. URINARY ALKALINIZATION
1. Alkaline diuresis—Urinary alkalinization should ACETAMINOPHEN (PARACETAMOL)
be chosen on the basis of the substance’s pKa, so that Overdosage of acetaminophen is the most common pe-
ionized drug will be trapped in the tubular lumen and diatric poisoning and can produce severe hepatotoxic-
not reabsorbed (see Table 12–1). Thus, if the pKa is less ity. The incidence of hepatotoxicity in adults and ado-
than 7.5, urinary alkalinization is appropriate; if it is lescents has been reported to be ten times higher than
over 8.0, this technique is not usually beneficial. The in children younger than age 5 years. In the latter
pKa is sometimes included along with general drug in- group, less than 0.1% develop hepatotoxicity after
formation. Urinary alkalinization is achieved with acetaminophen overdose. In children, toxicity most
sodium bicarbonate. It is important to observe for hy- commonly results from repeated overdosage arising
pokalemia, caused by the shift of potassium intracellu- from confusion about the age-appropriate dose, use of
larly. Follow serum K+ and observe for ECG evidence multiple products that contain acetaminophen, or use
of hypokalemia. If complications such as renal failure or of adult suppositories.
pulmonary edema are present, hemodialysis or hemo- Acetaminophen is normally metabolized in the liver.
perfusion may be required. A small percentage of the drug goes through a pathway
leading to a toxic metabolite. Normally, this elec-
B. DIALYSIS trophilic reactant is removed harmlessly by conjugation
Hemodialysis (or peritoneal dialysis if hemodialysis is with glutathione. In overdosage, the supply of glu-
unavailable) is useful in the poisonings listed below. tathione becomes exhausted, and the metabolite may
Dialysis should be considered part of supportive care if bind covalently to components of liver cells to produce
the patient satisfies any of the following criteria: necrosis. Some authors have proposed that therapeutic
doses of acetaminophen may be toxic to children with
1. Clinical criteria— depleted glutathione stores. However, there is no evi-
a. Potentially life-threatening toxicity that is caused dence that administration of therapeutic doses can
by a dialyzable drug and cannot be treated by conserva- cause toxicity, and only a few inadequate case reports
tive means. have been made in this regard.
 POISONING / 351

Treatment fever are the major source of toxicity in children

younger than age 10 years, and parents are often un-
Treatment is to administer acetylcysteine. In the aware of the significance of symptoms of toxicity, thus
United States, it may only be given PO. Consultation delaying its prompt recognition and therapy.
on difficult cases may be obtained from the Rocky
Mountain Poison Center (1-800-525-6115) or any poi-
Rumack BH: Acetaminophen hepatotoxicity: The first 35 years.
son center. Blood levels should be obtained as soon as J Toxicol Clin Toxicol 2002;40:3 [PMID: 11990202].
possible after 4 hours and plotted on Figure 12–1. The
Smilkstein M et al: Efficacy of oral N-acetylcysteine in the treat-
nomogram is used only for acute ingestion, not re- ment of acetaminophen overdose. N Engl J Med 1988;319:
peated supratherapeutic ingestions. If the patient has 1557 [PMID: 0003059186].
ingested acetaminophen in a liquid preparation, blood Sztajnkrycer MJ, Bond GR: Chronic acetaminophen overdosing in
levels obtained 2 hours after ingestion will give an accu- children: Risk assessment and management. Curr Opin Pedi-
rate reflection of the toxicity to be expected relative to atr 2001;13:177 [PMID: 11317062].
the standard nomogram (see Figure 12–1). Acetylcys-
teine is administered to patients whose acetaminophen ALCOHOL, ETHYL (ETHANOL)
levels plot in the toxic range on the nomogram. Acetyl-
cysteine is effective even when given more than Alcoholic beverages, tinctures, cosmetics, and rubbing
24 hours after ingestion although it is most effective alcohol are common sources of poisoning in children.
when given within 8 hours postingestion. Concomitant exposure to other depressant drugs in-
The dose of acetylcysteine is 140 mg/kg PO, diluted creases the seriousness of the intoxication. (Blood levels
to a 5% solution in sweet fruit juice or carbonated soft cited here are for adults; comparable figures for chil-
drink. The primary problems associated with adminis- dren are not available.) In most states, alcohol levels of
tration are nausea and vomiting. After this loading 50–80 mg/dL are considered compatible with impaired
dose, 70 mg/kg should be administered PO every faculties, and levels of 80–100 mg/dL are considered
4 hours for 72 hours. Aspartate aminotransferase evidence of intoxication.
(AST), alanine aminotransferase (ALT), serum biliru- Complete absorption of alcohol requires 30 minutes
bin, and plasma prothrombin time should be followed to 6 hours, depending on the volume, the presence of
daily. Significant abnormalities of liver function may food, and the time spent in consuming the alcohol. The
not develop until up to 72 hours after ingestion. Re- rate of metabolic degradation is constant (about
peated miscalculated overdoses given by parents to treat 20 mg/h in an adult). Absolute ethanol, 1 mL/kg, re-

200
150 1000

100
Acetaminophen serum concentration (µg/mL)

Acetaminophen serum concentration (µM/L)

Probable hepatic toxicity 500

50

100

10
No hepatic toxicity 50

5 30
Possible hepatic toxicity 25%

Figure 12–1. Semilogarithmic plot of plasma

10
acetaminophen levels versus time. (Modified and
1 reproduced, with permission, from Rumack BH,
0 4 8 12 16 20 24 Matthew H: Acetaminophen poisoning and toxic-
Hours after ingestion ity. Pediatrics 1975;55:871.)
352 / CHAPTER 12

sults in a peak blood level of about 100 mg/dL in 2–3 days. Heavy users, taking more than 100 mg/d,
1 hour after ingestion. Acute intoxication and chronic have restlessness, incoordination of thought, insomnia,
alcoholism increase the risk of subarachnoid hemor- nervousness, irritability, and visual hallucinations. Psy-
rhage. chosis may be precipitated by the chronic administra-
tion of high doses. Depression, weakness, tremors, GI
Treatment complaints, and suicidal thoughts occur frequently.
Management of hypoglycemia and acidosis is usually
the only measure required. Start an IV drip of D5W or Treatment
D10W if blood glucose is under 60 mg/dL. Fructose has Standard decontamination procedures should be used:
been suggested as an accelerator of metabolism, but it gastric emptying followed by charcoal in recent inges-
may cause vomiting, intensify lactic acidosis, and de- tions; activated charcoal alone if ingestion occurred
crease blood volume via osmotic diuresis. Glucagon hours earlier. The treatment of choice is diazepam,
does not correct the hypoglycemia, because hepatic titrated in small increments to effect. Very large total
glycogen stores are reduced. Death is usually caused by doses may be needed. In case of extreme agitation or
respiratory failure. In severe cases, cerebral edema hallucinations, droperidol (0.1 mg/kg/dose) or
should be treated with IV dexamethasone, 0.1 mg/kg haloperidol (up to 0.1 mg/kg) parenterally has been
every 4–6 hours. Dialysis is indicated in life-threatening used. When combinations of amphetamines and barbi-
intoxication. turates (diet pills) are used, the action of the ampheta-
mines begins first, followed by a depression caused by
Ernst AA et al: Ethanol ingestion and related hypoglycemia in a pe- the barbiturates. In these cases, treatment with addi-
diatric and adolescent emergency department population. tional barbiturates is contraindicated because of the risk
Acad Emerg Med 1996;3:46 [PMID: 8749967].
of respiratory failure.
Roy M et al: What are the adverse effects of ethanol used as an anti-
dote in the treatment of suspected methanol poisoning in
Chronic users may be withdrawn rapidly from am-
children? J Toxicol Clin Toxicol 2003;41:155 [PMID: phetamines. If amphetamine–barbiturate combination
12733853]. tablets have been used, the barbiturates must be with-
drawn gradually to prevent withdrawal seizures. Psychi-
AMPHETAMINES & RELATED DRUGS atric treatment should be provided.
(METHAMPHETAMINE)
Kolecki P: Inadvertent methamphetamine poisoning in pediatric
Clinical Presentation patients. Pediatr Emerg Care 1998;14:385 [PMID:
9881979].
A. ACUTE POISONING Schwartz RH, Miller NS: MDMA (ecstasy) and the rave: A review.
Amphetamine and methamphetamine poisoning is Pediatrics 1997;100:705 [PMID: 9310529].
common because of the widespread availability of “diet
pills” and the use of “speed,” “crank,” “crystal,” and ANESTHETICS, LOCAL
“ice” by adolescents. (Care must be taken in the inter-
pretation of slang terms because they have multiple Intoxication from local anesthetics may be associated
meanings.) A new cause of amphetamine poisoning are with CNS stimulation, acidosis, delirium, ataxia, shock,
drugs for treating attention deficit hyperactivity disor- convulsions, and death. Methemoglobinuria has been
der, such as methylphenidate. Symptoms include CNS reported following local dental analgesia. The maxi-
stimulation, anxiety, hyperactivity, hyperpyrexia, hy- mum recommended dose for subcutaneous (SQ) infil-
pertension, abdominal cramps, nausea and vomiting, tration is 4.5 mg/kg. The temptation to exceed this
and inability to void urine. Severe cases often include dose in procedures lasting a long time is great and may
rhabdomyolysis. A toxic psychosis indistinguishable result in inadvertent overdosage. PO application of vis-
from paranoid schizophrenia may occur. Methamphet- cous lidocaine may produce toxicity. Hypercapnia may
amine laboratories in homes are a potential cause of lower the seizure threshold to locally injected anesthet-
childhood exposure to a variety of hazardous and toxic ics.
substances. Local anesthetics used in obstetrics cross the placen-
tal barrier and are not efficiently metabolized by the
B. CHRONIC POISONING fetal liver. Mepivacaine, lidocaine, and bupivacaine can
Chronic amphetamine users develop tolerance; more cause fetal bradycardia, neonatal depression, and death.
than 1500 mg of IV methamphetamine can be used Prilocaine causes methemoglobinemia, which should be
daily. Hyperactivity, disorganization, and euphoria are treated if levels in the blood exceed 40% or if the pa-
followed by exhaustion, depression, and coma lasting tient is symptomatic.
 POISONING / 353

Accidental injection of mepivacaine into the head of Cetaruk EW, Aaron CK: Hazards of nonprescription medications.
the fetus during paracervical anesthesia has caused Emerg Med Clin North Am 1994;12:483 [PMID: 8187693].
neonatal asphyxia, cyanosis, acidosis, bradycardia, con- Skare JA: Antihistamine-containing cough/cold medications pre-
vulsions, and death. sent a low hazard in pediatric accidental exposure incidents:
Analysis of Poison Control Center data. Vet Hum Toxicol
1997;39:367 [PMID: 9397509].
Treatment Ten Eick AP et al: Safety of antihistamines in children. Drug Saf
2001;24:119 [PMID: 11235817].
If the anesthetic has been ingested, mucous membranes
should be cleansed carefully and activated charcoal may
be administered. Oxygen administration is indicated, ARSENIC
with assisted ventilation if necessary. Methemoglobine-
mia is treated with methylene blue, 1%, 0.2 mL/kg Arsenic is used in some insecticides (fruit tree or to-
(1–2 mg/kg/dose, IV) over 5–10 minutes; this should bacco sprays), rodenticides, weed killers, and wood
promptly relieve the cyanosis. Acidosis may be treated preservatives. It is well absorbed primarily through the
with sodium bicarbonate, seizures with diazepam, GI and respiratory tracts, but skin absorption may
bradycardia with atropine. Therapeutic levels of mepi- occur. Arsenic can be found in the urine, hair, and nails
vacaine, lidocaine, and procaine are less than 5 mg/mL. by laboratory testing.
Highly toxic soluble derivatives of this compound,
Bozynski MEA et al: Lidocaine toxicity after maternal pudendal
such as sodium arsenite, are frequently found in liquid
anesthesia in a term infant with fetal distress. Am J Perinatol preparations and can cause death in as many as 65% of
1987;4:164 [PMID: 3566884]. victims. The organic arsonates found in persistent or
Spiller HA et al: Multi-center retrospective evaluation of oral ben- preemergence weed killers are relatively less soluble and
zocaine exposure in children. Vet Hum Toxicol 2000;42:228 less toxic. Poisonings with a liquid arsenical preparation
[PMID: 10928690]. that does not contain alkyl methanearsonate com-
pounds should be considered potentially lethal. Patients
ANTIHISTAMINES exhibiting clinical signs other than gastroenteritis
should receive treatment until laboratory tests indicate
Although antihistamines typically cause CNS depres- that treatment is no longer necessary.
sion, children often react paradoxically with excite-
ment, hallucinations, delirium, ataxia, tremors, and
convulsions followed by CNS depression, respiratory Clinical Presentation
failure, or cardiovascular collapse. Anticholinergic ef- A. ACUTE POISONING
fects such as dry mouth, fixed dilated pupils, flushed
face, fever, and hallucinations may be prominent. Abdominal pain, vomiting, watery and bloody diarrhea,
Antihistamines are widely available in allergy, sleep, cardiovascular collapse, paresthesias, neck pain, and
cold, and antiemetic preparations, and many are sup- garlic odor on breath occur. Convulsions, coma, anuria,
plied in sustained-release forms, which increases the and exfoliative dermatitis are later signs. Inhalation may
likelihood of dangerous overdoses. They are absorbed cause pulmonary edema. Death is the result of cardio-
rapidly and metabolized by the liver, lungs, and kid- vascular collapse.
neys. A potentially toxic dose is 10–50 mg/kg of the B. CHRONIC POISONING
most commonly used antihistamines, but toxic reac-
tions have occurred at much lower doses. Anorexia, generalized weakness, giddiness, colic, ab-
dominal pain, polyneuritis, dermatitis, nail changes,
alopecia, and anemia often develop.
Treatment
Activated charcoal should be used to reduce drug ab- Treatment
sorption. Emetics may be ineffective if the antihista-
mine is structurally related to phenothiazines. Whole In acute poisoning, empty the stomach and administer
bowel irrigation may be useful for sustained-release activated charcoal. Then immediately give dimercaprol
preparations. Physostigmine, 0.5–2 mg IV slowly ad- (commonly known as BAL), 3–5 mg/kg intramuscu-
ministered, dramatically reverses the central and pe- larly (IM), and follow with 2 mg/kg IM every 4 hours.
ripheral anticholinergic effects of antihistamines, but it The dimercaprol-arsenic complex is dialyzable. A sec-
should be used only for diagnostic purposes. Diazepam, ond choice is succimer. The initial dose is 10 mg/kg
0.1–0.2 mg/kg IV, can be used to control seizures. every 8 hours for 5 days. A third choice is penicil-
Forced diuresis is not helpful. Exchange transfusion was lamine, 100 mg/kg PO to a maximum of 1 g/d in four
reported to be effective in one case. divided doses.
354 / CHAPTER 12

Chronic arsenic intoxication should be treated with with Down syndrome. Many common plants and over-
succimer or penicillamine. Collect a 24-hour baseline the-counter medications contain belladonna alkaloids.
urine specimen and then begin chelation. If the
24-hour urine arsenic level is greater than 50 mg, con- Treatment
tinue chelation for 5 days. After 10 days, repeat the
5-day cycle once or twice depending on how soon the Emesis or lavage should be followed by activated char-
urine arsenic level falls below 50 mg/24 h. coal. Gastric emptying is slowed by anticholinergics, so
that gastric decontamination may be useful even if de-
layed. Physostigmine, 0.5–2 mg IV, administered
Abernathy CO et al: Arsenic: Health effects, mechanisms of ac-
tions, and research issues. Environ Health Perspect 1999;107: slowly, dramatically reverses the central and peripheral
593 [PMID: 10379007]. signs of atropinism but should be used only as a diag-
Cullen MN et al: Pediatric arsenic ingestion. Am J Emerg Med nostic agent. High fever must be controlled. Catheteri-
1995;13:432 [PMID: 7605532]. zation may be needed if the patient cannot void.

Burns MJ et al: A comparison of physostigmine and benzodi-

BARBITURATES azepines for the treatment of anticholinergic poisoning. Ann
The toxic effects of barbiturates include confusion, Emerg Med 2000;35:374 [PMID: 10736125].
poor coordination, coma, miotic or fixed dilated pupils, Schultz U et al: Central anticholinergic syndrome in a child under-
and respiratory depression. Respiratory acidosis is com- going circumcision. Acta Anesthesiol Scand 2002;46:224
[PMID: 11942877].
monly associated with pulmonary atelectasis, and hy-
potension occurs frequently in severely poisoned pa-
tients. Ingestion of more than 6 mg/kg of long-acting CARBON MONOXIDE
or 3 mg/kg of short-acting barbiturates is usually toxic. The degree of toxicity correlates well with the carboxy-
hemoglobin level taken soon after acute exposure but
Treatment not after oxygen has been given or when there has been
Activated charcoal should be administered. Careful, some time since exposure. Onset of symptoms may be
conservative management with emphasis on maintain- more rapid and more severe if the patient lives at a high
ing a clear airway, adequate ventilation, and control of altitude, has a high respiratory rate (ie, infants), is preg-
hypotension is critical. Urinary alkalinization and the nant, or has myocardial insufficiency or lung disease.
use of multiple-dose charcoal may decrease the elimina- Normal blood may contain up to 5% carboxyhemoglo-
tion half-life of phenobarbital but have not been shown bin (10% in smokers).
to alter the clinical course. Hemodialysis is not useful in The most prominent early symptom is headache.
the treatment of poisoning with short-acting barbitu- Other effects include confusion, unsteadiness, and coma.
rates. Analeptics are contraindicated. Proteinuria, glycosuria, elevated serum aminotransferase
levels, or electrocardiogram (ECG) changes may be pre-
Amitai Y, Degani Y: Treatment of phenobarbital poisoning with
sent in the acute phase. Permanent cardiac, liver, renal,
multiple dose activated charcoal in an infant. J Emerg Med or CNS damage occurs occasionally. The outcome of se-
1990;8:449 [PMID: 2212564]. vere poisoning may be complete recovery, vegetative
Cote CJ et al: Adverse sedation events in pediatrics: Analysis of state, or any degree of mental injury between these ex-
medications used for sedation. Pediatrics 2000;4:633 [PMID: tremes. The primary mental deficits are neuropsychiatric.
11015502].
Treatment
BELLADONNA ALKALOIDS The biologic half-life of carbon monoxide on room air
(Atropine, Jimsonweed, Potato is approximately 200–300 minutes; on 100% oxygen, it
Leaves, Scopolamine, Stramonium) is 60–90 minutes. Hyperbaric oxygen therapy at
2–2.5 atm of oxygen shortens the half-life to 30 min-
The effects of anticholinergic compounds include dry utes. After the level has been reduced to near zero, ther-
mouth; thirst; decreased sweating with hot, dry, red apy is aimed at the nonspecific sequelae of anoxia. Dex-
skin; high fever; and tachycardia that may be preceded amethasone, 0.1 mg/kg IV or IM every 4–6 hours,
by bradycardia. The pupils are dilated, and vision is should be added if cerebral edema develops.
blurred. Speech and swallowing may be impaired. Hal-
lucinations, delirium, and coma are common. Leukocy-
Chou KJ: Characteristics and outcome of children with carbon
tosis may occur, confusing the diagnosis. monoxide poisoning with and without smoke exposure re-
Atropinism has been caused by normal doses of at- ferred for hyperbaric oxygen therapy. Ped Emerg Care
ropine or homatropine eye drops, especially in children 2000;3:151 [PMID: 10888449].
 POISONING / 355

Walker AR: Emergency department management of house fire of sodium hypochlorite) are usually not toxic. When
burns and carbon monoxide poisoning in children. Curr sodium hypochlorite comes in contact with acid in the
Opin Pediatr 1996;8:239 [PMID: 8814401].
stomach, hypochlorous acid, which is very irritating to
the mucous membranes and skin, is formed. Rapid in-
CAUSTICS activation of this substance prevents systemic toxicity.
Chlorinated bleaches, when mixed with a strong acid
1. Acids (Hydrochloric, Hydrofluoric, (toilet bowl cleaners) or ammonia, may produce irritat-
Nitric, & Sulfuric Acids; Sodium ing chlorine or chloramine gas, which can cause serious
Bisulfate) lung injury if inhaled in a closed space (eg, bathroom).
Alkalies can burn the skin, mucous membranes, and
Strong acids are commonly found in metal and toilet eyes. Respiratory distress may be due to edema of the
bowl cleaners, batteries, and other products. Hydrofluo- epiglottis, pulmonary edema resulting from inhalation
ric acid is the most toxic and hydrochloric acid the least of fumes, or pneumonia. Mediastinitis or other inter-
toxic of these household substances. However, even a current infections or shock can occur. Perforation of
few drops can be fatal if aspirated into the trachea. the esophagus or stomach is rare.
Painful swallowing, mucous membrane burns,
bloody emesis, abdominal pain, respiratory distress due
to edema of the epiglottis, thirst, shock, and renal fail- Treatment
ure can occur. Coma and convulsions sometimes are The skin and mucous membranes should be cleansed
seen terminally. Residual lesions include esophageal, with copious amounts of water. A local anesthetic can
gastric, and pyloric strictures as well as scars of the be instilled in the eye if necessary to alleviate ble-
cornea, skin, and oropharynx. pharospasm. The eye should be irrigated for at least
Hydrofluoric acid is a particularly dangerous poison. 20–30 minutes. Ophthalmologic consultation should
Dermal exposure creates a penetrating burn that can be obtained for all alkaline eye burns.
progress for hours or days. Large dermal exposure or in- Ingestions should be treated with water as a diluent.
gestion may produce life-threatening hypocalcemia Routine esophagoscopy is no longer indicated to rule
abruptly as well as burn reactions. out burns of the esophagus due to chlorinated bleaches
unless an unusually large amount has been ingested or
Treatment the patient is symptomatic. The absence of oral lesions
does not rule out the possibility of laryngeal or esopha-
Emetics and lavage are contraindicated. Water or milk geal burns following granular alkali ingestion. The use
(< 15 mL/kg) is used to dilute the acid, because a heat- of corticosteroids is controversial, but has not been
producing chemical reaction does not occur. Take care shown to improve long-term outcome except possibly
not to induce emesis by excessive fluid administration. in partial-thickness esophageal burns. Antibiotics may
Alkalies should not be used. Burned areas of the skin, be needed if mediastinitis is likely, but they should not
mucous membranes, or eyes should be washed with co- be used prophylactically. (See Caustic Burns of the
pious amounts of warm water. Opioids for pain may be Esophagus section in Chapter 20).
needed. An endotracheal tube may be required to alle-
viate laryngeal edema. Esophagoscopy should be per- Broto J et al: Conservative treatment of caustic esophageal injuries
formed if the patient has significant burns or difficulty in children: 20 years of experience. Pediatr Surg Int 1999;15:
in swallowing. Acids are likely to produce gastric burns 323 [PMID: 10415278].
or esophageal burns. Evidence is not conclusive, but Hamza AF et al: Caustic esophageal strictures in children: 30 years’
corticosteroids have not proved to be of use. experience. J Pediatr Surg 2003;338:828 [PMID: 12778375].
Hydrofluoric acid burns on skin are treated with Lamireau T et al: Accidental caustic ingestion in children: Is en-
10% calcium gluconate gel or calcium gluconate infu- doscopy always mandatory? J Pediatr Gastroenterol Nutr
2001;33:81 [PMID: 11479413].
sion. Severe exposure may require large doses of IV cal-
cium. Therapy should be guided by calcium levels, the Lovejoy FH Jr: Corrosive injury of the esophagus in children: Fail-
ure of corticosteroid treatment reemphasizes prevention.
ECG, and clinical signs. N Engl J Med 1990;323:668 [PMID: 2385270].

2. Bases (Clinitest Tablets, Clorox, COCAINE

Drano, Liquid-Plumr, Purex, Sani-Clor) Cocaine is absorbed intranasally or via inhalation or in-
Alkalies produce more severe injuries than acids. Some gestion. Effects are noted almost immediately when the
substances, such as Clinitest tablets or Drano, are quite drug is taken intravenously or smoked. Peak effects are
toxic, whereas the chlorinated bleaches (3–6% solutions delayed for about an hour when the drug is taken orally
356 / CHAPTER 12

or nasally. Cocaine prevents the reuptake of endoge- Health and Nutrition Examination Survey. Circulation
nous catecholamines, thereby causing an initial sympa- 2001;103:502 [PMID: 11157713].
thetic discharge, followed by catechol depletion after
chronic abuse. CONTRACEPTIVE PILLS
The only known toxic effects following acute ingestion
Clinical Findings of oral contraceptive agents are nausea, vomiting, and
A local anesthetic and vasoconstrictor, cocaine is also a vaginal bleeding in girls.
potent stimulant to both the CNS and the cardiovascu-
lar system. The initial tachycardia, hyperpnea, hyper- COSMETICS & RELATED PRODUCTS
tension, and stimulation of the CNS are often followed
The relative toxicities of commonly ingested products
by coma, seizures, hypotension, and respiratory depres-
in this group are listed in Table 12–2. Permanent wave
sion. In severe cases of overdose, various dysrhythmias
neutralizers may contain bromates, peroxides, or perbo-
may be seen, including sinus tachycardia, atrial arrhyth-
rates. Bromates have been removed from most products
mias, premature ventricular contractions, bigeminy,
because they can cause nausea, vomiting, abdominal
and ventricular fibrillation. If large doses are taken in-
pain, shock, hemolysis, renal failure, and convulsions.
travenously, cardiac failure, dysrhythmias, rhabdomyol-
Perborates can cause boric acid poisoning. Four grams
ysis, or hyperthermia may result in death.
of bromate salts is potentially lethal.
In addition to those poisoned through recreational
Poisoning is treated by gastric lavage with 1%
use of cocaine, others are at risk of overdose. A “body
sodium thiosulfate followed by demulcents to relieve
stuffer” is one who quickly ingests the drug, usually
gastric irritation. Sodium bicarbonate, 2%, in the
poorly wrapped, to avoid discovery. A “body packer”
lavage fluid may reduce hydrobromic acid formation.
wraps the drug carefully for prolonged transport. A
Sodium thiosulfate, 25%, 1.65 mL/kg, can be given in-
stuffer typically manifests toxicity within hours of in-
travenously, but methylene blue should not be used to
gestion; a packer is asymptomatic unless the package
treat methemoglobinemia in this situation, because it
ruptures, usually days later.
increases the toxicity of bromates. Dialysis is indicated
in renal failure but does not enhance excretion of bro-
Treatment mate.
Except in cases of body stuffers or body packers, decon- Fingernail polish removers used to contain toluene,
tamination is seldom possible. Activated charcoal but now usually have an acetone base, which does not
should be administered, and whole bowel irrigation may require specific treatment other than monitoring CNS
be useful in selected cases. Testing for cocaine in blood status.
or plasma is generally not clinically useful, but a quali- Cobalt, copper, cadmium, iron, lead, nickel, silver,
tative analysis of the urine may aid in confirming the bismuth, and tin are sometimes found in metallic hair
diagnosis. For severe cases, an ECG is indicated. In sus- dyes. In large amounts, they can cause skin sensitiza-
pected cases of body packing, radiographs of the GI
tract may show multiple packets. X-ray films are usually
not helpful for identifying stuffers. Seizures are treated Table 12–2. Relative toxicities of cosmetics
with IV diazepam titrated to response. Hypotension is and similar products.
treated with standard agents. Because cocaine abuse
may deplete norepinephrine, an indirect agent such as
dopamine may be less effective than a direct agent such High toxicity Low toxicity
Permanent wave Perfume
as norepinephrine. Agitation is best treated with a ben-
neutralizers Hair removers
zodiazepine. Deodorants
Moderate toxicity Bath salts
Delaney-Black V: Prenatal cocaine exposure as a risk factor for later Fingernail polish
developmental outcomes. JAMA 2001;286:46 [PMID: Fingernail polish remover No toxicity
11434823].
Metallic hair dyes Liquid makeup
King TA et al: Neurologic manifestations of in utero cocaine expo- Home permanent wave lotion Vegetable hair dye
sure in near-term and term infants. Pediatrics 1995;96:
259 [PMID: 7630680].
Bath oil Cleansing cream
Shaving lotion Hair dressing
Mott SH et al: Neurologic manifestations of cocaine exposure in
childhood. Pediatrics 1994;93:557 [PMID: 8134208].
Hair tonic (alcoholic) (nonalcoholic)
Cologne, toilet water Hand lotion or cream
Qureshi AI et al: Cocaine use and the likelihood of nonfatal myo-
cardial infarction and stroke: Data from the Third National
Lipstick
 POISONING / 357

tion, urticaria, dermatitis, eye damage, vertigo, hyper- producing initial hypertension followed by hypoten-
tension, asthma, methemoglobinemia, tremors, convul- sion. Treatment with physostigmine is contraindicated.
sions, and coma. Treatment for ingestions is to admin- Vasopressors are generally effective. Dopamine is the
ister demulcents and, only with large amounts, the agent of choice because it is readily available. If
appropriate antidote for the heavy metal involved. dopamine is ineffective, norepinephrine (0.1–1 µg/
Home permanent wave lotions, hair straighteners, kg/min, titrated to response) should be added. Diuresis
and hair removers usually contain thioglycolic acid and hemodialysis are not effective.
salts, which cause alkaline irritation and perhaps CNS
depression. Kerr GW et al: Tricyclic antidepressant overdose: A review. Emerg
Shaving lotion, hair tonic, hair straighteners, Med J 2001;18:236 [PMID: 11435353].
cologne, and toilet water contain denatured alcohol, McKinney PE et al: Reversal of severe tricyclic antidepressant-in-
which can cause CNS depression and hypoglycemia. duced cardiotoxicity with intravenous hypertonic saline solu-
Deodorants usually consist of an antibacterial agent tion. Ann Emerg Med 2003;42:20 [PMID: 12827118].
in a cream base. Antiperspirants are aluminum salts,
which frequently cause skin sensitization. Zirconium DIGITALIS & OTHER CARDIAC
oxide can cause granulomas in the axilla with chronic GLYCOSIDES
use.
Toxicity is typically the result of incorrect dosing or un-
recognized renal insufficiency. Clinical features include
CYCLIC ANTIDEPRESSANTS nausea, vomiting, diarrhea, headache, delirium, confu-
Cyclic antidepressants (eg, amitriptyline, imipramine) sion, and, occasionally, coma. Cardiac dysrhythmias
have a very low ratio of toxic to therapeutic doses, and typically involve bradydysrhythmias, but every type of
even a moderate overdose can have serious effects. dysrhythmia has been reported in digitalis intoxication,
Cyclic antidepressant overdosage causes dysrhythmias, including atrial fibrillation, paroxysmal atrial tachycar-
coma, convulsions, hypertension followed by hypoten- dia, and atrial flutter. Death usually is the result of ven-
sion, and hallucinations. These effects may be life- tricular fibrillation. Transplacental intoxication by digi-
threatening and require rapid intervention. One agent, talis has been reported.
amoxapine, differs in that it causes fewer cardiovascular
complications, but it is associated with a higher inci- Treatment
dence of seizures. If vomiting has not occurred, induce emesis or provide
lavage followed by charcoal. Potassium is contraindi-
Treatment cated in acute overdosage unless there is laboratory evi-
dence of hypokalemia. In acute overdosage, hyper-
Decontamination should include gastric lavage and ad- kalemia is more common. Hypokalemia is common in
ministration of activated charcoal. chronic toxicity.
An ECG should be taken in all patients. A QRS in- The patient must be monitored carefully for ECG
terval greater than 100 ms specifically identifies patients changes. The correction of acidosis better demonstrates
at risk to develop dysrhythmias. If dysrhythmias are the degree of potassium deficiency present. Bradycar-
demonstrated, the patient should be admitted and dias have been treated with atropine. Phenytoin, lido-
monitored until free of irregularity for 24 hours. An- caine, magnesium salts (not in renal failure), amio-
other indication for monitoring is persistent tachycar- darone, and bretylium have been used to correct
dia of more than 110 beats/min. The onset of dysrhyth- arrhythmias.
mias is rare beyond 24 hours after ingestion. Definitive treatment is with digoxin immune Fab
Alkalinization with sodium bicarbonate, 0.5–1.0 (ovine) (Digibind). Indications for its use include hy-
mEq/kg IV, or hyperventilation may dramatically re- potension or any dysrhythmia, typically ventricular dys-
verse ventricular dysrhythmias and narrow the QRS in- rhythmias and progressive bradydysrhythmias that pro-
terval. Lidocaine may be added for treatment of ar- duce clinical concern. Elevated T-waves indicated high
rhythmias. Bolus administration of sodium bicarbonate potassium and may be an indication for digoxin im-
is recommended for all patients with QRS widening to mune Fab (Digibind, DigiFab) use. Techniques of de-
above 120 ms and for those with significant dysrhyth- termining dosage and indications related to levels,
mias, to achieve a pH of 7.5–7.6. Forced diuresis is when available are described in product literature.
contraindicated. A benzodiazepine should be given for
convulsions. Woolf AD et al: The use of digoxin-specific Fab fragments for se-
Hypotension is a major problem. Cyclic antidepres- vere digitalis intoxication in children. N Engl J Med
sants block the reuptake of catecholamines, thereby 1992;326:1739 [PMID: 1997016].
358 / CHAPTER 12

DIPHENOXYLATE WITH ATROPINE the renal tubules by acid hematin crystals. Anuria may
(LOMOTIL) persist for 1–2 weeks and still be completely reversible.
Lomotil contains diphenoxylate hydrochloride, a syn- Ostlere L et al: Haemolytic anaemia associated with ingestion of
thetic narcotic, and atropine sulfate. Small amounts are naphthalene-containing anointing oil. Postgrad Med
potentially lethal in children; it is contraindicated in J 1988;64:444 [PMID: 3211822].
children younger than age 2 years. Early signs of intoxi- Siegel E, Wason S: Mothball toxicity. Pediatr Clin North Am
cation with this preparation result from its anticholin- 1986;33:369 [PMID: 3515301].
ergic effect and consist of fever, facial flushing, tachy-
pnea, and lethargy. However, the miotic effect of the 2. p-Dichlorobenzene,
narcotic predominates. Later, hypothermia, increasing Phenolic Acids, & Others
CNS depression, and loss of the facial flush occur.
Seizures are probably secondary to hypoxia. Disinfectants and deodorizers containing p-
dichlorobenzene or sodium sulfate are much less toxic
Treatment than those containing naphthalene. Disinfectants con-
taining phenolic acids are highly toxic, especially if they
Prolonged monitoring (24 hours) with pulse oximetry contain a borate ion. Phenol precipitates tissue proteins
is sufficient in most cases. If respiratory depression oc- and causes respiratory alkalosis followed by metabolic
curs, an airway should be established with an endotra- acidosis. Some phenols cause methemoglobinemia.
cheal tube. Gastric lavage and administration of acti- Local gangrene occurs after prolonged contact with
vated charcoal may be useful because of the prolonged tissue. Phenol is readily absorbed from the GI tract,
delay in gastric emptying time. causing diffuse capillary damage and, in some cases,
Naloxone hydrochloride (0.4–2 mg IV in children methemoglobinemia. Pentachlorophenol, which has
and adults) should be given. A transient improvement been used in terminal rinsing of diapers, has caused in-
in respiration may be followed by respiratory depres- fant fatalities.
sion. Repeated doses may be required because the dura- The toxicity of alkalies, quaternary ammonium
tion of action of diphenoxylate is considerably longer compounds, pine oil, and halogenated disinfectants
than that of naloxone. The anticholinergic effects do varies with the concentration of active ingredients.
not usually require treatment. Wick deodorizers are usually of moderate toxicity.
Iodophor disinfectants are the safest. Spray deodorizers
McCarron MM et al: Diphenoxylate-atropine (Lomotil) overdose are not usually toxic, because a child is not likely to
in children: An update. Pediatrics 1991;87:694 [PMID:
2020516].
swallow a very large dose.
Signs and symptoms of acute quaternary ammo-
nium compound ingestion include diaphoresis, strong
DISINFECTANTS & DEODORIZERS irritation, thirst, vomiting, diarrhea, cyanosis, hyperac-
1. Naphthalene tivity, coma, convulsions, hypotension, abdominal
pain, and pulmonary edema. Acute liver or renal failure
Naphthalene is commonly found in mothballs, disin- may develop later.
fectants, and deodorizers. Naphthalene’s toxicity is
often not fully appreciated. It is absorbed not only Treatment
when ingested but also through the skin and lungs. It is
potentially hazardous to store baby clothes in naphtha- Activated charcoal may be used prior to gastric lavage.
lene, because baby oil is an excellent solvent that may Castor oil dissolves phenol and may retard its absorption.
increase dermal absorption. Note: Most moth balls con- This property of castor oil, however, has not been proved
tain para-dichlorbenzene and not naphthalene—see clinically. Mineral oil and alcohol are contraindicated be-
next section. Metabolic products of naphthalene may cause they increase the gastric absorption of phenol. The
cause severe hemolytic anemia, similar to that due to metabolic acidosis must be managed carefully. Anticon-
primaquine toxicity, 2–7 days after ingestion. Other vulsants or measures to treat shock may be needed.
physical findings include vomiting, diarrhea, jaundice, Because phenols are absorbed through the skin, ex-
oliguria, anuria, coma, and convulsions. The urine may posed areas should be irrigated copiously with water.
contain hemoglobin, protein, and casts. Undiluted polyethylene glycol may be a useful solvent
as well.
Treatment
Mucklow ES: Accidental feeding of dilute antiseptic solution
Induced vomiting should be followed by activated char- (chlorhexidine 0.05% with cetrimide 1%) to five babies.
coal. Urinary alkalinization may prevent blocking of Hum Toxicol 1988;7:567 [PMID: 3229768].
 POISONING / 359

Van Berkel M, de Wolff FA: Survival after acute benzalkonium Litovitz TL, Schmitz BF: Ingestion of cylindrical and button bat-
chloride poisoning. Hum Toxicol 1988;7:191 [PMID: teries: An analysis of 2382 cases. Pediatrics
3378808]. 1992;89:747 [PMID: 2304794].

DISK-SHAPED BATTERIES GAMMA-HYDROXYBUTYRATE,

Small, flat, smooth disk-shaped batteries measure be-
GAMMA-BUTYROLACTONE,
tween 10 and 25 mm in diameter. About 69% of them & BUTANEDIOL
pass through the GI tract in 48 hours and 85% in Gamma-hydroxybutyrate (GHB), γ-butyrolactone
72 hours. Some may become entrapped. These batteries (GBL), and butanediol have become popular drugs of
contain caustic materials and heavy metals. abuse in adolescents and adults. GHB is a CNS depres-
Batteries impacted in the esophagus may cause sant that is structurally similar to the inhibitory neuro-
symptoms of refusal to take food, increased salivation, transmitter γ-aminobutyric acid. GBL and butanediol
vomiting with or without blood, and pain or discom- are converted in the body to GHB. These drugs cause
fort. Aspiration into the trachea may also occur. Fatali- deep but short-lived coma; the coma often lasts only
ties have been reported in association with esophageal 1–4 hours. Treatment consists of supportive care with
perforation. close attention to airway and endotracheal intubation if
When a history of disk battery ingestion is obtained, respiratory depression or decreased gag reflex compli-
radiographs of the entire respiratory tract and GI tract cates the poisoning. Atropine has been used successfully
should be taken so that the battery can be located and for symptomatic bradycardia.
the proper therapy determined. Withdrawal from GHB, GBL, or butanediol can
cause several days of extreme agitation, hallucination,
Treatment or tachycardia. Treatment with high doses of benzodi-
azepines or with butyrophenones (eg, haloperidol or
If the disk battery is located in the esophagus, it must droperidol) or secobarbital may be needed for several
be removed immediately. If the battery has been in the days.
esophagus for more than 24 hours, the risk of caustic
burn is greater. Dyer JE et al: Gamma-hydroxybutyrate withdrawal syndrome. Ann
Location of the disk battery below the esophagus has Emerg Med 2001;37:147 [PMID: 11174231].
been associated with tissue damage, but the course is Sporer KA et al: Gamma-hydroxybutyrate serum levels and clinical
benign in most cases. Perforated Meckel diverticulum syndrome after severe overdose. Ann Emerg Med
has been the major complication. It may take as long as 2003;42:3 [PMID: 12827115].
7 days for spontaneous passage to occur, and lack of
movement in the GI tract may not require removal in HYDROCARBONS (Benzene, Charcoal
an asymptomatic patient. Some researchers have sug- Lighter Fluid, Gasoline, Kerosene,
gested repeated radiographs and surgical intervention if
passage of the battery pauses, but this approach may be Petroleum Distillates, Turpentine)
excessive. Batteries that have opened in the GI tract Ingestion of hydrocarbons may cause irritation of mu-
have been associated with some toxicity due to mer- cous membranes, vomiting, blood-tinged diarrhea, res-
cury, but the patients have recovered. piratory distress, cyanosis, tachycardia, and fever. Al-
Emesis is ineffective. Asymptomatic patients may though a small amount (10 mL) of certain
simply be observed and stools examined for passage of hydrocarbons is potentially fatal, patients have survived
the battery. If the battery has not passed within 7 days ingestion of several ounces of other petroleum distil-
or if the patient becomes symptomatic, radiographs lates. The more aromatic a hydrocarbon is and the
should be repeated. If the battery has come apart or ap- lower its viscosity rating, the more potentially toxic it
pears not to be moving, a purgative, enema, or nonab- is. Benzene, gasoline, kerosene, and red seal oil furni-
sorbable intestinal lavage solution should be adminis- ture polish are the most dangerous. A dose exceeding
tered. If these methods are unsuccessful, surgical 1 mL/kg is likely to cause CNS depression. A history of
intervention may be required. Levels of heavy metals coughing or choking, as well as vomiting, suggests aspi-
(mainly mercury) should be measured in patients in ration with resulting hydrocarbon pneumonia. This is
whom the battery has opened or symptoms have devel- an acute hemorrhagic necrotizing disease that usually
oped. develops within 24 hours of the ingestion and resolves
without sequelae in 3–5 days. However, several weeks
Dane S: A truly emergent problem: Button battery in the nose. may be required for full resolution of a hydrocarbon
Acad Emerg Med 2000;7:204 [PMID: 10691084]. pneumonia. Pneumonia may be caused by the aspira-
360 / CHAPTER 12

tion of a few drops of petroleum distillate into the lung gested amount is more than 400 mg/kg, seizures or
or by absorption from the circulatory system. Pul- CNS depression may occur; therefore, gastric lavage
monary edema and hemorrhage, cardiac dilatation and may be preferred to emesis. Activated charcoal may also
dysrhythmias, hepatosplenomegaly, proteinuria, and be of value. There is no specific antidote. Neither alka-
hematuria can occur following large overdoses. Hypo- linization of the urine nor hemodialysis is helpful.
glycemia is occasionally present. A chest radiograph
may reveal pneumonia within hours after the ingestion. Cuzzolin L et al: NSAID-induced nephrotoxicity from the fetus to
An abnormal urinalysis in a child with a previously nor- the child. Drug Safety 2001;242:9 [PMID: 11219488].
mal urinary tract suggests a large overdose. Hall AH et al: Ibuprofen overdose in adults. J Toxicol Clin Toxicol
1992;30:23 [PMID: 1542147].
Treatment Lesko SM: The safety of ibuprofen suspension in children. Int
J Clin Pract (Supp) 2003;135:50 [PMID: 12723748].
Both emetics and lavage should be avoided when only a Oker EE et al: Serious toxicity in a young child due to ibuprofen.
small amount has been ingested. Mineral oil should not Acad Emerg Med 2000;7:821 [PMID: 10917334].
be given, because it can cause a low-grade lipoid pneu-
monia. INSECT STINGS
Epinephrine should not be used with halogenated
hydrocarbons because it may affect an already sensitized
(Bee, Wasp, & Hornet)
myocardium. The usefulness of corticosteroids is de- Insect stings are painful but not usually dangerous;
bated, and antibiotics should be reserved for patients however, death from anaphylaxis may occur. Bee
with infections. Oxygen and mist are helpful. Extracor- venom has hemolytic, neurotoxic, and histamine-like
poreal membrane oxygenation has been successful in at activities that can on rare occasion cause hemoglobin-
least two cases of failure with standard therapy. uria and severe anaphylactoid reactions. Massive enven-
omation from numerous stings may cause hemolysis,
Anas N et al: Criteria for hospitalizing children who have ingested rhabdomyolysis, and shock leading to multiple organ
products containing hydrocarbons. JAMA 1981;246:840 failure.
[PMID: 7253158].
Bysani GK et al: Treatment of hydrocarbon pneumonitis. High fre-
quency jet ventilation as an alternative to extracorporeal Treatment
membrane oxygenation. Chest 1994;106:300 [PMID: The physician should remove the stinger, taking care
8020296].
not to squeeze the attached venom sac. For allergic re-
Lifshitz M et al: Hydrocarbon poisoning in children: A 5-year ret-
rospective study. Wilderness Environ Med 2003;14:78
actions, epinephrine 1:1000 solution, 0.01 mL/kg,
[PMID: 12825880]. should be administered IV or SQ above the site of the
Lorenc JD: Inhalant abuse in the pediatric populations: A persis- sting. Three to four whiffs from an isoproterenol
tent challenge Cur Opin Ped 2003;15:204 [PMID: aerosol inhaler may be given at 3- to 4-minute intervals
12640280]. as needed. Corticosteroids (hydrocortisone), 100 mg
Sheridan RL: Burns with inhalation injury and petrol aspiration in IV, and diphenhydramine, 1.5 mg/kg IV, are useful an-
adolescents seeking euphoria through hydrocarbon inhala- cillary drugs but have no immediate effect. Ephedrine
tion. Burns 1996;22:566 [PMID: 8909762]. or antihistamines may be used for 2 or 3 days to pre-
vent recurrence of symptoms.
IBUPROFEN A patient who has had a potentially life-threatening
insect sting should be desensitized against the Hy-
Most exposures in children do not produce symptoms. menoptera group, because the honey bee, wasp, hornet,
In one study, for example, children ingesting up to and yellow jacket have common antigens in their
2.4 g remained asymptomatic. When symptoms occur, venom. For the more usual stings, cold compresses, as-
the most common are abdominal pain, vomiting, pirin, and diphenhydramine 1 mg/kg PO, are suffi-
drowsiness, and lethargy. In rare cases, apnea (especially cient.
in young children), seizures, metabolic acidosis, and
CNS depression leading to coma have occurred. Reisman RE, Livingstone A: Late-onset allergic reactions, including
serum sickness after insect stings. J Allergy Clin Immunol
Treatment 1989;84:331 [PMID: 2778239].
Ross RN et al: Effectiveness of specific immunotherapy in the treat-
If a child has ingested less than 100 mg/kg, dilution ment of hymenoptera venom hypersensitivity: A meta-analy-
with water or milk may be all that is necessary to mini- sis. Clin Ther 2000;22:351 [PMID: 10963289].
mize the GI upset. In children, the volume of liquid Vetter RS et al: Mass envenomations by honey bees and wasps.
used for dilution should be less than 4 oz. When the in- West J Med 1999;170:223 [PMID: 10344177].
 POISONING / 361

INSECTICIDES Although all organophosphates act by inhibiting

cholinesterase activity, they vary greatly in their toxic-
The petroleum distillates or other organic solvents used ity. Parathion, for example, is 100 times more toxic
in these products are often as toxic as the insecticide it- than malathion. The toxicity is influenced by the spe-
self. Decontamination may be performed by aspirating cific compound, the type of formulation (liquid or
the stomach with a nasogastric tube. solid), the vehicle, and the route of absorption (lungs,
skin, or GI tract).
1. Chlorinated Hydrocarbons
(eg, Aldrin, Carbinol, Chlordane, Treatment
DDT, Dieldrin, Endrin, Heptachlor, Decontamination of skin, nails, hair, and clothing with
Lindane, Toxaphene) soapy water is extremely important. Atropine plus a
cholinesterase reactivator, pralidoxime, is an antidote
Signs of intoxication include salivation, GI irritability, for organophosphate insecticide poisoning. After assess-
abdominal pain, vomiting, diarrhea, CNS depression, ment and management of the ABCs, atropine should
and convulsions. Inhalation exposure causes irritation be given and repeated every few minutes until airway
of the eyes, nose, and throat; blurred vision; cough; and secretions diminish. An appropriate starting dose of at-
pulmonary edema. ropine is 2–4 mg IV in an adult and 0.05 mg/kg in a
Chlorinated hydrocarbons are absorbed through the child. The patient should receive enough atropine to
skin, respiratory tract, and GI tract. Decontamination stop secretions (mydriasis in not an appropriate stop-
of skin with soap and evacuation of the stomach con- ping point). Severe poisoning may require gram quanti-
tents are critical. All contaminated clothing should be ties of atropine administered over 24 hours.
removed. Castor oil, milk, and other substances con- Because atropine antagonizes the muscarinic
taining fats or oils should not be left in the stomach be- parasympathetic effects of the organophosphates but
cause they increase absorption of the chlorinated hydro- does not affect the nicotinic receptor, it does not im-
carbons. Convulsions should be treated with diazepam, prove muscular weakness. Pralidoxime should also be
0.1–0.3 mg/kg IV. Epinephrine should not be used be- given immediately in more severe cases and repeated
cause it may cause cardiac arrhythmias. every 6–12 hours as needed (25–50 mg/kg diluted to
5% and infused over 5–30 minutes at a rate of no more
than 500 mg/min). Pralidoxime should be used in ad-
2. Organophosphate (Cholinesterase- dition to—not in place of—atropine if red cell
Inhibiting) Insecticides (eg, Chlorthion, cholinesterase is less than 25% of normal. Pralidoxime
Co-Ral, DFP, Diazinon, Malathion, is most useful within 48 hours after the exposure but
Paraoxon, Parathion, Phosdrin, TEPP, has shown some effects 2–6 days later. Morphine, the-
ophylline, aminophylline, succinylcholine, and tran-
Thio-TEPP) quilizers of the reserpine and phenothiazine types are
Dizziness, headache, blurred vision, miosis, tearing, contraindicated. Hyperglycemia is common in severe
salivation, nausea, vomiting, diarrhea, hyperglycemia, poisonings.
cyanosis, sense of constriction of the chest, dyspnea,
sweating, weakness, muscular twitching, convulsions, Eisenstein EM, Amitai Y: Index of suspicion: Case 1. Organophos-
loss of reflexes and sphincter control, and coma can phate intoxication. Pediatr Rev 2000;21:205 [PMID:
occur. 10854316].
The clinical findings are the result of cholinesterase Lifshitz M et al: Carbamate and organophosphate; poisoning in
inhibition, which causes an accumulation of acetyl- young children. Pediatr Emerg Care 1999;15:102 [PMID:
choline. The onset of symptoms occurs within 12 hours 10220078].
of the exposure. Red cell cholinesterase levels should be
measured as soon as possible. (Some normal individuals 3. Carbamates
have a low serum cholinesterase level.) Normal values
vary in different laboratories. In general, a decrease of
(eg, Carbaryl, Sevin, Zectran)
red cell cholinesterase to below 25% of normal indi- Carbamate insecticides are reversible inhibitors of
cates significant exposure. cholinesterase. The signs and symptoms of intoxication
Repeated low-grade exposure may result in sudden, are similar to those associated with organophosphate
acute toxic reactions. This syndrome usually occurs poisoning but are generally less severe. Atropine titrated
after repeated household spraying rather than agricul- to effect is sufficient treatment. Pralidoxime should not
tural exposure. be used with carbaryl poisoning but is of value with
362 / CHAPTER 12

other carbamates. In combined exposures to in patients with renal failure unless dialysis can be used.
organophosphates, give atropine but reserve prali- Institute IV deferoxamine chelation therapy if the pa-
doxime for cases in which the red cell cholinesterase is tient is symptomatic and a serum iron determination
depressed below 25% of normal or marked effects of cannot be obtained readily, or if the peak serum iron
nicotinic receptor stimulation are present. exceeds 400 µg/dL (62.6 µmol/L) at 4–5 hours after in-
gestion.
4. Botanical Insecticides (eg, Black Flag Deferoxamine should not be delayed until serum
iron levels are available in serious cases of poisoning. IV
Bug Killer, Black Leaf CPR Insect Killer, administration is indicated if the patient is in shock, in
Flit Aerosol House & Garden Insect which case it should be given at a dosage of
Killer, French’s Flea Powder, Raid) 15 mg/kg/h. Infusion rates up to 35 mg/kg/h have been
Allergic reactions, asthma-like symptoms, coma, and used in life-threatening poisonings. Rapid IV adminis-
convulsions have been reported. Pyrethrins, allethrin, tration can cause hypotension, facial flushing, urticaria,
and rotenone do not commonly cause signs of toxicity. tachycardia, and shock. Deferoxamine, 90 mg/kg IM
Antihistamines, short-acting barbiturates, and atropine every 8 hours (maximum, 1 g), may be given if IV ac-
are helpful as symptomatic treatment. cess cannot be established, but the procedure is painful.
The indications for discontinuation of deferoxamine
have not been clearly delineated. Generally, it can be
IRON stopped after 12–24 hours if the acidosis has resolved
Five stages of intoxication may occur in iron poisoning: and the patient is improving.
(1) Hemorrhagic gastroenteritis, which occurs Hemodialysis, peritoneal dialysis, or exchange trans-
30–60 minutes after ingestion and may be associated fusion can be used to increase the excretion of the dia-
with shock, acidosis, coagulation defects, and coma. lyzable complex. Urine output should be monitored
This phase usually lasts 4–6 hours. (2) Phase of im- and urine sediment examined for evidence of renal
provement, lasting 2–12 hours, during which patient tubular damage. Initial laboratory studies should in-
looks better. (3) Delayed shock, which may occur clude blood typing and cross-matching; total protein;
12–48 hours after ingestion. Metabolic acidosis, fever, serum iron, sodium, potassium, and chloride; PCO2;
leukocytosis, and coma may also be present. (4) Liver pH; and liver function tests. Serum iron levels fall
damage with hepatic failure. (5) Residual pyloric steno- rapidly even if deferoxamine is not given.
sis, which may develop about 4 weeks after the inges- After the acute episode, liver function studies and an
tion. upper GI series are indicated to rule out residual dam-
Once iron is absorbed from the GI tract, it is not age.
normally eliminated in feces but may be partially ex-
creted in the urine, giving it a red color prior to chela- Black J et al: Child abuse by intentional iron poisoning presenting
tion. A reddish discoloration of the urine suggests a as shock and persistent acidosis. Pediatrics 2003;111:197
serum iron level greater than 350 mg/dL. [PMID: 12509576].
Juurlink DN et al: Iron poisoning in young children: Association
with the birth of a sibling. CMAJ 2003;165:1539 [PMID:
Treatment 12796332].
GI decontamination is based on clinical assessment. Morris CC: Pediatric iron poisonings in the United States. South
Syrup of ipecac may be administered at home, with ap- Med J 2000;93:352 [PMID: 11142463].
propriate follow-up, provided the history does not war-
rant an emergency department visit. The patient should
be referred to a health care facility if symptomatic or if
LEAD
the history indicates toxic amounts. Gastric lavage and Lead poisoning (plumbism) causes vague symptoms,
whole bowel irrigation should be considered in these including weakness, irritability, weight loss, vomiting,
patients. personality changes, ataxia, constipation, headache, and
Shock is treated in the usual manner. Sodium bicar- colicky abdominal pain. Late manifestations consist of
bonate and Fleet Phospho-Soda left in the stomach to retarded development, convulsions, and coma associ-
form the insoluble phosphate or carbonate have not ated with increased intracranial pressure, which is a
shown clinical benefit and have caused lethal hyperna- medical emergency.
tremia or hyperphosphatemia. Deferoxamine, a specific Plumbism usually occurs insidiously in children
chelating agent for iron, is a useful adjunct in the treat- younger than age 5 years. The most likely sources of
ment of severe iron poisoning. It forms a soluble com- lead include flaking leaded paint, artist’s paints, fruit
plex that is excreted in the urine. It is contraindicated tree sprays, solder, brass alloys, home-glazed pottery,
 POISONING / 363

and fumes from burning batteries. Only paint contain- Markowitz M: Lead poisoning. Pediatr Rev 2000;21:327 [PMID:
ing less than 1% lead is safe for interior use (eg, furni- 11010979].
ture, toys). Repetitive ingestions of small amounts of Rogan WJ et al: Exposure to lead in children—How low is low
lead are far more serious than a single massive exposure. enough? N Engl J Med 2003;16:1515 [PMID: 12700370].
Toxic effects are likely to occur if more than 0.5 mg of Rogan WJ et al: Treatment of Lead-Exposed Children Trial
Group: The effect of chelation therapy with succimer on neu-
lead per day is absorbed. ropsychological development in children exposed to lead.
Blood lead levels are used to assess the severity of ex- N Engl J Med 2001;344:1421 [PMID: 11346806].
posure. A complete blood count and serum ferritin
concentration should be obtained; iron deficiency in-
creases absorption of lead. Glycosuria, proteinuria, MUSHROOMS
hematuria, and aminoaciduria occur frequently. Blood Toxic mushrooms are often difficult to distinguish
lead levels usually exceed 80 µg/dL in symptomatic pa- from edible varieties. Contact a poison center to obtain
tients. Abnormal blood lead levels should be repeated identification assistance. Symptoms vary with the
in asymptomatic patients to rule out laboratory error. species ingested, time of year, stage of maturity, quan-
Specimens must be meticulously obtained in acid- tity eaten, method of preparation, and interval since in-
washed containers. A normocytic, slightly hypochromic gestion. A mushroom that is toxic to one individual
anemia with basophilic stippling of the red cells and may not be toxic to another. Drinking alcohol and eat-
reticulocytosis may be present in plumbism. Stippling ing certain mushrooms may cause a reaction similar to
of red blood cells is absent in cases involving only re- that seen with disulfiram and alcohol. Cooking destroys
cent ingestion. some toxins but not the deadly one produced by
The CSF protein is elevated, and the white cell Amanita phalloides, which is responsible for 90% of
count is usually less than 100 cells/mL. CSF pressure deaths due to mushroom poisoning. Mushroom toxins
may be elevated in patients with encephalopathy; lum- are absorbed relatively slowly. Onset of symptoms
bar punctures must be performed cautiously to prevent within 2 hours of ingestion suggests muscarinic toxin,
herniation. whereas a delay of symptoms for 6–48 hours after in-
gestion strongly suggests Amanita (amanitin) poison-
Treatment ing. Patients who have ingested A phalloides may relapse
and die of hepatic or renal failure following initial im-
Standard GI decontamination is indicated if an acute provement.
ingestion has occurred or lead is noted on the abdomi- Mushroom poisoning may produce muscarinic
nal radiograph. Succimer is an orally administered symptoms (salivation, vomiting, diarrhea, cramping ab-
chelator approved for use in children and reported to be dominal pain, tenesmus, miosis, and dyspnea), coma,
as efficacious as calcium edetate. Treatment for blood convulsions, hallucinations, hemolysis, and delayed he-
lead levels of 20–45 µg/dL in children has not been de- patic and renal failure.
termined. Succimer should be initiated at blood lead
levels over 45 µg/dL. The initial dose is 10 mg/kg
(350 mg/m2) every 8 hours for 5 days. The same dose is
Treatment
then given every 12 hours for 14 days. At least 2 weeks Induce vomiting and follow with activated charcoal. If
should elapse between courses. Blood lead levels increase the patient has muscarinic signs, give atropine,
somewhat (ie, rebound) after discontinuation of ther- 0.05 mg/kg IM (0.02 mg/kg in toddlers), and repeat as
apy. Courses of dimercaprol (4 mg/kg/dose) and cal- needed (usually every 30 minutes) to keep the patient
cium edetate may still be used but are no longer the pre- atropinized. Atropine, however, is used only when
ferred method, except in cases of lead encephalopathy. cholinergic effects are present and not for all mush-
Anticonvulsants may be needed. Mannitol or corti- rooms. Hypoglycemia is most likely to occur in patients
costeroids and volume restriction are indicated in pa- with delayed onset of symptoms. Try to identify the
tients with encephalopathy. A high-calcium, high-phos- mushroom if the patient is symptomatic. Consultation
phorus diet and large doses of vitamin D may remove with a certified poison center is recommended. Local
lead from the blood by depositing it in the bones. A botanical gardens, university departments of botany,
public health team should evaluate the source of the and societies of mycologists may be able to help. Sup-
lead. Necessary corrections should be completed before portive care is usually all that is needed; however, in the
the child is returned home. case of A phalloides, penicillin, silibinin, or hemodialysis
may be indicated.
American Academy of Pediatrics Committee on Drugs: Treatment
guidelines for lead exposure in children. Pediatrics 1995;96: Lampe KF, McCann MA: Differential diagnosis of poisoning by
155 [PMID: 7596706]. North American mushrooms, with particular emphasis on
364 / CHAPTER 12

Amanita phalloides-like intoxication. Ann Emerg Med OPIOIDS (Codeine, Heroin,

1987;16:956 [PMID: 3631682].
Michelot D et al: Amanita muscaria: Chemistry, biology, toxicology
Methadone, Morphine,
and ethnomycology. Mycol Res 2003;107:131 [PMID: Propoxyphene)
12747324].
Opioid-related medical problems may include drug ad-
Pawlowska J et al: Liver transplantation in three family members
after Amanita phalloides mushroom poisoning. Transplant diction, withdrawal in a newborn infant, and accidental
Proc 2002;34:3313 [PMID: 12493457]. overdoses. Unlike other narcotics, methadone is ab-
sorbed readily from the GI tract. Most opioids, includ-
ing heroin, methadone, meperidine, morphine, and
NITRITES, NITRATES, ANILINE, codeine, are excreted in the urine within 24 hours and
PENTACHLOROPHENOL, & can be detected readily.
DINITROPHENOL Narcotic-addicted adolescents often have other
medical problems, including cellulitis, abscesses,
Nausea, vertigo, vomiting, cyanosis (methemoglobine-
thrombophlebitis, tetanus, infective endocarditis, HIV
mia), cramping abdominal pain, tachycardia, cardiovas-
infection, tuberculosis, hepatitis, malaria, foreign body
cular collapse, tachypnea, coma, shock, convulsions,
emboli, thrombosis of pulmonary arterioles, diabetes
and death are possible manifestations of nitrite or ni-
mellitus, obstetric complications, nephropathy, and
trate poisoning.
peptic ulcer.
Nitrite and nitrate compounds found in the home
include amyl nitrite, butyl nitrates, isobutyl nitrates, ni-
troglycerin, pentaerythritol tetranitrate, sodium nitrite, Treatment of Overdosage
nitrobenzene, and phenazopyridine. Pentachlorophenol
and dinitrophenol, which are found in wood preserva- Opioids can cause respiratory depression, stridor, coma,
tives, produce methemoglobinemia and high fever be- increased oropharyngeal secretions, sinus bradycardia,
cause of uncoupling of oxidative phosphorylation. and urinary retention. Pulmonary edema rarely occurs
Headache, dizziness, and bradycardia have been re- in children; deaths usually result from aspiration of gas-
ported. High concentrations of nitrites in well water or tric contents, respiratory arrest, and cerebral edema.
spinach have been the most common cause of nitrite- Convulsions may occur with propoxyphene overdosage.
induced methemoglobinemia. Symptoms do not usu- Although suggested doses for naloxone hydrochlo-
ally occur until 15–50% of the hemoglobin has been ride range from 0.01 to 0.1 mg/kg, it is generally un-
converted to methemoglobin. A rapid test is to com- necessary to calculate the dosage on this basis. This ex-
pare a drop of normal blood with the patient’s blood on tremely safe antidote should be given in sufficient
a dry filter paper. Brown discoloration of the patient’s quantity to reverse opioid binding sites. For children
blood indicates a methemoglobin level of more than under age 1 year, 1 ampoule (0.4 mg) should be given
15%. initially; if there is no response, five more ampoules
(2 mg) should be given rapidly. Older children should
Treatment be given 0.4–0.8 mg, followed by 2–4 mg if there is no
response. An improvement in respiratory status may be
Induce vomiting and administer activated charcoal. De- followed by respiratory depression, because the antago-
contaminate affected skin with soap and water. Oxygen nist’s duration of action is less than 1 hour. Neonates
and artificial respiration may be needed. If the blood poisoned in utero may require 10–30 mg/kg to reverse
methemoglobin level exceeds 30%, or if levels cannot the effect.
be obtained and the patient is symptomatic, give a 1%
solution of methylene blue, 0.2 mL/kg IV over
5–10 minutes. Avoid perivascular infiltration, because Withdrawal in the Addict
it causes necrosis of the skin and subcutaneous tissues.
A dramatic change in the degree of cyanosis should Diazepam, 10 mg every 6 hours PO, has been recom-
occur. Transfusion is occasionally necessary. Epineph- mended for the treatment of mild narcotic withdrawal
rine and other vasoconstrictors are contraindicated. If in ambulatory adolescents. Management of withdrawal
reflex bradycardia occurs, atropine should be used. in the confirmed addict may be accomplished with the
administration of clonidine, by substitution with
Herman MI et al: Methylene blue by intraosseous infusion for
methadone, or with reintroduction of the original ad-
methemoglobinemia. Ann Emerg Med 1999;33:111 [PMID: dicting agent, if available through a supervised drug
9867898]. withdrawal program. A tapered course over 3 weeks will
Kennedy N et al: Faulty sausage production causing methaemoglo- accomplish this goal. Death rarely, if ever, occurs. The
binaemia. Arch Dis Child 1997;76:367 [PMID: 9166036]. abrupt discontinuation of narcotics (cold turkey
 POISONING / 365

method) is not recommended and may cause severe prochlorperazine. They are commonly mistaken for
physical withdrawal signs. psychotic episodes.

Withdrawal in the Newborn B. OVERDOSE

A newborn infant in opioid withdrawal is usually small Lethargy and deep prolonged coma commonly occur.
for gestational age and demonstrates yawning, sneezing, Promazine, chlorpromazine, and prochlorperazine are
decreased Moro reflex, hunger but uncoordinated suck- the drugs most likely to cause respiratory depression
ing action, jitteriness, tremor, constant movement, a and precipitous drops in blood pressure. Occasionally,
shrill protracted cry, increased tendon reflexes, convul- paradoxic hyperactivity and extrapyramidal signs as well
sions, vomiting, fever, watery diarrhea, cyanosis, dehy- as hyperglycemia and acetonemia are present. Seizures
dration, vasomotor instability, seizure, and collapse. are uncommon.
The onset of symptoms commonly begins in the first
48 hours but may be delayed as long as 8 days depend- C. NEUROLEPTIC MALIGNANT SYNDROME
ing on the timing of the mother’s last fix and her prede- Neuroleptic malignant syndrome is a rare idiosyncratic
livery medication. The diagnosis can be confirmed eas- complication of phenothiazine use that may be lethal.
ily by identifying the narcotic in the urine of the It is a syndrome involving mental status change (confu-
mother and the baby. sion, coma), motor abnormalities (lead pipe rigidity,
Several treatment methods have been suggested for clonus), and autonomic dysfunction (tachycardia, hy-
narcotic withdrawal in the newborn. Phenobarbital, perpyrexia).
8 mg/kg/d IM or PO in four doses for 4 days and then
reduced by one third every 2 days as signs decrease, may
be continued for as long as 3 weeks. Methadone may be Treatment
necessary in those infants with congenital methadone
addiction who are not controlled in their withdrawal by Extrapyramidal signs are alleviated within minutes by
large doses of phenobarbital. Dosage should be the slow IV administration of diphenhydramine,
0.5 mg/kg/d in two divided doses but can be increased 1–2 mg/kg (maximum, 50 mg), or benztropine mesy-
gradually as needed. After control of the symptoms is late, 1–2 mg IV (1 mg/min). No other treatment is
achieved, the dose may be tapered over 4 weeks. usually indicated.
It is unclear whether prophylactic treatment with Patients with overdoses should receive conservative
these drugs decreases the complication rate. The mor- supportive care. Activated charcoal should be adminis-
tality rate of untreated narcotic withdrawal in the new- tered. Hypotension may be treated with standard
born may be as high as 45%. agents, starting with isotonic saline administration. Agi-
tation is best treated with diazepam. Neuroleptic malig-
American Academy of Pediatrics Committee on Drugs: Naloxone nant syndrome is treated by discontinuing the drug,
dosage and route of administration for infants and children: giving aggressive supportive care, and administering
Addendum to emergency drug doses for infants and children. dantrolene or bromocriptine.
Pediatrics 1990;86:484 [PMID: 2388800].
Traub SJ et al: Pediatric “body packing” Arch Pediatr Adolesc Med
2003;157:174 [PMID: 12580688]. Baker PB et al: Hyperthermia, hypertension, hypertonia, and coma
in massive thioridazine overdose. Am J Emerg Med
1988;6:346 [PMID: 3390252].
PHENOTHIAZINES (Chlorpromazine, Dyer KS et al: Use of phenothiazines as sedatives in children: What
Prochlorperazine, Trifluoperazine) are the risks? Drug Saf 1999;21:81 [PMID: 10456377].
O’Malley GF et al: Olanzapine overdose mimicking opioid intoxi-
Clinical Presentations cation. Ann Emerg Med 1999;34:279 [PMID: 10424936].
A. EXTRAPYRAMIDAL CRISIS
Episodes characterized by torticollis, stiffening of the PLANTS
body, spasticity, poor speech, catatonia, and inability to
communicate although conscious are typical manifesta- Many common ornamental, garden, and wild plants are
tions. These episodes usually last a few seconds to a few potentially toxic. Only in a few cases will small
minutes but have rarely caused death. Extrapyramidal amounts of a plant cause severe illness or death. Table
crises may represent idiosyncratic reactions and are ag- 12–3 lists the most toxic plants, symptoms and signs of
gravated by dehydration. The signs and symptoms poisoning, and treatment. Contact your poison center
occur most often in children who have received for assistance with identification.
366 / CHAPTER 12

Table 12–3. Poisoning due to plants.a

Symptoms and Signs Treatment

Arum family: Caladium, Burning of mucous membranes and airway Accessible areas should be thoroughly
Dieffenbachia, calla lily, dumb- obstruction secondary to edema caused by washed. Corticosteroids relieve airway ob-
cane (oxalic acid) calcium oxalate crystals. struction. Apply cold packs to affected mu-
cous membranes.
Castor bean plant (ricin—a toxalbu- Mucous membrane irritation, nausea, vomit- Fluid and electrolyte monitoring. Saline
min) ing, bloody diarrhea, blurred vision, circula- cathartic. Forced alkaline diuresis will pre-
Jequinty bean (abrin—a toxalbu- tory collapse, acute hemolytic anemia, vent complications due to hemagglutination
min) convulsions, uremia. and hemolysis.
Foxglove, lily of the valley, and ole- Nausea, diarrhea, visual disturbances, and See treatment for digitalis drugs in text.
anderb cardiac irregularities (eg, heart block).
Jimsonweed: See Belladonna Alka- Mydriasis, dry mouth, tachycardia, and hal- Activated charcoal.
loids section in text lucinations.
Larkspur (ajacine, Delphinium, Nausea and vomiting, irritability, muscular Symptomatic. Atropine may be helpful.
delphinine) paralysis, and central nervous system
depression.
Monkshood (aconite) Numbness of mucous membranes, visual Activated charcoal, oxygen. Atropine is
disturbances, tingling, dizziness, tinnitus, probably helpful.
hypotension, bradycardia, and convulsions.
Poison hemlock (coniine) Mydriasis, trembling, dizziness, bradycar- Symptomatic. Oxygen and cardiac monitor-
dia. Central nervous system depression, ing equipment are desirable. Assisted
muscular paralysis, and convulsions. Death respiration is often necessary. Give
is due to respiratory paralysis. anticonvulsants if needed.
Rhododendron (grayanotoxin) Abdominal cramps, vomiting, severe diar- Atropine can prevent bradycardia. Epin-
rhea, muscular paralysis. Central nervous ephrine is contraindicated. Antihyperten-
system and circulatory depression. sives may be needed.
Hypertension with very large doses.
Yellow jessamine (active ingre- Restlessness, convusions, muscular Symptomatic. Because of the relation to
dient, geisemine, is related to paralysis, and respiratory depression. strychnine, activated charcoal and diaze-
strychnine) pam for seizures are worth trying.
a
Many other plants cause minor irritation but are not likely to cause serious problems unless large amounts are ingested. See Lampe KF,
McCann MA: AMA Handbook of Poisonous and Injurious Plants. American Medical Association, 1985. See also Rumack BH, Spoerke DG (eds):
POISINDEX information System. Micromedex, Inc., Denver, CO. [Published quarterly.]
b
Done AK: Ornamental and deadly. Emerg Med 1973;5:255.

PSYCHOTROPIC DRUGS A. STIMULANTS

Psychotropic drugs consist of four general classes: stim- Agitation, euphoria, grandiose feelings, tachycardia, fever,
ulants (amphetamines, cocaine), depressants (eg, nar- abdominal cramps, visual and auditory hallucinations,
cotics, barbiturates), antidepressants and tranquilizers, mydriasis, coma, convulsions, and respiratory depression.
and hallucinogens (eg, LSD, PCP).
B. DEPRESSANTS
Emotional lability, ataxia, diplopia, nystagmus, vertigo,
Clinical Presentations poor accommodation, respiratory depression, coma,
The following clinical findings are commonly seen in apnea, and convulsions. Dilatation of conjunctival blood
patients abusing drugs. See also other entries discussed vessels suggests marijuana ingestion. Narcotics cause mi-
in alphabetic order in this chapter. otic pupils and, occasionally, pulmonary edema.
 POISONING / 367

C. ANTIDEPRESSANTS AND TRANQUILIZERS is not to terminate the drug effect but to help the pa-
Hypotension, lethargy, respiratory depression, coma, tient through the bad experience.
and extrapyramidal reactions. Drug therapy is often unnecessary and may compli-
cate the clinical course of a drug-related panic reaction.
D. HALLUCINOGENS AND PSYCHOACTIVE DRUGS Although phenothiazines have been commonly used to
treat bad trips, they should be avoided if the specific
Belladonna alkaloids cause mydriasis, dry mouth, nau- drug is unknown, because they may enhance toxicity or
sea, vomiting, urinary retention, confusion, disorienta- produce unwanted side effects. Diazepam is the drug of
tion, paranoid delusions, hallucinations, fever, hy- choice if a sedative effect is required. Physical restraints
potension, aggressive behavior, convulsions, and coma. are rarely indicated and usually increase the patient’s
Psychoactive drugs such as LSD cause mydriasis, unex- panic reaction.
plained bizarre behavior, hallucinations, and general- For treatment of life-threatening drug abuse, consult
ized undifferentiated psychotic behavior. the section on the specific drug elsewhere in this chap-
ter and the section on general management at the be-
Management of the Patient ginning of the chapter.
After the acute episode, the physician must decide
Who Abuses Drugs whether psychiatric referral is indicated; in general, pa-
Only a small percentage of the persons using drugs tients who have made suicidal gestures or attempts and
come to the attention of physicians; those who do are adolescents who are not communicating with their
usually experiencing adverse reactions such as panic families should be referred.
states, drug psychoses, homicidal or suicidal thoughts,
or respiratory depression. Dar KJ, McBrien ME: MDMA induced hyperthermia: Report of a
Even with cooperative patients, an accurate history fatality and review of current therapy. Intensive Care Med
is difficult to obtain. A drug history is most easily ob- 1996;22:995 [PMID: 8905441].
tained in a quiet spot by a gentle, nonthreatening, hon- Weir E: Raves: A review of the culture, the drugs and the preven-
est examiner, and without the parents present. The user tion of harm. CMAJ 2000;162:1843 [PMID: 10906922].
often does not really know what drug has been taken or
how much. Street drugs are almost always adulterated
with one or more other compounds. Multiple drugs are
SALICYLATES
often taken together. Friends may be a useful source of The use of childproof containers and publicity regard-
information. ing accidental poisoning have reduced the incidence of
The patient’s general appearance, skin, lymphatics, acute salicylate poisoning. Nevertheless, serious intoxi-
cardiorespiratory status, GI tract, and CNS should be cation still occurs and must be regarded as an emer-
focused on during the physical examination, because gency. In recent years, the frequency of poisoning has
they often provide clues suggesting drug abuse. begun to rise again.
Hallucinogens are not life-threatening unless the pa- Salicylates uncouple oxidative phosphorylation,
tient is frankly homicidal or suicidal. A specific diagno- leading to increased heat production, excessive sweat-
sis is usually not necessary for management; instead, the ing, and dehydration. They also interfere with glucose
presenting signs and symptoms are treated. Does the metabolism and may cause hypoglycemia or hyper-
patient appear intoxicated? In withdrawal? “Flashing glycemia. Respiratory center stimulation occurs early.
back?” Is some illness or injury (eg, head trauma) being Patients usually have signs of hyperventilation,
masked by a drug effect? (Remember that a known sweating, dehydration, and fever. Vomiting and diar-
drug user may still have hallucinations from menin- rhea sometimes occur. In severe cases, disorientation,
goencephalitis.) convulsions, and coma may develop.
The signs and symptoms in a given patient are a The severity of acute intoxication can in some mea-
function not only of the drug and the dose but also of sure be judged by serum salicylate levels. High levels are
the level of acquired tolerance, the “setting,” the pa- always dangerous irrespective of clinical signs, and low
tient’s physical condition and personality traits, the po- levels may be misleading in chronic cases. Other labora-
tentiating effects of other drugs, and many other factors. tory values usually indicate metabolic acidosis despite
A common drug problem is the “bad trip,” which is hyperventilation, low serum K+ values, and often ab-
usually a panic reaction. This is best managed by “talk- normal serum glucose levels.
ing the patient down” and minimizing auditory and vi- In mild and moderate poisoning, stimulation of the
sual stimuli. Allowing the patient to sit with a friend respiratory center produces respiratory alkalosis. In se-
while the drug effect dissipates may be the best treat- vere intoxication (occurring in severe acute ingestion
ment. This may take several hours. The physician’s job with high salicylate levels and in chronic toxicity with
368 / CHAPTER 12

lower levels), respiratory response is unable to overcome SCORPION STINGS

the metabolic overdose.
Once the urine becomes acidic, progressively smaller Scorpion stings are common in arid areas of the south-
amounts of salicylate are excreted. Until this process is western United States. Scorpion venom is more toxic
reversed, the half-life will remain prolonged, because than most snake venoms, but only minute amounts are
metabolism contributes little to the removal of salicy- injected. Although neurologic manifestations may last a
late. week, most clinical signs subside within 24–48 hours.
Chronic severe poisoning may occur as early as The most common scorpions in the United States
3 days after a regimen of salicylate is begun. Findings are Vejovis, Hadrurus, Androctonus, and Centruroides
usually include vomiting, diarrhea, and dehydration. species. Stings by the first three produce edema and
pain. Stings by Centruroides (the Bark scorpion) cause
tingling or burning paresthesias that begin at the site of
the sting; other findings include hypersalivation, rest-
Treatment lessness, muscular fasciculation, abdominal cramps,
opisthotonos, convulsions, urinary incontinence, and
Charcoal binds salicylates well, and, after emesis or respiratory failure.
lavage, it should be given for acute ingestions. Mild
poisoning may require only the administration of oral
fluids and confirmation that the salicylate level is
Treatment
falling. Moderate poisoning involves moderate dehy- Sedation is the primary therapy. Antivenom is reserved
dration and depletion of potassium. Fluids must be ad- for severe poisoning. In severe cases, the airway may be-
ministered at a rate of 2–3 mL/kg/h to correct dehydra- come compromised by secretions and weakness of res-
tion and produce urine with a pH of greater than 7.0. piratory muscles. Endotracheal intubation may be re-
Initial IV solutions should be isotonic, with sodium bi- quired. Patients may require treatment for seizures,
carbonate constituting half the electrolyte content. hypertension, or tachycardia.
Once the patient is rehydrated, the solution can contain The prognosis is good as long as the patient’s airway
more free water and approximately 40 mEq of K+ per is managed appropriately.
liter.
Severe toxicity is marked by major dehydration. Gibly R et al: Continuous intravenous midazolam infusion for
Symptoms may be confused with those of Reye syn- Centruroides exilicauda scorpion envenomation. Ann Emerg
drome, encephalopathy, and metabolic acidosis. Salicy- Med 1999;34:620 [PMID: 10533010].
late levels may even be in the therapeutic range. Major LoVecchio F et al: Incidence of immediate and delayed hypersensi-
fluid correction of dehydration is required. Once this tivity to Centruroides antivenom. Ann Emerg Med
has been accomplished, hypokalemia must be corrected 1999;34:615 [PMID: 10533009].
and sodium bicarbonate given. Usual requirements are
sodium bicarbonate, 1–2 mEq/kg/h over the first SNAKEBITE
6–8 hours, and K+, 20–40 mEq/L. A urine flow of
2–3 mL/kg/h should be established. Despite this treat- Despite the lethal potential of venomous snakes,
ment some patients will develop the paradoxical human morbidity and mortality rates are surprisingly
aciduria of salicylism. This is due to hypokalemia and low. The outcome depends on the size of the child, the
the saving of K+ and excretion of H+ in the renal tubule. site of the bite, the degree of envenomation, the type of
Correction of K+ will allow the urine to become alka- snake, and the effectiveness of treatment.
line and ionize the salicylate, resulting in excretion Nearly all poisonous snakebites in the United States
rather than reabsorption of nonionized salicylate in acid are caused by pit vipers (rattlesnakes, water moccasins,
urine. and copperheads). A few are caused by elapids (coral
Renal failure or pulmonary edema is an indication snakes), and occasional bites occur from cobras and
for dialysis. Hemodialysis is most effective, and peri- other nonindigenous exotic snakes kept as pets. Snake
toneal dialysis relatively ineffective. Hemodialysis venom is a complex mixture of enzymes, peptides, and
should be used in all patients with altered mental status proteins that may have predominantly cytotoxic, neu-
or deteriorating clinical status. Acetazolamide should rotoxic, hemotoxic, or cardiotoxic effects but other ef-
not be used. fects as well. Up to 25% of bites by pit vipers do not re-
sult in venom injection. Pit viper venom causes
predominantly local injury with pain, discoloration,
edema, and hemorrhage.
Yip L et al: Concepts and controversies in salicylate toxicity. Emerg Swelling and pain occur soon after rattlesnake bite
Med Clin North Am 1994;12:351 [PMID: 8187688]. and are a certain indication that envenomation has oc-
 POISONING / 369

curred. During the first few hours, swelling and ecchy- monly causes additional tissue damage. Early physio-
mosis extend proximally from the bite. The bite is often therapy minimizes contractures. In rare cases, fas-
obvious as a double puncture mark surrounded by ec- ciotomy to relieve pressure within muscular compart-
chymosis. Hematemesis, melena, hemoptysis, and other ments is required. The evaluation of function and of
manifestations of coagulopathy develop in severe cases. pulses will better predict the need for fasciotomy. Anti-
Respiratory difficulty and shock are the ultimate causes histamines and corticosteroids (hydrocortisone,
of death. Even in fatal rattlesnake bite, a period of 1 mg/kg, given PO for a week) are useful in the treat-
6–8 hours usually elapses between the bite and death; as ment of serum sickness or anaphylactic shock. Antibi-
a result, there is usually enough time to start effective otics are not needed unless clinical signs of infection
treatment. occur. Tetanus status should be evaluated and the pa-
Coral snake envenomation causes little local pain, tient immunized, if needed.
swelling, or necrosis; and systemic reactions are often
delayed. The signs of coral snake envenomation include Bond GR: Snake, spider, and scorpion envenomation in North
bulbar paralysis, dysphagia, and dysphoria; these signs America. Pediatr Rev 1999;20:147 [PMID: 10233171].
may appear in 5–10 hours and may be followed by total Dart RC, McNally J: Efficacy, safety, and use of snake antivenoms
peripheral paralysis and death in 24 hours. in the United States. Ann Emerg Med 2001;37:181 [PMID:
11174237].

Treatment
SOAPS & DETERGENTS
Children in snake-infested areas should wear boots and
long trousers, should not walk barefoot, and should be 1. Soaps
cautioned not to explore under ledges or in holes. Soap is made from salts of fatty acids. Some toilet soap
A. EMERGENCY (FIRST AID) TREATMENT bars contain both soap and detergent. Ingestion of soap
bars may cause vomiting and diarrhea, but they have a
The most important first aid measure is transportation low toxicity. Induced emesis is unnecessary.
to a medical facility. Splint the affected extremity and
minimize the patient’s motion. Tourniquets and ice
packs are contraindicated. Incision and suction are not 2. Detergents
useful for either crotalid or elapid snake bite. Detergents are nonsoap synthetic products used for
cleaning purposes because of their surfactant properties.
B. DEFINITIVE MEDICAL MANAGEMENT Commercial products include granules, powders, and
Blood should be drawn for hematocrit, clotting time liquids. Dishwasher detergents are very alkaline and can
and platelet function, and serum electrolyte determina- cause caustic burns. Low concentrations of bleaching
tions. Establish two secure IV sites for the administra- and antibacterial agents as well as enzymes are found in
tion of antivenom and other medications. many preparations. The pure compounds are moder-
Specific antivenom is indicated when signs of pro- ately toxic, but the concentration used is too small to
gressive envenomation are present. Two antivenoms are alter the product’s toxicity significantly, although occa-
available for treating pit viper envenomation: polyva- sional primary or allergic irritative phenomena have
lent pit viper antivenom and polyvalent Crotalidae Fab been noted in persons who frequently use such prod-
(CroFab). Both are effective, but their indications dif- ucts and in employees manufacturing these products.
fer. For coral snake bites, an eastern coral snake an-
tivenom (Wyeth Laboratories) is available. Patients Cationic Detergents (Ceepryn, Diaperene,
with pit viper bites should receive antivenom if progres-
sive local injury, coagulopathy, or systemic signs (eg,
Phemerol, Zephiran)
hypotension, confusion) are present. (Antivenom Cationic detergents in dilute solutions (0.5%) cause
should not be given IM or SQ.) See package labeling or mucosal irritation, but higher concentrations (10–15%)
call your certified poison center for details of use. Hem- may cause caustic burns to mucosa. Clinical effects in-
orrhage, pain, and shock diminish rapidly with ade- clude nausea, vomiting, collapse, coma, and convul-
quate amounts of antivenom. For coral snake bites, give sions. As little as 2.25 g of some cationic agents have
three to five vials of antivenom in 250–500 mL of iso- caused death in an adult. In four cases, 100–400 mg/kg
tonic saline solution. An additional three to five vials of benzalkonium chloride caused death. Cationic deter-
may be required. gents are rapidly inactivated by tissues and ordinary
To control pain, administer a narcotic analgesic, soap.
such as meperidine, 0.6–1.5 mg/kg/dose, given PO or Because of the caustic potential and rapid onset of
IM. Cryotherapy is contraindicated because it com- seizures, emesis is not recommended. Activated char-
370 / CHAPTER 12

coal should be administered. Anticonvulsants may be vivors, recovery from the acute phase is generally com-
needed. plete within 3 days. In contrast to popular opinion,
death is extremely rare.
Anionic Detergents Most authors recommend calcium gluconate as ini-
tial therapy (50 mg/kg IV per dose, up to
Most common household detergents are anionic. Laun- 250 mg/kg/24 h), although it is often not effective and
dry compounds have water softener (sodium phos- the effects are of short duration. Methocarbamol
phate) added, which is a strong irritant and may reduce (15 mg/kg PO) or diazepam titrated to effect is useful.
ionized calcium. Anionic detergents irritate the skin by Morphine or barbiturates may occasionally be needed
removing natural oils. Although ingestion causes diar- for control of pain or restlessness, but they increase the
rhea, intestinal distention, and vomiting, no fatalities possibility of respiratory depression. Antivenom is
have been reported. available but should be reserved for severe cases in
The only treatment usually required is to discon- which the above therapies have failed. Local treatment
tinue use if skin irritation occurs and replace fluids and of the bite is not helpful.
electrolytes. Induced vomiting is not indicated follow-
ing ingestion of electric dishwasher detergent, because
of its alkalinity. Dilute with water or milk. Brown Recluse Spider (Violin Spider)
The North American brown recluse spider is most
Nonionic Detergents (Brij Products; commonly seen in the central and Midwestern areas of
Tritons X-45, X-100, X-102, & X-144) the United States. Its bite characteristically produces a
localized reaction with progressively severe pain within
These compounds include lauryl, stearyl, and oleyl al- 24 hours. The initial bleb on an erythematous ischemic
cohols and octyl phenol. They have a minimal irritating base is replaced by a black eschar within 1 week. This
effect on the skin and are almost nontoxic when swal- eschar separates in 2–5 weeks, leaving an ulcer that
lowed. heals slowly. Systemic signs include cyanosis, morbilli-
form rash, fever, chills, malaise, weakness, nausea and
Klasaer AE et al: Marked hypocalcemia and ventricular fibrillation vomiting, joint pains, hemolytic reactions with hemo-
in two pediatric patients exposed to a fluoride-containing
wheel cleaner. Ann Emerg Med 1996;28:713 [PMID:
globinuria, jaundice, and delirium. Fatalities are rare.
8953969]. Fatal disseminated intravascular coagulation has been
Lovejoy FH Jr, Woolf AD: Corrosive ingestions. Pediatr Rev reported.
1995;16:473 [PMID: 8559706]. Although of unproved efficacy, the following thera-
Vincent JC, Sheikh A: Phosphate poisoning by ingestion of clothes pies have been used: dexamethasone, 4 mg IV four
washing liquid and fabric conditioner. Anesthesiology times a day, during the acute phase; polymorphonu-
1998;53:1004 [PMID: 9893545]. clear leukocyte inhibitors, such as dapsone or
colchicine, and oxygen applied to the bite site; and total
SPIDER BITES excision of the lesion to the fascial level.
Most medically important bites in the United States are
caused by the black widow spider (Latrodectus mactans) Clark RF et al: Clinical presentation and treatment of black widow
spider envenomation: A review of 163 cases. Ann Emerg Med
and the North American brown recluse (violin) spider 1992;21:782 [PMID: 1351707].
(Loxosceles reclusa). Positive identification of the spider Sams HH et al: Nineteen documented cases of Loxosceles reclusa en-
is helpful, because many spider bites may mimic those venomation. J Am Acad Dermatol 2001;44:603 [PMID:
of the brown recluse spider. 11260528].

Black Widow Spider

THYROID PREPARATIONS
The black widow spider is endemic to nearly all areas of (Thyroid Desiccated,
the United States. The initial bite causes sharp fleeting
pain. Local and systemic muscular cramping, abdomi-
Sodium Levothyroxine)
nal pain, nausea and vomiting, and shock can occur. Ingestion of the equivalent of 50–150 g of desiccated
Convulsions occur more commonly in small children thyroid can cause signs of hyperthyroidism, including
than in older children. Systemic signs of black widow irritability, mydriasis, hyperpyrexia, tachycardia, and
spider bite may be confused with other causes of acute diarrhea. Maximal clinical effect occurs about 9 days
abdomen. Although paresthesias, nervousness, and after ingestion—several days after the protein-bound
transient muscle spasms may persist for weeks in sur- iodine level has fallen dramatically.
 POISONING / 371

Induce vomiting. If the patient develops clinical hypervitaminosis A and D do occur, however, particu-
signs of toxicity, propranolol, 0.01–0.1 mg/kg (maxi- larly in patients with poor hepatic or renal function.
mum, 1 mg), is useful because of its antiadrenergic ac- The fluoride contained in many multivitamin prepara-
tivity. tions is not a realistic hazard, because a 2- or 3-year-old
child could eat 100 tablets, containing 1 mg of sodium
Brown RS et al: Successful treatment of massive acute thyroid hor- fluoride per tablet, without experiencing serious symp-
mone poisoning with iopanoic acid. J Pediatr 1998;132: toms. Iron poisoning has been reported with multivita-
903 [PMID: 9602214]. min tablets containing iron. Pyridoxine abuse has
Golightly LK et al: Clinical effects of accidental levothyroxine in- caused neuropathies; nicotinic acid, myopathy.
gestion in children. Am J Dis Child 1987;141:1025[PMID:
2887106].
Dean BS, Krenzelok EP: Multiple vitamins and vitamins with iron:
TOXIC ALCOHOLS Accidental poisoning in children. Vet Hum Toxicol 1988;
30:23 [PMID: 3354178].
Ethylene glycol and methanol are the toxic alcohols. Fraser DR: Vitamin D. Lancet 1995;345:104 [PMID: 7815853].
The primary source of ethylene glycol is antifreeze,
while methanol is present in windshield wiper fluid and
also as an ethanol denaturant. Ethylene glycol causes se- WARFARIN
vere metabolic acidosis and renal failure. Methanol
causes metabolic acidosis and blindness. Onset of Warfarin is used as a rodenticide. It causes hypopro-
symptoms with both agents occurs within several hours thrombinemia and capillary injury. It is absorbed read-
after ingestion, longer if ethanol was ingested simulta- ily from the GI tract but is absorbed poorly through the
neously. skin. A dose of 0.5 mg/kg of warfarin may be toxic in a
child. A prothrombin time is helpful in establishing the
severity of the poisoning.
Treatment If bleeding occurs or the prothrombin time is pro-
The primary treatment is to block the enzyme alcohol longed, give 1–5 mg of vitamin K1 (phytonadione) IM
dehydrogenase which converts both agents to their or SQ. For large ingestions with established toxicity,
toxic metabolites. This is accomplished with fomepi- 0.6 mg/kg may be given.
zole (loading dose of 15 mg/kg) or ethanol. Fomepizole Another group of long-acting anticoagulant rodenti-
is preferred for children, due to its reduced side effects cides (brodifacoum, difenacoum, bromadiolone, dipha-
in this age group. cinone, pinone, valone, and coumatetralyl) have been a
more serious toxicologic problem than warfarin. They
Barceloux DG et al: American Academy of Clinical Toxicology also cause hypoprothrombinemia and a bleeding
Practice Guidelines on the Treatment of Methanol Poison- diathesis that responds to phytonadione, although the
ing. J Toxicol Clin Toxicol 2002;40:415 [PMID: anticoagulant activity may persist for periods ranging
12216995]. from 6 weeks to several months. Treatment with vita-
Brent J et al: Fomepizole for the treatment of ethylene glycol poi- min K1 may be needed for weeks.
soning: Methylpyrazole for toxic alcohols study group.
N Engl J Med 1999;40:832 [PMID: 10080845].
Isbister GK, Whyte IM: Management of anticoagulant poisoning.
VITAMINS Vet Hum Toxicol 2001;43:117 [PMID: 11308119].
Mullins ME et al: Unintentional pediatric superwarfarin exposures:
Accidental ingestion of excessive amounts of vitamins Do we really need a prothrombin time? Pediatrics 2000;105:
rarely causes significant problems. Occasional cases of 402 [PMID: 10654963].
 Critical Care 13
Todd C. Carpenter, MD, Emily L. Dobyns, MD, Stephanie N. Mateev, MD,
Peter M. Mourani, MD, Margaret A. Ferguson, MD, & Kurt R. Stenmark, MD

Caring for critically ill children remains one of the most costs and length of stay. These findings suggest that pe-
demanding and challenging aspects of the field of pedi- diatric critical care services are relatively cost-effective
atrics. The care of patients with life-threatening condi- compared with similar services provided to adult pa-
tions, from serious medical illness to traumatic injuries tients. Along with the preceding discussion of the in-
and recovery from major surgery, requires a detailed tensivist’s role in ICU practice, the findings of these
understanding of the physiology of the body and the studies serve to highlight the complexities of this grow-
pathophysiology of major illnesses, as well as an under- ing field, as well as the key role of the ICU specialist in
standing of and experience with the rapidly changing caring for the sickest children.
technologies available in a modern intensive care unit
(ICU). In addition, the science of caring for the criti- Brilli RJ et al: Critical care delivery in the intensive care unit:
cally ill patient has evolved rapidly over the last decade, Defining clinical roles and the best practice model. Crit Care
as the molecular mediators of illness have become bet- Med 2001;29(10):2007 [PMID: 11588472].
ter defined and new therapies have been devised based Pollack MM et al: Impact of quality of care factors on pediatric in-
on those advances. As a result, critical care is more than tensive care unit mortality. JAMA 1994;272(12):941 [PMID:
ever a multidisciplinary field that requires a team-ori- 8084061].
ented approach, including critical care physicians and Seferian EG et al: Comparison of resource utilization and outcome
between pediatric and adult intensive care unit patients. Pedi-
nursing staff, pharmacists, referring physicians, consult- atr Crit Care Med 2001;2:2 [PMID: 12797880].
ing specialists, and social services specialists. Tilford JM et al: Volume-outcome relationships in pediatric inten-
The intensivist plays an essential role in coordinat- sive care units. Pediatr 2000;106:289 [PMID: 10920153].
ing and directing the care provided by the ICU team, Young MP, Birkmeyer JD: Potential reduction in mortality rates
and in so doing stands at the crossroads of the various using an intensivist model to manage intensive care units. Eff
participating disciplines. There are two primary models Clin Pract 2000;3(6):284 [PMID: 11151525].
of ICU organization: “open” units, where primary re-
sponsibility for the patient remains with the referring
physician and secondary responsibility lies with the in-
ACUTE RESPIRATORY FAILURE
tensivist as consultant; and “closed” units, where only Acute respiratory failure, defined as the inability of the
the on-site intensivist is allowed to write orders direct- respiratory system to adequately deliver oxygen or re-
ing the patient’s care. Although the merits of both of move CO2, contributes significantly to the morbidity
these organizational approaches are debated, a substan- and mortality of critically ill children. This condition
tial and growing body of evidence from studies con- accounts for approximately 50% of deaths in children
ducted in adult medical, surgical, and pediatric ICUs younger than age 1 year. Anatomic and developmental
suggests that the closed ICU model may lead to signifi- differences place infants at higher risk than adults for
cant reductions in ICU length of stay and resource use, respiratory failure. An infant’s thoracic cage is more
as well as to reductions in mortality of as much as 15%. compliant than that of the adult or older child. The in-
An additional factor to consider in the provision of tercostal muscles are poorly developed and unable to
critical care services for children is the cost of those ser- achieve the “bucket handle” motion characteristic of
vices in relation to the outcomes achieved. Critical care adult breathing. Furthermore, the diaphragm is shorter,
services in the United States are estimated to account relatively flat with fewer type I muscle fibers, and there-
for 30% of all acute-care hospital costs; some estimates fore less effective and more easily fatigued. The infant’s
run as high as 1% of the gross national product. One airways are smaller in caliber than those in older chil-
study has examined the cost-effectiveness of pediatric dren and adults, resulting in greater resistance to inspi-
ICU care compared with adult ICU care. Those inves- ratory and expiratory airflow and greater susceptibility
tigators found that the short- and long-term mortality to occlusion by mucus plugging and mucosal edema.
among pediatric patients was three times lower than it Compared with adults, the alveoli of children are
was among adult ICU patients, despite similar ICU smaller and have less collateral ventilation, resulting in
372
Copyright © 2005, 2001, by The McGraw-Hill Companies, Inc. Click here for terms of use.
 CRITICAL CARE / 373

a greater tendency to collapse and develop atelectasis. Clinical Findings

Finally, young infants may have an especially reactive
pulmonary vascular bed, impaired immune system, or A. SYMPTOMS AND SIGNS
residual effects from prematurity, all of which increase The clinical findings in respiratory failure are caused by
the risk of respiratory failure. the low PaO2, high PaCO2, and pH changes affecting
Respiratory failure can be classified into two types, the lungs, heart, kidneys, and brain. The clinical fea-
which usually coexist in variable proportion. The PaO2 tures of progressive respiratory failure are summarized
is low in both, whereas the PaCO2 is high only in pa- in Table 13–2. Hypercapnia depresses the CNS, and
tients with type II respiratory failure (Table 13–1). also results in acidemia that depresses myocardial func-
Type I respiratory failure is a failure of oxygenation and tion. Patients in respiratory failure can exhibit signifi-
occurs in three situations: (1) ventilation–perfusion cant changes in CNS and cardiac function. Features of
mismatch, or V/Q mismatch, which occurs when respiratory failure are not always clinically evident,
blood flows to parts of the lung that are inadequately however, and some signs or symptoms may have non-
ventilated, or when ventilated areas of the lung are in- respiratory causes. Furthermore, a strictly clinical assess-
adequately perfused; (2) diffusion defects, caused by ment of arterial hypoxemia or hypercapnia is not reli-
thickened alveolar membranes or excessive interstitial able. As a result, the precise assessment of the adequacy
fluid at the alveolar–capillary junction; and (3) intra- of oxygenation and ventilation must be based on both
pulmonary shunt, which occurs when structural clinical and laboratory data.
anomalies in the lung allow blood to flow through the
lung without participating in gas exchange. Type II res- B. LABORATORY FINDINGS
piratory failure generally results from alveolar hypoven- Laboratory findings are helpful in assessing the severity
tilation and is usually secondary to situations such as and acuity of respiratory failure and in determining spe-
central nervous system (CNS) dysfunction, overseda- cific treatment. Arterial oxygen saturation can be mea-
tion, or neuromuscular disorders (see Table 13–1). sured continuously and noninvasively by pulse oxime-
try, a technique that should be used in the assessment
and treatment of all patients with suspected respiratory
failure. End-tidal CO2 monitoring provides a continu-
ous noninvasive means of assessing arterial pCO2. Be-
Table 13–1. Types of respiratory failure. cause carbon dioxide diffuses freely across the alveo-

Findings Causes Examples Table 13–2. Clinical features of

Type I Ventilation/per- Positional (supine in respiratory failure.
Hypoxia fusion defect bed), adult respiratory
Decreased PaO2 distress syndrome
Respiratory
Normal PaCO2 (ARDS), atelectasis,
Wheezing
pneumonia, pul-
Expiratory grunting
monary embolus,
Decreased or absent breath sounds
bronchopulmonary
Flaring of alae nasi
dysplasia
Retractions of chest wall
Diffusion Pulmonary edema, Tachypnea, bradypnea, or apnea
impairment ARDS, interstitial Cyanosis
pneumonia Neurologic
Restlessness
Shunt Pulmonary arterio-
Irritability
venous malformation,
Headache
congenital adeno-
Confusion
matoid malformation
Convulsions
Type II Hypoventilation Neuromuscular dis- Coma
Hypoxia ease (polio, Guillain– Cardiac
Hypercapnia Barré syndrome), Bradycardia or excessive tachycardia
Decreased PaO2 head trauma, sedation, Hypotension or hypertension
Increased PaCO2 chest wall dysfunction General
(burns), kyphosis, se- Fatigue
vere reactive airways Sweating
374 / CHAPTER 13

lar–capillary barrier, the exhaled end-tidal CO2 A–a gradient is less than 15 mm Hg under normal con-
(ETCO2) level approximates the alveolar PCO2, which ditions, though it widens with increasing inspired oxy-
should equal the arterial PCO2. Though useful for fol- gen concentrations, to about 100 mm Hg in normal
lowing trends in ventilation, this technique is suscepti- patients breathing 100% oxygen. This number has
ble to significant error, particularly with patients who prognostic value in severe hypoxemic respiratory fail-
have rapid, shallow breathing or increased dead space ure, with A–a gradients over 400 mm Hg being
ventilation. Arterial blood gas (ABG) analysis re- strongly associated with mortality. Diffusion impair-
mains the gold standard for assessment of acute respira- ment, shunts, and V/Q mismatch all increase the
tory failure. ABGs give information on the patient’s A–aDO2 (Table 13–3).
acid–base status (with a measured pH and calculated In addition to the calculation of the A–aDO2, assess-
bicarbonate level) as well as PaO and PaCO2 levels. The ment of intrapulmonary shunting (the percentage of
PaO2 is a critical determinant of oxygen delivery to the pulmonary blood flow that passes through nonventi-
tissues, and the PaCO2 is a sensitive measure of ventila- lated areas of the lung) may be helpful. Normal individ-
tion related inversely to the minute ventilation (Figure uals have less than a 5% physiologic shunt from
13–1). Although measurement of capillary or venous bronchial, thebesian, and coronary circulations. Shunt
blood gases may provide some reassurance regarding fractions greater than 15% usually indicate the need for
ventilatory function if blood gas results are normal, aggressive respiratory support. When intrapulmonary
these tests yield virtually no useful information regard- shunt reaches 50% of pulmonary blood flow, PaO2 does
ing oxygenation and may generate highly misleading not increase regardless of the amount of supplemental
information about the ventilatory status of patients oxygen used.
who have poor perfusion or who had blood draws that
were difficult. As a result, ABG analysis is important for Treatment
all patients with suspected respiratory failure, particu-
larly those with abnormal venous or capillary gases. A. OXYGEN SUPPLEMENTATION
Knowing the ABG values and the inspired oxygen Patients with hypoxemia induced by respiratory failure
concentration also enables one to calculate the differ- may respond to supplemental oxygen administration
ence between alveolar oxygen concentration and the ar- alone (Table 13–4). Those with hypoventilation and
terial oxygen value, known as the alveolar–arterial diffusion defects respond better than do patients with
oxygen difference (A–aDO2, or A–a gradient). The shunts or V/Q mismatch. Severe V/Q mismatch gener-
ally responds only to aggressive airway management
and mechanical ventilation. Patients with severe hypox-
emia, hypoventilation, or apnea require assistance with
140 bag and mask ventilation until the airway is successfully
intubated and controlled artificial ventilation can be
120 PaO2 provided. Ventilation may be maintained for some time
Saturation (percent) or mm Hg

with a mask of the proper size, but gastric distention,

100 emesis, and inadequate tidal volumes are possible com-
SaO2
plications. An artificial airway may be lifesaving for pa-
80 tients who fail to respond to simple oxygen supple-
ments.
60
B. INTUBATION
40
Intubation of the trachea in infants and children re-
quires experienced personnel and the right equipment.
20 PaCO2 A patient in respiratory failure whose airway must be
0 stabilized should first be positioned properly to facili-
0 0.25 0.5 1 2 3 tate air exchange while supplemental oxygen is given.
Relative alveolar ventilation The sniffing position is used in infants. Head extension
with jaw thrust is used in older children without neck
Figure 13–1. Relationship between alveolar ventila- injuries. If obstructed by secretions or vomitus, the air-
tion, arterial oxygen saturation (SaO2), and partial pres- way must be cleared by suction. When not obstructed,
sures of oxygen and CO2 in the arterial blood (PaO2 and the airway should open easily with proper positioning
PaCO2, respectively). (Reproduced, with permission, from and placement of an oral or nasopharyngeal airway of
Pagtakhan RD, Chernick V: Respiratory failure in the pedi- the correct size. Patients with a normal airway may be
atric patient. Pediatr Rev 1982;3:244.) intubated under intravenous (IV) anesthesia by experi-
 CRITICAL CARE / 375

Table 13–3. Key equations describing pulmonary function and

oxygen delivery.

PiO2 = (barometric pressure − 47) × % inspired oxygen concentration

AaDO2 = PiO2 − (PaCO2/R) − PaO2 (normal = 5–15 mm Hg)
CO2 = (1.34 × hemoglobin × SaO2) + (0.003 × PaO2)
DO2 = CaO2 × CI × 10 (normal 620 + 50 mL/min/m2)
Oxygen consumption (VO2) = (CaO2 − CvO2) × CI × 10 (normal 120–200 mL/min/m2)
CCO2 − CaO2
Qs = (normal < 5%)
Qt CCO2 − CvO2
(PaCO2 − PeCO2 )
Vd = (normal approximately 2 mL/kg)
PcCO2
Volume (tidal volume)
Compliance = (normals vary with age)
Pressure (PIP − PEEP)
A–aDO2 = Alveolar–arterial oxygen difference (mm Hg)
CaO2 = Oxygen content of arterial blood (mL/dL)
CcO2 = Oxygen content of pulmonary capillary blood (mL/dL)
CI = Cardiac index (L/min)
CO2 = Oxygen content of the blood (mL/dL)
CvO2 = Oxygen content of mixed venous blood (mL/dL)
DO2 = Oxygen delivery (mL/min)
PaCO2 = Partial pressure of carbon dioxide in arterial blood (mm Hg)
PaO2 = Partial pressure of oxygen in arterial blood (mm Hg)
PcCO2 = Partial pressure of carbon dioxide in capillary blood (mm Hg)
PeCO2 = Partial pressure of carbon dioxide in expired air (mm Hg)
PiO2 = Partial pressure of oxygen in inspired air (mm Hg)
PIP = Peak inspiratory pressure
Qs/Qt = Intrapulmonary shunt (in patients without cardiac shunt) (%)
R = Respiratory quotient (usually 0.8)
SaO2 = Arterial oxygen saturation (fractional)
Vd = Physiologic dead space (anatomic dead space + alveolar dead
space) (mL)
Ve = Expiratory minute volume (L/min)
VO2 = Oxygen consumption per minute

enced personnel (Table 13–5). Patients with obstructed ing the correct size of endotracheal tube for a child are
upper airways (eg, patients with croup, epiglottitis, for- (1) measuring the child’s height with a Broselow tape
eign bodies, or subglottic stenosis) should be awake and then reading the corresponding endotracheal tube
when intubated unless trained airway specialists decide size on the tape, or (2) in children older than age
otherwise. 2 years, choosing a tube size equal to the simple com-
The size of the endotracheal tube is of critical im- putation (16 + age in years) ÷ 4.
portance in pediatrics (see Table 11–3 for sizes). An in- Correct placement of the endotracheal tube should
appropriately large endotracheal tube can cause pressure be confirmed by auscultation for the presence of equal
necrosis of the tissues in the subglottic region, leading bilateral breath sounds and if using a colorimetric filter
in some cases to scarring and permanent stenosis of the (pH-sensitive indicator that changes from purple to yel-
subglottic region that can require surgical repair. An in- low when exposed to carbon dioxide) by the detection
appropriately small endotracheal tube can result in in- of carbon dioxide. An assessment of air leakage around
adequate pulmonary toilet and excessive air leak around the endotracheal tube is also important. To do this,
the endotracheal tube, making optimal ventilation and connect an anesthesia bag and pressure manometer to
oxygenation difficult. Two useful methods for calculat- the endotracheal tube and allow it to inflate, creating
376 / CHAPTER 13

Table 13–4. Supplemental oxygen therapy.

Maximum % Range of
Source O2 Rates Advantages Disadvantages
Nasal cannula 35–40% 0.125–4 L/min Easily applied, relatively com- Uncomfortable at higher flow rates, requires
fortable open nasal airways, easily dislodged, lower
% O2, nosebleeds
Simple mask 50–60% 5–10 L/min Higher % O2, good for mouth Uncomfortable, dangerous for patients with
breathers poor airway control and at risk for emesis,
hard to give airway care, unsure of % O2
Face tent 40–60% 8–10 L/min Higher % O2, good for mouth Uncomfortable, dangerous for patients with
breathers, less restrictive poor airway control and at risk for emesis,
hard to give airway care, unsure of % O2
Rebreathing mask 80–90% 5–10 L/min Higher % O2, good for mouth Uncomfortable, dangerous for patients with
breathers, highest O2 concen- poor airway control and at risk for emesis,
tration hard to give airway care, unsure of % O2
Oxyhood 90–100% 5–10 L/min Stable and accurate O2 con- Difficult to maintain temperature, hard to
(mixed at wall) centration give airway care

Table 13–5. Drugs commonly used for controlled intubation.

Drug Class of Agent Dose Advantages Disadvantages

Atropine Anticholinergic 0.02 mg/kg, Prevents Tachycardia, fever; seizures and coma with high doses
minimum bradycardia, dries
of 0.1 mg secretions
Fentanyl Narcotic (sedative) 1–3 µg/kg Rapid onset, Respiratory depression, chest wall rigidity with rapid
IV hemodynamic administration in neonates
stability
Midazolam Benzodiazepine 0.1–0.2 Rapid onset, Respiratory depression, hypotension
(sedative) mg/kg IV amnestic
Thiopental Barbiturate 3–5 mg/kg Rapid onset, lowers Hypotension, decreased cardiac output, no analgesia
(anesthetic) IV intracranial provided
pressure
Ketamine Dissociative 1–2 mg/kg Rapid onset, Increases oral and airway secretions, may increase ICP
anesthetic IV bronchodilator, and pulmonary artery pressure
2–4 mg/kg hemodynamic
IM stability
Rocuronium Nondepolarizing 1 mg/kg Rapid onset, Requires refrigeration
muscle relaxant suitable for rapid
sequence
intubation, lasts 30
minutes
Pancuronium Nondepolarizing 0.1 mg/kg Longer duration of Tachycardia, slow onset (2–3 min)
muscle relaxant action (40–60 min)
IV = intravenously, IM = intramuscularly.
 CRITICAL CARE / 377

positive pressure. Check for the leak by auscultating choices in tailoring a mode of mechanical ventilation to
over the throat, noting the pressure at which air escapes particular clinical scenarios. This section will describe
around the endotracheal tube. Leaks at pressures of the modes of mechanical ventilation most commonly
15–20 cm H2O are acceptable. Leaks at lower pressures used in pediatric intensive care units.
may lead to ineffective ventilation, and the endotra-
cheal tube should be upsized if continued mechanical
ventilation is needed. Leaks at higher pressures are ac-
Pressure Ventilation
ceptable only with patients who have severe lung dis- In pressure-controlled modes of ventilation, air flow is
ease and poor compliance and who thus require high begun at the start of the inspiratory cycle and continues
pressures to ventilate and oxygenate. A chest radiograph until a preset airway pressure is reached. That airway
is necessary for final assessment of endotracheal tube pressure is then maintained until, at the end of the set
placement. inspiratory time, the exhalation valve on the ventilator
opens and gas exits into the machine. Because airway
Artigas A et al: The American-European Consensus Conference on pressure is the controlling variable with this mode of
ARDs, Part 2. Am J Respir Crit Care Med 1998;157:1332 ventilation, changes in the compliance of the respira-
[PMID: 9563759]. tory system will lead to fluctuations in the actual tidal
Bateman ST, Arnold JH: Acute respiratory failure in children. Curr volume delivered to the patient. The advantage of pres-
Opin Pediatr 2000;12(3):233 [PMID: 10836159]. sure-controlled ventilation lies primarily in the avoid-
Green KE, Peters JI: Pathophysiology of acute respiratory failure. ance of high airway pressures that might cause lung in-
Clin Chest Med 1994;15:1 [PMID: 8200186]. jury or barotrauma, particularly in those patients with
Hedenstierna G, Lattuada M: Gas exchange in the ventilated pa- fragile lung parenchyma, such as premature infants.
tient. Curr Opin Crit Care 2002;8:39 [PMID: 12205405]. The main disadvantage of pressure-controlled ventila-
Sagarin MJ et al; National Emergency Airway Registry (NEAR) in- tion is the possibility of delivering either inadequate or
vestigators: Pediatr Emerg Care 2002;18:417 [PMID: excessive tidal volumes during periods of changing lung
12488834].
compliance, as described earlier.
Shapiro MB et al: Respiratory failure. Conventional and high-tech
support. Surg Clin North Am 2000;80(3):871 [PMID:
10897266]. Volume Ventilation
Sigillito RJ, DeBlieux PM: Evaluation and initial management of
the patient in respiratory distress. Emerg Med Clin North Volume-controlled ventilation is the most commonly
Am 2003;21:239 [PMID: 12793613]. used mode of mechanical ventilation in most pediatric
Weiss IK et al: Clinical use of continuous arterial blood gas moni- intensive care units (PICUs). In contrast to pressure-
toring in the pediatric intensive care unit. Pediatrics controlled modes, volume ventilation delivers a preset
1999;103:440 [PMID: 9925838]. tidal volume to the patient. Changes in lung compli-
ance will lead to fluctuations in the airway pressure gen-
erated by the tidal volume. The main advantage of vol-
MECHANICAL VENTILATION ume ventilation is more reliable delivery of the desired
The increased compliance of an infant’s chest wall, the tidal volume and thus better control of ventilation.
relative alveolar hypoplasia in early childhood, the small More reliable tidal volume delivery may also help pre-
caliber of the airways, and the small tidal volumes of vent atelectasis from hypoventilation. Disadvantages of
young children make mechanical ventilation of the pe- volume ventilation include the risk of barotrauma from
diatric patient challenging. The goals of mechanical excessive airway pressures and difficulties overcoming
ventilation are to facilitate the movement of gas into leaks in the ventilator circuit. Older volume ventilators
and out of the lungs (ventilation) and to improve oxy- also suffered from a lack of continuous gas flow
gen uptake into the bloodstream (oxygenation). Mod- through the circuit, thus increasing the patient’s work
ern mechanical ventilators can accomplish these objec- of breathing on spontaneous breaths. Most modern
tives in a variety of ways. Depending on the mode of machines have overcome that problem by providing a
ventilation selected, the ventilator can deliver a ma- continuous flow through the circuit and by improved
chine-controlled breath (control ventilation), or can as- triggering mechanisms to deliver the breaths in syn-
sist the patient’s own spontaneous respiratory efforts chrony with the patient’s demands.
(support ventilation), or can do both (mixed mode ven-
tilation). Additionally, ventilator breaths can be deliv- Modes of Ventilation
ered as a targeted tidal volume (volume ventilation) or
as a targeted airway pressure (pressure ventilation). On- Most modern ventilators can deliver either a pressure-
going advances in microprocessor control and ventila- controlled or a volume-controlled breath in several
tor design give the clinician increasingly complex manners. Assist-control modes deliver breaths at a se-
378 / CHAPTER 13

lected rate and duration (inspiratory time) and can be tors open their expiratory limbs at the end of inspira-
targeted for either volume or pressure set by the clini- tion until a preset pressure is achieved; this is the PEEP
cian (as opposed to the patient). Spontaneous breaths value. During ventilation of normal lungs, physiologic
are not assisted, and the patient’s own respiratory ef- PEEP is in the range of 2–4 cm H2O pressure. This
forts are not considered. Synchronized intermittent pressure helps to prevent the end-expiratory collapse of
mandatory ventilation (SIMV) is a mode in which the open lung units, thus preventing atelectasis and shunt-
rate, inspiratory time, and volume or pressure settings ing. In disease states such as pulmonary edema, pneu-
are set by the clinician. But the ventilator allows a win- monia, or acute respiratory distress syndrome (ARDS),
dow of time around each breath in which it waits for a higher PEEP may increase the patient’s functional
the patient to make an inspiratory effort. The machine residual capacity (FRC), open previously collapsed alve-
breath is then synchronized with the patient’s effort, to oli, increase mean airway pressure, and improve oxy-
improve the comfort of those who are breathing spon- genation. High levels of PEEP, although often valuable
taneously. In pressure support, the patient’s own ef- in improving oxygenation, may also cause CO2 reten-
forts are assisted by the delivery of gas flow to achieve a tion, barotrauma with resultant air leaks, decreased cen-
certain airway pressure. This mode of ventilation allows tral venous return and thus decreased cardiac output,
the patient to determine the rate and inspiratory time and increased intracranial pressure (ICP). In general,
of breaths, thus improving patient comfort and decreas- PEEP should be set at 3–5 cm H2O initially and
ing the work of breathing. Perhaps the most common titrated up to maintain adequate oxygenation at an ac-
mode of ventilation in PICUs is SIMV with pressure ceptable fractional inspiratory oxygen (FiO2), while
support, a mixed mode allowing pressure-supported watching carefully for the adverse effects listed earlier.
breaths between the synchronized machine breaths.
Whether such mixed modes of ventilation provide any
measurable advantage over single modes remains un-
Monitoring the Ventilated Patient
clear, despite their popularity. Ventilated patients must be monitored carefully for res-
piratory rate and activity, chest wall movement, and
Setting the Ventilator quality of breath sounds. Oxygenation should be mea-
sured either by ABGs or by continuous pulse oximetry.
When initiating mechanical ventilation, the clinician Ventilation should be assessed by blood gas analysis or
will vary the parameters according to the mode of ven- by noninvasive means, such as transcutaneous monitor-
tilation selected. Volume-controlled modes of ventila- ing or end-tidal sampling. Transcutaneous PO2 (PtO2)
tion generally require a set tidal volume, inspiratory or PCO2 (PtCO2) measurements are most useful with
time, rate, and level of positive end-expiratory pressure younger patients who have good skin perfusion, but
(PEEP). A typical initial tidal volume is 8–12 mL/ kg, they become problematic with poorly perfused or obese
as long as that volume does not cause excessive airway patients. End-tidal CO2 monitoring is done by placing
pressures. The inspiratory time is typically set at 1 sec- a gas-sampling port on the endotracheal tube and ana-
ond or 33% of the respiratory cycle, whichever is lyzing expired gas for CO2. This technique appears to
shorter. Rate can be adjusted to patient comfort and be more valuable for patients with large tidal volumes,
blood gas measurements of ventilation, but generally lower respiratory rates, and without leaks around the
patients starting on mechanical ventilation will require endotracheal tube. In practice, end-tidal CO2 values
full support at least initially with a rate of 20–30 may differ significantly from measured PaCO2 values
breaths/min. and thus are most useful for following relative fluctua-
Pressure-controlled ventilation is set up in similar tions in ventilation. Frequent, preferably continuous,
fashion, though the sufficiency of the inspiratory pres- blood pressure monitoring is also necessary for patients
sure to provide an adequate tidal volume is assessed by receiving oxygen at a high PEEP, given the risk of ad-
observing the patient’s chest rise and by measuring the verse cardiovascular effects.
returned tidal volume. Typically, patients without lung
disease will require pressures of 15–20 cm H2O, and
patients with respiratory illnesses will initially require
Adjusting the Ventilator
20–30 cm H2O pressure to provide adequate ventila- Mechanical ventilation can assist with both ventilation
tion. (PCO2) and oxygenation (PO2). Ventilation is most
closely associated with the delivered minute-volume, or
the tidal volume multiplied by the respiratory rate. Ab-
Positive End-Expiratory Pressure normal PCO2 values can be most effectively addressed
The PEEP level is the final major setting required to by changes in the respiratory rate or the tidal volume.
initiate mechanical ventilation. All mechanical ventila- Increased rate or tidal volume should increase minute-
 CRITICAL CARE / 379

volume and thus decrease pCO2 levels; decreases in rate may facilitate oxygenation and ventilation. Nondepo-
or tidal volume should act in the opposite fashion. In larizing neuromuscular blocking agents are most com-
some circumstances, additional adjustments may also monly used for this purpose, and they may be given as
be necessary. For example, for patients with disease intermittent doses or as continuous infusions. When
characterized by extensive alveolar collapse, increasing muscle relaxants are given, extra care must be taken to
PEEP may improve ventilation by rerecruiting col- ensure that levels of sedation are adequate, as many of
lapsed lung units. Also, for patients with disease charac- the usual signs of patient discomfort are masked by the
terized by significant airway obstruction, decreases in paralytics.
respiratory rate may allow more time for exhalation and
improve ventilation despite an apparent decrease in the
minute-volume provided.
Alternative Methods of Ventilation
The variables most closely associated with oxygena- High-frequency oscillatory ventilation (HFOV) is a
tion are the inspired oxygen concentration and the mean mode of mechanical ventilation in which the ventilator
airway pressure during the respiratory cycle. Increases in provides very small, very rapid tidal volumes. Respira-
inspired oxygen concentration will generally increase ar- tory rates used during oscillatory ventilation typically
terial oxygenation, unless right-to-left intracardiac or in- range from 5 to 10 Hz (rates of 300–600 breaths/min)
trapulmonary shunting is a significant component of the in most PICU patients. This mode of ventilation has
patient’s illness. Concentrations of inspired oxygen above been used successfully for neonates, older pediatric pa-
60–65%, however, may lead to hyperoxic lung injury. tients, and adults, and for diseases as diverse as pneu-
Patients with hypoxemic respiratory failure requiring monia, pulmonary contusion, ARDS, and asthma.
those levels of oxygen or higher to maintain adequate ar- HFOV is increasingly being used as initial therapy in
terial saturations should have their hypoxemia addressed severe, diffuse lung diseases, such as ARDS, which re-
by increases in mean airway pressure. quire high mean airway pressures to maintain oxygena-
Mean airway pressure is affected by PEEP, peak in- tion. The advantage of HFOV is that these high levels
spiratory pressure, and inspiratory time. Increases in of mean airway pressure can be achieved without high
any one of those factors will increase mean airway pres- peak inspiratory pressures or large tidal volumes, thus
sure and should improve arterial oxygenation. It is im- theoretically protecting the lung from ventilator-in-
portant to bear in mind, however, that increases in duced lung injury. Disadvantages of HFOV include
mean airway pressure may also lead to decreases in car- generally poor tolerance by patients who are not heavily
diac output. In this circumstance, raising mean airway sedated or even paralyzed, the risk of cardiovascular
pressure may increase arterial oxygenation but actually compromise due to high mean airway pressures, and
compromise oxygen delivery to the tissues. For patients the risk of barotrauma in patients with heterogeneous
with severe hypoxemic respiratory failure, these trade- lung disease. Although HFOV clearly may be useful for
offs highlight the need for careful monitoring of these selected patients, it remains unsettled whether HFOV
variables by experienced personnel. provides a clear benefit in outcome compared with
carefully managed conventional modes of ventilation.
Managing the Ventilated Patient Inverse ratio ventilation is another strategy some-
times employed with patients who have severe hypox-
Patients undergoing mechanical ventilation generally emic respiratory failure. This approach entails increas-
require the same meticulous supportive care given to all ing the inspiratory time until it exceeds the expiratory
PICU patients. Since mechanical ventilation is often time in the respiratory cycle, thus “inverting” the I:E
frightening and uncomfortable for patients, leading to ratio from the usual 1:2 or 1:3 to 2:1 or even 3:1. This
dyssynchrony with the ventilator and impaired ventila- practice, most commonly done while using a pressure-
tion and oxygenation, they deserve careful attention controlled mode of ventilation, leads to significant in-
directed toward optimizing comfort and decreasing creases in mean airway pressure and may improve oxy-
anxiety. Sedative–anxiolytics are typically provided as genation in selected patients. Disadvantages of this
intermittent doses of benzodiazepines, with or without approach are the increased need for sedation and paral-
opioids. Some patients respond better to the steady ysis due to patient discomfort, hypercarbia due to less
state of sedation provided by continuous infusion of effective ventilation, and the risk of cardiovascular com-
these agents, although oversedation of the ventilated promise from high mean airway pressures. While useful
patient may lead to longer durations of ventilation and for selected patients as a rescue strategy, inverse-ratio
difficulties with weaning from the ventilator. ventilation has not yet been shown to provide any sig-
For a patient with severe respiratory illnesses, even nificant advantage over conventional modes of ventila-
small movements by the patient may compromise ven- tion or HFOV in managing severe hypoxemic respira-
tilation and oxygenation. In such cases, muscle paralysis tory failure.
380 / CHAPTER 13

Arnold JH et al: High-frequency oscillatory ventilation in pediatric oxygenate the patient. Numerous other diagnostic sys-
respiratory failure: A multicenter experience. Crit Care Med tems have been proposed.
2000;28:3913 [PMID: 11153635].
In addition, because the clinical disorder or disor-
Cheifetz IM: Invasive and noninvasive pediatric mechanical venti- ders that led to the development of acute lung injury
lation. Respir Care 2003;48:442 [PMID: 12667269].
clearly influence the patient’s prognosis for recovery,
Flaatten H et al: Outcome after acute respiratory failure is more de-
pendent on dysfunction in other vital organs than on the
precise definition of the underlying problem is impor-
severity of the respiratory failure. Crit Care 2003;7:R72 tant. Although the average mortality in this population
[PMID: 12930559]. is 40%, the rate is quite variable and dependent on the
Frank JA, Matthay MA: Science review: Mechanisms of ventilator- associated clinical disorder. Mortality can be as high as
induced injury. Crit Care 2003;7:233 [PMID: 12793874]. 90% among adult ARDS patients with underlying liver
Gattinoni L et al: Physiologic rationale for ventilator setting in failure, and less than 10% among pediatric ARDS asso-
acute lung injury/acute respiratory distress syndrome patients. ciated with respiratory syncytial virus infection. The de-
Crit Care Med 2003;31:S300 [PMID: 12682456]. velopment of multisystem organ failure is a frequent
Kallas HJ: Non-conventional respiratory support modalities applic- complicating factor in the care of the patient with
able in the older child: High frequency ventilation and liquid ARDS, and the failure of organs outside the lung has a
ventilation. Crit Care Clin 1998;14:655 [PMID:9891632].
large role in determining the prognosis. In fact, nonpul-
Matthews BD, Noviski N: Management of oxygenation in pedi-
atric acute hypoxemic respiratory failure. Pediatr Pulmonol
monary organ failures are the leading cause of death in
2001;32:459 [PMID: 11747250]. the most recent studies of adult or pediatric ARDS pa-
Riphagen S, Bohn D: High frequency oscillatory ventilation. Inten- tients.
sive Care Med 1999;25(12):1459 [PMID: 10702031].
Thompson BT et al: Clinicians’ approaches to mechanical ventila- Clinical Presentation & Pathophysiology
tion in acute lung injury and ARDS. Chest 2001;120:
1622 [PMID: 11713144]. ARDS may be precipitated by a variety of insults (Table
13–6), of which infection is the most common. Despite
ACUTE RESPIRATORY DISTRESS the diversity of causes, the clinical presentation is re-
SYNDROME markably similar in most cases. ARDS can be divided
roughly into four clinical phases (Table 13–7). In the
ARDS is a syndrome of acute respiratory failure charac- earliest phase, the patient may have dyspnea and tachy-
terized by increased pulmonary capillary permeability pnea with a relatively normal PO2 and a hyperventila-
and pulmonary edema that results in refractory hypox- tion-induced respiratory alkalosis. No significant ab-
emia, decreased lung compliance, and bilateral diffuse normalities are noted on physical or radiologic
alveolar infiltrates on chest radiography. Statistics of examination of the chest. Experimental studies suggest
ARDS reflect one of the true successes of current ICU that neutrophils accumulate in the lungs at this stage
management, as mortality has decreased over the past and that their products damage lung endothelium.
decade from approximately 50–60% to less than 40%. Over the next few hours, hypoxemia increases and
Our understanding of this illness has been ham- respiratory distress becomes clinically apparent, with
pered over the years by inconsistencies in the case defin-
itions used by various authors. An international consen-
sus conference was convened in 1997 to establish the Table 13–6. Acute respiratory distress syndrome
current guidelines defining diagnostic criteria for risk factors.
ARDS. The diagnosis of ARDS rests on four features:
(1) an underlying illness or injury that predisposes to
ARDS; (2) bilateral infiltrates on chest radiograph; Direct Lung Injury Indirect Lung Injury
(3) an absence of evidence of heart failure and, in par- Aspiration of gastric contents Sepsis
ticular, left ventricular (LV) failure; and, most impor- Hydrocarbon ingestion or aspiration Shock
tantly, (4) severe hypoxemic respiratory failure. Hypox- Inhalation injury (heat or toxin) Pancreatitis
emia is assessed using the ratio of the arterial oxygen Pulmonary contusion Burns
level (PaO2) to the inspired oxygen concentration Pneumonia Trauma
(FiO2). When the PaO2/FiO2 ratio is less than 200, and Near-drowning Fat embolism
the other two criteria are met, the case is defined as Drug overdoses (includ-
ARDS. When the PaO2/FiO2 ratio is between 200 and ing aspirin, opioids,
300, and the other two criteria are met, the case is de- barbiturates, tricyclic
fined as acute lung injury. This definition is debated, antidepressants)
however, particularly since the current criteria do not Transfusion of blood
include any assessment of the airway pressure needed to products
 CRITICAL CARE / 381

Table 13–7. Pathophysiologic changes of modern acute respiratory distress syndrome (low-pressure
pulmonary edema).

Symptoms Laboratory Findings Pathophysiology

Phase 1 (early changes)
Normal radiograph Dyspnea, tachypnea, normal Mild pulmonary hypertension, Neutrophil sequestration, no
chest examination normoxemic or mild hypox- clear tissue damage
emia, hypercapnia.
Phase 2 (onset of parenchymal changes)a
Patchy alveolar infiltrates Dyspnea, tachypnea, cyano- Pulmonary hypertension, nor- Neutrophil infiltration, vascular
beginning in dependent sis, tachycardia, course rales mal wedge pressure, in- congestion, fibrin strands,
lung creased lung permeability, platelet clumps, alveolar sep-
No perivascular cuffs (un- increased lung water, increas- tal edema, intraalveolar pro-
less a component of high- ing shunt, progressive de- tein, white cells, type I epi-
pressure edema is present) crease in compliance, mod- thelial damage
Normal heart size erate to severe hypoxemia.
Phase 3 (acute respiratory failure with progression, 2–10 days)
Diffuse alveolar infiltrates Tachypnea, tachycardia, Phase 2 changes persist. Pro- Increased interstitial and alve-
Air bronchograms hyperdynamic state, sepsis gression of abnormalities, in- olar inflammatory exudate
Decreased lung volume syndrome, signs of consolida- creasing shunt fraction, with neutrophil and mononu-
No bronchovascular cuffs tion, diffuse rhonchi further decrease in compli- clear cells, type II cell prolifer-
Normal heart ance, increased minute venti- ation, beginning fibroblast
lation, impaired oxygen proliferation, thromboembolic
extraction of hemoglobin. occlusion
Phase 4 (pulmonary fibrosis, pneumonia with progression, > 10 days)b
Persistent diffuse infiltrates Symptoms as above, recur- Phase 3 changes persist. Re- Type II cell hyperplasia, inter-
Superimposed new pneu- rent sepsis, evidence of multi- current pneumonia, progres- stitial thickening; infiltration of
monic infiltrates ple organ system failure sive lung restriction, impaired lymphocytes, macrophages, fi-
Recurrent pneumothorax tissue oxygenation, impaired broblasts; loculated pneumo-
Normal heart size oxygen extraction. Multiple nia or interstitial fibrosis; med-
Enlargement with cor organ system failure. ial thickening and remodeling
pulmonale of arterioles
a
The process is readily reversible at this stage if the initiating factor is controlled.
b
Multiple organ system failure is common. The mortality rate is greater than 80% at this stage, since resolution is more difficult.
Modified slightly and reproduced, with permission, from Demling RH: Adult respiratory distress syndrome: Current concepts. New Hori-
zons 1993;1:388.

cyanosis, tachycardia, irritability, and dyspnea. Radi- Alveolar epithelial injury in ARDS lowers the thresh-
ographic evidence of early parenchymal change is noted old for alveolar edema formation and impairs gas ex-
by “fluffy” alveolar infiltrates initially appearing in de- change. The functional integrity of the alveolar epithe-
pendent lung fields, indicative of pulmonary edema. lium, as measured by the ability of the alveoli to clear
The edema fluid typically has a high concentration of liquid out of the airspaces, has prognostic importance in
protein (75–95% of plasma protein concentration), ARDS. Those patients who still show evidence of func-
which is characteristic of an increased permeability-type tional alveolar liquid clearance mechanisms during the
edema and differentiates it from cardiogenic or hydro- first day of their illness have a much higher survival rate
static pulmonary edema. Protein in the airspaces acts to than those with evidence of severe epithelial impairment.
inactivate surfactant, which, combined with damage to Pulmonary hypertension, decreases in lung compli-
type 2 alveolar pneumocytes, leads to a marked defi- ance, and increases in airway resistance are also com-
ciency in surfactant content in the lung. As a result, the monly noted. Clinical studies suggest that airway resis-
lung is particularly prone to collapse and to shearing in- tance may be increased in 50% of patients with ARDS.
juries due to the high surface tension required to open Computed tomography (CT) studies of adult pa-
collapsed alveoli. tients in the acute phases of ARDS have established that
382 / CHAPTER 13

this illness is characterized by heterogeneous collapse of systemic hemodynamic instability rather than by hy-
the lung, with typical areas of dependent consolidation, poxemia.
overinflation in the upper zones, and relatively small
areas of normally expanded lung. These findings have Treatment
led to the opinion that the lung in ARDS is best viewed
as “small” rather than stiff, prompting a shift toward A. MONITORING
ventilating these patients with smaller tidal volumes and Multiorgan system monitoring is mandatory for pa-
tolerating the relative hypercarbia that may ensue. In ad- tients with ARDS. ABG analysis is required for accu-
dition, a large body of research in recent years has shown rate assessment of oxygenation and ventilation and for
that ventilation with large tidal volumes and low PEEP the rational titration of ventilator strategies that may
levels allows a pattern of cyclic alveolar overdistention have profound adverse effects. Hemodynamic monitor-
and collapse, which causes a lung injury histologically ing should include, at a minimum, central venous pres-
similar to ARDS even in normal lungs. This phenome- sure (CVP) measurements to help determine the level
non is now called ventilator-induced lung injury. Taken of cardiac preload, and an indwelling arterial catheter
together, these findings have given rise to the view that for continuous blood pressure measurements and ABG
acute ARDS can best be treated by rerecruiting those sampling. For patients with severe disease or concurrent
areas of dependent collapse and minimizing the stretch- cardiac dysfunction, consideration can be given to pul-
induced injury, or volutrauma, in the nondependent monary artery catheterization to help with fluid man-
areas of the lung. This approach has been termed the agement and to allow assessment of mixed venous
open-lung strategy and has been the subject of intense blood saturation as an index of overall tissue oxygena-
scrutiny in recent years (see below). tion. Obtaining chest films daily is important for pa-
The subacute phase of ARDS (5–10 days after lung tients receiving vigorous support because severe ARDS
injury) is characterized by type II cell and fibroblast pro- is associated with a 40–60% incidence of air leaks. Sec-
liferation in the interstitium of the lung. This results in ondary infections are common and increase mortality
decreased lung volumes and signs of consolidation that rates strikingly. Thus surveillance for infection is im-
are noted clinically and radiographically. Worsening of portant, requiring appropriate cultures and following
the hypoxemia with an increasing shunt fraction, as well the temperature curve and white blood cell count.
as a further decrease in lung compliance, are noted. Renal, liver, and gastrointestinal (GI) function should
Some patients develop an accelerated fibrosing alveolitis be watched closely because of the great likelihood of
in which fibroblasts and collagen formation in the inter- multiple organ dysfunction.
stitium are markedly increased. The mechanisms respon-
sible for these changes are unclear. Current investigation B. FLUID MANAGEMENT
centers on the role of growth and differentiation factors, Given the increases in pulmonary capillary permeability
such as transforming growth factor-β and platelet-de- in ARDS, pulmonary edema accumulation is likely
rived growth factor released by resident and nonresident with any elevation in pulmonary hydrostatic pressures.
lung cells such as alveolar macrophages, mast cells, neu- In this setting, most clinicians reduce intravascular vol-
trophils, alveolar type II cells, and fibroblasts. ume to the lowest level that is still compatible with an
During the chronic phase of ARDS (10–14 days after adequate cardiac output and adequate oxygen delivery
lung injury), fibrosis, emphysema, and pulmonary vascu- to the tissues.
lar obliteration occur. During this phase of the illness,
oxygenation defects generally improve, and the lung be- C. HEMODYNAMIC SUPPORT
comes more fragile and susceptible to barotrauma. Air Hemodynamic support is directed toward increasing
leak is common among patients still ventilated with high perfusion and oxygen delivery. In those circumstances
levels of airway pressure at this late stage in their illness. when volume expansion is necessary to improve oxygen
Also, patients have increased amounts of dead space, and delivery, this can best be achieved by giving packed red
difficulties with ventilation are common. Airway compli- blood cells to maintain the hematocrit between 35%
ance remains low, perhaps because of ongoing pul- and 40%, and by giving colloid or crystalloid solutions
monary fibrosis and insufficient surfactant production. to nonanemic volume-depleted patients. Inotropes
Secondary infections are common in the subacute should be used as needed to optimize oxygen delivery
and chronic phases of ARDS and significantly influence to the tissues.
the outcome. The mechanisms responsible for increased
host susceptibility to infection during this phase are not D. VENTILATORY SUPPORT
well understood. Basic principles of ventilator management were described
Mortality in the late phase of ARDS exceeds 80%. earlier (see Adjusting the Ventilator section). In addi-
Death is usually caused by multiple organ failure and tion to those principles, current ventilatory manage-
 CRITICAL CARE / 383

ment of ARDS is directed at the rerecruitment of areas ularly for patients early in the course of ARDS. The
of dependent alveolar collapse and the protection of oxygenation improvements are often not sustained,
noncollapsed areas from overdistention. Since an FiO2 however, necessitating repeat position changes to main-
greater than 60% over 24 hours can cause additional tain the effect. Whether prone positioning contributes
injury to the lung, mean airway pressure should be in- to improved outcomes for patients with ARDS remains
creased to provide an adequate PaO2 (> 55 mm Hg) at uncertain.
an FiO2 of 60% or less. In general, this can be accom- Based on the ability of inhaled nitric oxide (iNO)
plished by incremental increases in PEEP every to reduce pulmonary artery pressure and to improve the
15–30 minutes until adequate oxygenation is achieved matching of ventilation with perfusion without produc-
or until a limiting side effect of the PEEP is reached. ing systemic vasodilation, iNO has been proposed as a
Ventilation with high levels of PEEP acts by helping to beneficial therapy for ARDS. Several recent multicenter
prevent dependent collapse of edematous lung units. trials of iNO in the treatment of ARDS, both in adults
PEEP levels of 12–14 cm H2O are not unusual, and and in children, have shown acute improvements in
levels as high as 20–25 cm H2O have been used suc- oxygenation in subsets of patients but no significant
cessfully in these patients. Before increasing PEEP sig- improvement in overall survival. As a result, the current
nificantly, the physician should optimize conditions by role of iNO in the treatment of ARDS remains unclear.
making sure that the patient’s intravascular volume is Additional studies are now focusing on the anti-inflam-
appropriate, the endotracheal tube does not leak, and matory role (by reducing neutrophil adhesion and acti-
the patient is heavily sedated and paralyzed. vation) iNO may play in ARDS. Studies to evaluate the
The actual mode of ventilation employed (volume combined effects of several of these alternative therapies
or pressure) with an ARDS patient is probably unim- are also being planned.
portant. However, recent work from a large multicenter Surfactant replacement therapy has been tried with
trial sponsored by the National Institutes of Health some success in patients with ARDS. Surfactant re-
suggests that the tidal volumes used may be important. placement, in some instances, improves lung compli-
Using a PEEP strategy similar to that described in the ance and oxygenation, and hastens weaning from me-
preceding paragraph, the investigators compared the ef- chanical ventilation. In randomized trials of surfactant
fects of a low (6 mL/kg) tidal volume versus a normal replacement, there were no differences in outcome
(12 mL/kg) tidal volume in 861 adult ARDS patients. (death, length of ventilation, or hospitalization), but
Those patients ventilated with the lower tidal volume there was some evidence of decreased inflammation. A
demonstrated fewer extrapulmonary organ failures and multicenter trial of surfactant treatment for pediatric
an overall 25% decrease in mortality. In keeping with ARDS is currently in progress.
these findings and with experimental data demonstrat- Although corticosteroids have not been found to be
ing ventilator-induced lung injury at alveolar pressures beneficial in early stage ARDS, these agents may reduce
greater than 30 cm H2O, we suggest that current prac- the inflammation and fibrosis associated with later stage
tice for pediatric ARDS patients should consist of ven- ARDS. Indeed, the use of methylprednisolone in adults
tilation with tidal volumes in the 6–8 mL/kg range, or whose lung injury was not improving after 7 days of
at least with tidal volumes small enough to keep alveo- ARDS was associated with in improvement of lung in-
lar pressures below 30–35 cm H2O. jury and multiple organ dysfunction. Mortality was also
reduced, when compared with control subjects receiv-
E. OTHER THERAPIES ing placebo. A large multicenter trial is under way to
As previously described, HFOV is an increasingly pop- further evaluate the use of steroids in the late phase of
ular technique that has been used successfully in pedi- ARDS.
atric patients with ARDS. When used as part of a strat- Extracorporeal membrane oxygenation (ECMO)
egy of aggressive increases in mean airway pressure to has been used in pediatric patients with severe ARDS.
rerecruit deflated areas of the lung and to prevent cyclic In older studies, patients who received ECMO had
overdistention and collapse, HFOV is a physiologically better survival rates than did control subjects. ECMO
rational approach to this illness. It has not yet been de- has not been studied in comparison with current
termined whether HFOV provides additional benefits conventional ventilation strategies. In addition, recent
compared with open-lung strategy ventilation with improvements in outcome for pediatric ARDS patients
conventional ventilator modes. receiving conventional therapies have made the role
Prone positioning is a technique of changing the of ECMO less clear and have made further prospec-
patient’s position in bed from supine to prone, with the tive randomized studies of ECMO difficult to com-
goal of allowing postural drainage and improving venti- plete. For now, ECMO remains a rescue therapy for
lation of collapsed dependent lung units. This tech- patients with severe ARDS unresponsive to other
nique often dramatically improves oxygenation, partic- modalities.
384 / CHAPTER 13

F. FOLLOW-UP gressive intervention. Life-threatening asthma is caused

Information regarding the long-term outcome of pedi- by severe bronchospasm, excessive mucous secretion,
atric patients with ARDS remains limited. One report inflammation, and edema of the airways (see Chapter
of 10 children followed 1–4 years after severe ARDS 17). Reversal of these mechanisms is the key to success-
showed 3 still symptomatic and 7 with hypoxemia at ful treatment. Status asthmaticus remains a common
rest. Until further information is available, all patients diagnosis among children admitted to the PICU, and
with a history of ARDS need close follow-up of pul- asthma continues to be associated with surprisingly
monary function. high mortality rates.
The physical examination helps determine the sever-
Acute Respiratory Distress Syndrome Network: Ventilation with ity of illness. Accessory muscle (sternocleidomastoid)
lower tidal volumes as compared with traditional tidal vol- use correlates well with a forced expiratory volume
umes for acute lung injury and the acute respiratory distress (FEV1) and peak expiratory flow rates (PEFRs) less
syndrome. N Engl J Med 2000;342:1301 [PMID:
10793162]. than 50% of normal predicted values. A pulsus para-
Anderson MR: Update on pediatric acute respiratory distress syn-
doxus of over 22 mm Hg has been correlated with ele-
drome. Respir Care 2003;48:261 [PMID: 1266727]. vated PaCO2 levels. The absence of wheezing may be
Curley MA et al: The effects of early and repeated prone position- misleading because, in order to produce a wheezing
ing in pediatric patients with acute lung injury. Chest sound, the patient must take in a certain amount of air.
2000;118:156 [PMID: 10893373]. The ABG analysis remains the single most important
ECMO utilization. Pediatrics 2000;106:1339 [PMID: 11099586]. laboratory determination in the evaluation of a child in
Hintz SR et al: Decreased use of neonatal extracorporeal membrane severe status asthmaticus. Patients with severe respira-
oxigenation (ECMO): How new treatment modalities have tory distress, signs of exhaustion, alterations in con-
affected ECMO utilization. Pediatrics 2000 Dec; 106(6): sciousness, elevated PaCO2, or acidosis should be admit-
1339 [PMID: 11099586] ted to the PICU.
Krishnan JA, Brower RG: High-frequency ventilation for acute
lung injury and ARDS. Chest 2000:118:795 [PMID:
10988205]. Treatment
Lewandowski K: Extracorporeal membrane oxygenation for severe
acute respiratory failure. Crit Care 2000;4(3):156 [PMID: Much of the morbidity associated with the treatment of
11094500]. severe asthma is related to the complications of me-
McIntyre RC Jr et al: Thirty years of clinical trials in acute respira- chanical ventilation that occur in patients with severe
tory distress syndrome. Crit Care Med 2000;28:3314 airflow obstruction. As a result, the goal of initial treat-
[PMID: 11008997]. ment of the patient with life-threatening status asth-
Meduri GU et al: Effect of prolonged methylprednisolone therapy maticus is to improve the patient’s ability to ventilate
in unresolving acute respiratory distress syndrome: A ran- without resorting to intubation and mechanical ventila-
domized controlled trial. JAMA 1998;280:159 [PMID: tion. The medical therapies described in the following
9669790]. (Classic)
discussion should be undertaken swiftly and aggres-
Redding GJ: Current concepts in adult respiratory distress syn- sively with the goal of reversing the bronchospasm be-
drome in children. Curr Opin Pediatr 2001;13(3):261
[PMID: 11389362]. fore respiratory failure necessitates invasive ventilation.
Sachdeva RC, Guntupalli KK: Acute respiratory distress syndrome.
Due to inadequate minute-ventilation and V/Q
Crit Care Clin 1997;13:503 [PMID: 9246528]. mismatching, patients with severe asthma are almost al-
Shorr AF et al: D-Dimer correlates with proinflammatory cytokine ways hypoxemic and should receive supplemental hu-
levels and outcomes in critically ill patients. Chest 2002;121: midified oxygen immediately.
1262 [PMID: 11948062]. Inhaled ␤2-agonist therapy with agents such as al-
Sokol J et al: Inhaled nitric oxide for acute hypoxemic respiratory buterol remains first-line therapy to reverse acute bron-
failure in children and adults. Cochrane Database Syst Rev choconstriction. If the patient is in severe distress and
2000;4:CD002787 [PMID: 11914763]. has poor inspiratory flow rates, thus preventing ade-
Vincent JL: New management strategies in ARDS: Immunomodu- quate delivery of nebulized medication, subcutaneous
lation. Crit Care Clin 2002;18:69 [PMID: 11910733]. injection of epinephrine or terbutaline may be consid-
Ware LB, Matthay MA: The acute respiratory distress syndrome. ered. The frequency of β2-agonist administration varies
N Engl J Med 2000;342:1334 [PMID: 10793167].
according to the severity of the patient’s symptoms and
the occurrence of adverse side effects. Nebulized al-
ASTHMA (LIFE-THREATENING) buterol may be given intermittently at a dose of
Status asthmaticus may be defined as reversible small 0.1 mg/kg per nebulization up to 2.5 mg, or it can be
airway obstruction that is refractory to sympath- administered continuously at a dose of 0.5 mg/kg/h to
omimetic and anti-inflammatory agents and that may a maximum of 20 mg/h, usually without serious side ef-
progress to respiratory failure without prompt and ag- fects. The heart rate and blood pressure of these pa-
 CRITICAL CARE / 385

tients should be monitored closely, because excessive Magnesium sulfate has been reported to be an ef-
tachycardia and ventricular ectopy may occur. fective bronchodilator in patients with severe status
Systemic corticosteroids act by decreasing inflam- asthmaticus and may be considered for patients in dan-
mation, stabilizing mast cells, and increasing β2-recep- ger of worsening respiratory failure. The mechanism of
tor expression. These agents speed the resolution of se- action of magnesium is unclear, but its smooth muscle
vere asthma exacerbations refractory to bronchodilator relaxation properties are probably caused by interfer-
therapy and should be given to all patients admitted to ence with calcium flux in the bronchial smooth muscle
the hospital with severe asthma. The optimal dose is cell. Magnesium sulfate is given IV at a dose of
unknown, although a frequently used dosage is 25–50 mg/kg/dose. Though it is usually well tolerated,
1 mg/kg of IV methylprednisolone every 6 hours. The hypotension and flushing are side effects.
acute complications of corticosteroid usage include GI If the previously described aggressive management
bleeding, hyperglycemia, and hypertension. fails to result in significant improvement, mechanical
Inhaled anticholinergic agents may also be helpful ventilation may be necessary. In general, if there is
in patients with severe asthma. In some patients, steady deterioration (increased acidosis, rising PaCO2)
cholinergic-related bronchoconstriction is more marked despite intensive therapy for asthma, the patient should
than in others, so not all patients respond. Nebulized be intubated and ventilated mechanically. Mechanical
ipratropium bromide is the drug of choice, and is given ventilation for patients with asthma is difficult because
at a dose of 250–500 µg/dose. the severe airflow obstruction often leads to very high
Intravenous ␤-agonists should be considered in pa- airway pressures, air trapping, and resultant baro-
tients with severe bronchospasm unresponsive to in- trauma. The goal of mechanical ventilation with an in-
haled bronchodilators. The agent most commonly used tubated asthmatic patient is to maintain adequate oxy-
in the United States is terbutaline, a relatively specific genation and ventilation with the least amount of
β2-agonist, which can be given as a bolus dose or as a barotrauma until other therapies become effective.
continuous infusion. Owing to its relative specificity for Worsening hypercarbia after intubation should be an-
β2-receptors, terbutaline has fewer cardiac side effects ticipated and aggressive efforts to normalize blood gases
than previously available IV β-agonists like isopro- should be moderated, as such efforts may only lead to
terenol. Terbutaline is given as a bolus or loading dose complications. Due to the severe air flow obstruction,
of 10 µg/kg followed by a continuous infusion of these patients will require long inspiratory times to de-
0.5–5 µg/kg/min. In general, patients receiving IV β2- liver a breath and long expiratory times to avoid air
agonist therapy should have indwelling arterial lines for trapping. In general, the ventilator rate should be de-
continuous blood pressure and blood gas monitoring. creased until the expiratory time is long enough to
Theophylline remains a controversial agent in the allow emptying prior to the next machine breath. Ven-
management of severe asthma. Although some studies tilator rates of 8–12 breaths/min are typical initially. Ei-
suggest this drug may confer some additional benefit ther volume- or pressure-targeted modes of ventilation
when given with steroids and β2-agonists, other studies can be used effectively in these patients. PEEP should
of children hospitalized with moderate to severe asthma be kept low (0–2 cm H2O). Isolated reports have noted
have not shown a clear benefit in adding theophylline patients who respond to greater PEEP, but these cases
to other therapy. Besides causing bronchodilation, this are the exception. These ventilator strategies and the re-
agent decreases mucociliary inflammatory mediators sulting hypercarbia typically are uncomfortable, requir-
and reduces microvascular permeability. When the de- ing that patients be heavily sedated. Barbiturates should
cision to add theophylline to high-dose β2-agonist ther- be avoided if possible. If fentanyl and midazolam
apy for severe status asthmaticus is being weighed, the (Versed) are inadequate, or if ventilating the patient is
increased risk of serious side effects such as tachycardia difficult, bolus or continuous infusion of ketamine
and cardiac arrhythmias must be considered. Theo- should be considered because it has been shown to be
phylline is given IV as aminophylline. Each 1 mg/kg of beneficial in certain circumstances. Most patients, at
aminophylline given as a loading dose will increase the least initially, will also require neuromuscular blockade
serum level by approximately 2 mg/dL. For a patient to optimize ventilation and minimize airway pressures.
who has not previously received aminophylline or oral
(PO) theophylline preparations, load with 7–8 mg/kg
of aminophylline in an attempt to achieve a level of
Monitoring
10–15 mg/dL; then start a continuous infusion of Severely asthmatic patients should be monitored for
aminophylline at a dosage of 0.8–1 mg/kg/h. Watch heart rate, blood pressure, O2 saturation, and arterial
closely for toxicity (gastric upset, tachycardia, seizures) pH and PaCO2. Continuous blood pressure monitoring
and follow serum levels closely, trying to maintain is necessary because air-trapping can lead to increased
steady-state levels of 12–16 mg/dL. levels of occult PEEP (“auto-PEEP”), an effect that can
386 / CHAPTER 13

impair venous return and decrease cardiac output. ther with subsequent cellular breakdown and release of
Close ventilator monitoring is necessary because in- toxic substances, causing further redistribution of flow.
creases in inspiratory pressure or decreases in pul- At this point, the patient is hypotensive, with poor car-
monary compliance may signal worsening bronchocon- diac output.
striction, mucus plugging, or an extrapleural air leak. Shock can be classified by mechanism into hypov-
Chest films of ventilated asthmatic patients should be olemic (including distributive), cardiogenic, and septic.
obtained daily and immediately with sudden changes in Often, two or three of these occur together.
patient condition, due to the risk of pneumothorax and
pneumomediastinum. In addition, if the patient is re- A. HYPOVOLEMIC SHOCK
ceiving neuromuscular blocking agents, the degree of Hypovolemic shock is caused by decreased circulating
nerve block should be monitored closely because non- blood volume or preload. This may result from loss of
depolarizing agents such as pancuronium, when given whole blood or plasma or from fluid loss from the kid-
with corticosteroids, can cause prolonged paralysis and ney or gut. These patients usually have intact compen-
muscle weakness. satory mechanisms that maintain normal blood pres-
sure by increasing cardiac output and shunting blood
Bohn D: Lung salvage and protection ventilatory techniques. Pedi- away from certain organs. These responses protect
atr Clin North Am 2001;48(3):553 [PMID: 11411293]. blood flow to the heart and brain. Untreated, hypov-
DiNicola LK et al: Drug therapy approaches in the treatment of olemic shock can progress to an irreversible stage. Addi-
acute severe asthma in hospitalized children. Paediatr Drugs tionally, a relative hypovolemia occurs when arterial
2001;3:509 [PMID: 11513282]. and capillary shunting past tissue beds occurs with an
Kercsmar CM: Acute inpatient care of status asthmaticus. Respir increase in venous capacitance, causing blood to pool—
Care Clin North Am 2000;6(1):155 [PMID: 10639561]. so-called distributive shock. This results from anaphy-
Kreutzer ML, Louie S: Pharmacologic treatment of the adult hospi- laxis or vasodilating drugs.
talized asthma patient. Clin Rev Allergy Immunol 2001;20:
357 [PMID: 11413904]. B. CARDIOGENIC SHOCK/FAILURE
Sabato K, Hanson JH: Mechanical ventilation for children with
status asthmaticus. Respir Care Clin North Am 2000;6(1): Age-dependent differences occur in myocardial physiol-
171 [PMID: 10639562]. ogy that are relevant to therapy. Neonatal myocardium
Werner HA: Status asthmaticus in children: A review. Chest has reduced systolic performance and contractility. The
2001;119(6):1913 [PMID11399724 ]. sarcolemma, sarcoplasmic reticulum, and T-tubules are
less well developed, resulting in a greater dependency
on transsarcolemma Ca2+ flux (ie, serum Ca2+) for con-
SHOCK traction. A high resting state of myocardial contractility
Shock may be defined as failure of the cardiovascular occurs that limits the response to inotropic agents. Rel-
system to deliver critical substrates and to remove toxic atively minor increases in afterload can result in dimin-
metabolites. This failure leads to anaerobic metabolism ished stroke volume. Diastolic compliance is dimin-
in cells and ultimately to irreversible cellular damage. ished, and small changes in volume result in large
Shock has been categorized into a series of recognizable changes in ventricular wall tension. Consequently pre-
stages: compensated, uncompensated, and irreversible. load reserve is limited, and maximization of the Frank–
Patients in compensated shock have relatively normal Starling curve occurs relatively quickly (10–15 mm Hg
cardiac output and normal blood pressures, but they in animal models). Aggressive volume resuscitation be-
have alterations in the microcirculation that increase yond this is often ineffective and not tolerated. Stroke
flow to some organs and reduce flow to others. In in- volume is relatively fixed, and greater increases in car-
fants, compensatory increases in cardiac output are diac output are seen through increased heart rate.
achieved primarily by tachycardia rather than by in- Central to the understanding of cardiogenic failure
creases in stroke volume. Heart rates of 190–210/min are the progressive nature of ventricular dysfunction
are common in infants with compensated shock, but and the compensatory mechanisms that occur in the
heart rates over 220/min raise the possibility of presence of excessive hemodynamic demands. Inade-
supraventricular tachycardia. In older patients, cardiac quate cardiac output activates the renin–angiotensin
contractility (stroke volume) and heart rate increase to system. The consequent sodium and water retention
improve cardiac output. Blood pressure remains normal augments intravascular volume and increases cardiac
initially because of peripheral vasoconstriction and in- output through increased preload. With progression,
creased systemic vascular resistance. Thus hypotension cardiac compliance is decreased and preload augmenta-
occurs late and is more characteristic of the uncompen- tion via the Frank–Starling mechanism is maximized.
sated stage of shock. In the uncompensated stage, the Subsequently, small changes in ventricular volume can
oxygen and nutrient supply to the cells deteriorates fur- lead to large increases in ventricular pressure and, there-
 CRITICAL CARE / 387

fore, pulmonary venous pressure with resultant pul- monary edema will cause tachypnea, and the rales can be
monary edema. Thus, fluids should be cautiously ad- heard on auscultation. The pulmonary edema may be se-
ministered in this setting and should possibly be guided vere enough to compromise respiration and lead to hy-
by left atrial or pulmonary artery capillary wedge pres- poxemia and respiratory failure.
sure monitoring. The atrial distention that occurs in The work-up can be performed at the same time
the failing heart leads to increased production and re- treatment is initiated, and it should include an echocar-
lease of atrial natriuretic peptide (ANP). Though the diogram to evaluate cardiac anatomy and function. Ser-
function of this molecule is not completely understood, ial echocardiograms may also be helpful to specifically
ANP is a vasodilator and augments sodium and water assess the improvement in function with treatment. A
excretion. chest radiograph can reveal the amount of car-
Heart failure also induces autonomic nervous system diomegaly, pulmonary edema, and the presence of any
changes, including increased activation of the adrener- effusions. Laboratory tests should include electrolyte
gic sympathetic system and decreased parasympathetic measurements and renal and liver function tests.
stimulation. Increased adrenergic tone is associated Management of cardiogenic failure in the pediatric
with elevated circulating norepinephrine levels, in- patient is complicated by the varied underlying causes
creased vasoconstriction, and afterload. These com- that often require disparate therapies. The factors that
bined factors in turn lead to a cycle of increased after- influence cardiac output are preload, afterload, contrac-
load, increased energy expenditure, decreased cardiac tility, and heart rate and rhythm. An analysis of a low
output, myocyte death, and progressive ventricular dys- cardiac output state should consider the specific cardiac
function. The cardiomyocyte effects of prolonged lesion and should use these factors as a framework for
adrenergic stimulation include decreased β-receptors, therapy.
decreased norepinephrine stores, and, therefore, poten- Cardiogenic failure results from an imbalance of sys-
tially decreased responses to sympathetic stimulation. temic oxygen delivery and demand. Therapy is aimed at
Increased cellular concentrations of cyclic adenosine restoring oxygen delivery and reducing demand. Seda-
monophosphate and inositol triphosphate lead to in- tion, reduced environmental stress, temperature regula-
creased inward Ca2+ flux and at least transient increases tion, supplemental O2, red cell transfusion, and aug-
in contractility. Subsequently, excessive unremoved cal- mentation of cardiac output all have roles. The overall
cium impairs luciotropy and augments the propensity goal of increasing cardiac output should include restor-
for arrhythmias. Blood flow is redistributed away from ing an appropriate sinus rate and rhythm, optimizing
the splanchnic system, skin, and muscles toward the preload, augmenting myocardial contractility with min-
heart, brain, adrenal glands, and diaphragm. Endothe- imal increases in myocardial O2 consumption, and
lial dysfunction is common and contributes to the ab- maximizing afterload reduction. If bradycardia is exces-
normal vascular tone. Endothelin-1 production is ele- sive, temporary pacing with transthoracic, transesopha-
vated in the lung and increases pulmonary vascular geal, or intracardiac methods should be considered. Ex-
resistance (PVR) and systemic vascular resistance cessive tachycardia is to be avoided, as it shortens
(SVR). The release of endothelial-derived nitric oxide is ventricular diastole, leading to a reduction in diastolic
also impaired. Circulating arginine vasopressin and filling, shortened diastolic coronary perfusion, and in-
tumor necrosis factor alpha (TNF-α) levels have also creased myocardial O2 consumption.
been reported to be elevated. In the later stages of heart Cardiogenic failure is associated with elevated ven-
failure, cardiomyocyte hypertrophy, fibroblast hyper- tricular filling pressures (> 20 mm Hg). Thus, although
plasia, and increases in altered production and accumu- increasing preload can result in augmented cardiac out-
lation occur in extracellular matrix, leading to impaired put (to a degree), volume should be administered cau-
myocardial function. tiously—the Frank–Starling curve may remain flat with
Signs and symptoms of cardiac failure are produced little further improvement possible, occurring at the ex-
by the body’s attempts to compensate for the decreased pense of elevating pulmonary venous pressure with re-
pump function. The body compensates by activating the sultant pulmonary edema. Diuretics can be adminis-
sympathetic nervous and renin–angiotensin–aldosterone tered to reduce pulmonary edema and to improve
systems. The child in acute heart failure will present with pulmonary compliance, the work of breathing, and
hypotension and such evidence of poor perfusion as oxygenation. Contractility can be augmented through
metabolic acidosis and organ dysfunction. In response to inotropic stimulation of myocardial β1-receptors (Table
the poor output, tachycardia and vasoconstriction will be 13–8). Dopamine is an α- and β-agonist, which, at
evident with cool and mottled extremities. Although the lower doses (3–5 µg/kg/min), improves blood flow to
extremities are cool, the child’s core temperature will be the renal, coronary, and splanchnic beds (type D1 re-
elevated. To improve cardiac output, the body will retain ceptor). At higher doses the α-receptor effects predomi-
fluid and sodium, resulting in generalized edema. Pul- nate, with vasoconstriction increasing SVR and PVR.
388 / CHAPTER 13

Table 13–8. Pharmacologic support of the shock patient.

Alpha- Beta-
Adrenergic Adrenergic Vasodilator Actions and
Drug Dose Effecta Effecta Effect Advantages Disadvantages
Dopamine 1–20 µg/kg/min + to +++ + to +++ At low doses, re- Moderate inotrope, May cause worsen-
(dose-related) (dose-related) nal vasodilation wide and safe dosage ing of pulmonary
occurs (dopamin- range, short half-life. vasocon-
ergic receptors) striction
Dobuta- 1–10 µg/kg/min 0 +++ Moderate inotrope, Marked variation
mine less chronotropic, among patients
fewer dysrhythmias
than with isoproterenol
or epinephrine.
Epineph- 0.05–1 ++ to +++ +++ Significant increases Tachycardia, dys-
rine µg/kg/min (dose-related) in inotropy, chro- rhythmias, renal
notropy, and systemic ischemia, systemic
vascular resistance. and pulmonary vas-
cular resistance
Isoprotere- 0.05–1 0 +++ Peripheral Significant increase in Significant myocar-
nol µg/kg/min vasodilation inotropy and chro- dial oxygen con-
notropy. Systemic vas- sumption increases,
cular resistance can tachycardia, dysrhy-
drop, and pulmonary thmias
vascular resistance
should not increase
and may decrease.
Norepi- 0.05–1 +++ +++ Powerful vasoconstric- Reduced cardiac out-
nephrine µg/kg/min tor (systemic and pul- put if afterload is too
monary); rarely used high, renal ischemia
except possibly in pa-
tients with very low
systemic vascular re-
sistance or in conjunc-
tion with vasodilator.
Nitroprus- 0.05–8 0 0 Arterial and Decreases systemic Toxicities (thiocya-
side µg/kg/min venous dilation and pulmonary vascu- nates and cyanide),
(smooth muscle lar resistance, very increased intracranial
relaxation) short-acting. Blood pressure and ventila-
pressure returns to tion/perfusion mis-
previous levels within match, methemo-
1–10 minutes after globinemia, in-
infusion is stopped. creased intracranial
pressure
Milrinone 0.25–0.75 0 0 Blank Phosphodiesterase III inhibition. Decreases
g/kg/min SVR and PVR, increases myocardial contractil-
ity with only mild increase in myocardial O2
consumption. Usually used with low-dose
dopamine or dobutamine.
a
0 = no effect, + = small effect, ++ = moderate effect, +++ = potent effect.
SVR = systemic vascular resistance; PVR = pulmonary vascular resistance.
 CRITICAL CARE / 389

Dobutamine is predominately a β-agonist that addi- continuous positive airway pressure/bilevel positive air-
tionally effects a dose-dependant vasodilatation (β2-re- way pressure (CPAP/BIPAP). This must be taken into
ceptor) and has been shown to shift the ventricular account when weaning a patient with significant LV
pressure–volume loop toward normal, reducing LV fill- dysfunction from mechanical ventilation. If cardiac
ing pressure and hence pulmonary venous pressure. As output cannot be augmented sufficiently despite aggres-
first-line pharmacotherapy single agents or in combina- sive medical therapy, consideration should be given to
tion, low-dose dopamine and dobutamine are often ben- mechanical circulatory support as a bridge to cardiac
eficial by improving contractility without increasing af- transplantation. Such support is provided by ECMO,
terload and by limiting chronotropic effect. ventricular access device, or intraaortic balloon pump
Isoproterenol is a pure β-agonist that causes significant counterpulsation.
tachycardia (limiting its utility), increased myocardial Congenital heart defects pose special concerns. Aor-
O2 consumption, and systemic and pulmonary arterial tic stenosis, for instance, obstructs flow across the LV
vasodilatation. It is useful in instances of associated outflow tract, elevates intraventricular pressure, and in-
bradycardia, such as occur in heart transplantation and creases systolic workload and LV hypertrophy. Due to
heart block. Epinephrine is an α- and β-agonist that the outflow tract gradient and hypertrophy, diastolic
causes the greatest increase in myocardial O2 consump- flow in the coronaries is decreased, which can result in
tion of all inotropes. At a low dose (< 0.05 µg/kg/min) subendocardial ischemia. Dopamine is indicated for in-
it increases heart rate and contractility and decreases otropic support. Afterload reduction is relatively con-
SVR (β2-receptor). At higher doses the α-effects pre- traindicated, as it may further compromise coronary
dominate, increasing afterload. Despite these draw- flow.
backs, epinephrine can be useful as a second agent in Hypertrophic cardiomyopathy is associated with a
refractory cases. It should be administered in combina- hypertrophied nondilated left ventricle, often with dy-
tion with a vasodilator to offset the α-effects. Milrinone namic left or biventricular outflow tract obstruction.
(0.25–0.75 µg/kg/min) is a newer agent in the class of Coronary abnormalities with luminal compromise are
phosphodiesterase inhibitors. It causes a number of frequent. Systolic function is elevated, ejection fraction
beneficial effects, including a limited increase in myo- is increased, and diastolic dysfunction is evident. In-
cardial O2 consumption, decreased SVR and PVR, in- otropes are contraindicated due to increased dynamic
creased contractility, and improved luciotropy. Theo- gradient, coronary compromise, and subendocardial is-
retically it is the ideal agent and is frequently used as chemia. Preload should be maximized, and pharma-
the first-line drug, often in combination with low-dose cotherapy with β-blockers and calcium channel antago-
dopamine or dobutamine. nists is warranted.
Afterload reduction is an important additional ther- Aortic insufficiency is associated with retrograde
apy that increases stroke volume and decreases myocar- flow into the left ventricle during diastole. The amount
dial O2 consumption. Agents commonly used are nitro- of regurgitation depends in part on the pressure gradi-
prusside, hydralazine, and the angiotensin-converting ent across the aortic valve and on the heart rate. With
enzyme (ACE) inhibitors. Nitroprusside is a rapid-act- increasing heart rates, diastole is shortened and regurgi-
ing IV agent, which is readily titratable and causes ven- tation limited. Therapy should include inotropic sup-
odilation and arteriolar dilation, resulting in decreased port to improve overall cardiac output and aggressive
SVR and PVR. Venodilation can decrease preload, and afterload reduction to reduce the regurgitant fraction.
volume may therefore need to be coadministered to re- Heart rate can be increased with isoproterenol or
store an appropriate preload. Nitroprusside is a useful transesophageal pacing.
titratable IV agent to start while planning a transition In mitral regurgitation, blood is forced back into
to a PO agent. Hydralazine is a direct systemic arterio- the low-pressure left atrium during systole. The regur-
lar dilator of coronary, renal, and splanchnic vessels, gitant fraction depends partly on the relative resistance
which can be given IV or PO. It is less titratable intra- to flow across the mitral and aortic valves during sys-
venously than nitroprusside, and ACE inhibitors have tole. Therapy should include inotropic support to im-
largely replaced it as a PO agent. ACE inhibitors are prove total cardiac output, and aggressive afterload re-
now the agents of choice for oral afterload reduction duction to improve antegrade aortic flow.
and have been shown to improve survival and func- Anomalous left coronary artery typically arises
tional status in adults. Patients should be switched to from the pulmonary artery. Patients with this disorder
ACE inhibitors as soon as indicated. LV afterload is a exhibit myocardial dysfunction secondary to myocardi-
function of systolic transmural pressure (aortic pres- al ischemia. Pathophysiology includes blood flow from
sure/intrapleural pressure), and mechanical afterload re- the right coronary artery to the left coronary artery and
duction can be attained by delivering positive airway into the pulmonary artery, resulting in a “steal” phe-
pressure through mechanical ventilation or through nomenon in the left coronary distribution. Medical
390 / CHAPTER 13

therapy is futile, and urgent surgical correction is indi- surgically implanted foreign bodies, the changing epi-
cated. Prior to surgery, limited medical therapy can in- demiology of gram-positive pathogens, and antibiotic
clude inotropic support, although care must be exer- resistance among gram-positive organisms. It is impor-
cised not to reduce pulmonary arterial pressure (and tant to realize that the pathogenesis of gram-positive
increase steal) or excessively increase myocardial O2 septic shock is different from that of gram-negative sep-
consumption. Dopamine and milrinone have been used sis. Gram-positive infections most often arise from skin
with limited success. wounds, soft tissues, and catheter sites, rather than the
Cardiopulmonary bypass (high/low flow) and deep GI and genitourinary sources associated with gram-neg-
hypothermic circulatory arrest are frequently required ative infections. Gram-negative bacteria have an outer
to facilitate surgical correction of congenital defects. membrane composed of endotoxin that plays a key role
These techniques are associated with widespread organ in the pathogenesis of gram-negative infection, but the
system effects, including increased total body water, cell wall of gram-positive bacteria is embedded with
transient myocardial dysfunction, gas exchange abnor- molecules of lipoteichoic acid that are able to mimic
malities, coagulation abnormalities, and hormonal and some properties of endotoxin. Additionally, gram-posi-
stress responses. Impairment in myocardial contractility tive bacteria make a range of soluble extracellular tox-
is predictable 6–12 hours following surgery. The my- ins, including the pyrogenic toxin superantigens of
ocardium can be supported with increased preload, in- staphylococci and streptococci.
otropes, and afterload reduction. Dopamine and milri- These superantigens are unusual because they do
none are often used in combination. not require previous processing and specific presenta-
tion by antigen-presenting cells. These superantigens
C. SEPTIC SHOCK are able to bind and activate more lymphocytes than
Septic shock has components of both cardiogenic and conventionally processed antigens. It is hypothesized
hypovolemic shock. Septic shock is only indirectly that in gram-positive septic shock, toxins are released,
caused by microorganisms. Rather, septic shock is the resulting in a massive lymphocyte activation with a re-
direct result of the production and secretion of inflam- lease of T-cell cytokines, which then causes cellular in-
matory mediators. Proinflammatory mediators [TNF- jury and organ failure.
α, interleukin (IL)-1, IL-6, IL-8, and platelet-activating The host response to gram-positive sepsis is also dif-
factor] are produced and released in excess of the anti- ferent from that to gram-negative sepsis. Gram-negative
inflammatory mediators (IL-10, glucocorticoids, and endotoxin induces a rapid (1–5 hours) release of proin-
catecholamines), resulting in a proinflammatory cas- flammatory cytokines. Gram-positive toxins induce a
cade that initiates a number of pathophysiologic re- more delayed response (50–75 hours) dominated by
sponses. TNF-α and interferon-α.
Septic shock caused by gram-negative organisms ap-
pears to be mediated by endotoxins (lipopolysaccha- Other Organ Involvement
rides) and the subsequent release of cytokines (TNF,
IL-1, IL-10), eicosanoid products, bradykinin, and en- Organ dysfunction during and after an episode of
dorphins. These agents can directly mediate many of shock is common. Systems most often affected include
the manifestations of septic shock and also act to am- the kidney, the blood coagulation system, the lungs, the
plify the injury by attracting granulocytes and CNS, the liver, and the GI tract. The kidney responds
macrophages—cells that cause further cellular injury. to hypotension by increasing plasma renin and an-
Vasodilators (prostaglandin I2, endorphins) predomi- giotensin concentrations, thereby decreasing glomerular
nate early, causing a drop in systemic vascular resis- filtration rate and urine output. This can progress to
tance. Cardiac output generally is increased to compen- damage of the energy-consuming renal parenchyma,
sate for the decreased systemic vascular resistance. This causing acute tubular necrosis. Coagulopathies may
phase has been described as warm shock, because the exist in any type of shock but are especially common in
skin remains well perfused and warm. As septic shock septic shock. They result from the release of mediators
progresses, the heart is no longer able to maintain such that activate the clotting cascade, leading ultimately to
a high output, and vasoconstrictors (thromboxane, a consumptive coagulopathy (ie, disseminated intravas-
leukotrienes, endothelin) predominate, with resultant cular coagulation). The CNS dysfunction is related to
decreased peripheral perfusion. Extremities become decreased cerebral perfusion pressure and thus to de-
cool, urine output decreases, and oxygen delivery falls. creased substrate delivery to the brain. Liver dysfunc-
Shock caused by gram-positive organisms is becom- tion commonly occurs after shock and may be mani-
ing more common in the PICU. This may be due to fested by increases in liver enzymes and decreased
use of broad-spectrum empiric antibiotics, the increas- production of clotting factors leading to a bleeding
ing use of long-term intravascular catheters and other diathesis. GI problems include ileus, bleeding (eg, gas-
 CRITICAL CARE / 391

tritis, ulcers), and necrosis with sloughing of intestinal then to light touch, and finally to pain. Lack of motor
mucosa. Evaluation of multiorgan system dysfunction response and failure to cry in response to venipuncture
is mandatory in the work-up of shock. Multiple organ or lumbar puncture should alert the clinician to the
system failure secondary to shock greatly increases the severity of the situation. In uncompensated shock in
mortality of the disease. the presence of hypotension, brainstem perfusion may
be decreased. Poor thalamic perfusion can result in loss
Monitoring of sympathetic tone. Finally, poor medullary flow pro-
duces irregular respirations followed by gasping, apnea,
Both noninvasive and invasive monitoring of the pa- and respiratory arrest.
tient in shock provides information on the severity,
progression, and response to treatment. Extremely valu- B. INVASIVE MONITORING
able information can be derived from examination of Patients with poor cardiac output who are hypovolemic
the cardiovascular, mucocutaneous, musculoskeletal, often need invasive monitoring for diagnostic and ther-
renal, and central nervous systems. apeutic reasons. Arterial catheters give constant blood
A. CLINICAL FINDINGS pressure readings, and, to an experienced interpreter,
the shape of the waveform is helpful in evaluating car-
1. Cardiovascular system—Tachycardia is not always diac output. CVP monitoring gives useful information
present even when hypotension is profound. Hypoten- about relative changes in volume status as therapy is
sion occurs late in pediatric shock (median systolic given. CVP monitoring does not provide information
blood pressure for a child older than age 2 years can be about absolute volume status because intravascular vol-
estimated by adding 90 mm Hg to twice the age in ume, which is considered preload, is inferred most ac-
years). An important part of the cardiovascular exami- curately from LV end-diastolic pressures. Therefore, in-
nation is simultaneous palpation of distal and proximal travascular volume is assessed more accurately by
pulses. An increase in the amplitude difference of pulses monitoring pulmonary capillary wedge pressure or left
between proximal arteries (carotid, brachial, femoral) atrial pressure. Measurements of pulmonary capillary
and distal arteries (radial, posterior tibial, dorsalis pedis) wedge pressure can be obtained with a pulmonary
can be palpated in early shock and reflects increased artery catheter. The pulmonary artery catheter provides
systemic vascular resistance. Distal pulses may be additional valuable information on volume and cardiac
thready or absent even in the presence of normal blood status (Table 13–9) but is associated with a higher com-
pressure because of poor stroke volume compensated by plication rate than CVP lines. Placement of a pul-
tachycardia and increased systemic vascular resistance. monary artery catheter should be considered for pa-
In uncompensated shock, hypotension is present and tients with fluid-refractory (= 40–60 mL/kg) and
proximal pulses are also diminished. Early shock causes dopamine-resistant shock. Measurements of arterial
peripheral cutaneous vasoconstriction, which preserves and mixed venous oxygen saturations, along with car-
flow to vital organs. diac output data, are useful in calculating oxygen deliv-
2. Skin—Because of peripheral vasoconstriction, the ery, consumption, and extraction. Oxygen consump-
skin is gray or ashen in newborns and pale and cold in tion is frequently reduced long before hypotension is
older patients. Capillary refilling after blanching is slow present. With the use of a pulmonary artery catheter,
(> 3 seconds). Mottling of the skin may also be observed. the effects of manipulating hemoglobin, oxygen satura-
3. Musculoskeletal system—Decreased oxygen deliv- tion, and cardiac output (the determinants of oxygen
ery to the musculoskeletal system produces hypotonia. consumption and delivery) can be followed in attempts
Decreased spontaneous motor activity, flaccidity, and to achieve independence of oxygen delivery and con-
prostration are observed. sumption. Patients receiving significant inotropic or
ventilatory support may also benefit from the place-
4. Urinary output—Urine output is directly propor- ment of a pulmonary artery catheter.
tionate to renal blood flow and the glomerular filtration
rate and therefore is a good reflection of cardiac output.
Catheterization of the bladder is necessary to give accu- Treatment
rate and continuous information. (Normal urine out- Early stabilization of hemodynamics with fluid and in-
put is > 1 mL/kg/h; outputs < 0.5 mL/kg/h are consid- otropes is similar in either gram-positive or gram-nega-
ered significantly decreased.) tive sepsis.
5. Central nervous system—The patient’s level of
consciousness reflects the adequacy of cortical perfu- A. FLUID RESUSCITATION
sion. When cortical perfusion is severely impaired, the Fluid infusion should start with 20-mL/kg boluses
infant or child fails to respond first to verbal stimuli, titrated to clinical monitors of cardiac output, heart
392 / CHAPTER 13

Table 13–9. Hemodynamic parameters.a

Parameter Formula Normal Values Units

Cardiac output CO = HR × SV Wide age-dependent range L/min
Cardiac index CI = CO/BSA 3.5–5.5 L/min/m2
Stroke index SI = SV/BSA 30–60 mL/m2
Systemic vascular resistance (MAP − CVP) 800–1600 dyne s/cm−5/m2
SVR = 79.9
Cl
Pulmonary vascular resistance PVR = 79.9 (MPAP − PCWP) 80–240 dyne s/cm−5/m2
Cl
a
Formulas and normals from Katz RW, Pollack M, Weibley R: Pulmonary artery catheterization in pediatric intensive care.
Adv Pediatr 1983;30:169.
HR = heart rate, SV = stroke volume, BSA = body surface area, MAP = mean arterial pressure, CVP = central venous pres-
sure, MPAP = mean pulmonary artery pressure, PCWP = pulmonary capillary wedge pressure.

rate, urine output, capillary refill, and level of con- age may not have fully developed sympathetic vesicles
sciousness. Patients who do not respond rapidly to the and may therefore be resistant to dopamine. Dopamine
initial fluid bolus should be considered for invasive he- can increase renal, coronary, and cerebral blood flow by
modynamic monitoring (placement of a CVP, arterial its action on β-receptors and dopaminergic receptors.
line, and possibly pulmonary artery catheter). At higher doses (15 mg/kg/min), α-vasoconstrictor ac-
Initially, most patients tolerate crystalloid (salt solu- tions predominate. Dobutamine may be added to
tion), which is readily available and inexpensive. How- dopamine; however, children younger than 12 months
ever, 4 hours after a crystalloid infusion, only 20% of of age may be less responsive. Epinephrine should be
the solution remains in the intravascular space. Patients used for dopamine-refractory shock and is often consid-
with serious capillary leaks and ongoing plasma losses ered first for patients in cold septic shock. Norepineph-
(eg, burn cases) should initially receive crystalloid, be- rine, and in some instances phenylephrine, can be used
cause in these cases colloid (protein and salt solution) to increase peripheral vasoconstriction in patients
leaks into the interstitium. The protein draws intravas- whose perfusing pressure cannot be increased by
cular fluid into the interstitium, thus increasing ongo- dopamine and epinephrine (see Table 13–8). Hypocal-
ing losses. Patients with hypoalbuminemia or those cemia is often a contributor to cardiac dysfunction in
with intact capillaries who need to retain volume in the shock. Calcium replacement should be given to nor-
intravascular space (eg, patients at risk for cerebral malize ionized calcium levels.
edema) probably benefit from colloid infusions. Experi- The role of inflammatory mediators in the patho-
ence with dextran (a starch compound dissolved in salt genesis of septic shock continues to be defined. Drugs
solution) is limited. Patients with normal heart func- that block some of these mediators appear to be benefi-
tion tolerate increased volume better than those with cial when given early to animals. Human studies of
poor function. Additionally, large volumes of fluid for these same blockers have failed to demonstrate a clear
acute stabilization in children with shock have not been benefit. The differences in pathogenesis and host re-
shown to increase the incidence of ARDS or cerebral sponse to gram-positive or gram-negative sepsis may ex-
edema. Increased fluid requirements may persist for plain some of the differential responsiveness to anti-in-
several days. flammatory agents seen in past clinical trials.
Additionally, the discrepancies may result from low-
B. PHARMACOTHERAPY affinity binding by these antibodies. The molecular
Empiric antibiotics are chosen according to the most mechanisms by which lipopolysaccharide activates cells
likely cause of infection. Inotropic support should be are becoming better understood, which may assist in
considered for patients who continue to have clinical the development of more effective therapies. Modula-
evidence of decreased cardiac output after receiving tion of T cells (with glucocorticoids, cyclosporine, and
60 mL/kg of fluid resuscitation. Dopamine remains the antibodies directed at cytokines) in models of super-
first-line vasopressor. Dopamine causes vasoconstric- antigen-induced injury have proven beneficial, but re-
tion by stimulating the release of norepinephrine from main experimental. Ibuprofen, because of its ability to
sympathetic nerves. Infants younger than 6 months of block cyclooxygenase (cyclooxygenase metabolites are
 CRITICAL CARE / 393

potent modulators of cell function), has shown a trend Butt W: Septic shock. Pediatr Clin North Am 2001;48(3):601
toward stabilizing patients with septic shock, although [PMID: 114111296].
not enough evidence is yet available to recommend for Carcillo JA: Pediatric septic shock and multiple organ failure. Crit
or against the use of ibuprofen for septic shock. Re- Care Clin 2003;19:413 [PMID: 1284813]
cently, excess production of nitric oxide (NO) has been McCarthy RE III et al: Long term outcome of fulminant myocardi-
tis as compared with acute (nonfulminant) myocarditis.
demonstrated to contribute to the hypotension and N Engl J Med 2000;342:690 [PMID: 10706898].
poor perfusion occurring in shock. Analogs of L-argi- Patel GP et al: New treatment strategies for severe sepsis and septic
nine (L-NMA) have been used to block the production shock. Curr Opin Crit Care 2003;9:390 [PMID: 14508152].
of NO in animal models of septic shock with some im- Proft T, Fraser JD: Bacterial superantigens. Clin Exp Immunol
provement in survival. Anecdotal use in adults with se- 2003;133:299 [PMID: 12930353].
vere septic shock has demonstrated some success. Schwartz SM et al: Cellular and molecular aspects of myocardial
Protein C is a primary regulator of coagulation, fib- dysfunction. Crit Care Med 2001;29(10):S214 [PMID:
rinolysis, and coagulation-induced inflammation. 11593064].
Deficits in protein C activation correlate with morbid- Sessler CN, Shepherd W: New concepts in sepsis. Curr Opin Crit
ity and mortality in septic shock. Deficiencies of pro- Care 2002;8:465 [PMID: 12357117].
tein C have been found in children and adults with sep- Shekerdemian L: Nonpharmacologic treatment of acute heart fail-
sis. Recombinant activated protein C reduced mortality ure. Curr Opin Pediatr 2001;13:240 [PMID: 11389358].
rates in an animal model of sepsis. A large randomized, Tabbutt S: Heart failure in pediatric septic shock: Utilizing in-
double-blind, placebo-controlled trial of recombinant otropic support. Crit Care Med 2001;29:S231 [PMID:
11593066].
activated protein C in adults with severe sepsis showed
Takala A et al: Markere of inflammation in sepsis. Ann Med
a significant reduction in mortality rates in patients 2002;34:614 [PMID: 12553502].
treated with activated protein C. A similarly designed
Trager K et al: Metabolic alterations in sepsis and vasoactive drug-
clinical trial of activated protein C in pediatric patients related metabolic effects. Curr Opin Crit Care 2003;9:271
with severe sepsis is ongoing. [PMID: 12883281].
Corticosteroids, by virtue of their action on many van Deuren M et al: Update on meningococcal disease with em-
mediators, are thought to play a role in shock and— phasis on pathogenesis and clinical management. Clin Micro-
based on positive results in animal models of septic biol Rev 2000;13(1):144 [PMID: 10627495].
shock—have been advocated for treatment of shock in Vincent JL et al; Recombinant Human Activated Protein C World-
humans. Children with meningococcal meningitis and wide Evaluation in Severe Sepsis (PROWESS) Study Group:
AIDS patients with pneumocystis pneumonia have Effects of drotrecogin alfa (activated) on organ dysfunction in
the PROWESS trial. Crit Care Med 2003;31:834 [PMID:
shown improvement in oxygenation and a trend toward 12626993].
improved survival when treated with corticosteroids.
The use of hydrocortisone in adults with relative
adrenal insufficiency and septic shock was shown to im- INDICATIONS FOR CENTRAL VENOUS
prove short-term outcome. Importantly, a low aldos- & ARTERIAL CANNULATION
terone state may be more common in children with
septic shock than previously thought. Hydrocortisone Placement of catheters into the central venous or arterial
(50 mg/kg) should be considered for children at risk for circulation may be justified for continuous assessment of
adrenal insufficiency—those with purpura fulminans or intravascular volume or cardiac function; blood drawing
pituitary or adrenal abnormalities, those receiving for lab work; or administration of volume, drugs, or hy-
steroids for chronic illness, and those with septic shock peralimentation. One should always weigh the risks of
and multiorgan system dysfunction not responding well bleeding, infection, and clotting against the expected
to traditional inotropic therapy. benefits before placing any indwelling catheter.
ECMO has been considered in the treatment of
shock in patients with recoverable cardiac and pul- General Rules for Equipment Selection
monary function who require both pulmonary and car- & Technique
diac support.
1. Set up and examine all equipment needed before
getting started. Use of a limited number of kits
Annane D: Corticosteroids for septic shock. Crit Care Med and equipment will provide greater consistency
2001;29(7):S117 [PMID: 11445745].
and success.
Auslender M, Artman M: Overview of the management of pedi-
atric heart failure. Prog in Ped Cardiol 2000;11:231 [PMID: 2. Apply EMLA cream (eutectic mixture of lidocaine
1097876]. 2.5% and prilocaine 2.5%) to the area of puncture
Batra AS, Lewis AB: Acute myocarditis. Curr Opin Pediatr (45 minutes before the procedure) or infiltrate
2001;13:234 [PMID: 11389357]. with local anesthetic before prepping the skin.
394 / CHAPTER 13

3. The remainder of the procedure should occur

under aseptic technique (including gown, mask,
hair cover for operator and assistant).
External jugular vein
4. Sterilize and drape the area around the point of
entry. Sternocleidomastoid muscle
5. When searching for the vessel, make straight
passes while maintaining slight negative pressure.
Advance and withdraw the needle at the same
speed. Frequently, the blood return will occur
during withdrawal.
6. Once there is free flow of venous blood into the
syringe, remove the syringe without moving the
needle and, if using the Seldinger technique, pass
the J wire through the needle. When appropriate,
watch the electrocardiogram for arrhythmias, be-
cause they frequently occur when the J wire
touches the right side of the heart.
7. Withdraw the needle over the J wire and clean the
wire of blood.
8. Make a nick with a No. 11 blade at the point
where the J wire enters the skin. Pass the intro-
ducer or the intravascular catheter (or both) over
the J wire. 30°
9. With the catheters in place, remove the wire along
with the introducer. Figure 13–2. External jugular vein technique. (Repro-
10. Check to make sure that blood can be drawn eas- duced, with permission, from Chameides L: Textbook of Pe-
ily through the new line. diatric Advanced Life Support. American Heart Association,
11. Verify the position of the line on radiograph. 1988.)

Points of Entry for Venous Line Placement

A. EXTERNAL JUGULAR VEIN nal notch and then feel lateral to the trachea for the
carotid pulse. Just lateral to the carotid pulse, at a
Place a soft cloth roll beneath the patient’s shoulder and 30-degree angle from horizontal, insert a finder needle
turn the head to the contralateral side (Figure 13–2). (25-gauge), aiming between the ipsilateral nipple and
The Valsalva maneuver, Trendelenburg position, and shoulder. Once venous return is established, remove the
occlusion of the vessel at the clavicular level are ways of finder needle and repeat the procedure with the appro-
temporarily increasing jugular distention and visibility. priate-size larger needle.
To overcome the problems of this vessel’s mobility and
thick wall, apply cephalic retraction of the skin over the C. SUBCLAVIAN VEIN
vessel superior to the point of needle entry. Maintain After the patient has been prepped, draped, and posi-
gentle negative pressure in the syringe attached to the tioned (Figure 13–4), move the needle flat along the
needle as it is advanced toward the vessel. Needle entry chest, entering along the inferior edge of the clavicle
into the vessel lumen is usually signaled by a change in just lateral to the midclavicular line and aiming for the
resistance followed by appearance of venous blood in suprasternal notch. Once venous return is established,
the hub of the needle. Remove the syringe without use the Seldinger technique.
moving the needle and pass a soft J wire into the vessel
lumen. Remove the needle and pass the central line D. FEMORAL VEIN
over the J wire. With the patient’s leg slightly abducted (Figure 13–5),
find the femoral artery 3–4 cm below the inguinal liga-
B. INTERNAL JUGULAR VEIN ment. The femoral vein is just medial and parallel to
Once the patient has been prepped, draped, and posi- the femoral artery. Insert the needle at a 30- to 45-de-
tioned as shown in Figure 13–3, feel for the trachea gree angle. Once venous return is established, use the
halfway between the angle of the jaw and the supraster- Seldinger technique.
 CRITICAL CARE / 395

Common carotid artery

Internal jugular vein
Sternocleidomastoid
muscle

rd
Subclavian vein

towa
Suprasternal notch
Superior
Brachiocephalic vein

Aim
vena cava

A B

Figure 13–3. A: The internal jugular vein and its relationship to the surrounding anatomy. B: Technique of anterior
internal jugular cannulation. (Reproduced, with permission, from Chameides L: Textbook of Pediatric Advanced Life Sup-
port. American Heart Association, 1988.)

Subclavian
vein
Clavicle

Clavicle

Subclavian vein

First rib
A B 30°

Figure 13–4. Subclavian artery. A: Anatomy. B: Technique. (Reproduced, with permission, from Chameides L: Text-
book of Pediatric Advanced Life Support. American Heart Association, 1988.)
396 / CHAPTER 13

General Rules for Cannulation

of the Arterial System
The Seldinger technique can be applied for arterial tree
Anterior superior cannulation as well. Most arteries can be cannulated
iliac spine percutaneously.
Inguinal ligament
Femoral nerve 1. Puncture the skin at the insertion site to eliminate
Femoral artery any drag or resistance on the catheter advance-
Pubic tubercle ment.
2. Insert the cannula at a 30-degree angle to the skin
Femoral vein surface, advancing at a slow rate toward the arter-
ial pulse. Watch the hub of the cannula for a flash
of arterial blood.
3. When arterial flash is seen, lower the catheter to a
10-degree angle with the surface of the skin and
A advance the catheter into the lumen of the artery.
If successful, pulsatile arterial flow will continue
into the catheter.
4. Hold the catheter while removing the needle
stylet. Arterial blood will pulse out of the catheter
if the tip is in the arterial lumen.
5. Advance the catheter into the lumen; attach a sy-
ringe containing normal saline with 1 unit/mL of
heparin; aspirate to make certain that there are no
bubbles; and then gently flush the catheter.
6. If arterial flow into the needle stylet stops during
catheter advancement, advance this unit an addi-
tional centimeter. Remove the needle stylet and
45° place it on a sterile surface. Pull the catheter out
slowly. When the tip of the catheter flips into the
arterial lumen, the pulsatile arterial blood flow is
seen. Rotate the catheter to ensure that the
catheter is free within the vessel lumen, then ad-
vance the remainder of the catheter length into
B the vessel.
7. Suture the catheter in place while ensuring that
Figure 13–5. Femoral vein. A: Anatomy. B: Tech- the arterial trace is not damped.
nique. (Reproduced, with permission, from Chameides L: 8. Dress the insertion site with sterile gauze, and
Textbook of Pediatric Advanced Life Support. American tape it to the skin.
Heart Association, 1988.)
Points of Entry for Arterial Line Placement
Always consider whether collateral arterial blood is
E. ANTECUBITAL VEIN flowing to the structures distal to the insertion point.
Peripherally inserted catheter (PIC) lines (2.8–4 Fr) are The Allen test must be done prior to radial or ulnar
long, soft, Silastic, styletted catheters most commonly artery cannulation.
threaded from an antecubital vessel to the right atrium. Arterial sites, listed in order of preference, include:
These lines are not difficult to insert and are easy to 1. Radial artery (nondominant arm first)
dress and keep clean. They are suited for long-term use
because they are tolerable for the patient, good for infu- 2. Femoral artery (morbidity is the same as for the
sion of hyperalimentation and drugs, and less thrombo- radial artery beyond the newborn period)
genic. In general, they are not suitable for obtaining 3. Posterior tibial artery
blood for laboratory analysis. 4. Dorsalis pedis artery
 CRITICAL CARE / 397

5. Ulnar artery (if distal radial filling is present in Table 13–10. Pediatric illnesses commonly
that hand) associated with intracranial hypertension
6. Axillary artery
7. Brachial artery (poor collateral flow, used only Diffuse processes
during cardiac surgery in newborn-sized patients Trauma
with arterial access limitations) Hypoxic-ischemic
Near-drowning
Final Considerations Cardiorespiratory arrest
Infectious
1. Patient benefit should outweigh any risks from Encephalitis
central venous or arterial cannulation. Meningitis
Metabolic
2. Coagulation status of the patient at the time of Reye’s syndrome
placement and throughout the time of use must Liver failure
be considered, because deep venous and arterial Inborn error metabolism (IEM)
thrombus formation is partially related to the pa- Toxic
tient’s coagulation status. Lead
3. The incidence of catheter colonization and infec- Vitamin A
tion increases if central venous and arterial lines Focal processes
are left in for more than 6 days. Trauma
Hypoxic-ischemic
Johnson EM et al: Complications and risks of central venous Trauma
catheter placement in children. Surgery 1998;124:911 Stroke
[PMID: 9823406]. Infectious
Stovroff M, Teague WG: Intravenous access in infants and chil- Abscess
dren. Pediatr Clin North Am 1998;45:1373 [PMID: Mass lesions
9889758]. Tumors
Vrazas JI: Central venous catheter placement. Hosp Med Hematomas
1999;60:337 [PMID: 10396408].

BRAIN INJURY/CEREBRAL EDEMA The brain occupies about 80% of the volume of the
Intracranial hypertension is a common feature of many skull. Apart from solid tumors, increases in the brain
illnesses treated in the PICU (Table 13–10). The early compartment are generally a result of cerebral edema.
signs and symptoms of intracranial hypertension (Table Cerebral edema can be divided into three forms: vaso-
13–11) tend to be nonspecific. The classic Cushing genic, hydrostatic, and cytotoxic. Vasogenic edema oc-
triad of bradycardia, hypertension, and apnea occurs curs in areas of inflamed tissue characterized by in-
late and is often incomplete in children. creased capillary permeability, and is most typical
Accurate assessment and treatment of elevations in
ICP requires an understanding of the basic pathophysi-
ology of intracranial hypertension, as well as the current Table 13–11. Signs and symptoms of intracranial
evidence supporting the various treatment options. hypertension in children.
Most of our current understanding and approach to
treatment is based on studies of patients with traumatic Early
brain injuries. Whether those concepts are directly rele- Poor feeding, vomiting
vant to the pathophysiologic processes involved in more Irritability, lethargy
global CNS injuries, such as hypoxia and metabolic dis- Seizures
orders, remains a matter of debate. Hypertension
Within the constraints of a closed skull, an enlarge- Late
ment of brain tissue, an increased volume of cerebrospi- Coma
nal fluid (CSF), or an increased volume of blood (or the Decerebrate responses
presence of a space-occupying lesion such as a tumor or Cranial nerve palsies
an abscess) will reduce the size of the other compart- Abnormal respirations
ments or increase pressure. The factors contributing to Bradycardia
intracranial hypertension can be understood by consid- Hypertension
Apnea
ering each of these three primary compartments.
398 / CHAPTER 13

around CNS tumors, abscesses, and infarcts. This form determinant of cerebral blood volume. High metabolic
of edema is thought to be at least partially responsive to rates lead to vasodilation and increased blood volume,
corticosteroid therapy. Hydrostatic, or interstitial, whereas low metabolic rates allow the vessels to constrict
edema is a result of elevated CSF hydrostatic pressures. and reduce blood flow and blood volume. Partial pres-
It occurs primarily in lesions associated with obstruc- sure of carbon dioxide is another important determinant
tion to CSF flow, and in a typical periventricular distri- of cerebral blood volume, as elevations in blood PCO2
bution. This form of edema is best treated by CSF lead to cerebral vasodilation and decreases in PCO2 lead
drainage. The third form of cerebral edema, cytotoxic to vasoconstriction. Finally, cerebral blood volume is
edema, is the most common of the three forms seen in linked to cerebral blood flow through the phenomenon
the PICU and is, unfortunately, the least easily treated. of pressure autoregulation. As shown in Figure 13–6, at
Cytotoxic edema occurs as a result of direct injury to low systolic blood pressures, the cerebral vessels are maxi-
brain cells, often leading to irreversible cell swelling and mally dilated and blood flow is only increased by increas-
death. This form of cerebral edema is typical of trau- ing blood pressure. Within the range of autoregulation,
matic brain injuries as well as hypoxic-ischemic injuries the cerebral vessels attempt to maintain a constant flow
and metabolic disease. rate over a range of blood pressures; increased blood pres-
CSF occupies an estimated 10% of the intracranial sure results in vasoconstriction, in turn reducing cerebral
space. Intracranial hypertension due primarily to in- blood volume. Once the cerebral vessels are maximally
creases in CSF volume (eg, hydrocephalus, primary or constricted, continued increases in pressure may further
secondary) is generally easily diagnosed by CT scan and increase cerebral blood flow and volume.
easily treated with appropriate drainage and shunting. Treatments for intracranial hypertension are largely
Cerebral blood volume comprises the final 10% of derived from experience with traumatic brain injury.
the intracranial space. Changes in cerebral blood vol- An important concept in this regard is that of a “pri-
ume generally result from alterations in vascular diame- mary” as opposed to a “secondary” brain injury. In this
ter in response to local metabolic demands or to local context, primary injury refers to direct damage to brain
vascular pressures—so-called metabolic and pressure tissue resulting from the original insult to the CNS,
autoregulation. These physiologic responses are the such as physical damage from trauma. This injury is
means by which the CNS circulation regulates and complete before the patient reaches the health care sys-
maintains adequate blood flow to the brain. Given the tem. As the injured brain swells due to cytotoxic
difficulty in effectively treating cytotoxic brain swelling edema, intracranial hypertension develops, potentially
and the relative rarity of uncomplicated CSF obstruc- limiting cerebral blood flow to portions of the brain
tive lesions in the PICU, most of the current therapies and leading to extension of the initial injury (ie, sec-
aimed at controlling intracranial hypertension rely on ondary injury). Medical treatment of the patient with
altering cerebral blood volume. intracranial hypertension aims to prevent or reduce sec-
Several factors interact to control cerebral blood vol- ondary injuries.
ume via the autoregulatory responses of the cerebral vas- The primary goal of treatment is to optimize perfu-
culature. The rate of cerebral metabolism is an important sion of areas of the brain that are salvageable. This can

Cerebral
blood flow

60 150

Figure 13–6. Pressure autoregulation in

Blood pressure (mm Hg) the cerebral vasculature.
 CRITICAL CARE / 399

be accomplished by reducing ICP and by ensuring ade- ing the airway and providing adequate sedation. Addi-
quate perfusion. Rational guidance of treatment re- tional measures would include the removal of any mass
quires invasive monitoring so that it can be effectively lesions (eg, tumors, abscesses, hematomas) and ade-
titrated. Although a complete discussion of the indica- quate ventricular drainage. Further efforts are then
tions for ICP monitoring is beyond the scope of this largely directed at reducing cerebral blood volume.
chapter, the topic can be briefly summarized with the Osmotic diuretics such as mannitol are often used to
suggestion that an ICP monitor be used for patients at treat intracranial hypertension. They are thought to act
significant risk for intracranial hypertension, in whom first by decreasing blood viscosity, allowing for in-
the treatment of elevated CNS pressures is planned. creased flow and subsequent autoregulatory vasocon-
Monitoring other parameters of CNS oxygen delivery striction. The osmotic effects on the cells and intersti-
(ie, blood pressure, ABGs, intravascular volume) gener- tium of the brain prolong the reduction in ICP.
ally mandates the placement of arterial and central ve- Although mannitol has never been subjected to a
nous catheters. Little evidence exists to support the util- placebo-controlled trial, it has been shown to lead to
ity of ICP-directed therapies in conditions associated better outcomes than barbiturate therapy in patients
with global CNS injuries (eg, anoxic brain injuries). with refractory ICP elevations. Current guidelines sug-
Maintenance of adequate cardiac output and oxygen gest the use of mannitol in doses of 0.25 to 0.5 g/kg for
delivery to the CNS is critical in treating patients with intracranial hypertension unresponsive to sedation.
intracranial hypertension. Studies in both adult and pe- Renal failure due to acute tubular necrosis can be a
diatric head injury patients show that even a single treatment-limiting side effect, particularly if serum os-
episode of hypotension or arterial hypoxemia is associ- molarity is allowed to rise above 320 and intravascular
ated with a marked increase in mortality rates. Al- volume depletion occurs.
though studies have not delineated clear age-appropri- Hyperventilation—long a mainstay in the treatment
ate thresholds for blood pressure and arterial PO2 in this of intracranial hypertension—is controversial. Al-
setting, a rational starting point for therapy would seem though acutely effective in causing cerebral vasocon-
to be maintenance of an adequate circulating blood vol- striction, hyperventilation leads to much larger de-
ume, a blood pressure at least well within the normal creases in blood flow than in blood volume, such that
range for age, and an arterial PO2 of at least 60 mm Hg. hyperventilation to the point necessary to control ICP
Hypotension and hypoxemia should be treated urgently may actually compromise CNS perfusion and lead to
and aggressively. worsened secondary injury. This concept has been con-
In general, the threshold at which treatment for in- firmed by studies showing worse outcomes in head-in-
tracranial hypertension should be started is in the range jured patients consistently hyperventilated to a PCO2 of
of 15 to 20 cm H2O pressure. Above this pressure, the 25 mm Hg or less. Current guidelines suggest that
compliance of the skull worsens dramatically (Figure moderate hyperventilation (PCO2 of 30–35 mm Hg)
13–7), and very minor increases in intracranial contents may be used for mild to moderate intracranial hyper-
lead to large increases in ICP. Initial therapy for in- tension but that extreme hyperventilation (PCO2 <
tracranial hypertension should always consist of secur- 30 mm Hg) should be reserved for patients with ICP

Intracranial
pressure

20

Figure 13–7. Compliance curve of

the skull with changing volume of in-
Volume tracranial contents.
400 / CHAPTER 13

elevations unresponsive to other measures, including se- Glascow Coma Scale < 8
dation, paralysis, ventricular drainage, and osmotic di-
uretics. Due to the risks of worsened CNS ischemia, (and nonsurgical head injury)
monitoring cerebral perfusion by blood flow studies or
jugular bulb saturation is recommended for patients
Monitor ICP (consider placement of
undergoing extreme hyperventilation.
ventriculostomy at same time) and
The use of barbiturates in this setting is based on
their suppression of cerebral metabolism and the subse-
quent metabolic autoregulation effects on cerebral
blood volume. Although effective in many instances for If ICP remains elevated proceed through the following
ICP elevations, these agents are potent cardiac depres- steps until there is a positive response.
sants, and their use often leads to hypotension, necessi-
tating the use of a pressor to maintain perfusion. In ad-
dition, plasma barbiturate levels correlate poorly with FIRST TIER OF THERAPY:
effect on ICP, suggesting that monitoring of CNS elec-
1. Sedation, analgesia, elevate head of bed
trical activity by electroencephalography (EEG) is nec-
essary to accurately titrate the use of these agents. Cur- 2. Drain CSF via ventriculostomy if present
rent guidelines suggest the use of barbiturates for
treating intracranial hypertension refractory to seda- 3.Neuromuscular blockade
tion, paralysis, ventricular drainage, and osmotic di-
uretics. 4. Mannitol or 3% saline to maintain osmolarity
Another important concept in the management of > 320
intracranial hypertension is that of the cerebral perfu-
sion pressure (CPP). The CPP is the driving pressure 5. Hyperventilation to pCO2 of 30 – 35 mm Hg
across the cerebral circulation and is defined as mean
airway pressure – CVP (or ICP, whichever is higher).
Some authors have suggested that careful attention to
If ICP remains elevated proceed to second-
maintenance of a supranormal cerebral perfusion pres- tier therapy (order nonspecified)
sure may lead to better outcomes for head-injured pa-
tients. Although there are no well-controlled trials to
draw from (particularly for pediatric patients), current
guidelines suggest that maintenance of a “normal” CPP SECOND TIER OF THERAPY
for age (50–70 mm Hg) is a valid secondary goal of
treatment, as long as it is included in a plan to use the Decompressive cranectomy
other ICP-directed therapies discussed earlier.
A suggested treatment algorithm for patients with Barbiturate therapy
documented intracranial hypertension is presented in Moderate hypothermia (32–34°C)
Figure 13–8. As mentioned earlier, this algorithm rep-
resents the current best evidence for the management of Place lumbar drain
intracranial hypertension. The information is largely
drawn from experience with traumatic brain injuries, Hyperventilation to pCO2 < 30 mm Hg
and the direct applicability of these concepts to other
illnesses associated with intracranial hypertension re-
mains unclear. Figure 13–8. Proposed treatment algorithm for in-
tracranial hypertension in head injury. JvO2 = jugular ve-
nous oxygen saturation.
Albanese J et al: Decompressive craniectomy for severe traumatic
brain injury: Evaluation of the effects at one year. Crit Care
Med 2003;31:2535 [PMID: 14530763]. Goldstein LB: Neuropharmacology of TBI-induced plasticity.
Bayir H et al: Traumatic brain injury in infants and children: Brain Inj 2003;17:685 [PMID: 12850953].
Mechanisms of secondary damage and treatment in the inten- Heimann A et al: Effects of hypertonic/hyperoncotic treatment
sive care unit. Crit Care Clin 2003;19:529 [PMID: after rat cortical vein occlusion. Crit Care Med 2003;31:
12848319]. 2495 [PMID: 14530757].
Carney NA et al: Guidelines for the acute medical management of Littlejohns LR et al: Brain tissue oxygen monitoring in severe brain
severe traumatic brain injury in infants, children, and adoles- injury: I. Research and usefulness in critical care. Crit Care
cents. Pediatr Crit Care Med 2003;4:S1 [PMID: 12847355]. Nurse 2003;23:17 [PMID: 12961780].
 CRITICAL CARE / 401

McIntyre LA et al: Prolonged therapeutic hypothermia after trau- • It should be emphasized that decisions are not irrevo-
matic brain injury in adults: A systematic review. JAMA cable; if at any time the family or health care
2003;289:3007 [PMID: 12799408].
providers wish to reconsider the decision, full med-
Okonkwo DO, Stone JR: Basic science of closed head injuries and ical therapy should be reinstituted until the situation
spinal cord injuries. Clin Sports Med 2003;22:467 [PMID:
12852680]. is clarified.
Phillis JW, O’Regan MH: The role of phospholipases, cyclooxyge-
nases, and lipoxygenases in cerebral ischemic/traumatic in- Palliative Care
juries. Crit Rev Neurobiol 2003;15:61 [PMID: 14513863].
Roberts I et al: Mannitol for acute traumatic brain injury.
Helping a patient experience a dignified and pain-free
Cochrane Database Syst Rev 2003;(2):CD001049 [PMID: death is one of the many unique challenges facing care-
12804397]. givers in the PICU. Pediatric death is characterized by
its relative infrequency, by the prognostic uncertainties
of many pediatric illnesses, and by the fine line between
ETHICAL DELIBERATION AND congenital disorder and incurable disease. When a pre-
END-OF-LIFE CARE IN THE PICU dictable early death is likely, intensivists are often called
on to care for the patient and family during the final
Bioethics Consultation in the PICU days and hours of the patient’s life.
Advances in critical care medicine give PICU practi- In the past several years, palliative medicine has de-
tioners the ability to prolong life without being able to veloped as a specialized field of practice to address the
ensure a reasonable quality of life. Health care profes- needs of dying children. The practice of providing sup-
sionals in this setting are often called on to help pa- portive care at end-of-life in pediatrics is fundamentally
tients and families wrestle with questions of medical fu- different from that in adult medicine. In-hospital
tility. As conflict surrounding care and decision making deaths in pediatrics encompass a more heterogeneous
has arisen, the introduction of ethics consultation in patient population with developmental issues and fam-
the ICU setting has served to improve the process by ily dynamics that complicate the process.
helping to identify, analyze, and resolve ethical prob- Once the inclusive decision is made to limit or with-
lems. Ethics consultation can independently clarify draw LSMT, a palliative care plan should be agreed on
views and allow the health care team, patient, and fam- and instituted. The plan should address the following
ily to make decisions that respect patient autonomy and basic principles:
promote maximum benefit and minimal harm to the • Adequate pain control and sedation
patient. • Provision of warmth and cleanliness
• Nutrition
Managed Withdrawal of Treatment • Ongoing patient and family support
With increasing frequency, PICU deaths are pre- The decision to withhold or withdraw LSMT from
dictable and result from the withholding or withdraw- a pediatric patient does not suggest a plan to hasten the
ing of life-sustaining medical therapy (LSMT). Discus- death. The goal of palliative care remains optimization
sions with patients and families regarding the decision of the patient’s and family’s experience prior to and fol-
to limit resuscitation or to withdraw LSMT should re- lowing the death.
spect the following basic principles:
Tissue & Organ Donation
• Deliberations begin with a clear statement that the
patient’s good is the goal. Organ transplantation has become standard therapy.
Although the demand for tissue and solid organs has in-
• With the assistance of the health care team, the pa- creased, donations have remained largely unchanged.
tient and family can make reasonable decisions about The prospect of organ or tissue donation should be
limitation or withdrawal of LSMT based on goals of considered with all patients dying in the PICU. To be a
care for the patient. solid organ donor, the patient must be clinically brain
• The burden of continued life (pain and suffering) dead and have no conditions contraindicating dona-
should outweigh any potential benefit from contin- tion. With patients from whom life-support must be
ued therapy. withdrawn, tissue (heart valves, corneas, skin, bone) can
• Discussions with the patient and family are con- be obtained after cardiac death. The Required Request
ducted by experienced personnel with the ability to Law mandates that health care professionals approach
communicate in a clear and compassionate manner all donor-eligible families to inquire about organ pro-
at an appropriate time and place. curement. The decision to donate must be made free of
402 / CHAPTER 13

coercion, with informed consent, and without financial Hynson JL, Sawyer SM: Paediatric palliative care: Distinctive needs
incentive. and emerging issues. J Paediatr Child Health 2001;37:323
[PMID: 11532048].
Kunin H: Ethical issues in pediatric life-threatening illness: Dilem-
Brain Death (See Chapter 23.) mas of consent, assent, and communication. Ethics Behavior
1997;7:43 [PMID: 11654857].
The development of criteria and expertise in the clinical
McCallum DE et al: How children die in hospital. J Pain Symptom
brain death exam is borne out of the demand for solid Manage 2000;20:6 [PMID: 11131260].
organs from patients still receiving LSMT. Currently, Schneiderman LJ et al: Impact of ethics consultation in the inten-
the diagnosis of brain death is based on national guide- sive care setting: A randomized, controlled trial. Crit Care
lines that render some clarity and standardization to Med 2000;28:12 [PMID: 11153636].
this critical task.

Clinical Brain Death Exam

NUTRITIONAL SUPPORT
OF THE CRITICALLY ILL CHILD
Establish the cause of the disease or injury and exclude
potentially reversible syndromes that may produce signs Metabolic and Physiologic Responses
similar to brain death. Also establish the following: When severely ill pediatric patients are admitted to the
• Coexistence of coma and apneaa (“apnea test” intensive care unit, the initial therapy is directed at the
~ 3 minutes with PCO2 > 60 mm Hg) primary or underlying problem and at providing car-
diorespiratory and hemodynamic support. Although
• Absence of brainstem function this management is critical to sustaining life in these
• Normal blood pressure and temperature patients, provision of adequate nutritional support is
• Flaccid muscle tone, no spontaneous movements often overlooked early in the course of therapy. As in-
• Exam consistent throughout observation period creasing evidence demonstrates that nutritional status
and support affect the morbidity and mortality of criti-
Recommended observation periods for children of cally ill patients, it is vital that this aspect of care be ad-
the following ages: dressed early in the hospital course.
• Seven days to 2 months old—Two exams over Trauma, surgery, burns, and sepsis impose meta-
48 hours; with EEG bolic and physiologic disturbances that vary in degree,
but have many similarities. The insult triggers the affer-
• Two months to 1 year—Two exams over 24 hours; ent limb of the neurophysiologic reflex, which is com-
with EEG posed of pain and neurosensory pathways. In response,
• Over 1 year—Two exams over 12 to 24 hours the efferent limb consisting of neurologic and en-
docrine pathways, increases autonomic sympathetic ac-
American Academy of Pediatrics Committee on Bioethics and tivity with norepinephrine and epinephrine secretions
Committee on Hospital Care: Palliative care for children. Pe- and increases pituitary release of a host of hormones in-
diatrics 2000;106:351 [PMID: 10920167].
cluding adrenocorticotropic hormone (ACTH), growth
Arnold RM et al: Ethical issues in organ procurement: A review for hormone (GH), and antidiuretic hormone (ADH). Re-
intensivists. Crit Care Clin 1996; 12:29 [PMID: 8821008].
lease of catecholamines inhibits insulin secretion and
Brody H et al: Withdrawing intensive life-sustaining treatment:
Recommendations for compassionate clinical management.
activity, and stimulates glucagon and ACTH produc-
N Engl J Med 1997;336:652 [PMID: 9032053]. tion. ACTH and ADH increase corticosteroid release,
Canadian Neurocritical Care Group: Guidelines for the diagnosis inhibit insulin activity, and increase aldosterone. The
of brain death. Can J Neurol Sci 1999;26:64 [PMID: overall effect is to direct an end-organ increase in meta-
10068812]. bolic rate and to provide increased substrate availability
Feudtner C et al: Deaths attributed to pediatric complex chronic for energy use (Table 13–12). In addition, the body
conditions: National trends and implications for supportive has a cellular response to tissue injury. Cells migrate
care services. Pediatrics 2001;107:e99 [PMID: 11389297]. to the damaged area to facilitate wound healing and aid
Harrison AM, Botkin JR: Can pediatricians define and apply the in infection control with the release of inflammatory
concept of brain death? Pediatrics 1999;103: e82 [PMID: mediators. These cells are mainly dependent on glucose
10353979].
for their energy source, which is an important reason
the hypermetabolic state is necessary. These events
a
Cerebral angiography, radionuclide scanning, or transcranial
initiate a hypermetabolic response that influences the
Doppler ultrasonography can be used to assess brain function if mobilization and use of nutrients as substrates. Al-
apnea testing cannot be performed or if there is need for corrobora- though all substrates undergo increased use, the frac-
tive studies. tion of calories derived from glucose is reduced, and the
 CRITICAL CARE / 403

Table 13–12. Metabolic and physiologic stances are infused intravenously. Hyperglycemia and
responses to severe illness. secondary hyperinsulinemia also inhibit ketosis despite
the increased rate of lipolysis. The hyperglycemia does,
Physiologic however, maintain glucose supply to the brain. An ele-
Cardiovascular vated glucagon/insulin ratio and increased secretion
Increased cardiac output and plasma concentrations of catecholamines produce
Peripheral vasodilatation and capillary leak relative peripheral insulin resistance. Inefficient glucose
Expansion of vascular compartment and fatty acid uptakes are inadequate to meet increased
Pulmonary energy needs, leading to increased oxidation of
Increased minute ventilation branched-chain amino acids. Because branched-chain
Ventilation/perfusion mismatch amino acids are essential amino acids, their oxidation
Inefficient gas exchange depletes a valuable pool of precursors for protein syn-
Increased carbon dioxide responsiveness thesis. Administration of excess glucose can lead to hy-
Skeletal muscle perosmolar complications, excess energy expenditure,
Easier fatigability increased CO2 production, cholestasis, and fatty infil-
Slower relaxation tration of the liver.
Altered force-frequency pattern Lipids are the major source of energy used during
Renal periods of stress starvation. Thus, lipolysis is increased
Salt and water retention and lipogenesis is decreased despite high levels of glu-
Impaired concentrating ability cose and insulin. During stress starvation, peripheral
Metabolic tissues, such as skeletal muscle, myocardium, and respi-
Hormone and hormone-like levels ratory muscles are able to use lipids as their primary en-
Increased insulin ergy source. Turnover of medium- and long-chain fatty
Increased glucocorticoids acids is increased, although the clearance rate of long-
Increased catecholamines chain fatty acid and triglycerides is reduced, primarily
Increased interleukin-1 through a reduction in peripheral lipoprotein lipase ac-
Increased tumor necrosis factor tivity that is inhibited by TNF. If excess lipids are
Carbohydrate metabolism administered, complications such as hyperlipidemia,
Increased blood glucose bacteremia, and suppression of in vitro tests of poly-
Increased gluconeogenesis morphonuclear and lymphocyte function may occur.
Increased glucose turnover Protein catabolism is the hallmark of the metabolic
Glucose intolerance
stress response. Although the rate of protein synthesis is
Fat metabolism
Increased lipid turnover and utilization
actually increased in the hypermetabolic state, it is sig-
Insuppressible lipolysis nificantly reduced compared with the rate of protein
Decreased ketogenesis breakdown. Protein is broken down mainly to provide
Protein metabolism carbon skeletons for use in gluconeogenesis, but amino
Increased muscle protein catabolism acids are also used to support the cellular inflammatory
Increased muscle branched-chain amino acid oxidation response, the hepatic synthesis of acute-phase reactant
Increased serum amino acids proteins, and wound healing. Thus, the contribution of
Increased mitogen losses protein to total caloric expenditure increases from 10%
in normal children to 15–20% in critically ill children.
The discrepancy between protein catabolism and syn-
thesis leads to a negative nitrogen balance and loss of
fraction derived from protein and lipid breakdown is lean body mass. This condition can be reduced or even
increased. reversed with increased nonprotein calorie and protein
Hyperglycemia and glucose intolerance are charac- nutrition. Increased nutrient intake appears to make a
teristic traits of the hypermetabolic state. Although glu- difference in the ability of the patient to tolerate stress.
cose use is increased, serum glucose levels are elevated,
reflecting neuroendocrine stimulation of glycogenolysis Nutritional Assessment
and gluconeogenesis. Gluconeogenesis occurs primarily
from lactate, alanine, glutamine, and other amino acids The pediatric patient is at a marked disadvantage com-
derived from muscle breakdown and from glycerol de- pared with adults during periods of stress starvation. The
rived from lipolysis. The hepatic production of glucose child is a growing organism with little metabolic reserve
is increased, and fails to respond to increased plasma to compensate for the metabolic stresses created by
concentrations of glucose or insulin when these sub- surgery, trauma, and sepsis. Preexisting nutritional status
404 / CHAPTER 13

and the degree of stress imposed by the disease process Table 13–14. Activity and stress factors (× REE).
are important factors in estimating nutritional require-
ments of the critically ill patient. Accurate assessment of Condition Factor Condition Factor
nutritional requirements is important as both overfeed-
ing and underfeeding can lead to increased morbidity. ICU on vent Activity
One way to estimate nutritional requirements is to apply 1.0–1.15 Peritonitis Stress 1.2–1.5
US recommended dietary allowances (RDA). However, Confined Activity
since these recommendations are based on populations of to bed 1.1–1.2 Cardiac failure Stress 1.25–1.5
normal healthy subjects, applying RDAs to critically ill Light activity Activity
patients significantly overestimates their caloric require- 1.2–1.3 Head injury Stress 1.3–1.4
ments. Therefore, several equations have been formu-
lated in an attempt to predict basal energy needs of the Fever, per 1°C Stress
critically ill patient. Some of these formulas estimate the 1.12–1.13 Liver failure Stress 1.4–1.5
basal metabolic rate (BMR), which is the energy require- Major surgery Stress
ment for a fasting (10–12 hours) person who recently 1.2–1.3 Sepsis Stress 1.4–1.5
awoke from sleep and is at rest with a normal body tem-
perature in the absence of any stress. Other formulas esti- Multiple Stress
fractures 1.2–1.35 Burns Stress 1.5–2.0
mate the resting energy expenditure (REE), which is the
energy expenditure of a person at rest with a normal REE = resting energy expenditure.
body and ambient temperature, but not necessarily fast-
ing. The BMR and REE are similar, usually differing by
less than 10%. Harris-Benedict and the World Health suggests that even they may not be accurate enough to
Organization have recommended formulas that are use in critically ill children.
among the most commonly used (Table 13–13). Once Indirect calorimetry has been used to measure pa-
the basal metabolic demands have been estimated, it is tients’ REE and appears to reflect a more accurate
then multiplied by a stress factor correlating to underly- method of determining nutritional requirements. In-
ing disease process to determine the ultimate energy re- deed, indirect calorimetry measurements were used to
quirements for the patient (Table 13–14). Compared derive the stress factors used with prediction formulas.
with RDAs, these formulas better estimate energy re- Though this method was once used strictly for research,
quirements in sick patients. However, recent evidence technology has enabled the production of portable, ac-
curate devices that can be used anywhere in the hospi-
tal. Indirect calorimetry measures the amount of oxy-
gen absorbed across the lung. This value is assumed to
Table 13–13. Estimating needs for critically ill be equal to the amount of oxygen consumed in meta-
pediatric patients. bolic processes. The metabolic rate determined in milli-
liters of oxygen consumed per minutes can be con-
Resting Average Average verted to calories per hour, thereby providing a measure
Energy Range Range of of REE. Carbon dioxide production is also measured.
Expenditure of Energy Protein The ratio of CO2 production to O2 consumption yields
(REE) Needs Needs the respiratory quotient (RQ), which is a measure of
Age kcal/kg kcal/kg g/kg substrate use. Inefficiencies in substrate use can be dis-
covered and corrected by modification of RQ through
Infants 0–6 mo 55 90–120 2–3.5 alteration of energy substrates that are provided to the
6–12 mo 55 90–120 1.5–2.5 patient. A recent study with 55 critically ill children
Children 1–3 y 55 75–100 1.5–2.5 was performed comparing two well-known prediction
4–6 y 45 65–90 1.5–2.0 formulas with indirect calorimetry. The data suggest
7–10 y 40 55–70 1.0–2.0 that prediction methods are unreliable for clinical use,
Males 11–14 y 30 40–55 1.0–2.0 and that indirect calorimetry is the only useful way of
15–18 y 30 40–45 1.0–1.5 determining REE in sick children.
19–24 y 25 30–40 1.0–1.5
Females 11–14 y 30 40–55 1.0–2.0 Provision of Nutrition
15–18 y 25 30–40 1.0–1.5 Once energy requirements are determined, the practi-
19–24 y 25 30–40 1.0–1.5 tioner must decide to deliver nutritional support
Based on WHO formulas for protein and energy requirements. through either the enteral or the parenteral route. En-
 CRITICAL CARE / 405

teral feeding is preferred because it is more physiologic, complexity, caloric density, and cost are all factors that
associated with fewer complications, and in some cases, should be taken into consideration. An increasing num-
the only way to safely deliver some nutrients. More ber of commercially made formulas and additives are
knowledge exists about enteral feeding in relation to now available to meet the nutritional needs of the criti-
both energy requirements and utilization; and practi- cally ill patient (Table 13–15).
cally, it is less expensive than parental nutrition. Parenteral nutrition (PN) is indicated for patients
Patients should be screened shortly after admission who are unable to meet nutritional needs with enteral
for nutritional requirements and preferred route of ad- feeds. It consists of the IV delivery of nutrients, fluid,
ministration. Over the years, many practice patterns carbohydrates, protein, fat, electrolytes, vitamins, min-
have been developed that list specific conditions or erals, and trace elements. The proportions of these ele-
therapies in which enteral feeding may not be well tol- ments are individualized to suit the patient’s specific
erated by patients. Recent studies are proving that these nutritional needs. PN often requires central venous ac-
may not be based on true physiologic differences and cess, and thus this method also carries the risks associ-
that a majority of patients who are critically ill can tol- ated with central venous catheters (infection, clots, and
erate enteral feedings. The list of absolute contraindica- insertion-related complications).
tions for enteral feeding is shrinking and now may in- PN can be ordered in many ways, as nutrients can
clude just diseases of the GI tract. be ordered based on a child’s weight or per liter, or a
Because it provides for a more physiologic digestive combination of both. Standard ranges and guidelines
process, direct gastric feeding is preferable to the intesti- are usually provided on order forms. Parenteral energy
nal route. Patients supported with gastric feeds can usu- needs can be approximately 10–15% lower than esti-
ally tolerate higher osmotic loads and larger volumes, mated enteral needs due to reduced energy required for
and have a lower frequency of diarrhea. Gastric acid digestion, absorption, and fecal losses. The percentage
also has a bactericidal effect that may decrease a pa- of protein, carbohydrate, and fat that contributes to
tient’s susceptibility to infection. However, for severely ideal total energy intake varies with the individual and
ill patients sedated and on mechanical ventilation, the the disease condition. General guidelines for energy dis-
high risk of reflux and aspiration becomes an increasing tribution are 8–15% protein, 45–60% carbohydrate,
concern with this manner of feeding. Therefore, and 25–40% fat. Solutions should be instituted slowly
transpyloric feeding has been instituted in these pa- and advanced gradually over several days as tolerated by
tients and in any patient at high risk for aspiration. Al- the patient. Guidelines for the administration of a bal-
though transpyloric feeding may limit reflux and aspira- anced parenteral diet are provided in Chapter 10. A
tion, it does not entirely eliminate it. constant flow rate is important to maintaining steady
The choice of formulas must be based on age, GI glucose delivery. If PN must be stopped abruptly, a
function, history of feeding tolerance, nutrient require- 10% glucose solution should be started to prevent hy-
ments, and route of feeding. The osmolality, nutrient poglycemia. Administration of high glucose and amino

Table 13–15. Pediatric enteral formulas.

Formula Category Formula Examples Typical Uses

Standard, milk protein- Pediasure Nutritionally complete for ages 1–10 years. Can be used for tube feeds
based Pediasure with Fiber or oral supplements.
Kindercal (with/without fiber)
Nutren Junior
Food based Compleat Pediatric Made with beef protein, fruits, and vegetables—does contain lactose.
Fortified with vitamins/minerals.
Semielemental Peptamen Jr. Indicated for impaired gut function with peptides as protein source,
and high MCT content with lower total fat % than standard pediatric
formulas.
Elemental Pediatric Vivonex (24 kcal/oz) Indicated for impaired gut function or protein allergy, and contains free
Elecare amino acids and lower fat with majority as MCT.
Neocate One Plus
MCT = medium-chain triglycerides.
406 / CHAPTER 13

acid concentrations in total parenteral nutrition re- quire pain relief. Indeed, outcomes are improved in
quires central venous access. children receiving appropriate pain control. A child’s
Immunonutrition is an area of growing interest and anxiety in the PICU may heighten perception of pain
research. The term describes a point of view that dietary to a level that causes deterioration of his or her condi-
factors can confer an advantage to the immune system or tion. It is important to distinguish between anxiety and
other adaptive functions in infants and children. The pain, because pharmacologic therapy may be directed at
claims of health benefits ascribed to foods or dietary sup- one or both of these symptoms (Table 13–16). Further,
plements are not new, but until recently, these claims before initiating or increasing sedative drugs, it is im-
have not been supported by scientific review. Breast portant to exclude or address physiologic causes of agi-
milk, the model for infant formula manufacturers, has tation, such as hypoxemia, hypercapnia, and cerebral
long been recognized for its immunonutritive properties, hypoperfusion caused by low cardiac output.
containing such nutrients as secretory immunoglobulins,
lysozyme, interferon, and growth factors. However, the
contribution of specific components to a positive out- Sedation
come has yet to be elucidated. Growing evidence sup- Sedative (anxiolytic) drugs are used to induce calmness
ports the immunomodulatory effects of minerals (eg, without producing sleep—although at high doses, all
iron, zinc, selenium, vitamin A), amino acids (arginine anxiolytics will cause drowsiness and sleep. The five in-
and glutamine), and nucleotides. Evidence also points to dications for the use of sedative drugs are (1) to allay
the emergence of prebiotics, nondigestable food compo- fear and anxiety; (2) to manage acute confusional states;
nents that favor the colonization and growth of bacteria (3) to facilitate treatment or diagnostic procedures;
normally resident in the colon; and probiotics, live mi- (4) to facilitate mechanical ventilation; and (5) to ob-
crobial feed supplements with beneficial effects to the tund physiologic responses to stress—that is, reduce
host. Although some of these concepts hold promise, it is tachycardia, hypertension, or increases in ICP. Par-
still too early to advocate any specific guidelines, because enteral administration (bolus or infusion) allows titra-
some of these nutrients used in high doses have been re- tion of response in the critically ill child. Sedatives fall
ported to produce possible harmful effects. into several classes, with the opioid and benzodiazepine
classes serving as the mainstay of anxiety treatment in
Coss-Bu JA et al: Energy metabolism, nitrogen balance and sub- the ICU.
strate utilization in critically ill children. Am J Clin Nutr
2001;74:664 [PMID: 11684536]. A. BENZODIAZEPINES
Dominguez-Cherit G et al: Total parenteral nutrition. Curr Opin Benzodiazepines possess anxiolytic, hypnotic, anticon-
Crit Care 2002;8:285 [PMID: 12386487]. vulsant, and skeletal muscle relaxant properties. Al-
Fung EB: Estimating energy expenditure in critically ill adults and though their exact mode of action is unknown, it ap-
children. AACN Clin Issues 2000;11:480 [PMID:
11288413].
pears to be located within the limbic system of the CNS
and to involve the neuroinhibitory transmitter γ-amino
Griffiths RD: Specialized nutrition support in critically ill patients.
Curr Opin Crit Care 2003;9:249 [PMID: 12883278]. butyric acid. Most benzodiazepines are metabolized in
Irving SY et al: Nutrition for the critically ill child: Enteral and par-
the liver, with their metabolites subsequently excreted
enteral support. AACN Clin Issues 2000;11:541 [PMID: in the urine; thus, patients in liver failure are likely to
11288418]. have long elimination times.
Novak F et al: Glutamine supplementation in serious illness: A sys- Benzodiazepines can cause respiratory depression if
tematic review of the evidence. Crit Care Med 2002;30:2022 given rapidly in high doses, and they potentiate the
[PMID: 12352035]. analgesic and respiratory depressive effects of opioids
Suchner U et al: Immune-modulatory actions of arginine in the and barbiturates. Therefore, it is important to monitor
critically ill. Br J Nutr 2002;87:S121 [PMID: 11895148]. cardiorespiratory status and have resuscitation equip-
Wernerman J: Glutamine and acute illness. Curr Opin Crit Care ment available. Three benzodiazepines with differing
2003;9:279 [PMID: 12883282]. half-lives are presently used in the ICU setting:
Wyncoll D, Beale R: Immunologically enhanced enteral nutrition:
Current status. Curr Opin Crit Care 2001;7:128 [PMID: 1. Midazolam—Midazolam has the shortest half-life
11373522]. (11⁄2–31⁄2 hours) of the benzodiazepines and is the only
benzodiazepine that should be administered as a con-
PAIN & ANXIETY CONTROL tinuous IV infusion. It produces excellent retrograde
amnesia lasting for 20–40 minutes after a single IV
Anxiety control and pain relief are important responsi- dose. Therefore, it can be used either for short-term se-
bilities of the critical care physician. It is well recog- dation or for “awake” procedures such as endoscopy or
nized that infants and children experience pain and re- as a continuous infusion in the anxious, restless patient.
 CRITICAL CARE / 407

Table 13–16. Pain and anxiety control.

Dose and Method Usual Duration

Drug of Administrationa Advantages Disadvantages of Effect
Morphine IV, 0.1 mg/kg; Excellent pain relief, Respiratory depression, hypotension, nausea, 2–4 h
continuous infusion, reversible suppression of intestinal motility, histamine
0.01–0.05 mg/kg/h release
Meperidine IV, 1 mg/kg Good pain relief, Respiratory depression, histamine release, nausea, 2–4 h
reversible suppression of intestinal motility
Fentanyl IV, 1–2 µg/kg; Excellent pain relief, Respiratory depression, chest wall rigidity, severe 30 min
continuous infusion, reversible, short half- nausea and vomiting
0.5–2 µg/kg/h life
Diazepam IV, 0.1 mg/kg Sedation and seizure Respiratory depression, jaundice, phlebitis 1–3 h
control
Lorazepam IV, 0.1 mg/kg Longer half-life, Nausea and vomiting, respiratory depression, 2–4 h
sedation and seizure phlebitis
control
Midazolam IV, 0.1 mg/kg Short half-life, only Respiratory depression 30–60 min
benzodiazepine
given as continuous
infusion
a
Intravenous (IV) administration is most common in the ICU. The effects of morphine, meperidine, and fentanyl are reversible by adminis-
tration of naloxone (opioid antagonist).

The single IV dose is 0.1 mg/kg, whereas a continuous B. OTHER DRUGS

infusion should be started at a rate of 0.1 mg/kg/h after 1. Chloral hydrate—Chloral hydrate is an enteral
an initial loading dose of 0.1 mg/kg. The midazolam sedative and hypnotic agent frequently used in chil-
infusion dosage must be titrated upward to achieve the dren. After administration, it is rapidly metabolized by
desired effect. Midazolam is not an analgesic; therefore, the liver to its active form trichloroethanol, which has
small doses of an analgesic such as morphine or fen- an 8-hour half-life. A sedative dose is 6–20 mg/kg per
tanyl may be needed. dose, usually given every 6–8 hours, whereas the hyp-
notic dose is up to 50 mg/kg with a maximum dose of
2. Diazepam—Diazepam has a longer half-life than 1 g. The hypnotic dose is frequently used to sedate
midazolam and can be given PO as well as by the IV young children for outpatient radiologic procedures
route. Its disadvantage in the ICU is its intermediary such as computed tomography scanning and magnetic
metabolite, nordazepam, which has a very long half-life resonance imaging. There is little effect on respiration
and may accumulate, prolonging sedation. It produces or blood pressure with therapeutic doses of chloral hy-
excellent anxiolysis and amnesia. Additionally, it is used drate. The drug is irritating to mucous membranes,
to treat acute status epilepticus. The IV dose is however, and may cause gastric upset if administered
0.1 mg/kg and can be repeated every 15 minutes to on an empty stomach.
achieve the desired effect or until undesirable side ef-
fects (somnolence and respiratory depression) occur. 2. Ketamine—Ketamine is a phencyclidine derivative
that produces a trance-like state of immobility and am-
3. Lorazepam—Lorazepam possesses the longest half- nesia known as dissociative anesthesia. After IM or IV
life of the three benzodiazepines discussed here and can administration, it causes central sympathetic nervous
be used to achieve sedation for as long as 6–8 hours. It system stimulation with resultant increases in heart
has less effect on the cardiovascular and respiratory sys- rate, blood pressure, and cardiac output. Respiration is
tems than other benzodiazepines and can be given PO, not depressed at therapeutic doses. Because salivary and
IV, or intramuscularly (IM). The IV route is the most tracheobronchial mucous gland secretions are in-
common. The IV dosage is 0.1 mg/kg. Lorazepam can creased, atropine should be administered 20 minutes
also be used to treat acute status epilepticus. prior to the ketamine. A disadvantage of ketamine
408 / CHAPTER 13

usage is the occurrence of unpleasant dreams or halluci- centrations produce analgesia without sedation. In ad-
nations. The incidence is less in children than in adults, dition, opioids can cause respiratory depression, nausea,
and it can be reduced even further by the concurrent pruritus, slowed intestinal motility, miosis, urinary re-
administration of a benzodiazepine. Because of its in- tention, cough suppression, biliary spasm, and vasodila-
otropic properties, ketamine is useful for the sedation of tion. The dose of opioid required to produce adequate
certain critically ill patients whose conditions are unsta- analgesia varies greatly from one individual to the next.
ble. Additionally, its bronchodilator effects make it the Therefore, in the intensive care setting, a continuous
induction agent of choice for patients with status asth- infusion of morphine or fentanyl allows dosages to be
maticus requiring intubation. It is given as an IV injec- easily titrated to achieve the desired effect.
tion of 1–2 mg/kg over 60 seconds, with supplemen- In general, infants younger than age 3 months are
tary doses of 0.5 mg/kg being required every more susceptible than older children to the respiratory
10–30 minutes to maintain an adequate level of anes- depressant effects of opioids. Starting dosages for these
thesia. Alternatively, it can be administered as an IM patients should be about one third to one half the usual
injection of 3–7 mg/kg, which usually produces the de- pediatric dose. Most opioids (except meperidine) have
sired level of anesthesia within 3–4 minutes. If pro- minimal cardiac depressive effects, and critically ill pa-
longed anesthesia is required, ketamine can be adminis- tients generally tolerate them well. Fentanyl does not
tered by IV infusion at doses of 3–20 mg/kg/h. cause the histamine release that morphine does and
3. Antihistamines—The antihistamines diphenhy- thus produces less vasodilation and drop in systemic
dramine and hydroxyzine can be used as sedatives but blood pressure. Opioids are metabolized in the liver,
are not as effective as the benzodiazepines. Diphenhy- with metabolites excreted in the urine. Thus patients
dramine produces sedation in only 50% of those pa- with hepatic or renal impairment may have a prolonged
tients receiving it. It can be given IV, IM, or PO at a response to their administration. Patients who receive
dose of 1 mg/kg. Hydroxyzine can be given either IM regular doses of opioids for 2 weeks or more frequently
or PO. It is frequently used concurrently with mor- develop a physiologic dependence with the develop-
phine or meperidine, adding anxiolysis and potentiat- ment of withdrawal symptoms (agitation, tachypnea,
ing the effects of the opioid. The sedative effects of tachycardia, sweating, diarrhea) upon acute termination
both drugs can last from 4 to 6 hours following a single of the drug. In these patients, gradual tapering of the
dose. opioid dosage over a 5- to 10-day period will prevent
withdrawal symptoms. As with any potent sedative or
4. Propofol—Propofol is an anesthetic induction analgesic used in the ICU setting, appropriate patient
agent whose main advantages are a rapid recovery time monitoring (pulse oximetry, cardiorespiratory monitor-
and no cumulative effects resulting from its rapid he- ing, blood pressure monitoring) should be used during
patic metabolism. It has no analgesic properties and fre- the period of opioid administration, and equipment
quently causes pain on injection. Dose-related hypoten- should be available to support prompt intervention if
sion and metabolic acidosis have been reported in undesired side effects occur.
pediatric patients, and a recent FDA bulletin has rec- The ICU regimen for sedation and analgesia must
ommended against the use of propofol in pediatric pa- be carefully modified when the patient is transferred to
tients outside the controlled environment of the operat- the ward or a lower vigilance area. Patients with base-
ing room. line respiratory, hepatic, or renal insufficiencies are
5. Barbiturates—Barbiturates (phenobarbital, most predisposed to respiratory insufficiency from seda-
thiopental) can cause direct myocardial and respiratory tives or opioid analgesics.
depression and are, in general, poor choices for sedation Advantages of continuous infusions of sedatives are
of seriously ill patients. Phenobarbital has a very long that it provides a more constant level of sedation, in-
half-life (up to 4 days), and recovery from thiopental, creases patient comfort, and allows better tolerance of
although it is a short-acting barbiturate, can be pro- newer approaches to mechanical ventilation. Prolonga-
longed because remobilization of tissue stores occurs. tion of mechanical ventilation, hospitalization, and inabil-
ity to assess neurologic function and mental status have
Analgesia been recognized as disadvantages of continuous infusions.
A recent study of the daily interruption of continuous se-
A. OPIOID ANALGESICS dation, allowing the adult patient to “wake up,” was asso-
Opioid analgesics (morphine, fentanyl, codeine, ciated with a decrease in duration of mechanical ventila-
meperidine) are the mainstays of therapy for most tion and length of stay in the ICU. Currently, similar data
forms of acute severe pain as well as chronic cancer pain are not available for pediatric patients.
management. They possess both analgesic and dose-re- Frequently pediatric patients will require relatively
lated sedative effects, although a range of plasma con- deep levels of sedation while undergoing a procedure
 CRITICAL CARE / 409

(eg, vascular line placement, radiographic studies). tration should be titrated to achieve the desired effect
Often these patients are not intubated and are not ex- (eg, reversal of respiratory depression) because full re-
pected to require intubation and ventilatory support— versal using 1–10 µg/kg may cause acute anxiety, dys-
so called conscious sedation. (New American Academy phoria, nausea, and vomiting. Furthermore, because
of Pediatric guidelines will recommend a change in ter- the duration of effect of naloxone is shorter (30 min-
minology to “moderate sedation/analgesia”.) A system- utes) than that of most opioids, the patient must be ob-
atic approach should include the following: served carefully for reappearance of the undesired ef-
fect.
1. Pertinent history to elicit underlying illnesses
2. Physical exam focusing on the anatomy and ade- B. NONOPIOID ANALGESICS
quacy of the child’s airway (ie, large tonsils or fa-
cial deformity) Nonopioid analgesics used in the treatment of mild to
moderate pain include acetaminophen, aspirin, and
3. Informed consent other nonsteroidal anti-inflammatory drugs (NSAIDs)
4. Appropriate patient fasting from solids (6 hours) such as ibuprofen and naproxen.
and liquids (2 hours)
5. Age- and size-appropriate equipment 1. Acetaminophen—Acetaminophen is the most
6. Drug dosages calculated on a milligram per kilo- commonly used analgesic in pediatrics in the United
gram basis States and is the drug of choice for mild to moderate
pain because of its low toxicity and lack of effect on
7. Monitoring and documentation of vital signs (in- bleeding time. It is metabolized by the liver. Suggested
cluding continuous pulse oximetry, respiratory doses are 10–15 mg/kg PO to approximately
rate and pattern, level of arousability) 10–20 mg/kg PR every 4 hours.
8. Separate observer to monitor deeply sedated pa-
tients 2. Aspirin—Aspirin is also an effective analgesic for
9. Practitioner capable of intubating and treating pa- mild to moderate pain at doses of 10–15 mg/kg PO
tients who enter a deeper state of sedation than every 4 hours. However, its prolongation of bleeding
initially anticipated time, association with Reye syndrome, and propensity
10. Discharge criteria ensuring the patient has recov- to cause gastric irritation limit its usefulness in pediatric
ered to his or her baseline level of consciousness. practice. Aspirin and other NSAIDs are still useful, es-
pecially for pain of inflammatory origin, bone pain, and
Short-acting agents are preferred. Agents typically pain associated with rheumatic conditions.
used include an opioid (usually fentanyl or morphine)
and a benzodiazepine (most often midazolam). Another 3. Other NSAIDs—Ibuprofen and naproxen are
option is ketamine and midazolam. It is important to NSAIDs whose use has been limited in pediatrics to
select and become comfortable with a specific combina- date. Naproxen is FDA approved for children aged
tion; learn the indications and potential complications. 2–12 years (5–7 mg/kg PO every 8–12 hours), whereas
Using a familiar agent and following the systematic ap- ibuprofen requires more frequent dosing intervals
proach outlined earlier have reduced anesthetic compli- (4–10 mg/kg PO every 6–8 hours).
cations in this population of patients. All of the NSAIDs have a therapeutic ceiling after
Patient-controlled analgesia (PCA) is a computer- which no increase occurs in analgesic potency above the
governed infusion pump for constant infusion or pa- recommended dose. They all can cause gastritis and
tient-regulated bolus infusion of opioid analgesics. The should be given with antacids or with meals, and they
basal infusion mode is intended to provide a constant should be used with caution in people at risk for renal
serum level of analgesic. The bolus mode allows the pa- compromise. In addition, the analgesic effects of aceta-
tient, by pushing a button, to self-administer additional minophen, aspirin, and other NSAIDs are additive to
doses for breakthrough pain. The patient is usually per- those of opioids. Thus, if additional analgesia is re-
mitted six boluses an hour, with 10-minute lockouts. If quired, their use should be continued and an appropri-
the patient is using allotted hourly boluses, this usually ate PO opioid (codeine, morphine) or parenteral opioid
means that the basal infusion rate is too low. The pa- (morphine, fentanyl) begun.
tient must understand the concept of PCA in order to
be a candidate for its use. In some circumstances in pe- Cote CJ et al: Adverse sedation events in pediatrics: A critical inci-
diatrics it is more appropriate for the nurse or parent to dent analysis of contributing factors. Pediatr 2000;105:805
administer the bolus dose. [PMID: 10742324].
Naloxone reverses the analgesia, sedative, and respi- Cote CJ: Conscious sedation: Time for this oxymoron to go away.
ratory depressive effects of opioid agonists. Its adminis- J Pediatr 2001;139:15 [PMID: 11445787].
410 / CHAPTER 13

Cray SH et al: Lactic acidemia and bradyarrhythmia in a child se- Kress JP et al: Daily interruption of sedative infusions in critically
dated with propofol. Crit Care Med 1998;26:2087 [PMID: ill patients undergoing mechanical ventilation. N Engl J Med
9875925]. 2000;342:1471 [PMID: 10816184].
Gehlbach BK, Kress JP: Sedation in the intensive care unit. Curr Tobias JD: Sedation and analgesia in paediatric intensive care units.
Opin Crit Care 2002;8:290 [PMID: 12386488]. Paediatr Drugs 1999;109 [PMID: 10937446].
 Skin 14
Joseph G. Morelli, MD, & William L. Weston, MD

tory response. Replacement of water will correct this

GENERAL PRINCIPLES condition if evaporation is prevented. Therefore, dry
and scaly skin is treated by soaking the skin in water for
OF DIAGNOSIS OF SKIN 5 minutes and then adding a barrier to evaporation
DISORDERS (Table 14–2). Oils and ointments prevent evaporation
for 8–12 hours, so they must be applied once or twice a
day. In areas already occluded (axilla, diaper area), oint-
Examination of the skin requires that the entire surface ments or oils will merely increase retention of water and
of the body be palpated and inspected in good light. should not be used.
The onset and duration of each symptom should be Overhydration (maceration) can also occur. As envi-
recorded, together with a description of the primary le- ronmental humidity increases to 90–100%, the num-
sion and any secondary changes, using the terminology ber of water molecules absorbed by the stratum
set forth in Table 14–1. In practice, the characteristics corneum increases and the tight lipid junctions between
of skin lesions are described in an order opposite that the cells of the stratum corneum are gradually replaced
shown in the table. Begin with distribution, then con- by weak hydrogen bonds; the cells eventually become
figuration, color, secondary changes, and primary widely separated, and the epidermal barrier falls apart.
changes. For example, guttate psoriasis could be de- This occurs in immersion foot, diaper areas, axillae, and
scribed as generalized, discrete, red, scaly papules. the like. It is desirable to enhance evaporation of water
in these areas by air drying.

WET DRESSINGS
GENERAL PRINCIPLES
By placing the skin in an environment where the hu-
OF TREATMENT OF SKIN midity is 100% and allowing the moisture to evaporate
DISORDERS to 60%, pruritus is relieved. Evaporation of water stim-
ulates cold-dependent nerve fibers in the skin, and this
may prevent the transmission of the itching sensation
TOPICAL THERAPY via pain fibers to the central nervous system. It also is
Treatment should be simple and aimed at preserving vasoconstrictive, thereby helping to reduce the ery-
normal skin physiology, keeping in mind that one is thema and also decreasing the inflammatory cellular re-
treating the child and not the anxious parent or grand- sponse.
parent. Topical therapy is often preferred because med- The simplest form of wet dressing consists of one set
ication can be delivered in optimal concentrations to of wet underwear (eg, long johns) worn under a dry
the desired site. pair. The underwear should be soaked in warm (not
Water is an important therapeutic agent, and opti- hot) water and wrung out until no more drops come
mally hydrated skin is soft and smooth. This occurs at out. When covered by the dry layer, the wet dressings
approximately 60% environmental humidity. Because need to be changed only every 4–6 hours.
water evaporates readily from the cutaneous surface,
skin hydration (stratum corneum of the epidermis) is
dependent on the water concentration in the air, and
TOPICAL GLUCOCORTICOIDS
sweating contributes little. However, if sweat is pre- Twice-daily application of topical steroids is the main-
vented from evaporating (eg, in the axilla, groin), local stay of treatment for all forms of dermatitis (Table
humidity and hydration of the skin are increased. As 14–3). Topical steroids can also be used under wet
humidity falls below 15–20%, the stratum corneum dressings. Wet dressings are removed every 4–6 hours,
shrinks and cracks; the epidermal barrier is lost and al- and a topical steroid is applied; the skin is then covered
lows irritants to enter the skin and induce an inflamma- again with wet dressings. If treatment is applied
411
Copyright © 2005, 2001, by The McGraw-Hill Companies, Inc. Click here for terms of use.
412 / CHAPTER 14

Table 14–1. Examination of the skin.

Clinical
Appearance Description and Examples
Primary lesions (first to appear)
Macule Any circumscribed color change in the skin that is flat. Examples: white (vitiligo), brown (café au lait spot), pur-
ple (petechia).
Papule A solid, elevated area less than 1 cm in diameter whose top may be pointed, rounded, or flat. Examples: acne,
warts, small lesions of psoriasis.
Plaque A solid, circumscribed area more than 1 cm in diameter, usually flat-topped. Example: psoriasis.
Vesicle A circumscribed, elevated lesion less than 1 cm in diameter and containing clear serous fluid. Example: blisters
of herpes simplex.
Bulla A circumscribed, elevated lesion more than 1 cm in diameter and containing clear serous fluid. Example: bul-
lous erythema multiforme.
Pustule A vesicle containing a purulent exudate. Examples: acne, folliculitis.
Nodule A deep-seated mass with indistinct borders that elevates the overlying epidermis. Examples: tumors, granu-
loma annulare. If it moves with the skin on palpation, it is intradermal; if the skin moves over the nodule, it is
subcutaneous.
Wheal A circumscribed, flat-topped, firm elevation of skin resulting from tense edema of the papillary dermis. Exam-
ple: urticaria.
Secondary changes
Scales Dry, thin plates of keratinized epidermal cells (stratum corneum). Examples: psoriasis, ichthyosis.
Lichenification Induration of skin with exaggerated skin lines and a shiny surface resulting from chronic rubbing of the skin.
Example: atopic dermatitis.
Erosion and A moist, circumscribed, slightly depressed area representing a blister base with the roof of the blister
oozing removed. Examples: burns, bullous erythema multiforme. Most oral blisters present as erosions.
Crusts Dried exudate of plasma on the surface of the skin following acute dermatitis. Examples: impetigo, contact
dermatitis.
Fissures A linear split in the skin extending through the epidermis into the dermis. Example: angular cheilitis.
Scars A flat, raised or depressed area of fibrotic replacement of dermis or subcutaneous tissue. Examples: acne scar,
burn scar.
Atrophy Depression of the skin surface caused by thinning of one or more layers of skin. Example: lichen sclerosis.
Color The lesion should be described as red, yellow, brown, tan, or blue. Particular attention should be given to the
blanching of red lesions. Failure to blanch suggests bleeding into the dermis (petechiae).
Configuration of lesions
Annular Annular nodules represent granuloma annulare; annular scaly papules are more apt to be caused by
(circular) dermatophyte infections.
Linear Linear papules represent lichen striatus; linear vesicles, incontinentia pigmenti; linear papules with burrows,
(straight scabies.
lines)
Grouped Grouped vesicles occur in herpes simplex or zoster.
Discrete Discrete lesions are independent of each other.
Distribution Note whether the eruption is generalized, acral (hands, feet, buttocks, face), or localized to a specific skin
region.
 SKIN / 413

Table 14–2. Bases used for topical preparations. Table 14–3. Topical glucocorticoids.

Base Combined With Uses Glucocorticoid Concentrations

Liquids Wet dressings: relieve pru- Low potencya = 1–9
ritus, vasoconstrict Hydrocortisone 0.5% and 1%
Powder Shake lotions, drying pastes: Desonide 0.05%
relieve pruritus, vasocon-
Moderate potency = 10–99
strict
Mometasone furoate 0.1%
Grease and emulsifier; Cream: penetrates quickly
Hydrocortisone valerate 0.2%
oil in water (10–15 min) and thus
allows evaporation Fluocinolone acetonide 0.025%
Excess grease and Emollient cream: pene- Triamcinolone acetonide 0.01%
emulsifier; water in oil trates more slowly and
Amcinonide 0.1%
thus retains moisture on
skin High potency = 100–499
Desoximetasone 0.25%
Grease Ointments: occlusive (hold
material on skin for pro- Fluocinonide 0.05%
longed time) and prevent
Halcinonide 0.1%
evaporation of water
Super potency = 500–7500
Gel Transparent, colorless,
Betamethasone dipropionate 0.05%
semisolid emulsion: non-
greasy, more drying and Clobetasol propionate 0.05%
irritating than cream a
1% hydrocortisone is defined as having a potency of 1.
Powder Enhances evaporation
Characteristics of bases for topical preparations:
1. Most greases are triglycerides (eg, Aquaphor, petrolatum, Eu- Bikowski J: The use of therapeutic moisturizers in various dermatol-
cerin). ogy disorders. Cutis 2001;68(5 Suppl):3 [PMID: 11845952].
2. Oils are fluid fats (eg, Alpha Keri, olive oil, mineral oil). Brazzini B, Pimpinelli N: New and established topical corticoster-
3. True fats (eg, lard, animal fats) contain free fatty acids that oids in dermatology: Clinical pharmacology and therapeutic
cause irritation. use. Am J Clin Dermatol 2002;3:47 [PMID: 11817968].
4. Ointments (eg, Aquaphor, petrolatum) should not be used in Schnopp C et al. Topical steroids under wet-wrap dressings in
intertriginous areas such as the axillae, between the toes, and atopic dermatitis—A vehicle controlled trial. Dermatology
in the perineum, because they increase maceration. Lotions or 2002 204(1):56 [PMID: 11834851].
creams are preferred in these areas.
5. Oils and ointments hold medication on the skin for long peri-
ods and are therefore ideal for barriers or prophylaxis and for
dried areas of skin. Medication gets into the skin more slowly
from ointments. DISORDERS OF THE SKIN
6. Creams carry medication into skin and are preferable for inter-
triginous dermatitis.
IN NEWBORNS
7. Solutions, gels, or lotions should be used for scalp treatments.
TRANSIENT DISEASES IN NEWBORNS
Milia
throughout the 24-hour period, maximum benefit is Multiple white papules 1 mm in diameter scattered
obtained after 72 hours; if treatment is applied only at over the forehead, nose, and cheeks are present in up to
night, maximum benefit is obtained after 7 days. When 40% of newborn infants. Histologically, they represent
the condition has improved, the wet dressings are dis- superficial epidermal cysts filled with keratinous mater-
continued and a steroid ointment is applied twice daily. ial associated with the developing pilosebaceous follicle.
Daily application of steroids is not to be continued for Their intraoral counterparts are called Epstein pearls
more than 1 month. Only low-potency steroids (see and are even more common than facial milia. All of
Table 14–3) are applied to the face or intertriginous these cystic structures spontaneously rupture and exfoli-
areas. ate their contents.
414 / CHAPTER 14

Sebaceous Gland Hyperplasia eruption in newborns of African descent, benign pustu-

lar melanosis, shows mostly neutrophils and leaves hy-
Prominent yellow macules at the opening of each pi- perpigmentation. Herpes simplex virus infection is in
losebaceous follicle, predominantly over the nose, rep- the differential diagnosis, but the infants are not ill and
resent overgrowth of sebaceous glands in response to multinucleated giant cells are not present.
the same androgenic stimulation that occurs in adoles-
cence.
Sucking Blisters
Acne Neonatorum Bullae, either intact or as an erosion with a blister base
Open and closed comedones, erythematous papules, without inflammatory borders, may occur over the
and pustules identical in appearance to adolescent acne forearms, wrists, thumbs, or upper lip. These presum-
may occur in infants over the forehead, cheeks, and ably result from vigorous sucking in utero. They resolve
chin. The lesions may be present at birth but usually do without complications.
not appear until age 4–6 weeks. Spontaneous resolution
occurs over a period of 6 months to 1 year. Rarely, se-
vere neonatal acne may be a manifestation of a virilizing Miliaria
syndrome. Obstruction of the eccrine sweat ducts occurs often in
neonates and produces one of two clinical pictures. Ob-
Harlequin Color Change struction in the stratum corneum causes miliaria crys-
tallina, characterized by tiny (1- to 2-mm), superficial
A cutaneous vascular phenomenon unique to neonates grouped vesicles without erythema over intertriginous
in the first week of life occurs when the infant (particu- areas and adjacent skin (eg, neck, upper chest). More
larly one of low birth weight) is placed on one side. The commonly, obstruction of the eccrine duct deeper in
dependent half develops an erythematous flush with a the epidermis results in erythematous grouped papules
sharp demarcation at the midline, and the upper half of in the same areas and is called miliaria rubra. Rarely,
the body becomes pale. The color changes usually sub- these may progress to pustules. Heat and high humidity
side within a few seconds after the infant is placed predispose the patient to eccrine duct pore closure. Re-
supine but may persist for as long as 20 minutes. moval to a cooler environment is the treatment of
choice.
Mottling
A lace-like pattern of dilated cutaneous vessels appears Subcutaneous Fat Necrosis
over the extremities and often the trunk of neonates ex-
posed to lowered room temperature. This feature is Reddish or purple, sharply circumscribed, firm nodules
transient and usually disappears completely on rewarm- occurring over the cheeks, buttocks, arms, and thighs
ing. and occurring between 1 and 7 days of life represent
subcutaneous fat necrosis. Cold injury is thought to
play an important role. These lesions resolve sponta-
Erythema Toxicum neously over a period of weeks, although as in all in-
Up to 50% of full-term infants develop erythema toxi- stances of fat necrosis they may calcify.
cum. Usually at 24–48 hours of age, blotchy erythema-
tous macules 2–3 cm in diameter appear, most promi-
Orchard D: Rashes in infants: Pitfalls and masquerades. Aust Fam
nently on the chest but also on the back, face, and Physician 2001;30:1047 [PMID: 11759454].
extremities. These are occasionally present at birth.
Verbov J: Common skin conditions in the newborn. Semin Neona-
Onset after 4–5 days of life is rare. The lesions vary in tol 2000;5:303 [PMID: 11841650].
number from a few up to as many as 100. Incidence is
much higher in full-term infants than in premature
ones. The macular erythema may fade within PIGMENT CELL BIRTHMARKS, NEVI,
24–48 hours or may progress to formation of urticarial & MELANOMA
wheals in the center of the macules or, in 10% of cases,
pustules. Examination of a Wright-stained smear of the Birthmarks may involve an overgrowth of one or more
lesion will reveal numerous eosinophils. No organisms of any of the normal components of skin (eg, pigment
are seen on Gram stain. This may be accompanied by cells, blood vessels, lymph vessels). A nevus is a hamar-
peripheral blood eosinophilia of up to 20%. All of the toma of highly differentiated cells that retain their nor-
lesions fade and disappear within 5–7 days. A similar mal function.
 SKIN / 415

Mongolian Spot Giant Pigmented Nevus

A blue-black macule found over the lumbosacral area in (Bathing Trunk Nevus)
90% of infants of Native American, African, and Asian An irregular dark brown to black plaque over at least
descent is called a mongolian spot. These spots are oc- 5% of the body surface represents a giant pigmented
casionally noted over the shoulders and back and may nevus. Often the lesions are of such size as to cover the
extend over the buttocks. Histologically, they consist of entire trunk (bathing trunk nevi). Histologically, they
spindle-shaped pigment cells located deep in the der- are compound nevi. Transformation to malignant
mis. The lesions fade somewhat with time as a result of melanoma has been reported in as many as 10% of
darkening of the overlying skin, but some traces may cases in some series, although the true incidence is
persist into adult life. probably much lower. Malignant change may occur in
the neonatal period or at any time thereafter. Two
Café au Lait Macule thirds of melanoma in children with giant congenital
pigmented nevi develop in areas other than the skin.
A café au lait macule is a light brown, oval macule (dark Tissue expanders may be useful in excision of large
brown on brown or black skin) that may be found any- lesions. The risk of melanoma and the potential for cos-
where on the body. Café au lait spots over 1.5 cm in metic improvement should be evaluated carefully for
greatest diameter are found in 10% of white and 22% each patient.
of black children. These lesions persist throughout life
and may increase in number with age. The presence of
Fishman C et al: Diagnosis and management of nevi and cutaneous
six or more such lesions over 1.5 cm in greatest diame- melanoma in infants and children. Clin Dermatol 2002;20:
ter may be a clue to neurofibromatosis 1 (NF-1). Pa- 44 [PMID: 11849894].
tients with Albright syndrome (see Chapter 30) also Makkar HS, Frieden IJ: Congenital melanocytic nevi: An update
have increased numbers of café au lait macules. Most for the pediatrician. Curr Opin Pediatr 2002;14:397 [PMID:
newborns with NF-1 will acquire the macules later. 12130901].

Spitz Nevus VASCULAR BIRTHMARKS

A reddish brown solitary nodule appearing on the face Capillary Malformations
or upper arm of a child represents a Spitz nevus. Histo-
logically, it consists of pigment-producing cells of Flat vascular birthmarks can be divided into two types:
bizarre shape with numerous mitoses. those that are orange or light red (salmon patch) and
those that are dark red or bluish red (port-wine stain).
The salmon patch is a light red macule found over
Junctional Nevus & Compound Nevus the nape of the neck, upper eyelids, and glabella. Fifty
Dark brown or black macules, usually few in number at percent of infants have such lesions over their necks.
birth but becoming more numerous with age, represent Eyelid lesions fade completely within 3–6 months;
junctional nevi. Histologically, these lesions are clones those on the neck fade somewhat but usually persist
of melanocytes at the junction of the epidermis and into adult life.
dermis. With aging, they may become raised (papules) Port-wine stains are dark red or purple macules ap-
and contain intradermal melanocytes, creating a com- pearing anywhere on the body. A bilateral facial port-
pound nevus. The surface may at times become irregu- wine stain or one covering the entire half of the face
lar and roughened. may be a clue to Sturge–Weber syndrome, which is
Brown to blue solitary papules with smooth surfaces characterized by seizures, mental retardation, glaucoma,
represent intradermal nevi. When pigmentation is pre- and hemiplegia (Chapter 23). Most infants with
sent deeper in the dermis, the lesions appear blue or smaller, unilateral facial port-wine stains do not have
blue-black and are called blue nevi. Sturge–Weber syndrome. Similarly, a port-wine stain
over an extremity may be associated with hypertrophy
Melanoma of the soft tissue and bone of that extremity (Klippel–
Trénaunay syndrome). The pulsed dye laser is the treat-
Pigmented lesions with variegated colors (red, white, ment of choice for infants and children with port-wine
blue), notched borders, and nonuniform, irregular sur- stains.
faces should arouse a suspicion of melanoma. Ulcera-
tion and bleeding are advanced signs of melanoma. If Rothfleisch JE et al: Laser treatment of congenital and acquired vas-
melanoma is suspected, excisional biopsy for pathologic cular lesions: A review. Dermatol Clin 2002;20:1 [PMID:
examination should be done as the treatment of choice. 11859585].
416 / CHAPTER 14

Hemangioma EPIDERMAL BIRTHMARKS

A red, rubbery nodule with a roughened surface is a Epidermal Nevus
hemangioma. The lesion is often not present at birth
but is represented by a permanent blanched area on the Linear or groups of linear, warty, papular, unilateral le-
skin that is supplanted at age 2–4 weeks by red nodules. sions represent overgrowth of epidermis since birth.
Histologically, these are benign tumors of capillary en- These areas may range from dirty yellow to brown or
dothelial cells. Hemangiomas may be superficial, deep, may be darkly pigmented. The histologic features of the
or mixed. The terms strawberry and cavernous are mis- lesions include thickening of the epidermis and elonga-
leading and should not be used. The biologic behavior tion of the rete ridges and hyperkeratosis. Clinically,
of a hemangioma is the same despite its location. Fifty widespread lesions may be associated with focal motor
percent resolve spontaneously by age 5 years, 70% by seizures, mental subnormality, and skeletal anomalies.
age 7 years, and 90% by age 9 years, leaving redundant Treatment once or twice daily with topical cal-
skin, hypopigmentation, and telangiectasia. Local com- cipotriene may improve the lesions.
plications include superficial ulceration and secondary
pyoderma. Dosik JS: Epidermal nevus. Dermatol Online J 2001;7:14 [PMID:
Complications that require immediate treatment are 11328635].
(1) airway obstruction (hemangiomas of the head and Happle R, Rogers M: Epidermal nevi. Adv Dermatol 2002;18:
neck may be associated with subglottic hemangiomas), 175 [PMID: 12528406].
(2) visual obstruction (with resulting amblyopia), and Lee SH, Rogers M: Inflammatory linear verrucous epidermal naevi:
A review of 23 cases. Australas J Dermatol 2001;42:
(3) cardiac decompensation (high-output failure). In 252 [PMID: 11903156].
these instances, the treatment of choice is with pred-
nisone, 2–4 mg/kg orally daily for 4–6 weeks. Inter-
feron alfa-2a has been used to treat serious hemangio- Nevus Comedonicus
mas unresponsive to prednisone. Ten percent of The lesion known as nevus comedonicus consists of lin-
patients with hemangiomas treated with interferon alfa- ear groups of widely dilated follicular openings plugged
2a have developed spastic diplegia. Therefore, inter- with keratin, giving the appearance of localized nonin-
feron alfa-2a therapy should be reserved for truly life- flammatory acne. The treatment of choice is surgical re-
threatening hemangiomas. If the lesion is ulcerated or moval. If this is not feasible, topical retinoic acid may
bleeding, pulsed dye laser treatment may be helpful. be helpful.
The Kasabach–Merritt syndrome, which is platelet
trapping with consumption coagulopathy, does not
occur with hemangiomas. It is seen only with the very Lefkowitz A et al: Nevus comedonicus. Dermatology 1999;199:
204 [PMID: 10592398].
rare vascular tumors called hemangioendotheliomas
and tufted angiomas.
Nevus Sebaceus
Bruckner AL, Frieden IJ: Hemangiomas of infancy. J Am Acad The nevus sebaceus of Jadassohn is a hamartoma of se-
Dermatol 2003;48:477 [PMID: 12664009]. baceous glands and underlying apocrine glands that is
David LR et al: Br J Plast Surg 2003;56:317 [PMID: 12873458]. diagnosed by the appearance at birth of a yellowish,
hairless, smooth plaque in the scalp or on the face. The
Lymphatic Malformations lesion may be contiguous with an epidermal nevus on
the face and constitute part of the linear epidermal
Lymphatic malformations may be superficial or deep. nevus syndrome.
Superficial lymphatic malformations present as fluid- Histologically, nevus sebaceus represents an over-
filled vesicles often described as looking like frog abundance of sebaceous glands without hair follicles. At
spawn. Deep lymphatic malformations are rubbery, puberty, with androgenic stimulation, the sebaceous
skin-colored nodules occurring in the parotid area (cys- cells in the nevus divide, expand their cellular volume,
tic hygromas) or on the tongue. They often result in and synthesize sebum, resulting in a warty mass. Be-
grotesque enlargement of soft tissues. Surgical excision cause 15% of these lesions become basal cell carcino-
is the only treatment, although the results are not satis- mas after puberty, excision is recommended before pu-
factory. berty.

Fliegelman LJ et al: Lymphatic malformations: Predictive factors Cribier B et al: Tumors arising in nevus sebaceous: A study of
for recurrence. Otolaryngol Head Neck Surg 2000;123:706 596 cases. J Am Acad Dermatol 2000;42:263 [PMID:
[PMID: 11112962]. 10642683].
 SKIN / 417

CONNECTIVE TISSUE Epidermolysis Bullosa

BIRTHMARKS (Juvenile The diagnostic feature of this group of diseases is the
Elastoma, Collagenoma) formation of blisters in response to slight trauma. They
Connective tissue nevi are smooth, skin-colored can be divided into scarring and nonscarring types
papules 1–10 mm in diameter that are grouped on the (Table 14–5).
trunk. A solitary, larger (5–10 cm) nodule is called a Treatment usually consists of systemic antibiotics
shagreen patch and is histologically indistinguishable for infection, protection of the skin with petrolatum,
from other connective tissue nevi that show thickened, zinc oxide, or synthetic dressings, and cooling the skin.
abundant collagen bundles with or without associated If hands and feet are involved, reducing skin friction
increases of elastic tissue. Although the shagreen patch with 5% glutaraldehyde every 3 days is helpful.
is a cutaneous clue to tuberous sclerosis (Chapter 23),
Fine JD et al: Revised classification system for inherited epidermol-
the other connective tissue nevi occur as isolated events. ysis bullosa: Report of the Second International Consensus
These nevi remain throughout life and need no treat- Meeting on etiology and classification of epidermolysis bul-
ment. losa. J Am Acad Dermatol 2000;42:1051 [PMID:
10827412].
Moss C: Genetic skin disorders. Semin Neonatol 2000;5:311
Batta K: Management of large birthmarks. Semin Neonatol [PMID: 11036715].
2000;5:325 [PMID: 11032717]. Pai S, Marinkovich MP: Epidermolysis bullosa: New and emerging
trends. Am J Clin Dermatol 2002;3:371 [PMID: 12113646].

HEREDITARY SKIN DISORDERS

Ichthyosis COMMON SKIN DISEASES
Ichthyosis is a term applied to several heritable diseases IN INFANTS, CHILDREN, &
characterized by the presence of excessive scales on the ADOLESCENTS
skin. Major categories are listed in Table 14–4. Treat-
ment consists of controlling scaling with lactic acid
with ammonium hydroxide (Lac-Hydrin) 12% applied ACNE
once daily. Restoring water to the skin is also very help-
ful. The common forms of acne in pediatric patients occur
at two ages: in the newborn period and in adolescence.
Neonatal acne is a response to maternal androgen, first
DiGiovanni JJ, Robinson-Bostom L: Ichthyosis: Etiology, diagno- appearing at age 4–6 weeks and lasting until age
sis and management. Am J Clin Dermatol 2003;4:81 4–6 months. The lesions are primarily on the face,
[PMID: 12553849]. upper chest, and back, in a distribution similar to that

Table 14–4. Four major types of ichthyosis.

Name Age at Onset Clinical Features Genetic Defect Inheritance

Ichthyosis with normal epidermal turnover
Ichthyosis vulgaris Childhood Fine scales, deep palmar and plantar markings Filaggrin/profilaggrin Autosomal-
dominant
X-linked ichthyosis Birth Palms and soles spared; thick scales that Cholesterol sulfatase X-linked
darken with age; corneal opacities in patients
and carrier mothers
Ichthyosis with increased epidermal turnover
Epidermolytic hyper- Birth Verrucous, yellow scales in flexural areas and Keratins 1 and 10 Autosomal-
keratosis palms and soles dominant
Lamellar ichthyosis Birth; collodion Erythroderma, ectropion, large coarse scales; Transglutaminase 1 Autosomal-
baby thickened palms and soles recessive
418 / CHAPTER 14

Table 14–5. Types of epidermolysis bullosa.

Name Age at Onset Clinical Features Genetic Defect Inheritance

Nonscarring types
Epidermolysis bullosa simplex Birth Hemorrhagic blisters Keratins 5 and 14 Autosomal-dominant
over the lower legs;
cooling prevents blisters
Recurrent bullous eruption of First few years of life Blisters brought out by Keratins 5 and 14 Autosomal-dominant
the hands and feet (Weber– walking
Cockayne syndrome)
Junctional bullous dermolysis Birth Erosions on legs, oral Laminin V Autosomal-recessive
(Herlitz disease) mucosa; severe peri-
oral involvement
Scarring types
Epidermolysis bullosa dystro- Infancy Numerous blisters on Type VII collagen Autosomal-dominant
phica, dominant hands and feet; milia
formation
Epidermolysis bullosa dystro- Birth Repeated episodes of Type VII collagen Autosomal-recessive
phica, recessive blistering, secondary
infection and scarring—
“mitten hands and feet”

seen in adolescent acne. It has been hypothesized, but accumulates continuously within the cystic cavity. The
not proved, that infants who have severe neonatal acne resultant lesion is an enlarging sphere just beneath the
will develop severe adolescent acne. skin surface. Most authorities believe that closed come-
The onset of adolescent acne is between ages 8 and dones are precursors of inflammatory acne. If open or
10 years in 40% of children. The early lesions are usu- closed comedones are the predominant lesions on the
ally limited to the face and are primarily closed come- skin in adolescent acne, the condition is called come-
dones (whiteheads; see following discussion). Eventu- donal acne.
ally, 85% of adolescents develop some form of acne. In typical adolescent acne, several different types of
lesions are present simultaneously, for example, open
Clinical Findings and closed comedones and inflammatory lesions such
as papules, pustules, and cysts. Inflammatory lesions
Acne occurs in sebaceous follicles, which, unlike hair may also rarely occur as interconnecting, draining sinus
follicles, have large, abundant sebaceous glands and tracts. Adolescents with cystic acne require prompt
usually lack hair. They are located primarily on the medical attention, because ruptured cysts and sinus
face, upper chest, back, and penis. Obstruction of the tracts result in severe scar formation. New acne scars are
sebaceous follicle opening produces the clinical lesion highly vascular and have a reddish or purplish hue.
of acne. If the obstruction occurs at the follicular Such scars return to normal skin color after several
mouth, the clinical lesion is characterized by a wide, years. Acne scars may be depressed beneath the skin
patulous opening filled with a plug of stratum corneum level, raised, or flat to the skin. In adolescents with a
cells. This is the open comedo, or blackhead. Open tendency toward keloid formation, keloidal scars can
comedones are the predominant clinical lesion in early occur following acne lesions, particularly over the ster-
adolescent acne. The black color is caused not by dirt nal area.
but by oxidized melanin within the stratum corneum
cellular plug. Open comedones do not often progress to
inflammatory lesions. Closed comedones, or white-
heads, are caused by obstruction just beneath the follic-
Differential Diagnosis
ular opening in the neck of the sebaceous follicle, which Consider rosacea, nevus comedonicus, flat warts, mil-
produces a cystic swelling of the follicular duct directly iaria, molluscum contagiosum, and the angiofibromas
beneath the epidermis. The stratum corneum produced of tuberous sclerosis.
 SKIN / 419

Pathogenesis Table 14–6. Acne treatment.

The primary event in acne formation is obstruction of
the sebaceous follicle. Ordinarily the lining of such fol- Comedonal acne One of the following:
licles contains one or two layers of stratum corneum Retinoic acid, 0.025, 0.05, or
cells, but in acne the stratum corneum is overproduced. 0.1% cream; 0.01 or 0.025%
gel; or 0.1% microgel
This phenomenon is androgen-dependent in adolescent
Adapalene, 0.1% gel or solution
acne. The sebaceous follicles contain an enzyme, testos- Papular inflammatory acne One from first grouping, plus
terone 5α-reductase, which converts plasma testos- one of the following:
terone to dihydrotestosterone. This androgen is a po- Topical antibiotics
tent stimulus for nuclear division of the follicular Benzoyl peroxide, 2.5, 4, 5, 8, or
germinative cells and subsequently of excessive cell pro- 10% gel or lotion; 4 or 8%
duction. Thus obstruction requires the presence of both wash
circulating androgens and the converting enzyme. After Azaleic acid, 20% cream
the production or administration of androgens, a delay Clindamycin, 1% lotion, solu-
results until cellular proliferation occurs, followed by tion, or gel
follicular obstruction. Pustular inflammatory acne One from first grouping, plus
The pathogenesis of inflammatory acne is not well one of the following:
understood. Undoubtedly, physical manipulation of a Oral antibiotics
closed comedo could lead to rupture of the cavity con- Tetracycline or erythromycin,
tents into the dermis with a subsequent inflammatory 250–500 mg, bid
response. Spontaneous inflammation also occurs in ob- Minocycline or doxycycline,
structed follicles, but the reason for this is unclear. An 50–100 mg, bid
attractive hypothesis is that overgrowth of gram-posi- Nodulocystic acne Accutane, 1 mg/kg/day
tive bacteria in the obstructed follicle (either Propioni-
bacterium acnes or Staphylococcus epidermidis) might
stimulate factors that initiate inflammation. Overpro- daily, or the combination of a retinoid applied to acne-
duction of sebum and free fatty acid formation seem bearing areas of the skin once daily in the evening and a
unlikely as causes of inflammation in acne as presently benzoyl peroxide gel or azaleic acid applied once daily
understood. in the morning may be used. This regimen will control
Adolescent acne may be worsened by several external 80–85% of cases of adolescent acne.
causes. Frictional acne caused by headbands, football
helmets, or tight-fitting brassieres or other garments oc- B. TOPICAL ANTIBIOTICS
curs predominantly underneath the area where the gar- Topical antibiotics are used to avoid the side effects
ment is worn. Oil-based cosmetics may be responsible caused by systemic antibiotics. Topical antibiotics are
for predominantly comedonal acne, and hair sprays less effective than systemic antibiotics and at best are
may produce acne along the hair margin. equivalent in potency to 250 mg of tetracycline orally
Drug-induced acne should be suspected in teenagers once a day. One percent clindamycin phosphate solu-
if all lesions are in the same stage at the same time and tion is the most efficacious topical antibiotic. Most P
if involvement extends to the lower abdomen, lower acnes are now resistant to topical erythromycin solu-
back, arms, and legs. Drugs responsible for acne include tions.
corticotropin (ACTH), glucocorticoids, androgens, hy-
dantoins, and isoniazid, each of which increases plasma C. SYSTEMIC ANTIBIOTICS
testosterone. Antibiotics that are concentrated in sebum, such as
tetracycline, minocycline, and doxycycline, are very ef-
Treatment fective in inflammatory acne. The usual dose of tetracy-
cline is 0.5–1 g; of minocycline and doxycycline,
Different treatment options are listed in Table 14–6. 50–100 mg taken once or twice daily on an empty
stomach (nothing to eat 1 hour before or after the med-
A. TOPICAL KERATOLYTIC AGENTS ication). Treatment should be continued for
The mainstay of acne therapy is the use of potent topi- 2–3 months until the acne lesions are suppressed.
cal keratolytic agents applied to the skin to relieve fol-
licular obstruction. The most effective keratolytic D. ORAL RETINOIDS
agents are the retinoids; tretinoin (retinoic acid), adapa- An oral retinoid, 13-cis-retinoic acid (isotretinoin; Ac-
lene, and tazarotene. The agents may be used once cutane), is the most effective treatment for severe cystic
420 / CHAPTER 14

acne. The precise mechanism of its action is unknown, BACTERIAL INFECTIONS OF THE SKIN
but decreased sebum production, decreased follicular
obstruction, decreased skin bacteria, and general anti- Impetigo
inflammatory activities have been described. The initial Erosions covered by honey-colored crusts are diagnostic
dosage is 40 mg once or twice daily. This drug is not ef- of impetigo. Staphylococci and group A streptococci
fective in comedonal acne or other mild forms of acne. are important pathogens in this disease, which histolog-
Side effects include dryness and scaliness of the skin, ically consists of superficial invasion of bacteria into the
dry lips, and, occasionally, dry eyes and dry nose. Up to upper epidermis, forming a subcorneal pustule.
10% of patients experience mild, reversible hair loss. Impetigo should be treated with an antimicrobial
Elevated liver enzymes and blood lipids have rarely agent effective against Staphylococcus aureus (β-lacta-
been described. Acute depression may occur. mase-resistant penicillins or cephalosporins, clin-
Isotretinoin is teratogenic in young women of child- damycin, amoxicillin–clavulanate) for 7–10 days. Topi-
bearing age. Because of this and the other side effects, it cal mupirocin (three times daily) is also effective.
is not recommended unless strict adherence to the FDA
guidelines is ensured. Accutane prescribers must now
be certified. Bullous Impetigo
All impetigo is bullous, with the blister forming just be-
E. OTHER ACNE TREATMENTS neath the stratum corneum, but in bullous impetigo
No convincing evidence supports the contention that there is, in addition to the usual erosion covered by a
dietary management, mild drying agents, abrasive honey-colored crust, a border filled with clear fluid.
scrubs, oral vitamin A, ultraviolet light, cryotherapy, Staphylococci may be isolated from these lesions, and
and incision and drainage have any beneficial effects in systemic signs of circulating exfoliatin are absent. Bul-
the management of acne. lous varicella is a disorder that represents bullous im-
petigo as a superinfection in varicella lesions. Treat-
F. AVOIDANCE OF COSMETICS AND HAIR SPRAY ment with oral antistaphylococcal drugs for 7–10 days
is effective. Application of cool compresses to debride
Acne can be aggravated by a variety of external factors
crusts is a helpful symptomatic measure.
that result in further obstruction of partially occluded
sebaceous follicles. Discontinuing the use of oil-based
cosmetics, face creams, and hair sprays may alleviate the Ecthyma
comedonal component of acne within 4–6 weeks. Ecthyma is a firm, dry crust, surrounded by erythema
that exudes purulent material. It represents deep inva-
Patient Education & Follow-Up Visits sion by group A β-hemolytic streptococci through the
epidermis to the superficial dermis. Treatment is with
The mechanism of acne formation and the treatment systemic penicillin. This should not be confused with
plan must be explained to adolescent patients. Time ecthyma gangrenosum. Lesions of ecthyma gangreno-
should be set aside at the first visit to answer questions. sum may be similar in appearance, but they are seen in
Explain that there will not be much improvement for a severely ill or immunocompromised patient and are
4–8 weeks. Fifty percent improvement at 8–12 weeks is due to systemic dissemination of bacteria, usually
considered average. Establish guidelines for ideal con- Pseudomonas aeruginosa, through the bloodstream.
trol and explain that the best result the patient can ex-
pect is the appearance of only one or two new pimples a
month. No drug is available that will prevent an adoles- Cellulitis
cent from ever having another acne lesion. A written Cellulitis is characterized by erythematous, hot, tender,
education sheet is useful. ill-defined, edematous plaques accompanied by re-
Follow-up visits should be made every 6–8 weeks. gional lymphadenopathy. Histologically, this disorder
The criterion for ideal control is a few lesions every represents invasion of microorganisms into the lower
4 weeks. Explain again what medications are being used dermis and sometimes beyond, with obstruction of
and what the treatment is intended to achieve, and local lymphatics. Group A β-hemolytic streptococci
question the patient to determine whether the medica- and coagulase-positive staphylococci are the most com-
tions are being used properly. mon causes; pneumococci and Haemophilus influenzae
are rare causes. Staphylococcal infections are usually
Gollnick H, Cunliffe W: Management of acne: A report from a more localized and more likely to have a purulent cen-
global alliance to improve outcomes in acne. J Am Acad Der- ter; streptococcal infections spread more rapidly, but
matol 2003;49:S1 [PMID: 12833004]. these characteristics cannot be used to specify the in-
 SKIN / 421

fecting agent. An entry site of prior trauma or infection toxins from dermatophytes, especially those whose nat-
(eg, varicella) is often present. Septicemia is a potential ural host is animals or soil, for example, Microsporum
complication. Treatment is with an appropriate sys- canis and Trichophyton verrucosum—results in dermati-
temic antibiotic. tis. Fungal infection should be suspected with any red
and scaly lesion.
Folliculitis
Classification & Diagnosis
A pustule at a follicular opening represents folliculitis.
If the pustule occurs at eccrine sweat orifices, it is cor- A. TINEA CAPITIS
rectly called poritis. Staphylococci and streptococci are Thickened, broken-off hairs with erythema and scaling
the most frequent pathogens. Treatment consists of of underlying scalp are the distinguishing features
measures to remove follicular obstruction—either cool, (Table 14–7). In epidemic ringworm, hairs are broken
wet compresses for 24 hours or keratolytics such as off at the surface of the scalp, leaving a “black dot” ap-
those used for acne. pearance. Pustule formation and a boggy, fluctuant
mass on the scalp occur in M canis and T tonsurans in-
Abscess fections. This mass, called a kerion, represents an exag-
gerated host response to the organism. Diffuse scaling
An abscess occurs deep in the skin, at the bottom of a of the scalp may also be seen. Fungal culture should be
follicle or an apocrine gland, and is diagnosed as an ery- performed in all cases of suspected tinea capitis.
thematous, firm, acutely tender nodule with ill-defined
borders. Staphylococci are the most common organ- B. TINEA CORPORIS
isms. Treatment consists of incision and drainage and Tinea corporis presents either as annular marginated
systemic antibiotics. papules with a thin scale and clear center or as an annu-
lar confluent dermatitis. The most common organisms
Scalded Skin Syndrome are Trichophyton mentagrophytes and M canis. The diag-
nosis is made by scraping thin scales from the border of
This entity consists of the sudden onset of bright red, the lesion, dissolving them in 20% KOH, and examin-
acutely painful skin, most obvious periorally, perior- ing for hyphae.
bitally, and in the flexural areas of the neck, the axillae,
the popliteal and antecubital areas, and the groin. The C. TINEA CRURIS
slightest pressure on the skin results in severe pain and Symmetrical, sharply marginated lesions in inguinal
separation of the epidermis, leaving a glistening layer areas occur with tinea cruris. The most common organ-
(the stratum granulosum of the epidermis) beneath. isms are Trichophyton rubrum, T mentagrophytes, and
The disease is caused by a circulating toxin (exfoliatin) Epidermophyton floccosum.
elaborated by phage group II staphylococci. The site of
action of the exfoliatin is the intracellular area of the D. TINEA PEDIS
granular layer, resulting in a separation of cells. The The diagnosis of tinea pedis in a prepubertal child must
causative staphylococci may be isolated not from the always be regarded with skepticism; atopic feet or con-
skin but rather from the nasopharynx, an abscess, sinus,
blood culture, and so on. Treatment is with systemic
antistaphylococcal drugs.
Table 14–7. Clinical features of tinea capitis.
Chilller K et al: Skin microflora and bacterial infection of the skin.
J Investig Dermatol Symp Proc 2001;6:170 [PMID:
11924823].
Microscopic
Most Common Clinical Appearance in
Oumeish I et al: Acute bacterial skin infections in children. Clin
Dermatol 2000;18:667 [PMID: 11173202].
Organisms Appearance KOH
Trichophyton Hairs broken off Hyphae and spores
tonsurans (90%) 2–3 mm from folli- within hair
FUNGAL INFECTIONS OF THE SKIN cle; “black dot”; no
1. Dermatophyte Infections fluorescence

Dermatophytes become attached to the superficial layer Microsporum canis Thickened broken- Small spores out-
of the epidermis, nails, and hair, where they proliferate. (10%) off hairs that fluo- side of hair; hyphae
resce yellow-green within hair
They grow mainly within the stratum corneum and do
with Wood’s lamp
not invade the lower epidermis or dermis. Release of
422 / CHAPTER 14

tact dermatitis is a more likely diagnosis in this age in areas of sun-induced pigmentation. In winter, the
group. Tinea pedis occurs most commonly in postpu- polycyclic macules appear reddish brown.
bertal males with blisters on the instep of the foot. Fis- Treatment consists of application of selenium sul-
suring between the toes is occasionally seen. fide (Selsun), 2.5% suspension, or topical antifungals.
Selenium sulfide should be applied to the whole body
E. TINEA UNGUIUM (ONYCHOMYCOSIS) and left on overnight. Treatment can be repeated again
Loosening of the nail plate from the nail bed (onychol- in 1 week and then monthly thereafter. It tends to be
ysis), giving a yellow discoloration, is the first sign of somewhat irritating, and the patient should be warned
fungal invasion of the nails. Thickening of the distal about this difficulty.
nail plate then occurs, followed by scaling and a
crumbly appearance of the entire nail plate surface. T VanderStraten MR et al: Cutaneous infections dermatophytosis,
rubrum and T mentagrophytes are the most common onychomychosis and tinea versicolor. Infect Dis North Am
causes. The diagnosis is confirmed by KOH examina- 2003;17:87 [PMID: 12751262].
tion and fungal culture. Usually only one or two nails
are involved. If every nail is involved, psoriasis, lichen 3. Candida albicans Infections
planus, or idiopathic trachyonychia is a more likely di-
agnosis than fungal infection.
(See also Chapter 39.)
In addition to being a frequent invader in diaper der-
Treatment matitis, Candida albicans also infects the oral mucosa,
where it appears as thick white patches with an erythe-
The treatment of dermatophytosis is quite simple: If matous base (thrush); the angles of the mouth, where it
hair is involved, griseofulvin is the treatment of choice. causes fissures and white exudate (perleche); and the
Topical antifungal agents do not enter hair or nails in cuticular region of the fingers, where thickening of the
sufficient concentration to clear the infection. The ab- cuticle, dull red erythema, and distortion of growth of
sorption of griseofulvin from the gastrointestinal tract is the nail plate suggest the diagnosis of candidal parony-
enhanced by a fatty meal; thus, whole milk or ice cream chia. Candida dermatitis is characterized by sharply de-
taken with the medication increases absorption. The fined erythematous patches, sometimes with eroded
dosage of griseofulvin is 20 mg/kg/d. With hair infec- areas. Pustules, vesicles, or papules may be present as
tions, cultures should be done every 4 weeks, and treat- satellite lesions. Similar infections may be found in
ment should be continued for 6–8 weeks following a other moist areas, such as the axillae and neck folds.
negative culture. The side effects are few, and the drug This infection is more common in children who have
has been used successfully in the newborn period. Itra- recently received antibiotics.
conazole and terbinafine have been used when response A topical imidazole cream is the drug of first choice
to griseofulvin is unsatisfactory. For nails, daily admin- for C albicans infections. In diaper dermatitis, the
istration of topical ciclopirox 8% (Penlac nail lacquer) cream form can be applied every 3–4 hours. In oral
can be considered, as can pulsed-dose itraconazole thrush, nystatin suspension should be applied directly
given in three 1-week pulses separated by 3 weeks. to the mucosa with the parent’s finger or a cotton-
Tinea corporis, tinea pedis, and tinea cruris can be tipped applicator, because it is not absorbed and acts
treated effectively with topical medication after careful topically. In candidal paronychia, the antifungal agent
inspection to make certain that the hair and nails are is applied over the area, covered with occlusive plastic
not involved. Treatment with clotrimazole (Lotrimin), wrapping, and left on overnight after the application is
miconazole (Micatin), econazole (Spectazole), terbina- made airtight. Refractory candidiasis will respond to a
fine (Lamisil), or haloprogin (Halotex) applied twice brief course of oral fluconazole.
daily for 3–4 weeks is recommended.
Hay RJ: The management of superficial candidiasis. J Am Acad
Pomeranz AJ, Sabnis SS: Tinea capitis: Epidemiology, diagnosis Dermatol 1999;40:S35 [PMID: 10367915].
and management strategies. Paediatr Drugs 2002;4:779
[PMID: 1241130].
VIRAL INFECTIONS OF THE SKIN
(See Chapter 36.)
2. Tinea Versicolor
Herpes Simplex
Tinea versicolor is a superficial infection caused by
Pityrosporum orbiculare (also called Malassezia furfur), a Grouped vesicles or grouped erosions suggest herpes
yeast-like fungus. It characteristically causes polycyclic simplex. The microscopic finding of epidermal giant
connected hypopigmented macules and very fine scales cells after scraping the vesicle base with a No. 15 blade,
 SKIN / 423

smearing on a slide, and staining with Wright stain Recurrent staphylococcal pyodermas, tinea of the face,
(Tzanck smear) suggests herpes simplex or varicella- and onychomycosis are also observed. A generalized
zoster. Rapid immunofluorescent tests for herpes sim- dermatitis with features of seborrhea is extremely com-
plex virus and varicella-zoster virus are available. In in- mon. In general, persistent, recurrent, or extensive skin
fants, lesions resulting from herpes simplex type 1 are infections should make one suspicious of HIV infec-
seen on the gingiva and lips, periorbitally, or on the tion.
thumb in children who suck their thumbs. Recurrent
erosions in the mouth are usually aphthous stomatitis Garman ME, Tyring SK: The cutaneous manifestations of HIV in-
in children rather than recurrent herpes simplex. Her- fection. Dermatol Clin 2002;20:193 [PMID: 12120434].
pes simplex type 2 lesions are seen on the genitalia and Laude TA: Manifestations of HIV disease in children. Clin Derma-
in the mouth in adolescents. Cutaneous dissemination tol 2000;18:457 [PMID: 11024313].
of herpes simplex occurs in patients with atopic der- Stefanaki C et al: Skin manifestations of HIV-1 infection in chil-
matitis (eczema herpeticum, Kaposi varicelliform erup- dren. Clin Dermatol 2002;20:74 [PMID: 11849897].
tion). The treatment of herpes simplex virus infections Wananukul S et al: Mucocutaneous findings in pediatric AIDS re-
is discussed in Chapter 36. lated to degree of immunosuppression. Pediatr Dermatol
2003;20:289 [PMID: 1286945].
Whitley RJ: Herpes simplex virus in children. Curr Treat Options
Neurol 2002;4:231 [PMID: 11931730]. Virus-Induced Tumors
Varicella-Zoster A. MOLLUSCUM CONTAGIOSUM
Molluscum contagiosum is a poxvirus that induces the
Grouped vesicles in a dermatome, usually on the trunk epidermis to proliferate, forming a pale papule. Mollus-
or face, suggest varicella-zoster infection. Zoster in chil- cum contagiosum consists of umbilicated, white or
dren may not be painful and usually has a mild course. whitish yellow papules in groups on the genitalia or
In patients with compromised host resistance, the ap- trunk. They are common in sexually active adolescents
pearance of an erythematous border around the vesicles and in infants and preschool children. Molluscum le-
is a good prognostic sign. Conversely, large bullae with- sions in general are treated in the same manner as warts.
out a tendency to crusting and systemic illness imply a Treatment for molluscum includes benign neglect, top-
poor host response to the virus. Varicella-zoster and ical imiquimod, topical cantharidin, oral cimetidine,
herpes simplex lesions undergo the same series of and curettage.
changes: papule, vesicle, pustule, crust, slightly de-
pressed scar. Varicella appears in crops, and many dif-
ferent stages of lesions are present at the same time. Smith KJ, Skelton H: Molluscum contagiosum: Recent advances in
pathogenic mechanisms and new therapies. Am J Clin Der-
Itching is usually the only symptom, and cool baths matol 2002;3:535 [PMID: 12358555].
as frequently as necessary or drying lotions such as
calamine lotion are sufficient to relieve symptoms. In B. WARTS
immunosuppressed children, intravenous or oral acy- Warts are skin-colored papules with irregular (verru-
clovir should be used. cous) surfaces. They are intraepidermal tumors caused
by infection with human papillomavirus. This DNA
Chen TM et al: Clinical manifestations of varicella-zoster virus in-
fection. Dermatol Clin 2002;20:267 [PMID: 12120440].
virus induces the epidermal cells to proliferate, thus re-
Emmert DH: Treatment of common cutaneous herpes simplex
sulting in the warty growth. Flat warts are smoother
virus infections. Am Fam Physician 2000;15:1697 [PMID: and smaller than common warts and are often seen on
10750877]. the face.
No therapy for warts is ideal, and some types of
Human Immunodeficiency Virus Infection therapy should be avoided because the recurrence rate
of warts is high. For flat warts, a good response to
(See also Chapter 37.) 0.05% tretinoin cream or topical imiquimod (Aldara)
The average time of onset of skin lesions after perina- cream, applied once daily for 3–4 weeks, has been re-
tally acquired human immunodeficiency virus (HIV) ported.
infection is 4 months; after transfusion-acquired infec- The best treatment for the solitary common (vul-
tion, it is 11 months. Persistent oral candidiasis and re- garis) wart is to freeze it with liquid nitrogen. The liq-
calcitrant candidal diaper rash are the most frequent cu- uid nitrogen should be allowed to drip from the cotton-
taneous features of infantile HIV infection. Severe or tipped applicator onto the wart without pressure.
recurrent herpetic gingivostomatitis, varicella-zoster in- Pressure exaggerates cold injury by causing vasocon-
fection, and molluscum contagiosum infection occur. striction and may produce a deep ulcer and scar. Liquid
424 / CHAPTER 14

nitrogen is applied by drip until the wart turns com- and feces is necessary to confirm the diagnosis. Scrape
pletely white and stays white for 20–25 seconds. Large an unscratched papule or burrow with a No. 15 blade
and painful plantar warts are treated most effectively by and examine microscopically in immersion oil to con-
applying 40% salicylic acid plaster cut with a scissors to firm the diagnosis. In a child who is often scratching,
fit the lesion. The sticky brown side of the plaster is scrape under the fingernails. Examine the parents for
placed against the lesion, taped on securely with adhe- unscratched burrows.
sive tape, and left on for 5 days. The plaster is then re- Lindane (γ-benzene hexachloride; Kwell) and per-
moved, and the white necrotic warty tissue can be gen- methrin are excellent scabicides. However, because lin-
tly rubbed off with a pumice stone and a new salicylic dane is concentrated in the central nervous system,
acid plaster applied. This procedure is repeated every where toxicity from systemic absorption in infants has
5 days, and the patient is seen every 4 weeks. Most been reported, the following restricted use of this agent
plantar warts resolve in 6–8 weeks when treated in this is recommended: (1) For adults and older children, one
way. Vascular pulsed dye lasers are a useful adjunct treatment of lindane lotion or cream applied to the en-
therapy for the treatment of plantar warts. tire body and left on for 4 hours, followed by shower-
Sharp scalpel excision, electrosurgery, and nonspe- ing, is sufficient. (2) Infants tend to have more organ-
cific burning laser surgery should be avoided, because isms and many more lesions and may have to be
the resulting scar often becomes a more difficult prob- retreated in 7–10 days. All family members should be
lem than the wart itself and the wart may recur in the treated simultaneously. Permethrin 5% cream (Elimite)
area of the scar. may be substituted for lindane in infants.
Venereal warts (condylomata acuminata) (see Chap-
ter 40) may be treated with imiquimod, 25%
podophyllum resin (podophyllin) in alcohol, or pod- Pediculoses (Louse Infestations)
ofilox, a lower concentration of purified podophyllin. The presence of excoriated papules and pustules and a
Podophyllin should be painted on the lesions and then history of severe itching at night suggest infestation
washed off after 4 hours. Retreatment in 2–3 weeks with the human body louse. This louse may be discov-
may be necessary. Podofilox is applied daily, whereas ered in the seams of underwear but not on the body. In
imiquimod is used on Monday, Wednesday, and Fri- the scalp hair, the gelatinous nits of the head louse ad-
day. A wart not on the vulvar mucous membrane but here tightly to the hair shaft. The pubic louse may be
on the adjacent skin should be treated as a common found crawling among pubic hairs, or blue-black mac-
wart and frozen. ules may be found dispersed through the pubic region
For isolated warts and periungual warts, cantharidin (maculae ceruleae). The pubic louse is often seen on the
is effective and painless in children. It causes a blister eyelashes of newborns.
and sometimes is difficult to control. An undesirable Lindane (γ-benzene hexachloride; Kwell) is recom-
complication is the appearance of warts along the mar- mended: For head lice, a shampoo preparation is left on
gins of the cantharidin blister. Cantharidin is applied to the scalp for 5 minutes and rinsed out thoroughly. The
the skin, allowed to dry, and covered with occlusive hair is then combed with a fine-tooth comb to remove
tape or a bandage for 24 hours. nits. This may be repeated in 7 days. Lindane cream or
No wart therapy is immediately and definitively suc- lotion applied to the body for 4 hours may be necessary
cessful, and recurrences are reported in more than 30% for body lice, but boiling the clothing for 10 minutes
of cases even with the best care. followed by ironing the seams with a hot iron usually
eliminates them. Permethrin 1% creme rinse also elimi-
Allen AL, Siegfried EC: What’s new in human papillomavirus in- nates lice. Lindane cream or lotion applied to the pubic
fection. Curr Opin Pediatr 2000;12:365 [PMID: 10943818]. area for 24 hours is sufficient to treat pediculosis pubis.
Savrin C: Human papillomavirus in children. Adv Nurse Pract It may be repeated in 4–5 days. Permethrin 5% cream
2001;9:99 [PMID: 12400281]. (Elimite) may be substituted for lindane in infants.

INSECT INFESTATIONS Angel TA et al: Infestations in the pediatric patient. Pediatr Clin
North Am 2000;47:921 [PMID: 10943266].
Scabies Lafuente CR: Is it scabies? How to tell. Nurse Pract 2003;28:
57 [PMID: 12796625].
Scabies is suggested by linear burrows about the wrists, Roberts RJ: Clinical practice. Head lice. N Engl J Med 2002;
ankles, finger webs, areolas, anterior axillary folds, geni- 346:1645 [PMID: 12023998].
talia, or face (in infants). Often there are excoriations, Venna S et al: Scabies and lice: Review of the clinical features and
honey-colored crusts, and pustules from secondary in- management principles. Dermatol Nurs 2001;13:257
fection. Identification of the female mite or her eggs [PMID: 11917782].
 SKIN / 425

Papular Urticaria feet. This phase lasts from age 2 years to adolescence.
Some children will have involvement only of the soles
Papular urticaria is characterized by grouped erythema- of the feet, with cracking, redness, and pain, so-called
tous papules surrounded by an urticarial flare and dis- atopic feet. Only one third of children with typical flex-
tributed over the shoulders, upper arms, and buttocks ural eczema will progress to adolescent eczema, which is
in infants. Although not a true infestation, these lesions usually manifested by hand dermatitis only. Atopic der-
represent delayed hypersensitivity reactions to stinging matitis is quite unusual after age 30 years.
or biting insects and can be reproduced by patch testing Atopic dermatitis results from an interaction be-
with the offending insect. Fleas from dogs and cats are tween susceptibility genes, the host environment, skin
the usual offenders. Less commonly, mosquitoes, lice, barrier defects, pharmacologic abnormalities and im-
scabies, and bird and grass mites are involved. The sen- munologic response. The case for food and inhalant al-
sitivity is transient, lasting 4–6 months. Usually no lergens as specific causes of atopic dermatitis is not
other family members are affected. It is often difficult strong. However, since the cause of atopic dermatitis
for the parents to understand why no one else is af- remains unknown, there is debate between dermatolo-
fected. The logical therapy is to remove the offending gists and allergists on the exact role of allergy in atopic
insect, although in most cases it is very difficult to iden- dermatitis (see Chapter 34).
tify the exact cause. Topical corticosteroids and oral an- A few patients with atopic dermatitis have immuno-
tihistamines will control symptoms. deficiency with recurrent pyodermas, unusual susceptibil-
ity to herpes simplex viruses, hyperimmunoglobulinemia
Demain JG: Papular urticaria and things that bite in the night.
Curr Allergy Asthma Rep 2003;3:291 [PMID: 12791206].
E, defective neutrophil and monocyte chemotaxis, and
impaired T-lymphocyte function (see Chapter 29).
Stibich AS, Schwartz RA: Papular urticaria. Cutis 2001;68:89
[PMID: 11534921]. A faulty epidermal barrier may predispose the patient
with atopic dermatitis to itchy skin. Inability to hold
water within the stratum corneum results in rapid evap-
DERMATITIS (ECZEMA) oration of water, shrinking of the stratum corneum, and
The terms dermatitis and eczema are currently used in- cracks in the epidermal barrier. Such skin forms an inef-
terchangeably in dermatology, although the term fective barrier to the entry of various irritants—and, in-
eczema truly denotes an acute weeping dermatosis. All deed, it may be clinically useful to regard atopic der-
forms of dermatitis, regardless of cause, may present matitis as a primary-irritant contact dermatitis and
with acute edema, erythema, and oozing with crusting, simply tell the patient, you have sensitive skin. Chronic
mild erythema alone, or lichenification. Lichenification atopic dermatitis is frequently infected secondarily with
is diagnosed by thickening of the skin with a shiny sur- Staphylococcus aureus or Streptococcus pyogenes.
face and exaggerated, deepened skin markings. It is the
response of the skin to chronic rubbing or scratching. Treatment
Although the lesions of the various dermatoses are
histologically indistinguishable, clinicians have A. ACUTE STAGES
nonetheless divided the disease group called dermatitis Application of wet dressings and topical corticosteroids
into several categories based on known causes in some is the treatment of choice for acute, weeping atopic
cases and differing natural histories in others. eczema. A topical steroid preparation is applied two
times daily and covered with wet dressings as outlined
1. Atopic Dermatitis at the beginning of this chapter. Superinfection or colo-
nization with S aureus is common, and appropriate sys-
Atopic dermatitis is a general term for chronic superfi- temic antibiotics may be necessary. If the expected im-
cial inflammation of the skin that can be applied to a provement is not seen, bacterial cultures should be
heterogeneous group of patients. Many (not all) pa- obtained to identify the possibility of an organism resis-
tients go through three clinical phases. In the first, in- tant to standard therapy.
fantile eczema, the dermatitis begins on the cheeks and
scalp and frequently expresses itself as oval patches on B. CHRONIC STAGES
the trunk, later involving the extensor surfaces of the Treatment is aimed at avoiding irritants and restoring
extremities. The usual age at onset is 2–3 months, and water to the skin. No soaps or harsh shampoos should be
this phase ends at age 18 months to 2 years. Only one used, and the patient should avoid woolen or any rough
third of all infants with atopic eczema progress to phase clothing. Bathing is minimized to every second or third
2 childhood or flexural eczema in which the predomi- day. Twice-daily lubrication of the skin is very important.
nant involvement is in the antecubital and popliteal Nonperfumed lotions or creams are suitable lubri-
fossae, the neck, the wrists, and sometimes the hands or cants. Plain petrolatum is an acceptable lubricant, but
426 / CHAPTER 14

some people find it too greasy and it may also cause con- ops within a few hours, reaches peak severity at
siderable sweat retention. Liberal use of Cetaphil lotion 24 hours, and then disappears. Allergic eczematous
as a soap substitute four or five times a day is also satis- contact dermatitis (described in the next section) has a
factory as a means of lubrication. A bedroom humidifier delayed onset of 18 hours, peaks at 48–72 hours, and
is often helpful. Topical corticosteroids should be limited often lasts as long as 2–3 weeks even if exposure to the
to medium strength (see Table 14–3). There is never any offending antigen is discontinued.
reason to use super- or high-potency corticosteroids in Diaper dermatitis, the most common form of pri-
atopic dermatitis. In superinfected atopic dermatitis, sys- mary irritant contact dermatitis seen in pediatric prac-
temic antibiotics for 10–14 days are necessary. tice, is caused by prolonged contact of the skin with
Topical tacrolimus and pimecrolimus are new topi- urine and feces, which contain irritating chemicals such
cal immunosuppressive agents that are effective in as urea and intestinal enzymes. The diagnosis of diaper
atopic dermatitis. Tacrolimus should be reserved for dermatitis is based on the picture of erythema and scal-
children older than 2 years of age with atopic dermatitis ing of the skin in the perineal area and the history of
unresponsive to medium-potency topical steroids. prolonged skin contact with urine or feces. This is fre-
Pimecrolimus is helpful for chronic eczema of the face. quently seen in the “good baby” who sleeps many hours
Treatment failures in chronic atopic dermatitis are through the night without waking. In 80% of cases of
most often the result of patient noncompliance. This is diaper dermatitis lasting more than 3 days, the affected
a frustrating disease for parent and child. area is colonized with C albicans even before appearance
of the classic signs of a beefy red, sharply marginated
Cookson WO, Moffatt MF: The genetics of atopic dermatitis. dermatitis with satellite lesions.
Curr Opin Allergy Clin Immunol 2002;2:383 [PMID: Treatment consists of changing diapers frequently.
12582320]. Because rubber or plastic pants prevent evaporation of
Daniels J, Harper J: The epidemiology of atopic dermatitis. Hosp the contactant and enhance its penetration into the
Med 2002;63:649 [PMID: 12474607]. skin, they should be avoided as much as possible. Air
Eichenfield LF, Beck L: Elidel (pimecrolimus) cream 1%: A non- drying is useful. Streptococcal perianal cellulitis and in-
steroidal topical agent for the treatment of atopic dermatitis. fantile psoriasis should be included in the differential
J Allergy Clin Immunol 2003;111:1153 [PMID:
12743593].
diagnosis. Treatment of long-standing diaper dermatitis
should include application of nystatin or an imidazole
Gianni LM, Sulli MM: Topical tacrolimus in the treatment of
atopic dermatitis. Ann Pharmacother 2001;35:943 [PMID: cream with each diaper change.
11485148].
Lee DJ, Eichenfield LF: Atopic, contact, and seborrheic dermatitis Kazaks EL, Lane AT: Diaper dermatitis. Pediatr Clin North Am
in adolescents. Adolesc Med 2001;12:269 [PMID: 2000;47:909 [PMID: 10943265].
11404201].
Levy M: Diaper rash syndrome or dermatitis. Cutis 2001;67:
Leung DY, Bieber T: Atopic dermatitis. Lancet 2003;361: 37 [PMID: 11398268].
151 [PMID: 12531593].
Lewis-Jones: Atopic dermatitis in childhood. Hosp Med 2001;
62:136 [PMID: 11291461].
4. Allergic Eczematous Contact
Dermatitis (Poison Ivy Dermatitis)
2. Nummular Eczema
Plants such as poison ivy, poison sumac, and poison
Nummular eczema is characterized by numerous sym- oak cause most cases of allergic contact dermatitis in
metrically distributed coin-shaped patches of dermati- children. Allergic contact dermatitis has all the features
tis, principally on the extremities. These may be acute, of delayed-type (T-lymphocyte-mediated) hypersensi-
oozing, and crusted or dry and scaling. The differential tivity. Many substances may cause such a reaction;
diagnosis should include tinea corporis, impetigo, and nickel sulfate, potassium dichromate, and neomycin are
atopic dermatitis. the most common causes. Nickel is found to some de-
The same topical measures should be used as for gree in all metals. Nickel allergy is commonly seen on
atopic dermatitis, although treatment is often more dif- the ears secondary to the wearing of earrings, and near
ficult. the umbilicus from pants snaps and belt buckles. The
true incidence of allergic contact dermatitis in children
3. Primary Irritant Contact Dermatitis is unknown. Children often present with acute der-
matitis with blister formation, oozing, and crusting.
(Diaper Dermatitis) Blisters are often linear and of acute onset.
Contact dermatitis is of two types: primary irritant and Treatment of contact dermatitis in localized areas is
allergic eczematous. Primary irritant dermatitis devel- with topical corticosteroids. In severe generalized in-
 SKIN / 427

volvement, prednisone, 1–2 mg/kg/d orally for Frequent soaping of the skin impairs its water-hold-
10–14 days, can be used. ing capacity and serves as an irritating alkali, and all
soaps should therefore be avoided. Frequent use of
Bruckner AL, Weston WL: Allergic contact dermatitis in children: emollients (eg, Cetaphil, Eucerin, Lubriderm) should
A practical approach to management. Skin Therapy Lett be a major part of therapy.
2002;7:3 [PMID: 12548328].
Weston WL, Bruckner A: Allergic contact dermatitis. Pediatr Clin 8. Keratosis Pilaris
North Am 2000;47:897 [PMID: 10943264].
Follicular papules containing a white inspissated scale
5. Seborrheic Dermatitis characterize keratosis pilaris. Individual lesions are dis-
crete and may be red. They are prominent on the ex-
Seborrheic dermatitis is an erythematous scaly dermati- tensor surfaces of the upper arms and thighs and on the
tis accompanied by overproduction of sebum occurring buttocks and cheeks. In severe cases, the lesions may be
in areas rich in sebaceous glands (ie, the face, scalp, and generalized. Such lesions are seen frequently in children
perineum). This common condition occurs predomi- with dry skin and have also been associated with atopic
nantly in the newborn and at puberty, the ages at which dermatitis and ichthyosis vulgaris.
hormonal stimulation of sebum production is maximal. Treatment is with keratolytics such as topical
Although it is tempting to speculate that overproduc- retinoic acid, lactic acid, or urea creams followed by
tion of sebum causes the dermatitis, the exact relation- skin hydration.
ship is unclear.
Seborrheic dermatitis on the scalp in infancy is clini- Lateef A, Schwartz RA: Keratosis pilaris. Cutis 1999;63:205
cally similar to atopic dermatitis, and the distinction [PMID: 10228747]
may become clear only after other areas are involved.
Psoriasis also occurs in seborrheic areas in older chil- 9. Pityriasis Alba
dren and should be considered in the differential diag-
nosis. White, scaly macular areas with indistinct borders are
Seborrheic dermatitis responds well to low-potency seen over extensor surfaces of extremities and on the
topical corticosteroids. cheeks in children with pityriasis alba. Suntanning ex-
aggerates these lesions. Histologic examination reveals a
mild dermatitis. These lesions may be confused with
6. Dandruff tinea versicolor. Low-potency topical steroids may help
Physiologic scaling or mild seborrhea, in the form of decrease any inflammatory component and may lead to
greasy scalp scales, may be treated by medicated dan- faster return of normal pigmentation.
druff shampoos. The cause is unknown.
Blessman-Weber M et al: Pityriasis alba: A study of pathogenic fac-
tors. J Eur Acad Dermatol Venereol 2002;16:463 [PMID:
Warner RR et al: Dandruff has an altered stratum corneum ultra- 12428838].
structure that is improved with zinc pyrithione shampoo.
J Am Acad Dermatol 2001;45:897 [PMID: 11712036].
COMMON SKIN TUMORS
7. Dry Skin Dermatitis If the skin moves with the nodule on lateral palpation,
(Asteatotic Eczema, Xerosis) the tumor is located within the dermis; if the skin
moves over the nodule, it is subcutaneous. Seventy-five
Newborns and older children who live in arid climates percent of lumps in childhood will be either epidermal
are susceptible to dry skin, characterized by large inclusion cysts (60%) or pilomatrichomas (15%).
cracked scales with erythematous borders. The stratum
corneum is dependent on environmental humidity for
its water, and below 30% environmental humidity the
Epidermal Inclusion Cysts
stratum corneum loses water, shrinks, and cracks. Epidermal inclusion cysts are smooth, dome-shaped
These cracks in the epidermal barrier allow irritating nodules in the skin that may grow to 2 cm in diameter.
substances to enter the skin, predisposing the patient to In infants, they may be found near the eyes, and in
dermatitis. older children and adolescents on the chest, back, or
Treatment consists of increasing the water content scalp. They are the most common superficial lumps in
of the skin in the immediate external environment. children. Treatment, if desired, is surgical excision.
House humidifiers are very useful. Minimize bathing to Pilomatrichomas are benign tumors of the hair ma-
every second or third day. trix. They are most commonly seen on the face and
428 / CHAPTER 14

upper trunk. They are firm and may be irregular. Their Table 14–8. Papulosquamous eruptions
color varies from flesh-colored to pink or blue. The in children.
firmness is secondary to calcification of the tumor.
Treatment is by surgical excision. Psoriasis
Pityriasis rosea
Granuloma Annulare Tinea corporis
Lichen planus
Circles or semicircles of nontender intradermal nodules Chronic parapsoriasis
found over the lower legs and ankles, the dorsum of the Dermatomyositis
hands and wrists, and the trunk, in that order, suggest Lupus erythematosus
granuloma annulare. Histologically, the disease appears Pityriasis rubra pilaris
as a central area of tissue death (necrobiosis) sur- Secondary syphilis
rounded by macrophages and lymphocytes. No treat-
ment is necessary. Lesions resolve spontaneously within
1–2 years in most children.
whites, the lesions are primarily on the trunk; in blacks,
Pyogenic Granuloma lesions are primarily on the extremities and may be ac-
centuated in the axillary and inguinal areas. This disease
Rapid growth of a dark red papule with an ulcerated is common in school-age children and adolescents and
and crusted surface over 1–2 weeks following skin is presumed to be viral in origin. The role of human
trauma suggests pyogenic granuloma. Histologically, herpes virus 7 in the pathogenesis of pityriasis rosea is
this represents excessive new vessel formation with or debated. The condition lasts 6 weeks and may be pru-
without inflammation (granulation tissue). It is neither ritic the first 7–10 days. The major differential diagno-
pyogenic nor granulomatous but should be regarded as sis is secondary syphilis, and a VDRL test should be
an abnormal healing response. Pulsed dye laser and done if syphilis is suspected. A chronic variant of this
curettage followed by electrocautery are the treatments disease may last 2–3 years and is called chronic parapso-
of choice. riasis or pityriasis lichenoides chronica.
Exposing the skin to sunlight until a mild sunburn
Keloids occurs (slight redness) will hasten the disappearance of
Keloids are scars raised above the skin surface with lesions. Ordinarily, no treatment is necessary.
many radial projections of scar tissue. They continue to
enlarge over several years. They are often found on the Karnath B et al: Pityriasis rosea. Appearance and distribution of
face, earlobes, neck, chest, and back. Keloids show no macules aid diagnosis. Postgrad Med 2003;113:94 [PMID:
racial predilection. Treatment includes intralesional in- 12764899].
jection with triamcinolone acetonide, 20 mg/mL, or ex- Kempf W, Burg G: Pityriasis rosea—A virus-induced skin disease?
An update. Arch Virol 2000;145:1509 [PMID: 11003465].
cision and injection with corticosteroids.

Wyatt AJ, Hansen RC: Pediatric skin tumors. Pediatr Clin North 2. Psoriasis
Am 2000;47:937 [PMID: 10943267].
Psoriasis is characterized by erythematous papules cov-
ered by thick white scales. Guttate (drop-like) psoriasis
PAPULOSQUAMOUS ERUPTIONS is a common form in children that often follows an
Papulosquamous eruptions (Table 14–8) comprise episode of streptococcal pharyngitis by 2–3 weeks. The
papules or plaques with varying degrees of scale. sudden onset of small papules (3–8 mm), seen predom-
inantly over the trunk and quickly covered with thick
white scales, is characteristic of guttate psoriasis.
1. Pityriasis Rosea Chronic psoriasis is marked by thick, large scaly plaques
Erythematous papules that coalesce to form oval (5–10 cm) over the elbows, knees, scalp, and other sites
plaques preceded by a large oval plaque with central of trauma. Pinpoint pits in the nail plate are seen, as
clearing and a scaly border (the herald patch) establish well as yellow discoloration of the nail plate resulting
the diagnosis of pityriasis rosea. The herald patch has from onycholysis. Thickening of all 20 nails is an un-
the appearance of ringworm and is often treated as common feature. The sacral and seborrheic areas are
such. It appears 1–30 days before the onset of the gen- commonly involved.
eralized papular eruption. The oval plaques are parallel Psoriasis has no known cause and demonstrates ac-
in their long axis and follow lines of skin cleavage. In tive proliferation of epidermal cells, with a turnover
 SKIN / 429

time of 3–4 days versus 28 days for normal skin. These Table 14–9. Other causes of hair loss in children.
rapidly proliferating epidermal cells are producing ex-
cessive stratum corneum, giving rise to thick, opaque Hair loss with scalp changes
scales. Papulosquamous eruptions that present prob- Atrophy:
lems of differential diagnosis are listed in Table 14–8. Lichen planus
Lupus erythematosus
Treatment Nodules and tumors:
Epidermal nevus
All therapy is aimed at diminishing epidermal turnover Nevus sebaceus
time. Topical steroids are the initial treatment of Thickening:
choice. Penetration of topical corticosteroids through Burn
the enlarged epidermal barrier in psoriasis requires that Hair loss with hair shaft defects (hair fails to grow out
more potent preparations be used, for example, fluoci- enough to require haircuts)
nonide 0.05% (Lidex) or clobetasol 0.05% (Temovate) Monilethrix—alternating bands of thin and thick areas
ointment twice daily. Pili annulati—alternating bands of light and dark pigmen-
The second line of therapy is topical calcipotriene tation
(Dovonex) applied twice daily or the combination of a Pili torti—hair twisted 180 degrees, brittle
superpotent topical steroid twice daily on weekends and Trichorrhexis invaginata (bamboo hair)—intussusception
of one hair into another
calcipotriene twice daily on weekdays for 8 weeks.
Trichorrhexis nodosa—nodules with fragmented hair
Anthralin therapy is also useful. Anthralin is applied
to the skin for a short contact time (eg, 20 minutes
once daily) and then washed off with a neutral soap (eg,
Dove). A 6-week course of treatment is recommended. alopecia areata, tinea capitis (described earlier in this
Crude coal tar therapy is messy and stains bed- chapter), and trichotillomania.
clothes. The newer tar gels (Estar, psoriGel) cause less
staining and are most efficacious. They are applied twice Alopecia Areata
daily for 6–8 weeks. These preparations are sold over the Loss of every hair in a localized area is called alopecia
counter and are not usually covered by insurance plans. areata. This is the most common cause of hair loss in
Scalp care using a tar shampoo requires leaving the children. An immunologic pathogenic mechanism is
shampoo on for 5 minutes, washing it off, and then suspected because dense infiltration of lymphocytes
shampooing with commercial shampoo to remove precedes hair loss. Ninety-five percent of children with
scales. It may be necessary to shampoo daily until scal- alopecia areata completely regrow their hair within
ing is reduced. More severe cases of psoriasis are best 12 months, although as many as 40% may have a re-
treated by a dermatologist. lapse in 5–6 years. A rare and unusual form of alopecia
areata begins at the occiput and proceeds along the hair
Marcoux D, Prost Y: Pediatric psoriasis revisited. J Cutan Med margins to the frontal scalp. This variety, called ophia-
Surg 2002;6:22 [PMID: 11976986]. sis, often eventuates in total scalp hair loss (alopecia to-
Morris A et al: Childhood psoriasis: A clinical review of 1262 cases. talis). The prognosis for regrowth in ophiasis is poor.
Pediatr Dermatol 2001;18:188 [PMID: 11437997].
Treatment of alopecia areata is difficult. Systemic
Rogers M: Childhood psoriasis. Curr Opin Pediatr 2002;14:404
[PMID: 12130902].
corticosteroids given to suppress the inflammatory re-
sponse will result in hair growth, but the hair will fall
out again when the drug is discontinued. Superpotent
HAIR LOSS (ALOPECIA) topical steroids, minoxidil (Rogaine), and anthralin are
treatment options. In children with alopecia totalis, a
Hair loss in children (Table 14–9) imposes great emo- wig is most helpful.
tional stress on the patient and the parent. A 60% hair
loss in a single area is necessary before hair loss can be
Madani S, Shapiro J: Alopecia areata update. J Am Acad Dermatol
detected clinically. Examination should begin with the 2000;42:549 [PMID: 10727199].
scalp to determine whether there are color or infiltrative Tan E et al: A clinical study of childhood alopecia areata in Singa-
changes. Hairs should be examined microscopically for pore. Pediatr Dermatol 2002;19:298 [PMID: 12220271].
breaking and structural defects and to see whether
growing or resting hairs are being shed. Placing re- Trichotillomania
moved hairs in mounting fluid (Permount) on a glass
microscope slide makes them easy to examine. Three Traumatic hair pulling causes the hair shafts to be bro-
diseases account for most cases of hair loss in children: ken off at different lengths, with an ill-defined area of
430 / CHAPTER 14

hair loss, petechiae around follicular openings, and a Drug Eruptions

wrinkled hair shaft on microscopic examination. This
behavior may be merely habit, an acute reaction to se- Drugs may produce urticarial, morbilliform, scarlatini-
vere stress, or a sign of a psychiatric disorder. Eyelashes form, or bullous or fixed skin eruptions. Urticaria may
and eyebrows rather than scalp hair may be pulled out. appear within minutes after drug administration, but
If the behavior has a long history, psychiatric evaluation most reactions begin 7–14 days after the drug is first
may be helpful. Oiling the hair to make it slippery is an administered. These eruptions may occur in patients
aid to behavior modification. who have received these drugs for long periods, and
eruptions continue for days after the drug has been dis-
continued. Acute drug eruptions usually do not pro-
O’Sullivan RL et al: Characterization of trichotillomania. A phe- duce fever, elevated sedimentation rate, or serum sick-
nomenological model with clinical relevance to obsessive–
compulsive spectrum disorders. Psychiatr Clin North Am
ness. If any of these occur, a search for a concominant
2000;23:587 [PMID: 10986729]. infection is warranted. Drugs commonly implicated in
Walsh KH, McDougle CJ: Trichotillomania: Presentation, etiol- skin reactions are listed in Table 14–10.
ogy, diagnosis and therapy. Am J Clin Dermatol 2001;2:327
[PMID: 11721651]. Millikan LE, Feldman M: Pediatric drug allergy. Clin Dermatol
2002;20:29 [PMID: 11849892].

REACTIVE ERYTHEMAS
MISCELLANEOUS SKIN DISORDERS
Erythema Multiforme ENCOUNTERED IN PEDIATRIC
Erythema multiforme begins with papules that later de- PRACTICE
velop a dark center and then evolve into lesions with
central blisters and the characteristic target lesions (iris Aphthous Stomatitis
lesions) that have three concentric circles of color Recurrent erosions on the gums, lips, tongue, palate,
change. Primary injury is to endothelial cells, with later and buccal mucosa are often confused with herpes sim-
destruction of epidermal basal cells and blister forma- plex. A smear of the base of such a lesion stained with
tion. Erythema multiforme has sometimes been diag- Wright stain will aid in ruling out herpes simplex by
nosed in patients with severe mucous membrane in- the absence of epithelial multinucleate giant cells. A
volvement, but Stevens–Johnson syndrome is the usual culture for herpes simplex is also useful in this difficult
term when severe involvement of conjunctiva, oral cav- differential diagnostic problem. The cause remains un-
ity, and genital mucosa also occur.
Many causes are suspected, particularly concomitant
herpes simplex virus, drugs, especially sulfonamides,
and Mycoplasma infections. Recurrent erythema multi- Table 14–10. Common drug reactions.
forme is usually associated with reactivation of herpes
simplex virus. In the mild form, spontaneous healing Fixed drug eruption/erythema multiforme/toxic
occurs in 10–14 days, but Stevens–Johnson syndrome epidermal necrolysis
may last 6–8 weeks. Anticonvulsants
Treatment is symptomatic in uncomplicated ery- Nonsteroidal anti-inflammatory drugs
thema multiforme. Removal of offending drugs is an Sulfonamides
obvious measure. Oral antihistamines such as hydrox- Urticaria
yzine, 2 mg/kg/d orally, are useful. Cool compresses Barbiturates
and wet dressings will relieve pruritus. Steroids have not Opioids
been demonstrated to be effective. Chronic acyclovir Penicillins
therapy has been successful in decreasing attacks in Sulfonamides
those patients with herpes-associated recurrent ery- Morbilliform eruption
thema multiforme. Anticonvulsants
Cephalosporins
Penicillins
Forman R et al: Erythema multiforme, Stevens–Johnson syndrome Sulfonamides
and toxic epidermal necrolysis in children: A review of Photodermatitis
10 years’ experience. Drug Saf 2002;25:965 [PMID: Psoralens
12381216].
Sulfonamides
Leaute-Labreze C et al: Diagnosis, classification, and management Tetracyclines
of erythema multiforme and Stevens–Johnson syndrome.
Thiazides
Arch Dis Child 2000;83:347 [PMID: 10999875].
 SKIN / 431

known, but T-cell-mediated cytotoxicity to various cal and occur mainly on extensor surfaces. The depig-
viral antigens has been postulated. mentation results from a destruction of melanocytes.
There is no specific therapy for this condition. Rins- The basis for this destruction is unknown, but im-
ing the mouth with liquid antacids will provide relief in munologically mediated damage is likely and vitiligo
most patients. Topical corticosteroids in a gel base (eg, sometimes occurs in individuals with selective IgA defi-
fluocinonide gel) may provide some relief. In severe ciency, graft-versus-host disease, or autoimmune en-
cases that interfere with eating, prednisone, 1 mg/kg/d docrinopathies. Treatment is not very effective. Potent
orally for 3–5 days, will suffice to abort an episode. topical steroids for 4 months are the initial treatment.
Colchicine, 0.2–0.5 mg/d, sometimes reduces the fre- Topical tacrolimus and calcipotriene have also been
quency of attacks. used. Narrow-band ultraviolet B waves (UVB 311 nm)
may be used in severe cases.
Porter SR et al: Recurrent aphthous stomatitis. Clin Dermatol
2000;18:569 [PMID: 11134852]. Handa S, Dogra S: Epidemiology of childhood vitiligo: A study of
625 patients from north India. Pediatr Dermatol 2003;20:
207 [PMID: 12787267].
Vitiligo
Westerhof W: Vitiligo management update. Skin Therapy Lett
Vitiligo is characterized clinically by the development 2000;5:1 [PMID: 10889569].
of areas of depigmentation. These are often symmetri-
 Eye 15
Rebecca Sands, MD, Arlene Drack, MD, & Allan M. Eisenbaum, MD

Normal vision is a skill acquired during infancy and genital glaucoma, in which case photophobia and ble-
childhood. To become adept requires a normal visual pharospasm may also be present. Inflammation, allergic
environment. The child must experience equally good and viral diseases, or conjunctival and corneal irritation
visual inputs from well-aligned eyes during this period can also cause tearing.
while the visual nervous system is still exhibiting plas-
ticity. Thus, pediatric ophthalmology emphasizes early Discharge
diagnosis and treatment of pediatric eye diseases in
order to obtain the best possible visual outcome. Purulent discharge is usually associated with bacterial
But eye disease in children does not always originate conjunctivitis. In infants and toddlers with naso-
in the ocular system. Abnormal eye findings in a child lacrimal obstruction, a mucopurulent discharge may be
may be a sign of systemic disease. This chapter seeks to present with low-grade, chronic dacryocystitis. Watery
increase the reader’s awareness of pediatric ophthalmic discharge occurs with viral infection, iritis, superficial
disease and treatment in order to achieve more favor- foreign bodies, and nasolacrimal obstruction. Mucoid
able visual outcomes and healthier children. discharge may be a sign of allergic conjunctivitis or na-
solacrimal obstruction. Histologically, a mucoid dis-
COMMON NONSPECIFIC SIGNS charge due to allergy is expected to show eosinophils; a
purulent bacterial discharge will show polymorphonu-
& SYMPTOMS clear leukocytes.
Nonspecific signs and symptoms commonly occur as
the chief complaint or as an element of the history of a Pain & Foreign Body Sensation
child with eye disease. Five of these findings are pre-
sented in the following sections with a sixth—leukoco- Pain in or around the eye may be due to foreign bodies,
ria—which often has serious implications. Do not hesi- corneal abrasions, lacerations, acute infections of the
tate to seek the help of a pediatric ophthalmologist globe or ocular adnexa, iritis, and angle closure glau-
when you believe the diagnosis and treatment of these coma. Large refractive errors, poor accommodative abil-
signs and symptoms require in-depth clinical experi- ity, and sinus disease may manifest as headaches.
ence. Trichiasis (inturned lashes) and contact lens problems
are also causes of ocular discomfort.
Redness
Photophobia
Redness (injection) of the bulbar conjunctiva or deeper
vessels is a common presenting complaint. It may be Acute aversion to light may occur with corneal abra-
mild and localized or diffuse and bilateral. Causes in- sions, foreign bodies, and iritis. Squinting of one eye in
clude superficial or penetrating foreign bodies, infec- bright light is a common sign of intermittent exotropia.
tion, allergy, and conjunctivitis associated with systemic Photophobia is present in infants with glaucoma, al-
entities such as Stevens–Johnson syndrome or Kawasaki binism, aniridia, and retinal dystrophies such as achro-
disease. Irritating noxious agents also result in injection. matopsia. Photophobia is common after ocular surgery
Subconjunctival hemorrhage may be traumatic or spon- and after dilation of the pupil with mydriatic and cyclo-
taneous or may be associated with hematopoietic dis- plegic agents. Photophobia in individuals with no ocu-
ease, vascular anomalies, or inflammatory processes. lar pathology may be due to migraine headache, menin-
Uncommonly, an injected eye can be due to an intraoc- gitis, and retrobulbar optic neuritis.
ular or orbital tumor.
Leukocoria
Tearing Although not a common sign or complaint, leukocoria
In infants, tearing is usually due to nasolacrimal ob- (a white pupil) is associated with serious diseases and
struction, but tearing may also be associated with con- requires prompt ophthalmologic consultation. Causes
432
Copyright © 2005, 2001, by The McGraw-Hill Companies, Inc. Click here for terms of use.
 EYE / 433

rors require correction, but severe errors can cause am-

blyopia. Those that do can usually be corrected with
glasses. Less often, contact lenses are required, usually
for very high or asymmetrical refractive errors, or for
adolescents who do not want to wear spectacles. Laser
refractive surgery is not currently indicated for most
children, although studies are being reported. There are
three common refractive errors: myopia, hyperopia, and
astigmatism. Inequality of the refractive state between
the two eyes (anisometropia) can cause amblyopia (re-
duced vision with or without an organic lesion; see Am-
blyopia & Strabismus section). Children at particular
risk for refractive errors requiring correction with spec-
Figure 15–1. Leukocoria of left eye caused by retro- tacles include those who were born prematurely, who
lental membrane (persistent hyperplastic primary vitre-
have Down syndrome, who are offspring of parents
with refractive errors, or who have certain systemic con-
ous or persistent fetal vasculature).
ditions such as Stickler, Marfan, or Ehlers–Danlos syn-
drome.
of leukocoria include retinoblastoma, retinopathy of
prematurity (ROP), pupillary membrane, cataract, vit- Myopia (Nearsightedness)
reous opacities, retinal detachment, Toxocara infection,
and retinal dysplasia (Figure 15–1). For the myopic or nearsighted individual, objects
nearby are in focus; those at a distance are blurred. This
is because the plane of focus is anterior to the retina.
REFRACTIVE ERRORS The onset is typically at about age 8 years and may
Refractive error refers to the optical state of the eye progress throughout adolescence and young adulthood.
(Figure 15–2). It is a physical characteristic like height A myopic person may squint to produce a pinhole ef-
or weight and can be quantitated. Not all refractive er- fect, which improves distance vision. Divergent lenses

A B

C D Figure 15–2. Different refractive

states of the eye . A: Emmetropia.
Image plane from parallel rays of light
falls on retina. B: Myopia. Image plane
focuses anterior to retina. C: Hyper-
opia. Image plane focuses posterior to
retina. D: Astigmatism, myopic type.
Images in horizontal and vertical
E F planes focus anterior to retina. E:
Astigmatism, hyperopic type. Images
in horizontal and vertical planes focus
posterior to retina. F: Astigmatism,
mixed type. Images in horizontal and
vertical planes focus on either side of
the retina.
434 / CHAPTER 15

provide clear distance vision. Many studies have been presence or absence of scotomas and visual field defects
done to determine whether treatment can slow or stop occurring anywhere along the visual pathway. In the of-
myopic progression. Atropine eyedrops have shown fice setting, visual field testing may be done in a gross
some effect, but produce many side effects. A newer manner by confrontation, that is, bringing an object
drug, perenzipine, has shown promise in animal stud- from the periphery of the child’s field of vision in each
ies, and human studies are underway. of four quadrants or by having an older child count the
examiner’s fingers as they are presented in two quad-
Saw SM et al: Myopia: Attempts to arrest progression. Br J Oph- rants simultaneously. It must be emphasized that accu-
thalmol 2002 Nov;86(11):1306 Review [PMID: 12386095]. rate results can be difficult to achieve in young chil-
dren.
Hyperopia (Farsightedness)
Saying that the hyperopic child is sighted for far (not History
near) is somewhat misleading, because the child can Evaluation begins by ascertaining the chief complaint
focus on near objects if the hyperopia is not excessive. and taking a history of the present illness. Elements of
Large amounts of uncorrected hyperopia can cause es- the history include onset of the complaint, its duration,
otropia (inward deviation, or crossing, of the eyes) and whether it is monocular or binocular, treatment re-
amblyopia (see Amblyopia & Strabismus section). Most ceived thus far, and associated systemic symptoms. If an
infants have a hyperopic refraction that begins to di- infectious disease is suspected, ask about possible con-
minish during the toddler years and does not require tact with others having similar findings. The ocular his-
correction. tory is obtained, as is the perinatal and developmental
history and any history of allergy. The family history
Astigmatism should be explored for ocular disorders that may be fa-
When either the cornea or the crystalline lens is not milial or inherited.
perfectly spherical, an image will not be sharply focused
in one plane. Schematically, there will be two planes of Visual Acuity
focus. Both of the planes can be either in front of or be-
hind the retina, or one of the planes can be in front of Visual acuity testing is the single most important test of
the retina and the other behind it. This refractive state visual function and should be part of every general
is described as astigmatism. Large amounts of astigma- physical examination. This is the nonophthalmologist’s
tism not corrected at an early age can cause decreased most definitive test for amblyopia, refractive errors, and
vision from amblyopia, but proper refractive correction lesions along the optic pathways. The child’s visual acu-
can prevent this. ity should be tested and recorded after ocular trauma
and before and after any ophthalmologic treatment.
DeRespinis PA: Eyeglasses: Why and when do children need them? Acuity should be tested in each eye individually, using
Pediatr Ann 2001;30:455 [PMID: 11510343]. an adhesive eyepatch to prevent peeking. If latent nys-
tagmus, which becomes apparent when one eye is oc-
cluded, is present (see Nystagmus section), vision
EXAMINATION should be tested simultaneously in both eyes and in
Ophthalmic examination of the pediatric patient begins each eye individually. Vision is usually recorded with
with a calm demeanor and reassuring voice. Having a glasses in place (corrected vision). In older children
parent present is invaluable. The examination includes who can cooperate, use of a pinhole will improve vision
a history, assessment of visual acuity, external examina- in children not wearing the appropriate spectacle pre-
tion, observation of ocular alignment and motility, and scription.
ophthalmoscopic examination. Intraocular pressure is The type of test used to determine visual acuity is
less frequently measured. Testing of binocular status dictated by the child’s age. In the sleeping newborn, the
and near point is desirable when age and cooperation presence of a blepharospastic response to bright light is
permit. an adequate response. At age 6 weeks, eye-to-eye con-
Circumstances will dictate the use of ancillary proce- tact with slow following movements is becoming estab-
dures such as instilling fluorescein dye and radiologic lished and can be detected. By age 3 months, the infant
tests (magnetic resonance imaging [MRI] and com- should demonstrate fixing and following ocular move-
puted tomography [CT] scan). Electroretinography and ments for objects at a distance of 2–3 feet. At age
electrooculography test retinal function. Visual evoked 6 months, interest in movement across the room is the
response testing assesses the function of the cortical vi- norm. Vision can be recorded for the presence or ab-
sual pathways. Visual field testing demonstrates the sence of fixing and following behavior and for whether
 EYE / 435

vision is steady (unsteady when nystagmus is present) amination. Assessment of the entire anterior segment
and maintained. Vision should be tested and recorded except the trabecular meshwork and, to a lesser extent,
for each eye. Visual acuity can be quantified in infants the lens is possible.
using other techniques, such as the 15-diopter prism In cases of suspected foreign body, pulling down on
test, preferential looking technique, or the pattern vi- the lower lid provides excellent visualization of the infe-
sual evoked response. rior cul-de-sac (palpebral conjunctiva). Visualizing the
In the verbal child, the use of familiar icons will upper cul-de-sac and superior bulbar conjunctiva is
allow for a quantitative test. Allen or Lea symbols with possible by having the patient look inferiorly while the
familiar pictures can be used to test children age upper lid is pulled away from the globe and the exam-
21⁄2–3 years. Four-year-olds are often ready to play the iner peers into the upper recess. Illumination with a
tumbling E game (in which the child identifies the ori- penlight is necessary. The upper lid should be everted
entation of the letter E, which is turned in one of four to evaluate the superior tarsal conjunctiva (Figure
directions) or the HOTV letters game (in which these 15–3).
four letters are shown individually at a distance and When indicated for further evaluation of the cornea,
matched on a board that the child is holding). Literate a small amount of fluorescein solution should be
children are tested with letters. Typical acuity levels in instilled into the lower cul-de-sac. Blue light will
developmentally appropriate children are approxi- stain defects yellow-green. Disease-specific staining
mately 20/60 or better in 21⁄2-to 3 year-olds, patterns may be observed. For example, herpes sim-
20/40–20/30 in 3-year-olds, 20/30–20/25 in 4-year- plex lesions of the corneal epithelium produce a den-
olds, and 20/20 in literate 5- to 6-year-olds. Perhaps drite or branch-like pattern. A foreign body lodged be-
more important than the absolute visual acuity is the neath the upper lid shows one or more vertical lines of
presence of a difference of acuity between the two eyes, stain on the cornea due to the constant movement of
which might be a sign of amblyopia, uncorrected re- the foreign body over the cornea. Contact lens overwear
fractive error, or disease. As little as one line difference produces a central staining pattern. A fine, scattered
in acuity should be considered significant. punctate pattern may be a sign of viral keratitis or med-
The practitioner should be aware of two situations ication toxicity. Punctate erosions of the inferior third
complicated by nystagmus. Children who require a face of the cornea can be seen with staphylococcal blephari-
turn or torticollis (in which the head is tilted to the tis or exposure keratitis secondary to incomplete lid clo-
right or left) to quiet the nystagmus will have poor vi- sure.
sual acuity results when tested in the absence of the
compensatory head posture.
When latent nystagmus is present, acuity testing is
particularly challenging (see Nystagmus section). Nys-
tagmus appears or worsens when an eye is occluded, de-
grading central vision. To minimize the nystagmus, the
occluder should be held about 12 inches in front of the
eye not being tested. Testing both eyes simultaneously
without occlusion often gives a better visual acuity mea- A B
surement than when either eye is tested individually.

Becker R, et al: Examination of young children with Lea symbols.

Br J Ophthalmol 2002;86(5):513 [PMID: 11973243].
Simon JW, Kaw P: Vision screening performed by the pediatrician.
Pediatr Ann 2001;30(8):446 [PMID: 11510342].
C D
External Examination
Inspection of the anterior segment of the globe and its
adnexa requires adequate illumination and often mag-
nification. A penlight provides good illumination and
should be used in both straight-ahead and oblique illu- Figure 15–3. Eversion of the upper lid. A: The patient
mination. A Wood lamp or a blue filter cap placed over looks downward. B: The fingers pull the lid down, and
a penlight is needed for evaluation after applying a fluo- an index finger or cotton-tip is placed on the upper
rescent stain. Immobilization of the child may be neces- tarsal border. C: The lid is pulled up over the finger. D:
sary. A drop of topical anesthetic may facilitate the ex- The lid is everted.
436 / CHAPTER 15

Pupils Table 15–1. Function and innervation of each

The child’s pupils should be evaluated for reaction to of the extraocular muscles.
light, regularity of shape, and equality of size as well as
for the presence of afferent pupillary defect. This de- Muscle Function Innervation
fect, occurring in optic nerve disease, is evaluated by the Medial rectus Adductor Oculomotor (third)
swinging flashlight test (see Diseases of the Optic Nerve
section). Irregular pupils are associated with iritis, Lateral rectus Abductor Abducens (sixth)
trauma, pupillary membranes, and structural defects Inferior rectus Depressor Oculomotor
such as iris coloboma (see Iris Coloboma section). Adductor
Pupils vary in size due to lighting conditions and Extorter
also age. In general, infants have miotic (constricted) Superior rectus Elevator Oculomotor
pupils. Children have larger pupils than either infants Adductor
or adults, whereas the elderly have miotic pupils. Intorter
Anisocoria, a size difference between the two pupils,
may be physiologic if the size difference is within 1 mm Inferior oblique Elevator Oculomotor
and is the same in light and dark. Anisocoria occurs Abductor
with Horner syndrome, third nerve palsy, Adie tonic Extorter
pupil, iritis, and trauma. Medication could also cause Superior oblique Depressor Trochlear (fourth)
abnormal pupil size or reactivity. For example, contact Abductor
with atropine-like substances (belladonna alkaloids) Intorter
will cause pupillary dilation with little or no pupillary
reaction. Systemic antihistamines and scopolamine
patches, among other medicines, can dilate the pupils
and interfere with accommodation (focusing).
ered, a refixation movement of that eye indicates a pho-
ria, or latent deviation if alignment is reestablished. If
Alignment & Motility Evaluation the uncovered eyes picks up fixation and strabismus is
Alignment and motility should be tested because am- still present, then that eye can be presumed to be domi-
blyopia is associated with strabismus, a misalignment of nant and the nonpreferred eye possibly amblyopic. If
the visual axes of the eyes. Besides alignment, ocular ro- the eye remains deviated after the occluder is removed,
tations should be evaluated in the six cardinal positions a tropia is noted to be present (Figure 15–6). A devi-
of gaze (Table 15–1; Figure 15–4). A small toy is an in- ated eye that is blind or has very poor vision will not
teresting target for testing ocular rotations in infants; a fixate on a target. Consequently, spurious results to
penlight works well in older children. cover testing may occur, as can happen with disinterest
Alignment can be assessed in several ways. In order on the part of the patient, small-angle strabismus, and
of increasing accuracy, these methods are observation, inexperience in administering cover tests.
the corneal light reflex test, and cover testing. Observa-
tion includes an educated guess about whether the eyes
are properly aligned. Corneal light reflex evaluation
(Hirschberg test) is performed by shining a beam of a
SR IO IO SR
light at the patient’s eyes, observing the reflections off
each cornea, and estimating whether these “reflexes”
appear to be positioned properly. If the reflection of LR MR MR LR
light is noted temporally on the cornea, esotropia is sus-
pected (Figure 15–5). Nasal reflection of the light sug- IR SO SO IR
gests exotropia (outward deviation). Accuracy of these Right eye Left eye
tests increases with increasing angles of misalignment.
Another way of evaluating alignment is with the MR = medial rectus LR = lateral rectus
cover test, in which the patient fixes on a target while SR = superior rectus IR = inferior rectus
one eye is covered. If an esotropia or an exotropia is SO = superior oblique IO = inferior oblique
present, the deviated eye will make a corrective move-
ment to fixate on the target when the previously fixat- Figure 15–4. Cardinal positions of gaze and muscles
ing eye is occluded. The other eye is tested similarly. primarily tested in those fields of gaze. Arrow indicates
When the occluder is removed from the eye just uncov- position in which each muscle is tested.
 EYE / 437

promised by a retrolental membrane, such as in ROP.

Therefore, if an adequate view of the fundus is pre-
cluded by a miotic pupil, use of a dilating agent (eg,
1 drop each eye of 2.5% phenylephrine or 0.5% or 1%
tropicamide) should provide adequate mydriasis (dila-
tion). In infants, 1 drop of a combination of 1%
phenylephrine with 0.2% cyclopentolate (Cyclomydril)
is safer. Structures to be observed during ophthal-
Figure 15–5. Temporal displacement of light reflec- moscopy include the optic disk, blood vessels, the mac-
tion showing esotropia (inward deviation) of the right ular reflex, and retinal changes if present, as well as the
eye. Nasal displacement of the reflection would show clarity of the vitreous media. By increasing the amount
exotropia (outward deviation). of plus lens dialed into the instrument, the point of
focus moves anteriorly from the retina to the lens and
finally to the cornea.
Ophthalmoscopy should include assessment of the
Ophthalmoscopic Examination clarity of the ocular media, that is, the quality of the red
A handheld direct ophthalmoscope allows visualization reflex. The practitioner should take the time to become
of the ocular fundus. As the patient’s pupil becomes familiar with this reflex. The red reflex test (Brückner
more constricted, viewing the fundus becomes more test) is useful for identifying disorders such as media
difficult. Although it is taught that pupillary dilation opacities (eg, cataracts), large refractive errors, tumors
can precipitate an attack of closed-angle glaucoma in such as retinoblastoma, and strabismus. A difference in
the predisposed adult, children are very rarely predis- quality of the red reflexes between the two eyes consti-
posed to angle closure. Exceptions include those with a tutes a positive Brückner test and requires referral to an
dislocated lens, past surgery, or an eye previously com- ophthalmologist.

Eyes straight (maintained in position by fusion). Position of eye under cover in orthophoria (fusion-free
position). The right eye under cover has not moved.

Position of eye under cover in esophoria (fusion-free Position of eye under cover in exophoria (fusion-free
position). Under cover, the right eye has deviated inward. position). Under cover, the right eye had deviated outward.
Upon removal of cover, the right eye will immediately Upon removal of the cover, the right eye will immediately
resume its straight-ahead position. resume its straight-ahead position.

Figure 15–6. Cover testing. The patient is instructed to look at a target at eye level 20 feet away. Note that in the
presence of constant strabismus (ie, a tropia rather than a phoria), the deviation will remain when the cover is re-
moved. (Reproduced, with permission, from General Ophthalmology, 15th ed. Originally published by Appleton & Lange.
Copyright © 1999 by The McGraw-Hill Companies, Inc.)
438 / CHAPTER 15

The red reflex of each eye can be compared simulta-

neously when the observer is approximately 4 feet away
from the patient. The largest diameter of light is shown
through the ophthalmoscope, and no correction (zero
setting) is dialed in the ophthalmoscope unless it is to
compensate for the examiner’s uncorrected refractive
error. A red reflex chart is available through the Ameri-
can Academy of Pediatrics.

OCULAR TRAUMA
A foreign body of the globe or adnexa may be difficult
to visualize due to its small size or location. The clini-
cian should always maintain a high index of suspicion
for an occult or intraocular foreign body if the history A
suggests this. In cases such as these, ophthalmologic re-
ferral needs to be considered.
Foreign bodies on the globe and palpebral conjunc-
tiva usually cause discomfort and red eye. Magnifica-
tion may be needed for inspection. Foreign bodies that
lodge on the upper palpebral conjunctiva are best
viewed by everting the lid on itself and removing the
foreign body with a cotton applicator. The conjunctival
surface (palpebral conjunctiva) of the lower lid presents
no problem with visualization. After simple removal of
a foreign body that is thought not to be contaminated,
no other treatment is needed if no corneal abrasion has
occurred.
When foreign bodies are noted on the bulbar con-
junctiva or cornea (Figure 15–7), removal is facilitated
by using a topical anesthetic. If the foreign body is not
too adherent, it can be dislodged with a stream of irri- B
gating solution (Dacriose or saline) or with a cotton ap-
plicator after instillation of a topical anesthetic. Other- Figure 15–7. A: Corneal foreign body at the nasal
wise, a foreign body spud or needle is used to edge of the cornea. B: Subconjunctival foreign body of
undermine the foreign body. This must be done with graphite.
adequate magnification and illumination. An antibiotic
ointment is then instilled. Ferrous corneal bodies often
have an associated rust ring, which may be removed Suspected intraocular foreign bodies and corneal
under slitlamp visualization in cooperative children or and scleral lacerations require emergency referral to an
under anesthesia if necessary. ophthalmologist. In cases of suspected perforation of
Corneal abrasions are evaluated with fluorescein dye the globe, it may be best to keep the child at rest, gently
and treated with a topical antibiotic, but not necessarily shield the eye with a metal shield or cut-down paper
a pressure patch. Patching is not advised for corneal cup, and keep the extent of examination to a necessary
abrasions caused by contact lens wear, and it is being minimum to prevent expulsion of intraocular contents.
used less frequently for corneal abrasions and after re- In this setting, the child should be given nothing by
moval of corneal foreign bodies since the moist, hy- mouth in case eye examination under anesthesia or sur-
poxic environment predisposes to bacterial infection. gical repair is required. The diagnosis may be difficult if
One drop of topical cycloplegic agent such as 5% the signs of obvious corneal perforation (shallow anteri-
homatropine, 1% atropine (with appropriate warnings or chamber with hyphema and irregular pupil) are not
to parents about systemic side effects), or 0.25% sco- present (Figure 15–8). Furthermore, nonradiopaque
polamine is useful to relieve the discomfort of ciliary materials such as glass will not be seen on x-ray film. A
spasm and iritis. Daily follow-up is required until heal- CT scan may be useful in evaluating ocular trauma, in-
ing is complete. cluding bony injury and foreign body wound. MRI will
 EYE / 439

Figure 15–8. Corneal laceration with irregular pupil

and vitreous loss.
Figure 15–9. Laceration involving right lower lid and
canaliculus.

not provide bony detail and must be avoided if a mag- 15–9). These injuries are best repaired by an ophthal-
netic foreign body is suspected. mologist.

Zaidman GW et al: Successful surgical rehabilitation of children

with traumatic corneal laceration and cataract. Ophthalmol-
Burns
ogy 2001;108:338 [PMID: 11158810]. Eyelid burns can occur in toddlers from contact with a
lighted cigarette. The cornea is often involved as well.
INJURIES TO THE EYELIDS Curling irons can cause similar burns. These burns usu-
ally heal following application of antibiotic ointment.
Ecchymosis Severe thermal or chemical burns can cause scars result-
Orbital and soft tissue trauma may produce so-called ing in ectropion or entropion of the lid and scarring of
black eye or ecchymosis (blue or purplish hemorrhagic the conjunctiva and cul-de-sac.
areas) of the eyelids. The extent of the injury to the eye Burns of the conjunctiva and cornea may be ther-
and orbit may not correlate fully with its appearance. mal, radiant, or chemical. Superficial thermal burns
Blowout fracture, which occurs from blunt trauma frac- cause pain, tearing, and injection. Management is with
turing the walls of the orbit, must be suspected. Ocular topical antibiotics and patching. Add a cycloplegic
motility must be assessed, the globe examined, and in- agent if corneal involvement is present, because pain
traocular pressure measured, usually by an ophthalmol- from ciliary spasm and iritis may accompany the injury.
ogist. Cold compresses or ice packs for brief periods Radiant energy causes ultraviolet keratitis. Typical
(eg, 10 minutes at a time) are recommended in older examples are welder’s burn and burns associated with
children in the first 24 hours after injury to reduce he- skiing without goggles in bright sunlight. The fluores-
morrhage and swelling. Abuse needs to be considered cein dye pattern will show a uniformly stippled appear-
when orbital injury is poorly explained. ance of the corneal epithelium. Antibiotic ointment,
pressure patches, and a cycloplegic agent such as 5%
homatropine are usually followed by recovery within
Lacerations 24 hours.
The lids and lacrimal apparatus are susceptible to lacer- Chemical burns with strong acid and alkaline agents
ation. Except for superficial lacerations away from the can be blinding and constitute a true ocular emergency.
globe, repair in children is best performed in the oper- Examples are burns caused by exploding batteries,
ating room under general anesthesia. Special considera- spilled drain cleaner, and bleach. Alkali burns may not
tion must be given to lacerations involving the lid mar- cause significant injection because the conjunctival ves-
gin, to through-and-through lacerations, to lacerations sels become damaged. Alkalis tend to penetrate deeper
that may involve the levator muscle in the upper lid, than acids into ocular tissue. Immediate treatment con-
and to those that may involve the canaliculus (Figure sists of copious irrigation and removal of precipitates as
440 / CHAPTER 15

soon as possible after the injury. The patient should be Lai JC et al: Traumatic hyphema in children. Risk factors for com-
referred to an ophthalmologist after immediate first aid plications. Arch Ophthalmol 2001;119:64 [PMID:
11709038].
has been given.

Nonaccidental Trauma
Forbes BJ: Management of corneal abrasions and ocular trauma in
children. Pediatr Ann 2001;30:465 [PMID: 11510344]. & Shaken Baby Syndrome
From an ocular standpoint, in both nonaccidental
trauma and shaken baby syndrome, the hallmark of di-
Hyphema agnosis is retinal hemorrhage, although it need not be
Blunt trauma to the globe may cause hyphema, or present with rotational injury severe enough to cause
bleeding within the anterior chamber from a ruptured subdural hematoma. In general, the presence and sever-
vessel located near the root of the iris or in the anterior ity of the retinal hemorrhages correlates with the level
chamber angle. Bleeding may be microscopic or may of brain injury. Careful evaluation of the posterior and
fill the entire anterior chamber (Figure 15–10). Blunt peripheral retina requires pupillary dilation and indirect
trauma severe enough to cause hyphema may be associ- ophthalmoscopy.
ated with other ocular injury, including iritis, lens sub- The history of how the injuries or retinal findings
luxation, retinal edema or detachment, and glaucoma. occurred is often vague and not well correlated with the
In patients with sickle cell anemia or trait, even moder- extent of injury. Hemorrhages may be unilateral or bi-
ate elevations of intraocular pressure may quickly lead lateral and may be located in the posterior pole or pe-
to optic atrophy and permanent vision loss. Therefore, riphery. Whereas retinal hemorrhages tend to resolve
all African-Americans whose sickle cell status is un- fairly quickly, those in the vitreous do not. If a blood
known should be tested if hyphema is observed. These clot lies over the macula, deprivation amblyopia may
patients require extra vigilance in diagnosing and treat- occur. Retinal and vitreous hemorrhages associated
ing hyphema. with intracranial hemorrhage from skull injury are
Management of hyphema in an otherwise uninjured known as Terson syndrome. Retinal hemorrhages are
patient should include testing of visual acuity and as- rarely associated with cardiopulmonary resuscitation or
sessment of the integrity of the globe and orbit. A seizures. As a rule, retinal hemorrhages do not occur
shield should be placed over the eye, the head elevated, from major accidental trauma such as motor vehicle ac-
and arrangements made for ophthalmologic referral. cidents unless a compressive chest injury is present, but
Nontraumatic causes of hyphema include juvenile they have been associated with low fibrinogen levels
xanthogranuloma and blood dyscrasias. Rarely, hy- and blood dyscrasias. Other ocular findings associated
phema is noted in the newborn after a stressful birth. with nonaccidental trauma include lid ecchymosis, sub-
conjunctival hemorrhage, and hyphema. Additional
retinal findings include retinal folds and retinoschisis.
Acute-onset esotropia can also occur.

American Academy of Pediatrics. Committee on Child Abuse and

Neglect. Shaken baby syndrome: Rotational cranial in-
juries—Technical report. Pediatrics 2001;108:206 [PMID:
11433079].
Drack AV et al: Unilateral retinal hemorrhages in documented
cases of child abuse. Am J Ophthalmol 1999;128(3):340
[PMID: 10511029].
Kivlin JD et al: Shaken baby syndrome. Ophthalmology 2000;
107(7):1246 [PMID: 10889093].
Morris MW et al: Evaluation of infants with subdural hematoma
who lack external evidence of abuse. Pediatrics 2001;
105:549 [PMID: 10699108].

Prevention of Ocular Injuries

Air rifles, paint balls, and fireworks are responsible for
many serious eye injuries in children. Golf injuries can
Figure 15–10. Hyphema filling approximately 20% of also be very severe. Bungee cords have been associated
the anterior chamber. with multiple types of severe ocular trauma, including
 EYE / 441

corneal abrasion, iris tears, hyphema, vitreous hemor- ointment can be effective. Other bodily areas of in-
rhage, retinal detachment, and blindness. These activi- volvement must also be treated if involved. Family
ties should be avoided or very closely supervised. Safety members and contacts may also be infected (see Chap-
goggles should be used in laboratories and industrial ter 14).
arts classes and when operating snow blowers, power Papillomavirus may infect the lid and conjunctiva.
lawn mowers, and power tools or when using hammers Warts may be recurrent, multiple, and difficult to treat.
and nails. Sports-related eye injuries can be prevented Treatment modalities include cryotherapy, cautery, car-
with protective eyewear. Sports goggles and visors of bon dioxide laser, and surgery.
polycarbonate plastic will prevent injuries in games Localized staphylococcal infections of the glands of
using fast projectiles such as tennis or racquet balls, or Zeis within the lid cause a sty (hordeolum) (Figure
where opponents may swing elbows or poke at the eye. 15–11). When the infection coalesces and points inter-
The one-eyed individual should be specifically ad- nally or externally, it may discharge itself or require in-
vised to wear polycarbonate eyeglasses full time and cision. The lesion is tender and red. Warm compresses
goggles for all sports. High-risk activities such as boxing help to hasten the acute process. Some practitioners
and the martial arts should be avoided by one-eyed prescribe a topical antibiotic ointment. Any coexisting
children. blepharitis should be treated.
A chalazion is an inflammation of the meibomian
American Academy of Pediatrics Committee on Sports Medicine glands, which may produce a tender nodule over the
and Fitness and American Academy of Ophthalmology Com- tarsus of the upper or lower lid. In addition to localized
mittee on Eye Safety and Sports Ophthalmology: Protective erythema of the corresponding palpebral conjunctiva,
eyewear for young athletes. Pediatrics 1996;98:311 [PMID: there may be a yellow lipogranuloma (Figure 15–12).
8692640]. Treatment includes warm compresses for 10–15 min-
American Academy of Pediatrics. Committee on Injury and Poison utes four times a day for up to 6 weeks. If incision and
Prevention: Fireworks-related injuries to children. Pediatrics
2001;108:190 [PMID: 11433076].
curettage are needed because the lesion is slow to re-
solve, the child will require a general anesthetic.
Chorich LJ III et al: Bungee cord associated ocular injuries. Am
J Ophthalmol 1998;125:270 [PMID: 9467466].
Thompson CG et al: The aetiology of perforating ocular injuries in Viral Lid Disease
children. Br J Ophthalmol 2002;86(8):920 [PMID:
12140216]. Herpes simplex virus may involve the lids at the time of
primary herpes simplex infection. Vesicular lesions with
an erythematous base occur. Primary herpes simplex
DISORDERS OF THE OCULAR blepharoconjunctivitis should be treated with systemic
STRUCTURES acyclovir (liquid formulation available), valacyclovir, or
famciclovir. When either the conjunctiva or the cornea
Diseases of the Eyelids is involved, treatment should include topical 1% tri-
Blepharitis is inflammation of the lid margin character- fluridine or 3% vidarabine.
ized by crusty debris at the base of the lashes; varying
degrees of erythema at the lid margins; and, in severe
cases, secondary corneal changes such as punctate ero-
sions, vascularization, and ulcers. When conjunctival
injection accompanies blepharitis, the condition is
known as blepharoconjunctivitis. Staphylococcus is the
most common bacterial cause. Treatment includes lid
scrubs with a nonburning baby shampoo several times a
week and application of a topical antibiotic ointment
such as erythromycin or bacitracin at bedtime.
Rosacea can also occur in the pediatric age group
and cause chronic blepharoconjunctivitis with corneal
changes that decrease vision. Systemic antibiotics and
local treatment are required.
Pediculosis of the lids (phthiriasis palpebrarum) is
caused by Phthirus pubis. Nits and adult lice can be seen
on the eyelashes when viewed with appropriate magni-
fication. Mechanical removal and application to the lid Figure 15–11. Hordeolum and blepharitis, left upper
margins of phospholine iodide or 1% mercuric oxide lid.
442 / CHAPTER 15

Figure 15–13. Congenital ptosis of severe degree,

left upper lid.

dren owing to a defective levator muscle. Other causes

of ptosis are myasthenia gravis, lid injuries, third nerve
palsy, and Horner syndrome (see next section). Surgical
correction is indicated for moderate to severe ptosis.
Mild cases require operative management less often
than do more severe cases, and comesis may be better if
surgery is delayed until most of the facial growth has
occurred, usually aorund 5 years old. Ptosis may be as-
sociated with astigmatism and amblyopia.
An interesting association sometimes seen with con-
genital ptosis is the Marcus Gunn jaw-winking phe-
nomenon. An intermittent reduction of the ptosis oc-
curs during mastication or sucking. It is due to a
B
synkinesis or simultaneous firing of either the external
or internal pterygoid muscle (innervated by the trigemi-
Figure 15–12. Chalazion. A: Right lower lid, external nal nerve) and the levator muscle (innervated by the
view. B: Right lower lid conjunctival surface. oculomotor nerve).

Horner Syndrome
Herpes zoster causes vesicular disease in association
with a skin eruption in the dermatome of the oph- Horner syndrome, which may be congenital or ac-
thalmic branch of the trigeminal nerve. In older chil- quired, is the triad of miosis, ptosis, and anhidrosis.
dren, treatment of ophthalmic herpes zoster with oral The ptosis is usually mild with a well-defined upper lid
acyclovir, valacyclovir, or famciclovir within 5 days crease. This differentiates it from congenital ptosis,
after onset may reduce the morbidity. When vesicles are which typically has a poorly defined lid crease. Another
present on the tip of the nose with herpes zoster key finding of congenital Horner syndrome is hete-
(Hutchinson sign), ocular involvement, including iritis, rochromia of the two irides, with the lighter colored iris
may develop. Herpes simplex or herpes zoster can be occurring on the same side as the lesion (Figure
diagnosed by rapid viral culture (24–48 hours) or de- 15–14). Anhidrosis can occur in congenital and ac-
tection of antigen in skin lesions (3 hours). Impetigo is quired cases. Of note, not all of the three signs must be
in the differential diagnosis of vesicular lid disease. present to make the diagnosis. The syndrome is caused
Molluscum contagiosum lesions are typically umbil- by an abnormality or lesion to the sympathetic chain.
icated papules. If near the lid margin, the lesions may The congenital variety is most commonly the result of
shed and cause conjunctivitis. Cautery or excision of le- birth trauma. Acquired cases may occur in children
sions at the lid margin is useful. who have had cardiothoracic surgery, trauma, or brain-
stem vascular malformation. Most worrisome is a
Horner syndrome caused by neuroblastoma of the sym-
Lid Ptosis pathetic chain in the apical lung region. An excellent
Ptosis—a droopy upper lid (Figure 15–13)—may be screening test for this is the spot urine vanillylmandelic
congenital or acquired but is usually congenital in chil- acid/creatinine ratio.
 EYE / 443

Figure 15–14. Congenital Horner syndrome. Ptosis,

miosis, heterochromia. Lighter colored iris is on af-
fected left side.

Pharmacologic assessment of the pupils with topical

cocaine and hydroxyamphetamine or epinephrine will
help determine whether the Horner syndrome is due to
a preganglionic or postganglionic lesion of the sympa-
thetic chain. Physical examination, including palpation
of the neck and abdomen for masses, and MRI of struc- Figure 15–15. Nasolacrimal obstruction, right eye.
tures in the head, neck, chest and abdomen should be Mattering on upper and lower lids.
considered.

McDonnell JF et al: Pediatric Horner syndrome due to cervical

thymic rest. J Pediatr Ophthalmol Strabismus 2002;39(3): lacrimal obstruction is debated. Cleansing the lids and
185 [PMID: 12051288]. medial canthal area decreases the likelihood of infection
and irritation. Superinfection may occur, and treatment
Eyelid Tics with topical antibiotics may help decrease the dis-
charge. The mainstay of surgical treatment is probing,
Eyelid tics may occur as a transient phenomenon last- which is successful 80% or more of the time, but the
ing several days to months. Although a tic may be an success rate may decrease after the infant reaches age
isolated finding in an otherwise healthy child, it may 1 year. Other surgical procedures, including infracture
also occur in children with multiple tics, attention- of the inferior nasal turbinate, balloon dilation, and sili-
deficit/hyperactivity disorder, or Tourette syndrome. cone tube intubation, may be necessary if probing fails.
Caffeine consumption may cause or exacerbate eyelid Much less often, dacryocystorhinostomy is required.
tics. If the disorder is a short-lived annoyance, no treat-
ment is needed.
Mandeville JT et al: Obstruction of the lacrimal drainage system.
Curr Opin Ophthalmol 2002;13(5):303 [PMID 12218461].
DISORDERS OF THE NASOLACRIMAL Wagner RS: Management of congenital nasolacrimal obstruction.
SYSTEM Pediatr Ann 2001;30:481 [PMID: 11510346].

Nasolacrimal Duct Obstruction

Nasolacrimal obstruction occurs in up to 6% of infants.
Congenital Dacryocystocele
Most cases clear spontaneously during the first year. Congenital dacryocystocele is thought to result from
Signs and symptoms include a wet eye with mucoid obstructions proximal and distal to the nasolacrimal
discharge, erythema of one or both lids, and conjunc- sac. An intranasal duct cyst may be present beneath the
tivitis (Figure 15–15). Obstruction in any part of the inferior turbinate at the valve of Hasner. These cysts
drainage system may result from incomplete canaliza- may be associated with respiratory distress. At birth, the
tion of the duct or membranous obstructions. Naso- nasolacrimal sac is distended and has a bluish hue that
lacrimal obstruction may also occur in individuals with often leads to an erroneous diagnosis of hemangioma.
craniofacial abnormalities or amniotic band syndrome. The tense and swollen sac displaces the medial canthus
Differential diagnosis of tearing includes congenital superiorly (Figure 15–16). Massage and warm com-
glaucoma, foreign bodies, nasal disorders, and, in older presses are sometimes effective, but probing of the na-
children, allergies. solacrimal system often is necessary. Repeated probing
Massage over the nasolacrimal sac may empty debris and endoscopic marsupialization of the intranasal cyst
from the nasolacrimal sac and may clear the obstruc- under general anesthesia may be required. Dacryocysti-
tion, although the efficacy of massage in clearing naso- tis and sepsis can result from dacryocystocele.
444 / CHAPTER 15

junctive and is also used with recurrent chronic infec-

tions. Warm compresses are beneficial. After the acute
episode subsides—and in chronic cases—the naso-
lacrimal obstruction must be relieved surgically. If it
cannot be drained via the intranasal portion of the na-
solacrimal duct, external drainage may be necessary.
This should be done as a last resort since a fistula may
Figure 15–16. Congenital dacryocystocele on left develop.
side. Raised, bluish discolored mass of enlarged naso-
lacrimal sac. Note superiorly displaced medial canthus.
DISEASES OF THE CONJUNCTIVA
Conjunctivitis may be infectious, allergic, or associated
Levin AV et al: Nasal endoscopy in the treatment of congenital with systemic disease. Trauma, irritation of the con-
lacrimal sac mucoceles. Int J Pediatr Otorhinolaryngol junctiva, and intraocular inflammation also can result
2003;67(3):255 ?PMID: 12633925?. in injection of conjunctival vessels that can be confused
with conjunctivitis (Table 15–2).
Dacryocystitis
Acute and chronic dacryocystitis are typically bacterial Ophthalmia Neonatorum
and caused by organisms such as Staphylococcus aureus, Ophthalmia neonatorum (conjunctivitis in the new-
Streptococcus pneumoniae, Streptococcus pyogenes, viri- born) occurs during the first month of life. It is charac-
dans streptococci, Moraxella catarrhalis, and Haemo- terized by redness and swelling of the lids and conjunc-
philus species. Attempts at identifying the offending or- tiva and by discharge (Figure 15–18). Ophthalmia
ganism by culture and staining should be made when neonatorum may be due to inflammation resulting
possible. Acute dacryocystitis presents with inflamma- from silver nitrate prophylaxis given at birth, bacterial
tion, swelling, tenderness, and pain over the lacrimal infection (gonococcal, staphylococcal, pneumococcal,
sac (located inferior to the medial canthal tendon). chlamydial), or viral infection. In developed countries,
Fever may be present. The infection may point exter- Chlamydia is the most common cause. Neonatal con-
nally (Figure 15–17). A purulent discharge and tearing junctivitis is visually threatening if caused by Neisseria
can be expected, because the cause of infection is almost gonorrhoeae. Herpes simplex is a rare but serious cause
always nasolacrimal obstruction. of neonatal conjunctivitis. Gram staining, Giemsa
Signs of chronic dacryocystitis are mucopurulent de- staining for elementary bodies, enzyme immunoassay
bris on the lids and lashes, tearing, injection of the for chlamydia, and bacterial and viral cultures aid in
palpebral conjunctiva, and reflux of pus at the puncta making an etiologic diagnosis.
when pressure is applied over the sac. Chronic dacry- Although no single prophylactic medication can
ocystitis and recurrent episodes of low-grade dacryocys- eliminate all cases of neonatal conjunctivitis, povi-
titis are caused by nasolacrimal obstruction. done–iodine may provide broader coverage against the
Treatment of severe acute dacryocystitis is with in- organisms causing this disease than silver nitrate or
travenous antibiotics. Oral antibiotics can be tried in erythromycin ointment. Silver nitrate is not effective
milder cases. Topical antibiotic administration is ad- against chlamydia. The choice of prophylactic agent is
often dictated by local epidemiology and cost consider-
ations.
Treatment of these infections requires specific sys-
temic antibiotics because they can cause serious infec-
tions in other organs. Specifically, Chlamydia can cause
a delayed-onset pneumonitis. Parents should be exam-
ined and receive treatment when a sexually associated
pathogen is present.

Bacterial Conjunctivitis
In general, bacterial conjunctivitis is accompanied by a
purulent discharge and viral infection by a watery dis-
Figure 15–17. Acute dacryocystitis in an 11-week-old charge. One or both eyes may be involved. Regional
infant. lymphadenopathy is not a common finding in bacterial
 EYE / 445

Table 15–2. Clinical and laboratory features of conjunctivitis.

Viral Bacterial Chlamydial Allergic

Itching Minimal Minimal Minimal Severe
Hyperemia Generalized Generalized Generalized Generalized
Tearing Profuse Moderate Moderate Moderate
Exudation Minimal, mucoid Profuse, purulent Profuse; mucoid or mu- Minimal, slight mucus
copurulent
Preauricular adenopathy Common Uncommon Common in inclu- None
sion conjunctivitis
Stained conjunctival Lymphocytes, plasma cells, Neutrophils, bacteria Neutrophils, plasma Eosinophils
smears and scrapings multinucleated giant cells, cells, basophilic
eosinophilic intranuclear intracytoplasmic
inclusions inclusions
Associated sytemic Rash, sore throat, fever in Occasional fever, sore Pneumonia in neonates Variable—may or may
signs and symptoms some patients throat not be present
Modified from Vaughan D, Asbury T, Riordan-Eva P (eds): General Ophthalmology, 15th ed. Appleton & Lange, 1999.

conjunctivitis except in cases of oculoglandular syn- usually adequate. Systemic therapy is recommended for
drome due to S aureus, group A β-hemolytic strepto- conjunctivitis associated with Chlamydia trachomatis,
cocci, Mycobacterium tuberculosis or atypical mycobac- N gonorrhoeae, and N meningitidis.
teria, Francisella tularensis (the agent of tularemia), and
Bartonella henselae (the agent of cat-scratch fever). Viral Conjunctivitis
Common bacterial causes of conjunctivitis in older
children include nontypable Haemophilus species, S Adenovirus infection is often associated with pharyngi-
pneumoniae, M catarrhalis, and S aureus. If conjunctivi- tis, a follicular reaction of the palpebral conjunctiva,
tis is not associated with systemic illness, topical antibi- and preauricular adenopathy (pharyngoconjunctival
otics such as erythromycin, polymyxin–bacitracin, sul- fever). Epidemics of adenoviral keratoconjunctivitis
facetamide, tobramycin, and fluoroquinolones are occur. Treatment is supportive. Children with pre-
sumed adenoviral keratoconjunctivitis are considered
contagious 10–14 days from the day of onset. They
should stay out of school and group activities as long as
their eyes are red and tearing. Strict handwashing pre-
cautions are recommended.
During the prodromal period of measles infection,
conjunctivitis occurs; this is preceded by a transverse mar-
ginal line of conjunctival injection across the lower lids.
Herpes simplex virus may cause conjunctivitis or
blepharoconjunctivitis. Treatment is with topical tri-
fluridine 1% drops or 3% vidarabine ointment. Oral
acyclovir may be used prophylactically in children to
reduce recurrence of herpes simplex ocular disease.

Altemeier III WA: The importance of adenoviral infections in pedi-

atrics. Pediatr Ann 2001;30:439 [PMID: 11510341].

Figure 15–18. Ophthalmia neonatorum due to Allergic Conjunctivitis

Chlamydia trachomatis infection in a 2-week-old infant. In hay fever conjunctivitis, the eyes are red and itchy,
Note marked lid and conjunctival inflammation. with mucoid discharge. Symptomatic treatment is with
446 / CHAPTER 15

Table 15–3. Common ocular allergy medications.

Generic Name Brand Name Mechanism of Action Side Effects Dosage Indications
Lodoxamide tro- Alomide Mast-cell stabilizer Transient burning or 1 drop 4 times Vernal kerato-
methamine 0.1% stinging daily—taper conjunctivitis
Cromolyn Na 4% Crolom, Opticrom Mast-cell stabilizer Transient burning or 1 drop 4–6 Vernal kerato-
stinging times daily conjunctivitis
Olopatidine Patanol Mast-cell stabilizer, H1 Headache, burning or twice daily Itching due to
receptor antagonist stinging (interval 6–8 allergic conjunc-
hrs) tivitis
Ketorolac trometh- Acular NSAID Transient burning or 1 drop 4 times Itching due to
amine 0.5% stinging daily seasonal allergic
conjunctivitis
Levocobastine HCl Livostin H1 receptor antagonist Transient burning or 1 drop 4 times Relief of symp-
0.05% stinging, headache daily toms of seasonal
allergic conjunc-
tivitis
Naphazoline HCl AK-con, Naphcon, Ocular decongestant, Mydriasis, increased Varies by Temporary relief
0.1% Opcon, Vasocon vasoconstrictor redness, irritation, dis- preparation of redness due to
comfort, punctate ker- minor eye irritants
atitis, increased intra-
ocular pressure, dizzy,
HA, nausea, nervousness,
HTN, weakness, cardiac
effects, hyperglycemia
Pheniramine Component in Antihistamine 1 drop every Relief of symp-
maleate AK-Con A, 3–4 h, as toms of seasonal
Opcon-A, needed allergic conjunc-
Naphcon-A tivitis

a combination topical vasoconstrictor plus an antihista-

mine (naphazoline–antazoline); a nonsteroidal anti-
inflammatory drug such as ketorolac tromethamine
0.5%; a mast cell stabilizer such as lodoxamide
tromethamine 0.1%; or prednisolone 0.125% (Table
15–3). Corticosteroids should be used with caution be-
cause their extended use causes glaucoma and or
cataracts in some patients. Central nervous system
(CNS) depression has been reported with accidental in-
gestion of naphazoline.
Vernal conjunctivitis is a seasonal form of allergic
conjunctivitis associated with tearing, itching, and a
stringy discharge. It is more common in males. In the
palpebral form, dramatic changes of the superior palpe-
bral conjunctiva occur, with cobblestone papillae (Fig-
ure 15–19). Corneal ulcers can occur. Topical treat-
ments include a mast cell stabilizer such as 4%
cromolyn sodium or 0.1% lodoxamide tromethamine Figure 15–19. Vernal conjunctivitis. Cobblestone
and limited use of a topical corticosteroid. One form of papillae in superior tarsal conjunctiva.
 EYE / 447

vernal conjunctivitis (limbal vernal) presents with nod-

ules at the limbus (the corneal–conjunctival junction).
Contact lens wear may induce a conjunctivitis that ap-
pears similar to the palpebral form of vernal conjunc-
tivitis.

Mucocutaneous Diseases
Conjunctivitis and conjunctival changes are associated
with a number of systemic syndromes. Examples are
erythema multiforme (Stevens–Johnson syndrome; see
Chapter 14), Reiter syndrome (Chapter 40), and
Kawasaki disease (Chapter 19), which is also associated
with iritis. With Stevens–Johnson syndrome, conjunc-
tival changes include erythema, vesicular lesions that Figure 15–20. Iris coloboma located inferiorly.
frequently rupture, and symblepharon (adhesions) be-
tween the raw edges of the bulbar and palpebral (lid)
conjunctiva. Management may include artificial tears
and lubricants to provide comfort and a topical cortico- with Wilms tumor. Repeated examination and abdomi-
steroid to prevent adhesions and dry eye in severe cases nal ultrasonography are thus indicated. The aniridia
of erythema multiforme. Lysis of adhesions or use of a gene has been isolated to the 11p13 chromosome re-
scleral ring by an ophthalmologist may be required. gion. Aniridia, genitourinary abnormalities, and mental
Surgical treatment of severe cases of symblepharon with retardation have been linked to an 11p deletion.
amniotic membrane grafts are under investigation. Cy-
cloplegic agents and topical corticosteroids are pre-
scribed for iritis in Kawasaki disease. Albinism
Albinism is caused by defective melanogenesis. Most
Honavar SG et al: Amniotic membrane transplantation for ocular cases of albinism are autosomal recessive, but an X-
surface reconstruction in Stevens–Johnson syndrome. Oph- linked form does occur. Tyrosinase is an essential en-
thalmology 2000 May;107(5):975–979 [PMID 10811093].
zyme in the production of melanin. Many cases of
complete albinism are caused by mutations of the ty-
DISORDERS OF THE IRIS rosinase gene. Albinism with some pigment produc-
tion, especially in people of African descent, is more
Iris Coloboma commonly caused by mutations of the p gene.
Iris coloboma is a developmental defect due to incom- Affected individuals are usually legally blind and
plete closure of the anterior embryonal fissure. The have nystagmus (see nystagmus section). Iris, skin, and
child’s pupil will have an elongated shape reminiscent hair color varies according to the type and severity of al-
of a keyhole or cat’s eye (Figure 15–20). The affected binism as well as the individual’s race. Iris transillumi-
area is located inferonasally but may extend posteriorly, nation may be obvious or may require slitlamp exami-
involving the retina and choroid. The effect on visual nation with retroillumination to detect focal areas of
acuity is variable. Iris coloboma may be an isolated de-
fect or may be associated with a number of chromoso-
mal abnormalities and syndromes. Variable genetic ex-
pression of coloboma can include a broad spectrum,
from iris coloboma, to microphthalmia-with-cyst, and
even clinical anophthalmia.

Aniridia
Aniridia is a bilateral disorder that includes macular hy-
poplasia and absence of almost all of the iris (Figure
15–21). Cataract, corneal changes, and glaucoma are
often seen. Photophobia and nystagmus occur.
Aniridia may occur as an autosomal dominant in- Figure 15–21. Bilateral aniridia. Iris remnants present
heritance pattern or in a sporadic form that is associated temporally in each eye.
448 / CHAPTER 15

transillumination. Other ocular abnormalities include Pediatric glaucoma can be congenital or acquired
foveal hypoplasia, abnormal optic pathway projections, and unilateral or bilateral. In general, do not expect to
strabismus, and poor stereoacuity. These children see a red, inflamed eye with congenital or infantile glau-
should be evaluated by a pediatric ophthalmologist in coma. Although acute pupillary block glaucoma causes
order to optimize their visual function. a red, painful eye, pupillary block is quite rare in the
Albinism may be associated with other systemic pediatric age group.
manifestations. Bleeding problems occur in individuals Glaucoma may be inherited. Glaucoma can be clas-
with Hermansky–Pudlak syndrome (chromosome sified on an anatomic basis into two types: open-angle
10q23 or 5q13), in which oculocutaneous albinism is and closed-angle. Precipitating angle-closure glaucoma
associated with a platelet abnormality. Chédiak–Hi- in a child by dilating the pupil of an otherwise healthy
gashi syndrome (chromosome 1q42–44) is character- eye is a very rare occurrence.
ized by neutrophil defects, recurrent infections, and Glaucoma also occurs with ocular and systemic syn-
oculocutaneous albinism. Other conditions associated dromes. Aniridia and anterior segment dysgenesis are
with albinism are Waardenburg, Prader–Willi, and An- examples. Systemic syndromes associated with glau-
gelman syndromes. coma include Sturge–Weber syndrome, the oculocere-
The risk of skin cancer is much higher in individuals brorenal syndrome of Lowe, and the Pierre Robin syn-
with albinism. Parents and patients must be advised to drome. Glaucoma can also occur with hyphema, iritis,
use sunscreen and wear protective clothing. lens dislocation, intraocular tumor, and ROP. Treat-
ment depends on the cause, but surgery is often the
Dorey SE et al: The clinical features of albinism and their correla- choice unless the rise in intraocular pressure is tran-
tion with visual evoked potentials. Br J Ophthalmol 2003; sient, in which case medical treatment is indicated.
87(6):767–772 [PMID 12770978]. Be aware that some individuals are “steroid respon-
Russell-Eggitt I: Albinism. Ophthalmol Clin North Am 2001;1 ders” who develop increased intraocular pressure when
4(3):533–546 [PMID 11705153]. challenged with exogenous steroids. The optic nerve of
African Americans is probably prone to damage with
Other Iris Conditions acute increases in traocular pressure.
Heterochromia, or a difference in iris color, can occur
in congenital Horner syndrome, after iritis, or with tu-
mors and nevi of the iris and use of topical UVEITIS
prostaglandins. Malignant melanoma of the iris may Inflammation of the uveal tract can be subdivided ac-
also cause iris heterochromia. Acquired iris nodules cording to the uveal tissue primarily involved (iris,
(Lisch nodules), which occur in type I neurofibromato- choroid, retina) or by location, that is, anterior, inter-
sis, usually become apparent by age 8 years. When seen mediate, or posterior uveitis. Perhaps the most com-
on slitlamp examination, Lisch nodules are 1–2 mm in monly diagnosed form of uveitis in childhood is trau-
diameter and often beige in color, although their ap- matic iridocyclitis (iritis).
pearance can vary. Iris xanthogranuloma occurring with
juvenile xanthogranuloma can cause hyphema and
glaucoma. Patients with juvenile xanthogranuloma Anterior Uveitis
should be evaluated by an ophthalmologist for ocular
involvement. Injection, photophobia, pain, and blurred vision usu-
ally accompany iritis (anterior uveitis, iridocyclitis). An
DeBella K et al: Use of the National Institutes of Health criteria for
exception to this is iritis associated with juvenile
diagnosis of neurofibromatosis 1 in children. Pediatrics rheumatoid arthritis (Chapter 26), when the eye is
2000;105:608 [PMID: 10699117]. quiet and asymptomatic, but slitlamp examination will
reveal anterior chamber inflammation in which inflam-
matory cells and protein flare are seen.
GLAUCOMA Iridocyclitis associated with juvenile rheumatoid
Glaucoma is increased intraocular pressure, which arthritis occurs most often in girls with pauciarticular
causes damage to ocular structures and loss of vision. arthritis and a positive antinuclear antibody. All chil-
Signs of glaucoma presenting within the first year of life dren with juvenile rheumatoid arthritis need to be
include buphthalmos (enlargement of the globe due to screened according to a schedule recommended by the
low scleral rigidity in the infant eye) as well as tearing, American Academy of Pediatrics (www.aap.org). Treat-
photophobia, blepharospasm, corneal clouding due to ment with a topical corticosteroid and a cycloplegic
edema, and optic nerve cupping. After age 3 years, usu- agent is aimed at quieting the inflammation and pre-
ally only optic nerve changes occur. venting or delaying the onset of cataract and glaucoma.
 EYE / 449

Methotrexate and other immunosuppressive agents can cytomegalovirus [CMV], herpes simplex virus) and
be used in refractory cases. syphilis must be suspected in congenital infections that
Inflammatory bowel disease is also associated with cause chorioretinitis.
iritis—perhaps more commonly with Crohn disease Congenital lymphocytic choriomeningitis virus
than with ulcerative colitis. Other ocular findings of the (LCMV) may also present with chorioretinitis. The
anterior segment that can be associated with inflamma- virus is transmitted to humans by consumption of food
tory bowel disease include conjunctivitis, episcleritis, contaminated with rodent urine or feces. It most closely
and sterile corneal infiltrates. Posterior segment find- resembles congenital toxoplasmosis in presentation. Di-
ings may include central serous retinochoroidopathy, agnosis is done by immunofluorescent antibody or en-
panuveitis (inflammation of all uveal tissue), choroidi- zyme-linked immunosorbent assay (ELISA) laboratory
tis, ischemic optic neuropathy, retinal vasculitis, neu- testing. If possible, pregnant women should avoid ex-
roretinitis, and intermediate uveitis (see section on In- posure to rodents.
termediate Uveitis). Ocular candidiasis occurs typically in an immuno-
Posterior subcapsular cataracts can develop in pa- compromised host or an infant in the intensive care
tients with or without ocular inflammation. Most, if nursery receiving hyperalimentation. Candidal chori-
not all, of these patients have been taking corticoster- oretinitis appears as multifocal, whitish yellow, fluffy
oids as part of the long-term treatment of inflammatory retinal lesions that may spread into the vitreous and
bowel disease. Children with Crohn disease or ulcera- produce a so-called cotton/fungus ball vitritis.
tive colitis should have routine periodic ophthalmologic Acute retinal necrosis syndrome is caused most often
examinations to rule out ocular inflammation, which by varicella-zoster virus and occasionally by herpes sim-
may be asymptomatic, and cataracts associated with plex virus. Patients may present with a red and painful
systemic corticosteroids. eye. Ophthalmoscopy may show unilateral or bilateral
Other causes of anterior uveitis in children include patchy white areas of retina, arterial sheathing, vitreous
syphilis, tuberculosis, sarcoidosis, relapsing fever (borre- haze, atrophic retinal scars, retinal detachment, and
liosis), and Lyme disease, all but the last also causing optic nerve involvement.
posterior uveitis. Juvenile spondyloarthropathies, in- CMV is a cause of congenital infection that may be
cluding ankylosing spondylitis, Reiter syndrome, and accompanied by retinitis. CMV infection must be con-
psoriatic arthritis, are also associated with anterior sidered as a cause of retinitis in immunocompromised
uveitis. A substantial percentage of cases are of un- and human immunodificiency virus (HIV)-infected
known origin. children. CMV retinitis appears as a white retinal le-
sion, typically but not always associated with hemor-
Kodsi SR et al: Time of onset of uveitis in children with juvenile
rhage, or as a granular, indolent-appearing lesion with
rheumatoid arthritis. J AAPOS 2002;6(6):373 [PMID hemorrhage and a white periphery. Cotton wool spots
12506279]. (nerve fiber layer infarcts) also commonly occur in
Oren B et al: The prevalence of uveitis in juvenile rheumatoid HIV-positive patients.
arthritis. J Am Assoc Pediatr Ophthalmol Strabismus In toddlers and older youngsters, Toxocara canis or
2001;5:2 [PMID: 11182663]. T cati infections (ocular larva migrans; see Chapter 39)
occur from ingesting soil contaminated with parasite
eggs. The disease is usually unilateral. Common signs
Posterior Uveitis and symptoms include a red injected eye, leukocoria,
The terms choroiditis, retinitis, and retinochoroiditis de- and decreased vision. Fundus examination may show
note the tissue layer primarily involved in posterior endophthalmitis (vitreous abscess) or localized granu-
uveitis. Characteristic features occur with posterior loma. Diagnosis is based on the appearance of the le-
uveitis as a result of certain organisms. Active toxoplas- sion and serologic testing using ELISA for T canis and
mosis (see Chapter 39) produces a white lesion appear- T cati. Treatment options include periocular cortico-
ing as a “headlight in the fog” owing to the overlying steroid injections and vitrectomy.
vitritis. Inactive lesions have a hyperpigmented border.
Contiguous white satellite lesions suggest reactivation
of disease. Congenital infections must be treated aggres-
sively with a triple drug regimen (pyramethamine, sul-
Bresin AP et al: Ophthalmic outcomes after prenatal and postnatal
fadiazine, and leukovorin) for 1 year. Studies have treatment of congenital toxoplasmosis. Am J Ophthalmol
shown improved ophthalmic and neurologic outcomes 2003;135(6):779 [PMID 12788116].
with prolonged treatment. A granular “salt and pepper” Mets MB et al: Lymphocytic choriomeningitis virus: An underdiag-
retinopathy is characteristic of congenital rubella. In in- nosed cause of congenital chorioretinitis. Am J Ophthalmol
fants, the TORCH complex (toxoplasmosis, rubella, 2000;130(2):209 [PMID 11004296].
450 / CHAPTER 15

Intermediate Uveitis DISORDERS OF THE CORNEA

Pars planitis, often of uncertain cause, can be associated Conditions Causing Corneal Clouding
with vitreous floaters. The inflammation is described as
snowbanking because a heaped-up white precipitate is The differential diagnosis of corneal clouding in a new-
located in the far anterior periphery of the retina and born infant includes forceps trauma, congenital glau-
vitreous base. Pupillary dilation and indirect ophthal- coma, infection, congenital malformation, and tumor.
moscopy are required for observation. Macular edema In older children, corneal clouding is associated with
and decreased vision can result. mucopolysaccharidoses, Wilson disease, and cystinosis.
Toxocara infections with peripheral granuloma can Infiltrates occur with viral infections, staphylococcal lid
be associated with intermediate uveitis, as can inflam- disease, corneal dystrophies, and interstitial keratitis
matory bowel disease, multiple sclerosis, and sarcoido- due to congenital syphilis.
sis. Retinoblastoma and other neoplasms can imitate
uveitis, causing a so-called masquerade syndrome. Microcornea & Megalocornea
Microcornea—a corneal diameter less than 10 mm in a
ACQUIRED IMMUNODEFICIENCY full-term infant or older child—may be associated with
SYNDROME & THE EYE other anterior segment malformations or a microph-
Ocular infections are important manifestations of ac- thalmic globe. Megalocornea—diameter of 12.5 mm or
quired immunodeficiency syndrome (AIDS) (see Chap- greater—should be regarded as due to congenital glau-
ter 37). As CD4 T-lymphocyte counts fall below coma until proved otherwise.
200/µL, opportunistic infections increase in these pa-
tients. Pathogens commonly causing eye infection in- Keratitis
clude Toxoplasma gondii and CMV. Especially when Both herpes simplex and herpes zoster can infect the
CD4+ counts fall below 50/µL, the patient is at high cornea. When the epithelium breaks down, a dendritic
risk for CMV retinitis, the leading cause of vision loss or ameboid pattern can be seen with fluorescein stain-
in AIDS patients (see Posterior Uveitis section) and ing. Corneal involvement with herpes simplex can be
blindness. Active CMV retinitis must be treated with recurrent and lead to blindness. Topical antivirals such
intravenous foscarnet or ganciclovir. These medications as trifluridine and vidarabine are indicated when herpes
may be required in combination if the retinitis fails to simplex infection is limited to the corneal epithelium.
respond to a single drug regimen. Intravitreal ganci- Topical corticosteroids may be a useful addition when
clovir or ganciclovir implants in conjunction with oral stromal disease is present. The use of corticosteroids in
valganciclovir may be required in severe cases or in in- the presence of herpetic disease should be undertaken
dividuals intolerant to intravenous therapy. The inci- only by an ophthalmologist because of the danger of
dence of CMV retinitis has fallen dramatically with the worsening the disease. Oral acyclovir started in the early
use of multidrug antiretroviral therapy. phase (first 5 days) may be helpful in treating herpes
Acute retinal necrosis syndrome (see Posterior zoster eye disease. Acyclovir prophylaxis is helpful in
Uveitis section) is a severe necrotizing retinitis in AIDS preventing recurrent herpetic epithelial keratitis (see
patients that often results in blindness. Most cases are Viral Conjunctivitis section) and stromal keratitis
thought to be caused by varicella-zoster virus. Other caused by herpes simplex.
implicated agents are herpes simplex types 1 and 2 and Adenovirus conjunctivitis may progress to keratitis
occasionally CMV. Therapy with antiviral agents is re- 1–2 weeks after onset. Slitlamp examination reveals
quired, but the prognosis is poor. A specific HIV white infiltrates beneath the corneal epithelium. Vision
retinopathy not associated with other known infectious may be decreased. In most cases no treatment is neces-
agents also occurs. Various retinal abnormalities in- sary because adenovirus keratitis is most often self-lim-
clude cotton wool spots, retinal hemorrhages, microan- iting. However, adenovirus is highly contagious and
eurysms, perivasculitis, and decreased visual acuity from easily spread (see Conjunctivitis section).
ischemic maculopathy. Contact lens wearers are at risk for severe vision-
threatening Acanthamoeba keratitis from contaminated
Frenkel et al: Oral ganciclovir in children: Pharmacokinetics,
safety, tolerance, and antiviral effects. The Pediatric AIDS
contact lens solutions. Treatment is difficult and may
Clinical Trials Group. J Infect Dis 2000;182(6):1616 [PMID require corneal transplantation (see Chapter 39).
11069232].
Jabs DA et al: Characteristics of patients with cytomegalovirus re- The Herpetic Eye Disease Study Group: Acyclovir for the preven-
tinitis in the era of highly active antiretroviral therapy. Am tion of recurrent herpes simplex virus eye disease. N Engl
J Ophthalmol 2002;133(1):48 [PMID 11755839]. J Med 1998;339:300 [PMID: 9696640].
 EYE / 451

Schwartz GS et al: Oral acyclovir for the management of herpes

simplex virus keratitis in children. Ophthalmology
2000;107:278 [PMID: 10690825].

Corneal Ulcers
Bacterial corneal ulcers in healthy children who are not
contact lens wearers are usually secondary to corneal
trauma from corneal abrasion or a penetrating foreign
body. Decreased vision, pain, injection, a white corneal
infiltrate or ulcer (Figure 15–22), and hypopyon (pus
in the anterior chamber) may all be present. Prompt re-
ferral to an ophthalmologist is necessary for culture and
antibiotic treatment. Figure 15–23. Cataract causing leukocoria.

DISORDERS OF THE LENS

Lens disorders involve abnormality of clarity or posi- mental, that is, not related to infection or metabolic
tion. Lens opacification–cataract can affect vision de- problems. Laboratory investigation for infectious and
pending on its density, size, and position. Visual poten- metabolic causes is often indicated. Such investigation
tial is also influenced by age at onset and the success of would include cultures or serologic tests for toxoplas-
amblyopia treatment. mosis, rubella, CMV, herpes simplex virus, and syphilis
as well as evaluation for metabolic errors as may occur
Cataracts with galactosemia or Lowe syndrome.
Early diagnosis and treatment are necessary to pre-
Cataracts in children may be unilateral or bilateral, may vent deprivation amblyopia in children younger than
exist as isolated defects, or may be accompanied by age 9 years, because such children are visually imma-
other ocular disorders or systemic disease (Figure ture. Cataracts that are visually significant require re-
15–23). Congenital and infantile cataracts may also be moval. Rehabilitation with an intraocular lens is com-
part of a chromosomal syndrome. Leukocoria, poor fix- monplace, especially with cataracts removed after the
ation, and strabismus or nystagmus (or both) may be age of 2 years. But contact lenses and glasses still play a
the presenting complaints. In the newborn, absence of role, as does occlusion of the better-seeing eye to treat
a red reflex should suggest the possibility of cataract, es- the amblyopia.
pecially if the infant’s pupil has been dilated for the ex-
amination.
Fallaha N et al: Pediatric cataracts. Ophthalmol Clin North Am
The appearance of the cataract may sometimes sug- 2001;14(3):479 [PMID 11705148].
gest its cause. Anterior capsular cataracts are develop-
Wilson ME et al: Paediatric cataract blindness in the developing
world: Surgical techniques and intraocular lenses in the new
millennium. Br J Ophthalmol 2003;87(1):14 [PMID
12488254].

Dislocated Lenses
Lens dislocation is usually bilateral except when caused
by trauma. Subluxation causes refractive errors of large
magnitude that are difficult to correct. Another oph-
thalmologic concern is pupillary block glaucoma. In
this disorder, a malpositioned unstable lens interferes
with the normal flow of aqueous humor from where it
is produced in the ciliary body (posterior to the pupil)
into the trabecular meshwork (anterior to the pupillary
plane).
Dislocated lenses are associated with other ocular
conditions and systemic syndromes, including Mar-
Figure 15–22. Corneal ulcer. Note white infiltrate lo- fan syndrome, homocystinuria, Weill–Marchesani syn-
cated on inferior cornea. drome, sulfite oxidase deficiency, hyperlysinemia,
452 / CHAPTER 15

syphilis, and Ehlers–Danlos syndrome. Work-up and retina until term, the optic nerve is used as the central
treatment are multidisciplinary endeavors. landmark. The most immature zone of retina, zone 1, is
the most posterior concentric imaginary circle around
DISORDERS OF THE RETINA the optic nerve. Further out is zone 2, and beyond that
is zone 3. Zone 1 disease is, by definition, more high
Retinal Hemorrhages in the Newborn risk than disease in more anterior zones. Similarly, the
Retinal hemorrhages are commonly seen in the other- stages of the abnormal vessels are numbered from zero,
wise healthy newborn. Although it occurs most often or simply incomplete vascularization, through stages I,
after vaginal delivery, this finding can also be present II, and III. When 5 contiguous, or 8 noncontiguous
after suction delivery or cesarean section. The hemor- clock hours of stage 3 disease occur, “threshold” has
rhages may be unilateral or bilateral and be located any- been reached. At this stage in the CRYO-ROP study,
where in the retina. They may appear as dot, blot, sub- 50% of eyes had a bad outcome without treatment,
retinal, or preretinal hemorrhages. They may also break progressing to stage IV or V. This was therefore chosen
into the vitreous. as the stage for mandatory treatment. Plus disease (+)
In general, retinal hemorrhages of the newborn dis- refers to dilation and tortuosity of the vessels around
appear quickly, usually within the first month of life, the optic nerve, and is an ominous sign of active, wors-
which may help differentiate this condition from retinal ening ROP. Rush disease refers to cases in which the
hemorrhages that occur in the shaken baby syndrome. disease skips intervening stages and goes rapidly to reti-
Another cause of retinal hemorrhage is coagulopathy. nal detachment.
The risk of developing visually threatening ROP is
Emerson AV et al: Incidence and rate of disappearance of retinal
inversely proportional to birth weight and gestational
hemorrhage in newborns. Ophthalmology 2001;108:36 age. Infants weighing less than 1500 g at birth or born
[PMID: 11150261]. at less than 33 weeks’ gestation may develop visually
threatening ROP. The cause of this disorder—includ-
Retinopathy of Prematurity ing the role of supplemental oxygen in the neonatal pe-
riod—is still not fully understood. During the first epi-
Retinopathy of prematurity (ROP) continues to be an demic of ROP in the 1960s, delivery of high levels of
important cause of blindness, especially for infants born oxygen without arterial monitoring appeared to con-
at less than 28 weeks’ gestation and weighing less than tribute significantly to the development of ROP. Pulse
1250 g. Premature infants with incomplete retinal vas- oximetry and better regulation led to a decline in cases,
cularization are at risk for developing abnormal periph- but better survival for the smallest, sickest infants has
eral retinal vascularization, which may lead to retinal increased the numbers of affected infants once again,
detachment. However, most cases of ROP do not leading to speculation that low birth weight and gesta-
progress to retinal detachment and require no treat- tional age may be more important than oxygen in etiol-
ment. ogy. Anecdotal reports of improvement in near-thresh-
The CRYO-ROP study outlined a standard nomen- old ROP with high oxygen saturations led to the
clature to describe the progression and severity of ROP STOP-ROP study, which investigated whether keeping
(Table 15–4). Since retinal blood vessels emanate from PaO2 high at this critical stage reduced the need for
the optic nerve, and do not fully cover the developing laser. The results did not show a benefit. A study in
which infants were kept at relatively low oxygen satura-
tion from birth did show a reduction in severe ROP
cases and showed no increase in cerebral palsy at
Table 15–4. Stages of retinopathy of prematurity. 18 months follow-up, which had been reported in the
past with oxygen curtailment. Further study and fol-
Stage I Demarcation line or border dividing the vascular low-up of this method is needed. Other risk factors for
from the avascular retina. severe ROP are bronchopulmonary dysplasia, intraven-
tricular hemorrhage, sepsis, apnea and bradycardia, and
Stage II Ridge. Line of stage I acquires volume and rises
mutations of Norrie disease gene. White males, infants
above the surface retina to become a ridge.
with zone 1 disease, and infants with very low birth
Stage III Ridge with extraretinal fibrovascular proliferation. weight and gestational age have a higher risk of reach-
Stage IV Subtotal retinal detachment. ing threshold.
Another cofactor that has been investigated is ambi-
Stage V Total retinal detachment. ent light in the nursery. One early study found a corre-
“Plus disease” signifies arteriolar tortuosity and venular dilation of lation between light exposure and development of
posterior pole vessels. ROP, but the multicenter LIGHT-ROP trial found no
 EYE / 453

correlation. Recent studies suggest that the substance Onofrey CB et al: The outcome of retinopathy of prematurity
vascular endothelial growth factor (VEGF) may play a screening for retinopathy using an outcome predictive pro-
gram. Ophthalmology 2001;108:27 [PMID: 11150259].
key role in ROP development, and methods of modu-
lating VEGF are being investigated. Repka MX et al: Involution of retinopathy of prematurity. Arch
Ophthalmol 2000;118:645 [PMID: 10815156].
Screening guidelines and a uniform classification
Repka MX et al: The incidence of ophthalmologic intervention in
system have been adopted, but alternative screening children with birth weights less than 1251 grams: Results
paradigms have also been suggested. The first retinal ex- through 51⁄2 years: Cryotherapy for retinopathy of prematurity
amination is recommended at age 4–6 weeks after cooperative group. Ophthalmology 1998;105:1621 [PMID:
birth, or 31 weeks postmenstrual age, whichever is ear- 9754167].
lier. The frequency of follow-up examinations depends Reynolds JD et al, CRYO-ROP and LIGHT-ROP Cooperative
on the findings and the risk factors for developing the Study Groups: Evidence-based screening criteria for retinopa-
disease, but for most infants will be every 1–2 weeks. thy of prematurity: Natural history data from the CRYO-
ROP and LIGHT-ROP studies. Arch Ophthalmol
Acute-phase ROP begins to involute at a mean post- 2002;120(11):1470 [PMID: 12427059].
menstrual age of 38.6 weeks, but the range for onset of
STOP-ROP Multicenter Study Group: Supplemental therapeutic
involution is wide. Examinations can be discontinued oxygen for threshold retinopathy of prematurity (STOP-
when the retinas are fully vascularized, or when the ROP), a randomized, controlled trial. I: Primary outcomes.
baby is 45 weeks’ gestational age and has never had Pediatrics 2000;105:420 [PMID: 10654946].
prethreshold disease or worse, or is vascularized out to Subhani M et al: Screening guidelines for retinopathy of prematu-
zone 3 and never had zone 1 or 2 disease. The treat- rity: The need for revision in extremely low birth weight in-
ment of threshold ROP within 72 hours of diagnosis fants. Pediatrics 2001;108:27 [PMID: 11335739].
with cryotherapy reduced the occurrence of bad visual
outcomes by 50%. Diode laser treatment has largely re-
placed cryotherapy because it provides better access for
Retinoblastoma
treating zone 1 disease and causes less inflammation. Retinoblastoma is the most common primary intraocu-
Reported success rates are higher than with cryother- lar malignancy of childhood, with an incidence esti-
apy. However, some patients still develop blinding reti- mated between 1:17,000 and 1:34,000 live births (see
nal detachment. With smaller, sicker infants surviving, Chapter 28). Most patients present before age 3 years;
treatment guidelines may need to be amended to treat children with hereditary or bilateral retinoblastoma
earlier than threshold in some infants. Studies investi- usually present earlier than those with unilateral, spo-
gating this are underway. radic disease.
Other findings associated with ROP include strabis- Inherited forms of retinoblastoma are autosomal
mus, amblyopia, myopia, glaucoma, and loss of visual dominant with high penetrance. The disease may con-
field. sist of a solitary mass or multiple tumors in one or both
eyes. All bilateral cases and some unilateral cases are
American Academy of Pediatrics, the American Association for Pe- caused by germinal mutations; however, most unilateral
diatric Ophthalmology and Strabismus, and the American cases are caused by a somatic retinal mutation. In both
Academy of Ophthalmology: A joint statement: Screening ex- situations, the mutation occurs in the retinoblastoma
amination of premature infants for retinopathy of prematu- gene (Rb) at chromosome 13q14. This is a tumor sup-
rity. Revised 2001. pressor gene. One mutated copy may be inherited in an
http://www.aao.org/aao/education/library/information/rop.cfm autosomal dominant fashion (germline mutation). If a
Chow LC et al; CSMC Oxygen Administration Study Group: Can second mutation spontaneously occurs in any cell, tu-
changes in clinical practice decrease the incidence of severe morigenesis is likely. Individuals with a germinal muta-
retinopathy of prematurity in very low birth weight infants?
Pediatrics 2003;111(2):339 [PMID: 12563061]. tion are at risk for the development of tumors other
Cryotherapy for Retinopathy of Prematurity Cooperative Group:
than retinoblastoma (pineal tumors, osteosarcoma, and
Effect of retinal ablative therapy for threshold retinopathy of other soft tissue sarcomas). All children with unilateral
prematurity: Results of Goldmann perimetry at the age of or bilateral retinoblastoma must be presumed to have
10 years. Arch Ophthalmol 2001;119:1120 [PMID: the germline form, including being followed expec-
11483077]. tantly for other tumors in the remaining eye and sys-
Cryotherapy for Retinopathy of Prematurity Cooperative Group: temically. Approximately 15% of patients with unilat-
Multicenter trial for retinopathy of prematurity: Ophthalmo- eral disease have germline mutations.
logical outcomes at 10 years. Arch Ophthalmol 2001;119:
1110 [PMID: 11483076].
The most common presenting sign in a child with
previously undiagnosed retinoblastoma is leukocoria
Holmstrom G, el Azazi M: Ophthalmologic followup of preterm
infants: A population based, prospective study of visual acuity (see Figure 15–1). Evaluation of the pupillary red reflex
and strabismus. Br J Ophthalmol 1999;83:143 [PMID: is important, although a normal red reflex does not rule
10396188]. out retinoblastoma. This examination requires indirect
454 / CHAPTER 15

ophthalmoscopy with scleral depression and pupillary ophthalmologist, with prophylactic laser treatment, are
dilation, performed by an ophthalmologist. Other chil- often recommended.
dren present with strabismus, red eye, glaucoma, or
pseudohypopyon (appearance of pus-like material in Diabetes Mellitus
the anterior chamber).
Treatment of unilateral cases, especially of large tu- Diabetic retinopathy is a specific vascular complication
mors, usually has been enucleation, because at the time of diabetes mellitus. Patients with type 1, or insulin-de-
of presentation the eye is filled with tumor. Vision and pendent, diabetes are at higher risk of developing severe
eyes can be salvaged in some cases. Chemoreduction of proliferative retinopathy leading to visual loss than are
intraocular tumors is a newer treatment technique used those with type 2, or non-insulin-dependent, diabetes.
to reduce initial tumor volume. In conjunction with The American Diabetes Association recommends an-
local treatment such as laser photocoagulation, nual screening for retinopathy 5 years after onset of dia-
cryotherapy, plaque radiotherapy, and thermotherapy, betes in adults. In children older than age 9 years, refer-
it can preserve vision and spare the patient enucleation ral to an ophthalmologist for screening of retinopathy
and radiation that may lead to disfigurement and the should be begun 3–5 years after the onset of diabetes.
induction of secondary tumors, especially in eyes classi- Acute onset of diabetes may be accompanied by sudden
fied with less extensive disease. Agents used in chemore- myopia and by cataracts. Both conditions may be re-
duction include carboplatin, etoposide, and vincristine. versible with systemic glucose control. Young children
Eradication of tumor before infiltration into the optic with type 1 diabetes should be followed for the Wol-
nerve or choroid carries a good prognosis for survival. fram, or DIDMOAD, syndrome, in which diabetes
Genetic testing is available for patients with mellitus occurs in conjunction with diabetes insipidus,
retinoblastoma. Once the causative mutation is found optic atrophy, and deafness.
in an affected individual, unaffected members of the
family may be tested to determine their personal and American Academy of Pediatrics Section on Endocrinology and
reproductive risk. This testing may avoid many unnec- Ophthalmology: Screening for retinopathy in the pediatric
patient with type 1 diabetes mellitus. Pediatrics 1998;101;
essary examinations under anesthesia for young relatives 313 [PMID: 9457160].
of patients of with retinoblastoma. Raman V et al: Retinopathy screening in children and adolescents
with diabetes. Ann N Y Acad Sci 2002;958:387 [PMID:
Ganesh A et al: Retinoblastoma and the 13 q deletion syndrome. 12021146].
J Pediatr Ophthalmol Strabismus 2001;38:247 [PMID:
11495315].
Metz TH Jr et al: Pupillary dilation by pediatricians. Pediatrics
DISEASES OF THE OPTIC NERVE
1999;104:958 [PMID: 10506240]. Optic nerve function is evaluated by checking visual
Richter S et al: Sensitive and efficient detection of RB1 gene muta- acuity, color vision, pupillary response, and visual
tions enhances care for families with retinoblastoma. Am fields. Poor optic nerve function results in decreased
J Hum Genet 2003;72(2):253 Epub 2002 Dec
18 [PMID:12541220]. central or peripheral vision, decreased color vision, stra-
Sussman DA et al: Comparison of retinoblastoma reduction for
bismus, and nystagmus.
chemotherapy vs external beam radiotherapy. Arch Ophthal- The swinging flashlight test is used to assess func-
mol 2003;121(7):979 [PMID: 12860801]. tion of each optic nerve. It is performed by shining a
light alternately in front of each pupil to check for an
afferent pupillary defect or Marcus Gunn pupillary de-
Retinal Detachment fect. An abnormal response in the affected eye is pupil-
Retinal detachment occurs infrequently in children. lary dilation when the light is directed into that eye
Common causes are trauma and high myopia. Other after having been shown in the other eye with its
causes are ROP, Marfan syndrome, and Stickler syn- healthy optic nerve. This results from poorer conduc-
drome. tion along the optic nerve of the affected eye, which in
Symptoms of detachment are floaters, flashing turn results in less pupillary constriction of both eyes
lights, and loss of visual field; however, children often than occurs when the light is shined into the nonin-
cannot appreciate or verbalize their symptoms. A de- volved eye. Hippus—rhythmic dilating and constrict-
tachment may not be discovered until the child is re- ing movements of the pupil—can be confused with an
ferred after failing a vision screening examination, stra- afferent pupillary defect.
bismus supervenes, or leukocoria is noted. Treatment The optic nerve is evaluated as to size, shape, color,
of retinal detachment is surgical. For children with con- and vascularity. Occasionally, myelinization past the
ditions predisposing to retinal detachment, or a strong entrance of the optic nerve head occurs. It appears
family history, examinations under anesthesia by an white, with a feathered edge (Figure 15–24). Myeliniza-
 EYE / 455

cause, such as tumor or intracranial infection. This dys-

function appears as an elevated disc with indistinct
margins, increased vessel diameter, and increased capil-
larity, giving the disc a hyperemic appearance with sur-
rounding hemorrhages and exudates in more severe
cases. Observed changes may be subtle to striking.
Optic nerve head changes are bilateral and generally
symmetrical.
Besides known causes such as hydrocephalus and in-
tracranial tumor, papilledema is associated with so-
called benign intracranial hypertension, also known as
pseudotumor cerebri or idiopathic intracranial hyper-
tension. Papilledema occurs almost equally in boys and
girls and sometimes is associated with obesity or upper
respiratory tract infection. Other associated causes are
viral infections, corticosteroid use and withdrawal,
sinus infection, trauma, tetracycline use, growth hor-
mone, and venous sinus thrombosis. Early in the course
of the disorder, the patient may not notice a change in
vision, although the blind spot may be enlarged. Tran-
Figure 15–24. Myelinization extending from optic sient obscurations of vision (amaurosis fugax) may
nerve superiorly onto the retina. occur as the process becomes more long-standing. Fur-
ther effects on vision will occur as the papilledema be-
comes chronic and ultimately leads to optic atrophy.
Work-up and treatment are directed toward finding the
tion onto the retina can be associated with myopia and underlying systemic or CNS cause. Treatment of idio-
amblyopia. Anatomic defects of the optic nerve include pathic intracranial hypertension may be pharmaco-
colobomatous defects and pits. logic—for example, using acetazolamide, a carbonic an-
Optic nerve hypoplasia may be associated with ab- hydrase inhibitor, or a corticosteroid. Diagnostic
sence of the septum pellucidum and hypothalamic–pi- lumbar puncture may also be curative. Optic nerve
tuitary dysfunction, which is known as septooptic dys- sheath fenestration and lumboperitoneal shunt are sur-
plasia, or de Morsier syndrome. Children with gical interventions.
septooptic dysplasia and hypocortisolism are at risk for
sudden death during febrile illness from thermoregula-
Kesler A et al: Idiopathic intracranial hypertension in the pediatric
tory disturbance and dehydration from diabetes in- population. J Child Neurol 2002;17(10):745 [PMID
sipidus. Optic nerve hypoplasia may occur in infants of 12546428].
diabetic mothers and has also been associated with alco- Rekate HL et al: Lumboperitoneal shunts in children. Pediatr Neu-
hol use or ingestion of quinine or phenytoin during rosurg 2003;38(1):41 [PMID 12476026].
pregnancy. Anatomically, the size of the involved optic Salman MS et al: Idiopathic “benign” intracranial hypertension:
nerve may range from absent (aplasia) to almost full Case series and report. J Child Neurol 2001;16:465 [PMID:
size, with a segmental defect. However, the nerve often 11453440].
appears larger than it is because it is surrounded by a
depigmented halo. Visual function with optic nerve hy-
poplasia ranges from mildly decreased to absent light Papillitis
perception. If only one eye is involved, the child usually Papillitis is a form of optic neuritis seen on ophthalmo-
presents with strabismus. If both eyes are affected, nys- scopic examination as an inflamed optic nerve head.
tagmus is usually the presenting sign. Optic neuritis in the pediatric age group may be idio-
Because the optic nerve is an outgrowth of the brain, pathic, associated with multiple sclerosis, acute dissemi-
changes in this structure often reflect CNS disease and nated encephalomyelitis, Devic disease, or cat-scratch
defects of central midline structures. disease.
Papillitis may have the same appearance as pa-
pilledema. However, papillitis may be unilateral,
Papilledema whereas papilledema is almost always bilateral. Papillitis
Papilledema (optic disc edema, choked disc) is associ- can be differentiated from papilledema by an afferent
ated with increased intracranial pressure due to any pupillary defect (Marcus Gunn pupil), by its greater ef-
456 / CHAPTER 15

fect in decreasing visual acuity and color vision, and by immunization became available. Streptococcus pneumo-
the presence of a central scotoma. Papilledema that is niae bacteremia is still an occasional cause of this infec-
not yet chronic will not have as dramatic an effect on tion. Children with periorbital cellulitis from presumed
vision. Because increased intracranial pressure can cause bacteremia must be examined for additional foci of in-
both papilledema and a sixth (abducens) nerve palsy, fection.
papilledema can be differentiated from papillitis if es- Infection of the orbit almost always arises from con-
otropia and loss of abduction are also present. How- tiguous sinus infection, because the walls of three si-
ever, esotropia may also develop secondarily in an eye nuses make up portions of the orbital walls and infec-
that has lost vision from papillitis. In pseudopa- tion can breach these walls or extend by way of a richly
pilledema, a normal variant of the optic disc, the disc anastomosing venous system. The orbital contents can
appears elevated, with indistinct margins and a normal develop a phlegmon (orbital cellulitis), or frank pus can
vascular pattern. Pseudopapilledema sometimes occurs develop in the orbit (orbital abscess). When the orbit is
in hyperopic individuals. Retrobulbar neuritis, an in- infected, the signs of periorbital disease are joined by
flamed optic nerve but with a normal-appearing nerve proptosis (a protruding eye), restricted eye movement,
head, is associated with pain and the other findings of and pain with eye movement. Fever is usually high. CT
papillitis. scanning or MRI is required to establish the extent of
Work-up of the patient with papillitis includes lum- the infection within the orbit. Sinus imaging should be
bar puncture and cerebrospinal fluid analysis. Bar- obtained at the same time. The pathogenic agents are
tonella henselae can be detected by serology. MRI is the those of acute or chronic sinusitis—respiratory flora
preferred imaging study. An abnormal MRI is associ- and anaerobes. S aureus is also frequently implicated.
ated with a worse visual outcome. Treatment with cor- Therapy for preseptal and orbital cellulitis infection
ticosteroids is frequently used. is with systemic antibiotics. Treatment of orbital infec-
tions may require surgical drainage for subperiosteal ab-
scess in conjunction with intravenous antibiotics.
Optic Atrophy Drainage of infected sinuses is often part of the therapy.
Optic atrophy, noted as pallor of the nerve head with
loss of capillarity, occurs in children most frequently Ambati BK et al: Periorbital and orbital cellulites before and after
after neurologic compromise during the perinatal pe- the advent of Haemophilus influenzae type B vaccination.
riod. An example would be a premature infant who de- Ophthalmology 2000;107(8):1450 [PMID 10919886].
velops an intraventricular hemorrhage. Hydrocephalus, Starkey CR et al: Medical management of orbital cellulites. Pediatr
glioma of the optic nerve, craniosynostosis, certain neu- Infect Dis J 2001;20(10):1002 [PMID 11642617].
rologic diseases, and toxins such as methyl alcohol can
cause optic atrophy, as can certain inborn errors of me- Craniofacial Anomalies
tabolism, long-standing papilledema, or papillitis.
Craniofacial anomalies can affect the orbit and visual
system. Examples of changes associated with craniofa-
DISEASES OF THE ORBIT cial disease involving the orbits are proptosis, corneal
exposure, hypertelorism (widely spaced orbits), strabis-
Periorbital & Orbital Cellulitis mus, amblyopia, lid coloboma, papilledema, and optic
The fascia of the eyelids joins with the fibrous orbital atrophy. Craniofacial anomalies occur with craniosyn-
septum to isolate the orbit from the lids. This septum ostoses and midface syndromes such as Treacher
serves as a barrier to the posterior spread of infection Collins and Pierre Robin sequence. Fetal alcohol syn-
from preseptal infection. Infections arising anterior to drome is associated with similar changes of the ocular
the orbital septum are termed preseptal. Preseptal (peri- adnexa.
orbital) cellulitis, which indicates infection of the struc-
tures of the eyelid, is characterized by lid edema, ery- Orbital Tumors
thema, swelling, pain, and mild fever. It usually arises
from a local exogenous source such as an abrasion of Both benign and malignant orbital lesions occur in
the eyelid, from other infections (hordeolum, dacry- children. The most common tumor is capillary heman-
ocystitis, chalazion), or from infected varicella or insect gioma (Figure 15–25). This type of tumor may be lo-
bite lesions. Staphylococcus aureus and Streptococcus pyo- cated superficially in the lid or deep in the orbit and
genes are the most common pathogens cultured from can cause ptosis, refractive errors, and amblyopia.
these sources. Preseptal infections in children younger Deeper lesions may cause proptosis. Capillary hemangi-
than age 3 years also occur from bacteremia, although omas in infants initially increase in size before involut-
this is much less common since Haemophilus influenzae ing at about age 2–4 years. Therapy with intralesional
 EYE / 457

ptosis) or conditions in which the visual pathways are

hypoplastic, sometimes referred to as “sensory nystag-
mus.” Both optic nerve hypoplasia and macular hy-
poplasia, the latter occurring with aniridia or albinism,
are associated with nystagmus. Nystagmus can also
occur with normal ocular structures and seemingly nor-
mal CNS development, sometimes referred to as
“motor nystagmus.” In the latter instance, the nystag-
mus may be blocked in certain positions of gaze, in
Figure 15–25. Right upper lid hemangioma causing which case a face turn or torticollis may develop. Latent
ptosis. nystagmus occurs when one eye is occluded. This type
of nystagmus occurs in patients with congenital es-
otropia. An associated amblyopia may be present.
Most nystagmus occurring in childhood is of ocular
or systemic corticosteroids is indicated if the lesion is origin, but CNS disease and, less frequently, inner ear
large enough to cause amblyopia. disease are other causes. A CNS cause is likely when the
Orbital dermoid cysts vary in size and are usually nystagmus is acquired. The clinician should evaluate
found temporally at the brow and orbital rim or the fundus for optic nerve abnormalities and the quality
supranasally. These lesions are firm, well encapsulated, of the macular reflex, because both optic nerve hy-
and mobile. Rupture of the cyst causes a severe inflam- poplasia and macular hypoplasia can cause nystagmus.
matory reaction. Treatment is by excision. Lymphan- Evaluation of nystagmus begins with the pediatric
gioma occurring in the orbit is typically poorly encap- ophthalmologist. Careful evaluation for iris transillumi-
sulated, increases in size with upper respiratory nation defects caused by albinism should be performed.
infection, and is susceptible to hemorrhage. Other be- An electroretinogram (ERG) is usually required to rule
nign tumors of the orbit are orbital pseudotumor, neu- out retinal pathology as the cause. Some types of nys-
rofibroma, teratoma, and tumors arising from bone, tagmus, usually motor nystagmus, can be treated, gen-
connective tissue, and neural tissue. erally with surgery; less frequently, prisms are useful.
Of grave concern is orbital rhabdomyosarcoma, the Spasmus nutans, in which a rapid, shimmering,
most common primary orbital malignancy in child- dysconjugate nystagmus occurs with head bobbing and
hood (see Chapter 28). This tumor grows rapidly and torticollis, is said to improve with time. Glioma of the
displaces the globe. The average age at onset is hypothalamus can mimic spasmus nutans. Neuroimag-
6–7 years. The tumor is often initially mistaken for or- ing may be necessary to determine if the cause of the
bital swelling due to insignificant trauma. Radiation nystagmus is due to a CNS disease.
and chemotherapy are the mainstays of treatment after
biopsy confirms the diagnosis. With expeditious diag-
nosis and proper treatment, the survival rate of patients AMBLYOPIA & STRABISMUS
with orbital rhabdomyosarcoma confined to the orbit Visual development is a learned function. For it to pro-
approaches 90%. ceed normally, a child must experience a normal visual
Tumors metastatic to the orbit also occur; neuro- environment with well-aligned eyes that are free of vi-
blastoma is the most common. The patient may exhibit sually threatening disease and significant refractive er-
proptosis, orbital ecchymosis (raccoon eyes), Horner rors. The consequences of not meeting these require-
syndrome, or opsoclonus (dancing eyes). Ewing sar- ments during the sensitive period of visual development
coma, leukemia, Burkitt lymphoma, and the histiocyto- in the first decade of life are strabismus and decreased
sis X group of diseases may involve the orbit. vision, or amblyopia.

Shields JA et al: Pediatric ocular and intraocular tumors. Pediatr

Ann 2001;30:491 [PMID: 11510347].
Amblyopia
Amblyopia is a unilateral or bilateral reduction in cen-
tral visual acuity due to the sensory deprivation of a
NYSTAGMUS well-formed retinal image that occurs with or without a
Nystagmus is a rhythmic oscillation or jiggling of the visible organic lesion commensurate with the degree of
eyes. It may be unilateral or bilateral, more pronounced visual loss. Amblyopia can occur only during the criti-
in one eye, or gaze-dependent. Nystagmus may be asso- cal period of visual development in the first decade of
ciated with esotropia or may occur with ocular lesions life when the visual nervous system is plastic. Approxi-
that cause deprivation amblyopia (eg, cataract, eyelid mately 3% of the population is amblyopic. Screening
458 / CHAPTER 15

for amblyopia should be a component of periodic well- Misdiagnosis of strabismus when the eyes are well
child examinations. The single best screening technique aligned—pseudostrabismus—can occur when relying
to discover amblyopia is obtaining visual acuity in each on the gross observation of the appearance of the two
eye. In preverbal children unable to respond to visual eyes. If the child has prominent epicanthal folds, pseu-
acuity assessment, amblyogenic factors are sought, in- doesotropia may be diagnosed erroneously. Observa-
cluding strabismus; media opacities; unequal Brückner tion of the reflection of a penlight on the cornea,
reflexes (pupillary red reflexes); and a family history corneal light reflex, is a more accurate means of deter-
suggestive of strabismus, amblyopia, or ocular disease mining if the eyes are straight. If strabismus is present,
occurring in childhood (see Examination section). the corneal light reflex will not be centered in both
Amblyopia is classified according to its cause. Stra- eyes.
bismic amblyopia can occur in the nondominant eye of An infant whose eyes are destined to be well aligned
a strabismic child. Refractive amblyopia can occur in may appear intermittently esotropic, but this should
both eyes if significant refractive errors are untreated occur less frequently over the first few months of life.
(ametropic or refractive amblyopia). Another type of re- By age 5 or 6 months, the baby’s eyes should be con-
fractive amblyopia can occur in the eye with the worse stantly well aligned.
refractive error when imbalance is present between the Besides its effect on visual development, strabismus
eyes (anisometropic amblyopia). Deprivation ambly- may be a marker of other ocular or systemic disease.
opia occurs when dense cataracts or complete ptosis Twenty percent of patients with retinoblastoma exhibit
prevents formation of a formed retinal image. Of the strabismus. Patients with CNS disorders such as hydro-
three types of amblyopia, this form of amblyopia results cephalus, space-occupying lesions, and an amaurotic
in the worst vision. (blind) eye can also exhibit strabismus. In children
The earlier treatment is begun, the better the chance younger than age 3 or 4 years, blind eyes tend to as-
of improving visual acuity. Treatment is usually discon- sume a position of esodeviation, but after about age
tinued after age 9 years. Amblyogenic factors such as re- 4 years an amaurotic eye tends to show an exotropic
fractive errors are addressed. Because of the extreme shift.
sensitivity of the visual nervous system in infants, con-
genital cataracts and media opacities must be diagnosed A. ESOTROPIA
and treated within the first few weeks of life. Visual re- In esotropia, the visual axes of the eyes are excessively
habilitation and amblyopia treatment must then be convergent. In terms of cause and treatment, esotropia
started in order to foster visual development. can be categorized by age at onset. Congenital esotropia
After eradicating amblyogenic factors, the mainstay (infantile esotropia) has its onset in the first year of life
of treatment is patching the sound eye, which causes in healthy infants. The deviation is large and obvious.
the visual nervous system to process input from the am- Surgery is the mainstay of treatment. Controversy exists
blyopic eye and in that way permits the development of as to how young the child should be when surgery is
useful vision. Other treatment modalities include “fog- performed so that the child can obtain an optimal
ging” the sound eye with cycloplegic drops (atropine), binocular result. The age range is from younger than
lenses, and filters. 6 months to 2 years. Esotropia beginning in the first
year also occurs in premature infants or in children
Pediatric Eye Disease Investigator Group: A randomized trial of at-
with a complicated perinatal history associated with
ropine vs. patching for treatment of moderate amblyopia in CNS problems such as intracranial hemorrhage and
children. Arch Ophthalmol 2002;120(3):268 [PMID periventricular leukomalacia. Esotropia is associated
11879129]. with certain syndromes. In Möbius’ syndrome (congen-
Repka MX et al: A randomized trial of patching regimens for treat- ital facial diplegia), a sixth nerve palsy causing esotropia
ment of moderate amblyopia in children. Arch Ophthalmol is associated with palsies of the seventh and twelfth cra-
2003;121(5)603 [PMID 12742836]. nial nerves and limb deformities. Duane syndrome can
affect the medial or lateral rectus muscles (or both). It
may be an isolated defect or may be associated with a
Strabismus multitude of systemic defects (eg, Goldenhar syn-
Strabismus is misalignment of the visual axes of the two drome). Duane syndrome is often misdiagnosed as a
eyes. Its prevalence in childhood is about 2–3%. Stra- sixth (abducens) nerve palsy. The left eye is involved
bismus is categorized by the direction of the deviation more commonly than the right, but both eyes can be
and its frequency. Early diagnosis of strabismus and involved. Girls are affected more frequently than boys.
amblyopia, which often coexist, provides the best Children with unilateral paretic or restrictive causes of
chance of reaching full visual potential. Strabismus may esotropia may develop face turns toward the affected
cause or be due to amblyopia. eye in order to maintain binocularity.
 EYE / 459

larity away from the field of action of the paretic mus-

cle. Papilledema is often but not invariably present with
increased intracranial pressure. Besides the vulnerability
of the abducens nerve to increased intracranial pressure,
it is susceptible to infection and inflammation. Otitis
media and Gradenigo syndrome (inflammatory disease
of the petrous bone) can cause sixth nerve palsy. Less
commonly, migraine and diabetes mellitus are consid-
A erations in children with sixth nerve palsy. Work-up in-
cludes imaging studies and neurologic examination.
B. EXOTROPIA
Exotropia does not usually offer as many diagnostic pit-
falls as esotropia. The visual axes of the two eyes are de-
viated in a divergent position (Figure 15–27). The devi-
ation most often begins intermittently and occurs after
age 2 years. Congenital (infantile) exotropia is ex-
tremely rare in an otherwise healthy infant. Early-onset
exotropia may occur in infants and children with severe
neurologic problems. All children with constant, con-
B genital exotropia require CNS neuroimaging. Treat-
ment of exotropia is with surgery, orthoptic exercises,
patching, and occasionally glasses.

Havertape SA et al: Sensory strabismus—eso or exo? J Pediatr Oph-

thalmol Strabismus 2001;38(6):327 [PMID 11759769].

A
C

Figure 15–26. Accommodative esotropia. Without

glasses, esotropic (A). With glasses, well-aligned at dis-
tance (B) and at near with bifocal correction (C).

The most frequent type of acquired esotropia is the

accommodative type (Figure 15–26). Onset is usually
between ages 2 and 5 years. The deviation is variable in
magnitude and constancy and is often accompanied by B
amblyopia. One type of accommodative esotropia is as-
sociated with a high hyperopic refraction. In another
type, the deviation is worse with near than with distant
vision. This type of esodeviation is usually associated
with lower refractive errors. Management includes
glasses with or without bifocals, amblyopia treatment,
and in some cases surgery. After age 5 years, any es-
otropia of recent onset should arouse suspicion of CNS
disease. Infratentorial masses, hydrocephalus, demyeli-
nating diseases, and idiopathic intracranial hyperten-
sion are causes of abducens palsy, which appears as an
esotropia, lateral rectus paralysis or paresis, and face Figure 15–27. Exotropia. A: Fixation with left eye. B:
turn. The face turn is an attempt to maintain binocu- Fixation with right eye
460 / CHAPTER 15

Ing MR et al: Outcome study of stereopsis in relation to duration from very early childhood has had little or no opportu-
of misalignment in congenital esotropia. J AAPOS nity to form visual impressions of the physical world.
2002;6(1):3 [PMID 11907472].
Blind children and their families should receive the
Rubin SE: Management of strabismus in the first year of life. Pedi- benefit of knowledgeable therapists and support
atr Ann 2001;30:474 [PMID: 11510345].
groups.
Schworm HD et al: Comitant strabismus. Curr Opin Ophthalmol
2000;11(5):310 [PMID 11148695].
Blind infants reach developmental landmarks on a
different schedule from that of sighted children. In ad-
dition, some blind children are multiply handicapped.
UNEXPLAINED DECREASED VISION For example, the premature child who is blind from
IN INFANTS & CHILDREN ROP may also have cerebral palsy. Children with Usher
syndrome become both deaf and blind.
Some infants with delayed visual development during Leading causes of blindness in the pediatric age
the first few months of life who are otherwise normal group differ among regions of the world and between
neurologically will reach an appropriate level of visual industrialized nations and developing countries. The
maturation. Occult causes of poor vision and blindness most common causes of blindness in the pediatric age
in children are those for which there are no obvious oc- group are thought to be cerebral visual impairment,
ular defects: they include Leber congenital amaurosis, a ROP, and optic nerve hypoplasia. Albinism, optic atro-
childhood form of retinitis pigmentosa; achromatopsia, phy, cataract, retinitis pigmentosa, microphthalmia or
the absence of functioning cones in the retina; and anophthalmia, aniridia, and glaucoma are other diseases
optic nerve abnormalities, including optic nerve hy- causing blindness.
poplasia and atrophy as well as night blindness.
Cerebral visual impairment, also known as cortical
Thompson L et al: The visually impaired child. Pediatr Clin North
blindness, is manifested as decreased visual attentive- Am 2003;50(1):225 [PMID 12713115].
ness of varying degree. Cerebral visual impairment can
be congenital or acquired. Insults to the optic pathways
and higher cortical visual centers are responsible. As- LEARNING DISABILITIES & DYSLEXIA
phyxia, trauma, intracranial hemorrhage, and periven- Visits to the physician because of educational difficul-
tricular leukomalacia are some of the causes of cortical ties are common. Evaluation of the child with learning
visual impairment. disabilities and dyslexia should include ophthalmologic
Besides an ophthalmologic work-up, ERG and vi- examination to identify any ocular disorders that could
sual evoked response testing may be required in chil- cause or contribute to poor school performance. Most
dren with decreased vision of unexplained etiology. children with learning difficulties have no demonstrable
Imaging studies of the brain and a pediatric neurologic problems on ophthalmic examination.
evaluation may be useful. A low-vision assessment may A multidisciplinary approach as suggested by the
be indicated. Low-vision aids enhance remaining vi- American Academy of Pediatrics, the American Associ-
sion. Devices used include magnifiers for both distance ation for Pediatric Ophthalmology and Strabismus, and
and near vision, closed-circuit television, and large- the American Academy of Ophthalmology is recom-
print reading materials. mended in evaluating children with learning disabili-
ties. Although many therapies directed at “training the
Hoyt CS: Visual function in the brain-damaged child. Eye eyes” exist, scientific support for such approaches is
2003;17(3):369 [PMID 12724701]. weak.

THE BLIND CHILD Mathes PG et al: The prevention and identification of reading dis-
ability. Semin Pediatr Neurol 2002;9(3):185 [PMID
Vision is the principal route of sensory input. A child’s 12350039].
development will therefore be affected profoundly by
blindness or very poor vision. There are psychological
consequences for the child blind from birth, as well as
VISION SCREENING
for the family. It can be devastating to a young family Vision screening in the pediatric age group is a chal-
to find out that their newborn is blind. Although ac- lenge, especially in younger and developmentally de-
quired blindness may give an individual time to grow as layed children. Accuracy of the screening test being ad-
a sighted person and make preparations for life as a ministered to a particular population and expense in
nonsighted person if loss of vision is slow and pre- terms of time, equipment, and personnel are some of
dicted, psychological consequences for the child and the factors that must be considered in screening indi-
family must be addressed. The child blind from birth or viduals and groups. Vision screening is consistent with
 EYE / 461

the recommendations of the American Academy of Pe- toscreening are still being validated. Problems exist with
diatrics (www.aap.org). Risk factors that should be sensitivity and specificity of the instruments, and the
screened for because they interfere with normal visual role of their use in the pediatric population remains a
development and are amblyogenic include media opaci- controversy.
ties, strabismus, and refractive errors that are different
in the two eyes (anisometropia) or of large magnitude Donahue SP et al: Screening for amblyogenic factors using a volun-
in both eyes. teer lay network and the MTI photoscreener: Initial results
The practitioner should have an understanding of from 15,000 preschool children in a statewide effort. Oph-
thalmology 2000;107(9):1637; discussion 1645. [PMID:
the limitations of the screening test being administered. 10964820].
For example, one study cites the sensitivity and speci- Simon JW et al: Vision screening performed by the pediatrician.
ficity of visual acuity screening in preschool children as Pediatr Ann 2001;30:446 [PMID: 11510342].
90% and 44%, respectively. When possible, visual acu-
ity of each eye and alignment of the two eyes should be
assessed. (See Visual Acuity section for acceptable REFERENCES
acuities at different ages.) Two caveats are to be ob- American Academy of Ophthalmology: Orbit, Eyelids and Lacrimal
served when testing monocular visual acuity. First, in System: Basic and Clinical Science Course. Section 7,
an amblyopic patient who demonstrates the crowding 1999–2000.
phenomenon, an amblyopic eye may score better when American Academy of Ophthalmology: Pediatric Ophthalmology
presented with single, isolated targets than with multi- and Strabismus: Basic and Clinical Science Course. Section 6,
2002.
ple targets on a line. Second, monocular visual acuity is
worse in a patient with latent nystagmus. Preschool and Brodsky MC et al: Pediatric Neuro-Ophthalmology. Springer, 1996.
young school-age children often test better when look- Fraunfelder FT, Roy FH (eds): Current Ocular Therapy 5. WB
Saunders, 2002.
ing at a visual acuity chart at a 10-foot distance than at
Isenberg SJ (ed): The Eye in Infancy, 2nd ed. Mosby, 1994.
one placed at 20 feet or when looking into the type of
machine typically used at a motor vehicle department. Nussenblatt RB et al (eds): Uveitis Fundamentals and Clinical Prac-
tice, 2nd ed. Mosby, 1996.
When it is not possible to measure visual acuity or
Olitsky SE, Nelson LB: Common ophthalmologic concerns in in-
assess alignment in the preschool-age group, random fants and children. Pediatr Clin North Am 1998;45:993
dot stereopsis testing (for depth perception) is effective [PMID: 9728197].
in screening for manifest strabismus and amblyopia, Rhee DJ, Pyfer MF (eds): The Wills Eye Manual Office and Emer-
but this test may miss some cases of anisometropic (un- gency Room Diagnosis and Treatment of Eye Disease, 3rd ed.
equal refractive error) amblyopia and small-angle stra- Lippincott Williams & Wilkins, 1999.
bismus. This test is not designed to detect refractive er- Ritch R et al (eds): The Glaucomas, 2nd ed, 3 vols. Mosby, 1996.
rors. Simon J, Calhoun J: A Child’s Eye. Triad, 1998.
An innovative technique that is being used more fre- Tasman W, Jaeger EA (eds): Duane’s Clinical Ophthalmology,
quently in the pediatric age group and may prove useful 6 vols. Lippincott Williams & Wilkins, 1994. (1995 edition
for developmentally delayed children and perhaps in- on CD-ROM.)
fants is photoscreening. Photoscreening relies on the Vaughan DG et al (eds): General Ophthalmology, 15th ed. (Origi-
Brückner test of corneal light reflexes. Photoscreening nally published by Appleton & Lange.) McGraw-Hill, 1999.
does not screen directly for amblyopia but for amblyo- Wright KW, Spiegel PW: Pediatric Ophthalmology and Strabismus.
genic factors, which include strabismus, media opaci- Mosby, 1999.
ties, and refractive errors. Automated methods of pho-
 Oral Medicine & Dentistry 16
William A. Mueller, DMD

The American Academy of Pediatric Dentistry (AAPD) ORAL EXAMINATION OF THE

and the American Academy of Pediatrics recommend NEWBORN & INFANT
that a child’s first oral examination be performed no
later than age 12 months, and optimally within The mouth of the normal newborn is lined with an in-
6 months after eruption of the first tooth. This recom- tact, smooth, moist, and shiny mucosa (Figure 16–1).
mendation is intended to establish the child’s dental The alveolar ridges are continuous and relatively
home and provide an opportunity to implement pre- smooth. Within the alveolar bone are numerous tooth
ventive dental health habits. Because the bacterial infec- buds, which at birth are mostly primary teeth and a few
tion causing dental caries can be acquired as early as age permanent teeth just starting to calcify.
14 months, waiting until age 3 years, which was the
prior recommendation, allows for significant disease Teeth
progression before treatment. Pediatric dentists are
knowledgeable about nursing caries and other types of The primary teeth begin to form at approximately
caries, and their familiarity with the effectiveness of 6 weeks’ gestation, and their calcification starts in the
sealants, fluorides, and cariology makes them the par- second trimester. The permanent teeth are just begin-
ents’ best resource for help in rearing caries-free chil- ning to develop at birth. There is enough development
dren. Some experts have even suggested that infant oral of permanent teeth to permit their damage by perinatal
health begin with prenatal oral health counseling. or antenatal insults such as anoxia, severe jaundice, or
Most oral disease in children is preventable. Oral infection.
evaluation of a child should consist of infant risk assess- The primary teeth usually begin to erupt at approxi-
ment and anticipatory guidance. This approach ad- mately age 6–7 months. However, on rare occasions
vances dental care past tooth monitoring to health pro- (1:2000), teeth are present at birth (natal teeth) or
motion. Infant risk assessment determines the danger erupt within the first month (neonatal teeth). These are
for each child of developing oral disease. Anticipatory most common in the anterior mandible and can be
guidance is directed toward individualized cost-effective “real” primary teeth or supernumerary teeth. These can
use of dental services. Because pediatricians and other be differentiated radiographically. On occasion, these
pediatric health care professionals are far more likely to teeth must be removed to facilitate nursing, heal persis-
encounter new mothers and infants than are dentists, it tent ulceration of the tongue, or eliminate the risk of
is essential that they be aware of the infectious patho- aspiration.
physiology and associated risk factors of early child-
hood dental caries to make appropriate decisions re-
garding effective intervention. Frena
The primary goals for an infant oral health program Noticeable but small maxillary and mandibular labial
are (1) to establish with parents the goals of oral health, frena should be present (Figure 16–2). Several small ac-
(2) to inform parents of their role in reaching these cessory frena may also be present farther posteriorly.
goals, (3) to motivate parents to learn and practice good The extreme is multiple thick tightly bound frena, as in
preventive dental care, and (4) to initiate a long-term oral–facial–digital syndrome. Decisions about if and
dental care relationship with parents. Pediatricians when a labial frenum should be reduced surgically are
should incorporate oral health into anticipatory guid- best left until adolescence. Many thick frena need not
ance either by learning to provide this information in be corrected.
their offices or by referring the child to a pediatric den- The tongue is connected to the floor of the mouth
tal colleague. by the lingual frenum (Figures 16–1 and 16–3). This
462
Copyright © 2005, 2001, by The McGraw-Hill Companies, Inc. Click here for terms of use.
 ORAL MEDICINE & DENTISTRY / 463

Labial frenum (maxillary)

Hard palate

Soft palate
Alveolar ridge

Ventral tongue

Lingual frenum

Labial frenum (mandibular) Figure 16–1. Normal anatomy of

the newborn mouth.

connection should not impede the free movement of Palate

the tongue. If the attachment is tight and high up on
the alveolar ridge (Figure 16–4), it may restrict move- The palate of the newborn should be intact and contin-
ment and cause periodontal damage. This condition is uous from the alveolar ridge anteriorly to the uvula (see
called ankyloglossia (tongue-tie). If it needs to be cor- Figure 16–1). Cleft lip and palate are common defects
rected surgically, earlier (at age 3–4 years) is better than (1:700 live births). The cleft of the palate can be unilat-
later, but there is usually no urgency for surgery in the eral or bilateral (Figure 16–5). The cleft can involve
neonatal period. just the alveolar ridge, as in Figure 16–5, or the ridge

Upper lip

Labial frenum
Buccal frenum

Alveolar ridges

Buccal frenum

Lower lip

Figure 16–2. The frena.

464 / CHAPTER 16

Dental involvement in children with cleft palate is ex-

tensive and is coordinated by the cleft palate team.
Tongue tip
Other Soft Tissue Variations
Lingual frenum
Other minor soft tissue variations can exist in the new-
born mouth. Small (1–2 mm), round, smooth, whitish
Floor of mouth bumps can appear on the alveolar ridges or the palate.
These are keratin cysts and are called Epstein pearls or
dental lamina cysts. They are benign and require no
treatment because they usually disappear.
Some newborns may have small intraoral lymphan-
giomas on the alveolar ridge or the floor of the mouth.
These and any other soft tissue variations that are more
Figure 16–3. Normal position of lingual frenum. noticeable or larger than those just described should be
evaluated by a dentist familiar with neonates.

and entire palate. Clefts can also be isolated soft palate ERUPTION OF THE TEETH
defects. This is common in the Pierre Robin syndrome. Normal Eruption
Cleft palate may also present a submucous cleft, which
may be detected by passing a finger posteriorly along As the child grows and begins to develop teeth, prob-
the midline of the palate. Normally the posterior nasal lems of teething may occur. Primary teeth generally
spine is detectable, but if a submucous cleft is present, a begin to erupt at about age 6 months. They are usually
bony notch will be found. Affected children sometimes mandibular incisors, but can be maxillary, and appear
have a bifid uvula. as early as age 3–4 months or as late as age
Cleft lip and palate rehabilitation requires an exten- 12–16 months. Many side effects are ascribed to
sive program involving many specialties and can be a teething, such as diarrhea, drooling, fever, and rash. But
lifelong endeavor. Children with cleft palate are best any real correlation is doubtful.
treated by a cleft palate team with coordinated care Common treatment for teething pain has been ap-
from relevant specialties. Cleft lip and palate treatment plication of a topical anesthetic or “teething gel.” Most
begins immediately after birth with fabrication of a of these agents contain benzocaine or, less commonly,
palatal obturator as a feeding aid. This appliance also lidocaine. They can cause numbness of the entire oral
helps approximate the alveolar segments in order to fa- cavity and pharynx, and suppression of the gag reflex
cilitate the initial lip repair. In the case of bilateral cleft can be a serious side effect. Systemic analgesia (aceta-
lip and palate, the dentist will often apply extraoral or- minophen or ibuprofen) is safer and more effective.
thopedic traction to guide the protruding premaxilla Solid rubber or chilled fluid-filled teething toys are
back into the oral cavity to facilitate surgical lip closure. beneficial, if only for distraction purposes. Massaging
the gums can be very soothing.
Occasionally, swelling of the gingiva is seen during
teething. This condition can appear as red to purple,
round, raised, smooth lesions that may be symptomatic
but usually are not. They appear in the anterior or pos-
Tongue
terior alveolar ridge and on the crest. These so-called
Frenum eruption cysts or eruption hematomas are fluid-filled
attachment areas immediately overlying an erupting tooth and gen-
Frenum erally disappear spontaneously.
Alveolar ridge
Delayed Eruption
Floor of mouth
Premature loss of a primary tooth can either accelerate
or delay eruption of the underlying secondary tooth.
Early eruption occurs when the permanent tooth is be-
ginning its active eruption and the overlying primary
tooth is removed. This generally occurs when the pri-
Figure 16–4. Ankyloglossia (tongue-tie). mary tooth is within 1 year of its normal exfoliation. If,
 ORAL MEDICINE & DENTISTRY / 465

Frenum

Unilateral Alveolar cleft

Prolabium
Premaxilla

Vomer

Isolated cleft of palate Bilateral Figure 16–5. Types of clefts.

however, loss of the primary tooth occurs more than insufficient room, permanent teeth may erupt abnor-
1 year before expected exfoliation, the permanent tooth mally. In the mandible, lower incisors may be lingually
will probably be delayed in eruption owing to healing placed to such an extent that the primary incisors do
that results in filling in of bone and gingiva over the not exfoliate. The parents’ concern about a “double row
permanent tooth. The loss of a primary tooth may of teeth” may be the reason for the child’s first dental
cause adjacent teeth to tip into the space and lead to visit. If the primary teeth are not loose, they may be re-
impaction of the underlying permanent tooth. A space moved by the dentist; if they are loose, they are gener-
maintainer should be placed by a dentist to avoid this. ally allowed to exfoliate naturally. In the maxilla, inade-
Other local factors delaying or preventing eruption quate room for eruption of the permanent first molar
include supernumerary teeth, cysts, tumors, overre- may cause abnormal resorption of the distal root struc-
tained primary teeth, ankylosed primary teeth, and im- tures of the second primary molar. If the problem is se-
paction. A generalized delay in eruption may be due to vere, the permanent molar may even become caught
endocrinopathies (hypothyroidism, hypopituitarism) or under the unresorbed enamel crown of the deciduous
other systemic conditions (cleidocranial dysplasia, rick- molar and thus require extraction of the primary tooth
ets, trisomy 21). and orthodontic repositioning of the permanent first
molar after it has erupted. If the first molar is not repo-
Ectopic Eruption sitioned, the second premolar is likely to become im-
pacted. If problems are detected early, the dentist may
Ectopic eruption occurs when the position of an erupt- be able to redirect the permanent molar’s eruption
ing tooth is abnormal. In severe instances, the order in pathway so that it erupts correctly and the second pri-
which teeth erupt is affected. If the dental arch provides mary molar is not lost.
466 / CHAPTER 16

Impaction 2. Caries is an infectious disease that is transmissible

and caused by colonization with Streptococcus mu-
Impaction occurs when a tooth is prevented from tans.
erupting for any reason. The teeth most often affected
are the third molars (wisdom teeth) and the maxillary 3. S mutans is transmitted from a mother to her
canines. Patients with impacted third molars are at risk child and detectable by 26 months on average,
for developing odontogenic tumors or dentigerous with a range of 12–36 months.
cysts. The impacted third molar (along with its oppos- 4. Caries is a process present in all individuals. The
ing third molar) may be removed after it has been de- expression of cavities depends on its level of activ-
termined that eruption cannot occur, but this decision ity and the host’s resistance.
may not be possible until the late teens. Impacted max- 5. After establishment of S mutans in the oral cavity,
illary canines should not be extracted because of their caries is a dietary disease.
aesthetic importance and key role in facial development 6. Control of caries before age 3 years is aimed at
and dental occlusion. They can often be brought into limiting the establishment of S mutans by reduc-
correct alignment through surgical exposure and ortho- ing the number of episodes of direct transmission
dontic treatment. from highly infected mothers; reducing dietary
support for S mutans (refined carbohydrates); and
Other Variations ensuring proper levels of fluoride exposure topi-
cally and systemically.
Failure of teeth to develop—a condition sometimes
called congenitally missing teeth—is rare in the primary 7. Control of caries after age 3 years is aimed at lim-
dentition. However, it occurs in about 5% of permanent iting the acidogenesis of oral flora by reducing the
dentitions, with one or more of the third molars missing frequency of carbohydrate ingestion and main-
in about 25% of all individuals. The ones most fre- taining a high frequency of fluoride exposures.
quently missing are maxillary lateral incisors and 8. There is a threshold of caries activity below which
mandibular second premolars. The incidence of congeni- clinical disease does not develop.
tally missing teeth varies among different genetic groups. 9. Caries is largely a disease of poverty; the 29 mil-
Occasionally, extra teeth are present, most typically lion children and adolescents in low-income fami-
an extra (fourth) molar or extra (third) bicuspid. Mesio- lies account for 80% of tooth decay.
dens, which are peg-shaped supernumerary teeth situ-
ated at the maxillary midline that occur in about 5% of
individuals, may interfere with eruption of permanent Teeth can be attacked by acidogenic bacteria, espe-
incisors. Mesiodens should be considered for removal cially S mutans. Dental plaque accumulates on the sur-
even if they do not erupt. face of the teeth as an adherent film. As plaque grows,
bacteria accumulate within it in close proximity to the
tooth. An equally important factor is a substrate for the
DENTAL CARIES & PERIODONTAL bacteria. Carbohydrate—especially a refined carbohy-
DISEASE drate such as sucrose—is the most effective substrate for
The process of tooth decay (caries) and periodontal dis- caries, since bacteria readily metabolize sucrose to pro-
ease are among the most common and easily pre- duce acid. The acidic environment causes the enamel of
ventable of all infectious diseases. Current research is the teeth to dissolve, which is the beginning of caries.
changing the traditional view of dental caries as the After the decay process has penetrated the enamel, there
manifestation of caries activity (eg, “holes in the is very little to keep it from affecting the vital tissues
teeth”). Practitioners are now pursuing the more practi- (nerve) of the tooth. The tooth subsequently becomes
cal objective of diagnosing and treating the caries necrotic, and an abscess occurs (Figure 16–6). This
process in the context of a life continuum, rather than process is not always symptomatic, but it can lead to se-
only as cavitated teeth. The traditional “cavity” is irre- vere pain, fever, and swelling.
versible and requires surgical correction. Filling cavities In the early stages of decay, the tooth may be sensi-
does nothing to address the underlying pathologic tive to temperature changes or, especially, to sweets. At
process that caused them. Prevention, early diagnosis, this point, the tooth can be repaired by removing the
and prompt intervention offer greater efficiency and caries and filling the defect. As the decay progresses,
better health outcomes with lower costs. more pain may be involved, and root canal therapy may
The basic tenets of cariology are be necessary for both primary or permanent teeth.
Once an abscess has formed, with or without swelling, a
1. Caries is the most common chronic disease of choice must be made between root canal therapy and
childhood. removal of the tooth. In the presence of cellulitis or fa-
 ORAL MEDICINE & DENTISTRY / 467

Enamel
Caries Advanced
Dentin caries
Pulp Gingiva

Bone

Periapical
abscess

Figure 16–6. Tooth anatomy and progression of caries.

cial space abscess, extraction is usually the treatment of available to the bacteria. Eliminating refined carbohy-
choice. drates is very effective (low-sugar diets), but limiting ex-
Many people question the importance of the pri- posure to them is also beneficial because each exposure
mary dentition. Baby teeth allow the child to eat prop- produces an acidic environment for up to 30 minutes.
erly, speak properly, have a good self-image, and pre- The form of the substrate is important. Caramels, licorice,
serve the space for the permanent dentition. Premature raisins, gummy bears, and so on are concentrated sugar
loss of primary teeth can cause major orthodontic and with a sticky texture that will remain on the teeth much
dental growth and development problems. longer than the same sugar in liquid form. The primary
care physician can play an invaluable role in disseminat-
ing this information and reinforcing these ideas.
Preventing Dental Caries
To prevent dental caries, it is necessary to remove the bac-
teria on a regular basis. Oral hygiene for the infant should
Fluoride
start at birth. The gums can be cleaned gently with a Fluoride prevents dental caries predominantly after
moist, soft cloth. Once the teeth begin to erupt, oral hy- eruption of the tooth into the mouth. Its actions are
giene must be practiced in earnest. Again, a moist, soft primarily topical for both children and adults. The
cloth can be used after feeding to gently rub the teeth. A mechanisms of action include inhibition of demineral-
very small, very soft toothbrush can be used as well. ization, enhancement of remineralization, and inhibi-
Toothpaste at the start is not necessary but should be tion of bacterial activity in dental plaque. Table
added by age 2 years. Prior to age 6 years parents may 16–1 sets forth the current systemic fluoride dosages to
need to be involved in brushing and flossing. Brushing be administered to children as recommended by the
with a fluoride-containing toothpaste (at least twice daily) American Academy of Pediatrics and the AAPD. It is
and flossing the teeth regularly will minimize the oral important not to exceed these recommendations be-
flora. A second step is to decrease the amount of substrate cause doing so may lead to fluorosis, which is unsightly

Table 16–1. Fluoride dosages administered to children based on

tap water fluoride supply.

Dose of Fluoride Administered

If < 0.3 ppm F in If 0.3–0.6 ppm F in If > 0.6 ppm F in

Age (years) Drinking Water Drinking Water Drinking Water
6 months to 3 years 0.25 mg/d 0 0
3–6 years 0.5 mg/d 0.25 mg/d 0
6–16 years 1 mg/d 0.5 mg/d 0
468 / CHAPTER 16

staining of the permanent teeth. Children from low-in-

come families residing in areas with fluoridated water
Plaque Loss of attachment
incur treatment costs one half less than that for such
accumulation Destruction of bone
children in nonfluoridated areas, and they require less
(gingivitis) (periodontitis)
hospitalization for treatment.
Daily topical fluoride therapy is used in addition to
all other oral hygiene measures in certain high-risk chil-
dren. Children allowed to take their bottle to bed and
those who nurse at will and fall asleep nursing are at
risk for nursing caries. This particular type of decay in-
volves mostly the maxillary incisors. When a child is
lying in bed sucking on a bottle, the contents of the Figure 16–7. Periodontal disease.
bottle are “trapped” between the backs of the front
teeth and the tongue. This allows for more concen-
trated damage to the teeth as the acid produced by bac-
teria fails to dissipate. In addition, as the child falls
asleep, salivary function decreases dramatically. This
further endangers the teeth by eliminating the buffering
OROFACIAL TRAUMA
capacity of saliva and its remineralizing potential. Topi- Orofacial trauma often consists only of abrasions or lac-
cal fluoride may slow the decay process and, combined erations of the lips, gingiva, tongue, or mucosa, includ-
with elimination of high-risk nursing practices and in- ing the frena, without damage to the teeth. Lacerations
stitution of good oral hygiene, can prevent serious den- should be cleansed and inspected for foreign bodies and
tal problems in these infants. sutured if necessary. Occasionally, radiographs of the
Patients with chronically low oral pH may benefit tongue, lips, or cheeks are used to detect tooth frag-
from daily topical fluoride. This patient group includes ments or other foreign bodies.
those with gastroesophageal reflux, bulimia, or salivary Tooth-related trauma can result in displacement
dysfunction from radiation, graft-versus-host disease, or (luxation), fracture, or loss of teeth (avulsion). Figure
autoimmune disease. Saliva is a very effective oral cavity 16–8 demonstrates the different luxation injuries, and
buffer. It also helps remineralize minor enamel dissolu- Figure 16–9 shows the different degrees of tooth frac-
tion. Xerostomia can lead to rampant caries. These chil- ture.
dren need dental care more frequently than healthy chil- The least problematic luxation injury is mobility
dren. Multiply handicapped children who cannot without displacement (subluxation). Unless mobility is
maintain proper oral hygiene can also benefit from addi- extensive, this condition can be followed without active
tional topical fluoride. Any child with a serious medical intervention. An intrusive luxation in the primary den-
problem or disability should be referred to a pediatric tition is usually observed for a period of time to discern
dentist as early as possible, usually before age 1 year. whether the tooth or teeth will reerupt (see Figure
16–8). If this has not occurred after several months or if
Periodontal Disease the area becomes infected, the teeth are usually re-
moved. Permanent teeth may be damaged with any in-
Periodontal disease involves the supporting structures: trusive injury of primary teeth. Permanent teeth intru-
bone, gums, and ligaments. It begins as inflammation sions are corrected with surgical or orthodontic
of the gum tissue adjacent to the tooth. Bacterial accu- repositioning of teeth and placement of a splint for
mulation in the space between the tooth and gum (gin- 10–14 days. Root canal treatment may be necessary
gival sulcus) causes irritation that leads to inflamed tis- later. Lateral and extrusive luxations of permanent teeth
sue. This beginning phase is called gingivitis. As the are generally repositioned and splinted. Severe luxations
inflammation spreads through the sulcus, it involves in any direction in primary teeth are treated with ex-
more soft tissue. Eventually soft tissue destruction and traction.
loss of bone occur as disease spreads toward the apex of Avulsed primary dentition is not replanted. The area
the tooth. This is called periodontitis and requires pro- is investigated for fractured roots or foreign bodies.
fessional cleaning and often medication or surgery for Avulsed permanent teeth are gently cleansed and re-
correction. Figure 16–7 shows the different stages and planted with splinting. If replaced into the alveolar
progression of periodontal disease. bone within 1 hour, the prognosis for these teeth is
The prevention and initial management of peri- good. The prognosis worsens rapidly with increased
odontal disease in children involves removal of bacteria time outside of the mouth. Hank solution is the best
from the teeth with proper oral hygiene. storage and transport medium for avulsed teeth that
 ORAL MEDICINE & DENTISTRY / 469

cause of condylar fracture in the pediatric population.

Condylar fracture should be suspected when pain or
deviation occurs when the jaw is opened.

DENTAL EMERGENCIES
Dental emergencies other than trauma are usually asso-
ciated with pain or swelling due to advanced caries.
Odontogenic pain usually responds to acetaminophen,
Normal Intrusive ibuprofen, codeine, or, in severe cases, hydrocodone. As
with teething, topical application of medicaments is of
limited value.
Swelling confined to the gum tissue above or below
the tooth is usually not an urgent situation. This “gum-
boil” or parulis represents infection that has spread out-
ward from the root of the tooth through the bone and
periosteum into the gum. Usually it will begin to drain
and leave a fistulous tract. If the infection invades the
facial spaces, cellulitis can occur. Swelling of the mid-
face—especially the bridge of the nose and the lower
eyelid—should be urgently evaluated as a potential
Extrusive Avulsion dental infection. Extraction of teeth or root canal ther-
apy combined with antibiotics is the usual treatment.
Figure 16–8. Patterns of luxation injuries. With extensive facial cellulitis, many young children re-
quire hospitalization and intravenous antibiotics.

will be replanted. Milk or saline can be used if Hank ANTIBIOTICS IN PEDIATRIC DENTISTRY
solution is not accessible.
All luxated and replanted teeth need to be followed The antibiotics of choice for odontogenic infection are
carefully and regularly by a dentist. These teeth can be- amoxicillin and clindamycin. Several patient groups re-
come abscessed or fused to the bone (ankylosed) at any quire prophylactic antibiotic coverage prior to any inva-
time during the healing process. sive dental manipulation, including tooth cleaning.
A patient with fractured teeth should be seen Children with heart diseases that place them at risk for
promptly by a dentist. Fractured teeth need to be pro- subacute bacterial endocarditis head this list. Some im-
tected quickly to avoid sensitivity, pain, or infection of munosuppressed patients also receive coverage during
exposed pulp. Severe fracture may require immediate dental procedures. Although there is some controversy
root canal surgery. regarding the need for antibiotics in children with in-
All facial trauma needs to be evaluated for jaw frac- dwelling central venous catheters (eg, Broviac, Quin-
ture. Blows to the chin are among the most common ton, Hickman, and other lines), some experts medicate
childhood orofacial traumas. They are also a leading them prior to invasive dental treatment.
Children with a ventriculoperitoneal shunt should
not receive prophylaxis because there is no circulatory
connection to such a shunt.

SPECIAL PATIENT POPULATIONS

Children with Cancer
Exposed pulp Children with cancer should be evaluated by a dentist
Enamel only
(uncomplicated)
(complicated) knowledgeable about pediatric oncology soon after di-
agnosis. The aim is to eliminate all existing and poten-
Enamel and dentin tial sources of infection before the child receives
(uncomplicated) chemotherapy and becomes neutropenic. Areas of con-
cern include abscessed teeth, teeth with extensive caries,
Figure 16–9. Patterns of crown fractures. teeth that will soon exfoliate, ragged or broken teeth or
470 / CHAPTER 16

fillings, and orthodontic appliances. Once chemother- local anesthesia, even for simple fillings) (see Chapter
apy begins, there is a brief interval before its myelosup- 27). Some patients with very mild factor VIII defi-
pressive effects reach their nadir (7–14 days). Once the ciency or von Willebrand disease may respond to
child becomes neutropenic, abscessed, infected, or se- desmopressin acetate. Antifibrinolytic medications such
verely carious teeth can no longer be considered inno- as aminocaproic acid and tranexamic acid are used suc-
cent, even if asymptomatic. A loose tooth that will soon cessfully after dental treatment. Postoperative bleeding
exfoliate can become a nidus for infection as well as a can also be treated with a wide variety of topical
cause of bleeding for a thrombocytopenic patient. medicaments, such as Gelfoam and thrombin.
Sharp, ragged teeth can be an irritation that leads to in- The pediatric patient receiving anticoagulant ther-
fection. Chemotherapeutic drugs and local irradiation apy must undergo dosage adjustment before invasive
are cytotoxic to the oral mucosa, which becomes at- dental treatment. This is a relatively simple matter
rophic and ulcerates with ease (mucositis). This is when dealing with heparin, with its short half-life of
painful and often leads to inadequate oral intake and 4–6 hours. It is a much more difficult problem with
nutrition. Once the mucosal barrier is breached by ul- warfarin, which has a half-life of 40–70 hours.
ceration, the patient can become septic, especially with
α-hemolytic streptococci and other mouth flora. Her-
pes simplex virus is another pathogen that can enhance Children with Diabetes
drug-induced mucositis. Friction and damage to the Children who are insulin-dependent are prone to den-
mucosa is the main concern with braces. Therefore, all tal problems. They have an impaired capacity to heal, a
orthodontic hardware is removed prior to chemother- higher incidence of periodontal disease, and a higher
apy. caries rate. These children need to be followed carefully
The pediatric oncology patient should be monitored on a routine basis. Care must be taken not to disturb
throughout therapy to screen for infection, manage oral the regular cycle of eating and insulin dosage. Anxiety
bleeding, and control oral pain. These children can ex- associated with dental appointments can cause a major
perience spontaneous oral hemorrhaging, especially upset in the diabetic child’s routine. Postoperative pain
when the platelet count is below 20,000/mL. Poor oral or pain from dental abscess can prevent them from eat-
hygiene or areas of irritation can increase the chances of ing. Warnings about eating until the numbness wears
bleeding. off or until the filling gets hard can also alter their nor-
Children receiving radiation therapy to the head and mal schedule of food intake and insulin dosage. Insulin
neck are prone to develop extensive salivary dysfunction levels must be adjusted to conform to treatment needs
(xerostomia) when salivary tissue is in the path of the and vice versa.
primary beam of radiation. Xerostomia should be man-
aged aggressively to avoid rapid extensive destruction of
dentition. Customized fluoride applicators are used in
this situation in combination with close follow-up.
MATERNAL–FETAL RELATIONSHIP
Children undergoing bone marrow transplantation In addition to the discovery that childhood caries is an
may have acute graft-versus-host reaction as another infectious disease transmitted by bacteria from the
contributor to severe oral mucositis. Long-term follow- mother to the child, a number of other maternal–fetal
up includes managing salivary dysfunction from total relationships related to the oral cavity have been identi-
body radiation and treatment of oral graft-versus-host fied. A recent large prospective study has shown a sig-
disease. nificant association between maternal periodontitis at
The pediatric oncology patient also needs to be fol- 21–24 weeks’ gestation and preterm birth. It is un-
lowed by a dentist who is familiar with young children known whether treatment of periodontitis will reduce
and their growth and development. Oral and maxillofa- the risk of preterm birth.
cial growth disturbances can occur after therapy. Late The risk of preterm birth is elevated if a mother
effects of therapy include morphologic changes in tooth smokes and is of low socioeconomic status, both of
development (microdontia or extensive hypocalcifica- which also increase the risk for periodontitis. Second-
tion) and disturbances in eruption (blunted roots or de- hand or passive smoke also increases the risk of caries in
layed eruption). children who grow up around smokers. This associa-
tion is independent of age, family income, geographic
region, and frequency of dental visits.
Children with Hematologic Problems Given the known association between maternal peri-
The child with hemophilia needs to have the appropri- odontitis and preterm birth, passive smoke and chil-
ate clotting factor provided before and after any inva- dren’s dental caries, and the knowledge of maternal
sive dental procedures (including the administration of transmission of caries-causing bacteria, it is important
 ORAL MEDICINE & DENTISTRY / 471

to advise expectant teenage mothers about these risk and development. Most pediatric dentists will want to
factors. see a child for a first visit by age 12 months. The aver-
Moreover, low-birth-weight, preterm children have age child should be seen every 6 months for dental fol-
a greater predisposition to many oral developmental low-up. Any child with additional risk factors should be
anomalies than normal-birth-weight children. These seen earlier and more frequently.
include generalized enamel hypoplasia associated with
increased predisposition to early childhood caries, local- REFERENCES
ized enamel hypoplasia, crown dilaceration of the max-
illary left incisors, and palatal deformations associated Hale KJ, American Academy of Pediatrics Section on Pediatric
with laryngoscopy and endotracheal intubation. Dental Dentistry: Oral health risk assessment timing and establish-
ment of the dental home. Pediatrics 2003;111:1113 [PMID:
development in preterm infants is retarded in the erup- 12728101].
tion of the primary dentition and in the development Jeffcoat M et al: Periodontal infection and preterm birth: Results of
of the permanent teeth. a prospective study. J Am Dent Assoc 2001;132:875 [PMID:
11480640].
Seow W et al: A controlled study of the morphometric changes in
DENTAL REFERRAL the primary dentition of pre-term, very-low-birthweight chil-
Referral to a dentist is appropriate whenever there is a dren. J Dent Res 2000;79:63 [PMID: 10690662].
question about a child’s oral and maxillofacial health
 Ear, Nose, & Throat 17
Candice E. Johnson, MD, PhD, Peggy Kelley, MD, & Norman R. Friedman, MD

with otitis externa secondary to draining tubes or perfo-

I. THE EAR rations should be treated with topical therapy only in
the absence of systemic symptoms. The topical therapy
chosen must be safe for the inner ear because the perfo-
INFECTIONS OF THE EAR ration or the patent tube allows the drops access to the
middle and inner ear. Safe drops, such as fluoro-
The spectrum of ear diseases includes the structures of quinolone drops, have no aminoglycoside or toxic
the outer ear (otitis externa), the middle ear (acute otitis preservatives. Once the ear canal is open, instill antibi-
media), the mastoid bone (mastoiditis), and the inner otic ear drops two or three times daily. A corticosteroid
ear (labyrinthitis). may reduce the inflammatory response, but this is de-
bated. If the canal is too edematous to allow the ear
1. Otitis Externa drop to get in, an ear wick for the first few days may be
helpful. Oral antibiotics are indicated if any signs of in-
Otitis externa is inflammation of the skin lining the ear vasive infection, such as fever, cellulitis of the auricles,
canal and surrounding soft tissue. The most common or tender postauricular lymph nodes, are present. Pre-
cause is loss of the protective function of cerumen, lead- scribe an antistaphylococcal antibiotic while awaiting
ing to maceration of the underlying skin. Other causes the results of culture of the ear canal discharge. Sys-
are trauma to the ear canal from using cotton-tipped temic antibiotics alone without topical treatment will
applicators for cleaning or from using poorly fitted ear not clear up otitis externa. Analgesics may be required
plugs while swimming; contact dermatitis due to hair temporarily.
sprays, perfumes, or self-administered ear drops; sec- During the acute phase, the patient should avoid
ondary infection of the canal from otitis media with a swimming. A cotton ear plug is not helpful and may
patent tympanostomy tube; and chronic drainage from prolong the infection. Schedule a follow-up visit in
a perforated tympanic membrane (TM). Infections due 1 week to document an intact tympanic membrane
to Staphylococcus aureus or Pseudomonas aeruginosa are (Figure 17–1). Children who have intact TMs and are
the most common. predisposed to this problem should receive 2 or 3 drops
Symptoms include pain and itching in the ear, espe- of a 1:1 solution of white vinegar and 70% ethyl alco-
cially with chewing or pressure on the tragus. Move- hol into the ears before and after swimming.
ment of the pinna or tragus causes considerable pain.
Drainage may be minimal unless the otitis externa is
from a draining PE tube or TM perforation. The ear Hannley MT et al: Use of ototopical antibiotics in treating 3 com-
canal may be grossly swollen, and the patient may resist mon ear diseases. Otolaryngol Head Neck Surg 2000;6:934
any attempt to insert an ear speculum. Debris is notice- [PMID: 10828818].
able in the canal. It is often impossible to visualize the Hughes E, Lee JH: Otitis externa. Pediatr Rev 2001;22:191
TM. Hearing is normal unless complete occlusion has [PMID:11389206 ].
occurred.
2. Otitis Media
Treatment
Classification & Clinical Findings
Topical treatment usually suffices. The crucial initial
step is removal of desquamated epithelium and moist Otitis media is an infection associated with middle ear
cerumen. This debris can be irrigated out or suctioned effusion (a collection of fluid in the middle ear space)
out using warm Burow solution (one packet of Dome- or with otorrhea (a discharge from the ear through a
boro powder [aluminum acetate and acetic acid] to perforation in the TM or a ventilating tube). Otitis
250 mL tap water) or normal saline, as long as it is media can be further classified by its associated clinical
known that the TM is intact. If the TM cannot be seen, symptoms, otoscopic findings, duration, frequency, and
then a perforation may be presumed to exist. Children complications. These more specific classifications are
472
Copyright © 2005, 2001, by The McGraw-Hill Companies, Inc. Click here for terms of use.
 EAR, NOSE, & THROAT / 473

Right Tympanic Membrane

Otoscopic View Lateral View

(Nose is to right) Attic

Pars flaccida

Short process of malleus

Chorda tympani

Incus

Umbo

Pars tensa

Figure 17–1. Tympanic membrane.

acute otitis media, otitis media with effusion, and mild or a moderate conductive hearing impairment of
chronic suppurative otitis media. 15 dB or higher. OME can also be associated with neg-
ative middle ear pressure, which results in prominence
A. ACUTE OTITIS MEDIA of the malleus and a negative pressure peak on tympa-
Acute otitis media (AOM) is commonly defined as in- nometry.
flammation of the middle ear resulting in an effusion
and associated with rapid onset of symptoms such as C. CHRONIC SUPPURATIVE OTITIS MEDIA
otalgia, fever, irritability, anorexia, or vomiting. An ear This type of otitis media is defined as persistent otor-
effusion is best documented by pneumatic otoscopy or rhea lasting longer than 6 weeks. Most often it occurs
tympanometry. To distinguish AOM from otitis media in children with tympanostomy tubes or TM perfora-
with effusion (OME), signs of inflammation of the TM tions. Occasionally, it is an accompanying sign of
or symptoms of acute infection must be present. Oto- cholesteatoma. Organisms commonly isolated are
scopic findings specific for AOM are a bulging TM; Pseudomonas aeruginosa and Staphylococcus aureus, but
impaired visibility of the ossicular landmarks; a yellow, fungi and anaerobic bacteria may also play a role.
white, or bright red color; opacification of the eardrum;
and squamous exudate or bullae on the eardrum. OME Pathogenesis of Acute Otitis Media
is associated with a nonbulging eardrum, which may be
retracted or neutral, but always has decreased mobility, Factors that make otitis media more common in chil-
may have opacification, and may have white or amber dren than in adults include bacterial nasopharyngeal
discoloration. Children with OME may develop acute colonization in the absence of antibody, frequent upper
infection, but they will then exhibit inflammation of respiratory infections (URI), exposure to parental ciga-
the eardrum as described for AOM. rette smoke, unfavorable eustachian tube function, and
allergies.
B. OTITIS MEDIA WITH EFFUSION
Otitis media with effusion is defined as an asympto- A. BACTERIAL COLONIZATION
matic middle ear effusion that often follows AOM, but Nasopharyngeal colonization with Streptococcus pneu-
may have no such antecedent history. Otoscopic find- moniae, Haemophilus influenzae, or Moraxella ca-
ings that suggest OME include visualization of tarrhalis increases the risk of otitis media. Colonization
air–fluid levels or bubbles, and a clear or amber middle with normal flora such as viridans streptococci may pre-
ear fluid. Effusion is usually associated with either a vent otitis episodes by inhibiting the growth of these
474 / CHAPTER 17

pathogens, and a nasal spray of viridans streptococci is G. GENETIC SUSCEPTIBILITY

under study. Colonization usually occurs sequentially Although we know AOM to be multifactorial, and no
with different serotypes of pathogen, and there is a risk gene for susceptibility has yet been identified, recent
of AOM with each new serotype acquired. Infants in studies of twins and triplets suggest that as much as
daycare acquire these serotypes at a younger age than 70% of the risk is genetically determined. This has im-
those in home care. Since younger children are at plications for the subsequent offspring of parents with a
higher risk of AOM, the increased number of children child experiencing recurrent AOM. These families
in daycare over the last 3 decades has played a major might wish to consider breast-feeding and home care
role in the increase in AOM. for later children.
B. VIRAL UPPER RESPIRATORY INFECTIONS
These infections increase the colonization of the na-
sopharynx with otitis pathogens, perhaps because of in-
Microbiology of Acute Otitis Media
creased adherence to the mucosa. Viral infection also The role of respiratory viral infection in precipitating
impairs eustachian tube function by adenoidal swelling otitis media is unquestionable, yet fewer that 12% of
and edema. Therefore, factors that increase the fre- ear effusions grow viruses. Recent studies with sensitive
quency of viral respiratory infections, such as child care viral antigen or nucleic acid tests have detected virus in
attendance, smoke exposure, later birth order, and ab- over 40% of infected ears. The viral infection may pre-
sence of breast-feeding, promote colonization with oti- cede the bacterial otitis media by 3–14 days and pre-
tis pathogens and predispose to otitis. sumably causes adenoid hypertrophy and eustachian
tube dysfunction. The two viruses most clearly shown
C. SMOKE EXPOSURE to precipitate otitis media are respiratory syncytial virus
Passive smoking increases the risk of persistent middle and influenza, accounting for the annual surge in otitis
ear effusion by enhancing attachment of the pathogen, media cases in January to April in temperate climates.
prolonging the inflammatory response, and impeding About 50% of AOM in the Midwestern and north-
drainage through the eustachian tube. For infants age eastern United States is due to S pneumoniae, while the
12–18 months, exposure to each additional pack of cig- warmer, drier climates of southern Israel and Denver
arettes smoked at home is associated with an 11% in- report a preponderance of nontypable H influenzae—
crease in the duration of a middle ear effusion. the same two organisms most frequently associated
with sinusitis. Another pathogen, M catarrhalis, may
D. EUSTACHIAN TUBE DYSFUNCTION cause up to 25% of AOM in colder climates, but is
Infants born with craniofacial disorders, such as Down much less common in Denver and southern Israel, pos-
syndrome or a cleft palate, are often affected by AOM sibly because of the drier, hotter climate (Table 17–1).
and OME. The patency of the tube allows aeration of The fourth organism found is Streptococcus pyogenes;
the middle ear. When the tube is obstructed, a vacuum this organism and S pneumoniae are the predominant
develops, which can pull nasopharyngeal secretions into causes of mastoiditis. The microbiologic causes of
the middle ear. AOM in early infancy differ only slightly from those in
later life. The risk of gram-negative enteric infection is
E. HOST IMMUNE DEFENSES increased in infants younger than age 4 weeks who are
Immunocompromised children usually experience re- or have been hospitalized in a neonatal intensive care
current AOM and sinusitis, as well as pneumonia. nursery.
However, children who experience recurrent or persis- Resistant S pneumoniae is a common pathogen in
tent otitis may have selective impairments of immune acute otitis, representing up to 40% of isolates, as well
defenses against specific otitis pathogens. For example, as in persistent effusions and chronic suppurative otitis.
a recent study showed some such children have low-to- Children with resistant strains tend to be younger and
absent IgG2 or IgA pneumococcal polysaccharide anti- to have had more unresponsive infections. Antibiotic
body responses (or both) after vaccination, despite nor- treatment in the preceding 3 months also increases the
mal serum levels of total IgG2 and IgA. risk of harboring resistant pathogens. Penicillin resis-
tance develops through stepwise mutations in the struc-
F. BREAST-FEEDING ture of the penicillin-binding proteins. Strains for
Breast-feeding reduces the incidence of acute respira- which minimum inhibitory concentrations (MICs) of
tory infections, provides IgA antibodies that reduce col- penicillin range between 0.12 and 1.0 µg/mL are said
onization with otitis pathogens, and decreases the aspi- to exhibit “intermediate” resistance. Strains for which
ration of contaminated secretions into the middle ear MICs are equal to or higher than 2 µg/mL are said to
space. have a “high-level resistance.” The prevalence of resis-
 EAR, NOSE, & THROAT / 475

Table 17–1. Bacteriology of acute otitis media in two U.S. cities and Israel.

Minneapolis, MN Southern Israel

(Personal correspondence)a (Lebowitz and Dagan)b Denver, CO (Author)a
Streptococcus pneumoniae 49 22 23
Haemophilus influenzae 14 30 37
Moraxella catarrhalis 14 4 5
Streptococcus pyogenes 5 3 3
S pneumoniae + H influenzae Not reported 14 3
Staphylococcus aureus or other 6 0 0
No growth 6 30 28
a
Unpublished data. Updated 1998–2002.
b
Dagan R et al: Bacteriologic efficacies of oral azithromycin and oral cefaclor in treatment of acute otitis media in infants and young chil-
dren. Antimicrob Agents Chemother 2000;44:43.

tant strains no longer varies significantly among geo- ear speculum helps to create an adequate pneumatic
graphic areas within the United States. These strains are seal. The tubing should fit snugly on the speculum at a
also resistant to other drug classes. Approximate rates of distance about 0.5 cm from its end. The largest possible
resistance are 60% for trimethoprim–sulfamethoxazole, speculum (usually 3 or 4 mm) should be used to maxi-
15% for macrolides, and 2% for amoxicillin (dosed at mize the field of view, avoiding disposable specula if
90 mg/kg/d). Between 90% and 100% of highly peni- possible. When the rubber bulb is squeezed, the TM
cillin-resistant strains are susceptible to clindamycin will move freely to and fro if no fluid is present; if fluid
and rifampin, and 97% are susceptible to fluro- is present in the middle ear space, the mobility of the
quinolones. Second-generation fluroquinolones such as TM will be absent or resemble a fluid wave. The ability
ciprofloxacin and norfloxacin are much less active to assess mobility is compromised by low light inten-
against S pneumoniae than are the third-generation sity; a halogen source is necessary. These bulbs dim, but
agents such as gatifloxacin and levofloxacin. Unfortu- rarely ever “burn out.”
nately, fluroquinolones are not approved for children Disposable ear specula have become popular but are
younger than 16 years; however, studies are under way not needed for infection control, because reusable spec-
to assess their safety and efficacy in this age group. ula can be easily disinfected. The disposable specula are
sharp at the tip and often cause pain when pushed to
Diagnosis get an airtight seal.
A. PNEUMATIC OTOSCOPY B. CERUMEN REMOVAL
Acute otitis media is overdiagnosed. Contributing to Cerumen removal is an essential skill for anyone who
errors in diagnosis are the temptation to accept the di- cares for children. Impacted cerumen can cause itching,
agnosis without removing enough cerumen to ade- pain, hearing loss, or otitis externa. Parents should be
quately visualize the eardrum, and the mistaken belief advised that earwax protects the ear (cerumen contains
that a red eardrum establishes the diagnosis. In fact, lysozymes and immunoglobulins that inhibit infection)
redness of the eardrum can be caused by a viral URI, and will come out by itself; therefore, parents should
the child’s crying, or even efforts to remove cerumen. never put anything solid into the ear canal to remove
Failure to achieve an adequate seal with the otoscope, the earwax. Eardrops (discussed later) may be used.
poor visualization due to low light intensity, and mis- The physician may remove cerumen under direct vi-
taking the ear canal wall for the membrane can make it sion through the operating head of an otoscope, pro-
difficult to assess eardrum mobility. vided two adults are present to hold the child. Ceru-
A pneumatic otoscope with a rubber suction bulb men that obstructs the view of the TM can often be
and tube is used to assess mobility of the TM. The pushed aside, the pneumatic seal reestablished, and mo-
speculum inserted into the patient’s ear canal must be bility assessed without removing the speculum. Alterna-
large enough to provide an airtight seal. Placing a piece tively, a plastic disposable ear curette of about size
of rubber tubing 0.25–0.5 cm wide near the end of the 0 (often green) may be used.
476 / CHAPTER 17

Irrigation can also be used to remove cerumen. Very quired before this method can be recommended, and
hard cerumen may adhere to the wall of the ear canal the instrument is presently not being sold.
and cause pain or bleeding if one attempts to remove it
with a curette. This type of wax can be softened with
carbamyl peroxide solutions, mineral oil, or a few drops Treatment of Acute Otitis Media
of detergent before irrigation is attempted. After An algorithm for the management of AOM is pre-
20 minutes, irrigation with a soft bulb syringe can be sented in Figure 17–3. Drugs commonly used are listed
started with water warmed to 35–38°C to prevent ver- in Table 17–2.
tigo. A commercial jet tooth cleanser (eg, Water Pik) is
also an excellent device for removing cerumen, but it is
important to set it at low power (2 or less) to prevent A. THE OBSERVATION OPTION
damage to the TM. A perforated TM is a contraindica- Nontreatment: Few issues in clinical medicine are as
tion to any form of irrigation. In difficult cases, it may controversial as antibiotic treatment of otitis media, be-
be necessary to consult an otolaryngologist. cause of the increasing prevalence of resistant organisms
since 1990 and questions about how to measure effi-
C. TYMPANOMETRY cacy. The natural history of AOM is that it improves
clinically through host defenses; however, bacteriologic
Tympanometry can identify an effusion, and it requires
cure rates (determined by a second tympanocentesis
little training. It should supplement and not replace
while on therapy) were only 32% at 2–7 days on
pneumatic otoscopy because it does not identify in-
placebo in Dr Howie’s classic studies. In children re-
flammation. Because of the compliance of the cartilagi-
ceiving a placebo, the cure rate is 16% for S pneumo-
nous canal of the infants, tympanometry should be
niae, 84% for M catarrhalis, and 50% for nontypable
reserved for children older than age 6 months. Tympa-
H influenzae. Therefore, the absence of overt symptoms
nometry uses an electroacoustic impedance bridge to
does not necessarily mean that the bacterial infection
measure TM compliance and display it in graphic form
has been cured. In a meta-analysis of 33 trials of antibi-
(along the y-axis, expressed in mm H2O). Compliance
otic treatment of AOM, only 4 trials contained a
is determined at air pressures from +200 to –400 mm
placebo. Eighty-one percent of patients who received a
H2O that are created in the sealed external ear canal.
placebo became asymptomatic by 7–14 days, and treat-
The existing middle ear pressure can be measured by
ment with antibiotics increased the resolution rate by
determining the ear canal pressure at which the TM is
14%. This study has led to the assertion that seven chil-
most compliant. Because total visualization of the TM
dren must be treated with antibiotics to benefit one
is not necessary, tympanometry does not require re-
child. However, the age group younger than 2 years,
moval of cerumen unless the canal is completely
who experience the highest rate of AOM, were barely
blocked.
included in this meta-analysis. Although most clinicians
Tympanograms can be classified into four major
routinely treat acute otitis with antibiotics, it is also rea-
patterns, as shown in Figure 17–2. The pattern shown
sonable to individualize this decision and involve the
in Figure 17–2A, characterized by maximum compli-
family in the process. This calls for a trade-off between
ance at normal atmospheric pressure, indicates a nor-
the risks of antibiotic treatment (allergic reactions, side
mal TM, good eustachian tube function, and absence
effects, and colonization with an antibiotic-resistant
of effusion. The pattern shown in Figure 17–2B identi-
pathogen) and the benefit of a more rapid clinical re-
fies a nonmobile TM, which indicates middle ear effu-
sponse. More rapid pain relief may be a reasonable jus-
sion. The pattern shown in Figure 17–2C indicates an
tification for treatment. Patients not receiving treat-
intact mobile TM with poor eustachian tube function
ment who fail to improve within 48 to 72 hours should
and excessive negative pressure (> –300 mm H2O air
be reassessed and given antibiotics if symptoms of
pressure) in the middle ear. Figure 17–2D shows a flat
AOM are still present. It is advisable to treat otitis
tracing, which would have a very large middle ear vol-
media in all children younger than age 2 years with an-
ume on the printout, due to a patent tube or large per-
tibiotics because they respond less well to bacterial
foration.
polysaccharide and are more likely to develop complica-
tions. Of three recent studies of placebo compared with
D. ACOUSTIC REFLECTOMETRY antibiotics in children younger than 2 years, clinical
Acoustic reflectometry measures the spectral gradient of cure rates were 28–42% with placebo and 41–74%
the TM using a handheld instrument, without requir- with an antibiotic.
ing an airtight seal. However, recent data suggest that One can avoid the antibiotic treatment dilemma by
this method cannot reliably distinguish negative middle not overdiagnosing AOM. To summarize, to accurately
ear pressure from effusion. Much more study is re- diagnose otitis media, cerumen must first be thor-
 EAR, NOSE, & THROAT / 477

A B
+200 +200
1.5 1.5

2 2
Compliance (mmho)

Compliance (mmho)
1.0 1.0
1 1

0.5 0.5

0.0 0.0
-400 -200 0 +200 -400 -200 0 +200
Pressure — daPa Pressure — daPa

C D
+200 +200
1.5 1.5

2 2
Compliance (mmho)

Compliance (mmho)

1.0 1.0
1 1

0.5 0.5

0.0 0.0
-400 -200 0 +200 -400 -200 0 +200
Pressure — daPa Pressure — daPa

Figure 17–2. Four types of tympanograms obtained with Welch–Allyn MicroTymp 2. A: Normal middle ear. B: Oti-
tis media with effusion or acute otitis media. C: Negative middle ear pressure due to eustachian tube dysfunction. D:
Patent tympanostomy tube or perforation in the tympanic membrane. Same as B except for a very large middle ear
volume.

oughly removed. Pneumatic otoscopy is mandatory to in adults. Studies have shown that increasing the dosage
avoid misinterpreting red ears. from 40 mg/kg to 90 mg/kg yields a drug concentra-
tion in middle ear fluid that surpasses the minimal level
B. ANTIBIOTIC THERAPY needed to inhibit 98% of all pneumococcal otitis
Amoxicillin remains the first-line antibiotic for treating media. A second advantage is that dosing amoxicillin at
otitis media, even with a high prevalence of drug-resis- these higher levels may help delay stepwise emergence
tant S pneumoniae, because resistance to β-lactam an- of resistance. In recognition of this new pharmacody-
tibiotics, such as amoxicillin, develops as a stepwise namic data, the federal government in June 1999 dou-
process over many years. A bacterial strain resistant to bled the MIC used to define resistance to amoxicillin to
low levels of amoxicillin will usually be eradicated by a 8 µg/mL or greater. Because otitis media is not a life-
higher dosage. Amoxicillin dosage may be raised con- threatening disease, it is not necessary for a first-line an-
siderably without toxicity; for example, a dosage of tibiotic to achieve 100% cure. High-dose amoxicillin
200 mg/kg/d has been used to treat meningitis in chil- will usually eradicate the most invasive pathogen, S
dren, and a maximum daily dose of 4 g has been used pneumoniae, and if no improvement occurs, a second-
 Acute Otitis Media (AOM)

Treat with first-line antibiotic

Unresponsive AOM after 3 days Responding

Re-treat with second Reexamine 3–6 weeks later

line antibiotic

Otitis media with residual effusion (OME) Resolved AOM

Unresponsive AOM Resolved AOM

Evaulate monthly by pneumatic

Diagnostic tympanocentesis otoscopy or tympanometry
Superimposed AOM episode
478

Re-treat according to
bacterial sensitivities No AOM episodes
Refer to ENT

OME at 3 months Resolved OME

Speech and Audiology Evaluation

Speech delay, marked hearing Normal speech

deficit or higher risk social situation

Re-evaluate every 6 weeks

Refer to otolaryngologist for ventilating

OME at 6 months Resolved OME
tubes and/or adenoidectomy

Figure 17–3. Algorithm for acute otitis media. AOM = acute otits media; ENT = ear, nose, and throat consult; OME = otitis media with effusion.
 EAR, NOSE, & THROAT / 479

Table 17–2. Treatment of acute otitis media in an penicillin-resistant pneumococci, only the intermedi-
era of drug resistance. ately resistant class. Of these three drugs, only cefdinir
is palatable in the liquid form; the other two drugs have
First-line therapy a bitter aftertaste which is difficult, but not impossible,
1. Amoxicillin 90 mg/kg/d, up to 4 g d. For children over to conceal with milk or sweet food given after the drug.
2 years of age, give for 5 days; under 2 years of age, for A second-line agent is also indicated when a child expe-
10 days. riences symptomatic infection within 1 month of stop-
2. If amoxicillin has caused a rash, give cefuroxime (Ceftin), ping amoxicillin; however, repeat use of high-dose
cefdinir (Omnicef), or cefpodoxime (vantin). amoxicillin is indicated if more than 4 weeks has passed
3. If urticaria or other IgE-mediated events have occurred, without symptoms, because a new pathogen is usually
give trimethoprim-sulfa or azithromycin (Zithromax). present. Macrolides and sulfonamides are not recom-
4. If the child is unable to take oral medication, give single in- mended as second-line agents due to poor coverage of
tramuscular dose of ceftriaxone (Rocephin). H influenzae. The major use of these drug classes is in
Second-line therapy children with urticaria or anaphylactic reactions to β-
This is for clinical failure after 48–72 hours of treatment, or for lactams.
recurrences within 4 weeks. If a child remains symptomatic longer than 3 days
1. Amoxicillin-clavulanate (Augmentin ES-600), given so that while taking a second-line agent, a tympanocentesis
the patient receives amoxicillin at 90 mg/kg/d. may be useful to identify the causative pathogen or to
2. If amoxicillin has caused allergic symptoms, see recom- prove sterility. The parents may be noncompliant or
mendations above. the child may not have absorbed the antibiotic well, in
which case an organism sensitive to many drugs may be
Third-line therapy
found. If a highly resistant pneumococcus is found or if
1. Tympanocentesis is recommended to determine the
cause.
tympanocentesis is not feasible, intramuscular ceftriax-
2. Ceftriaxone (Rocephin), two doses given intramuscularly, one at 50 mg/kg/day for 3 consecutive days is the best
48 hours apart, with the option of a third dose. choice. Further studies are needed in children failing
second-line therapy. Table 17–2 also lists alternative
Recurrences > 4 weeks after the first episode drugs for penicillin-allergic children. If the child has ex-
1. A new pathogen is likely, so restart first-line therapy. perienced anaphylaxis to amoxicillin, cephalosporins
2. Be sure the diagnosis is not OM with effusion (OME), which should not be substituted. However, the maculopapular
may be observed for 3–6 months without treatment. rash frequently seen with amoxicillin is not IgE-medi-
ated, and cephalosporins may be used.
Figure 17–3 shows the recommended follow-up of
AOM that resolves with a residual effusion at
line antibiotic may be chosen to cover M catarrhalis and 3–4 weeks. Children, particularly those young enough
β-lactamase-producing H influenzae. to still be developing language skills, should be seen
Amoxicillin–clavulanate enhanced strength (ES), every 8 weeks for otoscopic exams to determine if the
with 90 mg/kg/d of amoxicillin dosing and unchanged effusion is persistent or occurs only with symptomatic
amounts of clavulanic acid, is an appropriate choice as a infections. Prophylactic antibiotics and corticosteroids
second-line antibiotic when a child is clinically failing are no longer recommended for OME. A hearing test
after 48 to 72 hours on amoxicillin (see Table 17–2). If should be performed after approximately 3 months of
generic dosing is preferred to reduce costs, two pre- continuous bilateral effusion in children younger than
scriptions are required: low-dose amoxicillin–clavu- 3 years and those at risk of language delay due to
lanate and 45 mg/kg of amoxicillin. The generic amoxi- poverty or craniofacial anomalies. Children with hear-
cillin–clavulanate should never be doubled in dosage, ing loss or speech delay should be referred to an oto-
since the amount of clavulanate will be too high In this laryngologist for possible ventilation tubes.
situation, the most likely pathogen is H influenzae, and
the addition of clavulanate to amoxicillin will broaden
the coverage while retaining efficacy against S pneumo- C. DURATION OF THERAPY
niae. The duration of antibiotic treatment is controversial.
Three oral cephalosporins are more β-lactamase-sta- Only three recent trials have used stringent entry and
ble (cefuroxime, cefpodoxime, and cefdinir), and these outcome criteria. Success rates were higher at
are alternative choices for second-line therapy for chil- 12–14 days following 10 days of therapy in all three
dren who develop papular rashes with amoxicillin (see studies, particularly for children younger than 2 years
Table 17–2). Unfortunately, these do not cover highly of age, and for those in daycare. At this time, short-
480 / CHAPTER 17

course (5-day) therapy can only be recommended for cated. The patient who is extremely difficult to hold
children older than 2 years and not in daycare. may be premedicated with meperidine, 1 mg/kg intra-
A recent study of preschoolers by Schrag and col- muscularly. Tetracaine has been used, but no studies
leagues demonstrated that drug-resistant pneumococcal are available on its efficacy in children with acute in-
carriage at day 28 posttherapy was lower in a short- flammation, which rapidly removes locally adminis-
course high-dose amoxicillin group compared with a tered drugs. Unquestionably, the best pain minimiza-
group given a standard course of therapy. This is an im- tion method is to perform the procedure rapidly and
portant finding, because we now know that the na- return the child immediately to the parent’s arms.
sopharyngeal flora determines the pathogen of the next
2. Restraint—The patient must be completely immo-
AOM. Efforts to reduce drug-resistant pneumococci
bile while the procedure is being performed. A papoose
include use of Prevnar vaccine and the 23-valent pneu-
board or a sheet can be used to immobilize the patient’s
mococcal vaccine in children older than 2 years.
body, and an extra attendant is required to hold the
D. PAIN MANAGEMENT child’s head steady. It is helpful to have the parent re-
Children with pain related to AOM may obtain relief main in sight of the child for reassurance.
from acetaminophen, ibuprofen, or a topical anesthetic 3. Site selection—With an open-headed operating
drop. In a randomized controlled trial, Auralgan (ben- otoscope (Figure 17–4), the operator carefully selects a
zocaine and antipyrine) ear drops were superior to olive target. This is best done in the anteroinferior quadrant,
oil in reducing pain. A recent study of 88 children, all although the posteroinferior quadrant is a safe but shal-
older than 2 years of age, found that Auralgan eardrops lower alternative. These sites avoid damage to the ossi-
provided enough pain relief that the majority did not cles during the procedure.
need antibiotic therapy. When pain persists after an-
timicrobial treatment, tympanocentesis should be con-
sidered for pain relief and to diagnose the causative
pathogen.
E. FOLLOW-UP VISITS
The optimal timing for follow-up visits depends on the
response to therapy. Children should be reassessed
when symptoms of AOM continue beyond 72 hours or
recur during treatment. The follow-up visit for
preschool children should be 3–6 weeks after start of
therapy. The need for follow-up visits for asymptomatic
school-age children without risk factors of recurrent
disease should be based on the history of speech delay
or the presence of OME in the past.
F. TYMPANOCENTESIS OR MYRINGOTOMY
Tympanocentesis is performed by placing a needle
through the TM and aspirating the middle ear fluid.
Myringotomy involves making an incision in the drum
with a myringotomy knife to drain the fluid. Indi-
cations for tympanocentesis or myringotomy are
(1) AOM in a patient with compromised host resis-
tance, (2) painful bulging of the TM, particularly in a
toddler younger than 48 months, (3) a complete work-
up for presumed sepsis or meningitis, such as in a
neonate, (4) unresponsive otitis media despite courses
of two appropriate antibiotics, and (5) acute mastoiditis
or other suppurative complications. The technique of
tympanocentesis is as follows:
1. Premedication—In the conditions mentioned, the
pain associated with tympanocentesis is only slightly Figure 17–4. Operating head and Alden-Senturia
greater than the pain of existing acute inflammation of trap for tympanocentesis. 18 gauge spinal needle at-
the TM. Therefore, no premedication is generally indi- tached and bent.
 EAR, NOSE, & THROAT / 481

4. Aspiration—An 8.8-cm spinal needle (No. 18 or child in a homecare setting with fewer children to
No. 20) with a short bevel is attached to a 3-mL sy- expose the child to URIs.
ringe. Alternatively, either an Alden-Senturia trap
(Storz Instrument Co., St. Louis, Mo.) or the Tymp- Another method of prophylaxis being studied in
Tap aspirator (Xomed Surgical Products, Jackson, Finland is xylitol, also known as birch sugar, found in
Florida) is attached to a suction pump. The operator plums, strawberries, and raspberries. It was first studied
then aspirates the middle ear effusion from the anterior in Europe as a chewing gum to reduce dental caries,
inferior quadrant. Aspirate should be placed directly and was effective. Recently a double-blind study of
onto culture plates for maximum recovery, and choco- chewing gum use in children with a mean age of 5 years
late agar suffices to grow all common pathogens. found a 42% reduction in episodes of AOM. For chil-
dren too young to chew gum safely, the same investiga-
G. NONVACCINE PROPHYLAXIS tors studied a xylitol syrup given five times daily after
meals or snacks, and found a 33% reduction. The main
Chemoprophylaxis has been used successfully since the problem here is the frequency of dosing, which needs to
1960s, and it is supported by a recent randomized, con- be addressed before this therapy could be practical.
trolled trial by Teele’s group in Boston. Though con- Surgical prevention of AOM is an effective, albeit
ducted in the era of drug-resistant pneumococci, this expensive, alternative to antibiotic prophylaxis. A meta-
study found that the AOM attack rate in infants analysis has shown that PE tubes reduce rates of AOM,
younger than 1 year was cut in half by the dose of but that adenoidectomy has only limited efficacy. Un-
amoxicillin (20 mg/kg/d) used in older studies. Sul- fortunately, the rate of posttube otorrhea is 16%, and a
fisoxazole was not as effective, and the sample size was small number of children will develop perforations after
inadequate to determine if it was superior to placebo. tube extrusion that require surgical repair. Adenoidec-
Nonetheless, the widespread use of chemoprophylaxis tomy reduces the need for PE tube reinsertion and
is likely to lead to bacterial resistance in the commu- therefore will continue to play a role with the second
nity, and it can thus be recommended only for selected insertion of PE tubes. The costs of the procedures and
non-daycare-attending children. For example, children the possibility of long-term complications after tube ex-
who have had three well-documented episodes within trusion have limited this method of prevention to chil-
6 months or four in 1 year may be candidates, as well as dren with long-standing problems.
infants younger that 6 months who have had more than
one episode. Prophylaxis for 3–4 months is still useful H. VACCINES FOR THE PREVENTION OF OTITIS MEDIA
in the spring season, because the absence of URIs in
summer may obviate the need for PE tube placement. With the increasing problems of antibiotic therapy and
It is also valuable for children with PE tubes who con- prophylaxis, the prevention of both viral and bacterial
tinue to experience AOM episodes. pathogens causing AOM has become an exciting area of
A second method of prophylaxis is to educate par- research. Unfortunately, the currently available hep-
ents about risk factors for recurrent disease. This is tavalent vaccine (Prevnar) does not contain the major-
time-consuming, but valuable. Specific topics: ity of strains of pneumococci causing AOM and yielded
only a 6% reduction in infections due to all causes. It
1. Smoking is a risk factor both for URI and for did produce a 57% reduction in otitis media due to
AOM, and primary care doctors can provide liter- those serotypes found in the vaccine, and these stains
ature on smoking cessation programs and nico- include the serotypes most likely to be penicillin- and
tine-containing gums or patches. macrolide-resistant. The heptavalent vaccine also re-
duced PE tube placements by 20% compared with a
2. Breast-feeding protects children from AOM, but control group in Kaiser of California and greatly re-
the mechanism is unknown. Some researchers be- duced AOM incidence in children having six or more
lieve that propping a bottle of milk in the crib in- episodes per year. Furthermore, studies are showing a
creases AOM risk. herd immunity effect on the older siblings of vaccinated
3. The pacifier has been implicated as a risk factor children, which may further reduce drug-resistant
by a study done in Finland in 2000; after nurses serotype circulation. Now that the shortage has ended,
had educated parents about the risk, children not the vaccine should be used as a single dose for children
given a pacifier continuously had a 29% lower 2–5 years with a history of either recurrent AOM or
rate of otitis media over the first 18 months of OME with superimposed AOM episodes, with consid-
life. eration of the 23-valent vaccine 8 weeks after the conju-
4. Daycare is clearly a risk factor for AOM, but few gate vaccine.
working parents can hire a nanny. Alternatives to In recent studies, intranasal influenza vaccine re-
suggest include care by relatives or care of the duced the number of influenza-associated cases of
482 / CHAPTER 17

AOM by 92%. For children older than 6 months with Centers for Disease Control: Appropriate Antibiotic Use
recurrent AOM, it seems prudent to recommend yearly (www.cdc.gov/antibiotresistance/files). This is a Centers for
Disease Control and Prevention site with excellent advice for
influenza vaccine, although this is not yet an official clinicians on (1) distinguishing OME from AOM, (2) careful
recommendation. antibiotic use for respiratory infections, and (3) patient edu-
Vaccines currently being studied in animals that cation material on these two topics.
hold promise for AOM prevention include a respiratory (www.resistanceimpactondemand.com). This site contains three
syncytial virus vaccine and a nontypeable H influenzae lectures on treatment of otitis media, study design pitfalls,
vaccine. Pregnant women in the third trimester may and pneumococcal drug resistance. Audio and video of the
have their antibody levels raised by a heptavalent pneu- speakers accompanies each slide.
mococcal vaccine. This may raise antibody levels in the (www.pedisurg.com/pteducent/otitis_media.htm). Information for
offspring. A recent study showed that low cord blood parents on AOM and PE tubes, with graphics.
levels of two common pneumococcal serotypes is a risk The Ear Treatment Group at the University of Texas Medical
Branch (www.atc.utmb.edu/aom/home.htm). This is an in-
factor for AOM and OME, so this passive route is a teractive site for medical students, residents, and physicians to
logical next step. learn about otitis media and to test their knowledge. The site
contains links to other otitis-media-related resources as well as
Dagan R et al: Bacteriologic and clinical efficacy of amoxicillin– parent educational material.
clavulanate versus azithromycin in acute otitis media. Pediatr
Infect Dis J 2000;19:95 [PMID: 10693993].
Dagan R et al: Bacteriologic and clinical efficacy of high-dose
Management of Otitis Media with Residual
amoxicillin/clavulanate (90/6.4 mg/kg/day) in children with and Persistent Effusions
acute otitis media, including penicillin-resistant Streptococcus
pneumoniae. Pediatr Infect Dis J 2001;20:829 [PMID: OME has been treated primarily to avoid any prolonged
11734759]. conductive hearing loss. Available data show a causal re-
Dowell SF et al: Acute otitis media: Management and surveillance lationship between severe sensorineural hearing loss and
in an era of pneumococcal resistance—A report from the language delay, but not between conductive hearing loss
Drug-Resistant Streptococcus pneumoniae Therapeutic Work- due to OME and language delay. Studies looking at
ing Group. Pediatr Infect Dis J 1999;18:1 [PMID: middle ear effusion (MEE) and its effects of language
9951971]. development do not show differences at age 3. But audi-
Heikkinen T et al: Prevalence of various respiratory viruses in the tory processing disorders are not testable until age
middle ear during acute otitis media. N Engl J Med 1999;
340:260 [PMID: 9920949].
5–7 years, so final results of these studies are still pend-
ing. Two thirds of children with AOM have an MEE or
Johnson CE, Belman S: The role of antibiotic therapy of acute oti-
tis media in promoting drug resistance. Paediatr Drugs 2001; high negative middle ear pressure 2 weeks after diagnosis
3:639 [PMID: 11688595]. and one third at 1 month after diagnosis regardless of
Klein JO et al:. Otitis media: A preventable disease? Proceedings of antibiotic therapy. The management options for otitis
an International Symposium organized by the Marcel Merieux media with residual effusion at 6 weeks to 4 months in-
Foundation, Veyrier-du-Lac, France, February 13–16, 2000. clude observation and corticosteroid therapy. Corticos-
Pediatr Infect Dis J 2001;20:473 [PMID: 11368103]. teroid (prednisone, 1 mg/kg/d) can be administered for
Leibovitz E, Dagan R: Otitis media therapy and drug resistance— 7 days. Unvaccinated children with no clear history of
Part 1: Management principles. Infect Med 2001;18:212. varicella infection who have been exposed in the preced-
Rosenfeld RM: Surgical prevention of otitis media. Vaccine ing month should not receive prednisone because of the
2000 (Suppl 1);S134 [PMID: 11163477]. potential risk of disseminated varicella-zoster viral dis-
Schrag SJ et al: Effect of short-course, high-dose amoxicillin ther- ease. Short courses of prednisone increase appetite and
apy on resistant pneumococcal carriage: A randomized trial.
JAMA 2001;286:49 [PMID: 11434826].
cause fluid retention, occasional vomiting, and, rarely,
Shriberg LD et al: Otitis media, fluctuant hearing loss, and speech
marked behavioral changes.
language outcomes: A preliminary structural equation model. If the patient clears the persistent MEE unilaterally
J Speech Lang Hear Res 2000;43:100 [PMID: 10668655]. or bilaterally, the physician should follow the patient
Takata GS et al: Evidence assessment of management of acute otitis monthly. Because of the increase in antibiotic resis-
media. Pediatrics 2001;108:239 [PMID: 11483783]. tance, the use of prophylaxis, even intermittently, must
be restricted to carefully selected patients. The guide-
Websites line recommendation developed by the Agency for
Health Care Policy and Research for the management
American Academy of Pediatrics (www.aap.org/otitismedia/www/). of OME is that ventilating tubes should be placed after
This is a website on diagnosis and treatment of acute otitis the effusion has persisted for 4 months and is accompa-
media, written for the American Academy of Pediatrics. It
features video clips of tympanic membranes being insufflated, nied by a bilateral hearing impairment of 20 dB or
to help clinicians learn normal landmarks and pathologic greater. Earlier placement of ventilating tubes should
states. It is designed for all learners in medicine or nursing. depend on the child’s developmental and behavioral
 EAR, NOSE, & THROAT / 483

status as well as on parental preference. The value of placed pinna. On examination, the mastoid area often
ventilating tubes for treating unilateral effusions in oth- appears swollen and reddened. In the late stage, it may
erwise healthy children is unclear. be fluctuant. The earliest finding is severe tenderness on
Children with otitis media and persistent effusion mastoid palpation.
have an increased incidence of cholesteatoma, adhesive AOM, by otoscopy, is almost always present. Late
otitis, retraction pockets, membrane atrophy, and per- findings are a pinna that is pushed forward by postau-
sistent membrane perforation. As there is no way to ricular swelling and an ear canal that is narrowed in the
identify the small proportion of candidate children for posterosuperior wall because of pressure from the mas-
whom insertion of ventilating tubes will prevent the toid abscess. In infants younger than age 1 year, the
damage, close follow-up of abnormal ears may be best swelling occurs superior to the ear and pushes the pinna
accomplished by an otolaryngologist. downward rather than outward. In the acute phase, dif-
fuse inflammatory clouding of the mastoid cells occurs,
Berman S: Management of otitis media and functional outcomes as in every case of AOM. In more severe cases, bony de-
related to language, behavior, and attention: Is it time to struction and resorption of the mastoid air cells may
change our approach? Pediatrics 2001;107:1175 [PMID: occur. The best way to determine the extent of disease
11331703]. is by computed tomography (CT) scan.
Paradise JL et al: Effect of early or delayed insertion of tympanos- Meningitis is a complication of acute mastoiditis
tomy tubes for persistent otitis media on developmental out- and should be suspected when a child has associated
comes at the age of three years. N Engl J Med 2001;344:
1179 [PMID: 11309632].
high fever, stiff neck, severe headache, or other
Paradise JL et al: Language, speech sound production, and cogni-
meningeal signs. Lumbar puncture should be per-
tion in three-year-old children in relation to otitis media in formed for diagnosis. Brain abscess occurs in 2% of pa-
their first three years of life. Pediatrics 2000;105:1119 tients and may be associated with persistent headaches,
[PMID: 10890473]. recurring fever, or changes in sensorium. Facial palsy,
cavernous sinus thrombosis, and thrombophlebitis may
be encountered.
3. Mastoiditis Treatment for noncoalescent mastoiditis is typically
Mastoiditis is a spectrum of disease that ranges from in- myringotomy, with or without tube placement, in
flammation of the mastoid periosteum to bony destruc- order to obtain material for culture. Hospitalization for
tion of the mastoid air system (coalescent mastoiditis) intravenous therapy follows. Reasonable initial therapy
or abscess development. Infection of the periosteum of is ceftriaxone plus nafcillin or clindamycin until culture
the mastoid bone is a rare complication of AOM in the results are returned. If clinical improvement does not
postantibiotic era. Mastoiditis can occur in any age occur after 24–48 hours of intravenous or intramuscu-
group, but more than 60% of the patients are younger lar therapy, or if any signs or symptoms of intracranial
than age 2 years. The most common pathogens are complications exist, immediate surgery to drain the
Streptococcus pneumonia and S pyogenes, with Staphylo- mastoid abscess is indicated. The primary management
coccus aureus and H influenzae occasionally seen. Rarely for coalescent mastoiditis is cortical mastoidectomy. A
gram-negative bacilli and anaerobes are isolated. Antibi- recent review from the University of Texas–Southwest-
otics may affect the incidence and morbidity of acute ern revealed that 39% of patients required a mastoidec-
mastoiditis. In the Netherlands, where only 31% of tomy. After significant clinical improvement is achieved
AOM patients receive antibiotics, the incidence of with parenteral therapy, oral antibiotics are begun and
acute mastoiditis is 4.2 per 100,000 people-years. In should be continued for 3 weeks.
the United States, where more than 96% of patients
with AOM receive antibiotics, the incidence of acute 4. Otitis Media with Complications
mastoiditis is 2 per 100,000 people-years. The higher
antibiotic usage in the United States correlates with a Complications of otitis media may involve damage to
higher rate of resistant organisms and more adverse the middle ear structures, such as tympanosclerosis, re-
drug interactions. Moreover, despite the routine use of traction pockets, adhesions, ossicular erosion,
antibiotics, the incidence of acute mastoiditis has been cholesteatoma, perforations, and intratemporal and in-
rising in some cities. The pattern change may be sec- tracranial injury.
ondary to the emergence of resistant S pneumoniae.
A. TYMPANOSCLEROSIS
A white plaque-like appearance on the TM is caused by
Clinical Findings chronic inflammation or trauma that produces granula-
The principal complaints of patients with mastoiditis tion tissue and hyalinization. The appearance of a small
are usually postauricular pain, fever, and outwardly dis- defect in the posterosuperior area of the pars tensa or in
484 / CHAPTER 17

the pars flaccida suggests a retraction pocket. Retraction conductive hearing loss is usually present, depending
pockets occur when chronic inflammation and negative on the size and location of the perforation. The site of
pressure in the middle ear space produce atrophy and perforation is important. Central perforations sur-
atelectasis of the TM. rounded by intact TM are usually relatively safe from
Continued inflammation can cause adhesions be- chloesteatoma formation. With a peripheral perfora-
tween the retraction pocket and the ossicles. This con- tion, especially in the pars flaccida, the perforation ex-
dition, referred to as adhesive otitis, predisposes to for- tends to the canal wall without any intervening TM.
mation of a cholesteatoma or fixation and erosion of Peripheral perforations create a risk for cholesteatoma
the ossicles (Figure 17–5). Erosion of the ossicles results because the ear canal epithelium may invade the perfo-
from osteitis and compromise of the blood supply. Os- ration.
sicular discontinuity may produce a maximal hearing Most perforations with AOM heal within 2 weeks.
loss with a 50-dB threshold. A tympanogram with very When perforations fail to heal after 3–6 months, surgi-
high compliance suggests ossicular discontinuity. cal repair may be needed. Repair of the defect in the
TM is generally delayed until the child is older and eu-
B. CHOLESTEATOMA stachian tube function has improved. Procedures in-
A greasy-looking mass or pearly white debris seen in a clude paper patch, fat myringoplasty, and tym-
retraction pocket or perforation suggests a panoplasty. Tympanoplasty is generally deferred until
cholesteatoma, whether or not there is discharge (see age 7–9 years. In otherwise healthy children without
Figure 17–5). A perforation is usually painless. If infec- any craniofacial anomalies, some surgeons repair the
tion is absent, the middle ear cavity generally contains perforated TM earlier if the contralateral nonperforated
normal mucosa. If infection is superimposed, serous or drum remains free of infection and effusion for 1 year.
purulent drainage will be seen, and the middle ear cav- This policy does not guarantee success. The age of the
ity may contain granulation tissue or even polyps. Per- child when repair is performed is the more probable in-
sistent or recurrent otorrhea following appropriate dicator of success. Occasionally, a perforation is closed
medical management should make one suspect a in a child of younger age if recurrent otorrhea is
cholesteatoma. thought to be secondary to water contamination or na-
sopharyngeal reflux. Earlier closure of the perforation
C. TYMPANIC MEMBRANE PERFORATION will seal the middle ear space and reestablish the air
Occasionally, an episode of AOM is associated with ot- cushion provided by the mastoid air system. An older
orrhea. An aural discharge indicates that the TM has child is more likely to have a successful outcome from
perforated. Most likely the perforation will heal sponta- closure of the perforation. Water activities should be
neously. If the perforation has not healed within limited to surface swimming, preferably with the use of
3 months, surgical intervention will be necessary. A an ear mold. Diving, jumping into the water, and un-
derwater swimming should be prohibited.
D. FACIAL NERVE PARALYSIS
Attic
cholesteatoma The facial nerve crosses the middle ear as it courses
through the temporal bone to its exit at the stylomas-
Cholesteatoma toid foramen. Occasionally, the nerve is incompletely
opening in encased in bone, which makes it susceptible to inflam-
Shrapnell's membrane
mation during an episode of AOM. The acute onset of
a facial nerve paralysis is not idiopathic Bell palsy until
all other causes have been excluded. If middle ear fluid
is present, a prompt myringotomy is indicated. Place-
ment of a ventilation tube will allow for prolonged ven-
tilation. CT is indicated if a cholesteatoma is suspected
or acute coalescent mastoiditis is present.
E. CHRONIC SUPPURATIVE OTITIS MEDIA
Chronic suppurative otitis media is present when per-
sistent otorrhea occurs in a child with tympanostomy
tubes or TM perforations. Occasionally, it is an accom-
panying sign of cholesteatoma. Visualization of the
Figure 17–5. Attic cholesteatoma, formed from an in- TM, meticulous cleaning with culture of the drainage,
drawing of an attic retraction pocket. and appropriate antimicrobial therapy are keys to man-
 EAR, NOSE, & THROAT / 485

agement of cases not related to cholesteatoma. The suc- Treatment of middle ear hematomas consists mainly
cessful treatment of chronic suppurative otitis usually of watchful waiting. Antibiotics are not necessary unless
requires therapy with an antibiotic that covers signs of infection appear. The prognosis for unimpaired
Pseudomonas and anaerobes. Oral quinolone antibiotics hearing depends on whether the ossicles are dislocated
effective against Pseudomonas infection are not yet ap- or fractured in the process. The patient needs to be fol-
proved for use in growing children. Recent studies sug- lowed with audiometry until hearing has returned to
gest that topical quinolones for 14 days may be effec- normal.
tive. It is very important to clean the ear canal by Traumatic perforations of the TM often do not heal
suction to allow penetration of drops, and it is often spontaneously, in which case the patient should be re-
useful to culture the secretions. An ear wick should be ferred to an otolaryngologist. Perforations caused by a
inserted and drops placed on the wick several times foreign body must be attended to immediately, espe-
daily. The child should be seen in 7 days, the wick re- cially if accompanied by vertigo.
moved, and suction repeated if necessary. When a
cholesteatoma is associated with chronic suppurative
otitis media, medical therapy is not effective (see Figure
EAR CANAL FOREIGN BODY
17–5). If the discharge does not respond to 2 weeks of Numerous objects can be inserted into the ear canal by
aggressive therapy, mastoiditis, cholesteatoma, tubercu- a child. If the object is large, wedged into place, or diffi-
losis, or fungal infection should be suspected. Serious cult to remove with available instruments, the patient
central nervous system (CNS) complications such as ex- should be referred to an otolaryngologist early rather
tradural abscess, subdural abscess, brain abscess, menin- than risk traumatizing the ear canal and causing edema
gitis, labyrinthitis, or lateral sinus thrombophlebitis can that will require removal under anesthesia. An emer-
occur with extension of this process. Therefore, patients gency condition exists if the foreign body is a disk-type
with facial palsy, vertigo, or other CNS signs should be battery used in clocks, watches, and hearing aids. An
immediately referred to an otolaryngologist. electric current is generated in the moist canal, and a se-
vere burn with resulting scarring can occur in less than
Bluestone CD: Clinical course, complications and sequelae of acute 4 hours.
otitis media. Pediatr Infect Dis J 2000;19:S37 [PMID:
10821471].
Ghaffar FA et al: Acute mastoiditis in children: A seventeen-year
HEMATOMA OF THE PINNA
experience in Dallas, Texas. Pediatr Infect Dis J 2001;20: Trauma to the ear can result in a hematoma between
376 [PMID: 11332661].
the perichondrium and cartilage. The hematoma ap-
Spratley J et al: Acute mastoiditis in children: Review of the current pears as a boggy purple swelling of the upper half of the
status. Int J Pediatr Otorhinolaryngol 2000;56:33 [PMID:
11074113]. ear. If this is not treated, it can cause pressure necrosis
Van Zuijlen DA et al: National differences in incidence of acute
of the underlying cartilage and result in “cauliflower
mastoiditis: Relationship to prescribing patterns of antibiotics ear.” To prevent this cosmetic deformity, physicians
for acute otitis media? Pediatr Infect Dis J 2001;20:140 should refer patients to an otolaryngologist for aspira-
[PMID: 11224830]. tion and application of a carefully molded pressure
Zapalac JS et al: Suppurative complications of acute otitis media in dressing. Recurrent or persistent hematoma of the ear
the era of antibiotic resistance. Arch Otolaryngol Head Neck may require surgical drainage.
Surg 2002;128(6):660 [PMID: 12049560].

Website
CONGENITAL EAR MALFORMATIONS
Agenesis of the external ear canal results in conductive
(www.entnet.org). This is the official website of the American
Academy of Otolarngology and Head and Neck Surgery. The hearing loss that requires evaluation in the first month
site contains patient information, clinical indications for of life by hearing specialists and an otolaryngologist.
common surgical procedures, and links to other ENT sites. “Lop ears,” folded down or protruding ears (so-
called Dumbo ears), are a source of much teasing and
ridicule. In the past, surgical correction at age 5 or
ACUTE TRAUMA TO THE MIDDLE EAR 6 years was the only answer. Taping the ears into a cor-
Head injuries, a blow to the ear canal, sudden impact rect anatomic position is very effective if performed in
with water, blast injuries, or the insertion of pointed in- the first 72–96 hours of life. Tape is applied over a
struments into the ear canal can lead to perforation of molding of wax and continued for 2 weeks. Another al-
the TM or hematoma of the middle ear. One study re- ternative for the ear that can be molded solely by finger
ported that 50% of serious penetrating wounds of the pressure into a normal configuration is an incisionless
TM were due to parental use of a cotton-tipped swab. otoplasty, which can be performed at a much earlier age
486 / CHAPTER 17

and is associated with little postoperative morbidity. The American Academy of Pediatrics recommends
Because no cartilage destruction is associated with this that hearing be assessed and language skills monitored in
technique, future growth is unaffected. children who have frequently recurring AOM or MEE
An ear is low-set if the upper pole is below eye level. persisting longer than 3 months. The effects of hearing
This condition is often associated with renal malforma- loss may be insidious and not discernible until the explo-
tions (eg, Potter syndrome), and renal ultrasound ex- sive phase of expressive language development occurs be-
amination is suggested. tween ages 16 and 24 months; therefore, the optimal
Preauricular tags, ectopic cartilage, fistulas, sinuses, time for screening language in young children is between
and cysts require surgical correction, mainly for cos- 18 and 24 months. An acceptable tool for language
metic reasons. Children exhibiting any of these findings screening at this time is the Early Language Milestone
should have their hearing tested. Most preauricular pits Scale. Children age 3, 4, and 5 years with recurring
cause no symptoms. If one should become infected, the OME should also be screened for language delays.
patient should receive antibiotic therapy and be referred To diminish the likelihood of communication disor-
to an otolaryngologist for eventual excision. der, the physician should inform the parents of a child
with middle ear disease that the child’s hearing may not
be normal and should instruct the parents to (1) turn
Fritsch MH: Incisionless otoplasty. Laryngoscope 1995;105 (5 pt
3 Suppl 70) (entire issue) [PMID: 7760682].
off sources of background noise (eg, televisions, radios,
Yotsuyanagi T et al: Nonsurgical treatment of various auricular de-
dishwashers) when speaking to the child, (2) focus on
formities. Clin Plast Surg 2002;29(2):327 [PMID: the child’s face and gain his or her direct attention be-
12120687]. fore speaking, (3) speak slightly louder than usual, and
(4) have the teacher place the child in the front of the
classroom.
DETECTION & MANAGEMENT
OF HEARING DEFICITS Sensorineural Hearing Loss
Hearing deficits are classified as conductive, sensorineu- Sensorineural hearing loss arises from a lesion in the
ral, or mixed. Conductive hearing loss results from cochlear structures of the inner ear or in the neural
blockage of the transmission of sound waves from the fibers of the auditory nerve (cranial nerve VIII). Most
external auditory canal to the inner ear and is character- sensorineural losses in children are congenital, with an
ized by normal bone conduction and reduced air con- estimated incidence of 2.0–3.0 per 1000 live births.
duction hearing. In children, conductive losses are most Causes can be classified as either congenital or postnatal
often caused by MEE. Sensorineural hearing loss occurs and, within each classification, as genetic or non-
when the auditory nerve or cochlear hair cells are dam- genetic. Approximately two thirds of genetic hearing
aged. Mixed hearing loss is characterized by compo- loss is autosomal recessive and is not associated with a
nents of both conductive and sensorineural loss. The known syndrome. Mutations in the Connexin
criteria for children are more stringent than for adults 26 (Cx26) gene have been found to account for approx-
because children are in the process of learning language. imately 20% of all childhood deafness. In older chil-
In children, a hearing loss of 15–30 dB is considered dren, one should suspect congenital hearing loss if the
mild, 31–50 dB moderate, 51–80 dB severe, and hearing is normal in the low and high frequencies, but
81–100 dB profound. poor in the middle frequencies (“cookie bite” or U-
shaped audiogram). Clues that a patient may have a
Conductive Hearing Loss syndrome associated with the hearing loss and should
be referred to a geneticist include the following physical
By far the most important cause of conductive hearing exam findings: asymmetrical face, skin tags, abnormal
loss during childhood is otitis media and its sequelae eye exam, widely spaced eyes, preauricular pits, abnor-
such as MEE. Other causes include atresia, stenosis, or mal ear appearance, café au lait spots, white forelock,
collapse of the ear canal; furuncle, cerumen, or foreign sinus tracts in the neck, abnormal digits, and thy-
body in the ear; aural discharge; bony growths; otitis romegaly. One should consider screening of first-degree
externa; perichondritis; and middle ear anomalies (eg, relatives if idiopathic sensorineural hearing loss is pre-
stapes fixation, ossicular malformation). sent. If a first-degree relative also has a sensorineural
The average hearing loss due to MEE (whether loss, the hearing loss is most likely genetic.
serous, purulent, or mucoid) is 27–31 dB, the equiva- A common congenital genetic cause is inner ear dys-
lent of a mild hearing loss. This loss may be intermit- plasia. Postnatal onset of sensorineural hearing loss
tent in nature and may occur in one or both ears. often occurs with associated genetic abnormalities (eg,
 EAR, NOSE, & THROAT / 487

Alport syndrome and Klippel–Feil syndrome). Non- A. SCREENING OF NEWBORNS (SEE CHAPTER 1.)
genetic causes of congenital hearing loss include prena- B. SCREENING OF INFANTS
tal infections, teratogenic drugs, and perinatal injuries.
Congenital syphilis is responsible for delayed-onset sen- Hearing screening for infants (29 days to 2 years) is rec-
sorineural hearing loss (usually after age 2 years). Com- ommended if one of the following risk criteria is identi-
mon postnatal nongenetic causes are infections, trauma, fied: (1) concerns regarding hearing, speech, language,
ototoxic drugs, metabolic disorders, neoplastic diseases, or developmental delay; (2) bacterial meningitis;
and autoimmune diseases. A major factor in hearing (3) neonatal risk factors (see Chapter 1); (4) head
loss in premature infants is hypoxia. A difficult delivery trauma; (5) ototoxic drug use; (6) neurodegenerative
or an Apgar score of 6 or less is associated with an in- disorders; and (7) childhood infectious diseases (eg,
creased risk of hearing loss. Neonates with a history of mumps, measles).
persistent pulmonary hypertension or children who In the past, the parents’ report of their infant’s be-
have been on ECMO are at an increased risk for late- havior was considered an adequate assessment of hear-
onset hearing loss and should be followed closely. Be- ing. However, a deaf infant’s behavior can appear nor-
fore the introduction of H influenzae type B vaccine, mal and mislead the parents as well as the professional,
meningitis was the most common cause of acquired especially if the infant has autosomal recessive deafness
hearing loss, with deafness occurring in about 10% of and is the firstborn child of carrier parents. The follow-
children who had bacterial meningitis. Pneumococcal ing office screening techniques should identify gross
and other bacterial meningitides still remain an indica- hearing losses but may not detect less severe losses due
tion to screen for hearing loss. to otitis media:
In the past, the effect of unilateral deafness on 1. Birth to 4 months—In response to a sudden loud
school performance was thought to be insignifi- sound (70 dB or more) produced by a horn, clacker, or
cant. Studies now show that more than one third of af- special electronic device, the infant should show a star-
fected children fail one or more grades in school. tle reflex or blink the eyes.
Therefore, merely recommending preferential class-
room seating for these children is no longer sufficient; 2. 4 months to 2 years—While the infant is dis-
they should be referred for full evaluation of their hear- tracted with a toy or bright object, a noisemaker is
ing needs. sounded softly outside the field of vision at the child’s
Acquisition of language skills is affected more se- waist level. Normal responses are as follows: at
verely by bilateral than by unilateral sensorineural hear- 4 months, there is widening of the eyes, interruption of
ing loss. The earlier the hearing loss occurs, the graver other activity, and perhaps a slight turning of the head
the consequences for language development; thus, the in the direction of the sound; at 6 months, the head
earlier a sensorineural loss is detected and treated (by turns toward the sound; at 9 months or older, the child
sound amplification and language habilitation), the is usually able to locate a sound originating from below
better the chances of a good outcome. The mild, fluctu- as well as turn to the appropriate side; after 1 year, the
ating hearing loss associated with OME is much less child is able to locate sound whether it comes from
likely to cause language problems, presumably because below or above.
it is intermittent and may often be unilateral. (See Oti- After responses to soft sounds are noted, a loud horn
tis Media with Effusion section.) or clacker should be used to produce an eye blink or
startle reflex. This latter maneuver is necessary because
deaf children are often visually alert and able to scan the
Screening for Hearing Deficits environment so actively that their scanning can be mis-
Screening procedures are established for early detection taken for an appropriate response to the softer noise
and diagnosis of hearing deficits. Infants at high risk for test. A deaf child will not blink in response to the loud
hearing loss are best tested by auditory brainstem re- sound. Consonant sounds such as “mama,” “dada,” and
sponse (ABR) screening or evoked otoacoustic emission “baba” should be present in speech by age 11 months.
(OAE) testing, preferably before discharge from the Children who fail to respond appropriately should be
hospital. Many states now mandate universal newborn referred for audiologic assessment.
hearing screening by physiologic test procedures. All
universal newborn hearing screening programs are C. SCREENING OF OLDER CHILDREN
using either ABR or OAE as the screening test. The When children reach age 3 years, their hearing can be
procedures listed in the following sections are intended tested by earphones and pure tone audiometry. The test
to serve as a guide, and confirmation of sensorineural frequencies for screening are 1000 Hz, 2000 Hz, and
hearing loss is dependent on audiologic testing. 4000 Hz, with the same tone presented at each fre-
488 / CHAPTER 17

quency. Normally, the screening level is 20 dB. If a

soundproof room is not available, the screening may be II. THE NOSE & PARANASAL
done at 25 dB. If the child does not respond at any one
of the test frequencies in either ear, the test should be SINUSES
repeated within 1 week. Failure on rescreening requires
referral for audiologic evaluation.
High-risk categories in older children include those ACUTE VIRAL RHINITIS
with osteogenesis imperfecta and conditions associated (Common Cold; see also Chapter 36.)
with deafness, such as Waardenburg, Hurler, Alport, The common cold is the most common pediatric infec-
Treacher Collins, Klippel–Feil, and fetal alcohol syn- tious disease, and the incidence is higher in early child-
dromes. Children with these disorders should always re- hood than in any other period of life. Children younger
ceive audiologic evaluation. In addition, before any than age 5 years have 6–12 colds per year, of which
child is labeled as having mental retardation, autism, or 30% are caused by rhinoviruses, 15% influenza or
severe behavior problems, the adequacy of the child’s parainfluenza, 10% coronavirus, and 5% enterovirus.
hearing must be determined. If a developmental speech
delay is diagnosed, the child’s hearing should be tested
as the first step in evaluating the language problem. Clinical Findings
The patient usually experiences a sudden onset of clear
Referral or mucoid rhinorrhea, nasal congestion, and fever.
Mild sore throat and cough may develop. Although the
In addition to the referrals for audiologic testing men- fever is usually low grade in older children, in the first
tioned in the preceding section, a child with confirmed 5 or 6 years of life it can be as high as 40.6°C without
hearing loss should be referred to an otolaryngologist superinfection. The nose, throat, and TM can appear
for evaluation and further treatment. Any child failing red and inflamed. Figure 17–6 shows the duration of
the language screen should be referred to a speech cough, sore throat, and rhinorrhea in adults with rhi-
pathologist for language evaluation. Home language novirus-proven infections. Note that one quarter are
enrichment programs for children with mild language still symptomatic at 14 days, although they may be im-
delays can be directed by the physician or by a speech proving.
pathologist. Programs for the deaf child vary from aural
to total communication; the latter includes elements of Treatment
aural programs plus signing. Each program should be
scrutinized thoroughly for its relevance to the deaf An algorithm for the management of acute nasal con-
child’s age and hearing level. gestion and sinusitis is presented in Figure 17–7. Treat-
ment for the common cold should be purely sympto-
matic; however, a recent study showed that 44% of
Prevention children younger than age 18 years seen by physicians
Appropriate care may treat or prevent conditions caus- were given an antibiotic prescription. Acetaminophen
ing hearing deficits. Aminoglycosides and diuretics, es- or ibuprofen is helpful for fever, sore throat, or muscle
pecially in combination, are potentially ototoxic and aches. A stuffy, congested nose can be treated with nor-
should be used judiciously and monitored carefully, es- mal saline nose drops (mix 1⁄2 tsp table salt with 6 oz of
pecially in premature infants and in patients with renal water), 3 drops in each nostril. After several minutes, a
insufficiency. Reduction of repeated exposure to loud suction bulb can be used to remove the secretions if the
noise in the child’s environment—loud music, fire- infant is unable to blow his or her nose. If this proce-
crackers, or shots from guns or cap pistols—may help dure fails after several attempts and the stuffy nose still
prevent high-frequency hearing losses. interferes with feeding or sleep, consider long-acting xy-
lometazoline or oxymetazoline 0.05% nose drops twice
daily. Drops should be used only when the nose is con-
Avraham KB: Inherited connexin mutations associated with hear- gested and discontinued within 4 days to prevent re-
ing loss. Cell Commun Adhes 2001;8(4–6):419 [PMID: bound chemical rhinitis.
12064629]
Antihistamines are not effective in relieving cold
Downs MP, Yoshinaga-Itano C: The efficacy of early identification
and intervention for children with hearing impairment. Pedi-
symptoms. In rhinoviral colds, increased levels of hista-
atr Clin North Am 1999;46:79 [PMID: 10079791]. mine are not observed. Antibiotics do not prevent su-
Grundfast KM et al: Genetics and molecular biology of deafness. perinfection and should not be used. Cough suppres-
Update. Otolaryngol Clin North Am 2000;33:1367 [PMID: sion at night is the number one goal of many parents;
11449793]. however, the effectiveness of dextromethorphan is un-
 EAR, NOSE, & THROAT / 489

70
Nasal Discharge
% of Patients with symptom

60 Sore Throat
Cough
50 Fever
40

30

20

10

0 Figure 17–6. Duration of symptoms

1 2 3 4 5 6 7 8 9 10 11 12 13 14 in the common cold in adults. (From
Day of illness Gwaltney JM: JAMA 1967;202:158.)

Acute nasal congestion and sinusitis

Assess presentation

≤ 10 days duration ≥ 10–14 days duration Any duration, with focal signs
without improvement (periorbital edema, sinus tenderness,
or severe headache)

Upper respiratory Bacterial sinusitis

tract infection likely
(viral sinusitis)

Mild symptoms Severe symptoms or

immunosuppressed
• Pain medication host
• Humidified air
• Saline nose drops
• Cough suppressants First line antibiotic • ß-lactamase
for 10 days stable antibiotic
(see Table 17–1) (see Table 17–1)
• Consider imaging and
evaluation for
complications
Poor response after ≥ 3 days

Second line antibiotic

Figure 17–7. Algorithm for acute nasal congestion and sinusitis.

490 / CHAPTER 17

clear. It is believed by most experts to be effective in Clinical Findings

adults and adolescents, but it has not been studied ade-
quately in children with colds. Use of codeine should The development of symptoms in acute sinusitis in
be discouraged because it has caused fatal respiratory children may be gradual or sudden. With gradual-onset
distress. A cool mist vaporizer or humidifier may help disease, nasal discharge or postnasal drip and daytime
the cough, but the device should be washed every cough persist longer than 10 days without improve-
3 days or less, to prevent mold growth. Parents should ment, but less than 30 days. Additional symptoms: a
be instructed that fast breathing or difficult breathing low-grade fever, malodorous breath, and painless peri-
with retraction is a sign of lower respiratory infection orbital swelling. Older patients may complain of
such as bronchiolitis or pneumonia. Prolonged fever headache, a sense of facial fullness, or facial pain overly-
may indicate otitis media or sinusitis. An antiviral agent ing the involved sinus. With the more sudden onset,
called pleconaril is being studied for URIs due to rhi- the patient has a fever of at least 102°F and concurrent
novirus or enterovirus. purulent nasal discharge present for 3–4 consecutive
days. The physical examination is rarely helpful in mak-
ing a diagnosis of acute bacterial sinusitis, as the find-
Clemens CJ et al: Is an antihistamine-decongestant combination ef- ings will be nearly the same as those in a child with viral
fective in relieving symptoms of the common cold in rhinosinusitis. Occasionally percussion tenderness over-
preschool children? J Pediatr 1997;130:463 [PMID:
9063425]. lying the sinus is present, but this is a finding typical
Nyquist AC et al: Antibiotic prescribing for children with colds,
only of the older child and is unreliable when compared
upper respiratory tract infections, and bronchitis. JAMA with antral irrigation results. Transillumination of the
1998;279:875 [PMID: 9516004]. sinuses is difficult to perform and not very helpful un-
less the sinuses are grossly asymmetrical.
The physician should consider sinus aspiration by
RHINOSINUSITIS an otolaryngologist for diagnostic purposes in patients
The use of the term sinusitis versus rhinosinusitis has with complications and in immunocompromised pa-
been debated. Rhinosinusitis implies that the nasal and tients. Gram stain or culture of nasal discharge does not
sinus mucosa are involved in similar and concurrent in- correlate with cultures of sinus aspirates. If the patient
flammatory processes. is hospitalized because of complications, a blood cul-
ture should be obtained.
Imaging studies of the paranasal sinuses during
1. Acute Bacterial Rhinosinusitis acute illness are not indicated except for evaluation of
Acute bacterial infection of the paranasal sinuses lasting complications. In the past, plain radiography was used
less than 30 days and in which the symptoms resolve to diagnose sinusitis when an air–fluid level or mucosal
completely is called acute bacterial sinusitis. The maxil- thickening greater than 4 mm was seen. Today, CT
lary and ethmoidal sinuses are most commonly in- scans should be ordered only in children with compli-
volved when mucociliary clearance and drainage are im- cations or lack of resolution following adequate antibi-
paired by a URI or allergic rhinitis. Both the ethmoid otic therapy. Findings consistent with sinusitis may be
and maxillary sinuses are present at birth, forming in found in asymptomatic patients with colds or nasal al-
the third to fourth gestational month. The sphenoid si- lergies. Because of the lack of specificity between abnor-
nuses pneumatize as an extension of a posterior eth- mal CTs or plain films, the Sinus and Allergy Health
moid cell by age 5 years, and the frontal sinuses form Partnership (see references) does not recommend any
from an anterior ethmoid cell appearing about age imaging study to diagnose uncomplicated cases of acute
7–8 years. Frontal sinusitis is unusual before age bacterial sinusitis in any age group.
10 years.
A combination of anatomic, mucosal, microbial,
and immune pathogenic processes is believed to under-
Complications
lie sinusitis in children. Both viral and bacterial infec- Complications are most apt to develop with ethmoidi-
tions have integral roles in the pathogenesis of sinusitis. tis. These complications represent a continuum begin-
Viral URIs commonly cause sinus mucosal injury and ning with preseptal cellulitis, then postseptal cellulitis,
swelling, resulting in osteomeatal obstruction, loss of subperiosteal abscess, orbital abscess, and cavernous
ciliary activity, and mucous hypersecretion. The bacter- sinus thrombosis. They are associated with decreased
ial pathogens that cause acute sinusitis are usually S extraocular movement, proptosis, chemosis, and altered
pneumoniae, H influenzae (nontypable), M catarrhalis, visual acuity (see Chapter 15). The most common com-
and β-hemolytic streptococci. Rarely, anaerobic bacter- plication of frontal sinusitis is osteitis of the frontal
ial infections can cause fulminant frontal sinusitis. bone (Pott puffy tumor). Intracranial extension leads to
 EAR, NOSE, & THROAT / 491

meningitis and to epidural, subdural, and brain ab- Their effectiveness has not been proved, and concern
scesses. The most common maxillary complication is has been raised about potential adverse effects related to
cellulitis of the cheek. Rarely, osteomyelitis of the max- impaired ciliary function, decreased blood flow to the
illa can develop. In a series of children admitted for se- mucosa, and reduced diffusion of antibiotic into the si-
vere sinusitis, 17% had intracranial abscesses identified nuses. Patients with underlying allergic rhinitis may
on CT scanning. In this and other studies, male adoles- benefit from intranasal cromolyn or corticosteroid nasal
cents predominated, for unknown reasons. Interest- spray. Vasoconstrictor nose drops and spray are associ-
ingly, only 1 of 13 children had a history of a previous ated with rebound edema if used for more than 4 days.
sinus infection. No information is available on the rate The patient may require acetaminophen, ibuprofen,
of complications in ambulatory sinusitis patients, but or even codeine to permit sleep until drainage is
the severity of the complications suggests that the pa- achieved. The application of ice over the sinus may help
tient should be carefully followed while receiving treat- to relieve pain.
ment.
Clinical Practice Guideline: Management of sinusitis: American
Treatment Academy of Pediatrics. Pediatrics 2001;108:798 [PMID:
11533355].
A meta-analysis of five randomized controlled trials Garbutt JM et al: A randomized, placebo-controlled trial of antimi-
suggested a modest benefit of antibiotics in reducing crobial treatment for children with clinically diagnosed acute
sinus symptoms; however, approximately six children sinusitis. Pediatrics 2001;107:619 [PMID: 11335733].
required therapy to achieve one additional cure. De- Morris P: Antibiotics for persistent nasal discharge (rhinosinusitis)
spite limited proof of efficacy, antibiotic treatment is in children. Cochrane Database Syst Rev 2000;3:CD001094
recommended for most children with acute and suba- [PMID: 10908484].
cute sinusitis because bacterial pathogens are recover- McAlister WH et al: Sinusitis in the pediatric population: Ameri-
can College of Radiology. ACR appropriateness criteria. Ra-
able from the majority of affected sinuses. Patients with diology 2000;215 (Suppl):811 [PMID: 11037504].
evidence of invasive infection or any CNS complica-
Nash D, Wald E: Sinusitis. Pediatr Rev 2001;22:111 [PMID:
tions should be hospitalized immediately. Intravenous 11283323].
therapy with nafcillin or clindamycin plus a third-gen- Sinus and Allergy Health Partnership: Antimicrobial treatment
eration cephalosporin such as cefotaxime should be ini- guidelines for acute bacterial rhinosinusitis. Otolaryngol
tiated until culture results become available. For un- Head Neck Surg 2004;13:1 [PMID: 14726904].
complicated sinus infections, oral antibiotics for Sinus and Allergy Health Partnership: Antimicrobial treatment
10 days is appropriate. Antibiotic treatment should guidelines for acute bacterial rhinosinusitis. Executive sum-
continue for another week if the patient has improved mary. Otolaryngol Head Neck Surg 2000;123:1 [PMID:
but is not totally asymptomatic. Amoxicillin at 10887345].
90 mg/kg/d can be used if the patient is older than
2 years old, not in daycare, has not had recent antibi-
otic therapy, and has sinusitis that is mild to moderate
2. Recurrent or Chronic Sinusitis
in severity. The majority of children, therefore, will Recurrent acute bacterial sinusitis is now defined as
need to be treated with high-dose amoxicillin–clavu- successive episodes of bacterial infections of the sinuses,
lanate ES-600 (amoxicillin, 90 mg/kg/d, and clavu- each lasting less than 30 days and separated by intervals
lanate, 6.4 mg/kg/d). Alternative therapy (eg, cefdinir, of at least 10 days, during which the patient is asympto-
cefuroxime, or cefpodoxime) is recommended for chil- matic. Chronic sinusitis is now defined as episodes of
dren intolerant of amoxicillin. Resistance to any bacte- inflammation of the paranasal sinuses lasting more than
riostatic antibiotic such as trimethoprim–sulfamethoxa- 90 days. Although recent meta-analysis evaluations
zole and erythromycin–sulfisoxazole is great enough have resulted in recommendations for acute sinusitis,
that these medications are no longer recommended un- there is a paucity of data for the treatment of recurrent
less the patient is allergic to both penicillin and or chronic sinusitis. Important factors to consider in-
cephalosporin. Clindamycin is another possible choice, clude allergies, anatomic variations, and disorders in
particularly in older patients, but it is not effective host immunity. Mucosal inflammation leading to ob-
against gram-negative organisms such as H influenzae. struction is most commonly caused by allergic rhinitis
Failure to improve after 48 hours suggests a resistant and occasionally by nonallergic rhinitis. Gastroesopha-
organism or potential complication. [See the section on geal reflux has also been found to be associated with
unresponsive AOM for antibiotic recommendations chronic sinusitis, and its treatment may result in dra-
(Table 17–2), which are also appropriate for sinusitis.] matic improvements in sinus symptoms. Rarely,
Topical decongestants and oral combinations are chronic sinusitis is caused by anatomic variations, such
frequently used in acute sinusitis to promote drainage. as septal deviation, polyp, or foreign body. Allergic
492 / CHAPTER 17

polyps are unusual in children younger than age Suskind DL et al: Gastroesophageal reflux and pediatric otolaryn-
10 years and therefore indicate a work-up for cystic fi- gologic disease: The role of antireflux surgery. Arch Otolaryn-
gol Head Neck Surg 2001;127:511 [PMID: 11346425].
brosis. In cases of chronic or recurrent pyogenic pansi-
nusitis, poor host resistance (eg, an immune defect,
Kartagener syndrome, or cystic fibrosis)—though CHOANAL ATRESIA
rare—must be ruled out by immunoglobulin studies,
Choanal atresia occurs in approximately 1 in 7000 live
microscopic studies of respiratory cilia, and a sweat
births. The female-to-male ratio is 2:1, and unilateral to
chloride test. Anaerobic and staphylococcal organisms
bilateral is also 2:1. Bilateral atresia results in severe res-
are often responsible for chronic sinusitis. Evaluation
piratory distress at birth and requires immediate place-
by an allergist and an otolaryngologist may be useful in
ment of an oral airway. Unilateral atresia usually ap-
determining the underlying causes.
pears later as a unilateral chronic nasal discharge that
can be confused with chronic sinusitis. Diagnosis may
Medical Treatment be suspected if a 6 Fr catheter cannot be passed through
Antibiotic therapy is similar to that used for acute si- the nose and is confirmed by axial CT scan. CHARGE
nusitis, but the duration is longer. Antimicrobial choice (coloboma, heart disease, atresia chonae, retarded
should include drugs effective against staphylococcal growth and retarded development and/or CNS anom-
organisms. Adjuvant therapies such as saline nasal irri- alies, genital hypoplasia, and ear anomalies and/or deaf-
gations, decongestants, antihistamines, and topical in- ness) association (see Chapter 33) or other congenital
tranasal steroids may be helpful depending on the un- anomalies are present in 50% of patients. An oral air-
derlying cause. way should be used when a newborn has been diag-
nosed with bilateral choanal atresia until more defini-
tive treatment by an otolaryngologist has been
Surgical Treatment accomplished.
A. ANTRAL LAVAGE
Keller JL, Kacker A: Choanal atresia, CHARGE association, and
Antral lavage, generally regarded as a diagnostic proce- congenital nasal stenosis. Otolaryngol Clin North Am
dure, may have some therapeutic value. An aspirate or a 2000;33:1343 [PMID: 11449791].
sample irrigated from the maxillary sinus is retrieved ei-
ther with a spinal needle or a curved-tip instrument
under anesthesia. In the very young child, this may be RECURRENT RHINITIS
the only procedure that should be performed. Recurrent rhinitis is frequently seen in the office prac-
tice of pediatrics. The child is brought in with the chief
B. ENDOSCOPIC SINUS SURGERY complaint of having “one cold after another,” “constant
No data are available comparing the outcome of this colds,” or “always being sick.” Approximately two
procedure with traditional surgical drainage procedures. thirds of these children have recurrent colds, and the re-
There are large variations in the reported uses of this mainder have either allergic rhinitis or recurrent sinusi-
procedure by otolaryngologists, especially in younger tis.
patients.
C. EXTERNAL DRAINAGE Allergic Rhinitis
External drainage procedures are reserved for complica- Allergic rhinitis has significant morbidity and may con-
tions arising from ethmoid and frontal sinusitis. tribute to the development of sinusitis and asthma exac-
erbations. Symptoms of frequent sneezing, rubbing of
Jailwala JA, Shaker R: Oral and pharyngeal complications of gastro- the nose, and clear drainage interfere with concentra-
esophageal reflux disease: Globus, dental erosions, and tion at school. Nighttime nasal congestion interferes
chronic sinusitis. J Clin Gastroenterol 2000;30 (3 Suppl): with sleep and causes daytime somnolence and hyperac-
S35 [PMID: 10777170]. tivity. On physical examination the nasal turbinates are
Jiang RS, Hsu CY: Functional endoscopic sinus surgery in children swollen, but may be red or pale pink. Treatment with
and adults. Ann Otol Rhinol Laryngol 2000;109:1113
[PMID: 11130821].
nasal steroids is effective in decreasing the airway ob-
struction and rhinorrhea. Sneezing and clear drainage
Nostrant TT, Rabine JC: Diagnosis and management of supra-
esophageal complications of reflux disease. Curr Gastroen- are controlled with nonsedating antihistamines. Iprat-
terol Rep 2000;2(3):210 [PMID: 10957932]. ropium can be used as an adjunctive therapy.
Phipps CD et al: Gastroesophageal reflux contributing to chronic
sinus disease in children: A prospective analysis. Arch Oto- Pullerits T et al: Comparison of a nasal glucocorticoid, an-
laryngol Head Neck Surg 2000;126:831 [PMID: 10888994]. tileukotriene, and a combination of antileukotriene and anti-
 EAR, NOSE, & THROAT / 493

histamine in the treatment of seasonal allergic rhinitis. J Al- inserted over the bleeding site and held in place by the
lergy Clin Immunol 2002;109(6):949 [PMID: 12063523]. parent.
The allergy report: http://www.aaaai.org/ar/working_vol1/073.asp. Friability of the nasal vessels can be decreased with
daily application of water-based ointment by cotton-
Vasomotor Rhinitis tipped applicator. The lubricant is applied daily until
5 days have passed without a nosebleed, then weekly for
Some children react to sudden changes in environmen- 1 month. Twice daily nasal saline irrigation and humid-
tal temperature with prolonged congestion and rhinor- ification of the patient’s bedroom may also be helpful.
rhea. Air pollution (especially tobacco smoke) may be a Aspirin and ibuprofen should be avoided, as should vig-
factor. Oral decongestants or nasal steroids can be used orous blowing of the nose.
to give symptomatic relief.
NASAL INFECTION
EPISTAXIS A nasal furuncle is an infection of a hair follicle in the
The nose is an extremely vascular structure. In most anterior nares. Hair plucking or nose picking can pro-
cases, epistaxis (nosebleed) is due to mild trauma to the vide a route of entry. The most common organism is S
anterior portion of the nasal septum (Kiesselbach area), aureus. The diagnosis is made by finding an exquisitely
usually due to vigorous nose rubbing, nose blowing, or tender, firm, red lump in the anterior nares. Treatment
nose picking. If a patient has been using a nasal steroid includes dicloxacillin or cephalexin orally for 5 days to
spray, check the patient’s technique to make sure he or prevent spread. The lesion should be gently incised and
she is directing the nozzle at the lateral canthus of the drained as soon as it points, usually with a needle. Top-
eye and not the septum. If this does not reduce the ical bacitracin ointment may be of additional value. Be-
nosebleeds, then the steroid spray should be discontin- cause this lesion is in the drainage area of the cavernous
ued. Examination of the Kiesselbach area usually reveals sinus, the patient should be followed closely until heal-
a red, raw surface with fresh clots or old crusts. Also ing is complete. Parents should be advised never to pick
look for telangiectasia, hemangiomas, or varicosities. or squeeze a furuncle in this location—and neither
Less than 5% of epistaxis is caused by a bleeding dis- should the physician. Associated cellulitis or spread re-
order such as von Willebrand disease. Patients need a quires hospitalization for administration of intravenous
hematologic work-up if any of the following is present: antibiotics.
a family history of a bleeding disorder; a medical his- A nasal septal abscess usually follows nasal trauma or
tory of easy bleeding, particularly with circumcision or a nasal furuncle. Examination reveals a fluctuant gray
dental extraction; spontaneous bleeding at any site; septal swelling, usually bilateral. The possible complica-
bleeding that lasts for over 30 minutes or blood that tions are the same as for nasal septum hematoma (see
will not clot with direct pressure by the physician; onset following discussion). In addition, spread of the infec-
before age 2 years; or a drop in hematocrit due to epi- tion to the CNS is possible. Treatment consists of im-
staxis. High blood pressure may rarely predispose to mediate hospitalization and incision and drainage by an
prolonged nosebleeds. otolaryngologist.
A nasopharyngeal angiofibroma may be manifested
by recurrent epistaxis. Adolescent boys are affected al-
most exclusively. CT scan of the nasal cavity and na- NASAL TRAUMA
sopharynx is diagnostic. Newborn infants rarely present with subluxation of the
quadrangular cartilage of the septum. In this disorder,
the top of the nose deviates to one side, the inferior sep-
Treatment tal border deviates to the other side, the columella
The following approach can be carried out in the office leans, and the nasal tip is unstable. This disorder must
or offered as phone advice: The patient should sit up be distinguished from the more common transient flat-
and lean forward so as not to swallow the blood. Swal- tening of the nose caused by the birth process. In the
lowed blood may cause nausea, and hematemesis alarms past, physicians were encouraged to reduce all subluxa-
the family. The nasal cavity should be cleared of clots tions in the nursery. Otolaryngologists are more likely
by gentle blowing. The soft part of the nose is pinched to perform the reduction under anesthesia for more dif-
firmly enough to prevent arterial blood flow, with pres- ficult cases.
sure over the bleeding site being maintained for 5 min- Most blows to the nose result in swallowing of
utes by the clock. If bleeding continues, the bleeding blood and hematoma formation without fracture. A
site needs to be visualized. A small piece of gelatin persistent nosebleed after trauma, crepitus or instability
sponge (Gelfoam) or collagen sponge (Surgicel) can be of the bones in the nasal bridge, and marked deviation
494 / CHAPTER 17

of the nose to one side indicate fracture. However, sep-

tal injury can be ruled out only by careful intranasal ex- III. THE THROAT & ORAL CAVITY
amination, not radiologically. Patients with suspected
nasal fractures should be referred to an otolaryngologist
for definitive therapy. Resetting of the nasal fracture ACUTE STOMATITIS
can be postponed up to 1 week without resulting in
permanent deformity. Recurrent Aphthous Stomatitis
After nasal trauma, it is essential to examine the in- Also referred to as canker sores, these small ulcers
side of the nose with a nasal speculum. Hematoma of (3–10 mm) are found on the insides of the lips or in the
the nasal septum imposes a considerable risk of pressure anterior mouth; rarely they may appear on the tonsils
necrosis and resorption of the cartilage, leading to sep- or palate. There is usually no associated fever and no
tal perforation or a saddle-back nose in adulthood. This cervical adenopathy. The ulcers may be painful and last
diagnosis is confirmed by the abrupt onset of nasal ob- 1–2 weeks. They may recur numerous times through-
struction following trauma and the presence of a boggy, out life. The cause is unknown, although an allergic or
widened nasal septum. The normal nasal septum is autoimmune basis is suspected.
only 2–4 mm thick, and the back end of a cotton swab Treatment consists of coating the lesions with be-
may be helpful for palpation. tamethasone valerate ointment twice daily, because un-
Treatment consists of prompt referral to an oto- like other topical steroids, it adheres to the mucosa.
laryngologist for evacuation of the hematoma and pack- Pain can also be reduced by eating a bland diet, avoid-
ing of the nose. ing salty or acidic foods and juices, and giving aceta-
minophen or ibuprofen at bedtime.
Other less common causes of recurrent aphthous ul-
FOREIGN BODIES IN THE NOSE cers include Behçet disease, familial Mediterranean
fever, and the fever, aphthous stomatitis, pharyngitis,
The most common foreign bodies in the nose are seeds and cervical adenopathy syndrome (FAPA) syndrome.
or beads. If the diagnosis is delayed, unilateral rhinor- A diagnosis of Behçet disease requires two of the fol-
rhea, foul smell, halitosis, bleeding, or nasal obstruction lowing: genital ulcers, uveitis, and erythema nodosum-
may occur. The leading cause of halitosis in children is like lesions. Patients with Mediterranean fever have a
a nasal foreign body, and not dental disease as in adults. positive family history, serosal involvement, and fever.
There are many ways to remove nasal foreign bod- FAPA syndrome was first described in 1987, and its
ies. The obvious first maneuver is vigorous nose blow- cause is unknown. It usually begins before a child is
ing if the child is old enough. The next step in removal 5 years of age and continues through adolescence, then
requires topical anesthesia, nasal decongestion, good resolves. It recurs at 4- to 6-week intervals, and an
lighting, correct instrumentation, and physical re- episode may be dramatically improved with prednisone
straint. Topical tetracaine or lidocaine can be used in bursts, but recurrences continue. In one case report it
young children. Nasal decongestion can be achieved by resolved totally with a 6-month course of cimetidine,
topical pseudoephedrine or oxymetazoline. When the suggesting an immune etiology. FAPA may also resolve
child is properly restrained, most nasal foreign bodies with tonsillectomy (see Tonsillectomy section), and an
can be removed using a pair of alligator forceps through otolaryngology referral is appropriate. The ulcers in all
an operating head otoscope. If the object seems unlikely of these syndromes respond to betamethasone valerate
to be removed on the first attempt, is wedged in, or is application.
quite large, the patient should be referred to an oto-
laryngologist rather than worsening the situation Dahn KA, Glode MP, Chan KH: Periodic fever and pharyngitis in
through futile attempts at removal. young children: A new disease for the otolaryngologist? Arch
Because the nose is a moist cavity, the electrical cur- Otolaryngol Head Neck Surg 2000;126:1146 [PMID:
rent generated by disk-type batteries—such as those 10979131].
used in clocks, watches, and hearing aids—can cause
necrosis of mucosa and cartilage destruction in less than Herpes Simplex Gingivostomatitis
4 hours. This constitutes a true foreign body emer- (see also Chapter 36)
gency.
Children having their first encounter with the herpes
simplex virus develop 10 or more small ulcers
Kelley PE: Foreign bodies in the nose and pharynx. In Burg FD et (1–3 mm) of the buccal mucosa, anterior pillars, inner
al (eds): Gellis and Kagan’s Current Pediatric Therapy, 16th lips, tongue, and especially the gingiva. The lesions are
ed. WB Saunders, 1999. often associated with fever lasting up to 7 days, tender
 EAR, NOSE, & THROAT / 495

cervical nodes, and generalized inflammation of the types of viral pharyngitis are sufficiently distinctive to
mouth. Affected children are commonly younger than support an educated guess about the specific cause (see
3 years of age. Gingivostomatitis lasts 7–10 days. Treat- Chapter 36).
ment is symptomatic, as described earlier for recurrent
aphthous stomatitis, with the exception that cortico- Clinical Findings
steroids are contraindicated because they may cause
spread of the infection. If seen early in the course, the A. INFECTIOUS MONONUCLEOSIS
physician should prescribe oral acyclovir suspension The findings are exudative tonsillitis, generalized cervi-
(200 mg/5 mL), 20 mg/kg/dose, 4 times daily for cal adenitis, and fever, usually in a patient older than
5 days. The patient must be followed closely because 5 years of age. A palpable spleen or axillary adenopathy
dehydration occasionally develops, requiring hospital- increases the likelihood of the diagnosis. The presence
ization. Herpetic laryngotracheitis is a rare complica- of more than 10% atypical lymphocytes on a peripheral
tion. blood smear or a positive mononucleosis spot test sup-
ports the diagnosis, although these tests are often falsely
Thrush (see also Chapter 39) negative in children younger than age 5 years. Ep-
stein–Barr virus serology showing an elevated IgM-cap-
Oral candidiasis mainly affects infants and occasionally sid antibody is definitive.
older children in a debilitated state. Candida albicans is
a saprophyte that normally is not invasive unless the B. HERPANGINA
mouth is abraded or the patient is immunocompro- Herpangina ulcers, 2–3 mm in size and surrounded by
mised. The use of broad-spectrum antibiotics and sys- a halo, are found on the anterior pillars, the soft palate,
temic or inhaled steroids may be contributing factors. and the uvula. No ulcers are present in the anterior
The symptoms include soreness of the mouth and re- mouth as there are in herpes simplex. Herpangina is
fusal of feedings. Lesions consist of white curd-like caused by several members of the coxsackie A group of
plaques predominantly on the buccal mucosa. These viruses, and a patient may have several bouts of her-
plaques cannot be washed away after a water feeding. pangina.
Specific treatment consists of nystatin oral suspen-
sion, 2 mL four times daily for 1 week, or miconazole C. LYMPHONODULAR PHARYNGITIS
gel. Treatment should be preceded by attempts to re- The classic finding is small, yellow-white nodules in the
move large plaques with a moistened cotton-tipped ap- same distribution as the small ulcers in herpangina. In
plicator or piece of gauze, or half the nystatin may be this condition, which is caused by coxsackievirus A10,
rubbed on the lesions with an applicator. Gentian violet the nodules do not ulcerate.
is probably also effective, but stains clothing and skin.
D. HAND, FOOT, AND MOUTH DISEASE
Traumatic Oral Ulcers This entity is caused by coxsackieviruses A5, A9, A10,
and A16. Ulcers occur on the tongue and oral mucosa.
Mechanical trauma most commonly occurs on the buc- Vesicles, which usually do not ulcerate, are found on
cal mucosa secondary to accidentally biting with the the palms, soles, interdigital areas, and buttocks.
molars. Thermal trauma, from very hot foods, can also
cause ulcerative lesions. Chemical ulcers can be pro- E. PHARYNGOCONJUNCTIVAL FEVER
duced by mucosal contact with aspirin, caustics, and This disorder is caused by an adenovirus and often is
the like. Oral ulcers can also occur with leukemia or on epidemic. Exudative tonsillitis, conjunctivitis, lym-
a recurrent basis with cyclic neutropenia. These lesions phadenopathy, and fever are the main findings, and
usually need no treatment. The pain subsides in 2 or treatment is symptomatic.
3 days.
ACUTE BACTERIAL PHARYNGITIS
ACUTE VIRAL PHARYNGITIS
Approximately 10% of children with sore throat and
& TONSILLITIS fever have a group A streptococcal infection. Less com-
Figure 17–8 is an algorithm for the management of a mon causes of bacterial pharyngitis are Mycoplasma
sore throat. pneumoniae, Chlamydia pneumoniae, groups C and G
Over 90% of cases of sore throat and fever in chil- streptococci, and Arcanobacterium hemolyticum. Of the
dren are due to viral infections. Most children develop five, M pneumoniae is by far the most common and
associated rhinorrhea and mild cough. The findings sel- may cause over one third of all pharyngitis cases in ado-
dom give any clue to the particular viral agent, but six lescents and adults.
496 / CHAPTER 17

Pharyngitis

Assess degree of illness

Mild to moderate Severe (see below)

Afebrile with Child febrile or tender cervical nodes

upper respiratory or tonsillar exudate or S. pyogenes exposure
tract infection or family history of rheumatic fever

Rapid Strep test

Symptomatic
care

Negative Positive

Send throat culture 10 days penicillin VK at 50 mg/kg up to

500 mg in 2 divided doses or intramuscular
benzathine penicillin or if penicillin-allergic,
Negative Positive erythromycin estolate 20 mg/kg/d
in two divided doses

Cure Failure or relapse in < 1 week

Repeat throat culture and consider

Severe pharyngitis serologic testing for mononucleosis

ENT consult
Mononucleosis Persistent
test positive S. pyogenes

Unilateral swelling Bilateral swelling of Airway compromised

of tonsils tonsils with airway problems
Counsel about 1. Intramuscular Bicillin® or
contact sports 2. ß-lactamase-active antibiotic
with sleep

Drain surgically if 1. Throat culture and Lateral neck or CT

abcess rapid test scan to identify
or treat intravenously 2. Mononucleosis retro-pharyngeal
if cellutitis diagnostic tests abcess and related
(complete blood count, problems
monospot, EBV-IgM)

Admit for observation Admit to intensive

care unit

Figure 17–8. Algorithm for pharyngitis.

Untreated streptococcal pharyngitis can result in the only way to make a definitive diagnosis is by throat
acute rheumatic fever, glomerulonephritis, and suppu- culture or rapid antigen test. Rapid antigen tests are
rative complications (eg, cervical adenitis, peritonsillar very specific, but have a sensitivity of 85–95%. There-
abscess, otitis media, cellulitis, and septicemia). Vesicles fore, a positive test indicates S pyogenes infection, but a
and ulcers are suggestive of viral infection, whereas ten- negative result requires confirmation with culture.
der anterior cervical nodes, petechiae, a beefy-red uvula, The physician should treat cases of suspected or
and a tonsillar exudate suggest streptococcal infection; proven group A streptococcal infection with a 10-day
 EAR, NOSE, & THROAT / 497

course of oral penicillin V potassium, a cephalosporin, If the child has a history of recurrent streptococcal
or intramuscularly injected penicillin G benzathine infection, the physician should document the absence
(Table 17–3). Penicillin VK is equally effective if given of S pyogenes in an asymptomatic patient following a
in two or three divided doses, except in adolescents, for course of therapy. If compliance or the adequacy of an-
whom three doses are recommended, but is not effec- tibiotic dosage was questionable, the infection may be
tive once daily. Amoxicillin, azithromycin, and ce- treated with intramuscular penicillin; otherwise, an an-
fadroxil may be given once daily. Cephalexin given tibiotic effective against β-lactamase-producing organ-
in four divided doses is inexpensive, but it has never isms (amoxicillin plus clavulanate, a cephalosporin, or a
been studied with fewer daily doses. Penicillin-allergic macrolide) may be used. If this therapy fails to eradicate
patients should be given erythromycin estolate in the organism, a course of clindamycin for 10 days
two or three divided doses, not the poorly absorbed should be considered.
ethylsuccinate preparation, which causes vomiting and In general, the carrier state is harmless, self-limited
abdominal cramping. The treatment failure rate (2–6 months), and not contagious. An attempt to erad-
after 10 days of penicillin VK administered three times icate the carrier state is warranted only if the patient or
daily varies from 6% to 23%. The small differences another family member has frequent streptococcal in-
between the cure rates of penicillin and cephalosporins fections or when a family member or patient has a his-
reported in the literature may represent eradication tory of rheumatic fever or glomerulonephritis.
of the carrier state rather than treatment failure. Causes Treatment should be considered for carriers who
of treatment failure include unrecognized carriers, live in closed or semiclosed community settings. If the
poor compliance, acquisition of a different strain, inac- patient has had three or more documented infections
tivation of penicillin by β-lactamase produced by within 6 months, daily penicillin prophylaxis may be
throat flora, or the development of tolerance by S pyo- given during the winter season. Patients may be re-
genes. Approximately 5% of S pyogenes are resistant to ferred for tonsillectomy if they continue to have fre-
erythromycin. Trimethoprim–sulfamethoxazole is not quent episodes or if persistently enlarged tonsils cause
an effective antibiotic against S pyogenes. Children chronic upper airway obstruction. “Frequent” is de-
should receive 24 hours of therapy before returning to fined as seven episodes in 1 year, five per year for
school. 2 years, or three per year for 3 years.

Table 17–3. Treatment of group A streptococcal pharyngitis.

Drug Dosage Maximum Adult Dose Formulations Comments

Penicillin VK 250 mg bid for 10 days, 500 mg 1000 mg 250 mg/tsp; 250 mg Preferred by American
bid or tid for adolescents & tablets and 500 mg Heart Association (AHA)
adults tablets
Amoxicillina 750 mg once daily for 10 days in 750 mg 250 mg/tsp; 250 mg For poorly compliant
patients older than age 3 years tablets patients
IM Benzathine If < 27 kg, 600,000 U; if > 27 kg, If preferred by parent.
penicillin 1.2 million U AHA endorsed
For penicillin-allergic patients
Erythromycin 20 mg/kg bid for 10 days 250 mg bid 250 mg/tsp; 250 mg Preferred by AHA
estolate (250/5) tablets
Zithromax 12 mg/kg/d for 5 days (not the 500 mg on day 1 and 15 ml of 100/5 mL; Expensive. For poorly
otitis media dose) 250 mg for 4 days more 15 ml of 200/5 mL; compliant patients
30 ml of 200/5 mL
First-generation Varies with agent These agents should not
cephalosporins be used to treat patients
with immediate-type hy-
persensitivity to -lac-
tam antibiotics
a
Preferred by some doctors for younger children because of taste.
498 / CHAPTER 17

Bisno AL et al: Practice guidelines for the diagnosis and manage- RETROPHARYNGEAL ABSCESS
ment of group A Streptococcal pharyngitis. Clin Infect Dis
2002;35:113 [PMID: 12087516]. Retropharyngeal nodes drain the adenoids, nasophar-
Lan AJ, Colford JM: The impact of dosing frequency on the effi- ynx, and paranasal sinuses and can become infected.
cacy of 10-day penicillin or amoxicillin therapy for Strepto- The most common causes are β-hemolytic streptococci
coccal tonsillopharyngitis: A meta-analysis. Pediatrics elec- and S aureus. If this pyogenic adenitis goes untreated, a
tronic pages 2000;105:e19 [PMID: 10654979].
retropharyngeal abscess forms. The process occurs most
commonly during the first 2 years of life. Beyond this
PERITONSILLAR CELLULITIS OR age, retropharyngeal abscess usually results from super-
ABSCESS (QUINSY) infection of a penetrating injury of the posterior wall of
the oropharynx.
Tonsillar infection occasionally penetrates the tonsillar The diagnosis of retropharyngeal abscess should be
capsule, spreads to the surrounding tissues, and causes strongly suspected in an infant with fever, respiratory
peritonsillar cellulitis. If untreated, necrosis occurs and symptoms, and neck hyperextension. Dysphagia, drool-
a tonsillar abscess forms. This can occur at any age. The ing, dyspnea, and gurgling respirations are also found
most common cause is β-hemolytic streptococcal infec- and are due to impingement by the abscess. Prominent
tion. Other pathogens are group D streptococci, β-he- swelling on one side of the posterior pharyngeal wall
molytic streptococci, S pneumoniae, and anaerobes. confirms the diagnosis. Swelling usually stops at the
The patient complains of a severe sore throat even midline because a medial raphe divides the prevertebral
before the physical findings become marked. A high space. Lateral neck soft tissue films show the retropha-
fever is usually present, and the process is almost always ryngeal space to be wider than the C4 vertebral body.
unilateral. The tonsil bulges medially, and the anterior Although retropharyngeal abscess is a surgical emer-
tonsillar pillar is prominent. The soft palate and uvula gency, frequently it cannot be distinguished from retro-
on the involved side are edematous and displaced to- pharyngeal adenitis. Immediate hospitalization and in-
ward the uninvolved side. In cases of abscess formation, travenous antimicrobial therapy with a semisynthetic
trismus, ear pain, dysphagia, and, eventually, drooling penicillin or clindamycin is the first step for most cases.
occur. The most serious complication of inadequately Immediate surgical drainage is required when a definite
treated peritonsillar abscess is a lateral pharyngeal ab- abscess is seen radiographically or when the airway is
scess. This causes fullness and tenderness of the lateral compromised markedly. In most instances, a period of
neck as well as torticollis. Without intervention, the lat- 12–24 hours of antimicrobial therapy will help to dif-
eral pharyngeal abscess threatens life by airway obstruc- ferentiate the two entities. In the child with adenitis,
tion or carotid artery erosion. If airway symptoms are fever will decrease and oral intake will increase. A child
present, an immediate otolaryngology consultation is with retropharyngeal abscess will continue to deterio-
indicated. rate. A surgeon should incise and drain the abscess
It is often difficult to differentiate peritonsillar cel- under general anesthesia to prevent its extension.
lulitis from abscess. In some children, it is possible to
aspirate the peritonsillar space to diagnose and treat an
abscess. However, it is reasonable to admit a child for LUDWIG ANGINA
12–24 hours of intravenous antimicrobial therapy, be-
cause aggressive treatment in early cases of peritonsillar Ludwig angina is a rapidly progressive cellulitis of the
cellulitis usually prevents suppuration. Therapy with submandibular space that can cause airway obstruction
penicillin or clindamycin is appropriate. Failure to re- and death. The submandibular space extends from the
spond to therapy during the first 12–24 hours indicates mucous membrane of the floor of the mouth to the
a high probability of abscess formation. An otolaryngol- muscular and fascial attachments of the hyoid bone.
ogist should be consulted for incision and drainage or This infection is encountered infrequently in infants
for aspiration under local anesthesia. and children. The initiating factor in over 50% of cases
Recurrent peritonsillar abscesses are so uncommon is dental disease, including abscesses and extraction.
(7%) that routine tonsillectomy for a single bout is not Some patients have a history of lacerations and injuries
indicated unless other tonsillectomy indications exist. to the floor of the mouth. Group A streptococcus is the
Hospitalized patients can be discharged on oral antibi- most common organism identified, but other
otics when fever has resolved for 24 hours and dyspha- pathogens cause the infection.
gia has improved. The manifestations are fever and tender swelling of
the floor of the mouth. The tongue can become en-
Herzon FS, Nicklaus P: Pediatric peritonsillar abscess: Manage- larged as well as tender and erythematous. Upward dis-
ment guidelines. Curr Probl Pediatr 1996;26:270 [PMID: placement of the tongue may cause dysphagia, drool-
8899288]. ing, and airway obstruction.
 EAR, NOSE, & THROAT / 499

Treatment consists of giving high doses of intra- mildly tender, but may suppurate and drain. About one
venous clindamycin or ampicillin plus nafcillin until third of children have fever and malaise, and, rarely,
the results of cultures and sensitivity tests are available. neurologic sequelae and prolonged fever occur. Cat-
Because the most common cause of death in Ludwig scratch disease, caused by B henselae, can be diagnosed
angina is sudden airway obstruction, the patient must by serologic testing available at commercial laborato-
be monitored closely in the intensive care unit and in- ries, but testing is not always confirmatory. Blood
tubation provided for progressive respiratory distress. should be drawn 2–8 weeks after onset of symptoms.
An otolaryngologist should be consulted to identify and Because most nodes caused by this pathogen sponta-
perform a drainage procedure. neously resorb within 1–3 months, the benefit of an-
tibiotics is controversial. In a placebo-controlled trial,
Britt JC et al: Ludwig’s angina in the pediatric population: Report azithromycin for 5 days caused a more rapid decrease in
of a case and review of the literature. Int J Pediatr Otorhino- node size. Other drugs likely to be effective include ri-
laryngol 2000;52:79. fampin, trimethoprim–sulfamethoxazole, erythromy-
cin, clarithromycin, doxycycline, ciprofloxacin, and
gentamicin.
ACUTE CERVICAL ADENITIS Cervical lymphadenitis can be caused by nontuber-
Local infections of the ear, nose, and throat can spread culous mycobacterial species or Mycobacterium avium
to a regional node and cause a secondary inflammation. complex. The adenitis is usually unilateral and indo-
The typical case involves a large, unilateral, solitary, an- lent, but may involve several adjacent nodes. A charac-
terior cervical node. About 70% of these cases are due teristic violaceous appearance may develop over a pro-
to β-hemolytic streptococcal infection, 20% to staphy- longed period of time without systemic signs or much
lococci, and the remainder to viruses, atypical mycobac- local pain. Atypical mycobacterial infections are often
teria, and Bartonella henselae. Surgeons report a higher associated with PPD skin reactions less then 10 mm.
incidence of staphylococcal infection, but they see a Once the diagnosis is suspected due to a positive
greater proportion of atypical cases that have failed to PPD, a chest radiograph should be done and all family
respond to penicillin therapy and thus require incision members tested for tuberculosis. The node should not
and drainage. The most common antecedent infection be incised and drained, because that may lead to a
is pharyngitis. Other entry sites for cervical adenitis in- draining sinus tract. Instead, a complete excision of all
clude a periapical dental abscess (usually producing a nodes should be done by an experienced surgeon.
submandibular adenitis), facial impetigo (infected cuts Nodes may recur, usually within 3 months of surgery.
or bug bites), infected acne, and otitis externa (usually In such cases, a newer macrolide in combination with a
producing a preauricular adenitis). second drug (rifampin or ethambutol) is given for
The initial evaluation of cervical adenitis should 3–6 months.
generally include a group A streptococcal diagnostic
test, a complete blood count with differential (looking Differential Diagnosis
for atypical lymphocytes), and a purified protein deriv-
ative skin test (PPD), looking for nontuberculous my- A. NEOPLASMS AND CERVICAL NODES
cobacteria. If no cause is found, a mononucleosis test is Malignant tumors usually are not suspected until the
useful. Early treatment with antibiotics prevents many adenopathy persists despite treatment. Classically, the
cases of pyogenic adenitis from progressing to suppura- nodes are painless, nontender, and firm to hard in con-
tion. However, once fluctuation occurs, antibiotic ther- sistency. They may be fixed to underlying tissues. These
apy alone is often insufficient. When fluctuation is pre- nodes may occur as a single node, as unilateral multiple
sent, needle aspiration may promote resolution. If nodes in a chain, as bilateral cervical nodes, or as gener-
needle aspiration is done, the pus should be sent for a alized adenopathy. Common malignancies that may
Gram stain, aerobic and anaerobic culture, an acid-fast present in the neck include Hodgkin disease, non-
stain for Mycobacteria, and an acid-fast smear and tu- Hodgkin lymphoma, rhabdomyosarcoma, and thyroid
berculosis culture. If needle aspiration is not effective, a carcinoma.
surgeon should incise and drain the abscess. Hospital-
ization is required only if the patient is toxic, dehy- B. IMITATORS OF ADENITIS
drated, dysphagic, or dyspneic. Several structures in the neck can become infected and
Cat-scratch disease is frequently implicated in cases resemble a node. The first three masses are of congeni-
of chronic cervical adenopathy. The diagnosis is aided tal origin and are listed in order of frequency.
by the finding of a primary papule on the face. In over
90% of patients, cat scratches are present or there is a 1. Thyroglossal duct cyst—When superinfected, this
history of contact with kittens. The node is usually only congenital malformation can become acutely swollen.
500 / CHAPTER 17

Helpful findings are the fact that it is in the midline, lo- When parents report that their child has nightly
cated between the hyoid bone and suprasternal notch, snoring and is a mouth breather even during the day,
and moves upward when the tongue is stuck out or one should be suspicious of obstructive sleep apnea
during swallowing. Occasionally, the cyst develops a (OSA). Figure 17–9 is an algorithm for management of
sinus tract and opening just lateral to the midline. these complaints. The adenoids can be assessed by mir-
2. Branchial cleft cyst—When superinfected, this ror examination, endoscopy, or radiographic studies.
malformation can become a tender mass 3–5 cm in di- Either adenoid hypertrophy or nasal obstruction can be
ameter. Aids to diagnosis are the fact that the mass is lo- assumed when a child has hyponasal speech. The con-
cated along the anterior border of the sternocleidomas- sonants “m,” “n,” and “ng” rely on the palate not
toid muscle and is smooth and fluctuant. Occasionally touching the posterior pharyngeal wall. By having a
it is attached to the overlying skin by a small dimple or child repeat the word “banana” or “ninety-nine” with
a draining sinus tract. the nose open or pinched closed, one may assess the
nasal and nasopharyngeal airways. If the voice does not
3. Lymphatic malformation (cystic hygroma)— change with occlusion of the nostrils, then either ade-
Most of these lymphatic cysts are located in the posteri- noid or nasal obstruction is present.
or triangle just above the clavicle. The mass is soft and Although nasal obstruction is usually due to allergic
compressible and can be transilluminated. Over 60% of rhinitis and can be diagnosed by a careful allergy his-
hygromas are noted at birth, and the remainder are usu- tory, there are other, less common causes. Nasal polyps
ally seen by the time the child is age 2 years. If cysts be- appear as glistening, gray to pink, jelly-like masses that
come large enough, they can compromise the patient’s are prominent just inside the anterior nares and occur
ability to swallow and breath. singly or in clusters. They occur in cystic fibrosis and
4. Parotitis—The most common pitfall in differential severe allergic rhinitis. Persistent mouth-breathing may
diagnosis of cervical adenopathy is mistaking parotitis also rarely be due to a nasopharyngeal tumor, or to a
for adenitis. However, a swollen parotid crosses the meningocele herniated into the nasal cavity. For male
angle of the jaw, is associated with preauricular percus- patients, if unilateral nasal obstruction and epistaxis
sion tenderness, and is bilateral in 70% of cases. There occur frequently, juvenile angiofibroma should be sus-
may be a history of exposure to mumps, but in the pected. If allergic rhinitis is the suspected cause of snor-
United States other viruses are now the main cause. An ing, a trial of intranasal corticosteroid spray is indi-
amylase level will be elevated in parotitis. cated. If enlarged tonsils (Figure 17–10) or adenoids are
5. Ranula—A ranula is a cyst in the floor of the mouth present, a referral to an otolaryngologist or a pediatric
caused by obstruction of the ducts of the sublingual sleep laboratory is in order.
gland. A plunging ranula extends below the mylohyoid
muscle and can appear as a neck mass. Diagnosis
6. Sternocleidomastoid muscle hematoma—This The gold standard for diagnosis of OSA is a
cervical mass is noted at age 2–4 weeks. On close exam- polysomnogram. A patient’s history and clinical exami-
ination, it is found to be part of the muscle body and nation cannot predict the presence or severity of OSA.
not movable. An associated torticollis usually confirms An overnight oximetry study is a poor screening test for
the diagnosis. OSA. The test may detect those patients with severe
disease but miss the milder cases. OSA is part of a spec-
Maltezou HC et al: Nontuberculous mycobacterial lymphadenitis
in children. Pediatr Infect Dis J 1999;18:968 [PMID:
trum of disorders that occur during sleep. A milder
10571431]. form of OSA is upper airway resistance syndrome. Pa-
Peters TR, Edwards KM: Cervical lymphadenopathy and adenitis. tients with this syndrome have an otherwise normal
Pediatr Rev 2000;21:399 [PMID: 11121496]. polysomnogram with the only evidence of obstruction
being increased respiratory effort. The criteria for diag-
SNORING, MOUTH BREATHING, & nosing OSA differ between children and adults. An ob-
structive event occurs when airflow stops despite persis-
UPPER AIRWAY OBSTRUCTION tence of respiratory effort. A hypopnea is counted when
In April 2002, the American Academy of Pediatrics airflow and respiratory effort decrease with an associ-
published a Clinical Practice Guideline for the diagno- ated oxygen desaturation or arousal. Normative values
sis and management of uncomplicated childhood ob- are just being established. An investigation of sleep-dis-
structive sleep apnea syndrome (OSAS). The guideline ordered breathing in children between the ages of 6 and
emphasizes that pediatricians should screen all children 11 years is the first study to evaluate clinical relevance
for snoring and that complex high-risk patients should using full polysomnograms. The study demonstrated
be referred to a specialist. that a respiratory disturbance index (RDI) of at least
 EAR, NOSE, & THROAT / 501

Snoring nightly

No craniofacial or Craniofacial abnormality or

Recurrent tonsillitis/ dysphagia?
neurologic problems neurologic problem

Yes No

Adenotonsillectomy Nasal turbinate hypertrophy Sleep study

Yes No

Treat nose w/ nasal steroid Assess tonsillar size

and reevaluate

Normal tonsils (1 or 2+) Enlarged tonsils (3+) Greatly enlarged tonsils (4+)

No gasping, apnea Gasping, apnea No gasping, apnea

Assess adenoid size w/
or pauses, and no or pauses, or or pauses, and no
lateral neck film
QOL issues QOL issues QOL issues

Normal Enlarged

Sleep study ENT referral Observe ENT referral Sleep study

Figure 17–9. Algorithm for snoring. QOL = quality of life.

Figure 17–10. A grading scale for tonsil size that ranges from 0 to 4. With grade 0 the tonsils are small and con-
tained within the tonsillar fossa; in grade 4 the tonsils are so large they almost touch (“kissing”). (Reprinted, with per-
mission, from Brodksy L: Modern assessment of tonsils and adenoids. Pediatr Clin North Am 1989;36(6):1551.)
502 / CHAPTER 17

one event an hour when associated with a 3% oxygen A possible new indication is FAPA syndrome (see
desaturation was associated with daytime sleepiness and previous discussion), in which the fever is predictable
learning problems. If oxygen desaturations were absent, and commonly occurs every 4–8 weeks. Removal of the
an RDI of five was associated with clinical symptoms. tonsils was shown to relieve the symptoms in five chil-
The importance of diagnosing OSA in children cannot dren in one recent study.
be underestimated. Recent studies have shown that OSA is associated with loud snoring during sleep
teenagers who are loud snorers exhibit impaired school with periods of respiratory pauses terminated with
performance, and that behavioral problems are associ- gasping and agitated arousal. The American Academy
ated with OSA. One should strongly consider the diag- of Pediatrics technical report on OSA (http://www
nosis of OSA in a snoring child who otherwise meets .pediatrics.org/cgi/content/full/109/4/e69) suggests that
the criteria for ADHD. For those patients who have se- primary snoring may also have developmental conse-
vere OSA by polysomnogram with large oxygen desatu- quences. Other symptoms of OSA include ADHD,
rations, obtain a chest radiograph and electrocardio- failure to thrive, and nocturnal enuresis.
gram to make sure that cor pulmonale has not Recently, a proliferation of new surgical techniques
developed. has occurred that can potentially reduce the morbidity
associated with an adenotonsillectomy.
Clinical Practice Guideline: Diagnosis and management of child-
hood obstructive sleep apnea syndrome. Pediatrics Dahn KA et al: Periodic fever and pharyngitis in young children.
2002;109:704 [PMID: 11927718]. Arch Otolaryngol Head Neck Surg 2000;126:1146 [PMID:
Gozal D, Pope DW Jr: Snoring during early childhood and acade- 10979131].
mic performance at ages thirteen to fourteen years. Pediatrics Derkay CS, Maddern BR: Innovative techniques for adenotonsillar
2001;107:1394 [PMID: 11389268]. surgery in children Laryngoscope 2002;112(8 Pt 2):2
Goodwin JL et al: Symptoms related to sleep-disordered breathing [PMID: 12172227]
in white and Hispanic children: The Tucson Children’s As- Sood S et al: Effectiveness of the ultrasonic harmonic scalpel for
sessment of Sleep Apnea Study. Chest 2003;124(1):196 tonsillectomy. Ear Nose Throat J 2001;80(8):514; 518
[PMID: 12853523]. [PMID: 11523467]
Marcus CL: Sleep-disordered breathing in children. Am J Respir
Crit Care Med 2001;164:16 [PMID: 11435234].
Schechter MS, Technical report: Diagnosis and management of Adenoidectomy
childhood obstructive sleep apnea syndrome. Pediatrics
2002;109:e69 [PMID: 11927742] The adenoids, composed of lymphoid tissue in the na-
sopharynx, are a component of the Waldeyer ring of
lymphoid tissue with the palatine tonsils and lingual
Websites tonsils. Enlargement of the adenoids with or without
Information for Health Care Professionals (http://sleepapnea.org/ infection can obstruct the upper airway, alter normal
promemb.html) orofacial growth, and interfere with speech, swallowing,
National Sleep Foundation (http://www.sleepfoundation.org/) or eustachian tube function. Most children with pro-
longed mouth breathing eventually develop dental mal-
occlusion and what has been termed an adenoidal fa-
TONSILLECTOMY & ADENOIDECTOMY cies. The face is pinched and the maxilla narrowed
Tonsillectomy because the molding pressures of the orbicularis oris
and buccinator muscles are unopposed by the tongue.
A tonsillectomy with or without adenoidectomy is typi- The role of hypertrophy and chronic infection in the
cally performed for either hypertrophy or recurrent in- pathogenesis of sinusitis is unclear, but adenoidectomy
fections. Adenotonsillar hypertrophy may produce has been shown to be effective in some patients with
upper airway obstruction, dysphagia, or dental maloc- chronic rhinosinusitis.
clusion. Rarely, the size may produce pulmonary hyper- Indications for adenoidectomy with or without ton-
tension or cor pulmonale. Recurrent infections are pre- sillectomy include pulmonary conditions such as
sent when a child has seven or more documented S chronic hypoxia related to upper airway obstruction,
pyogenes infections in 1 year, five per year for 2 years, or hypopnea, or obstructive sleep apnea; orofacial condi-
three per year for 3 years. A tonsillectomy is reasonable tions such as mandibular growth abnormalities, dental
if fewer infections are present but the child has missed malocclusion, and swallowing disorders; speech abnor-
multiple school days or has a complicated course. Re- malities; persistent middle ear effusion; recurrent and
current peritonsillar abscesses and persistent streptococ- chronic otitis media; and chronic sinusitis. Chronic
cal carrier state are other indications as well as unilateral adenoiditis can seed the sinuses and cause the ongoing
tonsil hypertrophy that appears neoplastic. sinus disease.
 EAR, NOSE, & THROAT / 503

Coyte PC et al: The role of adjuvant adenoidectomy and tonsillec- Inclusion Cyst
tomy in the outcome of the insertion of tympanostomy tubes.
N Engl J Med 2001;344:1188 [PMID: 11390633]. Inclusion (retention) cysts are due to the obstruction of
mucous glands or other mucous membrane structures.
Complications of Tonsillectomy In the newborn, they occur on the hard palate or gums
and are called Epstein pearls. These small cysts resolve
& Adenoidectomy spontaneously in 1–2 months. In older children, inclu-
The reported mortality rates associated with tonsillec- sion cysts usually occur on the palate, uvula, or tonsillar
tomy & adenoidectomy (T&A) now approximate that pillars. They appear as taut yellow sacs varying in size
of general anesthesia alone. The rate of hemorrhage from 2 mm to 10 mm. Inclusion cysts that do not re-
varies between 0.1% and 8.1% depending on the defin- solve spontaneously should undergo incision and
ition of hemorrhage; the rate of postoperative transfu- drainage. Occasionally a mucous cyst on the lower lip
sion is 0.04%. Other complications include hypernasal (mucocele) requires drainage for cosmetic reasons.
speech (< 0.01%), and more rarely nasopharyngeal Minor salivary glands are present at this site. Blockage
stenosis, atlantoaxial subluxation, mandible condyle of the outflow of the individual gland initiates the de-
fracture, and psychologic trauma. velopment.

Contraindications to Tonsillectomy DISORDERS OF THE TONGUE

& Adenoidectomy
Geographic Tongue
A. SHORT PALATE (Benign Migratory Glossitis)
Adenoids should not be removed completely in a child This condition of unknown cause occurs in 1–2% of
with a cleft palate or submucous cleft palate because of the population with no age, sex, or racial predilection
the risk of aggravating the velopharyngeal incompe- and is characterized by irregularly shaped areas on the
tence and causing hypernasal speech and nasal regurgi- tongue devoid of papillae and surrounded by parakera-
tation. A superior or partial adenoidectomy can be per- totic reddish borders. The pattern changes as alternat-
formed in a child with marked obstructive sleep apnea ing regeneration and desquamation occurs. The lesions
who has a submucous cleft palate or ongoing conduc- are generally asymptomatic and require no treatment.
tive hearing loss from middle ear effusion.
B. BLEEDING DISORDER Fissured Tongue (Scrotal Tongue)
If a chronic bleeding disorder is present, it must be di-
This condition is marked by numerous irregular fissures
agnosed and treated before T&A.
on the dorsum of the tongue. It occurs in approxi-
C. ACUTE TONSILLITIS mately 1% of the population and is usually a dominant
trait. It is also frequently seen in children with trisomy
An elective T&A can often be postponed until acute 21 and other mentally delayed patients who have the
tonsillitis is resolved. Urgent tonsillectomy may be re- habit of chewing on a protruded tongue.
quired for tonsillitis unresponsive to medical therapy.

Coated Tongue (Furry Tongue)

DISORDERS OF THE LIPS
The tongue normally becomes coated if mastication is
Labial Sucking Tubercle impaired and the patient is taking a liquid or soft diet.
A small baby may present with a small callus in the mid- Mouth breathing, fever, or dehydration can accentuate
upper lip. It usually is asymptomatic and disappears the process.
after cup feeding is initiated.
Macroglossia
Cheilitis Tongue hypertrophy and protrusion may be a clue to
Dry, cracked, scaling lips are usually caused by sun or Beckwith–Wiedemann syndrome, glycogen storage dis-
wind exposure. Contact dermatitis from mouthpieces ease, cretinism, Hurler syndrome, lymphangioma, or
or various woodwind or brass instruments has also been hemangioma. Tongue reduction procedures should be
reported. Licking the lips accentuates the process, and considered in otherwise healthy subjects when
the patient should be warned of this. Liberal use of lip macroglossia affects airway patency, eating, dental de-
balms gives excellent results. velopment, and normal mandibular growth. In trisomy
504 / CHAPTER 17

21, the normal-sized tongue protrudes because the pa- of obstructive process, but can be associated with Sjögren
tient’s oral cavity is small. syndrome, another autoimmune process, HIV infection,
or a calculus in the parotid duct. Serum amylase levels
Bezerra S, Costa I: Oral conditions in children from birth to are normal, which speaks against a diagnosis of viral
5 years: The findings of a children’s dental program. J Clin parotitis. Many episodes may occur from age 2 years on.
Ped Dent 2000;25(1):79 [PMID: 11314357]. The problem may resolve spontaneously at puberty.
Treatment includes analgesics if pain is present and
HALITOSIS an antistaphylococcal antibiotic for prophylaxis of in-
fection and quicker resolution at the onset of symp-
Bad breath is usually due to acute stomatitis, pharyngi- toms. A second attack of parotid swelling without fever
tis, sinusitis, a nasal foreign body, or dental hygiene should result in referral to an otolaryngologist to make
problems. In older children and adolescents, halitosis the diagnosis.
can be a manifestation of chronic sinusitis, gastric be-
zoar, bronchiectasis, or lung abscess. The presence of Huisman TA et al: MRI of chronic recurrent parotitis in child-
orthodontic devices or dentures can cause halitosis if hood. J Comput Assist Tomogr 2001;25:269 [PMID:
good dental hygiene is not maintained. Halitosis can 11242227].
also be caused by decaying food particles embedded in
cryptic tonsils. In adolescents, tobacco use is a common Tumors of the Parotid Gland
cause. Mouthwashes and chewable breath fresheners
give limited improvement. Treatment of the underlying Mixed tumors, hemangiomas, sarcoidosis, and
cause is indicated, and a dental referral may be in order. leukemia can be manifested in the parotid gland as a
hard or persistent mass. A cystic mass or multiple cystic
Amir E et al: Halitosis in children. J Pediatr 1999;134(3):338 masses may represent an HIV infection. Work-up may
[PMID: 10064672]. require consultation with oncology, infectious diseases,
hematology, and otolaryngology.
SALIVARY GLAND DISORDERS
Ranula
Parotitis
A ranula is a retention cyst of a sublingual salivary
A first episode of parotitis may safely be considered to gland. It occurs on the floor of the mouth to one side of
be of viral origin, unless fluctuance is present. The lead- the lingual frenulum. Ranula has been described as re-
ing cause was mumps until adoption of vaccination; sembling a frog’s belly because it is thin-walled and
now the leading viruses are parainfluenza and Ep- contains a clear bluish fluid. Referral to an otolaryngol-
stein–Barr virus. HIV should be considered if the child ogist for excision of the cyst and associated sublingual
is known to be at risk. gland is the treatment of choice.

Suppurative Parotitis CONGENITAL ORAL MALFORMATIONS

Suppurative parotitis is an uncommon clinical disorder
occurring chiefly in newborns and debilitated elderly
Tongue-Tie (Ankyloglossia)
patients. The parotid gland is swollen, tender, and The tightness of the lingual frenulum varies greatly
often reddened and is usually a unilateral process. The among normal people. A short frenulum prevents both
diagnosis is made by expression of purulent material protrusion and elevation of the tongue. Puckering of
from the Stensen duct. The material should be smeared the midline of the tongue occurring with tongue move-
and cultured. Fever and leukocytosis may be present. ment is noted on physical examination.
Treatment includes hospitalization and intravenous When mild, treatment consists of reassurance. If the
nafcillin because the most common causative organism tongue cannot protrude past the teeth or alveolar ridge
is S aureus. or move between the gums and cheek, referral to an oto-
laryngologist for evaluation is indicated. Frenulectomy
Recurrent Idiopathic Parotitis may be recommended if there is a question of suckling
difficulties, dental health (related to the inability to clear
Some children experience repeated episodes of parotid food from around the teeth), or articulation problems.
swelling that last 1–2 weeks and then resolve sponta-
neously, or can become infected and require antibiotics Messner AH, Lalakea ML: Ankyloglossia: Controversies in manage-
for resolution. There is usually pain and often no fever. ment. Int J Pediatr Otorhinolaryngol 2000;54:123 [PMID:
The process is most often unilateral, suggesting some sort 10967382].
 EAR, NOSE, & THROAT / 505

Messner AH et al: Ankyloglossia: Incidence and associated feeding mucous cleft palate causing abnormal speech or nasal
difficulties. Arch Otolaryngol Head Neck Surg 2000;126:36 regurgitation of food require referral for surgical repair.
[PMID: 10628708].

High-Arched Palate
Torus Palatini A high-arched palate is usually a genetic trait of no con-
sequence. It also occurs in children who are chronic
Hard midline masses on the palate are called torus pala-
mouth breathers and in premature infants who undergo
tini. They are bony protrusions that form at suture lines
prolonged oral intubation. Some rare causes of high-
of bone. Usually they are asymptomatic and require no
arched palate are congenital disorders such as Marfan
therapy. They can be surgically reduced if necessary.
syndrome, Treacher Collins syndrome, and Ehlers–
Danlos syndrome.
Cleft Lip & Cleft Palate (see Chapter 33)
Robin Sequence (Pierre Robin)
Submucous Cleft Palate This group of congenital malformation is characterized
A bifid uvula is present in 3% of healthy children. by the triad of micrognathia, cleft palate, and glossop-
However, a close association exists (as high as 75%) be- tosis. Affected children present as emergencies in the
tween bifid uvula and submucous cleft palate. A sub- newborn period because of infringement on the airway
mucous cleft can be diagnosed by noting a translucent by the tongue. The main objective of treatment is to
zone in the middle of the soft palate. Palpation of the prevent asphyxia until the mandible becomes large
hard palate reveals absence of the posterior bony pro- enough to accommodate the tongue. In some cases, this
trusion. Affected children have a 40% risk of develop- objective can be achieved by leaving the child in a
ing persistent middle ear effusion. They are at risk also prone position while unattended. In more severe cases,
of incomplete closure of the palate, resulting in hyper- a tracheostomy is required. The child requires close ob-
nasal speech. During feeding, some of these infants ex- servation and careful feeding until the problem is out-
perience nasal regurgitation of food. Children with sub- grown.
 Respiratory Tract & Mediastinum 18
Gwendolyn S. Kerby, MD, Gary L. Larsen, MD, Frank J. Accurso, MD, Robin R. Deterding,
MD, Vivek Balasubramaniam, MD, & Scott D. Sagel, MD

monary acinus: the canalicular stage (16–26 weeks’

RESPIRATORY TRACT gestation). During this stage alveolar type II cell differ-
entiate, the pulmonary capillary network develops, and
the alveolar type I cells closely approximate with the
Pediatric pulmonary diseases account for almost 50% developing capillary network. Abnormalities of
of deaths in children younger than age 1 year and about development during this stage include neonatal respira-
20% of all hospitalizations of children younger than age tory distress syndrome and lung hypoplasia. The next
15 years. Approximately 7% of children have some sort stage is the saccular stage (26–36 weeks’ gestation), dur-
of chronic disorder of the lower respiratory system. Un- ing which further branching of the terminal saccules
derstanding the pathophysiology of many pediatric pul- takes place as well as a thinning of the interstitium and
monary diseases requires an appreciation of the normal fusion of the type I cell and capillary basement mem-
growth and development of the lung. brane in preparation for the lungs’ function as a gas-ex-
change organ. The final stage of lung development is
the alveolar stage (36 weeks’s gestation to 3–8 years of
age). Controversy surrounds the length of this stage of
GROWTH & DEVELOPMENT lung development. This stage witnesses secondary sep-
The lung has its origins from an outpouching of the tal formation, further sprouting of the capillary net-
foregut during the fourth week of gestation. The devel- work, and the development of true alveoli. Abnormali-
opment of the lung is divided into five overlapping ties during this stage lead to lung hypoplasia and can
stages. The first stage is the embryonic stage result in the development of bronchopulmonary dys-
(3–7 weeks’ gestation) during which the primitive lung plasia.
bud undergoes asymmetrical branching and then subse- At birth, the lung assumes the gas-exchanging func-
quent dichotomous branching, leading to the develop- tion served by the placenta in utero, placing immediate
ment of the conducting airways. This stage of lung de- stress on all components of the respiratory system. Ab-
velopment is dependent on a complex crosstalk of normalities in the lung, respiratory muscles, chest wall,
various growth factors originating in both the pul- airway, respiratory controller, or pulmonary circulation
monary epithelium and the splanchnic mesenchyme. may therefore be present at birth. Survival after delivery
This stage also sees the development of the large pul- depends, for example, on the development of the sur-
monary arteries from the sixth aortic arch and the pul- factant system to maintain airway stability and allow
monary veins as outgrowths of the left atrium. Abnor- gas exchange. Immaturity of the surfactant system,
malities during this stage result in congenital often seen in infants born at less than 35 weeks’ gesta-
abnormalities such as lung aplasia, tracheoesophageal tional age, can result in severe respiratory morbidity in
fistula, and congenital pulmonary cysts. The embryonic the immediate neonatal period as well as subsequent
stage overlaps with the next stage: the pseudoglandular chronic lung disease. A lethal form of lung disease has
stage (5–17 weeks’ gestation). During this stage the recently been recognized in infants homozygous for ab-
lung has a glandular appearance and witnesses the com- normalities in the surfactant protein B gene. Persistent
pletion of the conducting airways (bronchi and bron- pulmonary hypertension of the newborn—failure of
chioles). The respiratory epithelium of these airways be- the normal transition to a low-resistance pulmonary
gins to differentiate, and the presence of cartilage, circulation at birth—can complicate a number of
smooth muscle cells, and mucus glands are first seen. In neonatal respiratory diseases. There is mounting evi-
addition, the pleuroperitoneal cavity divides into two dence that abnormalities during fetal and neonatal
distinct compartments. Abnormalities during this stage growth and development of the lung have long-stand-
lead to pulmonary sequestration, cystic adenomatoid ing effects into adulthood, such as reduced gas ex-
malformation, and congenital diaphragmatic hernia. change, exercise intolerance, asthma, and an increased
The next stage witnesses the delineation of the pul- risk of COPD.
506
Copyright © 2005, 2001, by The McGraw-Hill Companies, Inc. Click here for terms of use.
 RESPIRATORY TRACT & MEDIASTINUM / 507

Barker DJ: The intrauterine origins of cardiovascular and obstruc- define precipitants of symptoms, and evaluate response
tive lung disease in adult life: The Marc Daniels Lecture to therapy. They can help define the risks of anesthesia
1990. J R Coll Physicians Lond 1991;25(2):129 [PMID:
2066923].
and surgery and assist in the planning of respiratory
care in the postoperative period. However, the range of
Bogue CW: Genetic and molecular basis of airway and lung devel-
opment. In Haddad GG et al: Basic Mechanisms of Pediatric normal values for a test may be wide, and the predicted
Respiratory Disease. BC Decker, 2002 normal values change dramatically with growth. For
Burri P: Structural aspects of prenatal and postnatal development this reason, serial determinations of lung function are
and growth of the lung. In McDonald JA (ed): Lung Growth often more informative than a single determination. Pa-
and Development. BC Dekker, 1997. tient cooperation is essential for almost all physiologic
assessments. Most children are not able to perform the
necessary maneuvers before age 5 years. Lung functions
in infants and toddlers are available at specialized cen-
DIAGNOSTIC AIDS ters. Despite these problems, tests of lung function are
valuable in the care of children.
PHYSICAL EXAMINATION Spirometers are available on which forced vital ca-
OF THE RESPIRATORY TRACT pacity can be recorded either as a volume–time tracing
Assessing the rate, depth, ease, symmetry, and rhythm of (spirogram) or a flow–volume curve. The patient in-
respiration is critical to the detection of pulmonary dis- hales maximally, holds his or her breath for a short pe-
ease. In young children, an elevated respiratory rate may riod, and then exhales as fast as possible for at least
be an initial indicator of pneumonia. Attention should 3 seconds. The tracing produced by the exhalation
be paid to tracheal position and thoracic configuration. shows forced vital capacity (FVC), which is the total
Auscultation should assess the quality of breath sounds amount of air that is exhaled from maximum inspira-
and detect the presence of abnormal sounds such as fine tion, and the forced expiratory volume (FEV) in the
or coarse crackles, wheezing, or rhonchi. In older pa- first second of the exhalation (FEV1). The maximum
tients, unilateral crackles are the most valuable examina- midexpiratory flow rate (MMEF, or FEF25–75%), is the
tion finding in pneumonia. Extrapulmonary manifesta- mean flow rate during the middle portion of the FVC
tions of pulmonary disease include growth failure, maneuver. The FEV1/FVC ratio is calculated from
altered mental status (from hypoxemia or hypercapnia), these absolute values; a ratio greater than 0.85 in chil-
cyanosis, clubbing, and osteoarthropathy. In a study of dren and young adults shows unlimited normal airflow.
children with respiratory illnesses, abnormalities of at- These basic tests of lung function differentiate ob-
tentiveness, consolability, respiratory effort, color, and structive from restrictive processes. Examples of ob-
movement had a good diagnostic accuracy in detecting structive processes include asthma, chronic bronchitis,
hypoxemia. Evidence of cor pulmonale (loud pulmonic and cystic fibrosis (CF); restrictive problems include
component of the second heart sound, hepatomegaly, chest wall deformities that limit lung expansion and in-
elevated neck veins, and, rarely, peripheral edema) signi- terstitial processes due to collagen–vascular diseases, hy-
fies advanced lung disease. persensitivity pneumonitis, and interstitial fibrosis.
Respiratory disorders can be secondary to disease in Classically, diseases that obstruct airflow decrease the
other systems. It is therefore important to look for FEV1 more than the FVC, so that the FEV1/FVC ratio
other conditions such as congenital heart disease (mur- is low. In restrictive problems, however, the decreases in
mur, gallop), neuromuscular disease (muscle wasting, the FEV1 and FVC are proportionate; thus, the ratio of
scoliosis), immunodeficiency (rash, diarrhea), and auto- FEV1 to FVC is either normal or high. Clinical suspi-
immune disease or occult malignancy (arthritis, he- cion of a restrictive disease is usually an indication for
patosplenomegaly). referral to a specialist for evaluation.
The peak expiratory flow rate (PEFR), the maximal
flow recorded during an FVC maneuver, can be as-
Palafox M et al: Diagnostic value of tachypnea in pneumonia de-
fined radiologically. Arch Dis Child 2000;82:41 [PMID: sessed by handheld devices. The records of the PEFR
10630911]. can be helpful in following the course of pulmonary
Wipf JE et al: Diagnosing pneumonia by physical examination: disorders that are difficult to control and require multi-
Relevant or relic? Arch Intern Med 1999; 159:1082 [PMID: ple medications (eg, asthma). These devices can also be
10335685]. used to give patients with poor perception of their dis-
ease an awareness of a decrease in lung function, thus
facilitating earlier treatment.
PULMONARY FUNCTION TESTS
Lung function tests can help to differentiate obstructive Blonshine SB: Pediatric pulmonary function testing. Respir Care
from restrictive lung diseases, measure disease severity, Clin North Am 2000;6:27 [PMID: 10639555].
508 / CHAPTER 18

Evans SE, Scanlon PD: Current practice in pulmonary function Transcutaneous gas monitoring is a noninvasive as-
testing. Mayo Clin Proc 2003;78:758 [PMID: 12934788]. sessment of PaO2 and PaCO2 using electrodes that mea-
Sly PD et al: Lung function in cooperative patients. In Taussig LM, sure gas tension at the skin surface. Transcutaneous
Landau LI (eds): Pediatric Respiratory Medicine. Mosby, monitoring can underestimate the PaO2 and overesti-
1999.
mate the PaCO2 unless skin perfusion is maximal. Thus
heating of the skin site is required, and cardiac function
ASSESSMENT OF OXYGENATION should be stable.
AND VENTILATION Pulse oximetry (measuring light absorption by trans-
illuminating the skin) is the most reliable and easiest
Arterial blood gas determination defines the balance be- form of noninvasive monitoring of oxygenation. Oxy-
tween respiration at the tissue level and that in the genated hemoglobin absorbs red light at certain wave-
lungs. Assessment of blood gases is essential in critically lengths. Measurement during a systolic pulse allows es-
ill children and may be used also for determining the timation of arterial oxygen saturation as the machine
severity of lung involvement in chronic conditions. corrects for the light absorbed at the tissue level be-
Blood gas measurements are affected by abnormalities tween pulses. No heating of the skin is necessary. Val-
of respiratory control, gas exchange, respiratory me- ues of oxygen saturation are reliable as low as 80%. The
chanics, and the circulation. In pediatrics, hypoxia (low pulse oximeter has reduced reliability during conditions
PaO2) most commonly results from mismatching of causing reduced arterial pulsation such as hypothermia,
ventilation and perfusion. Hypercapnia (elevated hypotension, or infusion of vasoconstrictor drugs. Car-
PaCO2) results from inadequate alveolar ventilation, ie, bon monoxide bound by hemoglobin results in higher
inability to clear the CO2 produced. This is termed hy- than actual oxygen saturation readings.
poventilation. Causes include decreased central respira-
tory drive, paralysis of respiratory muscles, and low Hay WW Jr: Pulse oximetry: As good as it gets? J Perinatol
tidal volume breathing as seen in restrictive lung dis- 2000;20:181 [PMID: 10802844].
eases, severe scoliosis, or chest wall trauma. Table Hazinski MF (ed): Pediatric Advanced Life Support Provider Man-
18–1 gives normal values for arterial pH, PaO2, and ual. American Heart Association and the American Academy
PaCO2 at sea level and at 5000 feet. of Pediatrics, 2002.
Exhaled or end-tidal CO2 monitoring can be used to Soubani AO: Noninvasive monitoring of oxygen and carbon diox-
estimate arterial CO2 content. It is used to monitor ide. Am J Emerg Med 2001;19:141 [PMID: 11239260].
alveolar ventilation and is most accurate in patients Tobias JD, Meyer DJ: Noninvasive monitoring of carbon dioxide
without significant lung disease, particularly those with during respiratory failure in toddlers and infants: End-tidal
a good match of ventilation and perfusion and without versus transcutaneous carbon dioxide. Anesth Analg 1997;85:
55 [PMID: 9212122].
airway obstruction. Exhaled or end-tidal CO2 use has
increased to confirm endotracheal tube placement and
ensure endotracheal rather than esophageal intubation. CULTURE OF MATERIAL
This assessment is accurate in children who weigh more
than 2 kg and have a perfusing rhythm. Exhaled CO2
FROM THE RESPIRATORY TRACT
can be monitored by attaching a CO2 detector to an Expectorated sputum is rarely available from patients
endotracheal tube or to a nasal cannula. Qualitative younger than age 8 years. In older children, a Gram-
CO2 monitors use a chemical detector in a strip of stained smear of sputum showing significant numbers
paper that changes color when CO2 is present. Capnog- of organisms within neutrophils may identify a
raphy devices are quantitative and measure the concen- pathogen. Bacterial stains and cultures of nasopharyn-
tration of CO2 by infrared absorption detectors. These geal secretions are frequently misleading.
display continuous exhaled CO2 concentration as a Cultures from the lower respiratory tract can be ob-
waveform and with a digital display of end-tidal CO2. tained invasively by tracheal aspiration through an en-
dotracheal tube or rigid bronchoscope, or by perform-
ing a bronchoalveolar lavage through a flexible
Table 18–1. Normal arterial blood gas values bronchoscope. Sputum induction, performed by inhal-
on room air. ing aerosolized hypertonic saline, is a relatively safe
noninvasive means of obtaining lower airway secre-
tions. Where thoracoscopic lung biopsy by a skilled op-
pH PaO2 (mm Hg) PaCO2 (mm Hg) erator is unavailable, lung puncture directed to an area
Sea level 7.38–7.42 85–95 36–42 of consolidation by computed tomography (CT) scan
or fluoroscopy may be the best approach for a child
5000 feet 7.36–7.40 65–75 35–40 who deteriorates after initial antibiotic therapy or who
 RESPIRATORY TRACT & MEDIASTINUM / 509

is critically ill or immunocompromised. However, Barium swallow is indicated for patients with sus-
pneumothorax may result. Open-lung biopsy, though a pected aspiration to detect swallowing dysfunction, tra-
major intervention, should be considered in the wors- cheoesophageal fistula, gastroesophageal reflux, and
ening or critically ill child when other approaches are achalasia. This technique is also important in detecting
unsuccessful. In skilled hands, thoracoscopic lung vascular rings and slings, because most of these abnor-
biopsy may avoid open biopsy and its potential compli- malities compress the esophagus. Airway fluoroscopy is
cations. Thoracentesis should be performed when another important tool for assessing both fixed airway
pleural fluid is present. Blood glucose and lactate dehy- obstruction (eg, tracheal stenosis) and dynamic airway
drogenase should be drawn simultaneously for compar- obstruction (eg, tracheomalacia). Fluoroscopy or ultra-
ison with pleural fluid levels. Blood cultures must be sound of the diaphragm can detect paralysis by demon-
obtained in children with acute pneumonia. strating paradoxic movement of the involved hemidi-
Specimens obtained by invasive means should be aphragm.
tested for viruses, Mycoplasma pneumoniae, Chlamydia, High-resolution CT scanning is useful to evaluate dif-
Legionella pneumophila, Bordetella pertussis, fungi, fuse infiltrative lung disease, metastatic disease, mediasti-
Pneumocystis jiroveci (formerly Pneumocystis carinii), nal masses, and chest wall disease. Characteristic patterns
acid-fast bacteria, and anaerobes or other bacteria. seen in interstitial lung disease (eg, honeycombing in pul-
Rapid diagnostic techniques such as immunofluores- monary fibrosis) or airway disease (eg, bronchiectasis) are
cent antibody and enzyme-linked immunosorbent assay often missed on chest radiographs. Magnetic resonance
(ELISA) are best. Counterimmunoelectrophoresis of imaging (MRI) is useful for defining subtle or complex
pleural fluid, serum, or concentrated urine may help abnormalities and vascular rings. Ventilation–perfusion
identify disease due to Streptococcus pneumoniae or scans can provide information about regional ventilation
Haemophilus influenzae. Because these tests can be per- and perfusion and can help detect vascular malformations
formed quickly, they may obviate further, more inva- and pulmonary emboli (rare in children). Pulmonary an-
sive studies. giography is occasionally necessary to define the pul-
monary vascular bed more precisely.
Wiersma HE et al: Sputum induction for the diagnosis of pul-
monary tuberculosis. Arch Dis Child Apr 2000;82:305 Cooper MI, Slovis TL: Imaging of the respiratory system. In Taus-
[PMID: 10991758]. sig LM, Landau LI (eds): Pediatric Respiratory Medicine.
Wood RE: Diagnostic and therapeutic procedures in pediatric pul- Mosby, 1999.
monary patients. In Taussig LM, Landau LI (eds): Pediatric Harty MP et al: Current concepts on imaging of thoracic vascular
Respiratory Medicine. Mosby, 1999. abnormalities. Curr Opin Pediatr 2000;12(3):194 [PMID:
10836152].
Marchant JM et al: Application of chest high-resolution computer
IMAGING OF THE RESPIRATORY TRACT tomography in young children with cystic fibrosis. Pediatr
Pulmonol 2001;31:24 [PMID: 11180671].
The plain chest radiograph remains the foundation for
Williams HJ, Alton HM: Imaging of paediatric mediastinal abnor-
investigating the pediatric thorax. Both frontal and lat- malities. Paediatr Respir Rev 2003;4(1):55 [PMID:
eral views should be obtained. The radiograph is useful 12615033].
for evaluating air trapping caused by airway obstruc-
tion, volume loss caused by pneumonia, and interstitial
problems such as pulmonary edema. Hyperaeration is LARYNGOSCOPY & BRONCHOSCOPY
best demonstrated in lateral views as flattening of the The indications for laryngoscopy include undiagnosed
diaphragm. It is often seen because young children hoarseness, stridor, symptoms of obstructive sleep
commonly develop small airway obstruction and apnea, and laryngeal wheezing consistent with a diag-
asthma. Parenchymal changes may cause increased in- nosis of vocal cord dysfunction; indications for bron-
terstitial markings, consolidation, air bronchograms, or choscopy include wheezing, suspected foreign body,
loss of diaphragm or heart contours. When pleural fluid pneumonia, atelectasis, chronic cough, hemoptysis, and
is suspected, lateral decubitus radiographs may be help- placement of an endotracheal tube and assessment of
ful in determining the extent and mobility of the fluid. patency. In general, the more specific the indication,
When a foreign body is suspected, forced expiratory ra- the higher the diagnostic yield.
diographs may show focal air trapping and shift of the Pediatric bronchoscopy instruments are of either the
mediastinum to the contralateral side. Lateral neck ra- flexible fiberoptic or the rigid open tube type. Flexible
diographs can be useful in assessing the size of adenoids bronchoscopy has the following advantages:
and tonsils and also in differentiating croup from
epiglottitis, the latter being associated with the 1. With sedation and topical anesthetics, the proce-
“thumbprint” sign. dure can be done at the bedside.
510 / CHAPTER 18

2. Evaluation of the upper airway can be done with tension of 65–90 mm Hg or an oxygen saturation
little risk in patients who are awake. above 92%. The actual oxygen concentration achieved
3. The distal airways of intubated patients can be ex- by nasal cannula or mask depends on the flow rate, the
amined without removing the endotracheal tube. type of mask used, and the patient’s age. Small changes
4. The instrument can be used as an obturator to in- in flow rate during oxygen administration by nasal can-
tubate a patient with a difficult upper airway. nula can lead to substantial changes in inspired oxygen
concentration in young infants. The amount of oxygen
5. Endotracheal tube placement and patency can be required to correct hypoxemia may vary according to
checked. the child’s activity. It is not unusual, for example, for
6. Assessment of airway dynamics is generally better. an infant with chronic lung disease to require
7. It is possible to examine more distal airways. 0.75 L/min while awake but 1 L/min while asleep or
feeding.
Improved digital optics has greatly enhanced the Although the head hood is an efficient device for de-
image quality. The advantages of using a rigid instru- livery of oxygen in young infants, the nasal cannula is
ment are (1) easier removal of foreign bodies (so rigid used more often because it allows the infant greater mo-
bronchoscopy is preferred for suspected foreign body bility. The cannula has nasal prongs that are inserted in
aspiration); and (2) better airway control, allowing the the nares. Flow through the nasal cannula should gen-
patient to be ventilated through the bronchoscope. In erally not exceed 3 L/min to avoid excessive drying of
addition, this approach to the airway allows better as- the mucosa. Even at high flow rates, oxygen by nasal
sessment of the subglottic space for stenosis. The choice cannula rarely delivers inspired oxygen concentrations
of procedures depends largely on the expertise available. greater than 40–45%. In contrast, partial rebreathing
Bronchoalveolar lavage through a flexible broncho- and nonrebreathing masks or head hoods achieve in-
scope is used to detect infection in immunocompetent spired oxygen concentrations as high as 90–100%.
and immunocompromised children. Aspiration and he- Because the physical findings of hypoxemia are sub-
morrhage are also suspected in the presence of lipid and tle, the adequacy of oxygenation should be measured as
hemosiderin-laden macrophages, respectively. Surfac- the arterial oxygen tension, or oxygen saturation can be
tant protein analysis of lavage fluid can also be com- determined by oximetry. The advantages of the latter
pleted. Transbronchial biopsy is used to look for infec- noninvasive method include the ability to obtain con-
tion and rejection in transplant patients and to tinuous measurements during various normal activities
diagnose other conditions such as sarcoidosis. and to avoid artifacts caused by crying or breath hold-
ing during attempts at arterial puncture. For children
Green CG et al: Technique. In Holinger LD et al (eds): Pediatric with chronic cardiopulmonary disorders that may re-
Laryngology and Bronchoesophagology. Lippincott-Raven, 1997. quire supplemental oxygen therapy (eg, bronchopul-
Nicolai T: Pediatric bronchoscopy. Pediatr Pulmonol 2001;31: monary dysplasia or CF), frequent noninvasive assess-
150 [PMID: 11180692]. ments are essential to ensure the safety and adequacy of
Schellhase DE: Pediatric flexible airway endoscopy. Curr Opin Pe- treatment.
diatr 2002;14:327 [PMID: 12011674].
Tilles SA: Vocal cord dysfunction in children and adolescents. Curr
Allergy Asthma Rep 2003;6:467 [PMID: 14531966]. Hazinski MF (ed): Pediatric Advanced Life Support Provider Man-
ual. American Heart Association and the American Academy
of Pediatrics, 2002.
Sivan Y et al: Assisted ventilatory support and oxygen treatment. In
GENERAL THERAPY OF PEDIATRIC Taussig LM, Landau LI (eds): Pediatric Respiratory Medicine.
Mosby, 1999.
LUNG DISEASES
OXYGEN THERAPY INHALATION OF BRONCHODILATORS
Oxygen therapy in children with respiratory disease can Airway obstruction that is at least partially reversed by a
reduce the work of breathing, resulting in fewer respira- bronchodilator can be seen in CF, bronchiolitis, and
tory symptoms; relax the pulmonary vasculature, less- bronchopulmonary dysplasia as well as in acute and
ening the potential for pulmonary hypertension and chronic asthma.
congestive heart failure; and improve feeding. Patients The β-adrenergic agonists may be delivered by me-
breathing spontaneously can be treated by nasal can- tered-dose inhaler (MDI), dry powder inhaler, or nebu-
nula, head hood, or mask (including simple, rebreath- lizer. MDIs are convenient and best combined with
ing, nonrebreathing, or Venturi masks). The general valved holding chambers, especially for children who
goal of oxygen therapy is to achieve an arterial oxygen lack the ability to coordinate actuation of the MDI
 RESPIRATORY TRACT & MEDIASTINUM / 511

with inhalation. In contrast, the nebulizer is an effective McIlwaine PM et al: Long-term comparative trial of positive expi-
method of delivering medication to infants and young ratory pressure versus oscillating positive expiratory pressure
(flutter) physiotherapy in the treatment of cystic fibrosis.
children. Long-acting inhaled β2-adrenergic agents that J Pediatr 2001;138(6):845 [PMID: 11391327].
are relatively selective for the respiratory tract are de-
van der Schans C et al: Chest physiotherapy compared to no chest
scribed in Chapter 34. Inhaled bronchodilators are as physiotherapy for cystic fibrosis (Cochrane Review). In The
effective as injected agents for treating acute episodes of Cochrane Library, Issue 3, 2003. Oxford: Update Software
airway obstruction and have fewer side effects. These Ltd.
drugs can be safely administered at home as long as Wagener JS, Headley AA: Cystic fibrosis: Current trends in respira-
both the physician and the family realize that a poor re- tory care. Respir Care 2003;48(3):234; discussion
sponse may signify the need for corticosteroids to help 246 [PMID: 12667274].
restore β-adrenergic responsiveness.
Anticholinergic agents may also acutely decrease air- AVOIDANCE OF ENVIRONMENTAL
way obstruction. Furthermore, they may yield a longer
duration of bronchodilation than do many adrenergic
HAZARDS
agents. Selected patients may benefit from receiving All parents or other caregivers should be counseled
both β-adrenergic and anticholinergic agents. In gen- about environmental hazards to the lung. The list of
eral, this class of drugs is most effective in the treatment potential hazards includes small objects that may be as-
of chronic bronchitis. pirated, allergens that can precipitate respiratory symp-
toms in atopic children, and cigarette smoke.
The harmful effects of smoking in the home deserve
Everard ML, Le Souëf PN: Aerosol therapy and delivery systems. In special emphasis. Children from families where the par-
Taussig LM, Landau LI (eds): Pediatric Respiratory Medicine. ents and others smoke have decreased lung growth as
Mosby, 1999. well as decreased pulmonary function in comparison
Kercsmar CM: Aerosol treatment of acute asthma. J Pediatr with children raised in smoke-free homes. Exposure of
2000;136:428 [PMID: 10753237].
children to tobacco smoke also leads to an increased
Onhøj J et al: Lung deposition of inhaled drugs increases with age. frequency of lower respiratory tract infections and an
Am J Respir Crit Care Med 2000;162:1819 [PMID:
11069819]. increased incidence of respiratory symptoms, including
Rubin BK, Fink JB: The delivery of inhaled medication to the
recurrent wheezing. Health care providers must in-
young child. Pediatr Clin North Am 2003;50:717 [PMID: crease their efforts to educate patients and their families
12877243]. about the hazards of smoking.

Chan-Yeung M, Dimich-Ward H: Respiratory health effects of ex-

AIRWAY CLEARANCE THERAPY posure to environmental tobacco smoke. Respirology
2003;8:131 [PMID: 12753526].
Chest physical therapy, with postural drainage, percus- Li Y-F et al: Effects of in utero and environmental tobacco smoke
sion, and forced expiratory maneuvers, has been widely exposure on lung function in boys and girls with and without
used to improve the clearance of lower airway secretions asthma. Am J Respir Crit Care Med 2000;162:2097 [PMID:
11112121].
even though there is limited data on the efficacy of
these techniques. Schwartz J et al: Respiratory effects of environmental tobacco
smoke in a panel study of asthmatic and symptomatic chil-
Children with CF have been shown to benefit from dren. Am J Respir Crit Care Med 2000;161:802 [PMID:
routine airway clearance. Many airway clearance tech- 10712325].
niques exist, but only a few long-term studies have
compared the various options. The various techniques
currently available include chest physiotherapy, auto-
genic drainage, positive expiratory pressure (PEP, Flut- DISORDERS OF THE CONDUCTING
ter, or Acapella), intrapulmonary percussive ventilation AIRWAYS
(IPV), or high-frequency chest compression (Vest). The
decision on which technique to use should be based on The conducting airways (the nose, mouth, pharynx, lar-
the patient’s age and preference after trying different ynx, trachea, bronchi, and bronchioles) direct inspired
approaches. Often bronchodilators or mucolytic med- air to the gas-exchange units of the lung; they do not
ications are given prior to or during airway clearance participate in gas exchange themselves. Airflow obstruc-
therapy. Inhaled corticosteroids and inhaled antibiotics tion in the conducting airways occurs by (1) external
should be given after airway clearance therapy so that compression (eg, vascular ring, tumor), (2) abnormali-
the airways are first cleared of secretions, allowing the ties of the airway structure itself (eg, congenital defects,
medications to maximally penetrate into the lung. thickening of an airway wall due to inflammation), or
512 / CHAPTER 18

(3) material in the airway lumen (eg, foreign body, Leung AK, Cho H: Diagnosis of stridor in children. Am Fam
mucus). Physician 1999;60:2289 [PMID:10593320].
Airway obstruction can be fixed (airflow limited in
both the inspiratory and the expiratory phases) or vari- INTRATHORACIC AIRWAY
able (airflow limited more in one phase of respiration OBSTRUCTION
than in the other). Variable obstruction is common in
children because their airways are more compliant and Intrathoracic airway obstruction usually causes expira-
susceptible to dynamic compression. With variable ex- tory wheezing. The history should include the follow-
trathoracic airway obstruction (eg, croup), airflow limi- ing:
tation is greater during inspiration, leading to inspira-
tory stridor. With variable intrathoracic obstruction 1. Age at onset
(bronchomalacia), limitation is greater during expira- 2. Precipitating factors (eg, exercise, upper respira-
tion, producing expiratory wheezing. Thus determining tory illnesses, allergens, choking while eating)
the phase of respiration in which obstruction is greatest 3. Course—acute (bronchiolitis, foreign body),
may be helpful in localizing the site of obstruction. chronic (tracheomalacia, vascular ring), recurrent
(reactive airways disease), or progressive (CF,
EXTRATHORACIC AIRWAY bronchiolitis obliterans)
OBSTRUCTION 4. Presence and nature of cough
5. Production of sputum
Patients with abnormalities of the extrathoracic airway
6. Previous response to bronchodilators
may present with snoring and other symptoms of ob-
structive apnea, hoarseness, brassy cough, or stridor. 7. Symptoms with positional changes (vascular
The course of the illness may be acute (eg, infectious rings)
croup), recurrent (eg, spasmodic croup), chronic (eg, 8. Involvement of other organ systems (malabsorp-
subglottic stenosis), or progressive (eg, laryngeal papil- tion in CF)
lomatosis). Significant risk factors are difficult delivery,
ductal ligation, and intubation. Examination should Physical examination should include growth mea-
determine if obstructive symptoms are present at rest or surements and vital signs. The examiner should look
with agitation, if they are positional, or if they are re- for cyanosis or pallor, barrel-shaped chest, retractions
lated to sleep. The presence of agitation, air hunger, se- and use of accessory muscles, and clubbing. Ausculta-
vere retractions, cyanosis, lethargy, or coma should alert tion should define the pattern and timing of respira-
the physician to a potentially life-threatening condition tion, detect the presence of crackles and wheezing, and
that may require immediate airway intervention. Help- determine whether findings are localized or generalized.
ful diagnostic studies in the evaluation of upper airway Routine tests include plain chest radiographs, a
obstruction include chest and lateral neck radiographs, sweat test, and pulmonary function tests in older chil-
airway fluoroscopy, and barium swallow. In patients dren. Other diagnostic studies are dictated by the his-
who have symptoms of severe chronic obstruction, an tory and physical findings. Treatment should be di-
electrocardiogram (ECG) should be obtained to evalu- rected toward the primary cause of the obstruction but
ate for right ventricular hypertrophy and pulmonary generally includes a trial of bronchodilators.
hypertension. Patients with obstructive sleep apnea
should have polysomnography (measurements during
sleep of the motion of the chest wall, airflow at the nose CONGENITAL DISORDERS
and mouth, heart rate, oxygen saturation, and selected
electroencephalographic leads to stage sleep) to deter- OF THE EXTRATHORACIC AIRWAY
mine severity and to evaluate the need for tonsillectomy
and adenoidectomy, oxygen, or continuous positive air-
LARYNGOMALACIA
way pressure (CPAP). In older children, pulmonary Laryngomalacia is a benign congenital disorder in
function tests can differentiate fixed from variable air- which the cartilaginous support for the supraglottic
flow obstruction and identify the site of variable ob- structures is underdeveloped. It is the most common
struction. If noninvasive studies are unable to establish cause of persistent stridor in infants and usually is seen
the cause, direct laryngoscopy and bronchoscopy re- in the first 6 weeks of life. Stridor has been reported to
main the procedures of choice to establish the precise be worse in the supine position, with increased activity,
diagnosis. Treatment should be directed at relieving air- with upper respiratory infections, and during feeding;
way obstruction and correcting the underlying condi- however, the clinical presentation can be variable. Pa-
tion if possible. tients may have slight oxygen desaturation during sleep.
 RESPIRATORY TRACT & MEDIASTINUM / 513

Gastroesophageal reflux may also be associated with Altman KW et al: Congenital airway abnormalities in patients re-
laryngomalacia requiring treatment. The condition quiring hospitalization. Arch Otolaryngol Head Neck Surg
1999;125:525 [PMID: 10326809].
usually improves with age and resolves by age 2 years,
but in some cases symptoms persist for years. The diag- Sichel JY et al: Management of congenital laryngeal malformations.
Am J Otolaryngol 2000;21:22 [PMID: 10668673].
nosis is established by direct laryngoscopy, which shows
inspiratory collapse of an omega-shaped epiglottis (with
or without long, redundant arytenoids). In mildly af-
fected patients with a typical presentation (those with-
out stridor at rest or retractions), this procedure may ACQUIRED DISORDERS OF THE
not be necessary. No treatment is usually needed. How- EXTRATHORACIC AIRWAY
ever, in patients with severe symptoms of airway ob-
struction associated with feeding difficulties, failure to CROUP SYNDROME
thrive, obstructive sleep apnea, or severe dyspnea, surgi-
cal epiglottoplasty may be necessary. Croup describes acute inflammatory diseases of the lar-
ynx, including viral croup (laryngotracheobronchitis),
epiglottitis (supraglottitis), and bacterial tracheitis.
Olney DR et al: Laryngomalacia and its treatment. Laryngoscope These are the main entities in the differential diagnosis
1999;109:1770 [PMID: 10569405]. for patients presenting with acute stridor, although
Toynton SC et al: Aryepiglottoplasty for laryngomalacia: 100 con- spasmodic croup, angioneurotic edema, laryngeal or
secutive cases. J Laryngol Otol 2001;115:35 [PMID: esophageal foreign body, and retropharyngeal abscess
11233619]. should be considered as well.

OTHER CONGENITAL PROBLEMS 1. Viral Croup

Other rare congenital lesions of the larynx (laryngeal Viral croup generally affects younger children in the fall
atresia, laryngeal web, laryngocele and cyst of the lar- and early winter months and is most often caused by
ynx, subglottic hemangioma, and laryngeal cleft) are parainfluenza virus serotypes. Other organisms causing
best evaluated by direct laryngoscopy. Laryngeal atresia croup include respiratory syncytial virus (RSV), in-
obviously presents immediately after birth with severe fluenza virus, rubeola virus, adenovirus, and My-
respiratory distress and is usually fatal. Laryngeal web, coplasma pneumoniae. Although inflammation of the
representing fusion of the anterior portion of the true entire airway is usually present, edema formation in the
vocal cords, is associated with hoarseness, aphonia, and subglottic space accounts for the predominant signs of
stridor. Surgical correction may be necessary depending upper airway obstruction.
on the degree of airway obstruction.
Congenital cysts and laryngoceles are believed to
have similar origin. Cysts are more superficial, whereas Clinical Findings
laryngoceles communicate with the interior of the lar-
ynx. Cysts are generally fluid-filled, whereas laryngo- A. SYMPTOMS AND SIGNS
celes may be air- or fluid-filled. Airway obstruction is Usually a prodrome of upper respiratory tract symp-
usually prominent and requires surgery or laser therapy. toms is followed by a barking cough and stridor. Fever
Subglottic hemangiomas are seen in infancy with is usually absent or low-grade but may on occasion be
signs of upper airway obstruction and are often (but as high as in patients with epiglottitis. Patients with
not always) associated with similar lesions of the skin. mild disease may have stridor when agitated. As ob-
Although these lesions tend to regress spontaneously, struction worsens, stridor occurs at rest, accompanied
airway obstruction may require laser surgical treatment in severe cases by retractions, air hunger, and cyanosis.
or even tracheostomy. On examination, the presence of cough and the absence
Laryngeal cleft is a very rare condition resulting of drooling favor the diagnosis of viral croup over
from failure of posterior cricoid fusion. Patients with epiglottitis.
this condition may have stridor but always aspirate se-
verely, resulting in recurrent or chronic pneumonia and
failure to thrive. Barium swallow is always positive for B. IMAGING
severe aspiration, but diagnosis can be very difficult Lateral neck radiographs can be diagnostically helpful
even with direct laryngoscopy. Patients often require by showing subglottic narrowing and a normal epiglot-
tracheostomy and gastrostomy, because surgical correc- tis. This is not done routinely in the child with a classic
tion is not always successful. presentation.
514 / CHAPTER 18

Treatment has not been determined if this was present prior to the
croup episode or if the croup episode itself altered air-
Treatment of viral croup is based on the symptoms. way function. Recurrence of croup occurs in some in-
Mild croup, signified by a barking cough and no stridor stances, implying airway hyperreactivity.
at rest, requires supportive therapy with oral hydration
and minimal handling. Mist therapy is used by some
Castro-Rodriguez JA et al: Relation of two different subtypes of
physicians, although clinical studies demonstrating its croup before age three to wheezing, atopy, and pulmonary
effectiveness are lacking. Conversely, patients with stri- function during childhood: A prospective study. Pediatrics
dor at rest require active intervention. Oxygen should 2001;170:512 [PMID: 11230591].
be administered to patients with oxygen desaturation. Stroud RH, Friedman NR: An update on inflammatory disorders
Nebulized racemic epinephrine (2.25% solution; of the pediatric airway: Epiglottis, croup, and tracheitis. Am
0.05 mL/kg to a maximum of 1.5 mL diluted in sterile J Otolaryngol 2001;22:268 [PMID: 11264324].
saline) is commonly used because it has a rapid onset of Wright RB et al: New approaches to respiratory infections in chil-
action within 10–30 minutes. Both racemic epineph- dren: Bronchiolitis and croup. Emerg Med Clin North Am
2002;20:93 [PMID: 11826639].
rine and epinephrine hydrochloride are effective in alle-
viating symptoms and decreasing the need for intuba-
tion. Once controversial, the efficacy of glucocorticoids 2. Epiglottitis
in croup is now more firmly established. Dexametha-
Epiglottitis is a true medical emergency. In published
sone, 0.6 mg/kg intramuscularly as one dose, improves
case series, it is almost always caused by Haemophilus
symptoms, reduces the duration of hospitalizations and
influenzae type B, although other organisms such as
frequency of intubations, and permits earlier discharge
nontypable H influenzae, Streptococcus pneumoniae,
from the emergency room. Oral dexamethasone ap-
groups A and C Streptococcus pyogenes, Neisseria menin-
pears equally effective, and limited data suggest that
gitides, and staphylococci have been implicated. Result-
lower doses of oral dexamethasone (0.15 mg/kg) may
ing inflammation and swelling of the supraglottic struc-
be as effective as the higher dose. Inhaled budesonide
tures (epiglottis and arytenoids) can develop rapidly
(2–4 mg) also improves symptoms and decreases hospi-
and lead to life-threatening upper airway obstruction.
tal stay. Onset of action occurs within 2 hours, and this
The incidence has decreased dramatically since H in-
agent may be as effective as dexamethasone; however,
fluenzae conjugate vaccine was introduced.
dexamethasone is still the most cost-effective steroid of
choice. If symptoms resolve within 3 hours of glucocor-
ticoids and nebulized epinephrine, patients can safely Clinical Findings
be discharged without fear of a sudden rebound in A. SYMPTOMS AND SIGNS
symptoms. If, however, recurrent nebulized epineph-
rine treatments are required or if respiratory distress Typically, patients present with a sudden onset of fever,
persists, patients require hospitalization for close obser- dysphagia, drooling, muffled voice, inspiratory retrac-
vation, supportive care, and nebulization treatments as tions, cyanosis, and soft stridor. They often sit in the
needed. In patients with impending respiratory failure, so-called sniffing dog position, which gives them the
an airway must be established (see following para- best airway possible under the circumstances. Progres-
graph). Hospitalized patients with persistent symptoms sion to total airway obstruction may occur and result in
over 3–4 days despite treatment should arouse suspi- respiratory arrest. The definitive diagnosis is made by
cion of another cause of airway obstruction. direct inspection of the epiglottis, a procedure that
Patients with impending respiratory failure require should be done by an experienced airway specialist
an artificial airway. Intubation with an endotracheal under controlled conditions (usually the operating
tube of slightly smaller diameter than would ordinarily room). The typical findings are cherry-red and swollen
be used is reasonably safe. Extubation should be accom- epiglottis and arytenoids.
plished within 2–3 days to minimize the risk of laryn- B. IMAGING
geal injury. If the patient fails extubation, tracheostomy
may be required. Diagnostically, lateral neck radiographs may be helpful
in demonstrating a classic “thumbprint” sign. Obtain-
ing radiographs, however, may delay important airway
Prognosis intervention.
Most children with viral croup have an uneventful Treatment
course and improve within a few days. Some evidence
suggests that patients with a history of croup associated Once the diagnosis of epiglottitis is made, endotracheal
with wheezing may have airway hyperreactivity, but it intubation must be performed immediately. Most anes-
 RESPIRATORY TRACT & MEDIASTINUM / 515

thesiologists prefer general anesthesia (but not muscle re- tients develop high fever, toxicity, and progressive
laxants) to facilitate intubation. After an airway is estab- upper airway obstruction that is unresponsive to stan-
lished, cultures of the blood and epiglottis should be ob- dard croup therapy. The incidence of sudden respira-
tained and the patient started on appropriate intravenous tory arrest or progressive respiratory failure is high; in
antibiotics to cover H influenzae (ceftriaxone sodium or such instances, airway intervention is required. Find-
equivalent cephalosporin). Extubation can usually be ac- ings of toxic shock and the acute respiratory distress
complished in 24–48 hours, when direct inspection syndrome (ARDS) may also be seen.
shows significant reduction in the size of the epiglottis.
Intravenous antibiotics should be continued for 2–3 days, B. LABORATORY FINDINGS
followed by oral antibiotics to complete a 10-day course. The white cell count is usually elevated, with left shift.
If a physician who has little experience in treating air- Cultures of tracheal secretions usually demonstrate one
way disorders and is located far from a pediatric care facil- of the causative organisms.
ity encounters a patient with epiglottitis, the following is
recommended. Start the patient on oxygen and assemble C. DIAGNOSIS
all the airway equipment available. Manipulate the pa- Lateral neck radiographs show a normal epiglottis but
tient as little as possible, and allow the child to remain sit- often severe subglottic and tracheal narrowing. Irregu-
ting up. Enlist the help of the most experienced airway larity of the contour of the proximal tracheal mucosa
person available, or call a transport team. Start an intra- can frequently be seen radiographically. Bronchoscopy
venous line and give antibiotics. If the patient obstructs showing a normal epiglottis and the presence of copi-
completely and experiences respiratory arrest, attempt to ous purulent tracheal secretions confirm the diagnosis.
establish an airway by any means possible: bag and mask
ventilation, intubation, transtracheal ventilation with a Treatment
large-bore angiocatheter attached to a 3-mm endotracheal
tube adapter and resuscitation bag, or tracheostomy. Suspected bacterial tracheitis should be managed in a
fashion similar to that for epiglottitis. Because the inci-
dence of respiratory arrest or progressive respiratory
Prognosis failure is high, intubation is usually necessary. Because
Prompt recognition and appropriate treatment usually these patients often have thick, purulent tracheal secre-
results in rapid resolution of swelling and inflamma- tions, humidification, frequent suctioning, and inten-
tion. Recurrence is unusual. sive care monitoring are required to prevent endotra-
cheal tube obstruction. Intravenous antibiotics to cover
Levy RJ, Helforr MA: Pediatric airway issues. Crit Care Clin
Staphylococcus aureus, H influenzae, and the other or-
2000;16:489 [PMID: 10941587]. ganisms are indicated. Because thick secretions persist
Rotta AT, Wiryawan B: Respiratory emergencies in children. for several days, the required period of intubation is
Respir Care 2003;48:248 [PMID: 12667275]. longer for bacterial tracheitis than for epiglottitis. De-
spite the severity of this illness, the reported mortality
rate is very low.
3. Bacterial Tracheitis
Bacterial tracheitis (pseudomembranous croup) is a se- Rotta AT, Wiryawan B: Respiratory emergencies in children.
vere form of laryngotracheobronchitis. The organism Respir Care 2003;48:248 [PMID: 12667275].
most often isolated is Staphylococcus aureus, but organ- Stroud RH, Friedman NR: An update on inflammatory disorders
of the pediatric airway: Epiglottis, croup, and tracheitis. Am
isms such as H influenzae, group A Streptococcus pyo- J Otolaryngol 2001;22:268 [PMID: 11464324].
genes, Neisseria species, Moraxella catarrhalis, and others
Ward MA: Lower respiratory tract infections in adolescents. Ado-
have been reported. The disease probably represents lo- lesc Med 2000;11:251 [PMID: 10916123].
calized mucosal invasion of bacteria in patients with
primary viral croup, resulting in inflammatory edema,
purulent secretions, and pseudomembranes. Although VOCAL CORD PARALYSIS
cultures of the tracheal secretions are frequently posi- Unilateral or bilateral vocal cord paralysis may be con-
tive, blood cultures are almost always negative. genital or, more commonly, may result from injury to
the recurrent laryngeal nerves. Risk factors for acquired
Clinical Findings paralysis include difficult delivery (especially face pre-
sentation), neck and thoracic surgery (eg, ductal liga-
A. SYMPTOMS AND SIGNS tion, repair of tracheoesophageal fistula), trauma, medi-
The early clinical picture is similar to that of viral astinal masses, pulmonary hypertension, and central
croup. However, instead of gradual improvement, pa- nervous system (CNS) disease (eg, Arnold–Chiari mal-
516 / CHAPTER 18

formation). Patients usually present with varying de- Walner DL et al: Neonatal subglottic stenosis—incidence and
grees of hoarseness, aspiration, or high-pitched stridor. trends. Laryngoscope 2001;111:48 [PMID: 11192899].
Unilateral cord paralysis is more likely to occur on the
left because of the longer course of the left recurrent lar- LARYNGEAL TRAUMA
yngeal nerve and its proximity to major thoracic struc-
tures. Patients with unilateral paralysis are usually Injury to the larynx may result from external trauma,
hoarse but rarely have stridor. With bilateral cord paral- such as automobile accidents, snowmobile accidents
ysis, the closer to midline the cords are positioned, the (clothesline injury), and hanging; or internal trauma,
greater the airway obstruction; the more lateral the such as noxious inhalation (burns and caustic sub-
cords are positioned, the greater the tendency to aspi- stances) and intubation. External trauma can cause lar-
rate and experience hoarseness or aphonia. If partial yngeal fracture, which requires an emergency tra-
function is preserved (paresis), the adductor muscles cheostomy to prevent death. After appropriate airway
tend to operate better than the abductors, with a resul- intervention, attention should be directed to debride-
tant high-pitched inspiratory stridor and normal voice. ment and closure of lacerations. Reduction of laryngeal
Airway intervention (intubation, tracheostomy) is fractures should be performed as soon as the patient is
rarely indicated in unilateral paralysis but is often nec- stabilized.
essary for bilateral paralysis. Recovery is related to the
Jewett BS et al: External laryngeal trauma: Analysis of 392 patients.
severity of nerve injury and the potential for healing. Arch Otolaryngol Head Neck Surg 1999;125:87 [PMID:
10448735].
de Jong AL et al: Vocal cord paralysis in infants and children. Oto-
laryngol Clin North Am 2000;33:131 [PMID: 10637348]. LARYNGEAL PAPILLOMATOSIS
Portier F et al: Respiratory obstruction as a sign of brainstem dys-
function in infants with Chiari malformations. Int J Pediatr Papillomas of the larynx are benign, warty growths that
Otorhinolaryngol 2001;57:195 [PMID: 11223451]. are difficult to treat and are the most common laryngeal
neoplasm in children. Human papillomaviruses 6, 11,
and 16 have been implicated as causative agents. A sub-
SUBGLOTTIC STENOSIS stantial percentage of mothers of patients with laryngeal
Subglottic stenosis may be congenital or, more com- papillomas have a history of genital condylomas at the
monly, may result from endotracheal intubation. time of delivery, so the virus may be acquired during
Neonates and infants are particularly vulnerable to sub- passage through an infected birth canal.
glottic injury from intubation: The subglottis is the The age at onset is usually 2–4 years, but juvenile-
narrowest part of an infant’s airway, and the cricoid onset recurrent respiratory papillomatosis is well docu-
cartilage, which supports the subglottis, is the only car- mented. A younger age of onset may be a worse prog-
tilage that completely encircles the airway. The clinical nostic indicator. Patients usually develop hoarseness,
presentation may vary from totally asymptomatic to the voice changes, croupy cough, or stridor that can lead to
typical picture of severe upper airway obstruction. Pa- life-threatening airway obstruction. Diagnosis is by di-
tients with signs of stridor who repeatedly fail extuba- rect laryngoscopy. The larynx was involved at the time
tion are likely to have subglottic stenosis. Subglottic of diagnosis in over 95% of patients, most of whom
stenosis should also be suspected in children with mul- had only one site involved.
tiple, prolonged, or severe episodes of croup. As with Treatment is directed toward relieving airway ob-
other conditions, diagnosis is made by direct laryn- struction, usually by surgical removal of the lesions.
goscopy and bronchoscopy. Tracheostomy is often re- Tracheostomy is necessary when life-threatening ob-
quired when airway compromise is severe. Surgical in- struction or respiratory arrest occurs. Various surgical
tervention is ultimately required to correct the stenosis. procedures (laser, cup forceps, cryosurgery) have been
Depending on the type of stenosis, a cricoid split in used to remove papillomas, but recurrences are the rule,
which the cricoid cartilage is surgically opened (better and frequent reoperation may be needed. The lesions
for acquired than for congenital lesions) may be tried. occasionally spread down the trachea and bronchi,
Laryngotracheal reconstruction in which a cartilage making surgical removal more difficult. The use of in-
graft from another source (eg, rib) is used to expand the terferon therapy remains controversial. Fortunately,
airway has become the standard procedure for sympto- spontaneous remissions do occur, usually by puberty,
matic subglottic stenosis in children. so that the goal of therapy is to maintain an adequate
airway until remission occurs.

Cotton RT: Management of subglottic stenosis. Otolaryngol Clin Derkay CS: Recurrent respiratory papillomatosis. Laryngoscope
North Am 2000;33:111 [PMID: 10637347]. 2001;111:57 [PMID: 11192901].
 RESPIRATORY TRACT & MEDIASTINUM / 517

Reeves WC et al: National Registry for juvenile-onset recurrent res- VASCULAR RINGS & SLINGS
piratory papillomatosis. Arch Otolaryngol Head Neck Surg
2003;129:976 [PMID: 12975271]. The most common vascular anomalies to compress the
trachea or esophagus are a double aortic arch, right aor-
tic arch with left ligamentum arteriosum or patent duc-
tus arteriosus, pulmonary sling, anomalous innominate
CONGENITAL DISORDERS OF THE or left carotid artery, and aberrant right subclavian
INTRATHORACIC AIRWAYS artery. All but the latter can cause tracheal compression
and present in infancy with symptoms of chronic air-
MALACIA OF AIRWAYS way obstruction (stridor, coarse wheezing, and croupy
Tracheomalacia or bronchomalacia exists when the car- cough). Symptoms are often worse in the supine posi-
tilaginous framework of the airway is inadequate to tion. Respiratory compromise is most severe with dou-
maintain airway patency. Because cartilage of the infant ble aortic arch and may lead to apnea, respiratory arrest,
airway is normally soft, all infants may have some de- or even death. Esophageal compression, present in all
gree of dynamic collapse of a central airway when pres- but anomalous innominate or carotid artery, may result
sure outside the airway exceeds intraluminal pressure. in feeding difficulties, including dysphagia and vomit-
In tracheomalacia, whether congenital or acquired, dy- ing. Barium swallow showing esophageal compression
namic collapse leads to airway obstruction. The con- is the mainstay of diagnosis. An anomalous innominate
genital variety may be isolated or associated with an- or carotid artery is best diagnosed by cinefluoroscopy,
other developmental defect, such as tracheoesophageal MRI, or bronchoscopy.
fistula or vascular ring. It may be localized to part of the Patients with significant symptoms require surgical
trachea or, more commonly, may involve the entire tra- correction, especially those with double aortic arch.
chea as well as the remainder of the conducting airways. Controversy exists about whether angiography is neces-
In severe cases, cartilage in the involved area may be sary to define the anatomy prior to surgery. Patients
missing or underdeveloped. The acquired variety has usually improve following correction but may have per-
been associated with long-term ventilation of prema- sistent but milder symptoms of airway obstruction due
ture newborns that results in chronic tracheal injury. to associated tracheomalacia.
Patients present with coarse wheezing, a prolonged
expiratory phase, and a croupy cough, all of which in- Krummel TM: Congenital malformations of the lower respiratory
crease with agitation and upper respiratory tract infec- tract. In Chernick V, Boat TF (eds): Kendig’s Disorders of the
tions. Diagnosis can be made by cinefluoroscopy or Respiratory Tract in Children, 6th ed. WB Saunders, 1998.
bronchoscopy. Barium swallow may be indicated to McLaughlin RB Jr et al: Vascular anomalies causing symptomatic
tracheobronchial compression. Laryngoscope 1999;109:312
rule out coexisting conditions. No treatment is usually [PMID: 10890785].
indicated for the isolated condition, which generally
Sebening C et al: Vascular tracheobronchial compression syn-
improves over time. Coexisting lesions such as tracheo- dromes—Experience in surgical treatment and literature re-
esophageal fistulas and vascular rings need primary re- view. Thorac Cardiovasc Surg 2000;48:164 [PMID:
pair. In severe cases of tracheomalacia, intubation or 10903065].
tracheostomy may be necessary, but this procedure
alone is seldom satisfactory because airway collapse con-
tinues to exist below the tip of the artificial airway. BRONCHOGENIC CYSTS
CPAP through an artificial airway can sometimes stabi- Bronchogenic cysts generally occur in the mid medi-
lize the collapsing airway. When conventional therapy astinum (see Mediastinal Masses section) near the ca-
fails, surgical approaches to the problem (tracheopexy, rina and adjacent to the major bronchi but can be
aortopexy, placement of stents) may be considered. found elsewhere in the lung. They range in size from
2 to 10 cm. Cyst walls are thick and may contain pus,
Austin J, Ali T: Tracheomalacia and bronchomalacia in children: mucus, or blood. These cysts develop from abnormal
Pathophysiology, assessment, treatment and anaesthesia man- lung budding of the primitive foregut. They do not
agement. Paediatr Anaesth 2003;13:3 [PMID: 12535032]. contain distal lung parenchyma and generally do not
Finder JD: Primary bronchomalacia in infants and children. J Pedi- communicate with the airway.
atr 1997;130:59 [PMID: 9003852].
Clinically, respiratory distress can appear acutely in
Masters IB et al: Series of laryngomalacia, tracheomalacia, and
bronchomalacia disorders and their associations with other
early childhood or present as chronic wheezing, chronic
conditions in children. Pediatr Pulmonol 2002;34:189 cough, tachypnea, recurrent pneumonia, or stridor, de-
[PMID: 12203847]. pending on the location and size of the cysts and the
Paston F, Bye M: Tracheomalacia. Pediatr Rev 1996;17:328 degree of airway compression. On examination, the tra-
[PMID: 8806208]. chea may deviate from the midline, and the percussion
518 / CHAPTER 18

noted over involved lobes may be hyperresonant. Breath like. Poor child-proofing in the home and cases in
sounds over such areas will also be decreased. The chest which an older sibling feeds age-inappropriate foods
radiograph shows air trapping and hyperinflation of the (eg, peanuts, hard candy, carrot slices) to the younger
affected lobes. Smaller lesions or those detected early child are typical. If the obstruction is only partial,
may not be seen on chest radiographs or may appear coughing, stridor, and the ability to vocalize may per-
spherical. Initial assessment of a suspected bron- sist. If complete, an inability to cough or vocalize
chogenic cyst usually includes barium swallow to look (aphonia) and cyanosis with marked distress are ob-
for a mass. This study also helps determine whether the served. Without treatment, progressive cyanosis, loss of
lesion communicates with the gastrointestinal tract. CT consciousness, seizures, bradycardia, and cardiopulmo-
scans or ultrasonography can differentiate solid versus nary arrest follow.
cystic mediastinal masses and define the cyst’s relation-
ship to the rest of the lung.
Treatment is by surgical resection. Postoperatively, Treatment
vigorous pulmonary physiotherapy is required to pre-
vent complications (atelectasis, infection of lung distal The emergency treatment of upper airway obstruction
to the site of resection of the cyst). due to foreign body aspiration is somewhat controver-
sial. In general, it is recommended that if partial ob-
struction is present, children should be allowed to use
Ahrens B et al: Symptomatic bronchogenic cyst in a six-month-old
infant: Case report and review of the literature. J Thorac Car-
their own cough reflex to extrude the foreign body. If
diovasc Surg 2001;122:1021 [PMID: 11689810]. after a brief observation period, the obstruction in-
Clements BS: Congenital malformations of the lungs and airways. creases or the airway becomes completely obstructed,
In Taussig LM, Landau LI (eds): Pediatric Respiratory Medi- acute intervention is required. The American Academy
cine. Mosby, 1999. of Pediatrics and the American Heart Association dis-
McAdams HP et al: Bronchogenic cyst: Imaging features with clini- tinguish between children younger than and older than
cal and histopathologic correlation. Radiology 2000;217: age 1 year. A choking infant younger than age 1 year
441 [PMID: 11058643]. should be placed face-down over the rescuer’s arm, with
the head positioned below the trunk. Five measured
back blows are delivered rapidly between the infant’s
scapulas with the heel of the rescuer’s hand. If obstruc-
ACQUIRED DISORDERS OF THE tion persists, the infant should be rolled over and five
INTRATHORACIC AIRWAYS rapid chest compressions performed (similar to cardio-
pulmonary resuscitation). This sequence is repeated
FOREIGN BODY ASPIRATION until the obstruction is relieved. In children older than
Aspiration of a foreign body into the respiratory tract is age 1 year, abdominal thrusts (Heimlich maneuver)
rarely observed, so it is the abrupt onset of cough, may be performed, with special care in younger chil-
choking, or wheezing—especially in children who have dren because of concern about possible intraabdominal
access to high-risk objects such as peanuts, hard candy, organ injury.
and small toys—that suggests the diagnosis. Children In both groups, blind probing of the airway to dis-
age 6 months to 4 years are at highest risk, and many lodge a foreign body is discouraged because of the risk
deaths are caused by respiratory obstruction each year. of impaction. The airway may be opened by jaw thrust,
and if the foreign body can be directly visualized, care-
ful removal with the fingers or instruments (Magill for-
1. Foreign Bodies in the Upper ceps) can be attempted. Patients with persistent apnea
Respiratory Tract and inability to achieve adequate ventilation may re-
The diagnosis is established by acute onset of cyanosis quire emergency intubation, tracheostomy, or needle
and choking along with inability to vocalize or cough cricothyrotomy, depending on the setting and the res-
(complete obstruction) or with drooling and stridor cuer’s skills.
(partial obstruction).
Foreign bodies that lodge in the esophagus may
Friedman EM: Tracheobronchial foreign bodies. Otolaryngol Clin
compress the airway and cause respiratory distress. North Am 2000;33:179 [PMID: 10637351].
More typically, the foreign body lodges in the supra- Hazinski MF (ed): Pediatric Advanced Life Support Provider Man-
glottic airway, triggering protective reflexes that result ual. American Heart Association and the American Academy
in laryngospasm. Onset is generally abrupt, with a his- of Pediatrics, 2002.
tory of the child’s running with food in his or her Halvorson DJ et al: Management of subglottic foreign bodies. Ann
mouth or playing with seeds, small coins, toys, and the Otol Rhinol Laryngol 1996;105:541 [PMID: 8678431].
 RESPIRATORY TRACT & MEDIASTINUM / 519

Walner DL et al: Utility of radiographs in the evaluation of pedi- Treatment

atric upper airway obstruction. Ann Otol Rhinol Laryngol
1999;108:378 [PMID: 10214786]. If the imaging is positive or if, despite negative imaging,
clinical suspicion persists, a bronchoscopy is indicated.
Rigid bronchoscopy under general anesthesia is recom-
mended. Flexible bronchoscopy may be helpful for fol-
2. Foreign Bodies in the Lower low-up evaluations (after the foreign object has been re-
Respiratory Tract moved).
Children with suspected acute foreign body aspira-
tion should be admitted to the hospital for evaluation
ESSENTIALS OF DIAGNOSIS and treatment. Chest postural drainage is no longer rec-
& TYPICAL FEATURES ommended because the foreign body may become dis-
lodged and obstruct a major central airway. Bron-
• Sudden onset of coughing, wheezing, or respira- choscopy should not be delayed in children with
tory distress. respiratory distress but should be performed as soon as
• Asymmetrical physical findings of decreased the diagnosis is made—even in children with more
breath sounds or localized wheezing. chronic symptoms. Following the removal of the for-
eign body, β-adrenergic nebulization treatments fol-
• Asymmetrical radiographic findings, especially
lowed by chest physiotherapy are recommended to help
with forced expiratory view. clear related mucus or bronchospasm. Failure to iden-
tify a foreign body in the lower respiratory tract can re-
sult in bronchiectasis and lung abscess. This risk justi-
fies an aggressive approach to suspected foreign bodies
in suspicious cases.
Clinical Findings
Dunn GR et al: Management of suspected foreign body aspiration
A. SYMPTOMS AND SIGNS in children. Clin Otolaryngol 2002;27:384 [PMID:
Respiratory symptoms and signs vary depending on the 12383302].
site of obstruction and the duration following the acute Rovin JD, Rodgers BM: Pediatric foreign body aspiration. Pediatr
Rev 2000;21:86 [PMID: 10702322].
episode. For example, a large or central airway obstruc-
tion may cause marked distress. The acute cough or Skoulakis CE et al: Bronchoscopy for foreign body removal in chil-
dren: A review and analysis of 210 cases. Int J Pediatr Otorhi-
wheezing caused by a foreign body in the lower respira- nolaryngol 2000;53:143 [PMID: 10906520].
tory tract may diminish over time only to recur later
and present as chronic cough or persistent wheezing.
Foreign body aspiration should be suspected in chil- BRONCHITIS
dren with chronic cough, persistent wheezing, or recur-
rent pneumonia. Long-standing foreign bodies may
lead to bronchiectasis or lung abscess. Hearing asym- ESSENTIALS OF DIAGNOSIS
metrical breath sounds or localized wheezing also sug- & TYPICAL FEATURES
gests a foreign body.
• Cough that usually progresses from dry to pro-
ductive.
B. IMAGING
• Rhonchi heard on auscultation.
Inspiratory and forced expiratory (obtained by manu-
ally compressing the abdomen during expiration) chest
radiographs should be obtained if foreign body aspira-
tion is suspected. The initial inspiratory view may show
localized hyperinflation due to the ball-valve effect of
the foreign body, causing distal air trapping. A positive
General Considerations
forced expiratory study shows a mediastinal shift away Bronchitis is inflammation of the major conducting air-
from the affected side. If airway obstruction is com- ways within the lung and is unusual as an isolated en-
plete, atelectasis and related volume loss will be the tity in children. However, inflammation within this
major radiologic findings. Chest fluoroscopy is an alter- section of the airways commonly occurs in viral lower
native approach for detecting air trapping and mediasti- respiratory tract infections, on exposure to environmen-
nal shift. tal irritants including tobacco smoke, and in association
520 / CHAPTER 18

with other disease entities such as CF or primary ciliary older children. In patients of all ages, the potential role
dyskinesia. In adults, the diagnosis of chronic bronchi- of irritants within the environment must also be evalu-
tis is based on a history of at least 3 months of produc- ated.
tive cough occurring for 2 or more years, but no gener-
ally acceptable criteria for this diagnosis exist in Complications
children.
In otherwise healthy children, complications of acute
Clinical Findings bronchitis are extremely uncommon. If persistent,
bronchiectasis, an irreversible dilatation and destruction
A. SYMPTOMS AND SIGNS of the bronchial walls, can result.
Acute bronchitis usually begins as a nonproductive
cough that may be associated with other features of an Treatment
upper respiratory illness of viral origin. The longer the
When bronchitis is secondary to an uncomplicated
cough persists, the more likely it is to become produc-
acute viral infection, supportive therapy is all that is
tive. In general, children with uncomplicated acute
necessary. Expectorants and cough suppressants,
bronchitis appear nontoxic, and fever, if present, is low-
though commonly used, are seldom indicated. Avoid-
grade. Diffuse rhonchi are heard on auscultation. In
ance of irritants during the viral infection may also de-
uncomplicated acute bronchitis, mucus production de-
crease symptoms and morbidity. Antibiotics are indi-
creases, and the cough disappears over a period of
cated if a bacterial infection of the airway is suspected
7–10 days.
or proven.
B. LABORATORY FINDINGS
The white blood count is usually normal and, if ele- Gonzales R, Sande MA: Uncomplicated acute bronchitis. Ann In-
tern Med 2000;133:981 [PMID: 11119400].
vated, may suggest a viral infection. Pulmonary func-
Loughlin GM: Bronchitis. In Chernick V, Boat TF (eds): Kendig’s
tion tests may reveal variable degrees of airway obstruc- Disorders of the Respiratory Tract in Children, 6th ed. WB
tion. Saunders, 1998.
C. IMAGING Meeks M, Bush A: Primary ciliary dyskinesia. Pediatr Pulmonol
2000;29:307 [PMID: 10738019].
Radiographic examination of the chest may be normal
or may show a mild increase in bronchovascular mark-
ings. BRONCHIOLITIS

Differential Diagnosis ESSENTIALS OF DIAGNOSIS

Most attacks of acute bronchitis are caused by viral in- & TYPICAL FEATURES
fections. Certain viral pathogens (eg, adenovirus) can
produce a more severe clinical picture that resembles • Clinical syndrome characterized by coughing,
a pertussis-like illness. Bacteria that may produce dis- tachypnea, labored breathing, and/or hypoxia.
ease in which bronchitis is a prominent symptom in- • Irritability, poor feeding, vomiting.
clude Bordetella pertussis, Mycobacterium tuberculosis, • Wheezing and crackles on chest auscultation.
Corynebacterium diphtheriae, and Mycoplasma pneumo-
niae.
Noninfectious diseases need to be considered in the
evaluation of acute bronchitis that differs from the clin- Bronchiolitis is the most common serious acute respira-
ical picture described earlier and in cases of chronic or tory illness in infants and young children. One to three
recurrent bronchitis. Asthma may present as a persis- percent of infants with bronchiolitis will require hospi-
tent cough with little or no wheezing. Sinus infections talization, especially during the winter months. The
may provide a source of persistent irritation to the res- typical presentation is acute onset of tachypnea, cough,
piratory tract and lead to a chronic cough. CF, an im- rhinorrhea, and expiratory wheezing. Respiratory syn-
munodeficiency, or primary ciliary dyskinesia must also cytial virus (RSV) is by far the most common pathogen;
be considered if the bronchitis persists or recurs and if parainfluenza and influenza viruses, adenovirus, My-
bronchiectasis is present or suspected. In the younger coplasma, Chlamydia, Ureaplasma, and Pneumocystis are
child, respiratory tract anomalies, foreign bodies, and less common causes of bronchiolitis during early in-
recurrent aspiration must also be considered. Tobacco fancy. Major concerns include not only the acute effects
or marijuana smoking may contribute to this process in of bronchiolitis but also the possible development of
 RESPIRATORY TRACT & MEDIASTINUM / 521

chronic airway hyperreactivity (asthma). Bronchiolitis use remains controversial and empiric, and patients
due to RSV infection contributes substantially to mor- should be assessed individually to determine responsive-
bidity and mortality in children with underlying ness.
medical disorders, including chronic lung disease of In immunocompromised patients, especially bone
prematurity, CF, congenital heart disease, and immun- marrow transplant recipients, a combination of RSV
odeficiency. intravenous immune globulin (RSV-IVIG) and the an-
tiviral ribavirin has been tried. Therapy for RSV, how-
Clinical Findings ever, remains limited, controversial, and mostly sup-
portive.
A. SYMPTOMS AND SIGNS
The usual course of RSV bronchiolitis is 1–2 days of
fever, rhinorrhea, and cough, followed by wheezing, Prognosis
tachypnea, and respiratory distress. Typically the The prognosis for the majority of infants with acute
breathing pattern is shallow, with rapid respirations. bronchiolitis is very good. With improved supportive
Nasal flaring, cyanosis, retractions, and rales may be care and prophylaxis with palivizumab, the mortality
present, along with prolongation of the expiratory rate among high-risk infants has decreased substan-
phase and wheezing, depending on the severity of ill- tially.
ness. Some young infants present with apnea and few
findings on auscultation but may subsequently develop
rales, rhonchi, and expiratory wheezing. Paes BA: Current strategies in the prevention of respiratory syncy-
tial virus disease. Paediatr Respir Rev 2003;4:21 [PMID:
B. LABORATORY FINDINGS 12615029].
Schlesinger C, Koss MN: Bronchiolitis: Update 2001. Curr Opin
The peripheral white blood cell count may be normal Pulm Med 2002;8:112 [PMID: 11845006].
or may show a mild lymphocytosis.
C. IMAGING
BRONCHIECTASIS
Chest radiographic findings typically include hyperin-
flation with mild interstitial infiltrates, but segmental
atelectasis is common. ESSENTIALS OF DIAGNOSIS
& TYPICAL FEATURES
Prevention & Treatment
The most effective prevention against RSV infection is • Chronic cough with sputum production.
to use proper hand-washing techniques and to reduce • Rhonchi and/or wheezes on chest auscultation.
exposure to potential environmental risk factors. Major • Diagnosis confirmed by high-resolution CT scan.
challenges have impeded the development of an RSV
vaccine, but a licensed product may be expected in the
near future. Prophylaxis with a monoclonal antibody
(palivizumab or Synagis) has proven effective in reduc-
ing the rate of hospitalization in high-risk premature
infants and those with chronic cardiopulmonary condi-
General Considerations
tions. Bronchiectasis is the permanent dilatation of bronchi.
Although most children with RSV bronchiolitis are The dilation may be regular, with the airway continu-
readily treated as outpatients, hospitalization is fre- ing to have a smooth outline (cylindric bronchiectasis);
quently required in young infants (younger than irregular, with areas of dilation and constriction (vari-
6 months of age) and in patients with hypoxemia on cose bronchiectasis); or marked, with destruction of
room air, a history of apnea, moderate tachypnea with structural components of the airway wall (saccular or
feeding difficulties, marked respiratory distress with re- cystic bronchiectasis).
tractions, or underlying chronic cardiopulmonary dis- Bronchiectasis results from airway obstruction by re-
orders. Supportive strategies including frequent suc- tained mucus secretions or inflammation in response to
tioning and providing adequate fluids to maintain chronic or repeated infection. It occurs either as a con-
hydration form the mainstays of treatment for bronchi- sequence of a preceding illness (severe pneumonia or
olitis. If hypoxemia is present, supplemental oxygen foreign body aspiration) or as a manifestation of an un-
should be administered. Although bronchodilators and derlying systemic disorder (CF or primary ciliary dyski-
corticosteroids may attenuate airway obstruction, their nesia).
522 / CHAPTER 18

Clinical Findings Complications

A. SYMPTOMS AND SIGNS Major concerns are severe pneumonia, hemoptysis, and
Persons with bronchiectasis will typically have chronic cor pulmonale. Less frequent complications are ab-
cough, purulent sputum, fever, and weight loss. Recur- scesses of the lung, empyema, and bronchopleural fis-
rent respiratory infections and dyspnea on exertion are tula.
also common. Some children present with recurrent
fevers. Hemoptysis occurs less frequently in children Treatment
than in adults with bronchiectasis. On physical exami- Aggressive antibiotic therapy during pulmonary exacer-
nation, finger clubbing may be seen, and there may be bations and routine airway clearance are mainstays of
evidence of sinusitis. Persistent moist rales, rhonchi, treatment. Inhaled mucolytic agents and bronchodila-
and decreased air entry are often noted over the tors may also be of benefit in individual patients.
bronchiectatic area when saccular changes are present. Surgical removal of an area of lung affected with se-
vere bronchiectasis is considered when the response to
B. LABORATORY FINDINGS AND IMAGING medical therapy is poor. Other indications for opera-
Cultures from the lower respiratory tract usually reveal tion include severe localized disease, repeated hemopty-
normal oropharyngeal flora. These include Streptococcus sis, and recurrent pneumonia in one area of lung. If
pneumoniae, Staphylococcus aureus, and nontypable H bronchiectasis is widespread, surgical resection offers
influenzae. Pseudomonas aeruginosa can also be found in little advantage.
children with bronchiectasis, even in those without CF.
Chest radiographs may be mildly abnormal with Prognosis
slightly increased bronchovascular markings or areas of
atelectasis, or they may demonstrate cystic changes in The prognosis depends on the underlying cause and
one or more areas of the lung. The extent of bronchiec- severity of bronchiectasis, the extent of lung involve-
tasis is best defined by high-resolution CT scan of the ment, and the response to medical management. Good
lung, which often reveals far wider involvement of lung pulmonary hygiene and avoidance of infectious compli-
than expected from the plain chest radiograph. Con- cations in the involved areas of lung may reverse cylin-
trast bronchography is rarely performed today. dric bronchiectasis.
Pulmonary function testing often reveals an obstruc-
tive pattern even in the absence of asthma, CF, or other Barker AF: Bronchiectasis. N Engl J Med 2002;346:1383 [PMID:
11986413].
disease processes leading to airway obstruction. Evalua-
Chang AB et al: Non-CF bronchiectasis: Clinical and HRCT eval-
tion of lung function after use of a bronchodilator is uation. Pediatr Pulmonol 2003;35:477 [PMID: 12746947].
helpful in assessing the benefit a patient may have from
bronchodilators. Serial assessments of lung function
help define the progression or resolution of the disease. BRONCHIOLITIS OBLITERANS
Bronchiolitis obliterans is characterized by obstruction
of bronchi and bronchioles by fibrous tissue. The disor-
Differential Diagnosis der follows damage to the lower respiratory tract, such
Bronchiectasis has numerous causes. It can occur fol- as inhalation of toxic gases, infections (adenovirus, in-
lowing severe respiratory tract infections by bacteria fluenza virus, rubeola virus, Bordetella, Mycoplasma),
(Bordetella pertussis), viruses (adenovirus), or other or- connective tissue diseases, transplantation, and aspira-
ganisms (Mycobacterium tuberculosis). Bronchiectasis is tion. Bronchiolitis obliterans may also develop in chil-
commonly seen in patients with CF, immunodefi- dren who have Stevens–Johnson syndrome with pul-
ciency, rheumatic conditions, and primary ciliary dyski- monary involvement. Many cases of bronchiolitis
nesia. Other diagnostic considerations include foreign obliterans are idiopathic. Adenovirus-induced bronchi-
body aspiration, chronic aspiration of gastric or oropha- olitis obliterans occurs more frequently in the Native-
ryngeal contents, and allergic bronchopulmonary as- American population and in Polynesian children in
pergillosis. New Zealand.
And though uncommon, bronchiectasis may result
from defective development of bronchial cartilage Clinical Findings
(Williams–Campbell syndrome) and developmental
failure of elastic and muscular tissues of the trachea and A. SYMPTOMS AND SIGNS
bronchi (tracheobronchomegaly, or Mounier–Kuhn Bronchiolitis obliterans should be considered when per-
syndrome). sistent cough, wheezing, or sputum production is pre-
 RESPIRATORY TRACT & MEDIASTINUM / 523

sent after an episode of acute pneumonia. Prolonged Prognosis

rales or wheezing or persistent exercise intolerance fol-
lowing a pulmonary insult should also suggest this dis- Prognosis may depend in part on the underlying cause
ease. as well as the age at which the insult occurred. The
course varies from mild asthma-like symptoms to
rapidly fatal deterioration despite therapy.
B. LABORATORY FINDINGS AND IMAGING
Chest radiograph abnormalities include evidence of lo- Kim CK et al: Bronchiolitis obliterans in the 1990s in Korea and
calized or generalized air trapping as well as (in some the United States. Chest 2001;120:1101 [PMID: 11591545].
cases) nodular densities and alveolar opacification. Scat- Mauad T, Dolhnikoff M; São Paulo Bronchiolitis Obliterans Study
tered areas of matched decreases in ventilation and per- Group: Histology of childhood bronchiolitis obliterans. Pedi-
fusion are seen when the lung is scanned. Pulmonary atr Pulmonol 2002;33:466 [PMID: 12001281].
angiograms reveal decreased vasculature in involved Zhang L et al: Clinical course of postinfectious bronchiolitis oblit-
lung, and bronchograms show marked pruning of the erans. Pediatr Pulmonol 2000;29:341 [PMID: 10790245].
bronchial tree. An assessment of lung function demon-
strates an obstructive process that may be combined
with evidence of restriction. Inhaled bronchodilators or
BRONCHOPULMONARY DYSPLASIA
corticosteroids provide little improvement in lung func-
tion. ESSENTIALS OF DIAGNOSIS
& TYPICAL FEATURES
Differential Diagnosis
• Acute respiratory distress in first week of life.
Poorly treated asthma, CF, and bronchopulmonary
dysplasia must be considered in children with persistent • Required oxygen therapy or mechanical ventila-
airway obstruction. A trial of medications (including tion, with persistent oxygen requirement at
bronchodilators and corticosteroids) may help to deter- 36 weeks’ gestational age.
mine the reversibility of the process when the primary • Persistent respiratory abnormalities, including
differential is between asthma and bronchiolitis obliter- physical signs and radiographic findings.
ans. Although the results of imaging and pulmonary
function testing are very suggestive, the most definitive
way to establish a diagnosis is by lung biopsy.

General Considerations
Complications
Bronchopulmonary dysplasia (BPD) remains one of the
Sequelae of bronchiolitis obliterans include persistent most significant sequelae of acute respiratory distress in
airway obstruction, recurrent wheezing, bronchiectasis, the neonatal intensive care unit, with an incidence of
chronic atelectasis, recurrent pneumonia, and unilateral about 30% for infants with a birth weight of less than
hyperlucent lung syndrome. 1000 g. This disease was first characterized in
1967 when Northway and coworkers reported the clin-
ical, radiologic, and pathologic findings in a group of
Treatment premature newborns that required prolonged mechani-
Supplemental oxygen should be given to patients with cal ventilation and oxygen therapy to treat hyaline
oxygen desaturation during normal activities or sleep. membrane disease. The progression from acute hyaline
In addition, early treatment should be directed at pre- membrane disease to chronic lung disease was divided
venting ongoing airway damage due to problems such into four stages: acute respiratory distress shortly after
as aspiration, which may be either the primary insult or birth, usually hyaline membrane disease (stage I); clini-
an acquired problem secondary to marked hyperinfla- cal and radiographic worsening of the acute lung dis-
tion. The effectiveness of other forms of treatment may ease, often due to increased pulmonary blood flow sec-
be more difficult to evaluate. Oral and inhaled bron- ondary to a patent ductus arteriosus (stage II); and
chodilators may reverse airway obstruction if the disease progressive signs of chronic lung disease (stages III and
has a reactive component. Many children also receive at IV). The pathologic findings and clinical course of
least one course of corticosteroid treatment in an at- BPD in recent years have changed due to a combina-
tempt to reverse the obstruction or prevent ongoing tion of new therapies (surfactants, prenatal glucocorti-
damage. Antibiotics should be used as indicated for coids, and different ventilation strategies) and increased
pneumonia. survival of infants born at earlier gestational ages. Al-
524 / CHAPTER 18

though the incidence of BPD has not changed, the Differential Diagnosis
severity of the lung disease has decreased. Pathologically
this “new” BPD is characterized by a reduction in in- The radiologic appearance of BPD is changing, and se-
flammation, decreased alveolar number, and a dysmor- vere chronic lung findings of fibrosis with infiltrate are
phic vascular structure. less common. The changes in severe BPD necessitate
A recent summary of a National Institutes of Health ruling out meconium aspiration syndrome, congenital
workshop on BPD proposes a definition of the disease infection (eg, with cytomegalovirus [CMV] or Ure-
that includes oxygen requirement for more than aplasma), cystic adenomatoid malformation, recurrent
28 days, a history of positive pressure ventilation or aspiration, pulmonary lymphangiectasia, total anom-
continuous positive airway pressure, and gestational alous pulmonary venous return, overhydration, and id-
age. The new definition accommodates several key ob- iopathic pulmonary fibrosis.
servations regarding the disease, including: (1) Al-
though most of these children were premature and had
hyaline membrane disease, full-term newborns with
Clinical Course & Treatment
such disorders as meconium aspiration or persistent The clinical course of infants with bronchopulmonary
pulmonary hypertension can also develop bronchopul- dysplasia ranges from a mild increased oxygen require-
monary dysplasia; (2) some extremely preterm new- ment that gradually resolves over a few months to more
borns require minimal ventilator support yet subse- severe disease requiring chronic tracheostomy and me-
quently develop a prolonged oxygen requirement chanical ventilation for the first 2 years of life. In gen-
despite the absence of severe acute manifestations of eral, patients show slow, steady improvements in oxy-
respiratory failure; (3) newborns dying within the first gen or ventilator requirements but can have frequent
weeks of life can already have the aggressive, fibroprolif- respiratory exacerbations leading to frequent and pro-
erative pathologic lesions that resemble bronchopul- longed hospitalizations. Clinical management generally
monary dysplasia; and (4) physiologic abnormalities includes careful attention to growth, nutrition (caloric
(increased airway resistance) and biochemical markers requirements of infants with oxygen dependence and
of lung injury (altered protease and antiprotease ratios, respiratory distress are quite high), metabolic status, de-
increased inflammatory cells and mediators), which velopmental and neurologic status, and related prob-
may be predictive of bronchopulmonary dysplasia, are lems, along with the various cardiopulmonary abnor-
already present in the first week of life. malities described in a later discussion.
The precise mechanism that results in the develop- Short courses of postnatal glucocorticoid therapy
ment of BPD is unclear. The premature lung makes in- has been helpful in increasing the success of weaning
sufficient functional surfactant; furthermore, the an- from the ventilator. This therapy is controversial, how-
tioxidant defense mechanisms are not sufficiently ever, because data show decreased alveolarization in
mature to protect the lung from the toxic oxygen preterm and postnatal animals given long courses of
metabolites generated from hyperoxia. Lungs destined corticosteroids. Longer courses of postnatal glucocorti-
to develop BPD show early inflammation and hypercel- coids have been linked to an increased incidence of
lularity followed by healing with fibrosis. Thus abnor- cerebral palsy. Inhaled glucocorticoids may help reduce
mal lung mechanics due to structural immaturity, sur- the need for systemic steroids, but the overall incidence
factant deficiency, atelectasis, and pulmonary of bronchopulmonary dysplasia has not been affected.
edema—plus lung injury secondary to hyperoxia and Early use of surfactant therapy increases the chance for
mechanical ventilation—lead to further abnormalities survival without bronchopulmonary dysplasia and can
of lung function, causing increases in ventilator and decrease the overall mortality and reduce the need for
oxygen requirements and resulting in a vicious cycle ventilation. Thus early interventions are important
that compounds the progression of lung injury. Exces- prior to the development of bronchopulmonary dyspla-
sive fluid administration, patent ductus arteriosus, pul- sia to decrease morbidity and mortality. Ongoing stud-
monary interstitial emphysema, pneumothorax, infec- ies on the imbalance of proteolytic enzymes, elastolytic
tion, pulmonary hypertension, and inflammatory lung damage, and the role of specific antiinflammatory
stimuli secondary to lung injury or infection also play medications during the early development of bron-
important roles in the pathogenesis of the disease. Al- chopulmonary dysplasia are needed.
though the exact mechanisms leading to chronic lung Because increased airway resistance and bronchial
disease are not completely understood, bronchopul- hyperreactivity are common in affected infants, inhaled
monary dysplasia represents the consequences of lung corticosteroids together with occasional use of β-adren-
injury caused by oxygen toxicity, barotrauma, and in- ergic agonists are commonly part of the treatment plan.
flammation superimposed on a susceptible, generally Part of the rationale for the use of corticosteroids is to
immature lung. decrease lung inflammation and enhance responsiveness
 RESPIRATORY TRACT & MEDIASTINUM / 525

to β-adrenergic drugs, as in the treatment of severe sion and the development of left ventricular hypertro-
asthma. β-Adrenergic agonists followed by chest phys- phy.
iotherapy are often used for the thick secretions that Nutritional problems in infants may be due to in-
may contribute to airway obstruction or recurrent at- creased oxygen consumption, feeding difficulties, gas-
electasis. troesophageal reflux, and chronic hypoxemia. Hyper-
Although bronchial hyperreactivity in affected in- caloric formulas and gastrostomies are often required to
fants is well recognized, structural lesions (eg, subglottic ensure adequate intake while avoiding overhydration.
stenosis, vocal cord paralysis, tracheal stenosis, tracheo- Influenza vaccine is recommended. With the onset of
malacia, bronchial stenosis, and granulomatous acute wheezing secondary to suspected viral infection,
bronchial polyps) often contribute to airflow limitation. rapid diagnostic testing for RSV infection may facilitate
Children with significant stridor, sleep apnea, chronic early treatment. Immune prophylaxis of RSV reduces
wheezing, or excessive respiratory distress need diagnos- the morbidity of bronchiolitis in infants with bron-
tic bronchoscopy. In addition, the contribution of gas- chopulmonary dysplasia.
troesophageal reflux and aspiration should be consid- For children who remain ventilator-dependent, at-
ered in the face of worsening chronic lung disease. tempts should be made to maintain PaCO2 below
Infants often have recurrent pulmonary edema, 60 mm Hg—even when pH is normal—because of the
which may be due to increased permeability of the in- potential adverse effects of hypercapnia on salt and
jured pulmonary circulation or to increases in hydrosta- water retention, cardiac function, and perhaps pul-
tic pressure if left ventricular dysfunction is present. monary vascular tone. Changes in ventilator settings in
Salt and water retention secondary to chronic hypox- children with severe lung disease should be slow, be-
emia, hypercapnia, or other stimuli may be present. cause the effects of many of the changes may not be ap-
Chronic or intermittent diuretic therapy is commonly parent for days. These signs may include poor feeding,
used if rales or signs of persistent pulmonary edema are irritability, weight loss, vomiting, increased retractions,
present and clinical studies show acute improvement in wheezing, increased somnolence, and CO2 retention.
lung function. Unfortunately, diuretics often have ad- Medical staff should meet frequently with the parents
verse effects, including severe volume contraction, hy- to review progress and changes in treatment plans and
pokalemia, alkalosis, and hyponatremia. Potassium and thereby ease some of the family stresses involved in car-
arginine chloride supplements are commonly required. ing for a child who has a chronic disease. Patience, con-
Infants with BPD are at risk of developing pul- tinued family support, attention to developmental is-
monary hypertension, and in many of these children sues, and speech and physical therapy help to improve
even mild hypoxemia can cause significant elevations of the long-term outlook.
pulmonary arterial pressure. To minimize the harmful
effects of hypoxemia, the SaO2 should be kept above
93%, with care to avoid hyperoxia during retinal vascu-
Prognosis
lar development. Electrocardiographic and echocardio- Surfactant replacement therapy has had a significant ef-
graphic studies should be performed to monitor for the fect on reducing morbidity and mortality from bron-
development of right ventricular hypertrophy. If hyper- chopulmonary dysplasia. Infants of younger gestational
trophy persists or if it develops where it was not previ- age are surviving in greater numbers. Surprisingly, the
ously present, intermittent hypoxemia should be con- effect of neonatal care has not decreased the incidence
sidered and further assessments of oxygenation of bronchopulmonary dysplasia significantly, as half the
pursued, especially while the infant sleeps. Even inter- survivors go on to develop this diagnosis. The disorder
mittent hypoxia contributes to the development or pro- typically develops in the most immature infants, but
gression of pulmonary hypertension and cor pul- the long-term outlook for most survivors is generally fa-
monale; therefore, noninvasive assessments of vorable. Long-term follow-up studies suggest that lung
oxygenation must be made during all activities, includ- function may be altered for life. Hyperinflation and
ing the infant’s waking, sleeping, and feeding periods. damage to small airways has been reported in children
Infants with a history of intubation can develop ob- 10 years out from the first signs of bronchopulmonary
structive sleep apnea secondary to a high-arched palate dysplasia. In addition, these infants are at a higher risk
or subglottic narrowing. Barium swallow, esophageal for developing such sequelae as persistent airway hyper-
pH probe studies, bronchoscopy, and cardiac catheteri- reactivity, exercise intolerance, pulmonary hyperten-
zation will diagnose unsuspected cardiac or pulmonary sion, increased risk for COPD, and perhaps abnormal
lesions that contribute to the underlying pathophysiol- lung growth. As smaller, more immature infants sur-
ogy, such as aspiration, tracheomalacia, obstructive vive, abnormal neurodevelopmental outcomes become
sleep apnea, and anatomic cardiac lesions. Long-term more likely. The incidence of cerebral palsy, hearing
care should include monitoring for systemic hyperten- loss, vision abnormalities, spastic diplegia, and develop-
526 / CHAPTER 18

mental delays is increased. Feeding abnormalities, be- • Pulmonary, gastrointestinal, or hepatic dysfunc-
havior difficulties, and increased irritability have all tion.
been reported. Finally, children with bronchopul-
monary dysplasia frequently develop airway obstruc-
tion, hyperreactive airways, and decreased oxygen satu-
ration during exercise. This should be taken into
account for children residing at higher altitudes. A
focus on good nutrition, prophylaxis against respiratory General Considerations
pathogens and airway hyperreactivity, and attention to Cystic fibrosis is the most common lethal genetic dis-
school performance continue to provide the best out- ease in the United States, with an incidence of
comes. 1:3000–1:4000 among Caucasians. It is a major cause
of pulmonary and gastrointestinal morbidity in chil-
Abman SH: Bronchopulmonary dysplasia: “A vascular hypothesis.”
dren and a leading cause of death in early adulthood.
Am J Respir Crit Care Med 2001;164(10 Pt 1):1755 [PMID: Although CF is characterized by abnormalities in the
11734417]. hepatic, gastrointestinal, and male reproductive sys-
Allen J et al; American Thoracic Society: Statement on the care of tems, lung disease is the major cause of morbidity and
the child with chronic lung disease of infancy and childhood. mortality. Almost all patients develop obstructive lung
Am J Respir Crit Care Med 2003;168(3):356 [PMID: disease associated with chronic infection that leads to
12888611]. progressive loss of pulmonary function. The prognosis
Bancalari E et al: Bronchopulmonary dysplasia: Changes in patho- has improved steadily over the past 20 years, so that the
genesis, epidemiology and definition. Semin Neonatol median survival is now 33 years—perhaps because of
2003;8(1):63 [PMID: 12667831].
antibiotics, better treatment of malabsorption, and de-
Charafeddine L et al: Atypical chronic lung disease patterns in
neonates. Pediatrics 1999;103:759 [PMID: 10103299].
velopment of a network of CF clinical care centers. The
centers usually emphasize a multidisciplinary approach
Cole CH: Inhaled glucocorticoid therapy in infants at risk for
neonatal chronic lung disease. J Asthma 2000;37:533 to patient care (www.cff.org).
[PMID: 11060660]. The gene for CF is on the long arm of human chro-
Gracey K et al: The changing face of bronchopulmonary dysplasia. mosome 7 and codes for the cystic fibrosis transmem-
Adv Neonatal Care 2002;2(6):327 [PMID: 12881945]. brane conductance regulator (CFTR) protein. CFTR
Jobe AH, Bancalari E: Bronchopulmonary dysplasia. Am J Respir functions as an ion channel and controls the movement
Crit Care Med 2001;163:1723 [PMID: 11401896]. of salt and water into and out of epithelial cells where it
Jobe AH, Ikegami M: Prevention of bronchopulmonary dysplasia. is expressed. Over 1000 mutations in the CF gene have
Curr Opin Pediatr 2001;13:124 [PMID: 11317052]. been identified. The most common mutation, called
Kresch MJ, Clive JM: Meta-analysis of surfactant replacement ther- delta F508, is a deletion of three base pairs at position
apy of infants with birth weights less than 2000 grams. J Peri- 508 in the gene. These gene mutations lead to defects
natol 1998;18:276 [PMID: 9730197]. or deficiencies in CFTR, causing cells to produce ab-
Northway WH et al: Pulmonary disease following respiratory ther- normally thick mucus.
apy of hyaline membrane disease: Bronchopulmonary dyspla-
sia. N Engl J Med 1967;276:357 [PMID: 5334613].
Parker TA, Abman SH: The pulmonary circulation in bronchopul-
monary dysplasia. Semin Neonatol 2003;8(1):51 [PMID: Clinical Findings & Treatment
12667830].
A. CLINICAL PRESENTATIONS AND DIAGNOSIS
Saugstad OD: Bronchopulmonary dysplasia—Oxidative stress
and antioxidants. Semin Neonatol 2003;8(1):39 [PMID: Approximately 15% of newborns with CF present at
12667829]. birth with meconium ileus, a severe intestinal obstruc-
Speer CP: Inflammation and bronchopulmonary dysplasia. Semin tion resulting from inspissation of tenacious meconium
Neonatol 2003;8(1):29 [PMID: 12667828]. in the terminal ileum. In the past, surgical removal of
the meconium was common and often led to resection
of bowel. Improved techniques of enema administra-
CYSTIC FIBROSIS tion under radiologic observation have reduced the
need for surgery.
Roughly 50% of patients with CF present in infancy
ESSENTIALS OF DIAGNOSIS with failure to thrive, respiratory compromise, or both.
& TYPICAL FEATURES The age at presentation, however, can be variable; some
patients are not diagnosed until adulthood. Newborn
• Sweat chloride > 60 mmol/L. screening based on elevations of immunoreactive
• Mutated CFTR protein. trypsinogen (IRT), a pancreatic enzyme precursor, in
 RESPIRATORY TRACT & MEDIASTINUM / 527

the blood is an alternative method of case identifica- because of stool loss of fat and protein and ongoing
tion. pulmonary infection and inflammation.
In the presence of clinical symptoms such as meco-
nium ileus, failure to thrive, or recurrent respiratory in- C. PULMONARY FINDINGS AND TREATMENT
fections, or with elevated IRT levels, the diagnosis of Infants with CF frequently have respiratory symptoms
CF is confirmed by a sweat chloride level above severe enough to require hospitalization. Cough, tachy-
60 mEq/L or by the presence of two known CF muta- pnea, rales, and wheezing are common findings. RSV
tions. The most acceptable sweat testing procedure is infection is associated with added morbidity in early in-
the quantitative pilocarpine iontophoresis sweat test. fancy. Some patients develop cough only later in child-
Measurements of electrical conductivity alone can be hood or adolescence, but by adulthood almost all per-
unreliable. sons with CF have productive coughs. In more
advanced disease, hemoptysis due to bronchiectasis, ex-
B. GASTROINTESTINAL AND NUTRITIONAL FINDINGS ercise limitation, and cor pulmonale may be present.
AND TREATMENT Rales may be heard on physical examination. Clubbing
Patients with untreated CF have abdominal distention also develops as the lung disease progresses.
and discomfort; bulky, greasy stools; and increased flat- Pulmonary function abnormalities initially show ob-
ulence secondary to exocrine pancreatic insufficiency structive patterns with diminished flow rates and in-
and malabsorption. Some infants present with hypoal- creased lung volumes. As the disease progresses, vital ca-
buminemia, anemia, edema, and hepatomegaly. Infants pacity is also affected. The incidence of airway
with severe protein–calorie malnutrition have particu- reactivity in CF has been estimated to be 25–50%, sev-
larly difficult courses, with high morbidity and mortal- eral times the incidence in the general population. Ini-
ity rates. Children and adults with CF are subject to in- tially, the airway is colonized with Staphylococcus au-
testinal blockage from inspissated stool. This so-called reus, but in most persons Pseudomonas aeruginosa
meconium ileus equivalent is now most often treated eventually becomes the predominant pathogen. Acqui-
with cathartics and enemas and only rarely requires sition of the characteristic mucoid Pseudomonas is asso-
surgery. Persons with CF are more prone to intussus- ciated with a more rapid decline in pulmonary func-
ception (especially of the appendix) than are those tion. In addition, infection with Burkholderia cepacia
without the disease. has been associated with rapid deterioration and death.
The cornerstone of gastrointestinal treatment is pan- Pathologically, the earliest lesions involve hyperplasia of
creatic enzyme supplementation. Patients are required the mucus glands of the bronchial epithelium and mu-
to take the enzyme capsules with each meal and with cosal and submucosal cellular infiltrates. Bronchiolecta-
snacks. Newer enzyme preparations contain more lipase sis and bronchiectasis throughout all lung fields usually
per capsule than older preparations; therefore, patients follow.
take fewer capsules, making administration easier. Oc- Airway clearance therapy and aggressive antibiotic
casionally, enzyme supplementation alone does not use form the mainstays of treatment for CF lung dis-
control the malabsorption, and antacids are added to ease. Two evidence-based medications that are now
the regimen. routinely used in many persons with CF are inhaled re-
Individuals with CF may have fat-soluble vitamin combinant human DNase (Pulmozyme) and inhaled
deficiency, hypoalbuminemia, and poor growth with tobramycin (TOBI). These therapies have been shown
decreased stores of body fat. In the past, fat-restricted to maintain lung function and reduce the need for hos-
diets were recommended. It is now recognized that per- pitalizations and intravenous antibiotics. Bronchodila-
sons with CF need all the calories they can take, and tors and antiinflammatory therapies are also frequently
unrestricted diets are the norm in most centers. More- used.
over, caloric supplements, such as high-calorie commer- Although corticosteroids have been shown to be ef-
cial supplements or formulas or food modules (includ- fective in maintaining lung function in persons with
ing Polycose and medium-chain triglycerides), are often CF, adverse effects, including glucose intolerance, frank
added to the patient’s diet. In patients who do not re- diabetes, and decreased linear growth, have limited
spond to oral supplementation, night-time nasogastric their use. Persons with CF derive hope from the range
feeding or feeding by means of gastrostomy or jejunos- of agents being evaluated for restoring CFTR function.
tomy has been tried. Although there is general agree- Gene therapy trials are also under way.
ment that quality of life is enhanced by improved nutri- A subgroup of patients with CF have frequent pul-
tion, it is not known whether aggressive nutritional monary exacerbations characterized by difficult breath-
treatment increases longevity. The goals of nutritional ing, increased sputum production, decreased exercise
treatment are to achieve normal height and weight. Pa- tolerance, and diminished pulmonary function. These
tients may require many more calories than predicted patients often benefit from hospital treatment, includ-
528 / CHAPTER 18

ing intensified airway clearance therapy, intravenous ographs show a mediastinal shift toward the affected
antibiotics, bronchodilators, and concentrated efforts at side, and vertebral abnormalities may be present. Ab-
nutritional rehabilitation. Increasingly, outpatient in- sent or incomplete lung development may be associated
travenous therapy is being used to shorten or eliminate with other congenital abnormalities, such as absence of
the hospital stay. one or both kidneys or fusion of ribs, and the outcome
is primarily related to the severity of associated lesions.
D. HEPATIC DISEASE About 50% of patients survive; the mortality rate is
Although most patients with CF have cirrhosis at au- higher with agenesis of the right lung than of the left
topsy, only a small percentage develop portal hyperten- lung. This difference is probably not related to the
sion. In these individuals, however, the clinical findings higher incidence of associated anomalies but rather to a
of the liver disease may be severe, with esophageal greater shift in the mediastinum that leads to tracheal
varices leading to life-threatening gastrointestinal bleed- compression and distortion of vascular structures.
ing and hypersplenism requiring splenic embolization. Pulmonary hypoplasia is incomplete development of
one or both lungs, characterized by a reduction in alve-
E. REPRODUCTIVE TRACT INVOLVEMENT olar number and a reduction in airway branches. Pul-
Failure of development of the vas deferens leaves more monary hypoplasia is present in up to 10–15% of peri-
than 95% of males with CF infertile. CF is occasionally natal autopsies. The hypoplasia can be a result of an
diagnosed through infertility evaluations in men with intrathoracic mass, resulting in lack of space for the
relatively mild involvement of the respiratory and gas- lungs to grow; decreased size of the thorax; decreased
trointestinal tracts. In general, women with CF are fer- fetal breathing movements; decreased blood flow to the
tile, but pregnancy may place considerable stress on pa- lungs; or possibly a primary mesodermal defect affect-
tients with limited pulmonary function. ing multiple organ systems. Congenital diaphragmatic
hernia is the most common cause, with an incidence of
Prognosis 1:2200 births. Other causes include extralobar seques-
tration, diaphragmatic eventration or hypoplasia, tho-
The rate of progression of lung involvement usually de- racic neuroblastoma, fetal hydrops, and fetal hydrochy-
termines survival. Most patients now reach adulthood. lothorax. Chest cage abnormalities, diaphragmatic
Lung transplant for end-stage disease is an accepted elevation, oligohydramnios, chromosomal abnormali-
treatment. In addition, new treatments, including gene ties, severe musculoskeletal disorders, and cardiac le-
therapy trials, are being developed based on improved sions may also result in hypoplastic lungs. Postnatal fac-
understanding of the disease at the cellular and molecu- tors may play important roles. For example, infants
lar levels. with advanced bronchopulmonary dysplasia can have
pulmonary hypoplasia.
Ratjen F, Doring G: Cystic fibrosis. Lancet 2003;361:681 [PMID:
12606185].
Welsh MJ et al: Cystic fibrosis. In Scriver CR et al (eds): The Meta- Clinical Findings
bolic and Molecular Bases of Inherited Disease, McGraw Hill, A. SYMPTOMS AND SIGNS
2001, pp 521–588.
The clinical presentation is highly variable and is re-
lated to the severity of hypoplasia as well as associated
abnormalities. Lung hypoplasia is often associated with
CONGENITAL MALFORMATIONS pneumothorax. Some newborns present with perinatal
OF THE LUNG stress, severe acute respiratory distress, and persistent
pulmonary hypertension of the newborn secondary to
What follows is a brief description of selected congeni- primary pulmonary hypoplasia (without associated
tal pulmonary malformations. anomalies). Children with lesser degrees of hypoplasia
may present with chronic cough, tachypnea, wheezing,
PULMONARY AGENESIS and recurrent pneumonia.
& HYPOPLASIA B. LABORATORY FINDINGS AND IMAGING
With unilateral pulmonary agenesis (complete absence Chest radiographic findings include variable degrees of
of one lung), the trachea continues into a main volume loss in a small hemithorax with mediastinal
bronchus and often has complete tracheal rings. The shift. Pulmonary agenesis should be suspected if tra-
left lung is affected more often than the right. With cheal deviation is evident on the chest radiograph. The
compensatory postnatal growth, the remaining lung chest CT scan is the optimal diagnostic imaging proce-
often herniates into the contralateral chest. Chest radi- dure if the chest radiograph is not definitive. Ventila-
 RESPIRATORY TRACT & MEDIASTINUM / 529

tion–perfusion scans, angiography, and bronchoscopy can be associated with other anomalies, including bron-
are often helpful in the evaluation, demonstrating de- chogenic cysts, heart defects, and diaphragmatic hernia,
creased pulmonary vascularity or premature blunting of the latter occurring in over half of cases.
airways associated with the maldeveloped lung tissue. Intralobar sequestration is an isolated segment of
The degree of respiratory impairment is defined by lung within the normal pleural investment that often
analysis of arterial blood gases. receives blood from one or more arteries arising from
the aorta or its branches. Intralobar sequestration is
usually found within the lower lobes (98%), two thirds
Treatment & Prognosis are found on the left side, and it is rarely associated
Treatment is supportive. The outcome is determined with other congenital anomalies (less than 2% versus
by the severity of underlying medical problems, the ex- 50% with extralobar sequestration). It rarely presents in
tent of the hypoplasia, and the degree of pulmonary hy- the newborn period (unlike extralobar sequestration).
pertension. Some researchers have hypothesized that intralobar se-
questration is an acquired lesion secondary to chronic
Chinoy MR: Pulmonary hypoplasia and congenital diaphragmatic infection. Clinical presentation includes chronic cough,
hernia: Advances in the pathogenetics and regulation of lung wheezing, or recurrent pneumonias. Rarely, patients
development. J Surg Res 2002;106(1):209 [PMID: with intralobar sequestration can present with hemop-
12127828]. tysis. Diagnosis is often made by angiography, which
Laudy JA, Wladimiroff JW: The fetal lung. 2: Pulmonary hypopla- shows large systemic arteries perfusing the lesion. Re-
sia. Ultrasound Obstet Gynecol 2000;16(5):482 [PMID: cently, spiral CT scans with contrast, or magnetic reso-
11169336]. nance angiography, have proven useful in identifying
Nowotny T et al: Right-sided pulmonary aplasia: Longitudinal anomalous systemic arterial supply to the lung. Treat-
lung function studies in two cases and comparison to results
from term healthy neonates. Pediatr Pulmonol 1998;26:138
ment is usually by surgical resection.
[PMID: 9727767].
Winn HN et al: Neonatal pulmonary hypoplasia and perinatal Alton H: Pulmonary vascular imaging. Paediatr Respir Rev
mortality in patients with midtrimester rupture of amniotic 2001;2(3):227. [PMID: 12052324].
membranes—a critical analysis. Am J Obstet Gynecol 2000; Blesovsky A: Pulmonary sequestration. A report of an unusual case
182:1638 [PMID: 10871491]. and a review of the literature. Thorax 1967;22(4):351
[PMID: 6035799].
Conran RM, Stocker JT: Extralobar sequestration with frequently
PULMONARY SEQUESTRATION associated congenital cystic adenomatoid malformation, type
2: Report of 50 cases. Pediatr Dev Pathol 1999;2:454
Pulmonary sequestration is nonfunctional pulmonary [PMID: 10441623].
tissue that does not communicate with the tracheo- Halkic N et al: Pulmonary sequestration: A review of 26 cases. Eur
bronchial tree and receives its blood supply from one or J Cardiothorac Surg 1998;14(2):127 [PMID: 9754996].
more anomalous systemic arteries. This abnormality Salmons S: Pulmonary sequestration. Neonatal Netw 2000;19(7):
originates during the embryonic period of lung devel- 27 [PMID: 11949021].
opment. It is classified as either extralobar or intralobar. Zylak CJ et al: Developmental lung anomalies in the adult: Radio-
Extralobar sequestration is a mass of pulmonary logic-pathologic correlation. Radiographics 2002;22 Spec
parenchyma anatomically separate from the normal No:S25 [PMID: 12376599].
lung, with a distinct pleural investment. Its blood sup-
ply derives from the systemic circulation (more typical),
from pulmonary vessels, or from both. Rarely it com-
CONGENITAL LOBAR EMPHYSEMA
municates with the esophagus or stomach. Pathologi- Patients with congenital lobar emphysema—also
cally, extralobar sequestration appears as a solitary tho- known as infantile lobar emphysema, congenital local-
racic lesion near the diaphragm. Abdominal sites are ized emphysema, unilobar obstructive emphysema,
rare. Size varies from 0.5 to 12 cm. The left side is in- congenital hypertrophic lobar emphysema, or congeni-
volved in over 90% of cases. In contrast to intralobar tal lobar overinflation—present most commonly with
sequestrations, venous drainage is usually through the severe neonatal respiratory distress or progressive respi-
systemic or portal venous system. ratory impairment during the first year of life. Rarely
Histologic findings include uniformly dilated bron- the mild or intermittent nature of the symptoms in
chioles, alveolar ducts, and alveoli. Occasionally the older children or young adults results in delayed diag-
bronchial structure appears normal; however, often the nosis. Most patients are white males. Although the
cartilage in the wall is deficient, or no cartilage-contain- cause of congenital lobar emphysema is not well under-
ing structures can be found. Lymphangiectasia is some- stood, some lesions show bronchial cartilaginous dys-
times found within the lesion. Extralobar sequestration plasia due to abnormal orientation or distribution of
530 / CHAPTER 18

the bronchial cartilage. This leads to expiratory col- Babu R et al: Prenatal sonographic features of congenital lobar em-
lapse, producing obstruction and the symptoms out- physema. Fetal Diagn Ther 2001;16(4):200 [PMID:
11399878].
lined in the following discussion.
Horak E et al: Congenital cystic lung disease: Diagnostic and thera-
peutic considerations. Clin Pediatr 2003;42(3):251 [PMID:
Clinical Findings 12739924].
Mandelbaum I et al: Congenital lobar obstructive emphysema: Re-
A. SYMPTOMS AND SIGNS port of eight cases and literature review. Ann Surg
Clinical features include tachypnea, cyanosis, wheezing, 1965;162(6):1075 [PMID: 5845589].
retractions, and cough. Breath sounds are reduced on Ozcelik U et al: Congenital lobar emphysema: Evaluation and
long-term follow-up of thirty cases at a single center. Pediatr
the affected side, perhaps with hyperresonance to per- Pulmonol 2003;35(5):384 [PMID: 12687596].
cussion, mediastinal displacement, and bulging of the
chest wall on the affected side.
CONGENITAL CYSTIC ADENOMATOID
B. IMAGING MALFORMATION
Radiologic findings include overdistention of the af- Patients with congenital cystic adenomatoid malforma-
fected lobe (usually an upper or middle lobe; > 99%), tions (CAMs), which are unilateral hamartomatous le-
with wide separation of bronchovascular markings, col- sions, generally present with marked respiratory distress
lapse of adjacent lung, shift of the mediastinum away within the first days of life. This disorder accounts for
from the affected side, and a depressed diaphragm on 95% of cases of congenital cystic lung disease.
the affected side. The radiographic diagnosis may be Right and left lungs are involved with equal fre-
confusing in the newborn because of retention of alveo- quency. These lesions originate during the first
lar fluid in the affected lobe causing the appearance of a 4–6 weeks of gestation during the embryonic period of
homogeneous density. Other diagnostic studies include lung development. These lesions appear as gland-like
chest radiograph with fluoroscopy, ventilation–perfu- space-occupying masses or have an increase in terminal
sion study, and chest CT scan followed by bron- respiratory structures, forming intercommunicating
choscopy, angiography, and exploratory thoracotomy. cysts of various sizes, lined by cuboidal or ciliated pseu-
dostratified columnar epithelium. They may have poly-
Differential Diagnosis poid formations of mucosa, with focally increased elas-
tic tissue in the cyst wall beneath the bronchial type of
The differential diagnosis of congenital lobar emphy- epithelium. Air passages appear malformed and tend to
sema includes pneumothorax, pneumatocele, atelectasis lack cartilage.
with compensatory hyperinflation, diaphragmatic her- There are three types of such malformations. Type
nia, and congenital cystic adenomatoid malformation. 1 is most common (55%) and consists of single or mul-
The most common site of involvement is the left upper tiple large cysts (> 2 cm in diameter) with features of
lobe (42%) or right middle lobe (35%). Evaluation mature lung tissue. Type 1 is amenable to surgical re-
must differentiate regional obstructive emphysema section. A mediastinal shift is evident on examination
from lobar hyperinflation secondary to an uncompli- or chest radiograph in 80% of patients and can mimic
cated ball-valve mechanism due to extrinsic compres- infantile lobar emphysema. Approximately 75% of type
sion from a mass (ie, bronchogenic cyst, tumor, lym- 1 lesions are on the right side. A survival rate of 90% is
phadenopathy, foreign body, pseudotumor or plasma generally reported.
cell granuloma, vascular compression) or intrinsic ob- Type 2 lesions (40% of cases) consist of multiple
struction from a mucus plug due to infection and in- small cysts (< 2 cm) resembling dilated simple bronchi-
flammation from various causes. oles and are often (60%) associated with other anom-
alies, especially renal agenesis or dysgenesis, cardiac
Treatment malformations, and intestinal atresia. Approximately
60% of type 2 lesions are on the left side. Mediastinal
When respiratory distress is marked, a segmental or shift is evident less often (10%) than in type 1, and the
complete lobectomy is usually required. Less sympto- survival rate is worse (40%).
matic older children may do equally well with or with- Type 3 lesions consist of small cysts (< 0.5 cm).
out lobectomy. They appear as a bulky, firm mass. The reported sur-
vival rate is 50%.
Al-Bassam A et al: Congenital cystic disease of the lung in infants Recently, two additional types have been described:
and children (experience with 57 cases). Eur J Pediatr Surg type 0, a malformation of the proximal tracheo-
1999;9:364 [PMID: 10661844]. bronchial tree (incompatible with life), and type 4, a
 RESPIRATORY TRACT & MEDIASTINUM / 531

malformation of the distal acinus. Both types are ex- ACQUIRED DISORDERS INVOLVING
tremely uncommon.
ALVEOLI
Clinical Findings BACTERIAL PNEUMONIA
A. SYMPTOMS AND SIGNS
Clinically, respiratory distress is noted soon after birth.
Expansion of the cysts occurs with the onset of breath- ESSENTIALS OF DIAGNOSIS
ing and produces compression of normal lung areas & TYPICAL FEATURES
with mediastinal herniation. Breath sounds are de-
creased. With type 3 lesions, dullness to percussion may • Fever, cough, dyspnea.
be present. Older patients can present with a sponta- • Abnormal chest examination (rales or decreased
neous pneumothorax or with pneumonia-like symp- breath sounds).
toms. • Abnormal chest radiograph (infiltrates, hilar
B. IMAGING adenopathy, pleural effusion).
With type 1 lesions, chest radiograph shows an intra-
pulmonary mass of soft tissue density with scattered ra-
diolucent areas of varying sizes and shapes, usually with
a mediastinal shift and pulmonary herniation. Place- General Considerations
ment of a radiopaque feeding tube into the stomach
helps in the differentiation from diaphragmatic hernia. Bacterial pneumonia is inflammation of the lung classi-
Type 2 lesions appear similar except that the cysts are fied according to the infecting organism. It usually de-
smaller. Type 3 lesions may appear as a solid homoge- velops when one or more of the defense mechanisms
neous mass filling the hemithorax and causing a normally protecting the lung is inadequate. Patients
marked mediastinal shift. Differentiation from seques- with the following problems are particularly predis-
tration is not difficult because congenital cystic adeno- posed to this disease: aspiration, immunodeficiency or
matoid malformations have no systemic blood supply. immunosuppression, congenital anomalies (intrapul-
monary sequestration, tracheoesophageal fistula, cleft
palate), abnormalities in clearance of mucus (CF, ciliary
Treatment dysfunction, tracheomalacia, bronchiectasis), congestive
Treatment of types 1 and 3 lesions involves surgical re- heart failure, and perinatal contamination.
moval of the affected lobe. Resection is often indicated
because of the risk of infection and air trapping, since Clinical Findings
the malformation communicates with the tracheo-
bronchial tree but mucous clearance is compromised. A. SYMPTOMS AND SIGNS
Because type 2 lesions are often associated with other The bacterial pathogen, severity of the disease, and age
severe anomalies, management may be more complex. of the patient may cause substantial variations in the
Segmental resection is not feasible because smaller cysts presentation of acute bacterial pneumonia. Infants may
may expand after removal of the more obviously af- have few or nonspecific findings on history and physi-
fected area. CAMs have been reported to have malig- cal examination. Immunocompetent older patients may
nant potential; therefore, expectant management with not be extremely ill. Some patients may present with
observation alone should proceed with caution. Recent fever only or only with signs of generalized toxicity.
development of intrauterine surgery for congenital mal- Others may have additional symptoms or signs of lower
formations has led to promising results. respiratory tract disease (respiratory distress, cough,
sputum production), pneumonia (rales, decreased
Breckenridge RL et al: Congenital cystic adenomatoid malforma- breath sounds, dullness to percussion, abnormal tactile
tion of the lung. J Pediatr 1965;67(5):863 [PMID: or vocal fremitus), or pleural involvement (splinting,
5845450]. pain, friction rub, dullness to percussion). Some pa-
Duncombe GJ et al: Prenatal diagnosis and management of con- tients may have additional extrapulmonary findings,
genital cystic adenomatoid malformation of the lung. Am
J Obstet Gynecol 2002;187(4):950 [PMID: 12388984].
such as meningismus or abdominal pain, due to pneu-
monia itself. Others may have evidence of infection at
MacSweeney F et al: An assessment of the expanded classification
of congenital cystic adenomatoid malformations and their re- other sites due to the same organism causing their
lationship to malignant transformation. Am J Surg Pathol pneumonia: meningitis, otitis media, sinusitis, peri-
2003;27(8):1139 [PMID: 12883247]. carditis, epiglottitis, or abscesses.
532 / CHAPTER 18

B. LABORATORY FINDINGS splenectomy or who have hemoglobin SS or SC disease

Elevated white blood cell counts (> 15,000/µL) fre- or thalassemia, are especially prone to overwhelming
quently accompany bacterial pneumonia. However, a sepsis with these organisms. Distal infection of the
low white blood count (< 5000/µL) can be an ominous bones, joints, or other organs (eg, liver abscess) may
finding in this disease. occur in certain hosts with specific organisms.

C. IMAGING Treatment
Chest radiographic findings (lateral and frontal views)
define bacterial pneumonia. Patchy infiltrates, atelecta- Antimicrobial therapy should be guided by Gram stain
sis, hilar adenopathy, or pleural effusion may be ob- of sputum, tracheobronchial secretions, or pleural fluid
served. Radiographs should be taken in the lateral decu- if available; radiographic findings; age and known or
bitus position to identify pleural fluid. Complete lobar suspected immunocompetence of the host; and local
consolidation is not a common finding in infants and epidemiologic information. Reasonable coverage for
children. Severity of disease may not correlate with ra- pneumonia in the sick, immunocompromised, or debil-
diographic findings. Clinical resolution precedes resolu- itated patient, pending the results of bronchoalveolar
tion apparent on chest radiograph. lavage or thoracoscopic biopsy, should include cef-
tazidime, clindamycin, vancomycin, erythromycin for
D. SPECIAL EXAMINATIONS Legionella and Mycoplasma, and possibly trimetho-
Invasive diagnostic procedures (transtracheal aspiration, prim–sulfamethoxazole for P jiroveci. Depending on
bronchial brushing or washing, lung puncture, or open the circumstances and the level of illness, empiric anti-
or thoracoscopic lung biopsy) should be undertaken in fungal or antiviral therapy may be considered. In spe-
critically ill patients when other means do not ade- cific circumstances such as aspiration due to neurologic
quately identify the cause (see Culture of Material from impairment or in patients with tracheostomies, clin-
the Respiratory Tract section). damycin is indicated, pending culture and sensitivity
studies, owing to the likely presence of resistant anaer-
obes.
Differential Diagnosis Less severe pneumonias can often be treated with
The differential diagnosis of pneumonia varies with the oral antibiotics based on the patient’s age and suspected
age and immunocompetence of the host. The spectrum organism. Lobar pneumonias presumed to be due to S
of potential pathogens to be considered includes aero- pneumoniae can be treated initially with oral β-lactams,
bic, anaerobic, and acid-fast bacteria as well as Chlamy- including cefuroxime axetil, amoxicillin, or amoxi-
dia trachomatis and C psittaci, Rickettsia quintana (Q cillin–clavulanate. However, persistence or worsening
fever), Pneumocystis jiroveci, Bordetella pertussis, My- of symptoms within 3–5 days suggests the presence of a
coplasma pneumoniae, Legionella pneumophila, and res- resistant organism, and newer quinolones, clindamycin,
piratory viruses. or vancomycin may be required. When possible, ther-
Noninfectious pulmonary disease (including gastric apy can be guided by the antibiotic sensitivity pattern
aspiration, foreign body aspiration, atelectasis, congeni- of the organisms isolated.
tal malformations, congestive heart failure, malignant Whether a child should be hospitalized depends on
growths, tumors such as plasma cell granuloma, chronic his or her age, the severity of illness, the suspected or-
interstitial lung diseases, and pulmonary hemosiderosis) ganism, and the anticipated reliability of compliance at
should be considered in the differential diagnosis of lo- home. Home treatment is adequate for most older chil-
calized or diffuse infiltrates. When effusions are pre- dren. With febrile pneumonias, infants generally—and
sent, additional noninfectious disorders such as colla- toddlers often—require admission. Moderate to severe
gen diseases, neoplasm, and pulmonary infarction respiratory distress, apnea, hypoxemia, poor feeding,
should also be considered. clinical deterioration on treatment, or associated com-
plications (large effusions, empyema, or abscess) indi-
cate the need for immediate hospitalization. Careful
Complications follow-up within 12 hours to 5 days is often indicated
Empyema may occur frequently with staphylococcal, in those not admitted. Cefuroxime or a macrolide, de-
pneumococcal and group A β-hemolytic streptococcal pending on the clinical picture, may be appropriate ini-
disease. Distal sites of infection—meningitis, otitis tial therapy for patients in this category.
media, sinusitis (especially of the ethmoids), and sep- Additional therapeutic considerations include oxy-
ticemia—may be present, particularly with disease due gen, humidification of inspired gases, hydration and
to S pneumoniae or H influenzae. Certain immunocom- electrolyte supplementation, and nutrition. Removal of
promised patients, such as those who have undergone pleural fluid for diagnostic purposes is indicated ini-
 RESPIRATORY TRACT & MEDIASTINUM / 533

tially to guide antimicrobial therapy. Many feel that B) viruses are responsible for more than 75% of cases.
early chest tube drainage of empyema fluid due to S au- Severity of disease, height of fever, radiographic findings,
reus is indicated. Empyema due to group A β-hemolytic and the characteristics of cough or lung sounds do not re-
streptococci, S pneumoniae or H influenzae can also ne- liably differentiate viral from bacterial pneumonias. Fur-
cessitate chest tube drainage. Repeat pleural taps should thermore, such infections may coexist. However, substan-
be considered in the patient who has persistent high tial pleural effusions, pneumatoceles, abscesses, lobar
fever for more than 10 days in association with signifi- consolidation with lobar volume expansion, and “round”
cant pleural effusions. The persistence of organisms in pneumonias are generally inconsistent with viral disease.
this fluid or the persistence of toxicity, malaise,
anorexia, and wasting in the patient suggests the poten- Clinical Findings
tial need for pleural decortication, a procedure that can
be made less morbid by thoracoscopy in skilled hands. A. SYMPTOMS AND SIGNS
Endotracheal intubation or mechanical ventilation An upper respiratory infection frequently precedes the
may be indicated in patients with respiratory failure or onset of lower respiratory disease due to viruses. Al-
in those too debilitated or overwhelmed to handle their though wheezing or stridor may be prominent in viral
secretions. disease, cough, signs of respiratory difficulty (retrac-
tions, grunting, nasal flaring), and physical findings
Prognosis (rales, decreased breath sounds) may not be distinguish-
able from those in bacterial pneumonia.
For the immunocompetent host in whom bacterial
pneumonia is adequately recognized and treated, the B. LABORATORY FINDINGS
survival rate is high. For example, the mortality rate The peripheral white blood cell count can be normal or
from uncomplicated pneumococcal pneumonia is less slightly elevated and is not useful in distinguishing viral
than 1%. If the patient survives the initial illness, per- from bacterial disease. A markedly elevated neutrophil
sistently abnormal pulmonary function following count, however, indicates that viral disease is less likely.
empyema is surprisingly uncommon, even when treat- Rapid viral diagnostic methods—such as fluorescent
ment has been delayed or inappropriate. antibody tests or ELISA for RSV or other visuses—
should be performed on nasopharyngeal secretions to
McCracken GH Jr: Diagnosis and management of pneumonia in confirm this diagnosis in high-risk patients and for epi-
children. Pediatr Infect Dis J 2000;19:924 [PMID: demiology or infection control. Rapid diagnosis of RSV
11001128].
infection does not preclude the possibility of concomi-
McIntosh K: Community-acquired pneumonia in children. N Engl tant infection with other pathogens.
J Med 2002;346:429 [PMID: 11832532].
Owayed AF et al: Underlying causes of recurrent pneumonia in C. IMAGING
children. Arch Pediatr Adolesc Med 2000;154:190 [PMID:
10665608]. Chest radiographs frequently show perihilar streaking,
increased interstitial markings, peribronchial cuffing, or
patchy bronchopneumonia. Lobar consolidation may
VIRAL PNEUMONIA occur, however, as in bacterial pneumonia. Patients
with adenovirus disease may have severe necrotizing
pneumonias, resulting in the development of pneuma-
ESSENTIALS OF DIAGNOSIS toceles. Hyperinflation of the lungs may occur when in-
& TYPICAL FEATURES volvement of the small airways is prominent.
• Upper respiratory infection prodrome (fever,
Differential Diagnosis
coryza, cough, hoarseness).
• Wheezing or rales. The differential diagnosis of viral pneumonia is the
same as for bacterial pneumonia. Patients with promi-
• Myalgia, malaise, headache (older children).
nent wheezing may have asthma, airway obstruction
caused by foreign body aspiration, acute bacterial or
viral tracheitis, or parasitic disease.

General Considerations Complications

Most pneumonias in children are caused by viruses. RSV, Bronchiolitis obliterans or severe chronic respiratory
parainfluenza (1, 2, and 3) viruses, and influenza (A and failure may follow adenovirus pneumonia. Bronchiolitis
534 / CHAPTER 18

or viral pneumonia may contribute to persistent reac- CHLAMYDIAL PNEUMONIA

tive airway disease in some patients. Bronchiectasis,
persistent interstitial lung diseases (fibrosis and desqua-
mative interstitial pneumonitis), and unilateral hyperlu- ESSENTIALS OF DIAGNOSIS
cent lung (Swyer–James syndrome) may follow measles, & TYPICAL FEATURES
adenovirus, and influenzal pneumonias. Viral pneumo-
nia or laryngotracheobronchitis may predispose the pa- • Cough, tachypnea, rales, few wheezes, and no
tient to subsequent bacterial tracheitis or pneumonia as fever.
immediate sequelae. Plasma cell granuloma may de-
• Appropriate age: 2–12 weeks.
velop as a rare sequel to viral or bacterial pneumonia.
• Inclusion conjunctivitis, eosinophilia, and ele-
vated immunoglobulins can be seen.
Treatment
General supportive care for viral pneumonia does not
differ from that for bacterial pneumonia. Patients can
be quite ill and should be hospitalized according to the
level of their illness. Because bacterial disease often can- General Considerations
not be definitively excluded, antibiotics may be indi- Pulmonary disease due to C trachomatis usually evolves
cated. gradually as the infection descends the respiratory tract.
Patients at risk for life-threatening RSV infections Infants may appear quite well despite the presence of
(eg, those with bronchopulmonary dysplasia or other significant pulmonary illness. Infant infections are now
severe pulmonary conditions, congenital heart disease, at epidemic proportions in urban environments world-
or significant immunocompromise) should be hospital- wide. Other sexually transmitted organisms such as
ized and given ribavirin. Rapid viral diagnostic tests Ureaplasma urealyticum may also be widespread and
may be a useful guide for such therapy (see Bronchioli- contribute to lung disease in infants.
tis section regarding prevention). These high-risk pa-
tients should be immunized annually against influenza
A and B viruses. Despite immunization, however, in- Clinical Findings
fluenza can still occur. When available epidemiologic A. SYMPTOMS AND SIGNS
data indicate an active influenza A infection in the
community, rimantadine, amantadine hydrochloride, About 50% of patients with chlamydial pneumonia
or oseltamivir phosphate should be considered early for have active inclusion conjunctivitis or a history of it.
high-risk infants and children who appear to be in- Rhinopharyngitis with nasal discharge or otitis media
fected. Children with suspected viral pneumonia may have occurred or may be currently present. Female
should be placed in respiratory isolation. patients may have vulvovaginitis.
Cough is usually present. It can have a staccato char-
acter and resemble the cough of pertussis. The infant is
Prognosis usually tachypneic. Scattered inspiratory rales are com-
Although most children with viral pneumonia recover monly heard, but wheezes rarely. Significant fever sug-
uneventfully, worsening reactive airway disease, abnor- gests a different or additional diagnosis.
mal pulmonary function or chest radiographs, persis-
B. LABORATORY FINDINGS
tent respiratory insufficiency, and even death may
occur in high-risk patients such as newborns or those Although patients may frequently be hypoxemic, CO2
with underlying lung, cardiac, or immunodeficiency retention is not common. Peripheral blood eosinophilia
disease. Patients with adenovirus infection or those (400 cells/µL) has been observed in about 75% of pa-
concomitantly infected with RSV and second tients. Serum immunoglobulins are usually abnormal.
pathogens such as influenza, adenovirus, CMV, or P IgM is virtually always elevated, IgG is high in many,
jiroveci also have a poorer prognosis. and IgA is less frequently abnormal. C trachomatis can
usually be identified in nasopharyngeal washings using
fluorescent antibody or culture techniques.
Faul JL et al: Influenza pneumonia in a paediatric lung transplant
recipient. Transpl Int 2000;13:79 [PMID: 10743695].
C. IMAGING
Klig JE, Chen L. Lower respiratory infections in children. Curr
Opin Pediatr 2003;15:121 [PMID: 12544283]. Chest radiographs may reveal diffuse interstitial and
Shetty AK et al: Intravenous ribavirin therapy for adenovirus pneu- patchy alveolar infiltrates, peribronchial thickening, or
monia. Pediatr Pulmonol 2000;29:69 [PMID: 10613789]. focal consolidation. A small pleural reaction can be pre-
 RESPIRATORY TRACT & MEDIASTINUM / 535

sent. Despite the usual absence of wheezes, hyperexpan- Clinical Findings

sion is commonly present.
A. SYMPTOMS AND SIGNS
Differential Diagnosis Fever, cough, headache, and malaise are common
symptoms as the illness evolves. Although cough is usu-
Bacterial, viral, and fungal (P jiroveci) pneumonias ally dry at the onset, sputum production may develop
should be considered. Premature infants and those with as the illness progresses. Sore throat, otitis media, otitis
bronchopulmonary dysplasia may also have chlamydial externa, and bullous myringitis may occur. Rales are
pneumonia. frequently present on chest examination; decreased
breath sounds or dullness to percussion over the in-
Treatment volved area may be present.
Erythromycin or sulfisoxazole therapy should be ad- B. LABORATORY FINDINGS
ministered for 14 days. Hospitalization may be required The total and differential white blood cell counts are
for infants with significant respiratory distress, cough- usually normal. The cold hemagglutinin titer can be de-
ing paroxysms, or posttussive apnea. Oxygen therapy termined and may be elevated during the acute presen-
may be required for prolonged periods in some pa- tation. A titer of 1:64 or higher supports the diagnosis.
tients. Acute and convalescent titers for M pneumoniae
demonstrating a fourfold or greater rise in specific anti-
Prognosis bodies confirm the diagnosis.
An increased incidence of obstructive airway disease C. IMAGING
and abnormal pulmonary function tests may occur for Chest radiographs usually demonstrate interstitial or
at least 7–8 years following infection. bronchopneumonic infiltrates, frequently in the middle
or lower lobes. Pleural effusions are extremely uncom-
Hagiwara K et al: An epidemic of a pertussis-like illness caused by mon.
Chlamydia pneumoniae. Pediatr Infect Dis J 1999;18:271
[PMID: 10093951].
Jain S: Perinatally acquired Chlamydia trachomatis associated mor- Complications
bidity in young infants. J Matern Fetal Med 1999;8:130 Extrapulmonary involvement of the blood, CNS, skin,
[PMID: 10338068].
heart, or joints can occur. Direct Coombs-positive au-
Principi N, Esposito S: Emerging role of Mycoplasma pneumoniae
and Chlamydia pneumoniae in paediatric respiratory tract in-
toimmune hemolytic anemia, occasionally a life-threat-
fections. Lancet Infect Dis 2001;1:334 [PMID: 11871806]. ening disorder, is the most common hematologic ab-
normality that can accompany M pneumoniae infection.
Coagulation defects and thrombocytopenia can also
MYCOPLASMAL PNEUMONIA occur. Cerebral infarction, meningoencephalitis, Guil-
lain–Barré syndrome, cranial nerve involvement, and
psychosis all have been described. A wide variety of skin
ESSENTIALS OF DIAGNOSIS rashes, including erythema multiforme and
& TYPICAL FEATURES Stevens–Johnson syndrome, can occur. Myocarditis,
pericarditis, and a rheumatic fever-like illness can also
• Fever. occur.
• Cough.
• Appropriate age: older than 5 years. Treatment
Antibiotic therapy with a macrolide for 7–10 days usu-
ally shortens the course of illness. Ciprofloxacin is a
possible alternative. Supportive measures, including hy-
General Considerations dration, antipyretics, and bed rest, are helpful.
M pneumoniae is a common cause of symptomatic Prognosis
pneumonia in older children. Endemic and epidemic
infection can occur. The incubation period is long In the absence of the less common extrapulmonary
(2–3 weeks), and the onset of symptoms is slow. Al- complications, the outlook for recovery is excellent.
though the lung is the primary infection site, extrapul- The extent to which M pneumoniae can initiate or exac-
monary complications sometimes occur. erbate chronic lung disease is not well understood.
536 / CHAPTER 18

Hammerschlag MR: Mycoplasma pneumoniae infections. Curr should be tuberculin-tested. Spread is mainly respira-
Opin Infect Dis 2001;14:181 [PMID: 11979130]. tory, so isolated pulmonary parenchymal tuberculosis
Kim CK et al: Late abnormal findings on high-resolution com- constitutes more than 95% of presenting cases. The
puted tomography after Mycoplasma pneumonia. Pediatrics primary focus (usually single) and associated nodal in-
2000;105:372 [PMID: 10654958].
volvement may not be seen radiographically. Because
healing—rather than progression—is the usual course
TUBERCULOSIS in the uncompromised host, a positive tuberculin test
may be the only manifestation. However, for patients
born outside the United States, a positive test may indi-
ESSENTIALS OF DIAGNOSIS cate only a previous bacille Calmette–Guérin (BCG)
& TYPICAL FEATURES immunization.
The tuberculous complications listed previously
• Positive tuberculin skin test or anergic host. most often occur during the first year of infection.
• Positive culture for Mycobacterium tuberculosis. Thereafter, infection remains quiescent until adoles-
cence, when reactivation of pulmonary tuberculosis is
common. At any stage, chronic cough, anorexia, weight
loss or failure to gain weight, and fever are useful clini-
cal signs if present. Except in cases with complications
General Considerations or advanced disease, physical findings are few. Most
children with pulmonary tuberculosis are asympto-
There is a resurgence of tuberculosis in all age groups, matic.
including children. The clinical spectrum of tuberculo-
sis includes a positive tuberculin skin test without evi-
dent disease, asymptomatic primary infection, the B. LABORATORY FINDINGS
Ghon complex, bronchial obstruction with secondary A positive tuberculin skin test is defined as 10 mm or
collapse or obstructed airways, segmental lesions, calci- more of induration 48–72 hours after intradermal in-
fied nodules, pleural effusions, progressive primary cav- jection of 5 tuberculin units of purified protein deriva-
itating lesions, contiguous spread into adjacent thoracic tive (PPD). Tine tests should not be used. Appropriate
structures, acute miliary tuberculosis, ARDS, over- control skin tests, such as those for hypersensitivity to
whelming reactivation infection in the immunocom- diphtheria–tetanus, mumps, or Candida albicans,
promised host, occult lymphohematogenous spread, should be applied at the same time PPD is applied. If
and metastatic extrapulmonary involvement at almost the patient fails to respond to PPD and all of the con-
any site. Symptoms of airway obstruction, sometimes trols, the possibility of tuberculosis is not excluded.
with secondary bacterial pneumonia resulting from Anteroposterior and lateral chest radiographs should
hilar adenopathy, are common presenting features in be obtained in all suspected cases. Culture for M tuber-
children. culosis is critical for proving the diagnosis and for defin-
ing drug susceptibility. Early morning gastric lavage fol-
Clinical Findings lowing an overnight fast should be performed on three
occasions in infants and children with suspected active
A. SYMPTOMS AND SIGNS pulmonary tuberculosis before treatment is started,
The most important aspect of the history is contact when the severity of illness allows. Although stains for
with an individual with tuberculosis—often an elderly acid-fast bacilli on this material are of little value, this is
relative, a caregiver, or a person previously residing in a the ideal culture site. Despite the increasing importance
region where tuberculosis is endemic—or a history of of isolating organisms because of multiple drug resis-
travel to or residence in such an area. Homeless and ex- tance, only 40% of children will yield positive cultures.
tremely impoverished children are also at high risk, as Sputum cultures from older children and adoles-
are those in contact with high-risk adults (acquired im- cents are similarly useful. Stains and cultures of
munodeficiency syndrome [AIDS] patients, residents or bronchial secretions are useful if bronchoscopy is per-
employees of correctional institutions or nursing formed as part of the patient’s evaluation. When pleural
homes, drug users, and health care workers). Once ex- effusions are present, pleural biopsy for cultures and
posed, pediatric patients at risk for developing active histopathologic examination for granulomas or organ-
disease include infants and those with malnutrition, isms provide diagnostic information. Meningeal in-
AIDS, diabetes mellitus, or immunosuppression (can- volvement is a possibility in young children, and lum-
cer chemotherapy, corticosteroids). In suspected cases, bar puncture should be considered in their initial
the patient, immediate family, and suspected carriers evaluation.
 RESPIRATORY TRACT & MEDIASTINUM / 537

Differential Diagnosis ance, or advanced complications is guarded. Organisms

resistant to multiple drugs are increasingly common.
Fungal diseases that affect mainly the lungs, such as Resistance emerges either because the physician pre-
histoplasmosis, coccidioidomycosis, cryptococcosis, and scribes an inadequate regimen or because the patient
North American blastomycosis, may resemble tubercu- discontinues medications. When resistance to or intol-
losis and in doubtful cases should be excluded by ap- erance of isoniazid and rifampin prevents their use, cure
propriate serologic studies. Atypical tuberculous organ- rates are 50% or less.
isms may involve the lungs, especially in the
immunocompromised patient. Depending on the pre-
Smith KC: Tuberculosis in children. Curr Probl Pediatr
sentation, diagnoses such as lymphoreticular and other 2001;31:1 [PMID: 11217659].
malignancies, collagen–vascular disorders, or other pul-
Starke JR: Diagnosis of tuberculosis in children. Pediatr Infect Dis
monary infections may be considered. J 2000;19:1095 [PMID: 11099094].
Starke JR: Directly observed therapy for tuberculosis in children.
Complications Pediatr Pulmonol 1999; (Suppl) 18:131 [PMID: 10093122].

In addition to those complications listed in the General

Considerations and Clinical Findings sections, lym- ASPIRATION PNEUMONIA
phadenitis, meningitis, osteomyelitis, arthritis, enteritis, Patients whose anatomic defense mechanisms are im-
peritonitis, and renal, ocular, middle ear, and cutaneous paired are at risk of aspiration pneumonia (Table
disease may occur. The infant born to tuberculous par- 18–2). Acute disease is commonly caused by bacteria
ents is at great risk for developing illness. The possibil- present in the mouth (especially gram-negative anaer-
ity of life-threatening airway compromise must always obes). Chronic aspiration often causes recurrent bouts
be considered in patients with large mediastinal or hilar of acute febrile pneumonia. It may also lead to chronic
lesions. focal infiltrates, atelectasis, illness resembling asthma or
interstitial lung disease, or failure to thrive.
Treatment
Because the risk of hepatitis due to isoniazid is ex- Clinical Findings
tremely low in children, this drug is indicated in those
with a positive tuberculin skin test. This greatly reduces A. SYMPTOMS AND SIGNS
the risk of subsequent active disease and complications Acute onset of fever, cough, respiratory distress, or hy-
with minimal morbidity. Isoniazid plus rifampin treat- poxemia in a patient at risk suggests aspiration pneu-
ment for 6 months, plus pyrazinamide during the first monia. Chest physical findings, such as rales, rhonchi,
2 months, is indicated when the chest radiograph is ab- or decreased breath sounds, may initially be limited to
normal or when extrapulmonary disease is present. the lung region into which aspiration occurred. Al-
Without pyrazinamide, isoniazid plus rifampin must be though any region may be affected, the right side—es-
given for 9 months. In general, the more severe tuber- pecially the right upper lobe in the supine patient—is
culous complications are treated with a larger number commonly affected. In patients with chronic aspiration,
of drugs. Enforced, directly observed therapy (twice
weekly or more often) is indicated when noncompli-
ance is suspected. Recommendations for antituberculo-
sis chemotherapy, based on disease stage, are continu- Table 18–2. Risk factors for
ously being updated. The most current edition of the aspiration pneumonia.
AAP Red Book is a reliable source for these protocols.
Corticosteroids are used to control inflammation in Seizures
selected patients with potentially life-threatening airway Depressed sensorium
compression by lymph nodes, acute pericardial effu- Recurrent gastroesophageal reflux, emesis, or gastrointestinal
sion, massive pleural effusion with mediastinal shift, or, obstruction
perhaps, miliary tuberculosis with respiratory failure. Neuromuscular disorders with suck–swallow dysfunction
Anatomic abnormalities (laryngeal cleft, tracheoesophageal
fistula, vocal cord paralysis)
Prognosis Debilitating illnesses
In patients with an intact immune system, modern an- Occult brainstem lesions
tituberculous therapy offers good potential for recovery. Near-drowning
The outlook for patients with immunodeficiencies, or- Nasogastric, endotracheal, or tracheostomy tubes
ganisms resistant to multiple drugs, poor drug compli- Severe periodontal disease
538 / CHAPTER 18

diffuse wheezing may occur. Generalized rales may also Treatment of recurrent and chronic aspiration pneu-
be present. Such patients may not develop acute febrile monia may include the following: surgical correction of
pneumonias. anatomic abnormalities; improved oral hygiene; im-
proved hydration; and inhaled bronchodilators, chest
B. LABORATORY FINDINGS AND IMAGING physical therapy, and suctioning. In patients with com-
Chest radiographs may reveal lobar consolidation or at- promise of the CNS, exclusive feeding by gastrostomy
electasis and focal or generalized alveolar or interstitial and (in some) tracheostomy may be required to control
infiltrates. In some patients with chronic aspiration, airway secretions. Gastroesophageal reflux, often re-
perihilar infiltrates with or without bilateral air trap- quiring surgical correction, is commonly present in
ping may be seen. such patients.
In severely ill patients with acute febrile illnesses, a
bacteriologic diagnosis should be made. In addition to Prognosis
blood cultures, cultures of tracheobronchial secretions
and bronchoalveolar lavage or lung puncture specimens The outlook is directly related to the disorder causing
may be desirable (see Culture of Material from the Res- aspiration.
piratory Tract section).
In patients with chronic aspiration pneumonitis, Brook I: Anaerobic infections in children. Microbes Infect
2002;4:1271 [PMID: 12467770].
solid documentation of aspiration as the cause of illness
Colombo JL, Hallberg TK: Pulmonary aspiration and lipid-laden
may be elusive. Barium contrast studies may provide macrophages: In search of gold (standards). Pediatr Pulmonol
evidence of suck–swallow dysfunction, laryngeal cleft, 1999;28:79 [PMID: 10423305].
occult tracheoesophageal fistula, or gastroesophageal re- Morton RE, Wheatley R, Minford J: Respiratory tract infection
flux. Overnight or 24-hour esophageal pH probe stud- due to direct and reflux aspiration in children with severe
ies may also help establish the latter. Although radionu- neurodisability. Dev Med Child Neurol 1999; 41:329
clide scans are commonly used, the yield from such [PMID: 10378759].
studies is disappointingly low. Rigid bronchoscopy in
infants or flexible bronchoscopy in older children can PNEUMONIA IN THE
be useful in more definitively excluding tracheoesopha- IMMUNOCOMPROMISED HOST
geal fistula and obtaining bronchoalveolar lavage speci-
mens to search for lipid-laden macrophages, which can Pneumonia in an immunocompromised host may be
suggest chronic aspiration. due to any common bacteria (streptococci, staphylo-
cocci, M pneumoniae) or less common pathogens such
as Toxoplasma gondii, P jiroveci, Aspergillus species,
Differential Diagnosis Mucor, Candida species, Cryptococcus neoformans, gram-
In the acutely ill patient, bacterial and viral pneumonias negative enteric and anaerobic bacteria, Nocardia, Le-
should be considered. In the chronically ill patient, the gionella pneumophila, mycobacteria, and viruses (CMV,
differential diagnosis may include disorders causing re- varicella-zoster, herpes simplex, influenza virus, RSV,
current pneumonia (eg, immunodeficiencies, ciliary adenovirus). Multiple organisms are commonly pre-
dysfunction, foreign body), chronic wheezing, or inter- sent.
stitial lung disorders (see Interstitial Lung Disease sec-
tion), depending on the presentation. Clinical Findings
A. SYMPTOMS AND SIGNS
Complications
Patients often present with subtle signs such as mild
Empyema or lung abscess may result from acute aspira- cough, tachypnea, or low-grade fever that can rapidly
tion pneumonia. Chronic disease may result in progress to high fever, respiratory distress, and hypox-
bronchiectasis. emia. An obvious portal of infection, such as an in-
travascular catheter, may predispose to bacterial or fun-
Treatment gal infection.
Antimicrobial therapy for acute aspiration pneumonia B. LABORATORY FINDINGS AND IMAGING
includes coverage for gram-negative anaerobic organ- Fungal, parasitic, or bacterial infection, especially with
isms. In general, clindamycin is appropriate initial cov- antibiotic-resistant bacteria, should be suspected in the
erage. However, in some hospital-acquired infections, neutropenic child. Cultures of peripheral blood, spu-
additional coverage for multiply resistant P aeruginosa, tum, tracheobronchial secretions, urine, nasopharynx
streptococci, and other organisms may be required. or sinuses, bone marrow, pleural fluid, biopsied lymph
 RESPIRATORY TRACT & MEDIASTINUM / 539

nodes, or skin lesions or cultures through intravascular Complications

catheters should be obtained as soon as infection is sus-
pected. Respiratory failure, shock, multiple organ damage, dis-
Invasive methods are commonly required to make a seminated infection, and death commonly occur in the
diagnosis. Appropriate samples should be obtained infected immunocompromised host.
soon after a patient with pneumonia fails to respond to
initial treatment. The results of these procedures usu- Treatment
ally lead to important changes in empiric preoperative Broad-spectrum intravenous antibiotics are indicated
therapy. Sputum is often unavailable. Bronchoalveolar early in febrile, neutropenic, or immunocompromised
lavage frequently provides the diagnosis of one or more children. Trimethoprim–sulfamethoxazole (for Pneu-
organisms and should be done early in evaluation. The mocystis) and erythromycin (for Legionella) are also in-
combined use of a wash, brushing, and lavage has a dicated early in the treatment of immunocompromised
high yield. In patients with rapidly advancing disease, children before an organism is identified. Further ther-
lung biopsy becomes more urgent. The morbidity and apy should be based on studies of specimens obtained
mortality rates of this procedure can be reduced by a from bronchoalveolar lavage or lung biopsy.
thoracoscopic approach by a skilled operator. Because
of the multiplicity of organisms that may cause disease,
a comprehensive set of studies should be done on lavage Prognosis
and biopsy material. These consist of rapid diagnostic Prognosis is based on the severity of the underlying im-
studies, including fluorescent antibody studies for Le- munocompromise, appropriate early diagnosis and
gionella; rapid culture and antigen detection for viruses; treatment, and the infecting organisms.
Gram, acid-fast, and fungal stains; cytologic examina-
tion for viral inclusions; cultures for viruses, anaerobic Hansen K, Singer DB: Asplenic-hyposplenic overwhelming sepsis:
and aerobic bacteria, fungi, mycobacteria, and Le- Postsplenectomy sepsis revisited. Pediatr Dev Pathol
gionella; and rapid immunofluorescent studies for P 2001;4:105 [PMID: 11178626].
jiroveci. Labenne M et al: Blind protected specimen brush and bronchoalve-
Chest radiographs may be useful. In P jiroveci pneu- olar lavage in ventilated children. Crit Care Med 1999;27:
monia, dyspnea and hypoxemia may be marked despite 2537 [PMID: 10579277].
minimal radiographic abnormalities. Neville K et al: Pneumonia in the immunocompromised pediatric
cancer patient. Semin Respir Infect 2002;17:21 [PMID:
11891516].
Perez Mato S et al: Pulmonary infections in children with HIV in-
Differential Diagnosis fection. Semin Respir Infect 2002;17:33 [PMID: 11891517].
The organisms causing disease vary with the type of im-
munocompromise present. For example, the splenec- HYPERSENSITIVITY PNEUMONIA
tomized patient may be overwhelmed by infection with
S pneumoniae or H influenzae. The infant receiving
adrenocorticotropic hormone therapy may be more ESSENTIALS OF DIAGNOSIS
likely to have P jiroveci infection. The febrile neu- & TYPICAL FEATURES
tropenic child who has been receiving adequate doses of
intravenous broad-spectrum antibiotics may have fun- • History of exposure (eg, birds, organic dusts, or
gal disease. The key to diagnosis is to consider all possi- molds).
bilities of infection. • Interstitial infiltrates on chest radiograph or dif-
Depending on the form of immunocompromise, fuse rales.
perhaps only one half to two thirds of new pulmonary
infiltrates in such patients represent infection. The re- • Recurrent cough, fever, wheezing, or weight loss
mainder are caused by pulmonary toxicity of radiation, can occur.
oxygen, chemotherapy, or other drugs; pulmonary dis-
orders, including hemorrhage, embolism, atelectasis, as-
piration, or ARDS; recurrence or extension of primary
malignant growths or immunologic disorders; transfu- General Considerations
sion reactions, leukostasis, or tumor cell lysis; or inter-
stitial lung disease, such as lymphocytic interstitial Hypersensitivity pneumonitis, or extrinsic allergic alve-
pneumonitis with human immunodeficiency virus olitis, is a T-cell-mediated disease involving the periph-
(HIV) infection. eral airways, interstitium, and alveoli. Both acute and
540 / CHAPTER 18

chronic forms may occur. In children, the most com- Prognosis

mon forms are brought on by exposure to domestic and
occasionally wild birds or bird droppings (eg, pigeons, With appropriate diagnosis and avoidance of offending
parakeets, parrots, doves). Inhalation of almost any or- antigens, the prognosis is excellent. A good prognosis,
ganic dust, however (moldy hay, compost, logs or tree however, is dependent on early diagnosis before pul-
bark, sawdust, or aerosols from humidifiers), can cause monary damage is irreversible.
disease. Methotrexate-induced hypersensitivity has also
been described in a child with juvenile rheumatoid Fan LL: Hypersensitivity pneumonitis in children. Curr Opin Pe-
diatr 2002;14:323 [PMID: 12011673].
arthritis. A high level of suspicion and a thorough his-
tory are required for diagnosis. Grech V et al: Pigeon breeder’s lung in childhood: Varied clinical
picture at presentation. Pediatr Pulmonol 2000;30:
145 [PMID: 10922137].

Clinical Findings
INTERSTITIAL LUNG DISEASE
SYMPTOMS AND SIGNS
Episodic cough and fever can occur with acute expo-
sures. Chronic exposure results in weight loss, fatigue, ESSENTIALS OF DIAGNOSIS
dyspnea, cyanosis, and, ultimately, respiratory failure. & TYPICAL FEATURES

B. LABORATORY FINDINGS • Tachypnea, dyspnea, retractions, or hypoxemia.

Acute exposure may be followed by polymorphonuclear • Cough or rales.
leukocytosis with eosinophilia and evidence of airway • Bilateral pulmonary infiltrates.
obstruction on pulmonary function testing. Chronic
disease results in a restrictive picture on lung function
tests. Arterial blood gases may reveal hypoxemia with a
decreased PaCO2 and normal pH.
The serologic key to diagnosis is the finding of pre- General Considerations
cipitins (precipitating IgG antibodies) to the organic Interstitial disorders in children are commonly caused
dusts that contain avian proteins or fungal or bacterial by infection, immunodeficiency, aspiration, cardiac dis-
antigens. Ideally, to identify avian proteins, the pa- ease, or pulmonary vascular disease. Genetic causes
tient’s sera should be tested with antigens from drop- such as SP-B and SP-C mutations are now also identi-
pings of the suspected species of bird. However, expo- fied. Children are less likely than adults to have primary
sure may invoke precipitins without causing disease. (idiopathic) pulmonary interstitial lung disorders
(eg, desquamative, usual, or lymphocytic interstitial
pneumonitis), hypersensitivity pneumonitis, or colla-
Differential Diagnosis gen–vascular diseases.
Patients with mainly acute symptoms must be differen-
tiated from those with atopic asthma. Patients with Clinical Findings
chronic symptoms must be distinguished from those
with collagen–vascular, immunologic, or primary inter- A. SYMPTOMS AND SIGNS
stitial pulmonary disorders. Children may present with a chronic dry cough or a
history of dyspnea on exertion. The child with more
advanced disease may have increased dyspnea, tachy-
Complications pnea, retractions, cyanosis, clubbing, failure to thrive,
or weight loss. Physical examination may reveal these
Prolonged exposure to offending antigens may result in
findings, and dry (“Velcro”) rales may be present on
pulmonary hypertension due to chronic hypoxemia, cor
chest auscultation, especially at the lung bases.
pulmonale, irreversible restrictive lung disease due to
pulmonary fibrosis, or respiratory failure. B. LABORATORY FINDINGS AND IMAGING
Chest radiographs are normal in up to 10–15% of pa-
Treatment tients. More commonly, diffuse or perihilar bilateral
reticular interstitial infiltrates are present. Nodular and
Complete elimination of exposure to the offending anti- reticulonodular diseases are uncommon in children ex-
gens is required. Corticosteroids may hasten recovery. cept in HIV infection. Bilateral disease is the rule ex-
 RESPIRATORY TRACT & MEDIASTINUM / 541

cept in cases of infection and aspiration-related disor- sidered in addition to the groups of disorders men-
ders, which may be unilateral. tioned earlier.
On pulmonary function testing, interstitial disorders
often show a restrictive pattern of decreased lung vol- Complications
umes, compliance, and diffusing capacity for carbon
monoxide, whereas the FEV1/FVC ratio may be normal Respiratory failure or pulmonary hypertension with cor
or increased. However, exercise-induced hypoxemia is pulmonale may occur.
often the earliest detectable abnormality of lung func-
tion. Blood gas abnormalities include hypoxemia, a low Treatment
PaCO2, and normal pH.
Many chronically ill patients can be investigated in a Therapy for interstitial lung disease due to infection, as-
sequence of (1) serologic, (2) bronchoscopic, and piration, or cardiac disorders should be directed toward
(3) biopsy steps. Although bronchoalveolar lavage may the primary disorder. Most of the primary pulmonary
be useful in identifying patients who have pulmonary interstitial disorders are treated initially with pred-
hemosiderosis (hemosiderin-laden macrophages), aspi- nisone (2 mg/kg/d) for 6 weeks to 6 months depending
ration (lipid-laden macrophages), and infectious disor- on the severity of disease and the response. Many pa-
ders, lung biopsy is the most reliable method for defini- tients require even more protracted therapy with alter-
tive diagnosis. nate-day prednisone. Chloroquine (5–10 mg/kg/d)
During the initial phase, the following diagnostic may be useful in selected disorders such as desquama-
studies may be considered: radiographs, barium swal- tive interstitial pneumonitis. In refractory cases, aza-
low, pulmonary function tests, skin tests (see Tubercu- thioprine and cyclophosphamide may be tried. Pulse
losis section); complete blood count and erythrocyte steroids given intravenously in doses of 10 to 30 mg/kg
sedimentation rate; sweat chloride test for CF; ECG or for 1 to 3 days have shown benefit in case reports of
echocardiogram; serum immunoglobulins and other children with pulmonary fibrosis. Newer antifibrotic
immunologic evaluations; sputum studies (see Pneu- agents such as interferon gamma, being investigated in
monia in the Immunocompromised Host section); and adult patients with interstitial pulmonary fibrosis, have
studies for Epstein–Barr virus, CMV, M pneumoniae, not been tried in children to date. Addition of cytotoxic
Chlamydia, Pneumocystis, and U urealyticum. drugs (azathioprine, cyclophosphamide) has not been
During the second phase, bronchoscopy should be shown to be more beneficial than prednisone alone.
performed to exclude anatomic abnormalities and ob-
tain multiple bronchial biopsies or brushings to exam- Prognosis
ine cilia. At the same procedure, bronchoalveolar lavage
should be done for microbiologic and cytologic testing. The prognosis is guarded in children with interstitial
In some instances, an SP-B protein analysis should also lung disease due to collagen–vascular and primary pul-
be performed. In patients with static or slowly progress- monary interstitial diseases, immunodeficiency diseases,
ing disease, one can then await results of bronchoscopic surfactant protein mutations, and cancer.
studies. In patients with acute, rapidly progressive dis-
ease, this stage should be combined with thoracoscopic Amin RS et al: Surfactant protein deficiency in familial interstitial
lung disease. J Pediatr 2001;139:85 [PMID: 11445799].
biopsy. Special stains and cultures, immunofluores-
cence for immune complexes, and electron microscopy Howenstine MS, Eigen H: Current concepts on interstitial lung
disease in children. Curr Opin Pediatr 1999;11:200 [PMID:
should be ordered. Genomic analysis of tissue or blood 10349096].
for SP-B and SP-C should be sought if clinically indi- Whitsett JA: Genetic basis of familial interstitial lung disease. Am
cated. Although transbronchial biopsy may be useful in J Respir Crit Care Med 2002;165:1201 [PMID: 11991863].
diagnosing a few disorders (eg, sarcoidosis), its overall
usefulness in pediatrics is limited.
EOSINOPHILIC PNEUMONIA

Differential Diagnosis ESSENTIALS OF DIAGNOSIS

Malignant disorders (histiocytosis X, disseminated car- & TYPICAL FEATURES
cinoma), congenital disorders (Gaucher disease, neu-
rofibromatosis, tuberous sclerosis, familial interstitial • Pulmonary infiltrates, often migratory, seen on
lung disease), pulmonary hemosiderosis, pulmonary chest radiograph.
telangiectasia or lymphangiectasia, bronchiolitis obliter- • Persistent cough; wheezes or rales on chest aus-
ans, sarcoidosis, and ciliary dyskinesia should be con- cultation.
542 / CHAPTER 18

• Increased eosinophils in peripheral blood or in In allergic bronchopulmonary aspergillosis and re-

lung biopsy specimens. lated disorders, patients may show central bronchiecta-
sis on chest radiograph (so-called tramlines) or CT
scan. Saccular proximal bronchiectasis of the upper
lobes is pathognomonic. Although the chest radiograph
may be normal, peribronchial haziness, focal or plate-
General Considerations like atelectasis, or patchy to massive consolidation can
A spectrum of diseases should be considered under this occur. Positive immediate skin tests, serum IgG precipi-
heading: (1) allergic bronchopulmonary helminthiosis tating antibodies, or IgE specific for the offending fun-
(ABPH), (2) pulmonary eosinophilia with asthma (al- gus is present.
lergic bronchopulmonary aspergillosis and related
disorders), (3) hypereosinophilic mucoid impaction, Differential Diagnosis
(4) bronchocentric granulomatosis, and (5) collagen–
vascular disorders. The old term, Löffler syndrome These disorders must be differentiated from exacerba-
(transient migratory pulmonary infiltrates and tions of asthma, CF, or other underlying lung disorders
eosinophilia), is no longer used because most patients that cause infiltrates to appear on chest radiographs. Al-
had undiagnosed ABPH, medication reactions lergic bronchopulmonary aspergillosis can occur in pa-
(www.pneumotox. com), or allergic bronchopulmonary tients with CF.
aspergillosis. Many of these disorders occur in children
with personal or family histories of allergies or asthma.
APBH may be related to hypersensitivity to migratory Complications
parasitic nematodes (Ascaris, Strongyloides, Ancylostoma, Delayed recognition and treatment of allergic bron-
Toxocara, Trichuris) and larval forms of filariae chopulmonary aspergillosis may cause progressive lung
(Wuchereria bancrofti). Allergic bronchopulmonary as- damage and bronchiectasis. Lesions of the conducting
pergillosis is related to hypersensitivity to the fungus airways in bronchocentric granulomatosis can extend
Aspergillus. Hypersensitivity to other fungi has also been into adjacent lung parenchyma and pulmonary arteries,
documented. Eosinophilic pneumonias are rare but can resulting in secondary vasculitis.
be associated with drug hypersensitivity, sarcoidosis,
Hodgkin disease or other lymphomas, and bacterial in-
fections, including brucellosis and those caused by M Treatment
tuberculosis and atypical mycobacteria.
Therapy for the specific parasite causing ABPH should
be given, and corticosteroids may be required when ill-
Clinical Findings ness is severe. Treatment of disease due to microfilariae
A. SYMPTOMS AND SIGNS is both diagnostic and therapeutic. Allergic bron-
chopulmonary aspergillosis and related disorders are
Cough, wheezing, and dyspnea are common presenting treated with prolonged courses of oral corticosteroids,
complaints. In ABPH, fever, malaise, sputum produc- bronchodilators, and chest physical therapy. In patients
tion, and, rarely, hemoptysis may be present. In allergic with CF, itraconazole may decrease steroid doses for
bronchopulmonary aspergillosis, patients may present those with allergic bronchopulmonary aspergillosis.
all of these findings and occasionally produce brown Pulmonary vasculitis associated with collagen vascular
mucus plugs. Anorexia, weight loss, night sweats, and disease usually is treated with high-dose steroids or cy-
clubbing can also occur. totoxic agents.
B. LABORATORY FINDINGS AND IMAGING
Elevated absolute peripheral blood eosinophil counts Carroll JL, Sterni LM: Eosinophilic lung disorders and hypersensi-
(3000/µL and often exceeding 50% of leukocytes) are tivity pneumonitis. In Taussig LM, Landau LI (eds): Pedi-
present in APBH and allergic bronchopulmonary atric Respiratory Medicine. Mosby, 1999.
aspergillosis. Serum IgE levels as high as Nepomuceno IB et al: Allergic bronchopulmonary aspergillosis in
cystic fibrosis: Role of atopy and response to itraconazole.
1000–10,000 IU/mL are common. In allergic bron- Chest 1999;115:364 [PMID: 10027433].
chopulmonary aspergillosis, the serum IgE concentra- Oermann CM et al: Pulmonary infiltrates with eosinophilia syn-
tion appears to correlate with activity of the disease. dromes in children. J Pediatr 2000;136:351 [PMID:
Stools should be examined for ova and parasites—often 10700692].
several times—to clarify the diagnosis. Isohemagglu- Wubbel C et al: Chronic eosinophilia pneumonia. Chest 2003;
tinin titers are often markedly elevated in APBH. 123:1763 [PMID: 12740299].
 RESPIRATORY TRACT & MEDIASTINUM / 543

LUNG ABSCESS compromised host with appropriate broad-spectrum an-

tibiotics directed at S aureus, H influenzae, and strepto-
Lung abscesses are most likely to occur in immunocom- cocci. Additional coverage for anaerobic and gram-nega-
promised patients; in those with severe infections else- tive organisms should be provided for others. Prolonged
where (embolic spread); or in those with recurrent aspi- therapy (3 weeks or more) may be required. Attempts to
ration, malnutrition, or blunt chest trauma. Although drain abscesses via bronchoscopy have caused life-threat-
organisms such as S aureus, H influenzae, S pneumoniae, ening airway compromise. Surgical drainage or lobec-
and viridans streptococci more commonly affect the tomy is occasionally required, primarily in immuno-
previously normal host, anaerobic and gram-negative compromised patients. However, such procedures may
organisms as well as Nocardia, Legionella species, and themselves cause life-threatening complications.
fungi (Candida, Aspergillus) should also be considered
in the immunocompromised host.
Prognosis
Clinical Findings Although radiographic resolution may be very slow, res-
olution occurs in most patients without risk factors for
A. SYMPTOMS AND SIGNS lower respiratory tract infections or loss of pulmonary
High fever, malaise, and weight loss are often present. function. In the immunocompromised host, the out-
Symptoms and signs referable to the chest may or may look depends on the underlying disorder.
not be present. In infants, evidence of respiratory dis-
tress can be present. Tan TQ et al: Pediatric lung abscess: Clinical management and
outcome. Pediatr Infect Dis J 1995;14:51 [PMID: 7715991].
B. LABORATORY FINDINGS AND IMAGING
Wali SO et al: Percutaneous drainage of pyogenic lung abscess.
Elevated peripheral white blood cell count with a neu- Scand J Infect Dis 2002;34:673 [PMID: 12374359].
trophil predominance or an elevated erythrocyte sedi-
mentation rate may be present. Blood cultures are
rarely positive except in the overwhelmed host. PULMONARY TUMORS
Chest radiographs usually reveal single or multiple Primary tumors of the airway and parenchyma of the
thick-walled lung cavities. Air–fluid levels can be pre- lung are unusual in pediatrics. Most intrathoracic tu-
sent. Local compressive atelectasis, pleural thickening, mors occur in or close to the mediastinum (see Medi-
or adenopathy may also occur. Chest CT scan may pro- astinal Masses section). Other pulmonary tumors may
vide better localization and understanding of the le- be classified as benign, malignant, or metastatic. Benign
sions. pulmonary tumors include plasma cell granulomas,
In patients producing sputum, stains and cultures hamartomas, adenomas, papillomas, angiomas, leiomy-
may provide the diagnosis. Direct percutaneous aspira- omas, lipomas, and neurogenic tumors. The most com-
tion of material for stains and cultures guided by fluo- mon malignant tumor in children, a bronchogenic car-
roscopy or ultrasonography should be considered in the cinoma, is also very rare. Other malignant tumors
severely compromised or ill. include fibrosarcomas and leiomyosarcomas. Metastatic
tumors in childhood include Wilms tumor; hepatoblas-
Differential Diagnosis toma; and osteogenic, chondrosarcoma, Ewing, reticu-
lum cell, and soft tissue sarcomas. Lung tumors in chil-
Loculated pyopneumothorax, an Echinococcus cyst, neo- dren are more often metastatic than primary.
plasms, plasma cell granuloma, and infected congenital
cysts and sequestrations should be considered.
Clinical Findings
Complications A. SYMPTOMS AND SIGNS
Although complications due to abscesses are now rare, Symptoms, when they occur, may include pain, fever,
mediastinal shift, tension pneumothorax, and sponta- cough, wheezing, weight loss, malaise, anemia,
neous rupture can occur. Diagnostic maneuvers such as anorexia, and hemoptysis. On physical examination,
lung puncture may also cause complications (pneu- signs of a pleural effusion, volume loss, or consolidation
mothorax). may be present if the tumor has led to significant air-
way obstruction.
Treatment B. LABORATORY FINDINGS AND IMAGING
Because of the risks of lung puncture, uncomplicated In addition to frontal and lateral chest radiographs, flu-
abscesses are frequently conservatively treated in the un- oroscopy, CT scans, and angiography may be helpful in
544 / CHAPTER 18

defining and delineating the tumor. Sputum cultures lar diseases as systemic lupus erythematosus, rheuma-
and cytology, as well as tuberculin and fungal skin tests toid arthritis, Wegener granulomatosis, polyarteritis no-
plus fungal serology, may be needed to exclude other dosa, Henoch–Schönlein purpura, and Behçet disease).
conditions. Idiopathic pulmonary hemosiderosis refers to the accu-
mulation of hemosiderin in the lung, especially the
Differential Diagnosis alveolar macrophage, as a result of chronic or recurrent
hemorrhage (usually from pulmonary capillaries) that is
The differential diagnosis includes acute, recurrent, or not associated with the previously listed causes. Chil-
persistent viral and bacterial pneumonia, tuberculosis, dren and young adults are mainly affected, with the age
and pulmonary infiltrates due to fungal infections. In at onset ranging from 6 months to 20 years. This group
infants, congenital malformations (pulmonary seques- of disorders includes milk allergy in young infants
tration, cystic adenomatoid malformation) may also (Heiner syndrome).
present as mass lesions. Several cases of pulmonary hemorrhage and pul-
monary hemosiderosis have been reported in infants ex-
Treatment & Prognosis posed to a toxigenic mold, Stachybotrys chartarum, and
other fungi. This association was initially noted in
The appropriate therapy and the response to therapy Cleveland, Ohio. The infants were primarily African
depend on the type and location of the tumor. Benign American, living in older homes, and often the homes
lesions may be cured with surgical resection, but the had recent water damage. Environmental tobacco
prognosis is more guarded with both primary and smoke was also frequently present in the environment.
metastatic malignant lesions. Other forms of hypersensitivity pneumonitis have also
been reported to cause pulmonary bleeding.
Brooks JW, Krummel TM: Tumors of the chest. In Chernick V,
Boat TF (eds): Kendig’s Disorders of the Respiratory Tract in
Children, 6th ed. WB Saunders, 1998. Clinical Findings
A. SYMPTOMS AND SIGNS
Pulmonary hemorrhage has as many symptoms as it has
DISEASES OF THE PULMONARY causes. Large airway hemorrhage presents with hemopt-
ysis and symptoms of the underlying cause, such as in-
CIRCULATION fection, foreign body, or bronchiectasis in CF. Hemop-
PULMONARY HEMORRHAGE tysis from larger airways is often bright red or contains
clots. Idiopathic pulmonary hemosiderosis usually pre-
Pulmonary hemorrhage is caused by a spectrum of dis- sents with nonspecific respiratory symptoms (cough,
orders affecting the large and small airways and alveoli. tachypnea, retractions) with or without hemoptysis,
It can occur as an acute or chronic process. Hemor- poor growth, and fatigue. Some children or young
rhage involving the alveoli is termed diffuse alveolar he- adults may present with massive hemoptysis, marked
morrhage. If pulmonary hemorrhage is subacute or respiratory distress, stridor, or a pneumonia-like syn-
chronic, hemosiderin-laden macrophages are found in drome. Fever, abdominal pain, digital clubbing, and
the sputum and tracheal or gastric aspirate. Many cases chest pain may be reported. Jaundice and he-
are secondary to infection (bacterial, mycobacterial, patosplenomegaly may be present with chronic bleed-
parasitic, viral, or fungal), lung abscess, bronchiectasis ing. Physical examination often reveals decreased breath
(CF or other causes), foreign body, coagulopathy (often sounds, rales, rhonchi, or wheezing.
with overwhelming sepsis), or elevated pulmonary ve-
nous pressure (secondary to congestive heart failure or B. LABORATORY FINDINGS AND IMAGING
anatomic heart lesions). Other causes include lung con- Laboratory studies vary depending on the cause of he-
tusion from trauma, arteriovenous fistula, multiple morrhage. Following long-standing idiopathic pul-
telangiectasia, pulmonary sequestration, agenesis of a monary hemorrhage, iron deficiency anemia and heme-
single pulmonary artery, and esophageal duplication or positive sputum are present. Nonspecific findings may
bronchogenic cyst. Rarer causes are tumors (eg, include lymphocytosis and an elevated erythrocyte sedi-
bronchial adenoma or left atrial myxoma) and pul- mentation rate. Peripheral eosinophilia is present in up
monary infarction secondary to pulmonary embolus. to 25% of patients. Chest radiographs demonstrate a
Diffuse alveolar hemorrhage may be idiopathic or range of findings, from transient perihilar infiltrates to
drug-related or may occur in Goodpasture syndrome, large, fluffy alveolar infiltrates with or without atelecta-
rapidly progressive glomerulonephritis, and systemic sis and mediastinal adenopathy. Pulmonary function
vasculitides (often associated with such collagen–vascu- testing generally reveals restrictive impairment, with
 RESPIRATORY TRACT & MEDIASTINUM / 545

low lung volumes, poor compliance, and an increased tic proliferative glomerulonephritis and circulating
diffusion capacity. Hemosiderin-laden macrophages are antiglomerular basement membrane antibody). We-
found in bronchial or gastric aspirates. The diagnostic gener granulomatosis also has renal involvement (gran-
usefulness of lung biopsy is controversial. ulomatous glomerulitis with necrotizing vasculitis, but
Diffuse alveolar hemorrhage with underlying sys- renal biopsy may be nonspecific) and other systemic
temic disease such as systemic lupus erythematosus, manifestations, especially with upper and lower respira-
Wegener granulomatosis, and occasionally Goodpas- tory tract inflammation. Upper tract involvement in-
ture syndrome can occur with the histologic entity cludes sinusitis, rhinitis, recurrent epistaxis, otitis
known as necrotizing pulmonary capillaritis. On lung media, saddle nose deformity, and subglottic stenosis.
biopsy the alveolar septa are infiltrated with neu- Wegener granulomatosis may occur without renal in-
trophils, and alveolar hemorrhage is acute or chronic. volvement early in the course of the disease. The diag-
The septa can fill with edema or fibrinoid necrosis. Id- nosis can be made by biopsy or an elevated c-ANCA
iopathic pulmonary hemosiderosis may represent a titer.
mild form of capillaritis associated with alveolar hemor-
rhage. It might represent a process that waxes and
wanes, and capillaritis may be focal or mild. Likewise, Treatment
an immune-mediated process may cause idiopathic pul-
monary hemosiderosis, although no serologic marker Therapy should be aimed at direct treatment of the un-
has yet been identified. Although capillaritis has been derlying disease. Supportive measures, including iron
described without evidence of underlying systemic dis- therapy, supplemental oxygen, and blood transfusions,
ease, the search for collagen–vascular disease, vasculitis, may be needed. A diet free of cow’s milk should be
or pulmonary fibrosis should be exhaustive. tried in infants. Systemic corticosteroids have been used
The investigation should include serologic studies for various causes of diffuse alveolar hemorrhage and
such as antineutrophil cytoplasmic antibodies (c- have been particularly successful in those secondary to
ANCA) for Wegener granulomatosis, p- (perinuclear) collagen–vascular disorders and vasculitis. Case reports
or c-ANCA for microscopic polyangiitis, antinuclear have been published on the variable effectiveness of
antibodies for systemic lupus erythematosus, and an- steroids, chloroquine, cyclophosphamide, and azathio-
tibasement membrane antibodies for Goodpasture syn- prine for idiopathic pulmonary hemosiderosis.
drome. α1-Antitrypsin deficiency has been associated
with vasculitides and should be considered.
Suspected cases of cow’s milk-induced pulmonary Prognosis
hemosiderosis can be confirmed by laboratory findings The outcome of idiopathic pulmonary hemosiderosis is
that include high titers of serum precipitins to multiple variable, characterized by a waxing and waning course
constituents of cow’s milk and positive intradermal skin of intermittent intrapulmonary bleeds and the gradual
tests to various cow’s milk proteins. Improvement after development of pulmonary fibrosis over time. The
an empiric trial of a diet free of cow’s milk also supports severity of the underlying renal disease contributes to
the diagnosis. the mortality rates associated with Goodpasture syn-
drome and Wegener granulomatosis. Diffuse alveolar
Differential Diagnosis hemorrhage is considered a lethal pulmonary complica-
tion of systemic lupus erythematosus.
The search for the site of respiratory bleeding, underly-
ing systemic illness, and cardiac or vascular abnormali-
ties will help define the diagnosis. When gross hemopt- Ben-Abraham R et al: Diffuse alveolar hemorrhage following allo-
ysis is present, large airway bronchiectasis, epistaxis, geneic bone marrow transplantation in children. Chest
foreign body, and arteriovenous or pulmonary malfor- 2003;124(2):660 [PMID: 12907557].
mations should be ruled out. MRI or CT-assisted an- Etzel RA et al: Acute pulmonary hemorrhage in infants associated
giography can localize abnormal or systemic arterial with exposure to Stachybotrys atra and other fungi. Arch Pedi-
flow. atr Adolesc Med 1998;152:757 [PMID: 9701134].
Alveolar bleeding with hemoptysis is often frothy Etzel RA: Stachybotrys. Curr Opin Pediatr 2003;15(1):103 Review
[PMID: 12544280].
and pink. The differential diagnosis includes the disor-
Franks TJ, Koss MN: Pulmonary capillaritis. Curr Opin Pulm
ders causing diffuse alveolar hemorrhage listed earlier. Med 2000;6(5):430. Review [PMID: 10958235].
In contrast to idiopathic pulmonary hemosiderosis,
Kiper N et al: Long-term clinical course of patients with idiopathic
Goodpasture syndrome occurs in a slightly older age pulmonary hemosiderosis (1979–1994): Prolonged survival
group (15–35 years), tends to have a more aggressive with low-dose corticosteroid therapy. Pediatr Pulmonol
pulmonary course, and has renal involvement (crescen- 1999;27:180 [PMID: 10213256].
546 / CHAPTER 18

Milman N, Pedersen FM: Idiopathic pulmonary haemosiderosis: pulmonary angiography is the gold standard. Further
Epidemiology, pathologic aspects, and diagnosis. Respir Med evaluation may include Doppler ultrasound studies of
1998;92:902 [PMID: 10070562].
the legs to search for deep venous thrombosis. Coagula-
Specks U: Diffuse alveolar hemorrhage syndromes. Curr Opin tion studies, including assessments of antithrombin III
Rheumatol 2001;13:12 [PMID: 11148710].
and protein C or S deficiencies or defective fibrinolysis,
Update: Pulmonary hemorrhage/hemosiderosis among infants–
Cleveland, Ohio, 1993–1996. MMWR Morb Mortal Wkly
may be indicated. Antiphospholipid antibodies and
Rep. 2000 Mar 10;49(9):180. Erratum in: MMWR Morb other coagulation regulatory proteins (protein C and S,
Mortal Wkly Rep 2000 Mar 17;49(10):213 [PMID: and factor V Leiden) should be checked as abnormali-
11795499]. ties have been demonstrated in 70% of the hematology
referrals in one pediatric institution.
PULMONARY EMBOLISM
Although pulmonary embolism is apparently rare in Treatment
children, the incidence is probably underestimated be- Acute treatment includes supplemental oxygen, sedation,
cause it is often not considered in the differential diag- and anticoagulation. Current recommendations include
nosis of respiratory distress. It occurs most commonly heparin administration to maintain an activated partial
in children with sickle cell anemia as part of the acute thromboplastin time that is one and one-half or more
chest syndrome and with rheumatic fever, infective en- times the control value for the first 24 hours. Urokinase
docarditis, schistosomiasis, bone fracture, dehydration, (2000–4000 U/kg for 36 hours) can be used to help
polycythemia, nephrotic syndrome, atrial fibrillation, dissolve the embolus. Tissue plasminogen activator (t-
and other conditions. A recent report suggests that a PA) is another option via central or peripheral adminis-
majority of children with pulmonary emboli referred tration. These therapies should be followed by warfarin
for hematology evaluation have coagulation regulatory therapy for at least 6 weeks with and INR of greater
protein abnormalities and antiphospholipid antibodies. than 2. In patients with identifiable deep venous
Emboli may be single or multiple, large or small, with thrombosis of the lower extremities and significant pul-
clinical signs and symptoms dependent on the severity monary emboli (with hemodynamic compromise de-
of pulmonary vascular obstruction. spite anticoagulation), inferior vena caval interruption
may be necessary. Long-term prospective data regard-
Clinical Findings ing this latter therapy are lacking, however.
A. SYMPTOMS AND SIGNS
Pulmonary embolism usually presents clinically as an Bounameaux H: Review: ELISA D-dimer is sensitive but not spe-
acute onset of dyspnea and tachypnea. Heart palpita- cific in diagnosing pulmonary embolism in an ambulatory
tions or a sense of impending doom may be reported. clinical setting. ACP J Club 2003;138(1):24 [PMID:
12511136].
Pleuritic chest pain and hemoptysis may be present
Hyers TM: Management of venous thromboembolism: Past, pre-
(not common), along with splinting, cyanosis, and sent, and future. Arch Intern Med 2003;163(7):759 [PMID:
tachycardia. Massive emboli may be present with syn- 12695266].
cope and cardiac arrhythmias. Physical examination is Kearon C: Duration of therapy for acute venous thromboem-
usually normal (except for tachycardia and tachypnea) bolism. Clin Chest Med 2003;24(1):63 [PMID: 12685057].
unless the embolism is associated with an underlying Konstantinides S et al: Heparin plus alteplase compared with he-
disorder. Mild hypoxemia, rales, focal wheezing, or a parin alone in patients with submassive pulmonary em-
pleural friction rub may be found. bolism. N Engl J Med 2002;347(15):1143 [PMID:
12374874].
B. LABORATORY FINDINGS AND IMAGING Remy-Jardin M et al: Pulmonary embolus imaging with multislice
Radiographic findings may be normal, but a peripheral CT. Radiol Clin North Am 2003;41(3):507 [PMID:
12797603].
infiltrate, small pleural effusion, or elevated hemidi-
aphragm can be present. If the emboli are massive, dif-
ferential blood flow and pulmonary artery enlargement
may be appreciated. The ECG is usually normal unless
PULMONARY EDEMA
the pulmonary embolus is massive. Echocardiography is Pulmonary edema is excessive accumulation of extravas-
useful in detecting the presence of large proximal em- cular fluid in the lung. This occurs when fluid is filtered
bolus. A negative D-dimer has a greater than 95% nega- into the lungs faster than it can be removed, leading to
tive predictive value for an embolus. Ventilation–perfu- changes in lung mechanics such as decreased lung com-
sion scans show localized areas of ventilation without pliance, worsening hypoxemia from ventilation–perfu-
perfusion. Spiral CT with contrast may be helpful, but sion mismatch, bronchial compression, and, if ad-
 RESPIRATORY TRACT & MEDIASTINUM / 547

vanced, decreased surfactant function. There are two Redding GJ: Current concepts in adult respiratory distress syn-
basic types of pulmonary edema: increased pressure drome in children. Curr Opin Pediatr 2001;13:261 [PMID:
11389362].
(cardiogenic or hydrostatic) and increased permeability
(noncardiogenic or primary). Hydrostatic pulmonary Van Kooy MA, Gargiulo RF: Postobstructive pulmonary edema.
Am Fam Physician 2000;62:401 [PMID: 10929702].
edema is usually due to excessive increases in pul-
monary venous pressure, which is most commonly due
to congestive heart failure from multiple causes. In con- CONGENITAL PULMONARY
trast, many lung diseases, especially ARDS, are charac- LYMPHANGIECTASIA
terized by the development of pulmonary edema sec-
ondary to changes in permeability due to injury to the Structurally, congenital pulmonary lymphangiectasia
alveolocapillary barrier. In these settings, pulmonary appears as dilated subpleural and interlobular lymphatic
edema occurs independently of the elevations of pul- channels and may present as part of a generalized lym-
monary venous pressure. phangiectasis (in association with obstructive cardiovas-
cular lesions—especially total anomalous pulmonary
venous return) or as an isolated idiopathic lesion.
Clinical Findings Pathologically, the lung appears firm, bulky, and non-
A. SYMPTOMS AND SIGNS compressible, with prominent cystic lymphatics visible
beneath the pleura. On cut section, dilated lymphatics
Cyanosis, tachypnea, tachycardia, and respiratory dis- are present near the hilum, along interlobular septa,
tress are commonly present. Physical findings include around bronchovascular bundles, and beneath the
rales, diminished breath sounds, and (in young infants) pleura. Histologically, dilated lymphatics have a thin
expiratory wheezing. More severe disease is character- endothelial cell lining overlying a delicate network of
ized by progressive respiratory distress with marked re- elastin and collagen.
tractions, dyspnea, and severe hypoxemia.

B. IMAGING Clinical Findings

Chest radiographic findings depend on the cause of the Congenital pulmonary lymphangiectasia is a rare, usu-
edema. Pulmonary vessels are prominent, often with ally fatal disease that generally presents as acute or per-
diffuse interstitial or alveolar infiltrates. Heart size is sistent respiratory distress at birth. Although most pa-
usually normal in permeability edema but enlarged in tients do not survive the newborn period, some survive
hydrostatic edema. longer, and there are isolated case reports of its diagno-
sis later in childhood. It may be associated with features
Treatment of Noonan syndrome, asplenia, total anomalous pul-
monary venous return, septal defects, atrioventricular
Although specific therapy depends on the underlying canal, hypoplastic left heart, aortic arch malformations,
cause, supplemental oxygen therapy and, if needed, and renal malformations. Chylothorax has been re-
ventilator support for respiratory failure are indicated. ported. Chest radiographic findings include a ground-
Diuretics, digoxin, and vasodilators may be indicated glass appearance, prominent interstitial markings sug-
for congestive heart failure along with restriction of salt gesting lymphatic distention, diffuse hyperlucency of
and water. Recommended interventions for permeabil- the pulmonary parenchyma, and hyperinflation with
ity edema are reduction of vascular volume and mainte- depression of the diaphragm.
nance of the lowest central venous or pulmonary arter-
ial wedge pressure possible without sacrificing cardiac
output or causing hypotension (see following discus- Prognosis
sion). β-Adrenergic agonists such as terbutaline have Although the onset of symptoms may be delayed for as
been shown to increase alveolar clearance of lung water, long as the first few months of life, prolonged survival is
perhaps through the action of a sodium–potassium extremely rare. Most deaths occur within weeks after
channel pump. Maintaining normal albumin levels and birth. Rapid diagnosis is essential in order to expedite
a hematocrit of greater than 30 maintains the filtration the option of pulmonary transplant.
of lung liquid toward the capillaries, avoiding low on-
cotic pressure.
Antonetti M et al: Congenital pulmonary lymphangiectasia: A case
report of thoracic duct agenesis. Pediatr Pulmonol
Cotter G et al: Pulmonary edema: New insight on pathogenesis 2001;32:184 [PMID: 11477737].
and treatment. Curr Opin Cardiol 2001;16:159 [PMID: Huber A et al: Congenital pulmonary lymphangiectasia. Pediatr
11357010]. Pulmonol 1991;10:310 [PMID: 1896243].
548 / CHAPTER 18

DISORDERS OF THE CHEST WALL ease, such as Duchenne muscular dystrophy, and can be
a major contributor to respiratory failure.
EVENTRATION OF THE DIAPHRAGM
Eventration of the diaphragm occurs when striated Dobbs MB, Weinstein SL: Infantile and juvenile scoliosis. Orthop
Clin North Am 1999;30:331 [PMID: 10393759].
muscle is replaced with connective tissue and is demon-
Jaskwhich D et al: Congenital scoliosis. Curr Opin Pediatr
strated on radiograph by elevation of part or all of the 2000;12:61 [PMID: 10676776].
diaphragm. This congenital disorder is thought to rep- Kearon C et al: Factors determining pulmonary function in adoles-
resent incomplete formation of the diaphragm in utero. cent idiopathic thoracic scoliosis. Am Rev Respir Dis
When defects are small, there is no paradoxic move- 1993;148:288 [PMID: 8342890].
ment of the diaphragm and little symptomatology.
Small eventrations may be detected on a chest radi-
ograph taken for another reason. When defects are PECTUS EXCAVATUM
large, there may or may not be paradoxic movement of Pectus excavatum is anterior depression of the chest
the diaphragm, depending on the nature of the tissue wall that may be symmetrical or asymmetrical with re-
replacing the normal diaphragm. The degree of respira- spect to the midline. Reports of exercise testing and
tory distress depends in large part on the amount of pulmonary function testing in patients with pectus ex-
paradoxic motion of the diaphragm. When the di- cavatum are controversial as to whether this disorder
aphragm moves upward during inspiration, instability causes physiologic limitations. Therefore, the decision
of the inferior border of the chest wall increases the to repair the deformity may be based on cosmetic or
work of breathing and can lead to respiratory muscle fa- physiologic considerations. Care of patients following
tigue. Treatment for respiratory distress is surgical pli- pectus excavatum repair requires mechanical ventilation
cation, which stabilizes the diaphragm. and careful respiratory monitoring because of the weak
The differential diagnosis of eventration includes chest wall following surgery.
phrenic nerve injury and partial diaphragmatic hernia.
The former can result from birth or other trauma and Borowitz D et al: Pulmonary function and exercise response in pa-
may also be seen following cardiac surgery. In most tients with pectus excavatum after Nuss repair. J Pediatr Surg
cases, only one phrenic nerve is involved. An elevated 2003;38:544 [PMID:12677562].
hemidiaphragm is noted on chest radiograph, and para- Fonkalsrud EW: Current management of pectus excavatum. World
doxic motion of the diaphragm may be seen by fluo- J Surg 2003;27:502 [PMID:12715210].
roscopy or ultrasonography. Patients often cannot be Malek MH et al: Ventilatory and cardiovascular responses to exer-
extubated or have persistent respiratory compromise, cise in patients with pectus excavatum. Chest 2003;124:870
particularly with feeding. If symptoms persist for [PMID: 12970011].
2–4 weeks, the diaphragm is surgically plicated as de-
scribed previously. Function returns to the diaphragm PECTUS CARINATUM
in about 50% of cases of phrenic nerve injury whether
or not plication was performed. Recovery periods of up Pectus carinatum is a bowing out of the sternum, usu-
to 100 days have been reported in these cases. ally apparent at birth. The abnormality may be associ-
ated with systemic diseases such as the mucopolysac-
charidoses. As with pectus excavatum, pulmonary
Clements BS: Congenital malformations of the lungs and airways.
In Taussig LM, Landau LI (eds): Pediatric Respiratory Medi- function tests are not usually abnormal in the absence
cine. Mosby, 1999. of other disorders. The decision to repair this deformity
de Vries TS et al: Surgical treatment of diaphragmatic eventration is based primarily on cosmetic grounds. Postoperative
caused by phrenic nerve injury in the newborn. J Pediatr Surg care similarly requires careful monitoring because of
1998;33:602 [PMID: 9574760]. chest wall instability produced by the repair.

SCOLIOSIS Robicek F: Surgical treatment of pectus carinatum. Chest Surg

Clin North Am 2000;10:357 [PMID: 10803339].
Scoliosis—lateral curvature of the spine—can, if uncor- Williams AM, Crabbe DC: Pectus deformities of the anterior chest
rected, lead to severe restrictive lung disease and death wall. Paediatr Respir Rev 2003;4:237 [PMID: 12880759].
from cor pulmonale. Most cases of idiopathic scoliosis
occur in adolescent girls and are corrected before signif-
icant pulmonary impairment occurs. Congenital scolio-
NEUROMUSCULAR DISORDERS
sis of severe degree or with other major abnormalities Weakness of the respiratory and pharyngeal muscles
carries a more guarded prognosis. Scoliosis may also leads to chronic or recurrent pneumonia secondary to
occur in patients with progressive neuromuscular dis- aspiration and infection, atelectasis, hypoventilation,
 RESPIRATORY TRACT & MEDIASTINUM / 549

and respiratory failure in severe cases. Scoliosis, which increased capillary permeability (eg, parapneumonic ef-
frequently accompanies long-standing neuromuscular fusions). Other pleural effusions include chylothorax
disorders, may further compromise respiratory func- and hemothorax.
tion. Typical physical findings are a weak cough, de- Thoracentesis is helpful in characterizing the fluid
creased air exchange, rales, wheezing, and dullness to and providing definitive diagnosis. Recovered fluid is
percussion. Signs of cor pulmonale (loud pulmonary considered an exudate (as opposed to a transudate) if
component to the second heart sound, hepatomegaly, any of the following are found: a pleural fluid to serum
elevated neck veins) may be evident in advanced cases. protein ratio greater than 0.5, a pleural fluid to serum
Chest radiographs generally show small lung volumes. lactic dehydrogenase (LDH) ratio greater than 0.6, or a
If chronic aspiration is present, increased interstitial in- pleural fluid LDH greater than 200 units/L. Important
filtrates and areas of atelectasis or consolidation may be additional studies on pleural fluid include cell count;
present. Arterial blood gases demonstrate hypoxemia in pH and glucose; Gram, acid-fast, and fungal stains; cul-
the early stages and compensated respiratory acidosis in tures; counterimmunoelectrophoresis for specific or-
the late stages. Typical pulmonary function abnormali- ganisms; and, occasionally, amylase concentration. Cy-
ties include low lung volumes and decreased inspiratory tologic examination of pleural fluid should be
force generated against an occluded airway. Treatment performed to rule out leukemia or other neoplasm.
is supportive and includes vigorous pulmonary toilet,
antibiotics with infection, and oxygen to correct hypox-
emia. Unfortunately, despite aggressive medical ther- Hilliard TN et al: Management of parapneumonic effusion and
empyema. Arch Dis Child 2003;88(10):915 [PMID:
apy, many neuromuscular conditions progress to respi- 14500314].
ratory failure and death. The decision to intubate and
ventilate is a difficult one; it should be made only when
there is real hope that deterioration, though acute, is
potentially reversible or when chronic ventilation is
PARAPNEUMONIC EFFUSION
wanted. Chronic mechanical ventilation using either & EMPYEMA
noninvasive or invasive techniques is being used more Bacterial pneumonia is often accompanied by pleural
frequently in patients with chronic respiratory insuffi- effusion. Some of these effusions harbor infection, and
ciency. others are inflammatory reactions to pneumonia. The
nomenclature in this area is somewhat confusing.
Birnkrant DJ: The assessment and management of the respiratory Some use the term empyema for grossly purulent fluid
complications of pediatric neuromuscular diseases. Clin Pedi- and parapneumonic effusion for nonpurulent fluid. It is
atr 2002;41:301 [PMID: 12086195]. clear, however, that some nonpurulent effusions will
Chatwin M et al: Cough augmentation with mechanical insuffla- also contain organisms and represent either partially
tion/exsufflation in patients with neuromuscular weakness. treated or early empyema. It is probably best to refer to
Eur Respir J 2003;21:502 [PMID: 12662009].
all effusions associated with pneumonia as parapneu-
Phillips MF et al: Changes in spirometry over time as a prognostic
marker in patients with Duchenne muscular dystrophy. Am
monic effusions, some of which are infected and some
J Respir Crit Care Med 2001;164:2191 [PMID: 11751186]. not.
Simonds AK: Nocturnal ventilation in neuromuscular disease— The most common organism associated with
When and how? Monaldi Arch Chest Dis 2002;57:273 empyema is S pneumoniae. Other common organisms
[PMID: 12814040]. include H influenzae and S aureus. Less common causes
are group A streptococci, gram-negative organisms,
anaerobic organisms, and M pneumoniae. Effusions as-
sociated with tuberculosis are almost always sterile and
DISORDERS OF THE PLEURA constitute an inflammatory reaction.
& PLEURAL CAVITY
The visceral pleura covers the outer surface of the lungs, Clinical Findings
and the inner surface of the chest wall is the parietal
pleura. Disease processes can lead to accumulation of A. SYMPTOMS AND SIGNS
air or fluid in the pleural space. Pleural effusions are Patients usually present with typical signs of pneumo-
classified as transudates or exudates. Transudates occur nia, including fever, tachypnea, and cough. They may
when there is imbalance between hydrostatic and on- have chest pain, decreased breath sounds, and dullness
cotic pressure, so that fluid filtration exceeds reabsorp- to percussion on the affected side and may prefer to lie
tion (eg, congestive heart failure). Exudates form as a on the affected side. With large effusions, there may be
result of inflammation of the pleural surface leading to tracheal deviation to the contralateral side.
550 / CHAPTER 18

B. LABORATORY FINDINGS Lewis RA, Feigin RD: Current issues in the diagnosis and manage-
ment of pediatric empyema. Semin Pediatr Infect Dis
The white blood cell count is often elevated, with left 2002;13(4):280. Review [PMID: 12491234].
shift. Blood cultures are sometimes positive. The tuber- Quadri A, Thomson AH: Pleural fluids associated with chest infec-
culin skin test is positive in most cases of tuberculosis. tion. Paediatr Respir Rev 2002;3(4):349 [PMID: 12457606].
Thoracentesis reveals findings consistent with an exu- Rodgers BM: The role of thoracoscopy in pediatric surgical prac-
date. Cells in the pleural fluid are usually neutrophils in tice. Semin Pediatr Surg 2003;12(1):62 [PMID: 12520474].
bacterial disease and lymphocytes in tuberculous effu-
sions. In bacterial disease, pleural fluid pH and glucose HEMOTHORAX
are often low. pH less than 7.2 suggests active bacterial
infection. The pH of the specimen should be deter- Accumulation of blood in the pleural space can be
mined in a blood gas syringe sent to the laboratory on caused by surgical or accidental trauma, coagulation de-
ice. Extra heparin should not be used in the syringe fects, and pleural or pulmonary tumors. With blunt
since it can falsely lower the pH. Although in adults the trauma, hemopneumothorax may be present. Symp-
presence of low pH and glucose necessitates aggressive toms are related to blood loss and compression of un-
and thorough drainage procedures, the prognostic sig- derlying lung parenchyma. There is some risk of sec-
nificance of these findings in children is unknown. ondary infection, resulting in empyema. Drainage of a
Gram stain, cultures, and counterimmunoelectrophore- hemothorax is required when significant compromise
sis are often positive for the offending organism. of pulmonary function is present, as with hemopneu-
mothorax. In uncomplicated cases, observation is indi-
C. IMAGING cated because blood is readily absorbed spontaneously
from the pleural space.
The presence of pleural fluid is suggested by a homoge-
Thoracoscopy with video assist has been used suc-
neous density on chest radiograph that obscures the un-
cessfully in the management of hemothorax. Chest CT
derlying lung. Large effusions may cause a shift of the
scan is helpful to select patients who may require
mediastinum to the contralateral side. Small effusions
surgery, as identification of blood and the volume of
may only blunt the costophrenic angle. Lateral decubi-
blood may be more predictive by this method than by
tus radiographs may help to detect freely movable fluid
chest radiograph.
by demonstrating a layering-out effect. If the fluid is
loculated, no such effect is perceived. Ultrasonography
Bliss D, Silen M: Pediatric thoracic trauma. Crit Care Med
can be extremely valuable in localizing the fluid and de- 2002;30 (11 Suppl):S409 [PMID: 12528782].
tecting loculations, especially when thoracentesis is con-
templated.
CHYLOTHORAX
The accumulation of chyle in the pleural space usually
Treatment & Prognosis results from accidental or surgical trauma to the tho-
After initial thoracentesis and identification of the or- racic duct. In the newborn, chylothorax can be congen-
ganism, appropriate intravenous antibiotics and ade- ital or secondary to birth trauma. This condition also
quate drainage of the fluid remain the mainstay of ther- occurs as a result of superior vena caval obstruction sec-
apy. Although there is a trend toward managing smaller ondary to central venous lines and following Fontan
pneumococcal empyemas without a chest tube, most procedures for tricuspid atresia. Symptoms of chylotho-
larger effusions require chest tube drainage. Often the rax are related to the amount of fluid accumulation and
empyema has been present for more than 7 days, in- the degree of compromise of underlying pulmonary
creasing the chance for loculation of fluid. Aggressive parenchyma. Thoracentesis reveals typical milky fluid
management with drainage of pleural cavity fluid and (unless the patient has been fasting) containing chiefly
release of adhesions is often sought in many institutions T lymphocytes.
as a first line approach after thoracentesis, allowing the Treatment should be conservative because many
chest tube to be placed in the operating room under chylothoraces resolve spontaneously. Oral feedings with
anesthesia. Some evidence suggests that thoracoscopi- medium-chain triglycerides reduce lymphatic flow
cally aided debridement may be beneficial in terms of through the thoracic duct. Drainage of chylous effu-
morbidity and length of hospital stay. Early decortica- sions should be performed only for respiratory compro-
tion using thoracoscopic techniques may reduce mor- mise because the fluid often rapidly reaccumulates. Re-
bidity and the need for prolonged hospitalization. peated or continuous drainage may lead to protein
The prognosis is related to the severity of disease but malnutrition and T-cell depletion, rendering the pa-
is generally excellent, with complete or nearly complete tient relatively immunocompromised. If reaccumula-
recovery expected in most instances. tion of fluid persists, surgical ligation of the thoracic
 RESPIRATORY TRACT & MEDIASTINUM / 551

duct or sclerosis of the pleural space can be attempted, Differential Diagnosis

though the results may be less than satisfactory.
Acute deterioration of a patient on a ventilator can be
caused by tension pneumothorax, obstruction or dis-
Beghetti M et al: Etiology and management of pediatric chylotho-
rax. J Pediatr 2000;136:653 [PMID: 10802499]. lodgment of the endotracheal tube, or ventilator failure.
Romero S: Nontraumatic chylothorax. Curr Opin Pulm Med
Radiographically, pneumothorax must be distinguished
2000;6:287 [PMID: 10912634]. from diaphragmatic hernia, lung cysts, congenital lobar
emphysema, and cystic adenomatoid malformation,
but this task is usually not difficult.
PNEUMOTHORAX & RELATED
AIR LEAK SYNDROMES
Treatment
Pneumothorax can occur spontaneously in newborns
and in older children or, more commonly, as a result of Small or asymptomatic pneumothoraces usually do not
birth trauma, positive-pressure ventilation, underlying require treatment and can be managed with close obser-
obstructive or restrictive lung disease, and rupture of a vation. Larger or symptomatic ones usually require
congenital or acquired lung cyst. Pneumothorax can drainage, although inhalation of 100% oxygen to wash
also occur as an acute complication of tracheostomy. out blood nitrogen can be tried.
Air usually dissects from the alveolar spaces into the in- Needle aspiration should be used to relieve tension
terstitial spaces of the lung. Migration to the visceral acutely, followed by chest tube or pigtail catheter place-
pleura ultimately leads to rupture into the pleural space. ment. Pneumopericardium requires immediate identifi-
Associated conditions include pneumomediastinum, cation and, if clinically symptomatic, needle aspiration
pneumopericardium, pneumoperitoneum, and subcu- to prevent death, followed by pericardial tube place-
taneous emphysema. These conditions are more com- ment.
monly associated with dissection of air into the intersti- In older patients with spontaneous pneumothorax,
tial spaces of the lung with retrograde dissection along recurrences are common; sclerosing and surgical proce-
the bronchovascular bundles toward the hilum. dures are often required.

Clinical Findings Damore DT, Dayan PS: Medical causes of pneumomediastinum in

children. Clin Pediatr 2001;40:87 [PMID: 11261455].
A. SYMPTOMS AND SIGNS Panitch HB et al: Abnormalities of the pleural space. In Taussig
LM, Landau LI (eds): Pediatric Respiratory Medicine. Mosby,
The clinical spectrum can vary from asymptomatic to 1999.
severe respiratory distress. Associated symptoms include
cyanosis, chest pain, and dyspnea. Physical examination
may reveal decreased breath sounds and hyperresonance
to percussion on the affected side with tracheal devia- DISORDERS OF THE CONTROL
tion to the opposite side. When pneumothorax is under
tension, cardiac function may be compromised, result- OF BREATHING
ing in hypotension or narrowing of the pulse pressure. PEDIATRIC SLEEP APNEA
Pneumopericardium is a life-threatening condition that
presents with muffled heart tones and shock. Pneumo- Sleep apnea has become recognized as a major public
mediastinum rarely causes symptoms by itself. health problem in adults, with the risk of excessive day-
time sleepiness, driving accidents, poor work perfor-
B. IMAGING mance, and effects on mental health. Pediatric sleep dis-
Chest radiographs usually demonstrate the presence of orders are less commonly recognized because the
free air in the pleural space. If the pneumothorax is presentation, risks, and outcome all differ from that in
large and under tension, compressive atelectasis of the adults. Sleep apnea is defined as cessation of breathing
underlying lung and shift of the mediastinum to the and can be classified as central (the lack of effort to
opposite side may be demonstrated. Cross-table lateral breathe) or obstructive (the attempt to breathe through
and lateral decubitus radiographs can aid in the diagno- an obstructed airway). Obstructive sleep apnea occurs in
sis of free air. Pneumopericardium is identified by the normal children with an incidence of about 2%, increas-
presence of air completely surrounding the heart, ing in children with craniofacial abnormalities, neu-
whereas in patients with pneumomediastinum, the ropathies, or other medical problems. The incidence
heart and mediastinal structures may be outlined with also increases when children are medicated with hyp-
air but the air does not involve the diaphragmatic car- notics, sedatives, or anticonvulsants. Central apnea,
diac border. often seen in premature infants, may indicate abnormal-
552 / CHAPTER 18

ities of the central control of breathing in the brainstem; Marcus CL: Sleep-disordered breathing in children. Am J Respir
however, with long-term obstructive sleep apnea, central Crit Care Med 2001;164:16 [PMID: 11435234].
components, or so-called mixed apnea, can develop. Schechter MS et al: Technical report: Diagnosis and management
The presentation of sleep apnea in children varies of childhood obstructive sleep apnea syndrome. Pediatrics
2002;109:e69 [PMID: 11927742].
with age. It can present with life-threatening apnea in
Section on Pediatric Pulmonology, Subcommittee on Obstructive
infants, hyperactivity and behavioral abnormalities in Sleep Apnea Syndrome. American Academy of Pediatrics:
the sleep-deprived toddler, or with mood changes and Clinical practice guideline: Diagnosis and management of
sleepiness in the teenager. Unlike chronic snoring childhood obstructive sleep apnea syndrome. Pediatrics
adults who tend to be obese, children with sleep apnea 2002;109:704 [PMID: 11927718].
may present with failure to thrive, and a work-up of
apnea is always indicated in these children. Another APPARENT LIFE-THREATENING EVENTS
complication in childhood obstructive sleep apnea is
the occurrence of partial obstruction, or hypopnea, IN INFANCY
which can cause long episodes of nighttime hypoventi- Apparent life-threatening events (ALTEs) are character-
lation without arousal from sleep. This can also occur ized as being frightening to the observer and commonly
without clues such as snoring or noisy breathing. Sleep include some combination of obstructive or central
apnea should be suspected whenever a child presents apnea, color change (usually cyanosis or pallor), a
with witnessed apnea, labored breathing, frequent marked change in muscle tone (usually extreme limp-
nighttime arousals, failure to thrive, oxygen desatura- ness), choking, or gagging. The observer sometimes
tion, life-threatening events, behavior abnormalities, fears the infant has died. A substantial number of in-
obesity, or craniofacial abnormalities. fants are brought to medical attention following
When sleep apnea is suspected, the polysomnogram ALTEs. The 50% of infants in whom no explanation
is the diagnostic test of choice. This test measures sleep for the episode can be found are said to have apnea of
state with electroencephalographic leads, plus breathing infancy. There is a relationship between apnea of in-
rate, airflow at the nose, heart rate and rhythm, oxygen fancy and sudden infant death syndrome (SIDS), with
saturation, with other data including esophageal pH, a small percentage of patients with apnea of infancy at
end-tidal CO2, body position, muscle activity, and op- risk for sudden death. In addition, only a small percent-
tional additions. The test allows diagnosis of various age of infants succumbing to SIDS have prior episodes
forms of apnea, sleep fragmentation, or other sleep dis- of apnea.
orders of children. The mechanism for ALTEs is unknown, but be-
First-line therapy for obstructive sleep apnea in chil- cause they don’t occur after infancy, immaturity is felt
dren is adenotonsillectomy, which improves the clinical to play a major role. Indeed, classic studies on the ner-
status of most children with normal craniofacial struc- vous system, reflexes, and responses to apnea or hypoxia
ture. Even children with underlying structural abnor- during sleep show profound cardiovascular compromise
malities of the face may benefit, although additional in infants during stimulation of the immature auto-
treatment with continuous positive airway pressure may nomic nervous system; adults would not be affected.
be indicated. Additional therapy is also helpful for chil- The following section describes an approach to the
dren with obstructive apnea and obesity, for whom ade- patient who has undergone an ALTE, taking note of
notonsillectomy may be only partially beneficial. Cen- the very broad differential diagnosis and uncertainties
tral hypoventilation, either primary or secondary to in both evaluation and treatment.
long-standing obstructive apnea, requires treatment
with positive airway pressure and a rated tidal volume.
This can be accomplished with tracheostomy and venti-
Differential Diagnosis
lation, or noninvasively with bilevel positive airway Table 18–3 classifies disorders associated with ALTEs.
pressure using a mask. A careful history is often the most helpful part of the
Because the differential diagnosis of sleepiness is evaluation. It is useful to determine whether the infant
quite varied among children, pediatric sleep disorder has been chronically ill or essentially well. A history of
centers are the referral of choice for testing and initia- several days of poor feeding, temperature instability, or
tion of therapy. Treatment of young or developmen- respiratory or gastrointestinal symptoms suggests an in-
tally delayed children with apnea also presents several fectious process. Reports of “struggling to breathe” or
challenges. “trying to breathe” imply airway obstruction. Associa-
tion of the episodes with feeding implies discoordinated
Carroll JL: Obstructive sleep-disordered breathing in children: swallowing, gastroesophageal reflux, or airway obstruc-
New controversies, new directions. Clin Chest Med tion. Episodes that typically follow crying may be re-
2003;24:261 [PMID:12800783]. lated to breath-holding. Association of episodes with
 RESPIRATORY TRACT & MEDIASTINUM / 553

Table 18–3. Potential causes of apparent an initial assessment of oxygenation and acid–base sta-
life-threatening events. tus, and low PaO2 or elevated PaCO2 (or both) implies
cardiorespiratory disease. A significant base deficit sug-
Infectious Viral: respiratory syncytial virus and gests that the episode was accompanied by hypoxia or
other respiratory viruses circulatory impairment. Oxygen saturation measure-
Bacterial: sepsis, pertussis, chlamydia ments in the hospital assess oxygenation status during
different activities and are more comprehensive than a
Gastrointestinal Gastroesophageal reflux with or with- single blood gas sample.
out obstructive apnea Because apnea has been associated with respiratory
Respiratory Airway abnormality; vascular rings, infections, diagnostic studies for RSV and other viruses,
pulmonary slings, tracheomalacia pertussis, and Chlamydia may help with diagnosis. The
Pneumonia apnea occurring with infection often precedes other
Neurologic Seizure disorder
physical findings. If the episode might have involved
Central nervous system infection: airway obstruction, the airway should be examined ei-
meningitis, encephalitis ther directly, by fiberoptic bronchoscopy, or radio-
Vasovagal response graphically, by CT or barium swallow. Barium swallow
Leigh encephalopathy is a useful tool to rule out the possibility of anatomic
Brain tumor abnormalities such as vascular ring and tracheoesopha-
geal fistula. This study may also demonstrate reflux and
Cardiovascular Congenital malformation aspiration. If reflux is suspected, it should be docu-
Dysrhythmias mented by esophageal pH monitoring coupled with
Cardiomyopathy
respiratory pattern recording. Most infants with reflux
Nonaccidental trauma Battering and apnea can be given medical antireflux treatment.
Drug overdose Infants with reflux and repeated episodes of apnea may
Munchausen-by-proxy syndrome benefit from a surgical antireflux procedure.
No definable cause Apnea of infancy ALTEs occur in the same age group as infants who
die of sudden death (2–4 months is the peak age).
Sleep-disordered breathing has been implicated as a
possible cause of ALTEs and perhaps sudden death.
Polysomnograms are used to determine abnormalities
sleeping may also suggest gastroesophageal reflux, apnea of cardiorespiratory function, sleep state, oxygen satura-
of infancy, or sleep-disordered breathing. Attempts tion, CO2 retention, and seizure activity. This tool can
should be made to determine the duration of the be used in conjunction with pH monitoring to deter-
episode, but this is often difficult. It is helpful to role- mine the contribution of reflux to apnea. Esophageal
play the episode with the family. Details regarding the pressure manometry can be useful to detect subtle
measures taken to resuscitate the infant and the infant’s changes in respiratory effort related to partial obstruc-
recovery from the episode are often useful in determin- tive breathing (hypopnea). Infants may be at more risk
ing severity. of adverse events from sleep-disordered breathing due
The physical examination provides further direction to their immature nervous system.
in pursuing the diagnosis. Fever or hypothermia sug- There are several neurologic causes of ALTEs.
gests infection. An altered state of consciousness implies Apnea as the sole manifestation of a seizure disorder is
a postictal state or drug overdose. Respiratory distress unusual but may occur. In cases of repeated episodes,
implies cardiac or pulmonary lesions. 24-hour electroencephalographic monitoring may be
Most patients are hospitalized for observation in helpful in detecting a seizure disorder. Leigh disease, a
order to reduce stress on the family and allow prompt brainstem disorder characterized pathologically by neu-
completion of the evaluation. Laboratory evaluation in- ronal dropout, may present with apneic episodes.
cludes a complete blood count for evidence of infec- Apneic episodes have been linked to child abuse in
tion. Serum electrolytes are usually obtained. Elevations several ways. Head injury following nonaccidental
in serum bicarbonate suggest chronic hypoventilation, trauma may be first brought to medical attention be-
whereas decreases suggest acute acidosis, perhaps due to cause of apnea. Other signs of abuse are usually imme-
hypoxia during the episode. Chronic acidosis suggests diately apparent in such cases. Drug overdose, either ac-
an inherited metabolic disorder. The chest radiograph cidental or intentional, may also present with apnea.
is examined for infiltrates suggesting acute infection or Several series document that apneic episodes may be
chronic aspiration and for cardiac size as a clue to in- falsely reported by parents seeking attention (ie, Mun-
trinsic cardiac disease. Arterial blood gas studies provide chausen-by-proxy syndrome). Parents may physically
554 / CHAPTER 18

interfere with a child’s respiratory efforts, in which case Farrell PA et al: SIDS, ALTE, apnea, and the use of home moni-
pinch marks on the nares are sometimes found. tors. Pediatr Rev 2002;23:3 [PMID: 11773587].
Poets CF, Southhall DP: Sudden infant death syndrome and ap-
parent life-threatening events. In Taussig LM, Landau LI
(eds): Pediatric Respiratory Medicine. Mosby, 1999.
Treatment
Therapy is directed at the underlying cause if one is
found. After blood cultures are taken, antibiotics SUDDEN INFANT DEATH SYNDROME
should be given to infants who appear toxic. Seizure SIDS is defined as the sudden death of an infant
disorders are treated with anticonvulsants. Vascular younger than age 1 year that remains unexplained after
rings and pulmonary slings must be corrected surgically a thorough case investigation, including performance of
because of severe morbidity and high mortality rates a complete autopsy, examination of the death scene,
when untreated. and review of the clinical history. The postmortem ex-
The approach to care of infants with ALTEs where amination is an important feature of the definition be-
no definable cause can be ascertained is controversial. cause approximately 20% of cases of sudden death can
Home monitoring has been used in the past as treat- be explained by autopsy findings. The incidence of
ment, but the efficacy of monitoring has not been SIDS in the United States has recently declined to less
demonstrated in controlled trials. With over 20 years of than 1:1000 live births. The part of the decline that has
home monitoring, the sudden infant death rate did not occurred since 1994 is likely due to alterations of risk
change due to this intervention. Yet a rationale for the factors (see following discussion).
use of monitors is that infants at risk for subsequent se- Epidemiologic and pathologic data constitute most
vere episodes can be identified. Although monitors can of what is known about SIDS. The number of deaths
detect apnea or bradycardia, they do not predict which peaks between ages 2 and 4 months, and most deaths
children will have future ALTEs. Parents should be occur in infants a few weeks to 6 months of age. Most
taught cardiopulmonary resuscitation prior to dis- deaths occur between midnight and 8 AM, while the in-
charge. They should also be aware of the possibility of fant and often the caregiver are sleeping. In fact, the
frequent false alarms. It must be noted that many par- only unifying features of all SIDS cases are age and
ents cannot handle the stress associated with having a sleep. Previous studies showed a peak in SIDS during
monitor in the home. the respiratory virus season, but the association be-
The decision to monitor these infants involves the comes weaker when the data are controlled for risk fac-
participation of the family. Infants with severe initial tors such as tobacco exposure. SIDS is more common
episodes or repeated severe episodes are now thought to among ethnic and racial minorities and socioeconomi-
be at significant increased risk and should probably be cally disadvantaged populations. There is a 3:2 male
monitored in the home. Episodes in these children are predominance in most series. Other risk factors include
so severe that the parents want to know the infant’s low birth weight, teenage or drug-addicted mothers,
condition at all times. The decision to discontinue maternal smoking, and a family history of SIDS. Most
monitoring is usually based on the infant’s ability to go of these risk factors are associated with a two- to three-
several months without triggering the alarm. fold elevation of incidence but are not specific enough
Oxygen has been used as therapy for ALTEs for sev- to be useful in predicting which infants will die unex-
eral reasons. First, it reduces periodic breathing of in- pectedly. Recent immunization is not a risk factor.
fancy, an immature pattern of breathing that can cause Since 1990, SIDS rates have declined more than
some degree of oxygen desaturation. Second, infants 60% worldwide. Population studies in New Zealand
have small chest capacities with increased chest wall and Europe identified risk factors, which when changed
compliance that reduces lung volume. Oxygen can in- had a major effect on the incidence of SIDS. Since
crease the baseline saturation, reducing the severity of 1994 the AAP’s “Back-to-Sleep” campaign has pro-
desaturation with short apneas. Respiratory stimulants moted education about SIDS risk factors in the United
such as caffeine and aminophylline have been used in States. Modifiable risk factors include sleeping position,
specific cases of central apnea or periodic breathing. bottle feeding, maternal smoking, and infant overheat-
ing; sleeping position and smoke exposure may have the
largest influence. The prone sleep position could con-
Brooks JG: Apnea of prematurity and apparent life-threatening
events. In Taussig LM, Landau LI (eds): Pediatric Respiratory
tribute to SIDS through decreased arousal during sleep
Medicine. Mosby, 1999. or during hypoxia, rebreathing of exhaled gases, or ef-
Davies F, Gupta R: Apparent life threatening events in infants pre- fects on the immature autonomic nervous system. The
senting to an emergency department. Emerg Med side position, often used in hospitals, also shows in-
J 2002;19:11 [PMID: 11777863]. creased risk of SIDS compared with the supine position.
 RESPIRATORY TRACT & MEDIASTINUM / 555

Maternal smoking, especially prenatal maternal smok- sleeping environment and sleep position. Pediatrics
ing, increases the risk of SIDS. Investigations of tobacco 2000;105:650 [PMID: 10699127].
effects on the autonomic nervous system of the develop- Committee on the Fetus and Newborn. American Academy of Pe-
ing fetus, pulmonary growth and function of the new- diatrics: Apnea, sudden infant death syndrome, and home
monitoring. Pediatrics 2003;111:914 [PMID: 12671135].
born, or its combination with viral infection all point to
Hunt CE: Sudden infant death syndrome and other causes of in-
differences in SIDS compared with control subjects. fant mortality: Diagnosis, mechanisms, and risk for recur-
The most consistent pathologic findings are in- rence in siblings. Am J Respir Crit Care Med
trathoracic petechiae and mild inflammation and con- 2001;164:346 [PMID: 11500332].
gestion of the respiratory tract. Subtler pathologic find- Nagler J: Sudden infant death syndrome. Curr Opin Pediatr
ings include brainstem gliosis, extramedullary 2002;14:247 [PMID: 11981299].
hematopoiesis, and increases in periadrenal brown fat. Ramanathan R et al: Cardiorespiratory events recorded on home
These latter findings suggest that infants who succumb monitors: Comparison of healthy infants with those at in-
to SIDS have had intermittent or chronic hypoxia be- creased risk for SIDS. JAMA 2001;285:2199 [PMID:
fore death. 11325321].
The mechanism or mechanisms of death in SIDS Toomey S, Bernstein H: Sudden infant death syndrome. Curr
Opin Pediatr 2001;13:207 [PMID: 11317067].
are unknown. For example, it is unknown whether the
initiating event at the time of death is cessation of
breathing, cardiac arrhythmia, or asystole. Suggested
hypotheses have included upper airway obstruction,
catecholamine excess, brainstem immaturity or injury, MEDIASTINUM
and increased fetal hemoglobin. It has been recognized
that some infants who presented with apneic episodes
subsequently died from SIDS; however, study of these MEDIASTINITIS
infants and prospective studies of large numbers of Acute infection of the mediastinum in children is usu-
newborns have indicated that most infants with apnea ally due to traumatic perforation of the esophagus. The
do not die from SIDS and that most infants with SIDS trauma may be self-induced (foreign body, puncture in-
have no identifiable episodes of apnea (see Apparent jury to the pharynx with a sharp object) or iatrogenic
Life-Threatening Events section). (endoscopy, attempted endotracheal intubation). Vom-
A history of mild symptoms of upper respiratory in- iting can perforate the esophagus and lead to medias-
fection before death is not uncommon, and SIDS vic- tinitis but this is rare. In addition, acute suppurative
tims are sometimes seen by physicians a day or so be- mediastinitis without trauma does occur but is unusual.
fore death. When infants are discovered blue, cold, and
motionless by parents or caregivers, they are most com-
monly taken to the emergency room, where resuscita- Clinical Findings
tion usually fails. Families must then be supported fol-
lowing the death. The National SIDS Resource Center A. SYMPTOMS AND SIGNS
(http://www.sidscenter.org/) provides information about The early symptoms and signs of acute mediastinitis
psychosocial support groups and counseling for families may be vague and include the gradual onset of fever,
of SIDS victims. The postmortem examination is essen- chills, and dysphagia with substernal pain. Dyspnea
tial for the diagnosis of SIDS and may help the family and cough may also be present. Inspiration may be ac-
by excluding other possible causes of death. A death companied by discomfort due to stretching of inflamed
scene investigation is also important in determining the mediastinal structures, leading to a pattern of spas-
cause of sudden unexpected deaths in infancy. modic or halting inspiration. On physical examination,
The health care provider is instrumental in parental evidence of obstruction of venous return may be pre-
education regarding the modifiable risk factors for sent, with substernal pain elicited on palpation of the
SIDS. Education includes promotion of the supine structures of the thorax. In addition, subcutaneous em-
sleeping position, breast-feeding, avoidance of overheat- physema may be appreciated in the thoracic and cervi-
ing, and smoking cessation (even prenatally). Hospitals cal areas.
should set an example by placing infants in the supine
position. With education, the mortality rate, and per-
haps the incidence of ALTEs, may continue to decline. B. LABORATORY FINDINGS AND IMAGING
The neutrophil and band count is usually high in medi-
American Academy of Pediatrics Task Force on Infant Sleep Posi- astinitis. The chest radiograph may show widening of
tion and Sudden Infant Death Syndrome: Changing concepts the upper mediastinum; the lateral view shows anterior
of sudden infant death syndrome: Implications for infant displacement of the trachea and the esophagus. Medi-
556 / CHAPTER 18

astinal emphysema, pleural effusions, and pyopneu- nerve can cause hoarseness due to paralysis of the left
mothorax may also be present. vocal cord. Superior vena caval obstruction can lead to
dilation of neck vessels and other signs and symptoms
Differential Diagnosis of obstruction of venous return from the upper part of
the body (superior mediastinal syndrome).
The differential diagnosis includes bacterial pneumo-
nia, septicemia, and retropharyngeal abscesses. B. LABORATORY FINDINGS AND IMAGING
The mass is initially defined by frontal and lateral chest
Complications radiographs together with thoracic CT scans and per-
haps MRI. A barium swallow may also help define the
Untreated mediastinitis can progress rapidly to death extent of a mass. Other studies that may be required in-
from infection or tracheal obstruction. Mediastinal ab- clude angiography (to define the blood supply to large
scess is a possible complication. tumors), electrocardiography, echocardiography, ultra-
sound of the thorax, fungal and mycobacterial skin
Treatment tests, and urinary catecholamine assays. MRI or myel-
Intravenous antibiotics should be given urgently. If sig- ography may be necessary in children suspected of hav-
nificant tracheal obstruction is present, an airway must ing a neurogenic tumor in the posterior mediastinum.
be provided. Drainage of abscesses in the mediastinum
may also be indicated. Differential Diagnosis
The differential diagnosis of mediastinal masses is de-
Kono T et al: CT findings of descending necrotizing mediastinitis
via the carotid space (“Lincoln Highway”). Pediatr Radiol
termined by their location. Within the superior medi-
2001;31:84 [PMID: 11214691]. astinum, one may find cystic hygromas, vascular or
Sztajnbok J et al: Descending suppurative mediastinitis: Nonsurgi- neurogenic tumors, thymic masses, teratomas, intratho-
cal approach to this unusual complication of retropharyngeal racic thyroid tissue, and esophageal lesions. A mediasti-
abscesses in childhood. Pediatr Emerg Care 1999;15:341 nal abscess may also be found in this region. Within the
[PMID: 10532666]. anterior mediastinum, thymic tissue (thymomas, hyper-
plasia, cysts) and teratomas, vascular tumors, and lym-
MEDIASTINAL MASSES phatic tissue (lymphomas, reactive lymphadenopathy)
give rise to masses. An intrathoracic thyroid and a pleu-
Mediastinal masses may present because of symptoms ropericardial cyst may also be found in this region.
produced by pressure on the esophagus, airways, nerves, Within the middle mediastinum one may again find
or vessels within the mediastinum or may be discovered lymphomas and hypertrophic lymph nodes, granulo-
on a routine chest radiograph. Once the mass is identi- mas, bronchogenic or enterogenous cysts, metastases,
fied, localization to one of four mediastinal compart- and pericardial cysts. Abnormalities of the great vessels
ments aids in the differential diagnosis. The superior and aortic aneurysms may also present as masses in this
mediastinum is the area above the pericardium that is compartment. Within the posterior mediastinum, neu-
bordered inferiorly by an imaginary line from the rogenic tumors, enterogenous cysts, thoracic meningo-
manubrium to the fourth thoracic vertebra. The anteri- celes, or aortic aneurysms may be present.
or mediastinum is bordered by the sternum anteriorly In some series, more than 50% of mediastinal tu-
and the pericardium posteriorly, and the posterior me- mors occur in the posterior mediastinum and are
diastinum is defined by the pericardium and diaphragm mainly neurogenic tumors or enterogenous cysts. Most
anteriorly and the lower eight thoracic vertebrae poster- neurogenic tumors in children younger than age 4 years
iorly. The middle mediastinum is surrounded by these are malignant (neuroblastoma, neuroganglioblastoma),
three compartments. whereas a benign ganglioneuroma is the most common
histologic type in older children. In the middle and an-
Clinical Findings terior mediastinum, tumors of lymphatic origin (lym-
phomas) are the primary concern. Bulky anterior medi-
A. SYMPTOMS AND SIGNS astinal tumors that compress the trachea and the great
Respiratory symptoms, when present, are due to pres- vessels can lead to a superior mediastinal syndrome,
sure on an airway (cough, wheezing) or an infection which presents a diagnostic problem because of anes-
(unresolving pneumonia in one area of lung). Hemopt- thesia hazards. Definitive diagnosis in most instances
ysis can also occur but is an unusual presenting symp- relies on surgery to obtain the mass or a part of the
tom. Dysphagia may occur secondary to compression mass for histologic examination. In cases of lymphoma,
of the esophagus. Pressure on the recurrent laryngeal the scalene nodes may also contain tumor, and a biopsy
 RESPIRATORY TRACT & MEDIASTINUM / 557

should be performed in an attempt to establish a diag- Buckley JA et al: CT evaluation of mediastinal masses in children:
nosis. Spectrum of disease with pathologic correlation. Crit Rev
Diagn Imaging 1998;39:365 [PMID: 9791749].
Esposito G: Diagnosis of mediastinal masses and principles of sur-
Treatment & Prognosis gical tactics and techniques for their treatment. Semin Pediatr
Surg 1999;8:54 [PMID: 10344301].
The appropriate therapy and the response to therapy Williams HJ, Alton HM: Imaging of paediatric mediastinal abnor-
depend on the cause of the mediastinal mass. malities. Paediatr Respir Rev 2003;4:55 [PMID: 12615033].
 Cardiovascular Diseases 19
Anji T. Yetman, MD, Shelley D. Miyamoto, MD, Henry M. Sondheimer, MD

Cardiovascular disease is a significant cause of death angiocardiography, nuclear imaging studies, and
and chronic illness in childhood. In North America cardiac magnetic resonance imaging (MRI)
8 in 1000 infants are born with a congenital heart de-
fect. In addition, acquired heart disease, including
Kawasaki disease, myocarditis, rheumatic heart disease, HISTORY
and others, remains a significant cause of pediatric mor- In obtaining a medical history from the family or the
bidity and mortality. With advances in medical and patient, one must keep in perspective the patient’s age
surgical care, more than 85% of children with congeni- and activity level. Most congenital defects will lead to
tal heart defects will live into adulthood. It is therefore either decreased pulmonary blood flow or increased
important that attention be paid not only to the diag- pulmonary blood flow with pulmonary congestion (see
nosis and treatment of congenital cardiac lesions but Table 19–10). Symptoms will vary according to the al-
also to the prevention of secondary comorbidities, teration in pulmonary blood flow (Table 19–1)
namely, hyperlipidemia and atherosclerosis. Mainte- The presence of other cardiovascular symptoms such
nance pediatric health visits must focus on the diagno- as palpitations and chest pain should also be deter-
sis and prevention of hypercholesterolemia and hyper- mined by history in the older child, paying particular
tension. Counseling regarding the hazards of smoking attention to the timing (rest or activity related), onset
and the benefits of regular exercise should be part of and termination (gradual vs sudden), and precipitating
routine pediatric care. Subspecialty clinics designed to and relieving factors.
address the needs of the young adult with congenital
heart disease will be needed to service this growing pa-
tient population. Previously rare clinical dilemmas, in- PHYSICAL EXAMINATION
cluding the impact of pregnancy on congenital cardiac General
lesions, risks of anticoagulation during pregnancy, and
vocational choices will need to be addressed. The examination should begin with a careful inspection
to note activity (agitation, lethargy), skin perfusion, and
skin color. Heart rate, respiratory rate, blood pressure
(in all four extremities), and oxygen saturation are re-
DIAGNOSTIC EVALUATION quired. Many congenital cardiac defects occur as part of
a genetic syndrome (Table 19–2), and the overall as-
sessment should include examination for dysmorphic
The presence of a heart murmur may suggest the possi- features that may provide clues to the associated cardiac
bility of heart disease. The murmur may be a functional defect.
or innocent one, however. Not all serious cardiovascu-
lar disorders are accompanied by an easily detectable
murmur. 1. Cardiovascular Examination
Inspection & Palpation
Sequence of Evaluation
The conformation of the chest should be noted by ob-
1. History serving the supine patient from the end of the examin-
2. Physical examination ing table. A left precordial bulge indicates long-stand-
3. Electrocardiogram ing cardiomegaly, which may be seen in association
with dilated cardiomyopathy, or right or left heart ob-
4. Chest radiograph structive lesions.
5. Echocardiogram Palpation may reveal increased precordial activity,
6. Other ancillary studies, including cardiopulmonary RV lift, or left-sided heave; a diffuse point of maximal
stress testing, 24-hour Holter or other ambulatory impulse; or a thrill caused by a greater than grade III/VI
ECG monitoring devices, cardiac catheterization, murmur. Thrills are located where the murmur is most
558
Copyright © 2005, 2001, by The McGraw-Hill Companies, Inc. Click here for terms of use.
 CARDIOVASCULAR DISEASES / 559

Table 19–1. Symptoms of increased and upper left sternal border. S2 has two component
decreased pulmonary blood flow. sounds, A2 and then P2 (aortic and pulmonary valve
closure). Splitting of S2 varies with respiration, widen-
Decreased Pulmonary Increased Pulmonary ing with inspiration and narrowing with expiration. It
Blood Flow Blood Flow is best heard at the second left intercostal space at the
sternal border. Abnormal splitting of S2 may provide
Infant/Toddler: clues to the presence of cardiac disease (Table 19–3).
Cyanosis Tachypnea with activity/feeds The third heart sound (S3) is the sound of rapid fill-
Squatting Diaphoresis ing of the LV. It occurs in early diastole, after S2, and is
Loss of consciousness Poor weight gain medium- to low-pitched. When heard in healthy chil-
Older child: dren, the sound diminishes or disappears when the po-
Dizziness Exercise intolerance
sition changes from supine to sitting or standing. It is
Syncope Dyspnea on exertion, Diaphoresis
usually intermittent. A persistent S3 is often heard in
the presence of a dilated LV caused by a cardiomyopa-
thy or large left-to-right shunt.
The fourth heart sound (S4) is associated with atrial
intense and can sometimes be felt at the point of radia- contraction and increased atrial pressure and has a low
tion. For example, a thrill in the suprasternal notch or pitch similar to that of S3. It occurs just prior to S1 and
carotid thrill is associated with aortic stenosis. In pa- is not normally audible. It is heard in the presence of
tients with severe pulmonary hypertension, palpable atrial contraction into a noncompliant ventricle as is
pulmonary closure is frequently noted at the upper left present in hypertrophic or restrictive cardiomyopathy
sternal border. A palpable fourth heart sound may be or a hypertrophied LV from other causes.
seen in association with a hypertrophied, noncompliant Ejection clicks are high-pitched and are usually re-
ventricle as in hypertrophic cardiomyopathy. lated to dilated great vessels or valve abnormalities.
They can be heard throughout ventricular systole and
Auscultation are classified as early, mid, or late. Early ejection clicks
at the mid left sternal border are usually of pulmonary
A. HEART SOUNDS origin. Aortic clicks are typically best heard at the apex.
The first heart sound (S1) is the sound of AV valve clo- In contrast to aortic clicks, pulmonic clicks vary with
sure. It is best heard at the lower left sternal border and respiration, becoming louder during inspiration. A mid
is usually medium-pitched. Although S1 has multiple to late ejection click at the apex is most typically caused
components, usually only one of these (M1) is heard by mitral valve prolapse. Early clicks may also be heard
with a stethoscope. with a closing ventricular septal defect (VSD).
The second heart sound (S2) is the sound of semilu-
nar valve closure. It is best heard along the mid and B. MURMURS
Murmurs are the most common cardiovascular finding
leading to a cardiology referral. Innocent, or functional,
heart murmurs are extremely common. Between 40%
Table 19–2. Cardiac defects in common
and 45% of children have an innocent murmur at some
syndromes. time during childhood.

Commonly Associated
Genetic Syndrome Cardiac Defect Table 19–3. Abnormal splitting of S2.
Down syndrome AVSD
Turner’s syndrome Bicuspid aortic valve, coarctation Causes of wide split S2
Noonan’s syndrome Dysplastic pulmonic valve, HCM RV volume overload: ASD, anomalous pulmonary venous
Williams–Beuren syndrome Supravalval aortic stenosis, PPS return, PI
Marfan’s syndrome MVP, MR, dilated aortic root RV pressure overload: Pulmonary valve stenosis
Fetal alcohol syndrome VSD, ASD Delayed RV conduction: RBBB
Maternal rubella PDA, PPS Causes of narrow split S2
Pulmonary hypertension
AVSD = atrioventricvular septal defect; HCM = hypertrophic car- Single semilunar valve (aortic atresia, pulmonary atresia,
diomyopathy; MVP = mitral valve prolapse; MR = mitral regurgita- truncus arteriosus)
tion; VSD = ventricular septal defect; ASD = atrial septal defect;
PDA = patent ductus arteriosus; PPS = peripheral pulmonary RV = right ventricle; ASD = atrial septal defect; PI = pulmonic in-
stenosis. sufficiency; RBBB = right bundle branch block.
560 / CHAPTER 19

1. Characteristics—All murmurs should be described drome or rubella syndrome), coarctation of the thoracic
based on the following characteristics: aorta, valvular pulmonary stenosis, and atrial septal de-
a. Location and radiation. Where the murmur is fect (ASD).
best heard and where the sound extends. c. Still murmur. This is the most common inno-
b. Relationship to cardiac cycle and duration. Sys- cent murmur of early childhood. It is most typically
tolic ejection (immediately following S1 with a heard from age 2 years until preadolescence. Still’s mur-
crescendo/decrescendo change in intensity), pansystolic mur is loudest midway between the apex and the lower
(occurring throughout most of systole and of constant left sternal border and often is transmitted to the re-
intensity), diastolic, and continuous. The timing of the mainder of the precordium. Still’s murmur is a musical
murmur provides valuable clues as to underlying or vibratory, short, high-pitched, grade I–III early sys-
pathology (Table 19–4). tolic murmur. It is loudest when the patient is in the
supine position; it diminishes or disappears with inspi-
c. Intensity. Classified as grade I, soft and heard ration, when the patient sits or stands, or during the
with difficulty; grade II, soft but easily heard; grade III, Valsalva maneuver. Still’s murmur will be louder in pa-
loud but without a thrill; grade IV, loud and associated tients with fever or tachycardia.
with a precordial thrill; grade V, loud, with thrill, and
audible with the edge of the stethoscope; or grade VI, d. Pulmonary ejection murmur. This is the most
very loud and audible with the stethoscope off the common innocent murmur in older children. It is
chest. heard throughout childhood from age 3 years onward.
It is usually a soft, systolic ejection murmur, grade I–II
d. Quality. Harsh, musical, or rough; high, in intensity and well localized to the upper left sternal
medium, or low in pitch. border. The murmur becomes louder when the patient
e. Variation with position. Audible when the pa- is supine or when cardiac output is increased and soft-
tient is supine, sitting, standing, or squatting. ens with standing or during the Valsalva maneuver.
The pulmonary ejection murmur must be differenti-
2. Functional murmurs—The six most common ated from other murmurs, such as those associated with
functional murmurs of childhood are: pulmonary stenosis, coarctation of the aorta, ASD, and
a. Newborn murmur. Heard in the first few days of peripheral pulmonary artery stenosis.
life, this murmur is at the lower left sternal border, e. Venous hum. This murmur is usually heard after
without significant radiation. It has a soft, short, vibra- age 2 years, is located in the left and right infraclavicu-
tory grade I–II/VI quality that often subsides when lar areas, and is usually louder on the right. It is a con-
mild pressure is applied to the abdomen. It usually dis- tinuous musical hum of grade I–II intensity and it may
appears by age 2–3 weeks. be accentuated in diastole and with inspiration. This
b. Functional murmur of peripheral arterial pul- murmur is best heard with the child sitting. Turning
monary stenosis. This is frequently heard in newborns the child’s neck, placing him or her in a supine posi-
and is caused by the normal mild bending of the tion, and compressing the jugular vein obliterates the
branches of the pulmonary artery. It is heard with equal venous hum. Venous hum is produced by turbulence at
intensity at the upper left sternal border, at the back, the confluence of the subclavian and jugular veins.
and in both axillae. It is a soft, short, high-pitched, f. Innominate or carotid bruit. This murmur is
grade I–II/VI systolic ejection murmur and usually dis- more common in the older child and adolescent. It is
appears by age 4. This murmur must be differentiated heard in the right supraclavicular area. This is a long
from true peripheral pulmonary stenosis (Williams syn- systolic ejection murmur, somewhat harsh and of grade

Table 19–4. Pathologic murmurs.

Systolic Ejection Pansystolic Diastolic Continuous

Semilunar valve stenosis VSD Semilunar valve regurgitation Runoff lesions
(AS/PS/truncal stenosis) AVVR (MR/TR) (AI/PI/truncal insufficiency) (PDA/AVM/aortopulmonary collaterals
ASD AV valve stenosis (MS/TS)
Coarctation
VSD = ventricular septal defect; AS/PS = aortic stenosis/pulmonic stenosis; MR/TR = mitral regurgitation/tricuspid regurgitation; AI/PI =
aortic insufficiency/pulmonic insufficiency; PDA/AVM = patent ductus arteriosus/arteriovenous malformation; ASD = atrial septal defect;
AV = atrioventricular; MS/TS = mitral stenosis/tricuspid stenosis.
 CARDIOVASCULAR DISEASES / 561

II–III intensity. The bruit can be accentuated by light femoral pulse that is absent, or weak, or that is delayed
pressure on the carotid artery and must be differenti- in comparison with the brachial pulse, suggests coarcta-
ated from all types of aortic stenosis. tion of the aorta. An absent or diminished femoral
When functional murmurs are found in a child, the pulse may be the only clue to the presence of this im-
physician should assure the parents that these are nor- portant clinical problem.
mal heart sounds of the developing child and that they
do not represent structural abnormality of the heart. C. ARTERIAL BLOOD PRESSURE
Blood pressures should be obtained in the upper and
2. Extracardiac Examination lower extremities. Systolic pressure in the lower extrem-
ities should be greater than or equal to that in the upper
Arterial Pulse extremities. The cuff must cover the same relative area
of the arm and leg. Measurements should be repeated
A. RATE AND RHYTHM
several times.
Cardiac rate and rhythm can vary greatly during in-
fancy and childhood, so multiple determinations D. VENOUS PRESSURE & PULSE
should be made. This caution is particularly important The level of the distended jugular vein above the
for infants (Table 19–5), whose heart rate varies with suprasternal notch, when the patient is placed at a
activity. In children, the rhythm may be regular, or 45-degree angle to the examination table, is a measure
there may be a phasic variation in the heart rate with of venous pressure. Normally, one may observe the
respiration (sinus arrhythmia), which is normal. transition between collapsed and distended jugular vein
B. QUALITY AND AMPLITUDE OF PULSE approximately 1–2 cm above the notch. Although the
venous pulse may not be helpful when examining in-
The pulses of the upper and lower extremities should fants and young children because of their short neck
be compared. A bounding pulse is characteristic of run- and increased subcutaneous tissue in this region, it may
off lesions, including patent ductus arteriosus (PDA), be a helpful adjunctive tool in the cardiac assessment of
aortic regurgitation, arteriovenous malformation the older child.
(AVM), or any condition with a low diastolic pressure
(fever, anemia, septic shock). These conditions may E. EXTREMITIES
also be associated with palpable palmar pulses, which
1. Cyanosis—Cyanosis is the result of an increased
otherwise are not normally present. Narrow or thready
concentration (4–5 g/dL) of reduced hemoglobin in the
pulses are found in patients with reduced cardiac out-
blood. Bluish skin color is usually, but not always, a
put as seen in cardiomyopathy, myocarditis, pericardial
sign. Anemic patients may not appear blue, and pa-
tamponade, or severe aortic stenosis. A reduction in
tients with polycythemia may appear cyanotic, even
pulse amplitude or blood pressure (> 10 mm Hg) with
though blood oxygen content is normal. Visible
inspiration is referred to as pulsus paradoxus and is a
cyanosis accompanies low cardiac output, hypothermia,
telltale sign of pericardial tamponade. With inspiration,
and systemic venous congestion, even in the presence of
venous return is increased to the right side of the heart.
adequate oxygenation. Cyanosis should be judged only
Because of a fixed pericardial constraint, an increase in
by the color of the mucous membranes (lips and nail
right heart volume must be accompanied by a reduc-
beds). Bluish discoloration around the mouth (acro-
tion in left heart volume and thus a reduction in cardiac
cyanosis) is a feature of skin that has not been exposed
output during the inspiratory phase of respiration. The
to sun, and it does not correlate with cyanosis.
femoral pulse should be palpable and equal in ampli-
tude and simultaneous with the brachial pulse. A 2. Clubbing of fingers and toes—Clubbing implies
the presence of fairly severe cyanotic congenital heart
disease. It usually does not appear until after age 1 year.
The first sign of clubbing is softening of the nail beds,
Table 19–5. Resting heart rates. followed by rounding of the fingernails and then by
thickening and shininess of the terminal phalanx, with
Age Low High loss of creases.
Hypoxemia producing cyanosis is by far the most
< 1 month 80 160 common cause of digital clubbing, but it also occurs in
1–3 months 80 200 patients with infective endocarditis, chronic liver dis-
2–24 months 70 120 ease, inflammatory bowel diseases, chronic pulmonary
2–10 years 60 90 insufficiency (PI), and lung abscess. Digital clubbing
11–18 years 40 90 may be a benign genetic variant.
562 / CHAPTER 19

3. Edema—Edema of dependent areas (lower extremi- inance of ventricles changes from RV dominance in the
ties in the older child and the face and sacrum in the newborn to LV dominance in the older infant, child,
younger child) is characteristic of elevated right heart and adult. The normal ECG of the 1-week-old infant
pressures, which may be seen with tricuspid valve would be highly abnormal for a 1-year-old child, and
pathology, or RV dysfunction from a variety of causes the ECG of a 5-year-old child is abnormal for an adult.
(right heart failure).
F. ABDOMEN Electrocardiographic Interpretation
Hepatomegaly is the cardinal sign of right heart failure Figure 19–1 defines the events recorded by the ECG.
in the infant and child. Presystolic pulsation of the liver A. RATE
may occur with right atrial hypertension and systolic
pulsation with tricuspid insufficiency. Apparent hepa- The paper speed at which ECGs are normally obtained
tomegaly may also be seen in the child with pulmonary is 25 mm/s. Each small square is 1 mm, and each large
edema from lesions causing left-to-right shunting or left square, 5 mm. Therefore, five large squares represent
heart failure. Pulmonary congestion and associated 1 second, one large square 0.2 second, and one small
lymphatic engorgement lead to lung hyperexpansion, square 0.04 second. A common method of estimating
pushing the liver further below the costal margin. the ventricular rate is to count the number of small
Splenomegaly may be present in patients who have had squares between two QRS complexes (see following dis-
long-standing congestive heart failure (CHF), and it is a cussion) and to divide this number into 1500. If QRS
characteristic feature of infective endocarditis. Ascites is complexes appear at a rate of one per 5 small squares,
also a feature of chronic right heart failure. Physical ex- the ventricular rate is 300; if QRS complexes appear
amination may be notable for shifting dullness or a every 12 small squares, the ventricular rate is 125, and
fluid wave on abdominal examination. so on.
B. RHYTHM
Advani N et al: The diagnosis of innocent murmurs in childhood.
Cardiol Young 2000;10(4):340 [PMID: 10950330].
Sinus rhythm should always be present in normal chil-
Murphy DJ: The patient population and requirements for optimal
dren. In contrast to adults, premature atrial and ven-
care: Adult congenital heart disease. Prog Pediatr Cardiol tricular contractions are uncommon during childhood.
2003;17(1):1.
C. AXIS
Williams CL et al: Cardiovascular health in childhood: A statement
for health professionals. Circulation 2002;106(1):143 P wave axis: The P wave is generated from atrial con-
[PMID: 12093785]. traction beginning in the high right atrium at the site of
the sinus node. The impulse proceeds leftward and in-
ELECTROCARDIOGRAPHY feriorally, thus leading to a positive deflection in all left-
sided and inferior leads (II, III and aVF). Conversely,
The electrocardiogram (ECG) is an essential part of the the P wave in patients in normal sinus rhythm should
evaluation of the cardiovascular system. A consistent be negative in lead aVR.
approach to the ECG will allow for interpretation of QRS axis: The net voltage should be positive in
even the most complex and initially confusing ECG leads I and aVF in children with a normal axis. In the
recording. The heart rate should first be determined (Is young child, RV dominance may persist, leading to a
it appropriate for the patient’s age and state of well- negative net deflection in lead I. Several congenital car-
being?), then the rhythm (Is the patient in a normal diac lesions are associated with alterations in the normal
sinus rhythm or other rhythm as evidenced by a P wave QRS axis (Table 19–6)
with a consistent PR interval before every QRS com-
plex?), and then the axis (Are the P and QRS axes nor- D. P WAVE
mal for the patient’s age?). Once this initial assessment In the pediatric patient, the amplitude of the P wave is
of rate, rhythm, and axis is performed, attention can be normally no greater than 2.5 mm or more than
directed toward assessment of chamber enlargement 0.08 second in duration. The P wave is usually best
and finally to assessment of cardiac intervals and ST seen in leads II and V1.
segments.
E. PR INTERVAL
This interval is measured from the beginning of the P
Age-Related Variations wave to the beginning of the QRS complex. It increases
The ECG evolves with age and thus must be inter- with age and with slower rates. The PR interval ranges
preted according to age-related norms. The rate gradu- from a minimum of 0.11 second in infants to a maxi-
ally decreases and intervals increase with age. The dom- mum of 0.18 second in older children with slow rates.
 CARDIOVASCULAR DISEASES / 563

PR segment

ST segment
V.A.T.
10 mm
Voltage (mV)

R
1 mm

T TP segment
P
U
Q S Isoelectric line

PR QRS
interval

QT interval

0.2 sec 0.04 sec

Figure 19–1. Complexes and intervals of the ECG.

The PR interval is commonly prolonged in patients tion may be prolonged as a primary condition or secon-
who have rheumatic heart disease and by digitalis. darily due to drugs or electrolyte imbalances (Table
19–7) The normal QT duration is rate-related and
F. QRS COMPLEX must be corrected using the Bazett formula:
This represents ventricular depolarization, and its am-
plitude and direction of force (axis) reveal the relative QT interval(s)
size of (viable) ventricular mass in hypertrophy, hy- QTC =
poplasia, and infarction. Abnormal ventricular conduc- R − R interval(s)
tion (eg, right bundle branch block [RBBB], anterior
fascicular block) is also revealed. The normal QTc is less than 0.44 second or less
G. QT INTERVAL than 0.46 second in postpubertal females.
This interval is measured from the beginning of the H. ST SEGMENT
QRS complex to the end of the T wave. The QT dura-
This segment, lying between the end of the QRS com-
plex and the beginning of the T wave, is affected by
Table 19–6. QRS axis deviation. drugs, electrolyte imbalances, or myocardial injury.
I. T WAVE
Right Axis Deviation Left Axis Deviation
The T wave represents myocardial repolarization and is
Tetralogy of Fallot Atrioventricular septal defect altered by electrolytes, myocardial hypertrophy, and is-
Dextro transposition of the Pulmonary atresia with intact chemia.
great arteries ventricular septum
Total anomalous pulmon- Tricuspid atresia J. IMPRESSION
ary venous return The ultimate impression of the ECG is derived from a
Atrial septal defect
systematic analysis of the features described earlier as
564 / CHAPTER 19

Table 19–7. Causes of QT prolongation.* Table 19–8. Radiographic changes with cardiac
chamber enlargement.
Cardiac Medications
Antiarrhythmics: IA (quinidine, procainamide, disopyra- Change in Cardiac Silhouette
mide) class III (amiodarone, sotalol) Chamber Enlarged on Anteroposterior Film
Inotropic Agents: dobutamine, dopamine, epinephrine,
isoproterenol Right ventricle Apex of the heart is tipped upward
Noncardiac medications Left ventricle Apex of the heart is tipped downward
Antibiotics/Antivirals: azithromycin, clarithromycin,
levofloxacin, amantadine Left atrium Double shadow behind cardiac sil-
Antipsychotics: risperidol, thioridazine, lithium, houette
haloperidol Increase in subcarinal angle
Other: albuterol, levalbuterol, ondansetron, phenytoin,
pseudoephedrine Right atrium Prominence of right atrial border of
Sedatives: chloral hydrate, methadone the heart
Electrolyte disturbances: hypokalemia, hypomagnesemia,
hypocalcemia
*Partial list only
The pulmonary vasculature should be assessed in
every patient. The presence of increased or decreased
compared with expected normal values for the child’s pulmonary blood flow provides a useful clue to cardiac
age. diagnosis, particularly in the cyanotic infant (Table
19–10)
Al-Khatib SM et al: What clinicians should know about the QT in- The standard posteroanterior and left lateral chest
terval. JAMA 2003;289(16):2120 [PMID: 12709470].
radiographs are used (Figure 19–2).
Benson DW Jr: The normal electrocardiogram. In Emmanouilides
GC et al (eds): Moss and Adams Heart Disease in Infants,
Children, and Adolescents, 5th ed. Williams & Wilkins, 1995. Dextrocardia
Viskin S et al: Long QT syndrome caused by noncardiac drugs.
Prog Cardiovasc Dis 2003;45(5):415 [PMID: 12704598]. Dextrocardia is a radiographic term used when the
heart is on the right side of the chest. When dextrocar-
dia occurs with reversal of position of the other impor-
CHEST RADIOGRAPH tant organs of the chest and abdomen (eg, liver, lungs,
Evaluation of the chest radiograph for cardiac disease and spleen), the condition is called situs inversus totalis,
should focus on: (1) position of the cardiac apex, and the heart is usually completely normal. When dex-
(2) position of the abdominal viscera, (3) cardiac size, trocardia occurs with otherwise normal organs (situs
(4) cardiac configuration, and (5) character of the pul- solitus), the heart usually has severe defects.
monary vasculature.
A segmental approach is used when evaluating car-
diac anatomy, either by chest radiograph or by echocar- Table 19–9. Lesion-specific chest radiographic
diography. The position of the cardiac apex should be findings.
noted as either levocardia (apex points to the left), dex-
trocardia (cardiac apex to the right), or mesocardia (car-
diac apex in the middle). The position of the liver and Chest radiograph
stomach bubble should be noted as either in the normal Diagnosis appearance
position (abdominal situs solitus), in reverse position Dextrotransposition of the great Egg on a string
with stomach bubble on the right (abdominal situs in- arteries
versus), or a variable stomach position with midline Tetralogy of Fallot Boot-shaped heart
liver (abdominal situs ambiguous). The heart appears
relatively large in normal newborns and decreases on Unobstructed total anomalous Snowman
the chest radiograph with age. The heart size should be pulmonary venous drainage
less than 50% of the chest diameter in children older Obstructed total anomalous Small heart with
than age 1 year. The cardiac configuration on chest ra- pulmonary venous drainage congested lungs
diograph may provide useful diagnostic information, as
certain cardiac lesions have a characteristic radiographic Coarctation Figure 3 sign + rib
notching
appearance (Tables 19–8 and 19–9).
 CARDIOVASCULAR DISEASES / 565

Table 19–10. Alterations in pulmonary blood testing is required prior to initial medical or surgical in-
flow in cyanotic cardiac lesions. tervention. Two-dimensional echocardiography with
Doppler ultrasonography (color, pulsed, or continuous-
Increased Pulmonary Decreased Pulmonary wave ultrasound measurements) is used to assess cardiac
Blood Flow Blood Flow output, magnitude of regurgitant and stenotic lesions,
diastolic LV relaxation, and pulmonary artery pressure.
Total anomalous pulmonary Pulmonic stenosis Stress echocardiography allows for quantification of
venous return ventricular systolic and diastolic function and assess-
TA/large ventricular septal Tricuspid atresia/restrictive ment of myocardial wall motion abnormalities in pa-
defect ventricular septal defect tients after exercise or pharmacologic stress with dobut-
Complete transposition of Tetralogy of Fallot amine infusion.
great arteries
Two-dimensional echocardiography should be per-
Truncus arteroisus Pulmonary atresia with intact
ventricular septum
formed with a systematic series of steps to define the in-
Hypoplastic left heart tracardiac anatomy:
syndrome 1. Position of the cardiac apex
2. Position of the abdominal vessels (inferior vena
cava [IVC] and aorta)
Rarely, the abdominal organs and lungs are neither 3. Relationship between the atria and ventricles
in situs solitus nor situs inversus. These states are called
situs ambiguous. The liver is central and anterior in the 4. Relationship between the ventricles and great ves-
upper abdomen, with the stomach pushed posteriorly. sels
Bilateral right-sidedness (asplenia syndrome) or bilat- 5. Evaluation of intracardiac defects
eral left-sidedness (polysplenia syndrome) may occur,
but, in virtually all cases of situs ambiguous, congenital The relationship between the atria and ventricles is
heart disease is present. noted. If the morphologic right atrium empties into a
morphologic right ventricle (RV) and, similarly, the
morphologic left atrium empties into a morphologic
Burrows PE et al: Imaging of the neonate with congenital heart dis-
ease. In Freedom RM (ed): Neonatal Heart Disease. Springer- LV, atrioventricular concordance is present. If the atria
Verlag, 1992. correspond to the wrong ventricle (eg, right atrium
emptying into LV), atrioventricular discordance is pre-
sent. Other possible atrioventricular (AV) relationships
ECHOCARDIOGRAPHY include double-inlet LV (both atria empty into the
Echocardiography is a useful noninvasive method for LV), double-inlet RV, and atresia of a right or left AV
diagnosing congenital heart defects and is used to fur- valve with associated single inlet (eg, tricuspid atresia).
ther define anatomy, function, chamber size, vessel size, Similarly, the relationship between the ventricles and
and valve abnormalities following cardiac examination, great vessels is noted. Normally, the pulmonay artery
chest radiograph, and ECG. In most cases two-dimen- (PA) arises from the RV and the aorta from the LV and
sional echocardiography is sufficient for the accurate di- ventriculoarterial concordance is present. If the rela-
agnosis of congenital cardiac lesions, and no further tionships are reversed (ie, aorta from RV and PA from

Ao Ao
SVC PA
PA
LA APP Figure 19–2. Position of cardiovas-
LA cular structures in principal radiograph
RA views. Ao = aorta, IVC = inferior vena
LV RV RA cava, LA = left atrium, LA APP = left
LV atrial appendage, LV = left ventricle,
RV
PA = pulmonary artery, RA = right
IVC
atrium, RV = right ventricle, SVC = su-
Posteroanterior Left lateral perior vena cava.
566 / CHAPTER 19

LV), then ventriculoarterial discordance is present (as Boxt LM, Rozenshtein A: MR imaging of congenital heart disease.
in complete transposition of the great arteries [TGA]). Magn Reson Imaging Clin North Am 2003;11(1)27 [PMID:
12797509].
Other possible ventriculoarterial relationships include
double-outlet RV, double-outlet LV, and atresia of one
outlet (eg, pulmonary or aortic atresia). If both AV dis- Cardiopulmonary Stress Testing
cordance and ventriculoarterial discordance are present, Most children with heart disease are capable of normal
the patient has what is referred to as congenitally cor- activity, and data on cardiac function after exercise are
rected transposition. essential to preventing the unnecessary restriction of ac-
tivities. The response to exercise is valuable in deter-
Pahl E et al: The role of stress echocardiography in children. mining the timing of, and need for, cardiovascular
Echocardiography 2000;17(5):507 [PMID: 10979027]. surgery as well as a useful objective outcome measure
Snider AR et al: Echocardiography in Congenital Heart Disease. for the evaluation of medical and surgical interventions.
Mosby, 1997.
Bicycle ergometers or treadmills can be used to test
children as young as age 5 years. The addition of a
NUCLEAR CARDIOLOGY metabolic cart enables one to assess whether exercise
impairment is secondary to cardiac limitation, pul-
Nuclear imaging may be used in patients with VSDs monary limitation, deconditioning, or lack of effort.
and other lesions with left-to-right shunting to nonin- Exercise variables include the ECG, blood pressure re-
vasively quantify the degree of shunting and thereby sponse to exercise, oxygen saturation, ventilation, maxi-
avoid cardiac catheterization. mal oxygen consumption, and peak work load attained.
Nuclear imaging may also be useful as an adjunct to Cardiopulmonary stress testing is routine in children
cardiopulmonary exercise testing in assessing both fixed with congenital cardiac lesions to ascertain limitations,
and reversible areas of myocardial ischemia. This test- develop exercise prescriptions, assess the effect of thera-
ing is valuable in evaluating myocardial perfusion in pa- pies, and decide on the need for cardiac transplanta-
tients with Kawasaki disease, repaired anomalous left tion. Stress testing is also employed in children with
coronary artery or other coronary anomalies, myocardi- structurally normal hearts to rule out cardiac or pul-
al bridging in the setting of hypertrophic cardiomyopa- monary pathology in children with chest pain, syncope,
thy or chest pain in association with ECG changes with or shortness of breath on exertion. Significant stress is-
exercise. chemia or dysrhythmias warrant physical restrictions or
appropriate therapy. Children with poor performance
MAGNETIC RESONANCE IMAGING due to suboptimal conditioning benefit from a planned
exercise program.
MRI is a valuable tool in the evaluation and noninva-
sive follow-up of many congenital heart defects. It is
McManus A, Leung M: Maximizing the clinical use of exercise
particularly useful in imaging the vascular structures of gaseous exchange testing in children with repaired cyanotic
the thorax, which are difficult to image by transthoracic congenital heart defects: The development of an appropriate
echocardiogram. The addition of cardiac gated imaging test strategy. Sports Med 2000;29(4)229 [PMID: 10783899].
allows dynamic evaluation of the structure and blood
flow in the heart and great vessels. MRI is invaluable in
the initial assessment and long-term follow-up of coarc-
ARTERIAL BLOOD GASES
tation of the aorta, in following the progression of aor- Quantitating the arterial PO2 or O2 saturation (eg, by
tic dilation in patients with Marfan syndrome, in quan- pulse oximetry) during the administration of 100%
tification of regurgitant lesions such as PI following oxygen is the most useful method of distinguishing
repair of tetralogy of Fallot (ToF), and in quantification cyanosis produced primarily by heart disease or by lung
of ventricular function in patients whose echocardio- disease in sick infants. In cyanotic heart disease, PaO2
graphic images are inadequate. Because it allows the op- increases very little when 100% oxygen is administered
erator to move the heart and great vessels on the com- over the values obtained while breathing room air.
puter screen, three-dimensional MRI is an ideal However, PaO2 usually increases very significantly when
method of noninvasive reconstruction of the entire oxygen is administered to a patient who has lung dis-
heart and useful for both assessing intracardiac anatomy ease. Table 19–11 illustrates the responses seen in pa-
and analyzing great vessel anatomy and relationships. tients with heart or lung disease during the hyperoxic
MRI combined with pharmacologic stress testing test. Routine pulse oximetry has been advocated as an
(dobutamine infusions) may allow for evaluation of car- adjunct to the current newborn screening evaluation as
diac reserve in patients who cannot undergo standard it is a simple, cost-effective means of screening for
exercise testing because of size or disability. major cardiac defects prior to hospital discharge.
 CARDIOVASCULAR DISEASES / 567

Table 19–11. Examples of responses to 10 Cardiac Catheterization Data

minutes of 100% oxygen in lung disease and Figure 19–3 shows oxygen saturation (in percent) and
heart disease. pressure (in mm Hg) values obtained at cardiac
catheterization from the chambers and great arteries of
Lung Disease Heart Disease the heart. These values are within the normal range for
Room 100% Room 100% a child.
Air O2 Air O2 A. OXYGEN CONTENT AND SATURATION;
Color Blue → Pink Blue → Blue PULMONARY (Qp) AND SYSTEMIC (QS) BLOOD FLOW
Oximetry 60% → 99% 60% → 62% (CARDIAC OUTPUT)
PaO2 (mm Hg) 35 → 120 35 → 38 In most laboratories, left-to-right shunting is deter-
mined by changes of blood oxygen content or satura-
tion during sampling through the right side of the
heart. A significant increase in oxygen saturation be-
tween one right chamber and the other indicates the
Koppel RI et al. Effectiveness of pulse oximetry screening for con- presence of a left-to-right shunt at the site of the in-
genital heart disease in asymptomatic newborns. Pediatrics crease. The oxygen saturation of the peripheral arterial
2003;111:451 [PMID: 12612220]. blood should always be determined during cardiac
catheterization. Normal arterial oxygen saturation is
95–97% at sea level and 92–94% at 5280 feet. Subnor-
CARDIAC CATHETERIZATION mal saturations suggest the presence of a right-to-left
& ANGIOCARDIOGRAPHY shunt, underventilation, or pulmonary disease.
Cardiac catheterization precisely defines the anatomic
and physiologic abnormalities in simple and complex
cardiac malformations. Cardiac catheterization, may be
performed for diagnostic purposes when further ana-
tomic or physiologic data are needed prior to a thera-
peutic decision or may be performed for therapeutic
purposes when the cardiac condition can be palliated or
treated in the catheterization laboratory.
100/65
95%
Therapeutic Cardiac Catheterization
—
Therapeutic procedures performed during cardiac 25/10 5
catheterization include coil embolization of a PDA, bal- — 75% 95%
3
loon aortoplasty of aortic coarctation, balloon atrial 75%
septostomy, valvuloplasty of stenotic aortic or pul-
monic valves, and placement of ASD and VSD devices.
Cardiac catheterization is also performed to evaluate 100/0/6
95%
the effects of pharmaceutical therapy. An example of
this use of catheterization is monitoring acute changes
in pulmonary vascular resistance during the administra- 25/0/6
tion of nitric oxide or prostacyclin in a child with pri- 75%
mary pulmonary hypertension. Electrophysiologic eval-
uation and ablation of abnormal electrical pathways in
children can be performed by qualified personnel in the
pediatric catheterization laboratory.
The risks of cardiac catheterization (morbidity and
mortality) must be explained to the patient’s family. Al-
though the risks are very low for elective studies in Figure 19–3. Pressures (in mm Hg) and oxygen satu-
older children (< 0.1%), the risk of major complica- ration (in percent) obtained by cardiac catheterization
tions in distressed infants is about 2%. Interventional in a healthy child. 3 = mean pressure of 3 mm Hg in the
procedures such as balloon valvuloplasties increase these right atrium, 5 = mean pressure of 5 mm Hg in the left
risks further. atrium.
568 / CHAPTER 19

The size of a left-to-right shunt is usually expressed tension that is so severe as to render the patient inoper-
as a ratio of pulmonary to systemic blood flow (Qp/Qs) able.
or as liters per minute as determined by the Fick princi-
ple: Freedom RM et al: Congenital Heart Disease: Textbook of Angiogra-
phy. Futura, 1997.
Cardiac output Oxygen consumption (mL / min) Simpson JM et al: Cardiac catheterization of low birth weight in-
= fants. Am J Cardiol 2001;87:1372 [PMID: 11397356].
(L / min) Arteriovenous difference (mL / L)

B. PRESSURES PERINATAL & NEONATAL

Pressures should be determined in all chambers and CIRCULATION
major vessels entered. Pressures should be recorded as a At birth, two events occur that affect the cardiovascular
catheter is pulled back from a distal chamber or vessel and pulmonary system: (1) the umbilical cord is
into a more proximal chamber. It is not normal for sys- clamped, removing the placenta from the maternal cir-
tolic pressure in the ventricles to exceed systolic pres- culation; and (2) breathing commences. As a result,
sure in the great arteries or mean diastolic pressure in marked changes in the circulation occur. During fetal
the atria to exceed end-diastolic pressure in the ventri- life, the placenta offers low resistance to blood flow. In
cles. If a gradient in pressure exists, an obstruction is contrast, the pulmonary arterioles are markedly con-
present, and the severity of the gradient is one criterion stricted and offer high resistance to the flow of blood
for the necessity of operative repair or catheter interven- into the lungs. Pulmonary vascular resistance is high in
tion. An RV systolic pressure of 100 mm Hg and a pul- the fetus, and pulmonary blood flow accounts for only
monary artery systolic pressure of 20 mm Hg yield a 7–10% of the combined in utero ventricular output. At
gradient of 80 mm Hg. In this case, the patient would birth, pulmonary blood flow dramatically increases 8- to
be classified as having severe pulmonary stenosis requir- 10-fold with a progressive fall in pulmonary vascular re-
ing balloon dilation of the pulmonic valve or surgery if sistance and pressure. Mechanisms responsible for main-
valvuloplasty fails to reduce the gradient to less than tenance of high pulmonary vascular resistance include
20 mm Hg. physical factors (lack of an air–liquid interface or venti-
C. PULMONARY AND SYSTEMIC VASCULAR RESISTANCE lation), relative low oxygen tension, and perhaps vasoac-
tive mediators such as elevated endothelin peptide levels
The vascular resistance is calculated from the following or leukotrienes. Clamping the cord causes a sudden in-
formula and reported in units or in dynes × cm–5/m2: crease in resistance to flow in the systemic circuit. As the
lung becomes the organ of respiration, the oxygen ten-
Pressure sion (PO2) increases in the vicinity of the small pul-
Re sistance = monary arterioles, resulting in a decrease in their con-
Flow
striction and thus a significant decrease in the
pulmonary vascular resistance. Increased oxygen ten-
The pressure drop used to determine pulmonary sion, rhythmic lung distention, and production of nitric
vascular resistance is calculated by subtracting the mean oxide as well as prostacyclin likely play major roles in the
pulmonary artery wedge or left atrial pressure from the fall in pulmonary vascular resistance at birth. The pul-
mean pulmonary artery pressure. This pressure drop is monary vascular resistance shortly after birth falls below
divided by pulmonary blood flow per square meter of that of the systemic circuit, resulting in a change in
body surface area. (Pulmonary blood flow is deter- blood flow across the ductus arteriosus to left to right.
mined by thermodilution or from the Fick principle, as Because of the changes in resistance, most of the RV
noted earlier.) Similarly, systemic vascular resistance is outflow now passes into the lungs rather than through
determined by subtracting the mean central venous the ductus arteriosus into the descending aorta. In fact,
pressure from the mean systemic arterial pressure and functional closure of the ductus arteriosus begins to de-
dividing this pressure drop by systemic blood flow. velop shortly after birth. The ductus arteriosus usually
Normally, the pulmonary vascular resistance ranges remains patent for 3–5 days. During the first hour after
from 1 to 3 units/m2, or from 80 to 240 dynes × birth, a small right-to-left shunting is present (as in the
cm–5/m2. Systemic vascular resistance ranges from 15 to fetus). However, after 1 hour, bidirectional shunting
20 units/m2, or from 1200 to 1600 dynes × cm–5/m2. If occurs, with the left-to-right direction predominating.
pulmonary resistance is greater than 10 units or the In most cases, right-to-left shunting disappears com-
ratio of pulmonary to systemic resistance is greater than pletely by 8 hours. In patients with severe hypoxia (eg,
0.5, all other diagnostic findings should be reviewed in the syndrome of persistent pulmonary hypertension
carefully to confirm the presence of pulmonary hyper- of the newborn), the pulmonary vascular resistance re-
 CARDIOVASCULAR DISEASES / 569

mains elevated, resulting in a continued right-to-left metabolic needs of the body. Almost all infants who de-
shunt. The cause of the functional closure of the ductus velop CHF from congenital heart lesions do so by age
arteriosus is not completely known. Evidence indicates 6 months. Common causes of CHF include VSD,
that the increased PO2 of the arterial blood causes PDA, coarctation of the aorta, AV septal defect, large
spasm of the ductus. Although flow through the ductus arteriovenous malformations (AVM), and chronic atrial
arteriosus usually is gone within 5 days, the vessel does tachyarrhythmias. CHF due to acquired cardiac condi-
not close anatomically for 7–14 days. tions, such as myocarditis, may occur at any age. Pa-
In fetal life, the foramen ovale serves as a one-way tients present with symptoms of pulmonary congestion
valve, permitting shunting of blood from the inferior as noted in Table 19–1.
vena cava through the right atrium into the left atrium.
At birth, because of the changes in the pulmonary and Treatment
systemic vascular resistance and the increase in the
quantity of blood returning from the pulmonary veins The therapy of CHF should be directed toward the un-
to the left atrium, the left atrial pressure rises above that derlying cause as well as the symptoms. Irrespective of
of the right atrium. This functionally closes the flap of the cause, neurohormonal activation occurs early when
the one-way valve, essentially preventing flow of blood ventricular systolic dysfunction is present. Plasma cate-
across the septum. The foramen ovale remains patent in cholamine levels increase and account for the patient’s
10–15% of adults. symptoms. Increased plasma norepinephrine causes
Persistent pulmonary hypertension is a clinical syn- tachycardia and diaphoresis and indirectly, through ac-
drome that occurs in full-term infants. The neonate de- tivation of the renin–angiotensin system, causes periph-
velops tachypnea, cyanosis, and clinical evidence of pul- eral vasoconstriction and salt and water retention. In-
monary hypertension during the first 8 hours after creased metabolic demands cause increased caloric
delivery. These infants have massive right-to-left ductal expenditure and failure to thrive. Inotropic agents, di-
or foramen shunting (or both) for 3–7 days because of uretics, afterload-reducing agents, and β-blockers may
high pulmonary vascular resistance. The clinical course be used, together with supportive measures (oxygen, se-
is one of progressive hypoxia and acidosis, terminating dation, mechanical ventilation, and intravenous nutri-
in early death unless the pulmonary resistance can be tion) in the treatment of the child with CHF.
lowered. Instituting appropriate means to increase alve-
olar pO2—hyperventilation, alkalosis, paralysis, surfac- Inpatient Management
tant administration, high-frequency ventilation, and of Congestive Heart Failure
cardiac pressors—can usually reverse the resistance. In-
haled nitric oxide is a selective pulmonary vasodilator Patients with cardiac decompensation may require hos-
that produces a sustained improvement in oxygenation pital admission for initiation or augmentation of anti-
and reduces the use of extracorporeal membrane oxy- congestive therapies. Patients are routinely admitted to
genation. Postmortem findings include increased thick- a cardiac intensive care unit where telemetry and inva-
ness of the pulmonary arteriolar media. sive hemodynamic monitoring (arterial and central ve-
In the normal newborn, pulmonary vascular resis- nous lines) are used to deliver and assess response to
tance and the pulmonary arterial pressure continue to therapy. Table 19–12 demonstrates intravenous in-
fall during the first few months of life. This phenome- otropic agents used to augment cardiac output and
non results from the involution of the pulmonary arte- their relative effect on heart rate, systemic vascular resis-
riole from a relatively thick-walled, small-lumen vessel tance, and cardiac index. The drug used will depend in
to a thin-walled, large-lumen vessel. Adult levels of pul- part on the cause of the CHF.
monary resistance and pressure are normally achieved A. INTRAVENOUS INOTROPIC SUPPORT
by age 2 months. It is at this time typically that signs
and symptoms of pulmonary overcirculation associated 1. Afterload reduction—
with moderate or large left-to-right shunting appear. a. Milrinone. This selective phosphodiesterase in-
hibitor increases the level of cyclic adenosine
Fineman JR, Soifer SJ: The fetal and neonatal circulations. In monophosphate (cAMP), thereby improving the in-
Rudolph AR: Congenital Diseases of the Heart: Clinical Physio- otropic state of the heart. In addition to a dose-depen-
logic Considerations, 2nd ed. Futura, 2001. dant increase in cardiac contractility, the drug is a
systemic and pulmonary vasodilator and thus an
effective agent in cases of right or left ventricular sys-
CONGESTIVE HEART FAILURE tolic dysfunction for increasing contractility and reduc-
Congestive heart failure (CHF) is the clinical condition ing afterload. Milrinone has been associated with a re-
in which the heart fails to meet the circulatory and duction in incidence of low cardiac output syndrome
570 / CHAPTER 19

Table 19–12. Intravenous inotropic agents.

Drug Dose Renal Perfusion Heart Rate Cardiac Index SVR

Dopamine 2–5 g/kg/min ↑via vasodilation 0 0 0
5–10 ↑via ↑cardiac index ↑ ↑ 0
> 10 ↓ ↑ ↑ ↑
Dobutamine 2.5–10 g/kg/min ↑via ↑cardiac index ↑ ↑ ↑↓
Epinephrine 0.2–2.0 g/kg/min ↓ ↑ ↑ ↑
Norepinephrine 0.05–0.1 g/kg/min ↓ 0 ↑ ↑↑
Isoproterenol 0.05–2.0 g/kg/min 0 ↑↑ ↑ ↓↓

after cardiac surgery. The usual dosage range is Outpatient Congestive Heart Failure
0.25–0.75 µg/kg/min. Management
b. Nitroprusside. This vasodilator acts directly on A. MEDICATIONS
vascular smooth muscle, causing both venous and arter-
ial vasodilation at dosages of 0.5–4.0 µg/kg/min. It is 1. Digitalis—Digitalis is a primary drug for the treat-
useful in the management of postoperative hyperten- ment of CHF. The desired effect is improvement in
sion. Prolonged use should be carefully monitored as myocardial performance (inotropic effect) with an asso-
thiocyanate toxicity may occur. ciated decrease in systemic vascular resistance. The
standard preparation used in pediatrics is digoxin,
c. Nitroglycerin. Nitroglycerin functions primarily which may be administered intravenously, intramuscu-
as a dilator of venous capacitance vessels and causes a larly, or orally depending on how rapidly a therapeutic
reduction of right and left atrial pressure. Systemic response is needed. The clinical urgency of the individ-
blood pressure may also fall, and reflex tachycardia may ual case dictates how quickly digitalization should be
occur. Nitroglycerin is used to improve coronary blood accomplished. Children require higher doses of digoxin
flow and has been shown to be useful in the setting of on a per kilogram basis than adults, because of their su-
low cardiac output following congenital heart surgery. perior renal function.
Usual intravenous dosage range is 1–3 µg/kg/min.
a. Digitalization. The routine schedule consists of
giving one half of the total digitalizing dose initially,
2. Extracorporeal membrane oxygenator (ECMO)— then one quarter of the total digitalizing dose at 6 and
Mechanical support devices including membrane oxy- 12 hours of therapy (Table 19–13). Twenty-four hours
genators may be used in children with myocardial dys- after the last digitalizing dose, maintenance therapy is
function following cardiac surgery or in children with started.
refractory CHF secondary to cardiomyopathy or my- Serum digoxin levels are not routinely monitored un-
ocarditis. In all cases, mechanical support is used for a less there are concerns regarding compliance or toxicity.
limited time while cardiac function improves, or as a
bridge to cardiac transplantation. A cannula is placed in b. Digitalis toxicity. Any dysrhythmia that occurs
the right atrium, either through direct mediastinal can- during digitalis therapy should be attributed to the
nulation, or through the internal jugular vein. An arter- drug until proven otherwise. Ventricular bigeminy and
ial catheter is placed either directly into the aorta or first-, second-, or third-degree AV block are characteris-
into an extrathoracic arterial site such as the common tic of digitalis toxicity. A trough level should be ob-
carotid artery. Flow from the venous return catheter tained if digitalis toxicity is suspected.
passes through a membrane oxygenator and then is de-
livered back to the patient via the arterial catheter. Flow
rates are adjusted to maintain adequate systemic perfu-
sion, as judged by mean arterial blood pressure, Table 19–13. Digitalis dosing schedule.
acid–base status, end-organ function, and mixed ve-
nous oxygen saturation. The patient is monitored Age Parenteral Oral
closely for return of cardiac contractility, and ECMO
flows are adjusted accordingly. Risks are significant and Premature 0.035 mg/kg 0.04 mg/kg
include severe internal and external bleeding, infection, 1 week to 2 years 0.05 mg/kg 0.06 mg/kg
< 1 week or > 2 years 0.04 mg/kg 0.05 mg/kg
thrombosis, and pump failure.
 CARDIOVASCULAR DISEASES / 571

c. Digitalis poisoning. This is an acute emergency to-right shunts in whom systemic vascular resistance is
that must be treated without delay. Digitalis poisoning elevated.
most commonly occurs in toddlers who have taken
their parents’ or grandparents’ medications. The child’s 4. Fluid restriction—Restricting fluids is a useful ad-
stomach should be emptied immediately even if several junct to medical therapy in children with CHF. When
hours have passed since ingestion. Patients who have restricting fluids in infants and toddlers it is often nec-
ingested massive amounts of digitalis should receive essary to fortify the formula and increase it caloric den-
large doses of activated charcoal. Induction of vomiting sity in order to maintain adequate caloric intake at re-
or gastric lavage may be indicated but should not be duced volumes.
performed if the patient is obtunded. In advanced heart 5. Beta blockade—β-blockers are a useful adjunctive
block, atropine or temporary ventricular pacing may be therapy in children with refractory CHF already taking
beneficial. Digoxin immune Fab can be used to reverse diuretics and ACE inhibitors. Carvedilol and other
potentially life-threatening intoxication. Antiarrhyth- β-blockers, through their antirenin and anticate-
mic agents may be useful. cholamine effects, decrease myocardial afterload and
2. Diuretics—Diuretics are almost always used in the improve ventricular systolic function in some patients.
treatment of CHF, either with or without digoxin.
a. Furosemide. This rapidly acting loop diuretic Azeka E et al: Delisting of infants and children from the heart
transplantation waiting list after carvedilol treatment. J Am
may be given intravenously or orally. Furosemide re- Coll Cardiol 2002;40(11):2034 [PMID: 12475466].
moves large amounts of potassium and chloride from Fiser WP et al: Pediatric arteriovenous ECMO as a bridge to car-
the body, producing hypochloremic metabolic alkalosis diac transplantation. J Heart Lung Transplant 2003;22(7):
when used chronically. Electrolytes should be moni- 770 [PMID: 12873545].
tored during long-term therapy. Hoffman TM et al: Efficacy and safety of milrinone in preventing
b. Thiazides The thiazides are distal tubular diuret- low cardiac output syndrome in infants and children after
ics used to complement furosemide in severe cases of corrective surgery for congenital heart disease. Circulation
2003;107(7):996 [PMID: 12600913].
CHF.
c. Spironolactone Spironolactone is a potassium-
sparing aldosterone inhibitor diuretic. It is used fre-
quently in conjunction with furosemide or thiazides for CONGENITAL HEART DISEASE
its enhanced diuretic function. Because it spares potas-
sium, supplemental potassium may be avoided.
Spironolactone may also be used as a neurohormonal Congenital heart disease occurs in 0.8% of North
antagonist with benefit in CHF irrespective of its di- American and European populations, making this the
uretic effect. In adults with CHF, it has been associated most common category of congenital structural malfor-
with LV remodeling and improved life expectancy. mation. Curative or palliative surgical correction is now
available for virtually all patients with congenital heart
d. Metolozone. This potent oral loop diuretic is fre- disease.
quently used in patients who have become refractory to
conventional doses of the other diuretics. Due to the
marked diuresis that can be associated with this agent, Etiology
electrolytes must be followed closely as even minor al- Congenital heart disease often has a genetic basis. The
terations in potassium may precipitate an arrhythmia in commonest abnormality now recognized is a microdele-
a patient with preexisting myocardial dysfunction. tion in the long arm of chromosome 22 (22q11) associ-
3. Afterload-reducing agents—Oral afterload-reduc- ated with the DiGeorge, Shprintzen, and conotruncal
ing agents improve cardiac output by decreasing sys- anomaly face syndromes. These children tend to have
temic vascular resistance. Angiotensin-converting en- either interrupted aortic arch or conotruncal abnormali-
zyme (ACE) inhibitors (captopril, enalapril, lisinopril) ties such as ToF or double-outlet RV. Intrauterine fac-
are used in patients requiring long-term treatment. tors such as maternal diabetes, alcohol consumption,
These agents, which block angiotensin II-mediated sys- progesterone use, viral infection, and other maternal ter-
temic vasoconstriction, are particularly useful in chil- atogen exposure are associated with an increased inci-
dren with structurally normal hearts but reduced LV dence of malformations. These factors probably repre-
myocardial function (ie, myocarditis or dilated car- sent environmental triggers in persons susceptible or
diomyopathies). These agents are also useful in amelio- predisposed to congenital heart defects. Even acquired
rating mitral and aortic insufficiency and have a role in heart diseases, such as rheumatic fever, appear to be
controlling refractory CHF in patients with large left- under strong genetic control. Atherosclerosis clearly oc-
572 / CHAPTER 19

curs in families although in some circumstances it can right-to-left shunting becomes the major clinical abnor-
also be influenced by diet, drugs, or lifestyle. mality.
Genetic diagnosis may allow for a more accurate
prediction of the risk of recurrence of a congenital heart Clinical Findings
disease in a subsequent pregnancy.
A. SYMPTOMS AND SIGNS
Boneva RS et al: Mortality associated with congenital heart defects Infants with ASD rarely present with CHF. Children
in the United States, trends and racial disparities. Circulation with ASDs most often have no cardiovascular symp-
2001;103(19):2376 [PMID: 11352887]. toms. Some patients remain asymptomatic throughout
life; others develop easy fatigability as older children or
NONCYANOTIC CONGENITAL HEART adults. Cyanosis does not occur unless pulmonary hy-
pertension develops.
DISEASE The peripheral pulses are normal and equal. The
1. Atrial Septal Defect of the Ostium heart is usually hyperactive, with an RV heave felt best
at the mid to lower left sternal border. No thrills are
Secundum Variety usually present. S2 at the pulmonary area is widely split
and often fixed. The pulmonary component is normal
ESSENTIALS OF DIAGNOSIS in intensity. A grade II–III/VI ejection-type systolic
murmur is heard best at the left sternal border in the
& TYPICAL FEATURES second intercostal space. This murmur is caused by in-
creased flow across the pulmonic valve. No murmur is
• RV heave. heard from the flow across the ASD. A middiastolic
• S2 widely split and usually fixed. murmur can often be heard in the fourth intercostal
• Grade I–III/VI ejection systolic murmur at the pul- space at the left sternal border. This murmur is caused
monary area. by increased flow across the tricuspid valve during dias-
• Widely radiating systolic murmur mimicking pe- tole. The presence of this murmur suggests a high flow
ripheral pulmonary artery stenosis (common in with a pulmonary to systemic blood flow ratio greater
infancy).
than 2:1.
• Diastolic flow murmur at the lower left sternal B. IMAGING
border (if the shunt is significant in size). Radiographs show cardiac enlargement. The main pul-
• ECG with rsR′ in lead V1. monary artery may be dilated and pulmonary vascular
markings increased owing to the increased pulmonary
blood flow.
C. ELECTROCARDIOGRAPHY
General Considerations
The usual ECG shows right axis deviation with a clock-
An ASD is an opening in the atrial septum permitting wise loop in the frontal plane. In the right precordial
the shunting of blood between the atria. There are three leads, a rsR′ pattern is usually present.
major types: (1) The ostium secundum type (discussed
here) is the most common and is in the middle of the D. ECHOCARDIOGRAPHY
septum in the region of the foramen ovale. (2) The Echocardiography shows a dilated RV. Direct visualiza-
sinus venosus type is positioned high in the atrial sep- tion of the ASD by two-dimensional echocardiography,
tum, is the least common, and is frequently associated plus demonstration of a left-to-right shunt through the
with partial anomalous pulmonary venous return. defect by color-flow Doppler, confirms the diagnosis
(3) The ostium primum type is low in position and is a and has eliminated the need for cardiac catheterization
form of AV septal defect. It is discussed in that section. prior to open-heart surgery or catheter closure of the
ASD of the ostium secundum variety occurs in ap- defect. During the echocardiography evaluation, a care-
proximately 10% of patients with congenital heart dis- ful assessment of the entry of all of the pulmonary veins
ease and is twice as common in females as in males. Di- into the left atrium is made to rule out associated
agnosis in infancy is becoming more common. anomalous pulmonary venous return.
Pulmonary hypertension and growth failure are uncom-
mon but occur occasionally in infancy and childhood. E. CARDIAC CATHETERIZATION
After the third decade, pulmonary vascular disease may Oximetry reveals a significant increase in oxygen satura-
develop; left-to-right shunting then decreases, and tion at the atrial level. The pulmonary artery pressure is
 CARDIOVASCULAR DISEASES / 573

usually normal, as is pulmonary vascular resistance. The 2. Ventricular Septal Defect

ratio of pulmonary to systemic blood flow may vary
from 1.5:1 to 4:1. Cardiac catheterization is rarely
needed for diagnostic purposes; however, placement of ESSENTIALS OF DIAGNOSIS
a device to close the ostium secundum ASD during car- & TYPICAL FEATURES
diac catheterization is becoming increasingly common.
Small- to moderate-sized left-to-right shunt with-
Treatment out pulmonary hypertension:
Surgical or catheterization laboratory closure with an • Acyanotic, relatively asymptomatic.
interventional device is generally recommended for os- • Grade II–IV/VI pansystolic murmur, maximal
tium secundum ASDs in which the ratio of pulmonary along the lower left sternal border.
to systemic blood flow is greater than 2:1. Closure is • P2 not accentuated.
performed electively in patients between ages 1 and
Large left-to-right shunt:
3 years. The mortality rate for surgical closure is less
than 1%. When closure is performed by age 3 years, • Acyanotic.
late complications of RV dysfunction and significant • Easy fatigability.
dysrhythmias are avoided. Early surgery is always indi- • CHF in infancy (often).
cated in infants with CHF or significant pulmonary hy- • Hyperactive heart; biventricular enlargement.
pertension. Surgical repair can now be safely performed
via a “mini” median sternotomy or posterior thoraco- • Grade II–IV/VI pansystolic murmur, maximal at
tomy approach. Many defects are amenable to nonop- the lower left sternal border.
erative device closure in the cardiac catheterization lab- • P2 usually accentuated.
oratory, but the defect must have adequate tissue rims • Diastolic flow murmur at the apex.
on either side on which to anchor the device. Insignificant left-to-right shunt or bidirectional
shunt with pulmonary hypertension:
Course and Prognosis
• Quiet precordium with RV lift.
Patients usually tolerate an ASD well in the first two • Palpable P2.
decades of life. Occasionally a patient may never de-
• Short ejection systolic murmur along the left ster-
velop symptoms, but exercise intolerance is common in
nal border; single accentuated S2.
adulthood. Pulmonary hypertension and reversal of the
shunt are rare late complications. Infective endocarditis • Systemic arterial oxygen desaturation may be
is uncommon. Spontaneous closure occurs, most fre- present; pulmonary arterial pressure and systemic
quently in children with a defect originally estimated as arterial pressures are equal; little or no oxygen
less than 4 mm in diameter. Exercise tolerance and oxy- saturation increase at the RV level by catheteriza-
gen consumption in surgically corrected children are tion.
generally normal, and restriction of physical activity is
unnecessary. Of all the forms of congenital heart dis-
ease, ostium secundum ASD is the most likely to pre-
sent in middle to late adulthood, either with increased
fatigue or with atrial tachyarrhythmias. General Considerations
Simple VSD is the most common congenital heart mal-
Fredriksen PM et al: Aerobic capacity in adults with various con-
genital heart diseases. Am J Cardiol 2001;87(3):310 [PMID:
formation, accounting for about 30% of all cases of
11165966]. congenital heart disease. Defects in the ventricular sep-
Lopez L et al: Echocardiographic considerations during deploy- tum occur both in the membranous portion of the sep-
ment of the Helex Septal Occluder for closure of atrial septal tum (most common) and in the muscular portion.
defects. Cardiol Young 2003;13(3):290 [PMID: 12903878]. VSDs follow one of four courses:
Roos-Hesselink JW et al: Excellent survival and low incidence of
arrhythmias, stroke and heart failure long-term after surgical A. SMALL, HEMODYNAMICALLY INSIGNIFICANT
ASD closure at a young age: A prospective follow-up study VENTRICULAR SEPTAL DEFECTS
of 21–33 years. Eur Heart J 2003;24(2):190 [PMID:
12573276]. Between 80% and 85% of all VSDs are small (< 3 mm
Ryan WH et al: Safety and efficacy of minimally invasive atrial sep- in diameter) at birth, and will close spontaneously. In
tal defect closure. Ann Thorac Surg 2003;75(5):1532 general, small defects in the muscular interventricular
[PMID: 12735575]. septum will close sooner than those in the membranous
574 / CHAPTER 19

interventricular septum. In most cases, a small VSD 1. Small left-to-right shunt—Usually no lifts, heaves,
never requires surgical closure. Fifty percent of small or thrills are present. The first sound at the apex is nor-
VSDs will close by age 2 years, and 90% will close by mal, and the second sound at the pulmonary area is
age 6 years. The remaining 10% will close during the split physiologically. The pulmonary component is nor-
school years, and parents should be told at the time of mal. A grade II–IV/VI, medium- to high-pitched, harsh
diagnosis and echocardiographic confirmation that all pansystolic murmur is heard best at the left sternal bor-
small VSDs will eventually close. der in the third and fourth intercostal spaces. The mur-
mur radiates over the entire precordium. No diastolic
B. MODERATE VENTRICULAR SEPTAL DEFECTS murmurs are heard.
Asymptomatic patients with moderate VSDs (3–5 mm
in diameter) account for only 3–5% of children with 2. Moderate left-to-right shunt—Slight prominence
VSDs. In general these children do not have CHF or of the precordium is common. Moderate LV heave is
pulmonary hypertension, the two indicators for surgical evident. A systolic thrill may be palpable at the lower
closure. In those who have cardiac catheterization, the left sternal border between the third and fourth inter-
ratio of pulmonary to systemic blood flow is usually less costal spaces. The second sound at the pulmonary area
than 2:1, and serial cardiac catheterizations demon- is most often split but may be single. A grade
strate that the shunts get progressively smaller. If there III–IV/VI, harsh pansystolic murmur is heard best at
is neither CHF nor pulmonary hypertension, these de- the lower left sternal border in the fourth intercostal
fects can be followed until spontaneous closure. space. A mitral diastolic flow murmur indicates that the
pulmonary venous return is large and that the pul-
C. LARGE VENTRICULAR SEPTAL DEFECTS WITH monary-to-systemic blood flow ratio is at least 2:1.
NORMAL PULMONARY VASCULAR RESISTANCE 3. Large ventricular septal defects with pulmonary
These defects are usually 6–10 mm in diameter. Unless hypertension—The precordium is prominent, and the
they become markedly smaller within a few months sternum bulges. An LV thrust and an RV heave are pal-
after birth, they will require surgery. The timing of pable. S2 may be felt at the pulmonary area. A thrill
surgery depends on the clinical situation. Many infants may be present at the lower left sternal border. S2 is
with large VSDs and normal pulmonary vascular resis- usually single or narrowly split, with accentuation of
tance will develop CHF and failure to thrive by age the pulmonary component. The murmur ranges from
3–6 months, and require correction at that time. In all grade II to grade IV/VI and is usually harsh and pansys-
cases, surgery before age 2 years is required so that the tolic. Occasionally, when the defect is large, a murmur
risk of pulmonary vascular disease can be minimized. is difficult to hear. A diastolic flow murmur may be
heard, depending on the size of the shunt.
D. LARGE VENTRICULAR SEPTAL DEFECTS WITH
PULMONARY VASCULAR OBSTRUCTIVE DISEASE B. IMAGING
The vast majority of patients with inoperable pul- Chest radiographic findings vary depending on the size
monary hypertension develop the condition progres- of the shunt. In patients with small shunts, the radi-
sively. The combined data of the multicenter National ograph may be normal. Patients with large shunts usu-
History Study indicate that almost all cases of irre- ally show significant cardiac enlargement involving
versible pulmonary hypertension can be prevented by both the left and right ventricles and the left atrium.
surgical repair of a large VSD before age 2 years. The aorta is small to normal in size, and the main pul-
monary artery segment is dilated. The pulmonary vas-
Clinical Findings cular markings are increased in patients with large
shunts.
A. SYMPTOMS AND SIGNS
Patients with small or moderate left-to-right shunts C. ELECTROCARDIOGRAPHY
usually have no cardiovascular symptoms. Patients with The ECG is normal in patients with small left-to-right
large left-to-right shunts are usually ill early in infancy. shunts. Left ventricular hypertrophy (LVH) usually oc-
Such patients have frequent upper and lower respira- curs in patients with large left-to-right shunts and nor-
tory infections. They grow slowly and gain weight mal pulmonary vascular resistance (moderate-sized de-
slowly. Dyspnea, exercise intolerance, and fatigue are fects). Combined ventricular hypertrophy (both right
common. CHF develops between 1 and 6 months. Pa- and left) occurs in patients with pulmonary hyperten-
tients who survive the first year usually improve, al- sion caused by increased flow, increased resistance, or
though easy fatigability may persist. With severe pul- both. Pure RV hypertrophy occurs in patients with pul-
monary hypertension (Eisenmenger syndrome), monary hypertension secondary to pulmonary vascular
cyanosis is present. obstruction (Eisenmenger syndrome).
 CARDIOVASCULAR DISEASES / 575

D. ECHOCARDIOGRAPHY tients with pulmonary artery pressures equal to systemic

Two-dimensional echocardiography can reveal defects pressure (pulmonary hypertension) undergo surgical re-
that are 2 mm or larger and often can be used to pin- pair well before age 2 years to avoid pulmonary vascular
point the anatomic location of the defect. The addition disease. In most centers these children have surgery be-
of color-flow Doppler allows detection of even the fore age 1 year. As a result of this management, the inci-
smallest VSDs. Multiple defects can be detected by dence of VSD with pulmonary vascular disease and
combining two-dimensional and color-flow imaging. right-to-left shunting (Eisenmenger syndrome) has been
Doppler can aid in the evaluation of VSDs by estimat- virtually eliminated. In all cases of VSD, the surgical
ing the pressure difference between the left and right mortality rate is below 2%.
ventricles. A pressure difference greater than 50 mm Hg
indicates the absence of severe pulmonary hyperten- Course & Prognosis
sion. The combination of excellent visualization of the
VSD using echocardiography and Doppler plus the Significant late dysrhythmias are uncommon. Func-
ability to estimate right-sided heart pressures by know- tional exercise capacity and oxygen consumption are
ing the systemic blood pressure, and using the pressure usually normal, and physical restrictions are unneces-
drop by Doppler from the left to the right ventricle, al- sary. Adults with corrected defects have a normal qual-
lows many VSDs to be repaired surgically without car- ity of life. With complete VSD closure, antibiotic pro-
diac catheterization and angiocardiography. phylaxis for bacterial endocarditis can be discontinued
6 months after surgery.
E. CARDIAC CATHETERIZATION
AND ANGIOCARDIOGRAPHY Thanopoulous B et al: Transcatheter closure of perimembranous
ventricular septal defects with the Amplatzer asymmetric ven-
Cardiac catheterization and angiocardiography is rarely tricular septal defect occluder: Preliminary experience in chil-
required for evaluation of an isolated VSD. The pul- dren. Heart 2003;89(8)918 [PMID: 12860872].
monary artery pressure may vary from normal to sys- Thanopoulous B et al: Transcatheter closure of muscular ventricu-
temic levels (equal to the aortic pressure). Left atrial lar septal defects with the Amplatzer ventricular septal defect
pressure (pulmonary wedge pressure) may be normal to occluder: Initial clinical applications in children. J Am Coll
increased. Pulmonary vascular resistance varies from Cardiol 1999;33(5):1395 [PMID: 10193744].
normal to markedly increased. Angiocardiographic ex-
amination defines the number, size, and location of the 3. Atrioventricular Septal Defect
defects.

Treatment ESSENTIALS OF DIAGNOSIS

& TYPICAL FEATURES
A. MEDICAL MANAGEMENT
Patients who develop CHF should receive vigorous • Murmur often inaudible in neonates.
treatment with anticongestive measures (see Congestive • Loud pulmonary component of S2.
Heart Failure section). If the patient does not respond
• Common in infants with Down syndrome.
to vigorous anticongestive measures, or if he or she
shows signs of progressive pulmonary hypertension, • ECG with left axis deviation.
surgery is indicated without delay. Transcatheter clo-
sure of muscular VSDs is currently being used in se-
lected cases.
B. SURGICAL TREATMENT General Considerations
The indications for surgical closure of a VSD are CHF AV septal defect is a congenital cardiac abnormality re-
combined with failure to thrive and pulmonary hyper- sulting from incomplete fusion of the embryonic endo-
tension. Primary closure of the defect with a synthetic cardial cushions. The endocardial cushions help to
patch is used. The age at which elective surgery is per- form the lower portion of the atrial septum, the mem-
formed has decreased in most pediatric cardiology cen- branous portion of the ventricular septum, and the sep-
ters; most defects are closed in infancy. Patients with tal leaflets of the tricuspid and mitral valves. These de-
cardiomegaly, poor growth, poor exercise tolerance, or fects are not very common. They account for about 4%
other clinical abnormalities who have a significant shunt of all cases of congenital heart disease. Forty-five per-
(> 2:1) without significant pulmonary hypertension typ- cent of children with Down syndrome have congenital
ically undergo surgical repair at age 3–6 months. Pa- heart disease. Of these, 20–25% have AV septal defects.
576 / CHAPTER 19

AV septal defects are divided into partial and com- The peripheral pulmonary vascular markings are usu-
plete forms. The complete form consists of a posterior- ally decreased.
inlet VSD, an ostium primum ASD that is continuous
with the ventricular defect, and a cleft in the anterior C. ELECTROCARDIOGRAPHY
leaflet of the mitral valve. In the partial form, any one In all forms of AV septal defect, left axis deviation with
of these components may be present. The most com- a counterclockwise loop in the frontal plane is present.
mon partial form of AV septal defect is the ostium pri- The mean axis varies from approximately –30 to
mum type of ASD with a cleft in the mitral valve and –90 degrees. Because left axis deviation is present in all
little or no VSD. patients with this condition, the ECG is an important
The complete form results in large left-to-right diagnostic tool. Only 5% of isolated VSDs have this
shunts at both the ventricular and atrial levels, tricuspid ECG abnormality. First-degree heart block is present in
and mitral regurgitation, and pulmonary hypertension, over 50% of patients. Right, left, or combined ventric-
usually with some increase in pulmonary vascular resis- ular hypertrophy is present depending on the particular
tance. When pulmonary hypertension is present, the type of defect and the presence or absence of pul-
shunts may be bidirectional. The hemodynamics in the monary hypertension.
partial form depend on the lesions present.
D. ECHOCARDIOGRAPHY
Clinical Findings Echocardiography is the diagnostic technique of choice.
The anatomy can be visualized directly by two-dimen-
A. SYMPTOMS AND SIGNS sional echocardiography, noting both AV valves to be
The clinical picture varies depending on the severity of at the same level. A primum ASD and an inlet VSD are
the defect. In the partial form, patients may be clini- present. AV valve regurgitation may be present. The
cally indistinguishable from children with ostium se- LV outflow tract is elongated and has been likened to a
cundum ASDs. They are often asymptomatic. Patients “gooseneck.” The LV outflow tract may be obstructed.
with complete AV septal defect usually are severely af-
fected. CHF often develops in infancy, and recurrent E. CARDIAC CATHETERIZATION
bouts of pneumonia are common. AND ANGIOCARDIOGRAPHY
In the neonate with the complete form, the murmur Cardiac catheterization is not routinely used in the di-
may be inaudible. After 4–6 weeks, a nonspecific sys- agnostic assessment of AV septal defects but may be of
tolic murmur develops. The murmur is usually not as value in assessing pulmonary artery pressures in the
harsh as that of an isolated VSD. The heart is signifi- older infant with Down syndrome as this patient group
cantly enlarged (both the right and left sides). S2 is split, is predisposed to early-onset pulmonary hypertension,
with an accentuated pulmonary component. A pro- which may prohibit surgical closure. If any anatomic
nounced diastolic flow murmur may be heard at the questions still need to be answered, cardiac catheteriza-
apex and the lower left sternal border. tion is of value. The results of cardiac catheterization
When severe pulmonary vascular obstructive disease vary with the type of defect. The catheter is easily
is present, dominant RV enlargement usually occurs. S2 passed across the atrial septum in its lowest portion and
can be palpated at the pulmonary area. No thrill is felt. frequently enters the LV directly from the right atrium.
S2 is markedly accentuated and single. A nonspecific This catheter course is a result of the very low ASD and
short systolic murmur is heard at the lower left sternal the cleft in the mitral valve. Increased oxygen saturation
border. No diastolic flow murmurs are heard. Cyanosis in the RV or the right atrium identifies the level of the
is detectable in severe cases with predominant right-to- shunt. Angiocardiography reveals the characteristic
left shunts. gooseneck deformity of the LV outflow tract in the
The physical findings in the incomplete form de- complete form.
pend on the lesions. In the most common variety (os-
tium primum ASD with mitral regurgitation), the find- Treatment
ings are similar to those of ostium secundum ASD with
or without findings of mitral regurgitation. Treatment consists of anticongestive measures; since
spontaneous improvement does not occur, surgery is al-
B. IMAGING ways required. In the partial form, surgery carries a low
Cardiac enlargement is always present. In the complete mortality rate (1–2%), but patients require ongoing fol-
form, all four chambers are enlarged. The pulmonary low-up because of the risk of late occurring LV outflow
vascular markings are increased. In patients with pul- tract obstruction and mitral valve dysfunction. The
monary vascular obstructive disease, only the main pul- complete form is associated with a somewhat higher
monary artery segment and its branches are prominent. mortality rate, but complete correction in the first year
 CARDIOVASCULAR DISEASES / 577

of life, prior to the onset of irreversible pulmonary hy- Clinical Findings

pertension, is obligatory. Patients with Down syn-
drome tend to have a lower incidence of associated mi- A. SYMPTOMS AND SIGNS
tral valve dysplasia and have a lesser risk of reoperation. The clinical findings and the clinical course depend on
Pulmonary artery banding procedures are rarely used the size of the shunt and the degree of pulmonary hy-
for AV septal defects. Primary correction should be per- pertension.
formed when the child is well and, if possible, weighs 1. Typical patent ductus arteriosus—The pulses are
more than 5 kg. At corrective surgery, transesophageal bounding, and pulse pressure is widened. S1 is normal.
echocardiography is useful in assessing the adequacy of S2 is usually narrowly split. Rarely, in large shunts, S2 is
repair in the operating room at the completion of car- paradoxically split; that is, S2 closes on inspiration and
diopulmonary bypass. splits on expiration. The paradoxical splitting is caused
by the volume overload of the LV and the prolonged
ejection of blood from this chamber.
Al-Hay AA et al: Complete atrioventricular septal defect, Down The murmur is quite characteristic. It is a very
syndrome and surgical outcome: Risk factors. Ann Thorac rough “machinery” murmur that is maximal at the sec-
Surg 2003;75(2)412 [PMID: 12607648]. ond intercostal space at the left sternal border and infe-
El-Najdawi EK et al: Operation for partial atrioventricular septal rior to the left clavicle. It begins shortly after S1, rises to
defect: A forty year review. J Thorac Cardiovasc Surg
2000;119(5):880 [PMID: 10788807].
a peak at S2, and passes through the S2 into diastole,
where it becomes a decrescendo murmur and fades be-
fore the S1. The murmur tends to radiate fairly well
over the lung fields anteriorly but relatively poorly over
PATENT DUCTUS ARTERIOSUS the lung fields posteriorly. A diastolic flow murmur is
often heard at the apex.
ESSENTIALS OF DIAGNOSIS 2. Patent ductus arteriosus with pulmonary hyper-
tension—The physical findings depend on the cause of
& TYPICAL FEATURES the pulmonary hypertension. If pulmonary hyperten-
sion is primarily the result of an increase in blood flow
• Variable murmur, with active precordium and full and only a slight increase in pulmonary vascular resis-
pulses, in newborn premature infants. tance, the physical findings are similar to those listed
• Continuous murmur and full pulses in older in- earlier. The significant difference is the presence of an
fants. accentuated pulmonary component of S2. Bounding
pulses and a loud continuous heart murmur are pre-
sent. In patients with increased pulmonary vascular re-
sistance, the findings are quite different. S2 is single and
accentuated, and no significant heart murmur is pre-
sent. The pulses are normal rather than bounding.
General Considerations
3. Patent ductus arteriosus in the premature
PDA is the persistence of the normal fetal vessel that neonate with associated respiratory distress syn-
joins the pulmonary artery to the aorta. It closes spon- drome—A preterm neonate during or after respiratory
taneously in normal full-term infants at 3–5 days of distress syndrome may have a significant PDA that is dif-
age. It is a common abnormality, accounting for about ficult to detect by auscultation but which may still be
10% of all cases of congenital heart disease. The inci- clinically significant. A soft, nonspecific systolic murmur
dence of PDA is higher in infants born at high altitudes or no murmur is heard rather than the classic continuous
(over 10,000 ft). It is twice as common in females as in murmur. Increase in peripheral pulses may be a helpful
males. In preterm infants weighing less than 1500 g, sign. Increasing oxygen requirement and increased need
the frequency of PDA ranges from 20 to 60%. for respiratory support or CHF may be signs that a PDA
The defect occurs as an isolated abnormality, but as- is causing significant left-to-right shunting. The chest ra-
sociated lesions sometimes occur. Coarctation of the diograph may show cardiomegaly. Echocardiography is
aorta and VSD are commonly associated with PDA. always required to confirm the presence or absence of a
Even more important to recognize are those patients PDA in the premature infant with lung disease.
with murmurs of PDA but without readily apparent
findings of other associated lesions who are being kept B. IMAGING
alive by the patent ductus (eg, a patient with PDA with In simple PDA, the radiographic appearance depends
unsuspected pulmonary atresia). on the size of the shunt. If the shunt is relatively small,
578 / CHAPTER 19

the heart is not enlarged. If the shunt is large, both left it is less successful in smaller infants. Indomethacin
atrial and LV enlargement may be present. The aorta (0.1–0.3 mg/kg orally every 8–24 hours or
and the main pulmonary artery segment may be promi- 0.1–0.3 mg/kg parenterally every 12 hours) can be used
nent. if adequate renal, hematologic, and hepatic function is
demonstrated. Management during indomethacin ther-
C. ELECTROCARDIOGRAPHY apy includes fluid restriction with or without diuretics
The ECG may be normal or may show LVH, depend- and close observation of the urinary output because of
ing on the size of the shunt. In patients with pulmonary indomethacin’s tendency to rapidly decrease renal func-
hypertension caused by increased blood flow, biventric- tion. If indomethacin is not successful and the ductus
ular hypertrophy usually occurs. In those with pul- remains hemodynamically significant, surgical ligation
monary vascular obstructive disease, pure right ventric- should be performed without hesitation. If the ductus
ular hypertrophy (RVH) occurs. closes substantially so that it is no longer hemodynami-
cally significant even with some residual flow from left
D. ECHOCARDIOGRAPHY to right, surgery is not needed, and a second course of
Echocardiography provides direct visualization of the indomethacin may complete ductal closure. Recent
ductus and confirmation of the direction and degree of studies from Europe indicate that ibuprofen may be as
shunting. Preterm infants with a suspected PDA should effective as indomethacin for the medical closure of the
have a complete echocardiographic evaluation to make preterm PDA.
a definitive diagnosis, assess the magnitude of the left-
to-right shunt, and rule out associated, particularly duc- Course & Prognosis
tal-dependent, lesions.
Patients with simple PDA and small-to-moderate
E. CARDIAC CATHETERIZATION shunts usually do well without surgery. However, in the
AND ANGIOCARDIOGRAPHY third or fourth decade of life, symptoms of easy fatiga-
Children with PDA never require a cardiac catheteriza- bility, dyspnea on exertion, and exercise intolerance ap-
tion for diagnostic reasons. However, children with a pear, usually as a consequence of the development of
small PDA routinely have the ductus closed in the pulmonary hypertension or CHF.
catheterization laboratory. This is the sole indication Spontaneous closure of a PDA may occur up to age
for cardiac catheterization in PDA. 1 year. This is especially true in preterm infants. After
age 1 year, spontaneous closure is rare. Because infec-
tive endocarditis is a potential complication, closure by
Treatment coil embolization or surgery is recommended if the de-
Treatment is surgical when the PDA is large, except in fect persists beyond age 1 year.
patients with pulmonary vascular obstructive disease. The prognosis for patients with large shunts or pul-
Patients with large left-to-right shunts and pulmonary monary hypertension is not as good. Poor growth and
hypertension should be operated on by age 1 year to development, frequent episodes of pneumonia, and the
prevent the development of progressive pulmonary vas- development of CHF occur in these children. There-
cular obstructive disease. A symptomatic PDA with fore, patients with PDA and large shunts who are be-
normal pulmonary artery pressure can be safely coil-oc- yond the newborn period should have immediate surgi-
cluded during cardiac catheterization after the child has cal ligation of their PDA.
reached 5 kg.
Patients with nonreactive pulmonary vascular ob- Liang CD et al: Echocardiographic guidance for transcatheter coil
occlusion of patent ductus arteriosus in the catheterization
struction who have resistance greater than 10 units and laboratory. J Am Soc Echocardiogr 2003;16(5):476 [PMID:
a ratio of pulmonary-to-systemic resistance greater than 12724658]
0.7 despite vasodilator therapy (eg, nitric oxide) should Overmeire BV et al: A Comparison of ibuprofen and indomethacin
not be operated on. These patients are made worse by for closure of patent ductus arteriosus. N Engl J Med
closure of the ductus, because the ductus serves as an es- 2000;343(10):674 [PMID: 10974130].
cape route for their pulmonary hypertension.
Symptomatic PDA is a common problem in
preterm infants. Indomethacin, a potent inhibitor of
prostaglandin synthesis, is routinely used to close the
PDA in premature infants. Indomethacin does not
close the PDA of full-term infants or children. The suc-
cess of indomethacin therapy is as high as 80–90% in
premature infants with a birth weight over 1200 g, but
 CARDIOVASCULAR DISEASES / 579

MALFORMATIONS ASSOCIATED When obstruction is severe and the ventricular sep-

WITH OBSTRUCTION TO BLOOD FLOW tum is intact, a right-to-left shunt will often occur at
the atrial level through a patent foramen ovale. Thus,
ON THE RIGHT SIDE OF THE HEART patients with this condition may have cyanosis, which
1. Valvular Pulmonary Stenosis with always indicates a severe degree of valvular obstruction.
Intact Ventricular Septum
Clinical Findings
A. SYMPTOMS AND SIGNS
ESSENTIALS OF DIAGNOSIS The history varies with the severity of the obstruction.
& TYPICAL FEATURES Patients with mild or even moderate valvular pulmonary
stenosis are completely asymptomatic. Patients with
• No symptoms with mild and moderately severe more severe valvular obstruction may develop cyanosis
cases. very early—even as neonates. Hypoxemic spells charac-
• Cyanosis and a high incidence of right-sided CHF terized by a sudden onset of marked cyanosis and dysp-
in very severe cases in infancy. nea occur, but are much less common than in ToF.
• RV lift; systolic ejection click at the pulmonary
Patients with mild to moderate obstruction are
acyanotic. These patients are usually well developed
area in mild to moderately severe cases.
and well nourished. They are not prone to lung infec-
• S2 widely split with soft to inaudible P2; grade tions. The pulses are normal. Clubbing may occur in
I–VI/VI obstructive systolic murmur, maximal at severe cases in which cyanosis has persisted for a long
the pulmonary area. time. On examination of the heart, the precordium
• Dilated pulmonary artery on posteroanterior may be prominent. An RV heave can frequently be pal-
chest radiograph. pated. A systolic thrill is often palpated in the pul-
monary area and occasionally in the suprasternal notch.
S1 is normal. In patients with mild to moderate steno-
sis, a prominent ejection click of pulmonary origin is
heard best at the third left intercostal space. This click
varies with respiration. It is much more prominent dur-
General Considerations ing expiration than inspiration. In patients with severe
stenosis, the click tends to merge with S1. S2 also varies
Pulmonic valve stenosis accounts for 10% of all cases of with the degree of stenosis. In mild valvular stenosis, S2
congenital heart disease. In the usual case, the cusps of is normal. In moderate degrees of obstruction, S2 is
the pulmonary valve are fused to form a membrane or more widely split and the pulmonary component is
diaphragm with a hole in the middle that varies from softer. In severe pulmonary stenosis, S2 is single because
2 to 10 mm in diameter. Occasionally, only two cusps the pulmonary component cannot be heard. An ejec-
may fuse, producing a bicuspid pulmonary valve. In the tion-type, rough, obstructive systolic murmur is best
more severe cases, a secondary infundibular stenosis is heard at the second interspace at the left sternal border.
present. The pulmonary valve annulus is usually small. It radiates very well to the back. With severe obstruc-
Moderate to marked poststenotic dilation of the main tion of the valve, the murmur is usually short and peaks
and left pulmonary arteries is usually evident. Patent in late systole. No diastolic murmurs are audible.
foramen ovale is fairly common.
Obstruction to blood flow across the pulmonary B. IMAGING
valve results in an increase in pressure developed by the In the mild form of pulmonary stenosis, the heart is
RV to maintain an adequate output across that valve. normal in size. Poststenotic dilation of the main pul-
Pressures greater than systemic are potentially life- monary artery segment and the left pulmonary artery
threatening and are associated with critical obstruction. often occurs. In moderate to severe cases, slight RV en-
Because of the increased work required of the RV, se- largement may occur, and poststenotic dilation of the
vere RVH and eventual RV failure can occur. In con- main pulmonary artery may or may not be present. In
trast to patients with severe pulmonic valve stenosis, pa- cyanotic patients, the pulmonary vascular markings
tients with this obstruction who also have a large VSD may be decreased.
(ie, ToF) are not at risk for heart failure. In this situa-
tion, the septal defect limits the pressure developed in C. ELECTROCARDIOGRAPHY
the RV to systemic pressure, making heart failure ex- Electrocardiography is usually normal in patients with
tremely uncommon. mild obstruction. RVH is present in patients with
580 / CHAPTER 19

moderate to severe valvular obstruction. In severe ob- After balloon pulmonic valvuloplasty or surgery,
struction, RV hypertrophy and the RV strain pattern most patients have good voluntary maximum exercise
(deep inversion of the T wave) are seen in the right pre- capacity unless they have significant PI after valvulo-
cordial leads. In the most severe form, right atrial hy- plasty. Patients with isolated PI, a common occurrence
pertrophy is also present. Right axis deviation also oc- after surgical pulmonary valvotomy, may be signifi-
curs in the moderate to severe forms. Occasionally, the cantly limited in exercise performance. Severe PI leads
axis is as great as +180 degrees. to progressive RV dilation and dysfunction, which may
precipitate ventricular arrhythmias or right heart failure
D. ECHOCARDIOGRAPHY in adulthood. Patients with severe PI may benefit from
The pulmonary valve may be unusually thickened with surgical placement of a pulmonic valve to restore RV
reduced valve leaflet excursion. The valve may bulge for- outflow tract competence. If relief of valvular obstruc-
ward in systole. The transvalvular pressure gradient can tion occurs before age 20 years, longevity is normal.
be estimated accurately by Doppler echocardiography. Limitation of physical activity is unwarranted. The
quality of life of adults with successfully treated pul-
E. CARDIAC CATHETERIZATION monary stenosis, and minimal PI is normal.
AND ANGIOCARDIOGRAPHY
Oxygen saturation or oxygen content does not increase Yetman AT et al: Comparison of exercise performance in patients
in the right side of the heart. In more severe cases, a after pulmonary valvulotomy for pulmonary stenosis and
tetralogy of Fallot. Am J Cardiol 2002;90(12) 1412 [PMID:
right-to-left shunt occurs at the atrial level. Pulmonary 12480060].
artery pressure is normal in milder cases and decreased
in moderate to severe cases. RV pressure is always
higher than pulmonary artery pressure. The gradient 2. Infundibular Pulmonary Stenosis
across the pulmonary valve varies from 10 to 200 mm Without Ventricular Septal Defect
Hg. In severe cases, the right atrial pressure is often ele-
vated, with a predominant a wave. Cineangiocardiogra- Pure infundibular pulmonary stenosis is rare. One
phy after injection of contrast material into the RV should suspect infundibular pulmonary stenosis when
shows thickening of the pulmonary valve and the very mild to moderate pulmonary stenosis, an intact ventric-
narrow opening of the pulmonary valve. This produces ular septum, no audible pulmonary ejection click, and a
a jet of contrast from the RV into the pulmonary murmur that is maximal in the third and fourth inter-
artery. Infundibular hypertrophy may be present. Diag- costal spaces rather than in the second intercostal space
nostic catheterization is rarely performed because pul- are present. The clinical picture is identical to that of
monic stenosis can be diagnosed easily using physical pulmonic valve stenosis. Intervention, if indicated, is al-
examination, the ECG, and echocardiography. ways surgical because this condition does not improve
Catheterization is performed only when balloon pul- with balloon catheter dilation.
monic valvotomy is planned.
3. Distal Pulmonary Stenosis
Treatment Supravalvular Pulmonary Stenosis
Relief of pulmonic stenosis is recommended for chil- Supravalvular pulmonary stenosis, a relatively rare con-
dren with RV systolic pressures greater than 60 mm Hg dition, is caused by narrowing of the main pulmonary
or higher than two thirds of systemic pressure. Immedi- artery. The clinical picture may be identical to that of
ate correction is indicated for patients with systemic or valvular pulmonary stenosis, although the murmur is
suprasystemic RV pressure. Percutaneous balloon maximal in the first intercostal space at the left sternal
valvuloplasty is the procedure of choice in most institu- border and in the suprasternal notch. No ejection click
tions. It appears to be as effective as surgery in relieving is audible. S2 is usually narrowly split, and the pul-
obstruction and causes less valve insufficiency. Surgery monary component is quite loud as a result of closure
is needed to treat pulmonic valve stenosis only when of the pulmonary valve under high pressure. The mur-
balloon pulmonic valvuloplasty is unsuccessful. mur radiates into the neck and over the lung fields.
This condition occurs most often in children with
Course & Prognosis Noonan syndrome.
Patients with mild pulmonary stenosis live normal lives. Peripheral Pulmonary Branch Stenosis
Those with stenosis of moderate severity rarely are
symptomatic. Those with severe valvular obstruction In peripheral pulmonary branch stenosis, multiple nar-
may develop severe cyanosis and CHF in infancy. rowings of the branches of the pulmonary artery occur
 CARDIOVASCULAR DISEASES / 581

at the bifurcation of the main pulmonary artery or in C. ECG

the periphery of the lung. Systolic murmurs may be ECG may be normal but more typically shows right
heard over both lung fields, both anteriorly and posteri- atrial enlargement. RBBB and LV enlargement may be
orly. Transient pulmonary branch stenosis murmurs of found. A delta wave from coexisting Wolff–Parkin-
infancy are innocent. The three most common causes son–White syndrome (WPW) may be seen.
of significant pulmonary artery branch stenosis are
Williams–Beuren syndrome, Alagille syndrome, and
congenital rubella syndrome. Surgery is often unsuc- D. ECHOCARDIOGRAPHY
cessful. Transvenous balloon angioplasty is currently Echocardiography is necessary to confirm the diagnosis
being used to treat this condition, with moderate suc- and may aid in predicting outcome. The degree of dis-
cess. placement, the size of the right atrium, the presence of
an associated atrial level shunt, and LV systolic function
all affect outcome. The ratio of the atrialized area of the
4. Other Congenital Right Heart Lesions right heart to the area of the remainder of the heart is
Ebstein Malformation determined by echocardiography. The greater the ratio,
the worse the prognosis.
of the Tricuspid Valve
In the Ebstein malformation of the tricuspid valve, the E. COURSE AND PROGNOSIS
tricuspid valve is displaced downward so that the septal
leaflet of the valve is attached to the RV wall (inside the In cyanotic neonates, prostaglandin E infusion is used
RV) rather than the to the tricuspid annulus. As a re- to maintain pulmonary blood flow until pulmonary
sult, the upper portion of the RV is physiologically vascular resistance decreases, facilitating antegrade pul-
within the right atrium. The so-called atrialized portion monary artery flow. If the patient remains significantly
of the RV is thin-walled and does not contribute to RV cyanotic, surgical intervention is required in the neona-
output. The portion of the ventricle below the dis- tal period.
placed tricuspid valve is diminished in volume and rep- Surgical repair consists of an annuloplasty to modify
resents the functioning RV. This is an uncommon con- the level of the tricuspid orifice and diminish tricuspid
dition. insufficiency. The success rate of this procedure is
highly variable. Late arrhythmias are common. Postop-
erative exercise tolerance increases but remains lower
Clinical Findings than that for age-related normals. If a significant Eb-
stein malformation is not treated, atrial tachyarrhyth-
A. SYMPTOMS & SIGNS mias will frequently begin during adolescence.
The degree of displacement of the tricuspid valve is
variable, and the clinical significance of Ebstein malfor-
mation varies with this displacement. In the most ex- Absence of a Pulmonary Artery
treme form, the septal leaflet is markedly displaced into
the RV outflow tract, leading to significant reduction in Absence of a pulmonary artery (left or right) may be an
antegrade flow to the pulmonary artery. Patients are isolated malformation or may occur in association with
cyanotic shortly after birth because of poor pulmonary other congenital heart diseases. It occurs occasionally in
artery flow. At the opposite extreme, symptoms may patients with ToF.
not develop until adulthood when tachyarrhythmias in
association with right atrial dilatation or an associated
reentrant pathway occur. These older patients typically Absence of the Pulmonary Valve
have minimal displacement of the septal leaflet of the Absence of the pulmonary valve is a rare abnormality
tricuspid valve. usually associated with VSD. In about 50% of cases, in-
fundibular pulmonary stenosis is also present (ToF with
B. IMAGING absent pulmonary valve).
The chest radiograph usually shows cardiomegaly with
prominence of the right heart border. The degree of
Driscoll DJ et al: Spectrum of exercise intolerance in 45 patients
cardiomegaly is influenced by the degree of tricuspid with Ebstein’s anomaly and observations on exercise tolerance
valve displacement and by the presence and size of the in 11 patients after surgical repair. J Am Coll Cardiol
atrial level shunt. Massive cardiomegaly with a “wall to 1988;11(4):831 [PMID: 3351151].
wall heart” occurs in the setting of severe displacement Yetman AT et al: Outcome in cyanotic neonates with Ebstein’s
and a restrictive atrial level defect. anomaly. AJC 1998;81(6):1 [PMID: 9527086].
582 / CHAPTER 19

MALFORMATIONS ASSOCIATED WITH than in the lower extremities. The actual level of blood
OBSTRUCTION TO BLOOD FLOW ON pressure in the arms may be elevated only moderately,
even in severe coarctation, or it may be elevated signifi-
THE LEFT SIDE OF THE HEART cantly. In any case, the pulses in the legs are diminished
1. Coarctation of the Aorta or absent in affected infants. The left subclavian artery
is occasionally involved in the coarctation, in which
case the left brachial pulse is also weak. An ejection sys-
ESSENTIALS OF DIAGNOSIS tolic murmur of grade II/VI intensity is often heard at
& TYPICAL FEATURES the aortic area and the lower left sternal border along
with an apical ejection click from the bicuspid aortic
• Pulse lag in lower extremities. valve. The pathognomonic murmur of coarctation is
heard in the left axilla and the left back. The murmur is
• Systolic blood pressure of 20 mm Hg or greater in
usually systolic but may spill into diastole. If the coarc-
the upper than in the lower extremities. tation is complicated by other malformations, murmurs
• Blowing systolic murmur in the left axilla. associated with these other abnormalities will be audi-
ble.

B. IMAGING
General Considerations In the older child, radiographic findings may show a
normal sized heart, although there is usually some evi-
Coarctation is common, accounting for about 6% of all
dence of LV enlargement. The aorta proximal to the
congenital heart disease. Three times as many males as
coarctation is prominent. The aortic outline indents at
females are affected. Many, though not all, affected fe-
the level of the coarctation. The poststenotic segment is
males have 45 XO Turner syndrome. Coarctation usu-
dilated. This combination of abnormalities results in
ally occurs in the thoracic portion of the descending
the “Figure 3” sign on chest radiograph. Notching or
aorta distal to the takeoff of the left subclavian artery in
scalloping of the ribs caused by marked enlargement of
the juxtaductal region. The abdominal aorta is rarely
the intercostal collaterals can be seen. MRI has become
involved. The term “Shone syndrome” refers to multi-
extremely useful for determining noninvasively the
ple levels of left heart obstructive disease, including
anatomy of the coarctation. In patients with a severe
mitral stenosis, bicuspid aortic valve with or without
coarctation and associated CHF, marked cardiac en-
aortic stenosis, tubular hypoplasia of the aortic isthmus,
largement and pulmonary venous congestion occur.
and coarctation of the aorta. The incidence of an asso-
ciated bicuspid aortic valve with coarctation is
80–85%. C. ELECTROCARDIOGRAPHY
ECGs in older children may be normal or may show
Clinical Findings slight LVH. ECG usually shows RVH in infants with
severe coarctation.
A. SYMPTOMS AND SIGNS
The cardinal physical finding is diminution or absence
of femoral pulses. Infants with severe coarctation have D. ECHOCARDIOGRAPHY
equal upper and lower extremity pulses from birth to Two-dimensional echocardiography and color-flow
2 days of age. Unequal pulses and clinical symptoms Doppler are used to visualize the coarctation directly,
develop between 4 and 10 days of age as the ductus ar- and continuous-wave Doppler may estimate the degree
teriosus closes. Approximately 40% of children with of obstruction. Diastolic run-off flow is found by con-
coarctation will present at this young age. Coarctation tinuous-wave Doppler if the obstruction is severe. If the
alone, or in combination with VSD, ASD, or other ductus arteriosus is patent, echocardiography may not
congenital cardiac anomalies, is the leading cause of detect the coarctation. Associated lesions such as a bi-
CHF in the first month of life. cuspid aortic valve or mitral abnormalities may suggest
Coarctation presents more insidiously in the 60% of the presence of a coarctation. In the face of poor LV
children with no symptoms in infancy. Their coarcta- systolic function, the coarctation may be difficult to vi-
tion is diagnosed by a pulse discrepancy between the sualize. Flow velocities will not be obviously increased
arms and legs on physical exam or by arm hypertension at the coarctation site due to reduced flow across the
on blood pressure measurement. Normally, the systolic obstruction. A high index of suspicion of coarctation is
blood pressure in the upper extremities is slightly lower required in such a patient.
 CARDIOVASCULAR DISEASES / 583

E. CARDIAC CATHETERIZATION AND Ovaert C et al. Balloon angioplasty of native coarctation: Clinical
ANGIOCARDIOGRAPHY outcomes and predictors of success. J Am Coll Cardiol
2000;35(4):988 [PMID: 10732899].
These studies demonstrate the position, anatomy, and
severity of the coarctation and will assess the adequacy
of collateral circulation. Cardiac catheterization and an- 2. Aortic Stenosis
giocardiography are rarely performed for infants or chil-
dren with coarctation unless an interventional proce- ESSENTIALS OF DIAGNOSIS
dure to dilate the coarctation is planned.
& TYPICAL FEATURES
• Systolic ejection murmur at the upper right ster-
Treatment nal border.
Infants with coarctation of the aorta and CHF may pre- • Thrill in the carotid arteries.
sent in extremus secondary to LV dysfunction and asso- • Systolic click at the apex.
ciated low cardiac output. Resuscitative measures
• Dilation of the ascending aorta on chest radi-
should include initiation of prostaglandin infusion at a
dose of 0.025–1.0 µg/kg/min to reopen the ductus ar- ograph.
teriosus as well as initiation of inotropic support. Surgi-
cal repair should not be delayed by undue medical in-
terventions. Once stabilized, the infant should undergo
corrective repair. Some centers perform primary bal- General Considerations
loon dilation aortoplasty in infants with coarctation,
but this is not universally standard. Infant surgery using Aortic stenosis is an obstruction to the outflow from
either the modified end-to-end anastomosis technique the LV at or near the aortic valve that causes a systolic
or the left subclavian approach has a high success rate, pressure gradient of more than 10 mm Hg between the
but there is a significant incidence (20–30%) of re- LV and the aorta. Aortic stenosis accounts for approxi-
coarctation after repair. Fortunately, recurrent coarcta- mately 7% of all cases of congenital heart disease.
tion is highly amenable to balloon aortoplasty in the Anatomically, congenital aortic stenosis is divided into
catheterization laboratory. Coarctation of the aorta in three types:
patients who do not have CHF in infancy is corrected
electively, In elective coarctation repair, either surgery A. VALVULAR AORTIC STENOSIS (75%)
or primary balloon aortoplasty can be used. In the older In critical aortic stenosis presenting in infancy, the aor-
patient, particularly when of adult size, aortic stent tic valve usually consists of a unicuspid diaphragm-like
placement is effective. structure without well-defined commissures. Preschool
and school-age children more commonly have a bicus-
pid aortic valve. Teenagers and young adults character-
istically have a tricuspid valve with partially fused
Course & Prognosis leaflets. This lesion is more common in males than in
Children with coarctation of the aorta who survive the females.
neonatal period without developing CHF do quite well
throughout childhood and adolescence. Fatal complica- B. SUBVALVULAR AORTIC STENOSIS (23%)
tions (eg, hypertensive encephalopathy, intracranial In this condition, a membranous or fibrous ring occurs
bleeding) occur uncommonly in childhood. Infective just below the aortic valve. The ring forms a diaphragm
endocarditis (actually endarteritis in this condition) is with a hole in the middle and results in obstruction to
rare before adolescence. LV outflow. The aortic valve itself and the anterior
Children with coarctation corrected after age 5 years leaflet of the mitral valve are often deformed.
are at increased risk for systemic hypertension and myo-
cardial dysfunction even with successful surgery. Care- C. SUPRAVALVULAR AORTIC STENOSIS (1–2%)
ful exercise testing is mandatory for these children prior In this type of aortic stenosis, constriction of the as-
to their participation in athletic activities. cending aorta occurs just above the coronary arteries.
This condition is often familial, and two different ge-
netic patterns are associated, one with an abnormal fa-
Hamdan MA et al: Endovascular stents for coarctation of the aorta: cies and mental retardation (Williams–Beuren syn-
Initial results and intermediate-term follow-up. J Am Coll drome) and one with normal facies and without
Cardiol 2001;38(5):1518 [PMID: 11691533]. developmental delay.
584 / CHAPTER 19

Clinical Findings they are well transmitted over the aortic area and near
the mid left sternal border. A difference in pulses and
A. SYMPTOMS AND SIGNS blood pressure between the right and left arms may be
Most patients with aortic stenosis have no cardiovascu- found, with the more prominent pulse and pressure in
lar symptoms. Except in the most severe cases, the pa- the right arm (Coanda effect).
tient may do well until the third to fifth decades of life,
although some patients have mild exercise intolerance B. IMAGING
and fatigability. A small percentage of patients have sig- In most cases the heart is not enlarged. The LV, how-
nificant symptoms (ie, dizziness and syncope) in the ever, is slightly prominent. In valvular aortic stenosis,
first decade. Sudden death, although uncommon, may dilation of the ascending aorta is frequently seen.
occur in all forms of aortic stenosis, the greatest risk by
far being in adolescents with hypertrophic cardiomy- C. ELECTROCARDIOGRAPHY
opathy. Patients with mild aortic stenosis have normal ECGs. Pa-
Although isolated valvular aortic stenosis seldom tients with severe obstruction frequently demonstrate evi-
causes symptoms in infancy, severe heart failure occa- dence of LVH and LV strain, but many do not. In about
sionally occurs when critical obstruction is present at 25% of severe cases, the ECG is normal. Progressive in-
birth. The response to medical management is poor; crease in LVH on serial ECGs indicates a significant de-
therefore, an aggressive approach using interventional gree of obstruction. LV strain is an indication for surgery.
catheterization or surgery is required. The physical
findings vary depending on the anatomic type of lesion: D. ECHOCARDIOGRAPHY
1. Valvular aortic stenosis—Affected patients are well This has become a reliable noninvasive technique for
developed and well nourished. The pulses are usually the initial diagnosis and follow-up evaluation of all
normal and equal throughout. If the stenosis is severe forms of aortic stenosis. Doppler accurately predicts the
and a gradient of greater than 80 mm Hg exists, the transvalvular gradient.
pulses are diminished with a slow upstroke. Examina-
tion of the heart reveals an LV thrust at the apex. A sys-
E. CARDIAC CATHETERIZATION
AND ANGIOCARDIOGRAPHY
tolic thrill at the right base, the suprasternal notch, and
both carotid arteries accompanies moderate disease. Left heart catheterization demonstrates the pressure dif-
S1 is normal. A prominent aortic ejection click is ferential between the LV and the aorta and the level at
best heard at the apex. The click corresponds to the which the gradient exists. Echocardiography is now the
opening of the aortic valve at the conclusion of the iso- standard method for following the severity of aortic
volumic contraction phase of systole. It is separated valve stenosis, and cardiac catheterization is reserved for
from S1 by a short but appreciable interval. It does not patients whose resting gradient has reached 60–80 mm
vary with respiration. S2 at the pulmonary area is nor- Hg and in whom intervention is planned. For those
mal. The aortic component of S2 is of good intensity. A with valvar aortic stenosis, balloon valvuloplasty is usu-
grade III–V/VI, rough, medium- to high-pitched ejec- ally the first option. In subvalvular or supravalvular aor-
tion-type systolic murmur is evident, loudest at the first tic stenosis, interventional catheterization is not useful
and second intercostal spaces, and radiates well into the and decisions must be made about surgical intervention.
suprasternal notch and along the carotids. The murmur
also radiates fairly well down the lower left sternal bor- Treatment
der and can be heard at the apex. The grade of the mur-
mur correlates well with the severity of the stenosis. Because operation offers less than a cure, surgical repair
should be considered only in patients with symptoms, a
2. Discrete membranous subvalvular aortic steno- large resting gradient (60–80 mm Hg) despite balloon
sis—The findings are essentially the same as those of angioplasty, or coexisting aortic insufficiency. In many
valvular aortic stenosis except for the absence of a click. cases, the gradient cannot be significantly diminished
The murmur and thrill are usually somewhat more in- without producing aortic insufficiency. Percutaneous
tense at the left sternal border in the third and fourth balloon valvuloplasty is now accepted as standard initial
intercostal spaces than at the aortic area. Frequently, treatment. Patients who develop significant aortic in-
however, the murmur is equally intense at both areas. A sufficiency following the procedure will require surgical
diastolic murmur of aortic insufficiency is commonly intervention to repair or replace the valve with either a
heard after age 5 years. prosthetic valve or with the patient’s own pulmonic
3. Supravalvular aortic stenosis—The thrill and valve (Ross procedure). In the Ross procedure, an RV-
murmur are characteristically best heard in the to-PA conduit is used to replace the pulmonic valve.
suprasternal notch and along the carotids, although Discrete subvalvular aortic stenosis is usually surgically
 CARDIOVASCULAR DISEASES / 585

repaired at a lesser gradient because continued trauma atric patients. It is secondary to redundant valve tissue
to the aortic valve by the subvalvular jet may damage or abnormal tissue comprising the mitral valve appara-
the valve and produce aortic insufficiency. Unfortu- tus. The mitral valve prolapses, moving posteriorly or
nately, simple resection is followed by recurrence in superiorly into the left atrium during ventricular systole
more than 25% of patients with subvalvular aortic as the mitral valve returns to its closed position. A
stenosis. All patients should have close follow-up, and midsystolic click occurs at the time of this movement
those older than age 6 years should undergo yearly exer- and is the clinical hallmark of this entity. Mitral insuffi-
cise testing. If exercise testing is normal, restriction of ciency may occur late in systole, causing an atypical,
physical activity may not be necessary in patients with short, late systolic murmur with variable radiation.
mild to moderate aortic stenosis. MVP occurs in about 2% of thin adolescent females, a
minority of whom have concomitant mitral insuffi-
Course & Prognosis ciency. Although MVP is most commonly an isolated
lesion, it can occur in association with other conditions,
All forms of LV outflow tract obstruction tend to be namely Marfan syndrome and Ehlers–Danlos syn-
progressive. However, regression of the obstruction has drome. These coexisting conditions should be ruled out
been documented in a few patients with supravalvular by clinical examination.
obstruction. Pediatric patients with LV outflow tract
obstruction—with the exception of those with critical
aortic stenosis of infancy—are usually asymptomatic. Clinical Findings
Symptoms accompanying severe unoperated obstruc-
tion (angina, syncope, CHF) are all rare because of de- A. SYMPTOMS AND SIGNS
tection and surgical or catheter intervention. Preopera- The majority of patients with MVP are asymptomatic.
tive or postoperative children whose obstruction is mild Chest pain, palpitations, and dizziness may be reported,
to moderate appear to have above-average oxygen con- but it is unclear whether these symptoms are more
sumption and maximum voluntary working capacity. common in affected patients than in the normal popu-
Children in this category with normal heart size and lation. Significant dysrhythmias have been reported, in-
normal resting and exercising ECG may safely partici- cluding increased ventricular ectopy and nonsustained
pate in vigorous physical activity, including nonisomet- ventricular tachycardia. If significant associated mitral
ric competitive sports. Children with severe aortic regurgitation is present, atrial arrhythmias may also
stenosis may demonstrate ventricular dysrhythmias. occur. The standard approach to auscultation must be
modified to diagnose MVP. Auscultation should be
Mitchell BM et al. Serial exercise performance in children with sur- performed with the patient placed in various positions.
gically corrected congenital aortic stenosis. Pediatr Cardiol Clicks, with or without systolic murmur, are elicited
2003;24(4):319 [PMID: 12632225].
more commonly in the standing and squatting posi-
Rao PS. Long-term follow-up results after balloon dilation of pul-
monic stenosis, aortic stenosis and coarctation of the aorta: A re-
tions than in the supine and sitting positions. The sys-
view. Prog Cardiovasc Dis 1999;42(1):59 [PMID: 10505493]. tolic click occurs earlier in children than in adults; that
is, it tends to be midsystolic rather than late systolic. Al-
though it is usually heard at the apex, it may be audible
3. Mitral Valve Prolapse at the left sternal border. A midsystolic or systolic mur-
mur after the click implies mitral insufficiency and is
much less common than isolated prolapse. The mur-
ESSENTIALS OF DIAGNOSIS mur is usually not typical of mitral insufficiency in that
& TYPICAL FEATURES it is not pansystolic and radiates to the sternum rather
than to the left axilla. Occasionally, a systolic “honk” is
• Midsystolic click best heard with the patient in the heard.
standing or squatting position.
• Occasional late systolic murmur. B. IMAGING
In the rare case of significant mitral insufficiency, the
left atrium may be enlarged. Left atrial enlargement
may produce a “double shadow” seen best on the AP
chest radiograph. In significant mitral regurgitation, the
General Considerations subcarinal angle will be increased to greater than 90 de-
Mitral valve prolapse (MVP) is a common entity associ- grees. Most chest radiographs are normal, and their use
ated with abnormal auscultatory findings in older pedi- is therefore largely unwarranted.
586 / CHAPTER 19

C. ELECTROCARDIOGRAPHY apex. Occasionally, only a middiastolic murmur can be

The ECG may be normal. Diffuse flattening or inver- heard. Rarely, no murmur at all is present. ECG shows
sion of T waves may be seen in the precordial leads. U right axis deviation, biatrial enlargement, and RVH.
waves are prominent. Chest pain on exertion is rare and Radiograph reveals left atrial enlargement and fre-
should be assessed with cardiopulmonary stress testing quently pulmonary venous congestion. Echocardiogra-
phy shows abnormal mitral valve structures with re-
D. ECHOCARDIOGRAPHY duced excursion and left atrial enlargement. Cardiac
Significant posterior systolic movement of the mitral catheterization reveals an elevated pulmonary capillary
valve leaflets to the atrial side of the mitral annulus dur- wedge pressure and pulmonary hypertension.
ing systole is diagnostic. Echocardiography will assess Mitral valve repair or mitral valve replacement with
the degree of myxomatous change of the mitral valve a prosthetic mitral valve may be performed even in the
and the degree of associated mitral insufficiency. young infant. Mitral valve repair is the preferred surgi-
cal option as mitral valve replacement is associated with
E. OTHER TESTING a poor outcome in very young children.
Invasive procedures are rarely indicated. Holter moni-
toring or event recorders may be useful in establishing Cor Triatriatum
the presence of ventricular dysrhythmias in patients
with palpitations. Cor triatriatum is a rare abnormality in which the pul-
monary veins join together in their confluence but the
Treatment & Prognosis confluence is not completely integrated into the left
atrium. The chamber communicates with the left atrium
Oral propranolol may be effective in treatment of coex- through an opening of variable size. The physiologic
isting arrhythmias. Prophylaxis for infectious endo- consequences of this condition are similar to those of mi-
carditis is indicated only in individuals with significant tral stenosis. The clinical findings depend on the size of
myxomatous change on echocardiography or with asso- the opening, and the size and position of any associated
ciated mitral insufficiency. atrial septal defect. If the opening is extremely small,
The natural course of this condition is largely un- symptoms develop very early in life. If the opening is
known. Twenty years of observation indicate that iso- larger, patients may be asymptomatic for a considerable
lated MVP in childhood is usually a benign entity. time. Echocardiography reveals a linear density in the left
Surgery for clinically significant mitral insufficiency is atrium with a gradient between the pulmonary venous
very rarely needed. chamber and the left atrium proper. Cardiac catheteriza-
tion may be needed if the diagnosis is in doubt. Finding
Bobkowski W et al. A prospective study to determine the signifi- a high pulmonary wedge pressure and a low left atrial
cance of ventricular late potentials in children with mitral pressure (if the catheter can be passed through the fora-
valve prolapse. Cardiol Young 2002;12(4):333 [PMID:
12206555].
men ovale into the true left atrial chamber) confirms the
diagnosis. Angiocardiographic studies will identify both
Freed LA et al: Prevalence and clinical outcome of mitral valve pro-
lapse. N Engl J Med 1999;341(1):1 [PMID: 10387935]. the proximal and distal left atrium. Surgical repair is al-
ways required in the presence of an obstructive mem-
brane, and long-term results are good. Coexisting mitral
4. Other Congenital Left valve abnormalities may be noted, including a supraval-
Heart Valvular Lesions val mitral ring or a dysplastic mitral valve.
Congenital Mitral Stenosis
Congenital Mitral Regurgitation
In congenital mitral stenosis, a rare disorder, the valve
leaflets are thickened and fused to produce a di- Congenital mitral regurgitation is a relatively rare ab-
aphragm-like or funnel-like structure with a central normality usually associated with other congenital heart
opening. When mitral stenosis is seen in conjunction lesions, such as congenitally corrected TGA, AV septal
with other left-sided obstructive lesions, such as subaor- defect, and anomalous left coronary artery. Isolated
tic stenosis and coarctation of the aorta, the complex is congenital mitral regurgitation is very rare. It is some-
known as Shone syndrome. Most patients develop times present in patients with Marfan syndrome, usu-
symptoms early in life with symptoms such as tachy- ally associated with a myxomatous prolapsing mitral
pnea, dyspnea, and failure to thrive. Physical examina- valve. Occasionally, congenital dilation of the valve ring
tion reveals an accentuated S1 and a loud pulmonary occurs with an otherwise normal valve. In other cases,
closure sound. No opening snap can be heard. In most the chordae tendineae are malformed, resulting in mi-
cases, a presystolic crescendo murmur is heard at the tral regurgitation.
 CARDIOVASCULAR DISEASES / 587

Congenital Aortic Regurgitation intervention is performed in patients of adult size when

the aortic root dimension reaches 50–55 mm. The ratio
Congenital aortic regurgitation is rare. The most com- of actual to expected aortic root dimension is used to de-
mon causes are bicuspid aortic valve, either uncompli- termine the need for surgery in the young child. Surgical
cated or with coarctation of the aorta; VSD with aortic options include replacement of the dilated aortic root
cusp prolapse and resultant aortic insufficiency; and with a composite valve graft (Bentall technique) or a
fenestration of the aortic valve cusp (one or more holes David procedure, wherein the patient’s own aortic valve
in the cusp). is spared and a Dacron tube graft is used to replace the
dilated ascending aorta. Although young age at diagno-
Eble BK et al: Mitral valve replacement in children: Predictors of sis was previously thought to confer a poor prognosis,
long-term outcome. Ann Thorac Surg 2003;76(3):853
[PMID: 12963215].
early diagnosis in association with close follow-up and
early initiation of medical therapy has been associated
with a favorable outcome in most patients. Ventricular
DISEASES OF THE AORTA dysrhythmias may contribute to the increased mortality
Aortic dilation and dissection may occur in childhood. seen in this patient group.
Although the aorta may not be dilated at birth, the
structural abnormality that predisposes to dilation is Turner Syndrome
presumed to be congenital in origin. Patients at risk for
Cardiovascular abnormalities are common in patients
progressive aortic dilation, and possible dissection, in-
with Turner syndrome. Patients are at risk for aortic
clude those with isolated bicuspid aortic valve, Marfan
dissection, typically during adulthood. Risk factors for
syndrome, Turner syndrome, and type IV Ehlers–Dan-
aortic dissection are usually present and include hyper-
los syndrome.
tension irrespective of cause, aortic dilation, bicuspid
aortic valve, and coarctation of the aorta. There have
Bicuspid Aortic Valve been rare reports of aortic dissection occurring in adult
Patients with bicuspid aortic valves have an increased Turner syndrome patients in the absence of any risk
incidence of aortic dilation and dissection, irrespective factors. Patients with Turner syndrome require routine
of the presence of aortic stenosis. Histologic examina- follow-up during adolescence and adulthood to moni-
tion demonstrates cystic medial degeneration of the tor this potentially lethal complication.
aortic wall, probably as a result of smooth muscle cell
apoptosis. Patients with isolated bicuspid aortic valve Bonderman D et al: Mechanisms underlying aortic dilation in con-
therefore require regular follow-up even in the absence genital aortic valve malformation. Circulation 1999;99(16):
2138 [PMID: 10217654].
of aortic insufficiency or aortic stenosis. Significant aor-
Bordeleau L et al: Aortic dissection and Turner’s syndrome: A re-
tic root dilation requiring surgical intervention, in the view of the literature. J Emerg Med 1998;16(4):593 [PMID:
absence of aortic stenosis, typically does not occur until 9696176].
adulthood. Yetman AT et al: Comparison of outcome of the Marfan’s syn-
drome in patients diagnosed at < or > 6 years of age. Am
Marfan Syndrome J Cardiol 2003;91(1):102 [PMID: 12505586].
Yetman AT et al: Long-term outcome in patients with Marfan’s
Marfan syndrome is an autosomal dominant disorder of syndrome: Is aortic dissection the only cause of sudden death?
connective tissue secondary to a mutation in the fib- J Am Coll Cardiol 2003;41(2):329 [PMID: 12535830].
rillin-1 gene. The incidence of spontaneous mutations is
25%, and thus family history is not always helpful. Pa- CORONARY ARTERY ABNORMALITIES
tients are diagnosed by the Ghent criteria and must
have, at a minimum, major involvement of two body A number of anomalies involve the origin, course, and
systems plus involvement of a third body system or a distribution of the coronary arteries. The only abnor-
positive family history. Body systems that may be in- mality seen with any regularity, which has disastrous
volved include cardiovascular, ocular, musculoskeletal, consequences if unrecognized, is anomalous origin of
pulmonary, and integumentary. Cardiac manifestations the left coronary artery.
include aortic root dilation and MVP, which may even
be present at birth. Patients are at risk for aortic dilation 1. Anomalous Origin of the Left
and dissection and are restricted from competitive ath-
letics, contact sports, and isometric activities. Beta-
Coronary Artery
blockers or ACE inhibitors are used to lower blood pres- In this condition, the left coronary artery arises from
sure and slow the rate of aortic dilation. Elective surgical the pulmonary artery rather than the aorta. In the
588 / CHAPTER 19

neonatal period, while the pulmonary arterial pressure E. CARDIAC CATHETERIZATION AND
is relatively high, the perfusion of the left coronary ANGIOCARDIOGRAPHY
artery is adequate and the child is asymptomatic. How- A small left-to-right shunt (a result of the flow of blood
ever, by age 2 months, the pulmonary arterial pressure from the right through the left coronary artery and into
falls, resulting in a progressive decrease in the myocar- the pulmonary artery) can sometimes be detected.
dial perfusion supplied by the left coronary artery. Is- Cineangiocardiography after injection of contrast into
chemia and infarction of the LV occur. These infants the root of the aorta fails to show the origin of the left
present at age 2–4 months with severe CHF due to LV coronary artery. A large right coronary artery fills directly
dysfunction and mitral insufficiency. Immediate from the aorta, and the contrast material flows from the
surgery is needed, after the child is stabilized with anti- right coronary system via collaterals into the left coronary
congestive therapy, to bring aortic flow into the left arteries and finally into the pulmonary artery.
coronary system. The surgery is relatively high risk, es-
pecially if infarction of the papillary muscles supporting
the mitral apparatus has occurred. Mitral valve replace- Treatment & Prognosis
ment is sometimes needed. Medical management with anticongestives and afterload
reduction fails to correct the anatomic defect and should
Clinical Findings not delay surgical intervention. Early surgery is required
to give a two coronary system. Simple ligation of the left
A. SYMPTOMS AND SIGNS coronary artery or subclavian to coronary artery anasto-
Patients appear healthy at birth. Growth and develop- mosis (without cardiopulmonary bypass) offer poor
ment are relatively normal for a few months, although long-term results. Because survival after coronary
detailed questioning of the parents often discloses a his- surgery is highly dependent on the degree of mitral in-
tory of intermittent episodes of abdominal pain, pallor, sufficiency, a decision must be made prior to bypass
and sweating, especially during or after feeding. These whether to leave or replace the mitral valve.
episodes are often thought to be secondary to colic but The prognosis is guarded. No therapeutic modality
in fact are anginal attacks similar to those seen in adults. has been shown to be superior in follow-up studies of
On physical examination, the patients are usually survivors.
well developed and well nourished. The pulses are typi-
cally weak but equal throughout. A prominent left pre- Michielon G et al: Anomalous coronary artery origin from the pul-
monary artery: Correlation between surgical timing and left
cordial bulge is present. The pansystolic murmur of mi- ventricular function recovery. Ann Thorac Surg
tral regurgitation is frequently present, although a 2003;76(2):581 [PMID: 12902108].
murmur need not be present to make this diagnosis.

B. IMAGING CYANOTIC CONGENITAL HEART

Chest radiographs show cardiac enlargement and left DISEASE
atrial enlargement and may show pulmonary venous Tetralogy Of Fallot
congestion.

C. ELECTROCARDIOGRAPHY ESSENTIALS OF DIAGNOSIS

The ECG is very helpful. There are T wave inversions & TYPICAL FEATURES
in leads I and aVL. The precordial leads show T wave
inversions from V4 to V7. Deep, and often wide, Q • Cyanosis after the neonatal period.
waves are present in leads I, aVL, and sometimes in
• Hypoxemic spells during infancy.
V4–V6. These findings of myocardial infarction are sim-
ilar to those in adults. • Right-sided aortic arch in 25% of patients.
• Systolic ejection murmur at the upper left sternal
D. ECHOCARDIOGRAPHY border.
The diagnosis can be made with two-dimensional tech-
niques by visualizing a single large right coronary artery
arising from the aorta in infants with severe LV dys-
function and mitral insufficiency. The anomalous left General Considerations
coronary artery may be seen arising from the main pul-
monary artery. The presence of flow reversal confirms In ToF, a VSD is present and obstruction to RV out-
the presence of an anomalous left coronary artery. flow occurs so that the intracardiac shunt is typically
 CARDIOVASCULAR DISEASES / 589

from right to left. This is the most common cyanotic Hypoxemic spells, also called cyanotic spells or (Tet)
lesion, accounting for 10% of all cases of congenital tetralogy spells, are one of the hallmarks of severe ToF
heart disease. The VSD is usually located in the mem- and are characterized by the following signs and symp-
branous portion of the septum but may be surrounded toms: (1) sudden onset of cyanosis or deepening of
completely by muscular tissue, and it is quite large. The cyanosis; (2) sudden onset of dyspnea; (3) alterations in
obstruction to RV outflow may be primarily at the in- consciousness, encompassing a spectrum from irritabil-
fundibular level (in 25–50% of cases), at the valvular ity to syncope; and (4) decrease in intensity or even dis-
level alone (rarely), or at both levels (most commonly). appearance of the systolic murmur. These episodes may
The primary embryologic abnormality is in the septa- begin in the neonatal period, but most commonly they
tion of the conus and truncus arteriosus with anterior start at age 4–6 months. Acute treatment of cyanotic
deviation of the conus into the RV outflow tract, result- spells consists of giving oxygen and placing the patient
ing in an enlarged overriding aorta and hypoplasia of in the knee-chest position. Acidosis, if present, should
the pulmonary outflow. Experimental lesions in specific be corrected with intravenous sodium bicarbonate.
loci of ectodermal (neural crest) tissue that migrate to Morphine sulfate should be administered cautiously by
the conus can reproduce the defects seen in ToF. The a parenteral route in a dosage of 0.1 mg/kg. Propra-
term “tetralogy” has been used to describe this combi- nolol, 0.1–0.2 mg/kg intravenously, is useful. Chronic
nation of lesions, because RVH is always present and a (daily) prophylaxis of cyanotic spells with propranolol,
varying degree of overriding of the aorta occurs in addi- 1 mg/kg orally every 4 hours while awake, remains con-
tion to the VSD and pulmonic and subpulmonic pul- troversial; however, in a significant number of patients,
monic stenosis. The overriding is caused by the anterior this regimen has prevented subsequent spells and made
deviation of the conus, which brings the anterior wall it possible to delay surgery. The degree of cyanosis in
of the aorta forward with it. A right-sided aortic arch is ToF is variable. The fingers and toes show varying de-
present in 25% of cases, and an ASD occurs in 15%. grees of clubbing depending on the age of the child and
Obstruction to RV outflow plus a large VSD results the severity of cyanosis.
in a right-to-left shunt at the ventricular level and de- On examination of the heart, an RV lift is palpable.
saturation of the arterial blood. The degree of desatura- S1 is normal; occasionally, an ejection click is eveident
tion depends on the resistance to outflow from the RV, at the apex that is aortic in origin. S2 is predominantly
and the systemic vascular resistance. The greater the ob- aortic and single. A grade II–IV/VI, rough, ejection-
struction, and the lower the systemic vascular resis- type systolic murmur is present that is maximal at the
tance, the greater the right-to-left shunting. Although left sternal border in the third intercostal space and that
the patient may be deeply cyanotic, the amount of pres- radiates well to the back.
sure the RV can develop is limited to that of the sys-
temic (aortic) pressure because the VSD is unrestrictive. B. LABORATORY FINDINGS
The RV is usually able to maintain this level of pressure The hemoglobin, hematocrit, and red blood cell count
without developing heart failure. A high association be- are usually elevated, depending on the degree of arterial
tween ToF and deletions in the long arm of chromo- oxygen desaturation.
some 22 (22q11) has now been established, and as
many as 15% of children with tetralogy appear to have C. IMAGING
this genetic abnormality.
Chest radiographs show a heart of normal size. Indeed,
the radiograph is sometimes interpreted as entirely nor-
mal. However, the RV is hypertrophied, which is often
Clinical Findings shown in the posteroanterior projection by an upturn-
A. SYMPTOMS AND SIGNS ing of the apex (boot-shaped heart). The main pul-
The clinical findings vary depending on the degree of monary artery segment is usually concave, and a right
RV outflow obstruction. Patients with a mild degree of aortic arch is present in 25% of cases, with the aortic
obstruction are only minimally cyanotic or may even be knob to the right of the trachea. The pulmonary vascu-
acyanotic. Those with maximal obstruction are deeply lar markings are usually decreased.
cyanotic from birth. Few children are asymptomatic.
Most have cyanosis by age 4 months, and the cyanosis D. ELECTROCARDIOGRAPHY
usually is progressive. Growth and development are not The cardiac axis is to the right, ranging from +90 to
typically retarded, but easy fatigability and dyspnea on +180 degrees. The P waves are usually normal, al-
exertion are common. When these children learn to though evidence may indicate slight right atrial hyper-
walk, they frequently squat suddenly to increase sys- trophy. RVH is always present, but RV strain patterns
temic vascular resistance to ward off cyanotic spells. are rare.
590 / CHAPTER 19

E. ECHOCARDIOGRAPHY trend is toward earlier repair based on the severity of

Two-dimensional imaging is diagnostic, revealing symptoms. Patients may be repaired in the neonatal pe-
thickening of the RV wall, with overriding of the aorta riod, although, if asymptomatic, surgery is deferred
and a large subaortic VSD. Furthermore, obstruction at until 6–8 months of age. During surgery, the VSD is
the level of the infundibulum and pulmonary valve can closed and the obstruction to RV outflow removed.
be identified, and the size of the proximal pulmonary The surgical death rate varies from 1% to 3%. The
arteries can be measured. The anatomy of the coronary major limiting anatomic feature of total correction is
arteries may be visualized. the size of the pulmonary arteries.

F. CARDIAC CATHETERIZATION AND Course & Prognosis

ANGIOCARDIOGRAPHY
Infants with the most severe form of ToF are usually
Cardiac catheterization reveals the presence of a right- deeply cyanotic at birth. Hypoxemic spells may occur
to-left shunt in most cases. Arterial desaturation of during the neonatal period. Death is extremely rare
varying degrees is present. The right-to-left shunt oc- during a severe hypoxemic spell. These children require
curs at the ventricular level. The RV pressure is at sys- early surgery, either a Blalock–Taussig shunt or primary
temic levels, and the pressure tracing in the RV is iden- correction.
tical to that of the LV. The pulmonary artery pressure All children with ToF require open-heart surgery.
is low. The pressure gradients may be noted at the Complete repair before age 5 years usually results in fair
valvular level or the infundibular level (or both). to good function, although patients occasionally die as
Cineangiocardiography is helpful. Injection of con- a result of ventricular dysrhythmias. A competent pul-
trast into the RV reveals the RV outflow obstruction monary valve without a dilated RV appears to diminish
and the right-to-left shunt at the ventricular level. The arrhythmias and enhance exercise performance.
major indications for cardiac catheterization are to es-
tablish coronary artery and distal pulmonary artery
Bacha EA et al: Long-term results after early primary repair of
anatomy. In addition, some patients may be palliated tetralogy of Fallot. J Thorac Cardiovasc Surg 2001;122:154
by balloon dilation of the RV outflow tract during in- [PMID: 11436019].
fancy to improve the pulmonary blood flow, thereby Botto LD et al. A population-based study of the 22q11.2 deletion:
delaying surgical intervention. Phenotype, incidence and contribution to major birth defects
in the population. Pediatrics 2003;112(1 Pt 1):101 [PMID:
12837874].
Treatment Mulder TJ et al. A multicenter analysis of the choice of initial surgi-
A. PALLIATIVE TREATMENT cal procedure in tetralogy of Fallot. Pediatr Cardiol 2002;
23(6):580 [PMID: 12530488].
Palliative treatment is performed at some centers for Therrien J et al: Impact of pulmonary valve replacement on ar-
small infants who have severe symptoms (severe rhythmia propensity late after repair of tetralogy of Fallot.
cyanosis, frequent severe hypoxic spells) and in whom Circulation 2001;103(20):2489 [PMID: 11369690].
complete correction is deemed too risky. Medical
(chronic oral β-blocking agents) or, more often, surgi- PULMONARY ATRESIA WITH
cal (creation of a systemic arterial to pulmonary arterial
anastomosis) palliation can be used. Balloon angio- VENTRICULAR SEPTAL DEFECT
plasty is being used for palliation in some centers. In This condition consists of complete atresia of the pul-
this procedure the pulmonic valve and the entire RV monary valve in association with VSD. Essentially, it is
outflow tract are dilated in order to reduce RV outflow an extreme form of ToF. Because there is no antegrade
tract obstruction and improve pulmonary artery flow from the RV into the pulmonary artery, the pul-
growth. The most common surgical palliation is the monary blood flow must be derived either from a PDA
creation of a GoreTex shunt from the subclavian artery or from aortopulmonary collateral arteries.
to the ipsilateral pulmonary artery (modified The clinical picture depends entirely on the size of
Blalock–Taussig shunt). This operation can be done the ductus and the collateral channels. If they are large,
with very low likelihood of mortality and with no sig- patients may be quite stable. If pulmonary blood flow is
nificant distortion of the pulmonary arteries. low, severe hypoxia results, and immediate palliation is
required. Newborns are stabilized with intravenous
B. TOTAL CORRECTION prostaglandin E1 (PGE1) to maintain patency of the
The timing of open-heart surgery for repair of ToF ductus arteriosus while being prepared for surgery.
ranges from birth to age 2 years, varying with the expe- Once the child is stabilized, a decision must be made
rience of each treatment center. The current surgical about whether to do a palliative Blalock–Taussig shunt
 CARDIOVASCULAR DISEASES / 591

or to proceed with primary correction. In most centers, Clinical Findings

a shunt is performed in the newborn period, with open-
heart surgery planned for age 9–18 months. A. SYMPTOMS AND SIGNS
Echocardiography or cardiac catheterization and an- Although patients may be normal at birth, they are usu-
giocardiography are diagnostic. A corrective surgical ally cyanotic. Cyanosis progresses as the ductus arterio-
procedure that has been successful in patients with ade- sus closes. A blowing systolic murmur resulting from
quate-sized pulmonary arteries consists of closing the the associated PDA may be heard at the pulmonary
VSD and inserting a homograft from the RV to the area. In addition, a pansystolic murmur is often heard
main pulmonary artery. Success depends on precise def- at the lower left sternal border, because most of these
inition of pulmonary arterial and collateral blood sup- children develop significant tricuspid insufficiency.
ply to the lung and, if needed, prior unifocalization of
segments with dual arterial blood supply into a single B. IMAGING
pulmonary arterial tree. The heart size may vary from small to markedly en-
larged, depending on the degree of tricuspid insuffi-
Mair DD, Puga FJ: Management of pulmonary atresia with ven- ciency. With striking tricuspid insufficiency, right atrial
tricular septal defect. Curr Treat Options Cardiovasc Med enlargement may be massive and the cardiac silhouette
2003;5(5):409 [PMID: 12941209]. may virtually fill the chest.

PULMONARY ATRESIA WITH INTACT C. ELECTROCARDIOGRAPHY

VENTRICULAR SEPTUM ECG reveals an axis that is leftward for age (45–90 de-
grees) in the frontal plane. Evidence for right atrial en-
largement is usually striking. There is LV dominance
ESSENTIALS OF DIAGNOSIS for age with reduced RV forces.
& TYPICAL FEATURES D. ECHOCARDIOGRAPHY
• Cyanosis at birth. Echocardiography shows absence of the pulmonary
valve, with varying degrees of hypoplasia of the RV cav-
• Chest radiograph with a concave pulmonary ity and tricuspid annulus. The severity of tricuspid re-
artery segment and the apex tilted upward. gurgitation correlates with RV size.
E. CARDIAC CATHETERIZATION AND
ANGIOCARDIOGRAPHY
General Considerations RV pressure is high and is almost always suprasystemic.
A cineangiocardiogram in the RV reveals no filling of
In this uncommon condition, the pulmonary valve is the pulmonary artery from the RV. It also demonstrates
atretic. The pulmonic annulus usually has a small di- the size of the RV chamber, relative hypoplasia of the
aphragm consisting of the fused valve cusps. The ven- components of the tripartite RV, and the presence or
tricular septum is intact. The main pulmonary artery absence of tricuspid regurgitation. Approximately 15%
segment is somewhat hypoplastic but almost always of children with pulmonic atresia and intact ventricular
present. Although the RV is always reduced in size in septum have sinusoids between the RV and the coro-
this condition, the degree of reduction is variable. This nary arteries. The presence of these sinusoids indicates
factor is critical because some children with pulmonic that the coronary circulation may depend on RV flow;
atresia may have an adequate ventricle for ultimate this situation is associated with a high risk for sudden
“two-ventricular” repair; therefore, the assessment of death.
the adequacy of the RV is important. The RV has three
component parts (inlet, trabecular, and outlet), and the Treatment & Prognosis
absence of any one of these three components makes
the ultimate use of the RV extremely unlikely. Even As in pulmonary atresia with VSD, a PGE1 infusion is
with all three components, some RVs are inadequate. used to stabilize the patient and maintain patency of
Following birth, the pulmonary circulation is main- the ductus until surgery can be performed. Surgery
tained by the PDA. Although a bronchial–pulmonary should be undertaken as soon as possible. A Rashkind
collateral network may be present, it is usually insuffi- balloon atrial septostomy is performed, depending on
cient to maintain the pulmonary circulation. Accord- RV size, to open up the communication across the
ingly, a continuous infusion of PGE1 must be started as atrial septum. If the RV is tripartite and an eventual
soon as possible after birth to maintain ductal patency. two-chamber repair is planned, the pulmonary valve
592 / CHAPTER 19

plate is opened during cardiac catheterization in the tion exists between the right atrium and the RV. Tri-
newborn period to allow antegrade flow from the RV cuspid atresia is divided into two types, depending on
to the pulmonary artery and to encourage RV cavity the relationship of the great vessels (Table 19–14).
growth. If the RV is inadequate, significant sinusoids Because no direct communication exists between the
are present, or the pulmonic valve cannot be opened right atrium and the RV, the entire systemic venous re-
successfully in the catheterization laboratory, an imme- turn must flow through the atrial septum (either an
diate Blalock–Taussig shunt is performed to establish ASD or patent foramen ovale) into the left atrium.
pulmonary blood flow. Later in infancy, a communica- Thus the left atrium receives both the systemic venous
tion between the RV and pulmonary artery can be cre- return and the pulmonary venous return. Complete
ated on bypass in an attempt to stimulate RV cavity mixing occurs in the left atrium, resulting in a greater
growth. If RV dimensions or function are inadequate or lesser degree of arterial desaturation.
for a two-ventricular repair, a one-ventricular systemic As a result of the lack of direct communication, the
venous to pulmonary artery palliation is indicated development of the RV depends on the presence of a
(Fontan procedure). Children with significant sinusoids left-to-right shunt at the ventricular level. Therefore,
receive a Blalock–Taussig shunt as immediate treat- severe hypoplasia of the RV occurs in those forms in
ment, but they are often considered for cardiac trans- which there is no VSD or in which the VSD is small.
plantation if they are deemed at risk for coronary insuf-
ficiency and sudden death.
The prognosis in this condition remains guarded. Clinical Findings
Our overall experience strongly favors opening the
atretic valve in the catheterization laboratory in the A. SYMPTOMS AND SIGNS
newborn period if possible. If this is impossible, a In most patients with tricuspid atresia, symptoms de-
Blalock–Taussig shunt should be placed. Ultimate velop early in infancy. Except in patients whose pul-
plans for a two-ventricular repair, a Fontan procedure, monary blood flow is high, cyanosis is present at birth.
or cardiac transplantation depend on the anatomy. Growth and development are poor, and the infant usu-
ally exhibits fatigability on feeding, tachypnea, dyspnea,
Humpl T et al: Percutaneous balloon valvotomy in pulmonary anoxic spells, and evidence of right heart failure. Pa-
atresia with intact ventricular septum: Impact on patient care. tients with marked increase in pulmonary blood flow—
Circulation 2003;108(7):826 [PMID: 12885744]. types 1(c) and 2(b)—may develop evidence of left heart
Minnich LL et al: Usefulness of the preoperative tricuspid/mitral failure as well.
valve ratio for predicting outcome in pulmonary atresia with Digital clubbing is present in older children. S1 is
intact ventricular septum. Am J Cardiol 2000;85(11):
1325 [PMID: 10831948].
normal. S2 is most often single. A murmur is usually
Powell AJ et al: Outcome in infants with pulmonary atresia, intact
present, although it is variable. It ranges from grade II
ventricular septum, and right ventricular-dependent coronary to grade III/VI in intensity and usually is a harsh blow-
circulation. Am J Cardiol 2000;86(11):1272 [PMID: ing murmur heard best at the lower left sternal border.
11090809].

TRICUSPID ATRESIA Table 19–14. Tricuspid atresia.

Type 1: Without transposition Type 2: With transposi-

ESSENTIALS OF DIAGNOSIS of the great arteries tion of the great arteries
& TYPICAL FEATURES
(a) No ventricular septal (a) With ventricular septal
• Marked cyanosis present from birth. defect; hypoplasia or defect and pulmonary
atresia of the pulmonary stenosis
• ECG with left axis deviation, right atrial enlarge- artery; patent ductus (b) With ventricular septal
ment, and LVH. arteriosus defect but without
(b) Small ventricular septal pulmonary stenosis
defect; pulmonary
stenosis; hypoplastic
pulmonary artery
General Considerations (c) Large ventricular septal
This relatively rare condition (< 1% of cases of congeni- defect and no pulmonary
stenosis; normal-sized
tal heart disease) is characterized by complete atresia of
pulmonary artery
the tricuspid valve. As a result, no direct communica-
 CARDIOVASCULAR DISEASES / 593

B. IMAGING The prognosis for all patients with tricuspid atresia

Chest radiographic findings are variable. The heart is depends on the achievement of a balance of pulmonary
slightly to markedly enlarged. The main pulmonary blood flow that permits adequate oxygenation of the
artery segment is usually small or absent. The size of the tissues without producing CHF. The long-term prog-
right atrium varies from moderately to massively en- nosis for children treated by the Fontan procedure is
larged, depending on the size of the communication at unknown. In the short term, the best results for the
the atrial level. The pulmonary vascular markings are Fontan procedure occur in children with low pul-
usually decreased, although in types 1(c) and 2(b) they monary artery pressures prior to open-heart surgery.
are increased.
Fogel MA et al: Caval contribution to flow in the branch pul-
C. ELECTROCARDIOGRAPHY monary arteries of Fontan patients with a novel application of
magnetic resonance presaturation pulse. Circulation 1999;
The ECG is usually helpful. It shows left axis deviation 99(9):1215 [PMID: 10069790].
with a counterclockwise loop in the frontal plane. The
Mair DD et al: The Fontan procedure for tricuspid atresia: Early
P waves are tall and peaked, indicative of right atrial hy- and late results of a 25-year experience with 216 patients.
pertrophy. LVH or LV dominance is found in almost J Am Coll Cardiol 2001;37(3):933 [PMID: 11693773].
all cases. RV forces on the ECG are usually low or ab-
sent.
HYPOPLASTIC LEFT HEART SYNDROME
D. ECHOCARDIOGRAPHY
M-mode and two-dimensional methods are diagnostic
and show absence of the tricuspid valve, the relation- ESSENTIALS OF DIAGNOSIS
ship between the great arteries, and the size of the pul- & TYPICAL FEATURES
monary arteries.
• Mild cyanosis at birth. Minimal auscultatory find-
E. CARDIAC CATHETERIZATION AND ings.
ANGIOCARDIOGRAPHY
• Rapid onset of shock with ductal closure.
This technique reveals the large right-to-left shunt at
the atrial level and desaturation of the left atrial blood.
Because of the complete mixing in the left atrium, oxy-
gen saturations in the LV, RV, pulmonary artery, and
aorta are identical to the that in left atrium. The right General Considerations
atrial pressure is increased. LV and systemic pressures
are normal. The catheter cannot be passed through the Hypoplastic left heart syndrome includes a number of
tricuspid valve from the right atrium to the RV. A bal- conditions in which lesions of the left heart result in hy-
loon atrial septostomy is performed if a restrictive fora- poplasia of the LV. The syndrome occurs in 1.4–3.8%
men ovale is present. of infants with congenital heart disease.
The most common lesions making up this syn-
drome are mitral atresia, aortic atresia, or both. Follow-
Treatment & Prognosis ing birth, survival depends on a PDA because the ante-
In infants with high pulmonary artery flow, conven- grade flow into the systemic circulation is inadequate
tional anticongestive therapy should be given until the and the ductus arteriosus provides flow to the aorta.
infant begins to outgrow the VSD. Occasionally, a pul- Children with hypoplastic left heart syndrome are usu-
monary artery band is needed to protect the pulmonary ally stable at birth, but they deteriorate rapidly as the
bed in preparation for a Fontan procedure. A Fontan ductus starts to close later in the first week of life. Un-
procedure (connection of the systemic venous return to treated, the average age at death is 5–7 days. In rare in-
the pulmonary artery) is performed when increasing stances, the ductus will remain widely patent on its
cyanosis occurs, typically at age 2–4 years. own, and children will survive for months without
In infants with diminished pulmonary blood flow, PGE1 therapy.
PGE1 is infused until an aortopulmonary shunt can be
performed. The Fontan procedure is frequently per- Clinical Findings
formed in stages; a Glenn procedure (superior vena
cava to pulmonary artery anastomosis) is performed A. SYMPTOMS AND SIGNS
with concomitant ligation of the aortopulmonary shunt Children with hypoplastic left heart syndrome appear
at age 3–9 months, and a completion Fontan procedure stable at birth, because the ductus is widely patent.
is performed at age 1–4 years. They deteriorate rapidly when the ductus starts to close
594 / CHAPTER 19

with findings first of CHF, followed almost immedi- heart syndrome remains one of the most challenging le-
ately by clinical shock with acidosis secondary to inade- sions in pediatric cardiology.
quate systemic perfusion.
Mahle WT et al: Impact of prenatal diagnosis on survival and early
B. IMAGING neurologic morbidity in neonates with the hypoplastic left
heart syndrome. Pediatrics 2001;107(6):1277 [PMID:
Chest radiographic findings at presentation are those of 11389243].
cardiac enlargement with severe pulmonary venous Mosca RS et al: Early results of the Fontan procedure in one hun-
congestion. dred consecutive patients with hypoplastic left heart syn-
drome. J Thorac Cardiovasc Surg 2000;119(6):1110 [PMID:
C. ELECTROCARDIOGRAPHY 10838526].
The ECG demonstrates right axis deviation, right atrial Tworetzky W et al: Improved surgical outcome after fetal diagnosis
of hypoplastic left heart syndrome. Circulation 2001;103(9):
hypertrophy, and RVH with relative paucity of LV 1269 [PMID: 11238272].
forces and absence of a Q wave in lead V6. A QR pat-
tern is often seen in lead V1.
TRANSPOSITION OF THE GREAT
D. ECHOCARDIOGRAPHY ARTERIES
Echocardiography is diagnostic and eliminates the need
for cardiac catheterization. A diminutive aorta and LV ESSENTIALS OF DIAGNOSIS
with an atretic mitral valve in the presence of a normal
and easily definable tricuspid valve are diagnostic. The & TYPICAL FEATURES
systemic circulation depends on the PDA. Color-flow
Doppler imaging shows retrograde flow in the ascend- • Cyanotic newborn without respiratory distress.
ing aorta. • More common in males.

Treatment & Prognosis

PGE1 infusion is essential initially because systemic cir- General Considerations
culation depends on a PDA. Further management de-
pends on balancing pulmonary and systemic blood flow Transposition of the great arteries (d-TGA or complete
because the RV provides both. Within a few days of TGA) is the second most common cyanotic congenital
birth, the pulmonary resistance falls, favoring pul- heart disease, accounting for 5% of all cases of congeni-
monary overcirculation and compromised systemic per- tal heart disease. The male-to-female ratio is 3:1. The
fusion. Therapy must be directed to increasing pul- disorder is caused by an embryologic abnormality in the
monary vascular tone using hypoxia or hypercapnic spiral division of the truncus arteriosus, in which the
ventilation. We now use nitrogen to decrease the in- aorta arises from the RV and the pulmonary artery
spired oxygen content below 21%. This therapy, which from the LV. In 60% of cases only the two usual new-
must be carefully monitored, results in an increase in born cardiac connections (patent foramen ovale and
pulmonary arterial tone and systemic perfusion. Nitro- PDA) are present, but VSDs, pulmonic stenosis, coarc-
gen is blended with room air, and the delivered O2 con- tation of the aorta, or aortic stenosis occurs in a signifi-
tent is monitored continuously. We typically start at cant number of patients. Left unrepaired, transposition
16–17% inspired oxygen with a goal of maintaining is associated with a high incidence of early pulmonary
systemic O2 saturation at 65–80% to balance the pul- vascular obstructive disease. TGA can be classified into
monary and systemic blood flows. two types (Table 19–15).
Shortly after birth a decision must be made between Because the aorta arises directly from the RV, sur-
several surgical options. In the Norwood procedure, the vival would be impossible without mixing between the
RV is used as the systemic ventricle while an aortopul- systemic and pulmonary circulations. Oxygenated
monary bypass is created for pulmonic flow. Alterna- blood from the pulmonary veins must reach the sys-
tively, the child can be listed for orthotopic cardiac temic arterial circuit. In patients with an intact ventric-
transplantation. Children who have a Norwood proce- ular septum, mixing occurs at the atrial and ductal lev-
dure (and subsequent Glenn anastomosis and comple- els. However, in most patients, these communications
tion Fontan procedure) or who are listed for receipt of a are small, and the ductus arteriosus closes shortly after
donor heart have a 50–60% chance for 5–year survival birth. These patients are therefore severely cyanotic. Pa-
at the best centers. Although this is a major improve- tients with a VSD may have better mixing and less
ment over nonsurgical intervention, hypoplastic left cyanosis. Patients with a VSD and pulmonary stenosis
 CARDIOVASCULAR DISEASES / 595

Table 19–15. Complete (D) transposition of the C. ELECTROCARDIOGRAPHY

great arteries. Because the newborn ECG normally has RV predomi-
nance, the ECG in transposition is of little help.
Type 1: With intact Type 2: With ventricular
ventricular septum septal defect D. ECHOCARDIOGRAPHY
(a) Without pulmonary (a) With pulmonary stenosis Two-dimensional imaging and Doppler evaluation ac-
stenosis (b) With pulmonary vascular curately describe the anatomy and physiology of trans-
(b) With pulmonary stenosis obstruction position. The abnormal relationship of the great arteries
subvalvular or valvular (c) Without pulmonary vas- is the hallmark of transposition on echocardiography. If
(or both) cular obstruction (normal clinically indicated, the balloon atrial septostomy may
pulmonary vascular be performed with echocardiographic guidance.
resistance)
E. CARDIAC CATHETERIZATION AND
ANGIOCARDIOGRAPHY
(types 2[a] and 2[b]) are usually severely cyanotic be- Cardiac catheterization is both diagnostic and thera-
cause of the limited blood flow to the lungs. Patients peutic in this malformation. If complete transposition
with a VSD and normal pulmonary vascular resistance of the great arteries exists and if there are two well-de-
(type 2[c]) have the least cyanosis but often develop veloped ventricles, a Rashkind balloon atrial sep-
heart failure early because of high pulmonary blood tostomy is performed to open the atrial septum unless a
flow. true ASD exists. The coronary anatomy is delineated by
ascending aortography.
Clinical Findings
A. SYMPTOMS AND SIGNS Treatment
Many of the neonates are large, some weighing 4 kg at Early corrective surgery is recommended for transposi-
birth, and most are severely cyanotic at birth. Infants tion. The arterial switch operation (ASO) is performed
with an intact ventricular septum are often quite strik- at age 4–7 days. The arteries are switched in the anteri-
ing in appearance because of their profound cyanosis or chest, and the coronaries are reimplanted into the
(unresponsive to increasing the ambient O2), the ab- neoaorta. Small associated VSDs may be left to close on
sence of a significant murmur, their lack of respiratory their own, but large VSDs are always closed at this
distress, and their large size. Only infants with a large time. The atrial septum is also closed. The ASO has re-
VSD will be less cyanotic, and they usually have a placed the atrial switch procedures (Mustard and Sen-
prominent murmur. The findings on cardiovascular ex- ning operations), which were previously performed. Be-
amination depend on the intracardiac defects. Patients cause the ASO must be performed while the LV
with type 1(a) defects have only soft murmurs or none musculature can still support systemic blood flow, it is
at all. S1 is usually normal in these patients. S2 is single rarely delayed beyond age 14 days in infants with an in-
and accentuated as the aortic valve is anterior. Patients tact ventricular septum or small VSD. If a large, unre-
with type 1(b) defects have loud obstructive systolic strictive VSD is present that maintains LV pressure at
murmurs that are maximal at the second and third in- systemic levels, corrective surgery can be delayed for a
tercostal spaces and the left sternal border, radiating few months. Surgery should still be performed by age
well to the first and second intercostal spaces. Patients 3–4 months because of the high risk of early pulmonary
with type 2(a) defects have a murmur of pulmonary vascular disease associated with transposition.
stenosis (obstructive systolic murmur at the base of the Survival after the ASO is now greater than 95% in
heart, best heard to the right of the sternum). Those major centers. In addition, the switch procedure greatly
with type 2(c) defects have a systolic murmur along the shortens the time that the child remains severely cyan-
lower sternal border and a mitral diastolic flow murmur otic before corrective surgery. Early relief of cyanosis
at the apex. may improve the developmental outcome for children
with transposition. Finally, the switch procedure leaves
B. IMAGING the LV as the systemic ventricle. The older atrial correc-
The chest radiograph in transposition is often nonspe- tive procedures (Senning and Mustard procedures) put
cific. Sometimes, however, there is an “egg on a string” the RV in this role, there was a significant incidence of
appearance because the aorta is directly anterior to the late RV failure. Since the LV is designed for systemic
main pulmonary artery, giving the image of a narrow pressures, late failure of the LV after the ASO has not
mediastinum. been reported.
596 / CHAPTER 19

Bellinger DC et al: Developmental and neurological status of chil- If the VSD is subaortic and no pulmonary stenosis is
dren at 4 years of age after heart surgery with hypothermic present, a large left-to-right shunt is present and the
circulatory arrest or low flow cardiopulmonary bypass. Circu-
lation 1999;100(5):526 [PMID: 10430767].
clinical picture resembles that of a large VSD. Early pri-
mary correction, with the VSD patch fashioned to the
Singh TP et al: Assessment of progressive changes in exercise per-
formance in patients with a systemic right ventricle following anterior aortic root, is very successful. If a subaortic
atrial switch repair. Pediatr Cardiol 2001;22(3):210 [PMID: VSD and pulmonic and subpulmonic stenosis are pre-
11343144]. sent, the physiology and the clinical management are
Wernovsky G et al: Factors influencing early and late outcome of the same as in ToF. However, if the VSD is subpul-
the arterial switch operation for transposition of the great ar- monic (Taussig–Bing malformation), the presentation
teries. J Thorac Cardiovasc Surg 1995;109(2):289 [PMID: and management are analogous to those of an infant
7583882. with transposition and an unrestrictive VSD.
In all forms of double-outlet RV, echocardiography
CONGENITALLY CORRECTED with Doppler flow assessment is useful in clarifying the
TRANSPOSITION OF THE GREAT anatomy and physiology. Preoperative cardiac catheter-
ization and angiocardiography are used if questions re-
ARTERIES main about the pulmonary or coronary arteries, or in
Congenitally corrected transposition of the great arter- children with the Taussig–Bing malformation who
ies (ccTGA or l-TGA) is a relatively uncommon form have severe cyanosis requiring balloon atrial septostomy
of congenital heart disease that may present with for atrial mixing.
cyanosis depending on the presence of associated le-
sions. In ccTGA, both AV and VA discordance occurs, Dearani JA et al: Late follow-up of 1095 patients undergoing oper-
such that the right atrium connects to a morphologic ation for complex congenital heart disease utilizing pul-
LV, which supports the pulmonary artery. Conversely, monary ventricle to pulmonary artery conduits. Ann Thorac
the left atrium empties via a tricuspid valve, into a mor- Surg 2003;75(2)399 [PMID: 12607647].
phologic RV, which supports the aorta. Commonly as- Sondheimer HM et al: Double outlet right ventricle: Clinical spec-
sociated lesions include VSDs and pulmonary stenosis. trum and prognosis. Am J Cardiol 1977;39(5):709 [PMID:
67796].
A dysplastic left-sided tricuspid valve is almost always
present. Previously, surgical repair was directed at VSD
closure and relief of pulmonary outflow tract obstruc- TOTAL ANOMALOUS PULMONARY
tion. This surgical technique maintained the RV as the VENOUS RETURN WITH
systemic ventricle supporting the aorta. It is now recog-
nized that these patients have a reduced lifespan, and OR WITHOUT OBSTRUCTION
thus other surgical techniques have been advocated.
The double-switch procedure is one such technique. In ESSENTIALS OF DIAGNOSIS
this procedure, an atrial level switch (Mustard or Sen-
ning technique) is performed, and an arterial switch op- & TYPICAL FEATURES
eration then restores the morphologic LV to its position
of systemic ventricle. In the absence of associated le- • Cyanosis.
sions, patients with ccTGA most often are undiagnosed • Systolic ejection murmur with lower left sternal
until the adult years, when they present with either left- border flow rumble and accentuated P2.
sided AV valve insufficiency or arrhythmias. Patients • Right atrial and RVH.
with ccTGA have an increased incidence of sponta- • Abnormal pulmonary venous connection.
neous complete heart block estimated at 1% per year
with an overall frequency of 50%.

Graham TP et al: Long-term outcome in congenitally corrected

transposition of the great arteries. J Am Coll Cardiol 2000; General Considerations
36(1):255 [PMID: 10898443].
This malformation accounts for approximately 2% of
all congenital heart lesions. The pulmonary venous
DOUBLE-OUTLET RIGHT VENTRICLE blood drains into a confluence behind the left atrium,
In this uncommon malformation, both great arteries but the confluence is not connected to the left atrium.
arise from the RV. There is always a VSD that allows The pulmonary venous blood therefore finds another
blood to flow from the LV. The presentation depends route to rejoin the circulation via the systemic veins.
on the relationship of the VSD to the semilunar valves. This leads to complete mixing at the level of the right
 CARDIOVASCULAR DISEASES / 597

atrium. The clinical presentation of total anomalous digital clubbing are usually absent. The arterial pulses
pulmonary venous return (TAPVR) depends on the are normal. An RV heave is palpable.
method of return and whether that return to the sys- The pulmonary component of the second sound is
temic veins is unrestricted or restricted. usually increased. A grade II–III/VI ejection-type sys-
This malformation is classified by the site of entry of tolic murmur is heard at the pulmonary area. It radiates
the pulmonary veins into the right side of the heart. Al- over the lung fields anteriorly and posteriorly. An early
though the most common form of TAPVR is unob- to middiastolic flow murmur is often heard at the lower
structed via the left superior vena cava, three other dis- left sternal border in the third and fourth intercostal
tinct types exist: spaces (tricuspid flow murmur).
Type 1 (50%): Entry into the left superior vena cava 2. Imaging—Chest radiography reveals cardiac en-
(persistent anterior cardinal vein) or right superior largement primarily involving the right heart and pul-
vena cava, unobstructed or obstructed. monary artery. Pulmonary vascular markings are
Type 2 (20%): Entry into the right atrium directly markedly increased. A characteristic cardiac contour
or via the coronary sinus, unobstructed. called a “snowman” or “figure of 8” is often seen when
the anomalous veins drain via a persistent left superior
Type 3 (20%): Entry below the diaphragm (usually vena cava to the innominate vein and then the right su-
into the portal vein), almost always obstructed. perior vena cava. This radiographic appearance is not
Type 4 (10%): Multiple sites of entry (mixed present until approximately 3 months of age because it
TAPVR). requires time for the vertical vein and innominate vein
to dilate.
Because the entire venous drainage from the body
comes to the right atrium, a right-to-left shunt is always 3. Electrocardiography—ECG shows right axis devi-
present at the atrial level. This may take the form of ei- ation and varying degrees of right atrial and right ven-
ther an ASD or a patent foramen ovale. Occasionally tricular hypertrophy. A QR pattern is often evident
the atrial septum is a restrictive foramen ovale, and a over the right precordial leads.
Rashkind procedure is needed at birth to allow filling of 4. Echocardiography—Demonstration by echocar-
the left heart. Complete mixing of the systemic and diography of a chamber posterior to the left atrium is
pulmonary venous return occurs in the right atrium, so strongly suggestive of the diagnosis. However, echocar-
that the left atrial and the systemic arterial saturation diographic discrimination between anomalies of pul-
levels approximately equal that of the right atrial satura- monary venous return and persistence of pulmonary
tion. fetal circulation can be challenging. The availability of
two-dimensional echocardiography plus color-flow
Clinical Findings Doppler has increased the diagnostic accuracy.
A. WITH UNOBSTRUCTED PULMONARY B. WITH OBSTRUCTED PULMONARY VENOUS RETURN
VENOUS RETURN This group includes all patients with subdiaphragmatic
This large group includes all children (type 2) with pul- TAPVR and a few of the patients in whom the venous
monary venous return to the right atrium and most drainage is into a systemic vein above the diaphragm.
children with supracardiac TAPVR. These patients
tend to have a high total pulmonary flow typically pre- 1. Symptoms and signs—These infants usually pre-
sent with cardiomegaly and early CHF rather than sent shortly after birth with severe cyanosis and require
cyanosis. Oxygen saturations in the high 80s or low 90s early corrective surgery. Cardiac examination discloses a
are common. Most patients in this group have mild to striking RV impulse. S1 is accentuated. S2 is markedly
moderate elevation of the pulmonary artery pressure accentuated and single. A grade I–III/VI ejection-type
owing to the elevated pulmonary blood flow. In most systolic murmur is frequently heard over the pulmonary
instances, the pressure does not reach systemic levels. area with radiation over the lung fields. Diastolic mur-
murs are uncommon. In many cases, no murmur is
1. Symptoms and signs—These patients may have a heard at all.
history of mild cyanosis in the neonatal period and dur-
2. Imaging—In the most severe cases, the heart is
ing early infancy. Thereafter, they do relatively well ex-
small and pulmonary venous congestion is marked. In
cept for frequent respiratory infections. They are usu-
less severe cases, the heart size may be normal or slightly
ally rather small and thin and resemble patients with
enlarged with slight pulmonary venous congestion.
very large ASDs.
Careful examination discloses duskiness of the nail 3. Electrocardiography—The ECG shows right axis
beds and mucous membranes, but definite cyanosis and deviation, right atrial hypertrophy, and RVH.
598 / CHAPTER 19

4. Echocardiography—Echocardiography shows a TRUNCUS ARTERIOSUS

combination of a small left atrium and LV and a vessel
lying parallel and anterior to the descending aorta and
to the left of the inferior vena cava. Color-flow Doppler ESSENTIALS OF DIAGNOSIS
echocardiography is useful in establishing the diagnosis & TYPICAL FEATURES
and is often diagnostic. Right-to-left atrial shunting oc-
curs. • Early CHF
• Mild or no cyanosis.
5. Cardiac catheterization and angiocardiogra- • Systolic ejection click.
phy—These procedures are diagnostic. Cardiac
catheterization and cineangiocardiography demonstrate
TAPVR and identify the site of entry of the anomalous
veins. They also demonstrate the ratio of pulmonary to
systemic blood flow and the degree of pulmonary hy-
pertension and pulmonary vascular resistance. General Considerations
Truncus arteriosus accounts for less than 1% of con-
genital heart malformations. A single great artery arises
Treatment from the heart giving rise to the systemic, pulmonary,
and coronary circulations. Truncus develops embry-
Surgery is always required for TAPVR. If pulmonary ologically as a result of complete lack of formation of
venous return is obstructed, surgery must be performed the spiral ridges that divide the primitive common
during the immediate newborn period. In infants with truncus arteriosus into the aorta and the pulmonary
unobstructed TAPVR, surgery is more elective and may artery. A high VSD is always present. The number of
be delayed for weeks to months. The timing of surgery valve leaflets varies from two to six, and the valve may
can then be determined by the child’s weight gain and be sufficient, insufficient, or stenotic.
the risk of pulmonary infection. If early surgery is not Although rare, truncus arteriosus is divided into four
planned and the atrial septum is restrictive, a balloon types by the anatomy of the pulmonary circulation:
atrial septostomy should be performed in the newborn
period. The results of surgery are excellent. Type 1 (48%): A main pulmonary artery arises from
the base of the trunk just above the semilunar valve
and runs parallel with the ascending aorta for a short
Course & Prognosis time before dividing.
Most children with TAPVR do very well after surgery. Type 2 (29%): Two pulmonary arteries arise side by
However, approximately 5% of surgical survivors de- side from the posterior aspect of the truncus.
velop late stenosis of the pulmonary veins. This devas- Type 3 (11%): Two pulmonary arteries arise inde-
tating condition is difficult to treat either with inter- pendently from either side of the trunk.
ventional catheterization or surgery, and it has a very Type 4 (12%): No demonstrable main left and
poor prognosis. Pulmonary vein stenosis, when it oc- right pulmonary arteries are present. Pulmonary
curs, is most often seen in children who initially had circulation is derived from bronchials arising from
obstructed total veins, but it occurs occasionally in chil- the descending thoracic aorta.
dren whose initial presentation was unobstructed. A
new surgical technique involving sutureless in situ peri- In this condition, blood leaves the heart through a
cardial repair of the recurrent pulmonary venous ob- single common exit. Therefore, the saturation of the
struction holds great promise. By avoiding direct sutur- blood in the pulmonary artery is the same as that in the
ing at the pulmonary venous ostia, the chance of systemic arteries. The degree of systemic arterial oxygen
recurrent stenosis at the anastamotic site is lessened. saturation depends on the ratio of pulmonary to sys-
temic blood flow. If pulmonary vascular resistance is
normal, the pulmonary blood flow is greater than the
Lacour-Gayet F et al: Surgical management of progressive pul- systemic blood flow and the saturation is relatively
monary venous obstruction after repair of total anomalous
pulmonary venous connection. J Thorac Cardiovasc Surg
high. If pulmonary vascular resistance is elevated be-
1999;117(4):679 [PMID: 10096962]. cause of pulmonary vascular obstructive disease or very
Monro JL et al. Reoperations and survival after primary repair of small pulmonary arteries, pulmonary blood flow is re-
congenital heart defects in children. J Thorac Cardiovasc duced and oxygen saturation is low. The systolic pres-
Surg 2003;126(2):511 [PMID: 12928652]. sures are systemic in both ventricles.
 CARDIOVASCULAR DISEASES / 599

Clinical Findings material into either ventricle demonstrates the VSD

and the single great artery arising from the heart. The
A. SYMPTOMS AND SIGNS exact type of truncus, however, is often best imaged
The clinical picture depends on the degree of pul- from an injection in the truncal root itself. This will
monary blood flow. also allow for evaluation of truncal insufficiency.
1. High pulmonary blood flow—This is the most
common presentation in truncus arteriosus. Patients Treatment
with high pulmonary blood flow are usually acyanotic.
Their clinical presentation resembles that of patients Anticongestive measures are needed for patients with
with large VSDs. Early CHF occurs. Examination of high pulmonary blood flow and congestive failure.
the heart reveals a hyperactive precordium. A systolic Surgery is always required in this condition. Because of
thrill is common at the lower left sternal border. S1 is the severe CHF, surgery is usually performed in the
normal. A loud early systolic ejection click is commonly neonatal period. The VSD is closed to allow LV egress
heard. S2 is single and accentuated. A grade III–IV/VI to the truncal valve as in ToF. The pulmonary artery
pansystolic murmur is audible at the lower left sternal (type 1) or arteries (types 2–3) are separated from the
border. A diastolic flow murmur can often be heard at truncus as a block, and a conduit is fashioned from the
the apex (mitral flow murmur). RV to the pulmonary circulation. The conduit may be
valved or nonvalved, but most surgeons prefer a valved
2. Low pulmonary blood flow—Patients with de- allograft for this repair. Children with type 4 truncus
creased pulmonary blood flow are cyanotic early and do arteriosus are usually stable in infancy with adequate
poorly. The most common manifestations are growth saturations and without CHF. This is fortunate, be-
retardation, easy fatigability, dyspnea on exertion, and cause their ultimate surgery depends on finding and
CHF. The heart is not hyperactive. S1 and S2 are single joining together (unifocalizing) their pulmonary artery
and loud. A systolic grade II–IV/VI murmur is heard at segments prior to attempted surgical correction.
the lower left sternal border. No diastolic flow murmur
is heard. A continuous heart murmur is uncommon ex-
cept in type 4, in which the large bronchial collateral Course & Prognosis
vessels cause the continuous murmur. A loud systolic Children with truncus types 1–3 with good surgical re-
ejection click is commonly heard. sults do well. They almost always outgrow the RV to
pulmonary conduit that is placed in infancy and require
B. IMAGING a revision of the conduit in later childhood. The rare
The most common radiographic findings are a boot- child with type 4 truncus arteriosus will need staged
shaped heart, absence of the main pulmonary artery preparation of the pulmonary arteries prior to correc-
segment, and a large aorta that has a right arch 30% of tive surgery. For children with types 1–3 truncus arte-
the time. The pulmonary vascular markings vary with riosus the risk of early pulmonary vascular obstructive
the degree of pulmonary blood flow. disease is high, and a decision to delay open-heart
surgery beyond age 4–6 months, even if the child is
C. ELECTROCARDIOGRAPHY clinically stable, must take this into account.
The axis is usually normal. RVH or combined ventricu-
lar hypertrophy is commonly present. LVH as an iso- McElhinney DB et al: Reinterventions after repair of common arte-
rial trunk in neonates and young infants. J Am Coll Cardiol
lated finding is rare. 2000;35(5):1317 [PMID: 10758975].

D. ECHOCARDIOGRAPHY
A characteristic image shows override of a single great
artery (similar to ToF). The origin of the pulmonary ar- ACQUIRED HEART DISEASE
teries and the degree of truncal valve abnormality can
be seen. Color-flow Doppler can aid in the description
of pulmonary flow and the function of the truncal RHEUMATIC FEVER
valve, both of which are critical to management. Rheumatic fever still occurs regionally in the United
States. Availability of penicillin, improvements in the
E. ANGIOCARDIOGRAPHY standard of living and hygiene, and greater availability
Cardiac catheterization is not routinely performed but of medical care have greatly reduced the incidence of
may be of value in the older infant in whom pulmonary this disease since the 1950s. Acute rheumatic fever has
vascular disease must be ruled out. Injection of contrast had a resurgence in several regions of the United States
600 / CHAPTER 19

(the Midwest in 1984 and the intermountain West Sydenham Chorea

since 1987). The character of the illness has changed,
however. The reason for these regional epidemics is un- Sydenham chorea is characterized by emotional insta-
known. In both the Salt Lake City and Denver pedi- bility and involuntary movements. These findings be-
atric referral centers, 30–50 new cases are now seen come progressively worse and may be accompanied by
each year. ataxia and slurring of speech. Muscular weakness be-
Group A β-hemolytic streptococcal infection of the comes apparent following the onset of the involuntary
upper respiratory tract is the essential trigger that acts movements. The attack of chorea is self-limiting, al-
on predisposed individuals. The latest attempts to de- though it may last up to 3 months. Sometimes only one
fine host susceptibility implicate immune response (Ir) side is involved. Chorea may not be apparent for
genes, which are present in approximately 15% of the months to years after the acute episode of rheumatic
population. The immune response triggered by colo- fever.
nization of the pharynx with group A streptococci con-
sists of (1) sensitization of B lymphocytes by strepto- Polyarthritis
coccal antigens, (2) formation of antistreptococcal The large joints (knees, hips, wrists, elbows, shoulders)
antibody, (3) formation of immune complexes that are most commonly involved. Joint swelling and associ-
cross-react with cardiac sarcolemma antigens, and ated limitation of movement should be present.
(4) myocardial and valvular inflammatory response. Arthralgia alone is not a major criterion.
The peak period of risk in the United States is age
5–15 years. The disease is slightly more common in
girls and in African Americans, perhaps a reflection of Erythema Marginatum
socioeconomic factors. The annual death rate from A macular erythematous rash with a circinate border
rheumatic heart disease in school-age children (whites appears primarily on the trunk and the extremities. The
and nonwhites) recorded in the 1980s was less than face is usually spared.
1:100,000.
The modified Jones criteria are used to diagnose
acute rheumatic fever. Two major or one major and
Subcutaneous Nodules
two minor manifestations (plus supporting evidence of These usually occur only in severe cases, and then most
streptococcal infection) are needed (Table 19–16). commonly over the joints, scalp, and spinal column.
They vary from a few millimeters to 2 cm in diameter
and are nontender and freely movable under the skin.

Table 19–16. Jones criteria (modified) for Essential Manifestation

diagnosis of rheumatic fever.
Except in cases of rheumatic fever manifesting solely as
Sydenham chorea or long-standing carditis, there
Major manifestations should be clear evidence of a streptococcal infection
Carditis
such as scarlet fever, a positive throat culture for group
Polyarthritis
Sydenham’s chorea
A β-hemolytic Streptococcus, and increased antistrep-
Erythema marginatum tolysin O or other streptococcal antibody titers. The
Subcutaneous nodules antistreptolysin O titer is significantly higher in
Minor manifestations rheumatic fever than in uncomplicated streptococcal
Clinical infections.
Previous rheumatic fever or rheumatic heart disease
Polyarthralgia Treatment & Prophylaxis
Fever
Laboratory A. TREATMENT OF THE ACUTE EPISODE
Acute phase reaction: elevated erythrocyte sedimenta- 1. Anti-infective therapy—Eradication of the strepto-
tion rate, C-reactive protein, leukocytosis coccal infection is essential. Long-acting benzathine
Prolonged PR interval penicillin is the drug of choice. Depending on the age
Plus and weight of the patient, give a single intramuscular
Supporting evidence of preceding streptococcal infection, injection of 0.6–1.2 million units; alternatively, give
that is, increased titers of antistreptolysin O or other strep- penicillin V, 125–250 mg orally four times a day for
tococcal antibodies, positive throat culture for group A 10 days. Erythromycin, 250 mg orally four times a day,
Streptococcus
may be substituted if the patient is allergic to penicillin.
 CARDIOVASCULAR DISEASES / 601

2. Anti-inflammatory agents— lifelong commitment. More commonly with transient

a. Aspirin. Currently, 30–60 mg/kg/d is given in cardiac involvement, 3–5 years of therapy or discontin-
four divided doses. This dosage is often more than suf- uance at adolescence is a practical and effective ap-
ficient to effect dramatic relief of the arthritis and fever. proach.
In general, higher dosages carry a greater risk of side ef- The following preventive regimens are in current
fects, and there are no proven short- or long-term bene- use:
fits of high doses to produce salicylate blood levels of a. Penicillin G. benzathine 1.2 million units intra-
20–30 mg/dL. The duration of therapy must be tai- muscularly every 21–28 days, is the drug of choice.
lored to meet the needs of the patient, but use of as- b. Sulfadiazine. 500 mg daily as a single oral dose
pirin for 2–6 weeks, with reduction in dosage toward for patients weighing over 27 kg is the drug of second
the end of the course, is usually sufficient. Other nons- choice. Blood dyscrasias and a lesser effectiveness in re-
teroidal antiinflammatory agents are commonly used ducing streptococcal infections make this drug less sat-
because of the concerns about Reye syndrome, but they isfactory than penicillin benzathine G.
appear to be less effective.
c. Penicillin V. 250,000 units orally twice daily of-
b. Corticosteroids. Corticosteroids are rarely indi- fers approximately the same protection afforded by sul-
cated. However, in the unusual patient with severe fadiazine but is much less effective than intramuscular
carditis and CHF, steroid therapy may be not only ef- penicillin benzathine G (5.5 vs 0.4 streptococcal infec-
fective but also lifesaving. Corticosteroids may be given tions per 100 patient-years).
as follows: prednisone, 2 mg/kg/d orally for 2 weeks (or
comparable doses of other corticosteroids); reduce d. Erythromycin. 250 mg orally twice a day may be
prednisone to 1 mg/kg/d during the third week, and given to patients who are allergic to both penicillin and
begin aspirin, 50 mg/kg/d; stop prednisone at the end sulfonamides.
of 3 weeks, and continue aspirin for 8 weeks or until
the C-reactive protein is negative and the sedimenta- 2. Residual valvular damage—Chronic CHF may
tion rate is falling. follow a single severe episode of acute rheumatic cardi-
tis or, more commonly, may follow repeated episodes.
3. Therapy of congestive heart failure—See Conges- In the United States, the typical manifestations of resid-
tive Heart Failure section. ual valvular damage in children are heart murmurs of
4. Bed rest and ambulation—Bed rest is not required mitral and aortic insufficiency. Murmurs are not ac-
for patients with arthritis and mild carditis without companied by CHF in most children as long as re-
CHF. Indoor activity followed by modified outdoor ac- peated attacks are prevented.
tivity may be ordered when symptoms have disappeared Methods of managing CHF have been discussed
but clinical and laboratory evidence of rheumatic activ- previously. Children with severe valvular damage that
ity remains. Modified bed rest for 2–6 weeks is gener- cannot be managed adequately on a medical regimen
ally adequate. Children should not return to school must be considered for valve replacement before the
while there is clear evidence of rheumatic activity. Most myocardium is irreversibly damaged.
acute episodes of rheumatic fever are managed on an
outpatient basis.
Ayoub EM: Resurgence of rheumatic fever in the United States:
B. TREATMENT AFTER THE ACUTE EPISODE The changing picture of a preventable illness. Postgrad Med
1. Prevention—The patient who has had a bout of 1992;92(3):139 [PMID: 1518750].
rheumatic fever has a greatly increased risk of develop- Dajani AS et al: Guidelines for the diagnosis of rheumatic fever:
ing rheumatic fever after the next inadequately treated Jones criteria, updated 1992. Circulation 1993;87(1):302.
group A β-hemolytic streptococcal infection. Preven- Veasey LG: Time to take soundings in acute rheumatic fever?
tion is thus the most important aim for the physician to Lancet 2001;357(9273):1994 [PMID: 11438128].
emphasize. The purpose of follow-up visits after the
acute episode is not so much to evaluate the evolution
of mitral or aortic insufficiency murmurs as to reinforce RHEUMATIC HEART DISEASE
the physician’s advice about the necessity for prophy- Mitral Insufficiency
laxis with regular long-acting benzathine penicillin. The
physician should stress that protection is better with in- Mitral insufficiency is the most common valvular resid-
tramuscular than oral medication and that failure to ual of acute rheumatic carditis. There are reports from
comply with regular medication programs increases the all over the world of silent mitral insufficiency with
risk for recurrence of rheumatic fever. If myocardial or echocardiographic findings characteristic of acute
valvular disease persists, antibacterial prophylaxis is a rheumatic fever.
602 / CHAPTER 19

Mitral Stenosis Table 19–17. Noncardiac manifestations of

Mitral stenosis after acute rheumatic fever is rarely en- Kawaski disease.
countered in the United States until 5–10 years after
the first episode. Thus, mitral stenosis is much more System Associated Signs and Symptoms
commonly seen in adults than in children. Interven- Gastrointestinal Vomiting, diarrhea, gallbladder hydrops,
tional cardiovascular balloon dilation of mitral stenosis elevated transaminases
is now being used in many patients prior to considera- Blood Elevated ESR or CRP, leukocytosis, hypoal-
tion of mitral valve replacement. buminemia, mild anemia in acute phase
and thrombocytosis in subacute phase
Aortic Insufficiency (usually second to third week of
illness)
This early decrescendo diastolic murmur is occasionally Renal Sterile pyuria, proteinuria
encountered as the sole valvular manifestation of Respiratory Cough, rhinorrhea, infiltrate on chest
rheumatic carditis. It is the second most common valve radiograph
affected in polyvalvular as well as in single valvular dis- Joint Arthralgia and arthritis
ease. It appears that the aortic valve is involved more Neurologic Mononuclear pleocytosis of cerebrospinal
often in males and in African Americans. fluid, irritability, facial palsy
ERS = erythrocyte sedimentation rate; CRP = creatinine phospho-
Aortic Stenosis kinase.
Dominant aortic stenosis of rheumatic origin does not
occur in pediatric patients. In one large study, the
shortest length of time observed for a patient to develop tion. Untreated patients have an approximately 25%
dominant aortic stenosis secondary to rheumatic heart risk of developing an aneurysm of the coronary arteries.
disease was 20 years. Those at greatest risk of aneurysm formation are males,
young children (< 6 months) and those not treated with
intravenous immunoglobulin (IVIG).
KAWASAKI DISEASE Although the gold standard for diagnosing coronary
Kawasaki disease was first described in Japan in artery aneurysms is angiography, two-dimensional
1967 and was initially called mucocutaneous lymph echocardiography is highly sensitive and is the current
node syndrome. The cause of Kawasaki disease is un- standard screening test in children with Kawasaki dis-
clear, and a specific diagnostic test does not exist. ease. Fortunately, most coronary artery aneurysms re-
Eighty percent of affected patients are younger than age solve within 5 years of diagnosis. However, as
5 years, and the male-to-female ratio is 1.5:1. The diag- aneurysms resolve, associated obstruction or stenosis
nostic criteria include fever for more than 5 days and at (19% of all aneurysms) may develop, which may result
least four of the following features: (1) bilateral, pain- in coronary ischemia. Giant aneurysms (> 8 mm) are
less, nonexudative conjunctivitis, (2) lip or oral cavity much less likely to resolve, and nearly 50% eventually
changes (eg, lip cracking and fissuring, strawberry become stenotic. Of additional concern, acute throm-
tongue, inflammation of the oral mucosa), (3) cervical bosis of an aneurysm can occur, resulting in a myocar-
lymphadenopathy (≥ 1.5 cm in diameter and usually dial infarction, which is fatal in approximately 20% of
unilateral), (4) polymorphous exanthema, and (5) ex- cases.
tremity changes (redness and swelling of the hands and The immediate management of Kawasaki disease
feet with subsequent desquamation). Clinical features consists of therapy with IVIG and high-dose aspirin.
not part of the diagnostic criteria, but frequently associ- This therapy is effective in decreasing the incidence of
ated are shown in Table 19–17. coronary artery dilation and aneurysm formation. The
The potential for adverse cardiovascular effects is the currently recommended therapeutic regimen consists of
most serious aspect of Kawasaki disease. Cardiovascular 2 g/kg of IVIG administered over 10–12 hours and
complications during the acute illness include my- 80–100 mg/kg/d of aspirin in four divided doses until
ocarditis, pericarditis, valvular heart disease (usually mi- the patient is afebrile. In an effort to prevent acute
tral or aortic regurgitation), and coronary arteritis. Pa- thrombosis of coronary aneurysms, 3–5 mg/kg of as-
tients with fever but fewer than four of the diagnostic pirin daily is prescribed throughout the subacute phase
features can be diagnosed with atypical Kawasaki dis- of the illness (6–8 weeks) or until coronary artery ab-
ease if they have coronary artery abnormalities. normalities resolve. If fever recurs within 48–72 hours
Coronary artery lesions range from mild transient of the initial treatment course and no other source of
dilation of a coronary artery to large aneurysm forma- the fever is detected, a repeat dose of IVIG is often rec-
 CARDIOVASCULAR DISEASES / 603

ommended; however, the effectiveness of this approach Although often idiopathic, known causes include acute
has not been clearly demonstrated. Currently, cortico- or chronic myocarditis, long-standing untreated tach-
steroids are not felt to be effective in Kawasaki disease. yarrhythmias, unrecognized left heart obstructive le-
During the acute and subacute phases of the illness, sions, anthracycline toxicity, and genetic and metabolic
patients should be monitored closely by serial electro- diseases (including inborn errors of fatty acid oxidation
cardiography, chest radiograph, and echocardiography. and mitochondrial oxidative phosphorylation defects).
Selective coronary angiography is recommended in pa- Genetic causes include abnormalities of the dystrophin
tients with evidence of myocardial ischemia. In 1994, gene as in Duchenne and Becker muscular dystrophy.
the American Heart Association published guidelines
for the long-term management of Kawasaki disease.
The risk stratification and recommended follow-up can
Clinical Findings
be reviewed in Table 19–18. A. SIGNS AND SYMPTOMS
As the heart dilates, cardiac output falls, and affected
American Heart Association: Diagnostic guidelines for Kawasaki children exhibit signs and symptoms of CHF. The
disease. Circulation 2001;103(2):335 [PMID: 11208699]. child experiences decreased exercise tolerance, failure to
Burns JC et al: Intravenous gamma-globulin treatment and retreat- thrive, diaphoresis, and tachypnea. As the heart deterio-
ment in Kawasaki disease. Pediatr Infect Dis J 1998;17(12): rates, the pulses and perfusion become weaker, hepato-
1144 [PMID: 9877364].
megaly and rales become prominent, and the cardiac
McMorrow Tuohy AM et al: How many echocardiograms are nec-
essary for follow-up evaluation of patients with Kawasaki dis-
examination shows a prominent gallop.
ease? Am J Cardiol 2001;88(3):328 [PMID: 11472722].
B. IMAGING
The chest radiograph shows generalized cardiomegaly
CARDIOMYOPATHY with or without pulmonary venous congestion.
As in adults, three patterns of cardiomyopathy are rec-
ognized in children: (1) dilated, (2) hypertrophic, and C. ELECTROCARDIOGRAPHY
(3) restrictive. Sinus tachycardia with ST-T segment changes are com-
monly seen on ECG. The criteria for right and left ven-
tricular hypertrophy may also be met. One must ensure
1. Dilated Cardiomyopathy that a narrow complex tachycardia seen in this instance
The most frequent of the childhood cardiomyopathies is in fact sinus tachycardia with a normal P wave axis as
occurs with an annual incidence of 4–8 cases per opposed to an atrial tachyarrhythmia that may be the
100,000 population in the United States and Europe. underlying cause of the cardiomyopathy.

Table 19–18. Long-term management in Kawasaki disease.

Risk
Level Definition Management Guidelines
I No coronary artery changes at any stage of the illness No ASA is needed beyond the subacute phase (6–8 weeks). No
follow-up beyond the first year
II Transient ectasia of coronary arteries during the Same as above, or clinical follow-up ± ECG every 3–5 years
acute phase
III Single small to medium coronary aneurysm ASA until abnormality resolves. Annual follow-up with ECG and
echo if < 10 years old and every other year stress testing if > 10
years
IV Giant aneurysm or multiple small to medium Long term ASA ± warfarin. Annual follow-up with ECG, echo and
aneurysms without obstruction stress testing (in those > 20 years)
V Coronary artery obstruction Long-term ASA ± warfarin ± calcium channel blocker to reduce
myocardial oxygen consumption. Echo and ECG every
6 months. Stress testing and Holter exam annually
ASA = acetyl salicylic acid; ECG = electrocardiogram; Echo = echocardiogram.
604 / CHAPTER 19

D. ECHOCARDIOGRAPHY monly presents in the older child, adolescent, or adult

The echocardiogram shows LV and left atrial enlarge- although it may be seen as early as the neonatal period.
ment with decreased LV shortening fraction. The cal- Other causes of HCM seen in the neonatal and child-
culated end diastolic and end-systolic dimensions are hood period include glycogen storage disease, mito-
increased. With more advanced disease, mitral insuffi- chondrial disorders, and other metabolic disorders.
ciency will occur as the LV dilates.
Familial Hypertrophic Cardiomyopathy
E. OTHER TESTING
Catheterization is most often done to obtain a biopsy In the familial form, HCM is most commonly caused
evidence of myocarditis. In addition, polymerase chain by a mutation in one of four genes that encode proteins
reaction testing may be performed on biopsy specimens of the cardiac sarcomere (the B-myosin heavy chain,
to detect the presence of viral genome remaining from cardiac troponin T, A-tropomyosin, and myosin-bind-
an earlier bout of myocarditis. Finally, the biopsy can ing protein C genes).
be analyzed by light and electron microscopy to look
for metabolic causes of dilated cardiomyopathy. Skele- Clinical Findings
tal muscle biopsy may also be helpful. Hemodynamic
assessment during catheterization will assess the pro- Patients may be asymptomatic, despite having signifi-
gression of the disease. The effect of drug therapy with cant hypertrophy, or may present with symptoms of in-
afterload-reducing agents can be assessed in the adequate coronary perfusion such as angina, syncope,
catheterization laboratory prior to their clinical use. or exercise intolerance. Patients may experience sudden
Cardiopulmonary stress testing is a useful clinical cardiac death, often precipitated by sporting activities.
tool in patients with cardiomyopathy for measuring the Cardiac examination will demonstrate a left precordial
response to medical therapies as well as deciding on the bulge with a diffuse point of maximal impulse. An LV
appropriate timing of cardiac transplantation. heave may be present. A palpable or audible S4 may be
present. If outflow tract obstruction is present, a sys-
tolic ejection murmur will be audible. A murmur may
Treatment & Prognosis not be audible at rest but is easily provoked with mini-
Patients with dilated cardiomyopathy may require in- mal exercise. Although the older patient with HCM
hospital management of CHF (see section on Conges- typically has disease primarily in the LV, RVH, either
tive Heart Failure). As outpatients they are treated with alone or in association with LVH, may be seen in the
digoxin, diuretics, afterload-reducing agents, and fluid neonate. Affected neonates may be cyanotic if RV out-
restriction. Once stabilized on these agents, some can flow tract obstruction is significant.
be treated with carvedilol. Anticoagulants such as war-
farin (Coumadin) may be used to prevent thrombus A. ECHOCARDIOGRAPHY
formation secondary to stagnant blood flow within the The diagnosis of HCM is made in most cases by
dilated, poorly contractile cardiac chambers. If arrhyth- echocardiography, which demonstrates an asymmetrical
mias occur, they require treatment. Antiarrhythmic septal hypertrophy. Younger patients may have concen-
agents that do not suppress myocardial contractility, tric hypertrophy, making the diagnosis less obvious.
such as digoxin and amiodarone, are preferred. Internal Systolic anterior motion of the mitral valve leaflet may
defibrillators are used in some patients with refractory occur and may contribute to the degree of LV outflow
arrhythmias in the setting of dilated cardiomyopathy. tract obstruction. The mitral valve leaflet may become
Specific therapy directed at the cause can have a dra- distorted with time, resulting in mitral insufficiency.
matic effect; for instance, in some of the mitochondrial LV outflow tract obstruction may be present at rest.
metabolic disorders. Treatment of carnitine deficiency Provokable outflow tract obstruction should be assessed
may result in improved cardiac function. Antiarrhyth- with either amyl nitrate or monitored exercise. Systolic
mic therapy in patients with arrhythmia-induced car- function is most often hypercontractile in the young
diomyopathy is often curative. Ultimately, if medical child but may deteriorate over time, often in association
management is unsuccessful, cardiac transplantation is with a change in morphology as hypertrophy develops
considered. into LV dilation. Diastolic function is often impaired.
Patients are at risk for myocardial ischemia, possibly as
a result of systolic compression of the intramyocardial
2. Hypertrophic Cardiomyopathy septal perforators, myocardial bridging of epicardial
The most common cause of hypertrophic cardiomy- coronary arteries, or an imbalance of coronary artery
opathy (HCM) is familial hypertrophic cardiomyopa- supply and demand due to the presence of massive
thy, which affects 1 in 500 individuals. It most com- myocardial hypertrophy.
 CARDIOVASCULAR DISEASES / 605

B. ELECTROCARDIOGRAPHY good results. Ethanol ablation is a technique being used

The ECG may be normal, but more typically will with increasing frequency for the adult with HCM and
demonstrate deep Q waves in the inferolateral leads (II, LV outflow tract obstruction. This procedure, per-
III, aVf, V5, and V6) secondary to depolarization of the formed in the cardiac catheterization laboratory, in-
hypertrophied septum. ST segment abnormalities may volves the selective infiltration of ethanol in a coronary
be seen in the same leads. Age-dependent criteria for septal artery branch, thereby inducing a small myocar-
LVH will often be met. Criteria for left atrial enlarge- dial infarction. This leads to a reduction in septal size
ment may be present. and improvement of obstruction. The long-term effects
of this procedure are unknown, and this procedure is
C. OTHER TESTING not currently employed for pediatric patients. Surgical
Cardiopulmonary stress testing is a valuable tool in this unroofing of a myocardial bridge may improve progno-
patient population to ascertain the presence of provok- sis in those with myocardial ischemia secondary to epi-
able LV outflow tract obstruction, to assess for ischemia cardial coronary compression. Internal defibrillators are
and arrhythmias, and to determine prognosis. A being placed in patients with documented ventricular
blunted blood pressure response and ventricular ar- arrhythmias, resuscitated sudden death, or a strong
rhythmias with exercise have both been associated with family history of HCM with associated sudden death.
increased mortality in this patient group. Nuclear stress
testing allows for assessment of myocardial perfusion
defects. Glycogen Storage Disease of the Heart
D. CARDIAC CATHETERIZATION At least 10 types of glycogen storage disease are recog-
nized. The type that primarily involves the heart is
Cardiac catheterization should be performed in patients Pompe disease (GSD IIa). The deficient enzyme (acid
with HCM who have recurrent angina, syncope, resus- maltase) is necessary for hydrolysis of the outer
citated sudden death, or a worrisome stress test. Hemo- branches of glycogen, and its absence results in marked
dynamic findings may include an elevated left atrial deposition of glycogen within the myocardium. Car-
pressure secondary to impaired diastolic filling. If mid- diac glycogenosis is a rare heritable (autosomal reces-
cavitary LV outflow tract obstruction is present, an as- sive) disorder.
sociated pressure gradient will be evident. Provocation Affected infants are well at birth, but onset occurs
of LV outflow tract obstruction with either rapid atrial by the sixth month of life. These children have a history
pacing or isoproterenol may be sought. Angiography of retardation of growth and development, feeding
demonstrates a “ballerina slipper” configuration of the problems, poor weight gain, and CHF. Physical exami-
LV secondary to the midcavitary LV obliteration dur- nation reveals generalized muscular weakness, a large
ing systole. Coronary angiography should be performed tongue, cardiomegaly, and no significant heart mur-
to evaluate possible associated myocardial bridging, murs. Chest radiographs reveal marked cardiomegaly
which may be an important source of myocardial is- with or without pulmonary venous congestion. The
chemia in these patients. Angiography will show sys- ECG shows a short PR interval with LVH with ST de-
tolic obliteration, typically of the middle left anterior pression and T wave inversion over the left precordial
descending coronary artery. leads. Echocardiography shows severe concentric LVH.
Children with this disease usually die before age
Treatment and Prognosis 1 year. Death may be sudden or the result of progres-
The prognosis is variable and depends in part on the sive CHF.
degree of hypertrophy, the degree of outflow tract ob-
struction, the particular genetic defect, and the presence
of coronary compression. Patients are restricted from 3. Restrictive Cardiomyopathy
strenuous athletics. Patients with resting or latent LV Restrictive cardiomyopathy is a rare entity in the pedi-
outflow tract obstruction may be treated with either β- atric population, accounting for less than 5% of all
blockers or disopyramide with good, albeit temporary, cases of cardiomyopathy.
relief of obstruction. Patients with a provokable LV
outflow tract gradient above 60 mm Hg require addi-
tional treatment. Although dual-chamber pacing has Clinical Findings
been used in some children with good relief of obstruc-
tion, larger series demonstrate no significant improve- Patients present with signs of CHF as outlined previ-
ment in obstruction. Surgical myectomy with resection ously. Physical examination is remarkable for a promi-
of part of the hypertrophied septum has been used with nent S4 and jugular venous distention.
606 / CHAPTER 19

A. ELECTROCARDIOGRAPHY ously. This is a malignant form of the disease and is

ECG demonstrates marked right and left atrial enlarge- thought to be secondary to overwhelming viremia and
ment with normal ventricular voltages. ST/T wave ab- tissue invasion of multiple organ systems, including the
normalities may be present. heart. (2) In the older child, the onset of cardiac find-
ings tends to be more gradual. There is often a history of
B. ECHOCARDIOGRAPHY an upper respiratory tract infection or gastroenteritis
The diagnosis may be confirmed echocardiographically, within the month prior to the development of cardiac
noting the presence of normal sized ventricles with findings. This is a more insidious form of the disease
massively dilated atrium. Due to infiltration of the ven- and may have a late postinfectious or autoimmune com-
tricular myocardium, the LV becomes “restrictive,” and ponent. However, clinical presentation can be acute or
atrial emptying is impaired. chronic in all ages and in all types of myocarditis.
In the newborn infant, the signs of CHF are usually
apparent. The skin is pale and gray, and peripheral pal-
Course and Prognosis lor may be present. The pulses are rapid, weak, and
The condition is usually idiopathic. Endocardial fibro- thready. Edema of the face and extremities may be pre-
elastosis, a histologic diagnosis, may be noted. The en- sent. Significant cardiomegaly is present, and the left
docardium has marked milky white thickening, as do and right ventricular impulses are weak. On ausculta-
the subendocardial layers of the LV and left atrium. tion, the heart sounds may be muffled and distant. S3
The mitral valve may be involved. Irrespective of cause, and S4 are common, resulting in a gallop rhythm. Mur-
the prognosis is poor. Anticongestive therapy may be murs are usually absent, although a murmur of tricus-
tried, but many patients will require cardiac transplan- pid or mitral insufficiency can occasionally be heard.
tation. Moist rales are usually present at both lung bases. The
liver is enlarged and frequently tender.
Hauser M et al: Diagnosis of anthracycline-induced cardiomyopa-
thy by exercise spiroergometry and stress echocardiography. B. IMAGING
Eur J Pediatr 2001;160(10):607 [PMID: 11686505]. Generalized cardiomegaly can be seen on radiograph.
Helton E et al: Metabolic aspects of myocardial disease and a role Moderate to marked pulmonary venous congestion is
for L-carnitine in the treatment of childhood cardiomyopa- evident. Pneumonia is commonly present.
thy. Pediatrics 2000;105(6):1260 [PMID: 10835067].
Malcic I et al: Epidemiology of cardiomyopathies in children and C. ELECTROCARDIOGRAPHY
adolescents: A retrospective study over the last 10 years. Car-
diol Young 2002;12(3):253 [PMID: 12365172].
The ECG is variable. Classically, there is evidence of
Nugent AW et al: Clinical, electrocardiographic, and histologic
low voltage of the QRS throughout all frontal and pre-
correlations in children with dilated cardiomyopathy. J Heart cordial leads and depression of the ST segment and in-
Lung Transplant 2001;20(11):1152 [PMID: 11704474]. version of the T waves in leads I, III, and aVF and in
Yetman AT et al: Myocardial bridging in children with hyper- the left precordial leads during the acute stage. Dys-
trophic cardiomyopathy—A risk factor for sudden death. rhythmias are common, and AV and intraventricular
N Engl J Med 1998;339(17):1201 [PMID: 9780340]. conduction disturbances may be present. With the
more benign form, or during the recovery phase of the
MYOCARDITIS malignant form, high-voltage QRS complexes are com-
monly seen and are indicative of LVH.
The most common causes of myocarditis are aden-
ovirus, coxsackie A and B, echovirus, and cy- D. ECHOCARDIOGRAPHY
tomegalovirus. In addition, the human immunodefi- Echocardiography demonstrates four-chamber dilation
ciency virus (HIV) causes myocarditis. Our ability to with poor ventricular function and AV valve regurgita-
determine the cause of myocarditis has been enhanced tion.
greatly by the availability of polymerase chain reaction
technology to replicate identifiable segments of viral E. MYOCARDIAL BIOPSY
genome from the myocardium of affected children. A tissue diagnosis obtained from either myocardium or
skeletal muscle is usually indicated in pediatric car-
Clinical Findings diomyopathy/myocarditis. Primary processes (meta-
bolic disorders such as mitochondrial oxidation chain
A. SYMPTOMS AND SIGNS defects and glycogen storage disease, and muscular dys-
The clinical picture usually falls into two separate pat- trophies such as Duchenne or Becker) can be differenti-
terns: (1) Onset of CHF is sudden in a newborn who ated from inflammatory diseases of the myocardium
has been in relatively good health 12–24 hours previ- (myocarditis).
 CARDIOVASCULAR DISEASES / 607

Treatment • Increasing symptoms of heart disease (ranging

from easy fatigability to heart failure).
The use of digitalis in a rapidly deteriorating child with
myocarditis is dangerous and should be undertaken • Splenomegaly (70% of cases).
with great caution as it may provoke ventricular dys- • Embolic phenomena (50% of cases).
rhythmias in this situation. The inpatient cardiac sup- • Leukocytosis, elevated erythrocyte sedimentation
ports outlined previously are used in the treatment of rate, hematuria, positive blood culture.
these patients.
The administration of corticosteroids for myocardi-
tis is controversial. If the patient’s condition continues
to deteriorate despite anticongestive measures, cortico-
steroids are commonly used, although conclusive data General Considerations
supporting their effectiveness in this condition are lack- Bacterial or fungal infection of the endocardial surface
ing. Other immunosuppressive agents, such as cy- of the heart or the intimal surface of certain arterial ves-
closporine, are now being tried in viral myocarditis. sels (coarcted segment of aorta or ductus arteriosus) is a
Subsequent to the successful use of intravenous im- rare condition that usually occurs when a preexisting
munoglobulin for children with Kawasaki disease, sev- abnormality of the heart or great arteries is present. It
eral trials have occurred using this product in presumed may develop in a normal heart during the course of sep-
viral myocarditis. The therapeutic value of this treat- ticemia.
ment still remains unconfirmed in many practitioners’ The frequency of infective endocarditis appears to
minds. be increasing owing to many factors, including (1) in-
creased survival rates for children with congenital heart
Prognosis disease, (2) greater long-term use of central venous
catheters, and (3) increased use of prosthetic material
The prognosis for a patient with myocarditis is related and valves. Pediatric patients without preexisting heart
to the age at onset and to the patient’s response to ther- disease are also at increased risk for infective endocardi-
apy. If the patient is younger than age 6 months or tis owing to (1) increased survival rates for children
older than age 3 years and responds poorly to therapy, with immune deficiencies, (2) greater long-term use of
the prognosis is poor. Many patients recover clinically indwelling lines in critically ill newborns, and (3) in-
but have persistent LV dysfunction with cardiomegaly. creased incidence of intravenous drug abuse.
It is possible that subclinical myocarditis in childhood Patients at greatest risk include those with left-sided
is the pathophysiologic basis for some of the idiopathic outflow obstruction or aorticopulmonary shunts and
dilated cardiomyopathies occurring later in life. Chil- those with allograft, heterograft, or prosthetic cardiac
dren with myocarditis whose ventricular function fails valves. The actual cause of the episode of infective en-
to return to normal are potential candidates for cardiac docarditis can be identified approximately 30% of the
transplantation. time, and these include dental procedures, nonsterile
surgical procedures, and cardiovascular surgery.
Baboonian C, McKenna W: Eradication of viral myocarditis: Is Organisms causing endocarditis include viridans
there hope? J Am Coll Cardiol 2003;42(3);473 [PMID: streptococci (about 50% of cases), Staphylococcus aureus
12906975].
(about 30%), and fungal agents (about 10%).
Bowles NE et al: Detection of viruses in myocardial tissues by poly-
merase chain reaction. Evidence of adenovirus as a common
cause of myocarditis in children and adults. J Am Coll Car- Clinical Findings
diol 2003;42(3):466 [PMID: 12906974].
Liu PP, Mason JW: Advances in the understanding of myocarditis. A. HISTORY
Circulation 2001;104(9):1076 [PMID: 11524405]. Almost all patients with infective endocarditis have a
history of heart disease. There may or may not be a his-
tory of infection or a surgical procedure (tooth extrac-
INFECTIVE ENDOCARDITIS tion, tonsillectomy).
B. SYMPTOMS, SIGNS, AND LABORATORY FINDINGS
ESSENTIALS OF DIAGNOSIS
Findings include changing murmurs, fever, positive
& TYPICAL FEATURES blood culture, weight loss, cardiomegaly, elevated sedi-
mentation rate, splenomegaly, petechiae, embolism,
• Preexisting organic heart murmur. and leukocytosis. Other findings are hematuria, signs of
• Persistent fever. CHF, clubbing, joint pains, and hepatomegaly. Vegeta-
608 / CHAPTER 19

tions are large enough to be seen by echocardiography PERICARDITIS

in 70% of children with endocarditis.

ESSENTIALS OF DIAGNOSIS
Prevention & TYPICAL FEATURES
Patients at risk for infective endocarditis should be
given appropriate antibiotics before any type of dental • Retrosternal pain made worse by deep inspiration
work (tooth extraction, cleaning), before operations and decreased by leaning forward.
within the oropharynx, gastrointestinal tract, and geni- • Fever.
tourinary tract, and for body piercing and tattooing,
which often are performed in less than sanitary condi- • Shortness of breath and grunting respirations are
tions. Continuous antibiotic prophylaxis (as in the common.
treatment of rheumatic fever) is not recommended in • Pericardial friction rub.
patients with congenital heart disease. • Tachycardia.
The following schedule is recommended: under • Hepatomegaly and distention of the jugular
40 kg, 50 mg/kg of oral amoxicillin; over 40 kg, veins.
2000 mg. This dose is to be given 1 hour prior to den-
tal procedures. If the patient is allergic to amoxicillin, • ECG with elevated ST segment.
an alternative prophylactic antibiotic is used.

Treatment
General Considerations
In a patient with known heart disease, the presence of
an otherwise unexplained fever should alert the physi- Involvement of the pericardium rarely occurs as an iso-
cian to the possibility of infective endocarditis. A posi- lated event. In most cases, pericardial disease occurs in
tive blood culture or other major findings of infective association with a more generalized process. Common
endocarditis confirm the diagnosis. If a positive blood causes include rheumatic fever, viral pericarditis, puru-
culture is obtained and the organism is identified, spe- lent pericarditis, rheumatoid arthritis, uremia, and tu-
cific treatment should be begun immediately. Even if berculosis. Pericarditis after cardiac surgery (postperi-
blood cultures are negative after 48 hours, it is advisable cardiotomy syndrome) is a common condition in
to begin antibiotic therapy (if other evidence of infec- pediatric cardiology, most commonly seen after surgical
tive endocarditis is present), because most positive cul- closure of an ASD.
tures are obtained within the first 48 hours. If CHF oc- In the pediatric age group, pericardial disease usually
curs and progresses unremittingly in the face of takes the form of acute pericarditis. In most cases, fluid
adequate antibiotic therapy, surgical excision of the in- effuses into the pericardial cavity. The consequences of
fected area and prosthetic valve replacement must be such effusion depend on the amount, type, and speed
considered. of fluid accumulation. Under certain circumstances, se-
rious compression of the heart occurs, which can lead
to cardiac tamponade. Unless the pericardial fluid is
Course & Prognosis evacuated in this situation, death may occur.
The prognosis depends on how early in the course of
the infectious process treatment is instituted. The prog- Clinical Findings
nosis is better in patients in whom the blood culture is
positive. If CHF develops, the prognosis is poor. Em- A. SYMPTOMS AND SIGNS
bolization may occur during or after treatment from The symptoms depend to a great extent on the cause of
the vegetations themselves. Infective endocarditis is a the pericarditis. Pain is common. It is usually sharp and
serious condition and should be avoided if at all possi- stabbing, located in the mid chest and in the shoulder
ble. and neck, made worse by deep inspiration, and consid-
erably decreased by sitting up and leaning forward.
Dajani AS et al: Prevention of bacterial endocarditis: Recommen-
Shortness of breath and grunting respirations are com-
dations by the American Heart Association. JAMA 1997; mon findings in all patients.
277(22):1794 [PMID: 9178793]. The physical findings depend on whether a signifi-
Friedel JM et al. Infective endocarditis after oral body piercing. cant amount of effusion is present: (1) In the absence of
Cardiol Rev 2003;11(5):252 [PMID: 12943601]. significant accumulation of fluid, the pulses are normal.
 CARDIOVASCULAR DISEASES / 609

The heart has a characteristic scratchy, high-pitched of impending circulatory collapse, an immediate peri-
friction rub. The rub is often systolic and diastolic and cardiocentesis is performed. If pericardiocentesis is un-
can be located at any point between the apex and the successful, a surgical pericardiectomy is required. Di-
left sternal border. The location and timing vary con- uretics are to be avoided in the patient with cardiac
siderably from time to time. The heart sounds are usu- tamponade because they reduce ventricular preload,
ally normal, and the heart is not enlarged to percussion. which can exacerbate the degree of cardiac compres-
(2) If considerable pericardial fluid has accumulated, sion.
the cardiovascular findings are different. The heart is
enlarged to percussion, but on auscultation it is very
quiet. Heart sounds are distant and muffled. A friction
Prognosis
rub may not be present. In the absence of cardiac tam- The prognosis depends to a great extent on the cause of
ponade, the peripheral, venous, and arterial pulses are the pericardial disease. Cardiac tamponade from any
normal. cause results in death unless the fluid is evacuated.
Cardiac tamponade is characterized by distention of
the jugular veins, tachycardia, enlargement of the liver,
peripheral edema, and pulses paradoxus in which the SPECIFIC DISEASES INVOLVING
systolic pressure drops by more than 10 mm Hg during THE PERICARDIUM
inspiration. This finding is best determined with the Acute Rheumatic Fever
use of a manual blood pressure cuff. At this point, the
patient is critically ill and has all the symptoms and When pericarditis occurs during the course of acute
signs suggestive of right-sided CHF. rheumatic fever, it is almost always associated with in-
Not all patients with marked cardiac compression volvement of the myocardium and the endocardium
demonstrate all of these findings. If the patient appears (pancarditis). Thus heart murmurs are almost always
critically ill and pericarditis and effusion are evident, present. The pericarditis is usually of the serofibrinous
treatment should be instituted even though all the clin- variety and is usually not associated with a significant
ical signs of cardiac tamponade are not present. pericardial effusion. The treatment of the pericardial ef-
fusion is accomplished by the therapy for the acute
B. IMAGING rheumatic fever.
In pericarditis without significant effusion, chest radio-
graphic findings are normal. With pericardial effusion, Viral Pericarditis
the cardiac silhouette is enlarged, often in the shape of a
water bottle. Viral pericarditis occurs in children and young adults.
The most common cause is coxsackie virus B. Influenza
C. ELECTROCARDIOGRAPHY virus has also been implicated. There is usually a history
A number of ECG abnormalities occur in patients with of a protracted upper respiratory tract infection. The
pericarditis. Low voltage is commonly seen in patients pericardial effusion may last for several weeks. Cardiac
with significant pericardial effusion. The ST segment is tamponade is rare. Constrictive pericarditis can occur as
commonly elevated during the first week of involve- a sequela of viral pericarditis.
ment. The T wave is usually upright during this time.
Following this, the ST segment is normal and the T Purulent Pericarditis
wave becomes flattened.
The most common causes of purulent pericarditis are
D. ECHOCARDIOGRAPHY pneumococci, streptococci, staphylococci, and
Echocardiography is essential in the diagnosis and man- Haemophilus influenzae. This disorder is always sec-
agement of pericarditis. Serial echo studies allow the ondary to infection elsewhere, although occasionally
cardiologist a direct noninvasive estimate of the volume the primary site is unknown. In addition to demon-
of fluid and its changes over time. In addition, echocar- strating signs of cardiac compression, patients are septic
diography will demonstrate cardiac tamponade by com- and run extremely high fevers. The purulent fluid accu-
pression of the atria by the pericardial effusion. mulating within the pericardial sac is usually quite thick
and filled with polymorphonuclear leukocytes. Al-
though antibiotics will sterilize the pericardial fluid,
Treatment pericardial tamponade commonly develops, and surgi-
Treatment depends on the cause of pericarditis. Car- cal excision of the pericardium is frequently necessary.
diac tamponade resulting from any cause must be Acutely, pericardiocentesis may be lifesaving if there are
treated by evacuation of the fluid. If there are findings findings of tamponade on presentation. The wide use
610 / CHAPTER 19

of the H influenzae vaccine in recent years has signifi- Table 19–19. The 95th percentile value for blood
cantly reduced the incidence of this condition. pressure (mm Hg) taken in the sitting position.a

Postpericardiotomy Syndrome Sea Level 10,000 ft

Postpericardiotomy syndrome is characterized by fever, S Dm Dd S Dm Dd
chest pain, friction rub, and elevation of the ST seg-
5 92 72 62
ment noted on ECG 1–2 weeks after open-heart
6 106 64 60 96 74 66
surgery. The syndrome appears to be an autoimmune 7 108 72 66 98 76 70
disease with high titers of antiheart antibody and with 8 110 76 70 104 80 70
detectable evidence of fresh or reactivated viral illness. 9 114 80 76 106 80 70
The syndrome is often self-limited and responds well to 10 118 82 76 108 80 70
short courses of aspirin or corticosteroid therapy. 11 124 82 78 108 80 72
Rarely, it lasts for months to years and may require 12 128 84 78 108 80 72
pericardiocentesis or pericardiectomy. 13 132 84 80 116 84 76
14 136 86 80 120 84 76
Cakir O et al: Purulent pericarditis in childhood: Ten years of ex- 15 140 88 80 120 84 80
perience. J Pediatr Surg 2002;37(10):1404 [PMID: 16 140 90 80 120 84 80
12378443]. 17 140 92 80 122 84 80
Roodpeyma S, Sadeghian N: Acute pericarditis in childhood: A 10- 18 140 92 80 130 84 80
year experience. Pediatr Cardiol 2000;21(4):363 [PMID: a
10865014]. Blood pressures: S = systolic (Korotkoff sound 1; onset of tap-
ping), Dm = diastolic muffling (Korotkoff sound 4), Dd = diastolic
disappearance (Korotkoff sound 5).
HYPERTENSION
Blood pressure should be determined at every pediatric
hypertensive therapy should be initiated in addition to
visit beginning at age 3 years. Because this is now being
nutritional and exercise counseling when applicable.
done, systemic hypertension has become more widely
Beta-blockers or ACE inhibitors are the usual first-line
recognized as a pediatric problem. Pediatric standards
medical therapies for essential hypertension in children.
for blood pressure have been published. Blood pressures
in children must be obtained when the child is relaxed,
and an appropriate-size cuff must always be used. The Gifford RW et al: The fifth report of the Joint National Committee
widest cuff that fits between the axilla and the antecu- on detection, evaluation, and treatment of high blood pres-
bital fossa is used in each case. Most children age sure. Arch Intern Med 1993;153(2):154 [PMID: 8422206].
10–11 years need a standard adult-size cuff (bladder Gillman MW et al: Identifying children at high risk for the devel-
width of 12 cm), and many high school students need a opment of essential hypertension. J Pediatr 1993;122(6):
837 [PMID: 8501557].
large adult-size cuff (width of 16 cm) or leg cuff (width
of 18 cm). The 95th percentile value for blood pressure
(Table 19–19) is similar for both sexes and all three eth- ATHEROSCLEROSIS
nic groups. Blood pressure varies more with altitude and AS A PEDIATRIC PROBLEM
body weight than with sex or ethnic origin. If the blood
pressure taken in a quiet atmosphere and sitting position Awareness of the importance of coronary artery risk fac-
exceeds the 95th percentile for systolic, diastolic muffle, tors in general—and atherosclerosis in particular—has
or diastolic disappearance pressures, it should be re- risen dramatically in the general population since the
peated several times over a 2- to 4-week interval. If it is mid 1970s. Although coronary artery disease is still the
elevated persistently, an evaluation for the cause of the leading cause of death in the United States, the age-ad-
hypertension should be undertaken. Although most hy- justed incidence of death from ischemic heart disease
pertension in children is essential, there is a higher inci- has been decreasing since that time as a result of an im-
dence of treatable conditions within pediatrics than in proved diet, decreased smoking, awareness and treat-
adult medicine, such as coarctation of the aorta, renal ment of hypertension, and an increase in physical activ-
artery stenosis, chronic renal disease, and pheochromo- ity. During this period, a large number of serum
cytoma. Over-the-counter and recreational drug use samples from the pediatric population have been col-
may be important causative or contributing factors. Pe- lected and analyzed for lipids, and epidemiologic stud-
diatricians must look for these conditions when a ies have been performed to determine the relationship
child presents with hypertension. If no secondary cause of lipid levels to coronary heart disease. The level of
is found, and the hypertension is deemed essential, anti- serum lipids in childhood usually remains the same
 CARDIOVASCULAR DISEASES / 611

through adolescence. Biochemical abnormalities in the General Considerations

lipid profile appear early in childhood and correlate
with higher risk for coronary artery disease in adult- Unexplained or primary pulmonary hypertension
hood. High-density lipoprotein (HDL) has been identi- (PPH) in children is a rare disease with an estimated
fied as an antiatherogenic factor. The most common overall incidence of 1–2 persons per million worldwide.
lipid profile referred to treatment centers has changed Pulmonary hypertension is defined as a mean pul-
to a high triglyceride level, modest elevation of low- monary pressure that is greater than 25 mm Hg at rest
density lipoprotein (LDL), and low HDL level associ- or greater than 30 mm Hg during exercise. PPH is a di-
ated with obesity, insulin resistance, and prediabetes. agnosis of exclusion of all other causes of pulmonary
The concept of routine universal pediatric screening hypertension. Secondary pulmonary hypertension is
after age 3 years remains controversial. The National most commonly associated with congenital heart dis-
Cholesterol Education Program recommends selective ease, pulmonary parenchymal disease, causes of chronic
screening in children with high-risk family members, de- hypoxia (upper airway obstruction), thrombosis, liver
fined as a parent with a total cholesterol over 240 mg/dL disease, and collagen vascular disease. The diagnosis of
or a parent or grandparent with early-onset cardiovascu- PPH is difficult to make in the early stages because of
lar disease. When children have LDL levels greater than its subtle manifestations. Most patients with PPH are
130 mg/dL on two successive tests, dietary lifestyle coun- young adults, predominantly women; however, the sex
seling is appropriate. Dietary modification may decrease incidence is equal in children. Familial PPH occurs in
cholesterol levels by 5–20%. If the patient is unrespon- 6% of affected individuals. The locus for familial PPH
sive to diet change and at extreme risk (ie, a LDL level > is found on chromosome 2 (2q33) and is caused by ab-
160 mg/dL, an HDL level < 35 mg/dL, and a history of normalities in the transforming growth factor beta fam-
cardiovascular disease in a first-degree relative at an age ily, specifically bone morphogenetic protein receptor II.
younger than 40 years), drug therapy may be indicated. Without treatment, the median survival is 2.5 years.
Cholestyramine, a bile exchange resin, has had moderate
success, but compliance is poor in children because of Clinical Findings
the drug’s unpalatability. Niacin and the HMG-CoA re-
ductase inhibitors are also used in the pediatric popula- A. SYMPTOMS AND SIGNS
tion and have had encouraging preliminary results. The clinical picture varies depending on the severity of
the pulmonary hypertension. Initial symptoms may be
brought on by strenuous exercise or competitive sports,
De Jongh S et al: Efficacy and safety of statin therapy in children and syncope may be the first symptom. Dyspnea on ex-
with familial hypercholesterolemia: A randomized double-
blind placebo-controlled trial with Simvastatin. Circulation ertion is present in most patients; syncope occurs in ap-
2002;106(17):2231 [PMID: 12390953]. proximately one third of patients. Palpitations or chest
Gidding SS: Preventive pediatric cardiology: Tobacco, cholesterol, pain may occur with exercise. As the disease progresses,
obesity, and physical activity. Pediatr Clin North Am 1999; patients have signs of low cardiac output and right heart
46(2):253 [PMID: 10218073]. failure. Right heart failure may be manifested by an in-
crease in hepatomegaly with peripheral edema and a gal-
lop rhythm on examination. Murmurs of pulmonary re-
PRIMARY PULMONARY gurgitation and tricuspid regurgitation are common. An
HYPERTENSION S3 is occasionally heard with advanced right heart failure.
B. IMAGING
ESSENTIALS OF DIAGNOSIS The chest radiograph typically shows an enlarged heart
& TYPICAL FEATURES with a prominent pulmonary artery and dilated proxi-
mal right and left pulmonary arteries. The peripheral
• Often subtle with symptoms of dyspnea, fatigue, pulmonary vascular markings may be normal or dimin-
chest pain, and syncope. ished.
• Exclusion of all causes of secondary pulmonary
hypertension.
C. ELECTROCARDIOGRAPHY
• Rare, progressive, and often fatal disease without
The ECG usually shows right atrial enlargement with
RVH and right axis deviation.
treatment.
• ECG with RVH. D. ECHOCARDIOGRAPHY
• Loud pulmonary component of S2. The echocardiogram is an important diagnostic tool for
excluding causes of congenital heart disease. It fre-
612 / CHAPTER 19

quently shows RVH and dilation. The tricuspid and CHEST PAIN
pulmonary insufficiency jets may be used to estimate
pulmonary artery systolic and diastolic pressures. Overview
Chest pain is a common complaint of pediatric pa-
E. CARDIAC CATHETERIZATION AND tients, accounting for 6 in 1000 visits to urban emer-
ANGIOCARDIOGRAPHY gency rooms and urgent care clinics. Although children
Cardiac catheterization has an increased risk in children with chest pain are commonly referred for cardiac eval-
with pulmonary hypertension and should be performed uation, chest pain in children is rarely due to cardiac
with great caution. The procedure is done first to rule pathology. Other possible causes of chest pain include
out cardiac causes of pulmonary hypertension and then musculoskeletal pain, esophagitis/gastritis, and func-
to define treatment strategies. Patients who have a pul- tional pain.
monary vascular bed that is reactive to short-acting va-
sodilator agents (nitric oxide, adenosine, prostacyclin)
may receive treatment with calcium channel blockers. Approach to the Work-up
In contrast, patients who have a pulmonary vascular A detailed history and physical exam should guide the
bed that does not improve with these short-acting pediatrician through an appropriate work-up of chest
agents often receive prostacyclin therapy. Angiography pain. (A known medical history of cardiac or respira-
may show a marked decrease in the number of small tory disease will of course provide additional guidance.)
pulmonary arteries with tortuous vessels. Rarely is there a need for laboratory tests or further
evaluation by a specialist. The duration, location, inten-
Treatment sity, frequency, and radiation of the pain should be
documented, and possible triggering events preceding
The goal of therapy is to reduce pulmonary artery pres- the pain should be explored. For instance, chest pain
sure and increase cardiac output. The cardiac catheteri- following exertion may lead to a more elaborate evalua-
zation data are used to define the treatment plan. Pa- tion for a cardiac disorder. Or the timing of the pain in
tients who have shown a response to pulmonary relation to meals may suggest a gastrointestinal cause.
vasodilators are given calcium channel blockers such as The patient should also be asked about how pain relief
nifedipine or diltiazem. Patients who are unreactive to is achieved. A social history to reveal psychosocial stres-
these vasodilators in the catheterization laboratory ini- sors and cigarette smoke exposure may assist in deter-
tially receive prostacyclin therapy. Patients with severe, mining the cause. On physical exam, attention must be
unreactive pulmonary hypertension may be considered placed on the vital signs, general appearance of the
for lung transplantation. Common therapies include child, the chest wall musculature, cardiac, pulmonary,
warfarin to prevent thromboembolic events. This ap- and abdominal exam findings, and quality of peripheral
proach is beneficial in adults. Digoxin and diuretics pulses. Attempts should be made to reproduce the pain
may be used if signs of right heart failure are present. by direct palpation and through forced resistance ap-
Receptor antagonists to the potent vasoconstrictor pep- plied to the patient’s upper extremities. If the pain is re-
tide endothelin show great promise in the treatment of produced, it is almost always musculoskeletal in origin.
pulmonary hypertension.
Survival rates of greater than 90% have been re-
ported using chronic oral calcium channel blockade in Clinical Considerations
patients who responded acutely to vasodilator testing.
In patients in whom calcium channel blockade fails, or Cardiac disease is a rare cause of chest pain, but if mis-
in those who do not respond acutely to vasodilator diagnosed it may be life-threatening. Myocardial infarc-
therapy, intravenous prostacyclin has been used with a tion rarely occurs in healthy children. Children with
5-year survival rate of greater than 80%. underlying illnesses such as diabetes mellitus, chronic
anemia, or an anomalous left coronary artery may be at
increased risk for ischemia. It is also important to ask
Archer S, Rich S: Primary pulmonary hypertension. Circulation the family specifically about a history of Kawasaki dis-
2000;102(22):2781 [PMID: 11094047]. ease, treated or untreated. These children are at risk for
Deng Z et al: Familial primary pulmonary hypertension (gene PPH cardiac sequelae including myocardial infarct secondary
I) is caused by mutations in the bone morphogenentic pro-
tein receptor II gene. Am J Hum Genet 2000;67(3):737
to thrombosis of their coronary aneurysms, cardiac ar-
[PMID: 10903931]. rhythmias, or sudden death. More than 50% of chil-
Ivy DD: Diagnosis and treatment of severe pediatric pulmon- dren and adolescents who exhibit sequelae from
ary hypertension. Cardiol Rev 2001;9(4):227 [PMID: Kawasaki disease arrive at the emergency department
11405903]. with chest pain.
 CARDIOVASCULAR DISEASES / 613

Other cardiac causes of chest pain include arrhyth- transplantation in the 1980s and early 1990s is approxi-
mias. The most common arrhythmia in children is mately 15 years. This is a rapidly developing field, and
supraventricular tachycardia (SVT), but atrial flutter the most recent data indicate an improved prognosis.
and premature ventricular contractions (PVCs) may also Cardiac transplantation is the paradigm of an in-
be associated with chest pain in children. Other struc- flammatory disease of the transplanted myocardium.
tural lesions that cause chest pain include aortic stenosis, Because the donor and the recipient are not matched
pulmonary stenosis, and mitral valve prolapse. Struc- for histocompatibility antigens, the potential for graft
tural cardiac lesions are usually detected prior to the rejection by the host immune system is always present.
child’s emergency room visit. They are accompanied by Long-term immunosuppressive medications are re-
significant findings on cardiac exam. Of children diag- quired to control this inflammatory process. The main-
nosed with mitral valve prolapse, 31% will complain of stay for immunosuppressive agents in cardiac transplant
chest pain, caused by papillary muscle ischemia. Other recipients remains cyclosporin A. Cyclosporine is usu-
cardiac lesions that cause chest pain include dilated car- ally well tolerated but has been associated with the po-
diomyopathy, hypertrophic obstructive cardiomyopa- tential for renal dysfunction, hypertension, and proba-
thy, myocarditis, rheumatic fever, aortic dissection, and bly an increased risk of malignancy. In addition,
pericarditis. Pain from hypertrophic obstructive car- adolescent patients are affected by the visible side effects
diomyopathy may be associated with exertion. of hirsutism and gingival hyperplasia. In the current
Noncardiac chest pain may be due to a respiratory era, the therapeutic blood levels of cyclosporine have
illness—for example, reactive airway disease, pneumo- been reduced, and most of these side effects occur less
nia, pneumothorax, or pulmonary embolism. Gastroin- frequently. Graft rejection can be triggered by lack of
testinal causes of chest pain include reflux, esophagitis, compliance, infection, and other issues, which are not
and foreign body. The most common cause of chest well understood. Although the greatest risk of rejection
pain (30% of children) is inflammation of muscu- is in the first 3 months after transplant, a low risk per-
loskeletal structures of the chest wall. Costochondritis sists even years after the transplant procedure.
involves inflammation of the costochondral or cos- Unlike other inflammatory diseases of the my-
tosternal junctions and is usually unilateral. Chest wall ocardium, the process of graft rejection is fairly well un-
pain is more common in girls and is reproducible on derstood. The T lymphocyte is the predominant effector
examination. cell, which receives antigen presentation, predominantly
After a complete history and physical are obtained, from tissue histiocytes and macrophages. These cells
the information gathered can guide the examiner to the present antigens to the T-cell receptor in a cradle. Be-
appropriate diagnosis or, if necessary, the appropriate cause the donor antigens are new to the host, a popula-
laboratory tests to be ordered. In most cases, additional tion of T lymphocytes can react to these antigens. This
tests are not necessary. If a cardiac origin is suspected, a process is in contrast to the presentation of host anti-
pediatric cardiologist should be consulted. Positive car- gens, which do not have T lymphocytes that are pro-
diac findings on initial evaluation should be followed grammed to respond. The process of elimination of self-
with a combination of the following: an ECG, chest ra- responding T lymphocytes takes place largely in the
diograph, echocardiogram, Holter monitor, and serum thymus in utero. However, a process of acquired toler-
troponin and creatinine kinase assays. ance, even to the foreign antigens of the donor, may also
involve the thymus and peripheral sites. Because the de-
fault mechanism for the immune system is to not react
to an antigen, with the passage of time and under the in-
CARDIAC TRANSPLANTATION fluence of immunosuppression, the host becomes less
and less responsive to donor antigens posttransplant.
The population of pediatric patients with a heart
Cardiac transplantation has developed into an effective transplant in the United States is approximately
therapeutic modality for end-stage inflammatory car- 3000 and growing; thus the major medical challenge is
diac diseases such as myocarditis and cardiomyopathies. surveillance and treatment of graft rejection.
In addition, transplantation has become a common
final therapeutic pathway for many structural cardiac
defects associated with cardiomyopathic changes. Car- Clinical Findings
diac damage from either long-standing congenital dis-
ease or surgery can also lead to transplantation. Approx- A. SYMPTOMS AND SIGNS
imately 300 pediatric cardiac transplant procedures are Transplant recipients undergoing the process of graft re-
performed annually in the United States. The current jection are usually asymptomatic in the early stages.
estimated half-life for children undergoing cardiac With progression they may develop tachycardia, tachy-
614 / CHAPTER 19

pnea, elevated central venous pressure, and a gallop must be maintained whenever a patient has a history of
rhythm. These findings are similar to what would be ex- cardiac transplantation. Usually graft function will re-
pected with CHF. As low cardiac output progresses, turn to the baseline state, although severe rejection
nausea and vomiting may ensue, followed by altered episodes can result in graft loss and patient death even
mental status, and finally peripheral circulatory collapse. with optimal therapy.
B. IMAGING
Chest radiographs often show cardiac enlargement and Course & Prognosis
increased pulmonary vascular markings.
The clinical course of cardiac transplantation in pedi-
C. ELECTROCARDIOGRAPHY atric patients is usually quite good. Despite the chronic
Abnormalities in conduction can be present, although immunosuppression, the risk of infection is low beyond
the most typical finding is a decrease in QRS voltage. the early posttransplant period. Most children seem to
Arrhythmias, both atrial and ventricular, can be evi- tolerate environmental pathogens quite readily. Over-
dence of rejection. whelming infection is uncommon. Noncompliance
with lifetime immunosuppression, especially among
D. ECHOCARDIOGRAPHY adolescents, is of great concern. Several recent studies
Echocardiography is a sensitive surveillance tool for have identified noncompliance as the leading cause of
graft rejection. Changes in ventricular compliance and late death after transplantation. Posttransplant lympho-
function are typical and become progressive with in- proliferative disorder, a syndrome related to
creasing duration of the rejection episode. Valval insuf- Epstein–Barr virus infection, can result in a Burkitt-like
ficiency may also indicate rejection. A new pericardial lymphoma that will usually respond to a reduction in
effusion can also indicate inflammation due to the re- immunosuppression. Most children are not physically
jection process. limited, and they do not require restrictions related to
the cardiovascular system. Because the heart is dener-
E. CARDIAC CATHETERIZATION vated, patients may exhibit a blunted response to exer-
AND ENDOMYOCARDIAL BIOPSY cise at the onset. The greatest concern over the long
term following heart transplantation is related to a syn-
The hemodynamic measurements can be relatively nor- drome of accelerated coronary atherosclerosis. This pre-
mal with mild rejection, but with progression the pul- mature form of atherosclerosis is unlike typical adult
monary capillary wedge pressure increases, indicating coronary disease in that it progresses quite rapidly. The
decreasing ventricular compliance. Often this is a global insult to the coronary endothelium is immune-medi-
process, and the RV filling pressures or central venous ated and can cause coronary obliteration. If the process
pressure may also be elevated. The endomyocardial is recognized and treated, its late appearance may
biopsy has remained the mainstay of tissue diagnosis for mimic the more typical adult atherosclerotic disease.
graft rejection. The appearance of infiltrating lympho- This observation has led some researchers to suggest
cytes with myocellular damage is the hallmark of graft that adult atherosclerotic disease is largely an inflamma-
rejection. Occasionally patients may have only a sparse tory process, perhaps initiated by environmental
lymphocytic infiltration despite profound myocardial pathogens.
performance abnormalities. Presumably, the depression Overall, despite the concerns of immunosuppression
in the myocardial function in the absence of lympho- and the risk of late rejection and graft atherosclerosis,
cytes is related to inflammatory mediators such as the majority of pediatric patients enjoy physiologic re-
tumor necrosis factor and the various interleukins. habilitation following cardiac transplantation with a
60–70% 10-year survival. Newer, more specific, and
Treatment more effective immunosuppressive agents are currently
The treatment for graft rejection depends on reversing being tried in clinical studies or are being evaluated in
the immunologic inflammatory cascade. High-dose preclinical studies, making the future almost certainly
corticosteroids are the first line of treatment. These can better for children after cardiac transplantation. Donor
stabilize or reverse most rejection episodes. Occasion- availability remains a major limitation to the expansion
ally additional therapy in the form of antithymocyte bi- of indications for cardiac transplantation.
ologic preparations such as antithymocyte globulin or
OKT-3 (a murine monoclonal antibody to the CD3 T-
Boucek MM et al: The Registry of the International Society of
lymphocyte epitope) is needed to reverse the rejection Heart and Lung Transplantation: Sixth official pediatric re-
process. Most rejection episodes can be treated effec- port—2003. J Heart Lung Transplant 2001;20(6):39
tively if diagnosed promptly. A high index of suspicion [PMID: 12821161].
 CARDIOVASCULAR DISEASES / 615

Moran AM et al: Non-invasive assessment of rejection in pediatric ercise intolerance) requires treatment (atropine or car-
transplant patients: Serologic and echocardiographic predic- diac pacing).
tion of biopsy-proven myocardial rejection. J Heart Lung
Transplant 2000;19(8):756 [PMID: 10967269].
Mulla NF et al: Late rejection is a predictor of transplant coronary Sinus Tachycardia
artery disease in children. J Am Coll Cardiol 2001;
37(1):243 [PMID: 11153746]. The heart rate normally accelerates in response to stress
(eg, fever, hypovolemia, anemia, CHF). Although sinus
tachycardia in the normal heart is well tolerated, symp-
tomatic tachycardia with decreased cardiac output is
more ominous and warrants evaluation for associated
DISORDERS OF RATE structural heart disease or true tachyarrhythmias. Treat-
& RHYTHM ment may be indicated for correction of the underlying
cause of sinus tachycardia (eg, transfusion for anemia,
correction of hypovolemia or fever).
The recognition and treatment of cardiac arrhythmias
have improved markedly since the 1980s. Better moni-
toring has increased the awareness and detection of PREMATURE ATRIAL CONTRACTIONS
rhythm disturbances. There is also a true rise in the in- Premature atrial contractions are triggered by an ec-
cidence of arrhythmias. More children are now surviv- topic focus in the atrium. They are one of the most
ing cardiac surgery and acute carditis and live chroni- common premature beats occurring in the pediatric
cally with altered hemodynamics, physiology, and population, particularly during the fetal and newborn
structural changes. These changes over time will create periods. They may be conducted (followed by a QRS)
altered conduction and new arrhythmias. or nonconducted (not followed by a QRS as the beat
The advent of invasive electrophysiology with has occurred so early that the AV node is still refrac-
recordings from the endocardium has greatly improved tory) (Figure 19–4). A less-than-compensatory pause
our understanding of the conduction system. Now, usually occurs until the next normal sinus beat. De-
with cardiac ablation techniques, we can offer these pending on the ectopic focus of the premature contrac-
children a “cure” rather than lifelong antiarrhythmia tion, the frontal plane vector of the P wave may be nor-
treatment. mal (+30–90 degrees) or abnormal. As an isolated
finding, premature atrial contractions are benign and
Sinus Arrhythmia require no treatment. They may need to be suppressed
with antiarrhythmic agents when they trigger tachy-
It is normal to have phasic variation in the heart rate arrhythmias or produce bradycardia secondary to non-
(sinus arrhythmia). Typically, the sinus rate varies with conduction.
the respiratory cycle, whereas P-QRS-T intervals re-
main normal. Marked sinus arrhythmia is defined as a PREMATURE JUNCTIONAL
greater than 100% variation in heart rate. It may occur
in association with respiratory distress or increased in- CONTRACTIONS
tracranial pressure, or it may be present in normal chil- Premature junctional contractions arise within the AV
dren. It alone never requires treatment; however, it may node or the bundle of His. Most often, they induce a
be associated with sinus node dysfunction or auto- normal QRS complex with no preceding P wave. When
nomic nervous system dysfunction. conducted aberrantly to the ventricles, they cannot be
distinguished from PVCs except by invasive electro-
physiologic study. Premature junctional contractions
Sinus Bradycardia are usually benign and require no specific therapy.
Depending on the patient’s age, sinus bradycardia is de-
fined as either (1) a heart rate below the normal limit PREMATURE VENTRICULAR
for age (neonates to 6 years, 60 beats/min; 7–11 years,
45 beats/min; older than 12 years, 40 beats/min) or
CONTRACTIONS
(2) a heart rate inappropriately slow for the functional PVCs may originate in either ventricle and are charac-
status of the patient (chronotropic incompetence). In terized by an abnormal QRS of over 80 ms duration in
critically ill patients, common causes of sinus bradycar- newborns and 120 ms in adolescents and adults (Figure
dia include hypoxia, central nervous system damage, 19–5). PVCs originating from a single ectopic focus all
and iatrogenic medication side effects. Only sympto- have the same configuration; those of multifocal origin
matic bradycardia (syncope, low cardiac output, or ex- show varying configurations. The consecutive occur-
616 / CHAPTER 19

1 2

3 4 5 6 7

Figure 19–4. Lead II rhythm strip with premature atrial contractions. Beats 1, 3, 7, and 8 are conducted to the ven-
tricles, whereas beats 2, 4, 5, and 6 are not.

Lead V5

Figure 19–5. Lead V5 rhythm strip with unifocal premature ventricular contractions in a bigeminy pattern. The
arrow shows a ventricular couplet.
 CARDIOVASCULAR DISEASES / 617

rence of two PVCs is referred to as a ventricular couplet mias are treated with vagolytic (atropine) or adrenergic
and of three or more as ventricular tachycardia. (aminophylline) agents or permanent cardiac pacemak-
Most unifocal PVCs in otherwise normal patients ers. Antiarrhythmic treatment of tachyarrhythmias
are benign. The significance of the PVCs can be con- often produces or enhances bradycardia, thus requiring
firmed by having the patient exercise. As the heart rate permanent cardiac pacing. In selected cases, a pace-
increases, benign premature contractions usually disap- maker is inserted prophylactically prior to the initiation
pear. If exercise results in an increase or coupling of of antiarrhythmic medications.
contractions, underlying disease may be present. Multi- The prognosis is excellent when appropriate treat-
focal PVCs are always abnormal and may be more dan- ment is provided, with total morbidity and mortality
gerous. They may be associated with drug overdose (tri- rates nearly equal to those of the underlying heart dis-
cyclic antidepressants, digoxin toxicity), electrolyte ease. However, in severe cases, if left untreated, sinus
imbalance, myocarditis, or hypoxia. Treatment is di- node dysfunction may become chronic and may even
rected at correcting the underlying disorder. lead to sudden death.

Miller MS et al: Neonatal bradycardia. Prog Pediatr Cardiol

SINUS NODE DYSFUNCTION 2000;11:19 [PMID: 10822186].
Sinus node dysfunction, or sick sinus syndrome, is a
clinical syndrome of inappropriate sinus nodal function SUPRAVENTRICULAR TACHYCARDIA
and rate. The abnormality may be a true anatomic de-
fect of the sinus node or its surrounding tissue, or it SVT, also known as paroxysmal SVT or paroxysmal
may be an abnormality of autonomic input. It is de- atrial tachycardia, is defined as an abnormal arrhythmia
fined as one or more of the following: mechanism arising above or within the bundle of His.
The mode of presentation depends on the tachycardia
1. Sinus bradycardia rate, the presence of underlying cardiac structural or
2. Marked sinus arrhythmia functional abnormalities, coexisting illness and the pa-
3. Chronotropic incompetence tient’s age. Tachycardia may be poorly tolerated in a
4. Sinus pause or arrest child who has preexisting CHF or an underlying sys-
temic disease such as anemia or sepsis, or it may go un-
5. Sinoatrial exit block noticed in an otherwise healthy child. Incessant tachy-
6. Combined bradyarrhythmias and tachyarrhyth- cardia in an otherwise healthy individual, albeit slow
mias (120–150 beats/min), may cause myocardial dysfunc-
7. Sinus node reentry tion and CHF if left untreated. The mechanisms of
8. Atrial muscle reentry tachycardia. tachycardia can be divided into three groups: reentry,
enhanced automaticity, and triggered dysrhythmias.
It is usually associated with postoperative repair of Reentry is conduction through two or more path-
congenital heart disease (most commonly the Mustard ways, creating a sustained repetitive circular loop. The
or Senning repair for complete transposition of the circuit can be confined to the atrium (intraatrial reen-
great arteries or the Fontan procedure), but it is also try, a form of atrial flutter) (Figure 19–6). It may be
seen in unoperated congenital heart disease, in acquired confined within the AV node (AV nodal reentrant
heart diseases, and in normal hearts. In some cases the tachycardia), or it may encompass an accessory connec-
disorder is inherited. Symptoms usually manifest be- tion between atria and ventricle (atrioventricular tachy-
tween ages 2 and 17 years and consist of episodes of cardia). The arrhythmia circuit includes conduction
syncope, presyncope, or disorientation. Some patients through the normal pathway (ie, the AV node) as well
may experience palpitations, pallor, or exercise intoler- as the accessory AV connection. If during tachycardia
ance. the electrical impulse travels antegrade (from atria to
The evaluation of sinus node dysfunction involves ventricle) through the AV node and retrograde (from
both surface ECG and invasive electrophysiologic test- ventricle to atria) back up the accessory pathway, ortho-
ing. Exercise testing, and ambulatory monitoring help dromic reciprocating tachycardia is present. If during
define any arrhythmias and correlate rhythm changes tachycardia the electrical impulse travels antegrade
with symptoms. through the accessory pathway and retrograde up
Treatment for sinus node dysfunction is indicated through the AV node, then antidromic reciprocating
only in symptomatic patients. Asymptomatic patients tachycardia is present. WPW syndrome is a subclass of
can just be observed for the onset of exercise intolerance reentrant tachycardia in which, during sinus rhythm,
or syncope because there is little chance of sudden the impulse travels antegrade down the accessory con-
death prior to the onset of symptoms. Bradyarrhyth- nection, bypassing the AV node and creating ventricu-
618 / CHAPTER 19

V1

Figure 19–6. Leads aVF (F) and V1, showing atrial flutter with “sawtooth” atrial flutter waves.

lar preexcitation (early eccentric activation of the ven- they are incessant, they are usually associated with CHF
tricle with a short PR interval and slurred upstroke of and a clinical picture of dilated cardiomyopathy.
the QRS, a delta wave) (Figure 19–7). Reentrant tachy- Triggered dysrhythmia is extremely rare. It is caused
cardia represents approximately 80% of pediatric ar- by enhanced afterdepolarizations of the action potential
rhythmias, has a wide range of rates, and may or may that reach the takeoff potential. These tachycardias are
not demonstrate P waves. Reentrant tachycardia initi- usually associated with diseased atrial myocardium, are
ates and terminates abruptly. Most patients with WPW triggered by premature atrial contractions or sinus
have otherwise structurally normal hearts. WPW how- tachycardia, initiate and terminate abruptly, and mimic
ever has been noted to occur with increased frequency intraatrial reentry (atrial flutter). However, they can be
in association with the following congenital cardiac le- distinguished from atrial flutter: they terminate with
sions: tricuspid atresia, Ebstein anomaly of the tricuspid the administration of adenosine, while atrial flutter
valve, HCM, and ccTGA. does not (see section on Artial Flutter & Fibrillation).
Enhanced automaticity (also known as automatic or
ectopic tachycardia) is created when a focus of cardiac
tissue develops an abnormally fast spontaneous rate of Clinical Findings
depolarization. These arrhythmias represent approxi-
mately 20% of childhood arrhythmias and are usually A. SYMPTOMS AND SIGNS
under autonomic influence. ECG demonstrates a nor- Clinical presentation varies with the patient’s age. In-
mal QRS complex preceded by an abnormal P wave fants tend to turn pale and mottled with onset of tachy-
(Figure 19–8). Junctional ectopic tachycardia does not cardia and may become irritable. With long duration of
have a P wave preceding the QRS waves and may be as- tachycardia, symptoms of CHF develop. Heart rates
sociated with AV dissociation or 1:1 retrograde conduc- can be from 240 to 300 beats/min. Older children may
tion. Ectopic tachycardias demonstrate a gradual onset complain of dizziness, palpitations, fatigue, and chest
and offset and may be paroxysmal or incessant. When pain. Heart rates usually range from 240 beats/min in

Spontaneous Intermittent Pre-excitation

I
Delta Delta No delta Delta Delta Delta No delta
II

Figure 19–7. Leads I and II with spontaneous intermittent ventricular preexcitation (Wolff–Parkinson–White syn-
drome).
 CARDIOVASCULAR DISEASES / 619

II II

0:00:18

II

0:00:36

II

0:00:57
0:01:13

Figure 19–8. Lead II rhythm strip of ectopic atrial tachycardia. The tracing demonstrates a variable rate with a
maximum of 260 beats/min, an abnormal P wave, and a gradual termination.

the younger child to 150–180 beats/min in the 4. The QRS complex is usually the same as during
teenager. CHF is less common in children than in in- normal sinus rhythm. However, the QRS com-
fants. Tachycardia may be associated with either con- plex is occasionally widened (SVT with aberrant
genital heart defects, as mentioned earlier, or acquired ventricular conduction), in which case the condi-
conditions such as cardiomyopathies and myocarditis. tion may be difficult to differentiate from ventric-
ular tachycardia.
B. IMAGING
Findings on chest radiograph are normal during the Treatment
early course of tachycardia. If CHF is present, the heart
is enlarged and pulmonary venous congestion is evi- A. ACUTE TREATMENT
dent. During initial episodes of SVT, patients require close
monitoring. Correction of acidosis and electrolyte ab-
C. ELECTROCARDIOGRAPHY
normalities is also indicated.
ECG is the most important tool in the diagnosis of
SVT. 1. Vagal maneuvers—The “diving reflex,” produced
by placing an ice bag on the nasal bridge for 20 seconds
1. The heart rate is rapid and out of proportion to (for infants) or by immersing the face in ice water (for
the patient’s physical status (ie, a rate of children or adolescents), will increase parasympathetic
140 beats/min with an abnormal P wave while tone and terminate some tachycardias. The Valsalva
quiet and asleep). maneuver, which can be performed by older compliant
2. The rhythm is extremely regular. There is little children, may also terminate SVT.
variation in the rate throughout the entire tracing. 2. Adenosine—Adenosine transiently blocks AV con-
3. P waves may or may not be present. If they are duction and terminates tachycardias that incorporate
present, the PR interval and appearance do not the AV node.
vary. P waves may be difficult to find because they Adenosine does not convert tachycardias whose
are superimposed on the preceding T wave. Fur- mechanism is confined to the atria (atrial ectopic tachy-
thermore, if the abnormal focus is located within cardia, intraatrial reentry). However, it serves as a diag-
the AV node, the P waves will not be seen. nostic tool in these arrhythmias by demonstrating con-
620 / CHAPTER 19

tinuation of the atrial tachycardia during AV block, im- 4. Other drugs—Recently introduced antiarrhythmic
plying that AV node conduction is not a crucial ele- medications (eg, flecainide, propafenone, sotalol, and
ment of the tachycardia circuit. The dose is amiodarone) have increased pharmacologic actions and
50–250 µg/kg by rapid intravenous bolus. It is antago- are extremely effective. However, these drugs also have
nized by aminophylline and should be used with cau- serious side effects, including proarrhythmia (produc-
tion in patients with sinus node dysfunction or asthma. tion of arrhythmias) and sudden death, and should be
3. Transesophageal atrial pacing—Atrial overdrive used only under the direction of a pediatric cardiolo-
pacing and termination can be performed from a bipo- gist.
lar electrode-tipped catheter positioned in the esopha- 5. Radiofrequency ablation—This is a nonsurgical
gus adjacent to the left atrium. Overdrive pacing at transvascular catheter technique that will desiccate an
rates approximately 30% faster than the tachycardia arrhythmia focus or accessory pathway and perma-
rate will interrupt the tachycardia circuit and restore nently “cure” an arrhythmia. The immediate success
sinus rhythm. rate is approximately 90%, with a rate of recurrence of
4. Direct current cardioversion—Direct current 10%. The risk of developing complete heart block is
(DC) cardioversion (0.5–2 synchronized J/kg) should approximately 2–10% when applying burns in the
be used immediately when a patient presents in cardio- vicinity of the AV node/His bundle. The procedure can
vascular collapse. be performed in infants or adults. In children younger
B. CHRONIC TREATMENT than age 4 years, the risks are higher, and the procedure
should be reserved for those whose arrhythmias are re-
1. Digitalis—Digoxin is still frequently used for long- fractory to medical management. In well-tolerated
term treatment and maintenance of sinus rhythm. The SVTs that respond to vagal maneuvers, no further
doses used are the same as those for CHF. Conversion treatment is necessary. However, the high success rate,
should be accomplished within 8–12 hours. In some low complication and recurrence rates, and the elimina-
patients digoxin can accelerate conduction over an ac- tion of the need for chronic antiarrhythmic medica-
cessory pathway, and in those children digitalis prod- tions have made radiofrequency ablation the primary
ucts are contraindicated. Patients with an accessory treatment option in most pediatric cardiovascular cen-
pathway (eg, those with WPW syndrome) often have ters.
primary atrial tachycardias (atrial flutter or fibrillation,
atrial ectopic tachycardias), and with enhanced conduc-
tion in the accessory pathway these primary atrial Prognosis
tachycardias can transmit to the ventricles, causing ven- SVT has an excellent prognosis. When it occurs in early
tricular fibrillation. Therefore, an evaluation of the ef- infancy, 90% will respond to initial treatment. Approx-
fect of digoxin on the accessory pathway should be per- imately 30% will recur at an average age of 8 years.
formed in the electrophysiology lab before chronic
digoxin use in patients with WPW syndrome.
2. Beta-adrenergic blocking agents—Propranolol Basson CT: A molecular basis for Wolff–Parkinson–White syn-
drome. N Engl J Med 2001;344(24):1861 [PMID:
decreases sinus heart rate and AV nodal conduction. It 11407351].
is effective in the treatment of both reentrant and ec- Dubin AM et al: Radiofrequency catheter ablation: Indications and
topic arrhythmias in doses ranging from 1 to complications. Pediatr Cardiol 2000;21(6):551 [PMID:
4 mg/kg/d. Long-acting β-blockers, such as atenolol 11050279].
and nadolol, are used because they have fewer central Moak JP: Supraventricular tachycardia in the neonate and infant.
nervous system side effects than propranolol and may Prog Pediatr Cardiol 2000;11(1):25 [PMID: 10822187].
be given only once or twice a day.
3. Calcium channel antagonists—Verapamil and
other calcium channel blockers markedly prolong con-
ATRIAL FLUTTER & FIBRILLATION
duction through the AV node and are effective in inter- Atrial flutter and fibrillation are rare in children and are
rupting and preventing reentrant tachycardias that in- most often associated with organic heart disease—par-
corporate the AV node. They are ineffective in ticularly postoperative congenital heart disease and
terminating atrial tachycardias but may be useful in sinus node dysfunction. Atrial flutter can occur in in-
controlling the ventricular response by producing AV fancy and can mimic SVT. The atrial rate is usually
blockade. Verapamil comes in short- and long-acting greater than 240 beats/min and often more than
preparations; the dose is 3–5 mg/kg/d. It may cause 300 beats/min. The ventricular rate depends on the rate
myocardial dysfunction and is contraindicated in in- of AV conduction and is usually slower than the atrial
fants. rate.
 CARDIOVASCULAR DISEASES / 621

Treatment & Prognosis VENTRICULAR TACHYCARDIA

Transesophageal atrial pacing is the treatment of choice Ventricular tachycardia is uncommon in childhood
to terminate atrial flutter. When it is not successful, an- (Figure 19–9). It is usually associated with underlying
tiarrhythmic medications (eg, digoxin, sotalol, and abnormalities of the myocardium (myocarditis, car-
amiodarone) may succeed; however, DC cardioversion diomyopathy, myocardial tumors, postoperative con-
is frequently necessary. genital heart disease) or toxicity (hypoxia, electrolyte
The prognosis in neonates without structural heart imbalance, drug toxicity). Sustained tachycardia is gen-
disease is excellent, and after conversion these patients erally an unstable situation and, if left untreated, will
may need no further treatment. usually degenerate into ventricular fibrillation.
Accelerated idioventricular rhythm is a sustained
ventricular tachycardia occurring in neonates with nor-
POSTOPERATIVE INCISIONAL mal hearts. The rate is within 10% of the preceding
INTRAATRIAL REENTRY sinus rate, and it is a self-limiting arrhythmia that re-
Improved surgical survival for patients with congenital quires no treatment.
heart disease has created a new, increasingly prevalent, Acute termination of ventricular tachycardia in-
chronic arrhythmia: incisional intraatrial reentry, or volves restoration of the normal myocardium when
postoperative atrial flutter. In these tachycardias, elec- possible (correct electrolyte imbalance, drug toxicity,
trically isolated corridors of atrial myocardium (eg, the and so on) and DC cardioversion (1–4 J/kg), cardiover-
tricuspid valve–inferior vena cava isthmus, or the re- sion with lidocaine (1 mg/kg), or both. Chronic sup-
gion between an atrial incision and the crista termi- pression of ventricular arrhythmias with antiarrhythmic
nalis) act as pathways for sustained reentrant circuits of drugs has many side effects (including proarrhythmia
electrical activity. These tachycardias are chronic, med- and death), and it must be initiated in the hospital
ically refractory, and clinically incapacitating. Electro- under the direction of a pediatric cardiologist.
magnetic mapping permits precise localization of these
corridors. Long linear radiofrequency or surgical lesions Alexander ME et al: Ventricular arrhythmias: When to worry. Pe-
are then used to interrupt the reentrant circuits. diatr Cardiol 2000;21(6):532 [PMID: 11050277].
Batra A et al: Ventricular arrhythmias. Prog Pediatr Cardiol
2000;11(1):39 [PMID: 10822188].
Delacretaz E et al: Multiple atrial macro-reentry circuits in adults
with repaired congenital heart disease: Entrainment mapping
combined with three-dimensional electroanatomic mapping. LONG QT SYNDROME
J Am Coll Cardiol 2001;37(6):1665 [PMID: 11345382].
Van Hare GF: Intra-atrial reentry tachycardia in pediatric patients. The congenital long QT syndromes (types 1–6) in chil-
Prog Pediatr Cardiol 2001;13(1):41 [PMID: 11413057]. dren are arrhythmic disorders in which ventricular re-

I aVR V1 V4

II aVL V2 V5

III aVF V3 V6

Figure 19–9. Twelve-lead ECG from a child with imipramine toxicity and ventricular tachycardia.
622 / CHAPTER 19

polarization is irregular and prolonged (QTc > be hereditary and should be looked for in patients with
0.44 seconds, or 0.46 seconds in postpubertal females). resuscitated cardiac arrest or family members of those
Some myocardial ion channelopathies predispose pa- who have died suddenly. Congenital structural anom-
tients to “torsade de pointes” (multifocal ventricular alies of the coronary arteries are the second most com-
tachycardia) and manifest as syncope, seizures, or sud- mon cause of sudden death in young athletes. These
den death in response to exercise. If untreated, they ac- anomalies are not hereditary. The coronary arteries
count for a very high mortality rate (5%/year). They are need to be evaluated in survivors of sudden death
inherited genetically in an autosomal dominant or re- events. Arrhythmias in patients with postoperative con-
cessive pattern (the latter being associated with congen- genital heart disease are important causes of morbidity
ital deafness, the Jervell–Lange–Nielsen syndrome). Or and mortality and may present as sudden death events.
they may arise spontaneously. Treatment with β-block- All survivors of cardiac arrest require thorough evalua-
ade and exercise limitation is only partially successful. tion for arrhythmias, including invasive electrophysiol-
In recurrent, medically refractory cases, implantable ogy. Episodes of seizures, syncope, and presyncope in
cardioverter defibrillators are necessary to prevent sud- congenital heart disease patients should be evaluated for
den death. Congenital long QT syndrome has now the possibilities of arrhythmias, and they may also re-
been demonstrated to be one of the causes of SIDS. quire thorough electrophysiologic evaluation and treat-
The SCN5A gene has been isolated from a child who ment.
died from SIDS. When a child dies suddenly and unexpectedly, or is
Acquired long QT syndrome—resulting from al- resuscitated from cardiac arrest that had no apparent
tered ventricular repolarization secondary to myocardial cause, it is necessary to conduct a detailed family his-
toxins, ischemia, or inflammation—also predisposes a tory looking for seizures, syncope, or early sudden
patient to ventricular arrhythmias. Numerous medica- death. Family members should be examined with an ar-
tions as outlined previously can also cause QT prolon- rhythmia screen, physical examination, ECG, and
gation. ECGs are recommended before therapy (for a echocardiography to detect arrhythmias or cardiomy-
baseline measurement) and after steady state is opathies.
achieved. Another drug capable of prolonging the QT
interval, cisapride (used for gastroesophageal reflux), Corrado D et al: Right bundle branch block, right precordial ST-
has now been removed from the US market. segment elevation, and sudden death in young people. Circu-
lation 2001;103(5):710 [PMID: 11156883].
Gutgesell H et al: Cardiovascular monitoring of children and ado- Gatzoulis MA et al: Risk factors for arrhythmia and sudden cardiac
lescents receiving psychotropic drugs. A statement for health- death later after repair of tetralogy of Fallot: A Multicentre
care professionals from the Committee on Congenital Car- Study. Lancet 2000;356(9234):975 [PMID: 11041398].
diac Defects, Counsel on Cardiovascular Diseases in the
Young-American Heart Association. Circulation 1999;99(7):
979 [PMID: 10027824].
HEART BLOCK
Kimbrough J et al: Clinical implications for affected parents and 1. First-Degree Heart Block
siblings of probands with long QT syndrome. Circulation
2001;104(5):557 [PMID: 11479253]. First-degree heart block is an ECG diagnosis of prolon-
Li H et al: Current concepts in long QT syndrome. Pediatr Cardiol gation of the PR interval. The block does not in itself
2000;21(6):542 [PMID: 11050278]. cause problems, but it is frequently associated with con-
Moss AJ et al: Effectiveness and limitations of β-blocker therapy in genital heart defects such as AV septal defects, ccTGA,
congenital long QT syndrome. Circulation 2000;101(6):616 and with diseases such as rheumatic carditis. The PR
[PMID: 10673253]. interval may also be prolonged as a result of digoxin
Wedekind H et al: De novo mutation in the SCN5A gene associ- therapy.
ated with early onset of sudden infant death. Circulation
2001;104(10):1158 [PMID: 11535573].
Zhang L et al: Spectrum of ST-T wave patterns and repolarization 2. Second-Degree Heart Block
parameters in congenital long QT syndrome ECG findings
identify genotypes. Circulation 2000;102(23):2849 [PMID: Mobitz type I (Wenckebach) heart block is recognized
11104743]. by progressive prolongation of the PR interval until
there is no QRS following a P wave (Figure 19–10).
Mobitz type I heart block occurs in normal hearts at
SUDDEN DEATH rest and is usually benign. In Mobitz type II heart
Hypertrophic cardiomyopathy (the most common block, there is no progressive lengthening of the PR in-
cause of sudden death in young athletes) and other car- terval before the dropped beat (Figure 19–11). Mobitz
diomyopathies (dilated cardiomyopathies, restrictive type II heart block is frequently associated with organic
cardiomyopathy, or arrhythmogenic RV dysplasia) may heart disease, and a complete evaluation is necessary.
 CARDIOVASCULAR DISEASES / 623

Lead I

Figure 19–10. Lead I rhythm strip with Mobitz type I (Wenckebach) second-degree heart block. There is progres-
sive lengthening of the PR interval prior to the nonconducted P wave (arrows).

3. Complete Heart Block Clinical Findings

In complete heart block, the atria and ventricles beat Prenatal bradycardia is frequently noted in infants with
independently. Ventricular rates can range from 40 to congenital complete heart block, and emergent delivery
80 beats/min, whereas atrial rates are faster (Figure is required if hydrops fetalis develops. Postnatal adapta-
19–12). tion largely depends on the heart rate; infants with
Congenital complete heart block, the most common heart rates lower than 55 beats/min are at significantly
form of complete heart block, has a very high associa- greater risk for low cardiac output, CHF, and death.
tion with maternal systemic lupus erythematosus. Sero- Wide QRS complexes and a rapid atrial rate are also
logic screening should be performed in the mother of poor prognostic signs. Most patients have an innocent
an infant with complete heart block even if she has no flow murmur from increased stroke volume. In symp-
symptoms of collagen vascular disease. Congenital tomatic patients, the heart can be quite enlarged, and
complete heart block is also associated with congeni- pulmonary edema may be present. In older patients,
tally corrected transposition of the great vessels and AV syncope can be the presenting symptom, or heart block
septal defect. Acquired complete heart block may be may be found unexpectedly on routine physical exami-
secondary to acute myocarditis, drug toxicity, elec- nation. Complete cardiac evaluation, including
trolyte imbalance, hypoxia, and cardiac surgery. echocardiography and Holter monitoring, is necessary

Lead III

Figure 19–11. Lead III rhythm strip with Mobitz type II second-degree heart block. There is a consistent PR interval
with occasional loss of AV conduction (arrow).
624 / CHAPTER 19

I aVR V1 V4

II aVL V2 V5

III aVF V3 V6

RHYTHM STRIP: II 25 mm/sec; 1 cm/mV

Figure 19–12. Twelve-lead ECG and lead II rhythm strip of complete heart block. The atrial rate is 150 beats/min,
and the ventricular rate is 60 beats/min.

to assess the patient for ventricular dysfunction and to nausea, or diaphoresis. Syncope, also known as auto-
relate any symptoms to concurrent arrhythmias. nomic dysfunction, can be evaluated with head-up tilt
table testing. The patient is placed supine on a tilt
Treatment table, and then—under constant heart rate and blood
pressure monitoring—is tilted to the upright position.
In patients thought to be at risk for syncope, CHF, or If symptoms develop, they can be classified as vasode-
sudden death, the treatment of choice for complete pressor (hypotension), cardioinhibitory (bradycardia),
heart block is insertion of a permanent pacemaker. or mixed.
Until permanent pacing can be instituted, patients can Syncope is usually self-limited (lasting approxi-
be assisted temporarily by infusions of isoproterenol or mately 6 months to 2 years) and can be controlled with
by temporary transcutaneous pacemakers. dietary salt and volume loading to prevent hypov-
olemia. In refractory cases, medications to manipulate
Eronen M et al: Short and long-term outcome of children with con- the autonomic nervous system have been useful. Fluro-
genital complete heart block diagnosed in utero or as a new-
born. Pediatrics 2000;106(1 Pt 1):86 [PMID: 10878154].
cortisone (0.1 mg/kg/d) is a mineralocorticoid that
Moak JP et al: Congenital heart block: Development of late-onset
causes renal salt resorption and thus increases intravas-
cardiomyopathy, a previously underappreciated sequela. J Am cular volume. Beta-blockade (atenolol, 0.5 to
Coll Cardiol 2001;37(1):238 [PMID: 11153745]. 2.0 mg/kg/d) can inhibit the catecholamine surge and
help prevent the rebound bradycardia and hypotension.
Vagolytic agents (disopyramide 2.5 mg/kg qid) help
SYNCOPE (Fainting) control hypervagotonia, and the selective serotonin re-
Syncope is a sudden transient loss of consciousness that uptake inhibitors have also been effective in alleviating
resolves spontaneously. The common form of syncope symptoms. Syncope that occurs during exercise or stress
(simple fainting) occurs in 15% of children and is a dis- or is associated with a positive family history is a warn-
order of control of heart rate and blood pressure by the ing sign that a serious underlying dysrhythmia may be
autonomic nervous system that causes hypotension or present, calling for further investigation.
bradycardia. It is often associated with rapid rising and
postural hypotension, prolonged standing, or hypov- Johnsrude CL: Current approach to pediatric syncope. Pediatr Car-
olemia. Patients exhibit vagal symptoms such as pallor, diol 2000;21(6):522 [PMID: 11050276].
 Gastrointestinal Tract 20
Judith M. Sondheimer, MD

nostic step in localizing the site of intestinal obstruc-

EVALUATION OF THE CHILD tion.
WITH VOMITING The evaluation of bloody vomitus should start with
confirmation that the material vomited is indeed blood.
Assessment of the child with recurrent episodes of vom- Numerous causes must be considered, including swal-
iting should start with a complete history, physical ex- lowed maternal blood in newborns, oropharyngeal le-
amination, and description of the vomitus (Table sions, nosebleed, peptic disease, bleeding disorders, for-
20–1). Emesis of gastric contents is characteristic of eign bodies, and esophageal varices. Mallory–Weiss tear
gastric outlet obstruction, central nervous system of the mucosa of the GE junction is common after pro-
masses or infection, peptic disease, urinary tract infec- longed vomiting. Careful assessment of the cardiovas-
tion, otitis or sinusitis, metabolic diseases (especially cular stability of the child is essential before extensive
those causing acidosis), rumination, and psychogenic evaluation is initiated. Passage of a nasogastric tube will
vomiting. Gastroesophageal (GE) reflux should be sus- help determine whether bleeding is ongoing. The
pected in a healthy child with effortless postprandial hematocrit should be measured. If further diagnostic
spitting. An upper gastrointestinal (GI) series is essen- investigation is desired, the most productive test is
tial to rule out anatomic causes in young infants. A uri- upper intestinal endoscopy.
nalysis and culture will rule out urinary tract infection
or urinary obstruction, which may cause vomiting, es-
pecially in young infants. Serum electrolytes should be
measured as abnormalities of sodium, potassium, mag-
GASTROESOPHAGEAL REFLUX
nesium and calcium may also cause vomiting by inter- Postprandial regurgitation is the most common symp-
fering with normal motor functions of the GI tract. In- tom of GE reflux in young infants. Regurgitation
creased intracranial pressure may cause vomiting. The ranges from effortless spitting to forceful vomiting. Al-
decision to obtain radiographs and scans of the central though usually a harmless condition of young infants,
nervous system, chest, or sinuses is based on a specific severe GE reflux may cause failure to thrive, esophagitis
indication from the history or physical examination. with hematemesis, occult blood loss, anemia, esophage-
The child who vomits bile-stained material may al stricture, and inflammatory esophageal polyps. Aspi-
have small intestinal obstruction and should be exam- ration pneumonia, chronic cough, wheezing, and
ined immediately. Bile staining may be gold or green in asthma-like attacks are reported. Dysphagia, colic after
color. The history and physical examination are the es- feedings, and neck contortions (Sandifer syndrome)
sential starting points and should include duration of may occur. Ruminative behavior is sometimes a symp-
vomiting, the presence of blood in the vomitus, the tom. Apneic spells in young infants, especially occur-
presence of abdominal pain or distention, the character ring with position change after feeding, may be caused
of the stools, and the presence of fever. Pain localized to by GE reflux. GE reflux is common in neurologically
the right lower quadrant suggests appendicitis. Midline impaired children. The underlying cause of GE reflux is
or diffuse abdominal pain suggests pancreatitis or gen- unknown, but the facilitating mechanism appears to be
eralized peritonitis. Abdominal distention suggests in- spontaneous relaxation of the lower esophageal sphinc-
testinal obstruction. Viral and bacterial gastroenteritis ter rather than a chronically weak or immature sphinc-
are associated with diarrhea and may produce general- ter.
ized ileus with bilious vomiting. Gallbladder disease is GE reflux is a clinical diagnosis in thriving infants
uncommon in childhood but should be suspected in younger than age 6 months. An upper GI series is im-
children with a family or personal history of hemolytic portant to rule out anatomic causes of vomiting, but is
disorders, hypercholesterolemia, or primary medical not an accurate test for GE reflux because of the 30%
conditions promoting gallstones. The presence of false-positive rate. Prolonged monitoring of esophageal
mucus and blood in the stool should arouse suspicion pH is a more sensitive test if the symptoms are not typi-
of intestinal intussusception or bacterial or toxic colitis. cal. Esophageal intraluminal impedance monitoring is a
Three-way radiographs of the abdomen are a first diag- pH-independent means to detect fluid movement in
625
Copyright © 2005, 2001, by The McGraw-Hill Companies, Inc. Click here for terms of use.
626 / CHAPTER 20

Table 20–1. Causes of vomiting the esophagus. It may be a more accurate method to
and regurgitation. detect and describe pathologic reflux once standards
have been clarified in children. Esophageal and gastric
GASTROINTESTINAL TRACT DISORDERS scintiscanning is sometimes helpful in identifying pul-
monary aspiration. Esophagoscopy is not diagnostic,
Esophagus Intestine and colon but esophagitis can be identified.
Achalasia Atresia and stenosis
Gastroesophageal Meconium ileus
reflux (chalasia) Malrotation, volvulus
Treatment & Prognosis
Hiatal hernia Duplication In 85% of infants with GE reflux, the condition is self-
Esophagitis Intussusception limited, disappearing between ages 6 and 12 months,
Atresia with or without Foreign body coincident with assumption of erect posture and initia-
fistula Polyposis tion of solid feedings. Regurgitation may be reduced by
Congenital vascular or Soy or cow’s milk protein offering small feedings at frequent intervals or by thick-
mucosal rings, webs intolerance ening feedings with rice cereal (2–3 tsp/oz of formula).
Stenosis Gluten enteropathy Prethickened antireflux formulas are available. Hista-
Duplication and divertic- Food allergy mine (H2)-receptor antagonists (ranitidine, 5 mg/kg/d
ulum Hirschsprung disease
in two doses) and proton pump inhibitors (eg, omepra-
Foreign body Chronic intestinal pseudo-
Periesophageal mass obstruction
zole, 0.5–1 mg/kg/d in one dose) are effective in con-
Stomach Appendicitis trolling esophagitis and often reduce pain secondary to
Hypertrophic pyloric Inflammatory bowel disease reflux. Prokinetic agents such as metoclopramide
stenosis Gastroenteritis, infections (0.1 mg/kg before meals) hasten gastric emptying and
Pylorospasm Other abdominal organs improve esophageal motor function, but studies have
Diaphragmatic hernia Hepatitis not supported their efficacy in controlling symptoms.
Peptic disease and Gallstones Antireflux surgery is indicated if reflux causes
gastritis Pancreatitis (1) persistent vomiting with failure to thrive,
Antral web Peritonitis (2) esophagitis or esophageal stricture, and (3) apneic
Duodenum spells or chronic pulmonary disease unresponsive to
Annular pancreas 2–3 months of medical therapy. Children older than
Duodenitis and ulcer age 18 months, children with large hiatal hernias, and
Malrotation neurologically handicapped children respond less well
Mesenteric bands to medical therapy.
Superior mesenteric
artery syndrome Rudolph CD et al: Guidelines for evaluation and treatment of gas-
EXTRAGASTROINTESTINAL TRACT DISORDERS troesophageal reflux in infants and children: Recommenda-
tions of the North American Society for Pediatric Gastroen-
Sepsis Adrenal insufficiency terology and Nutrition. J Pediatr Gastroenterol Nutr
Pneumonia Renal tubular acidosis 2001;23(Suppl):1.
Otitis media Inborn errors
Urinary tract infection Urea cycle disorders ACHALASIA OF THE ESOPHAGUS
Meningitis Phenylketonuria
Subdural effusion Maple syrup urine Esophageal achalasia is characterized by failure of relax-
Hydrocephalus disease ation of the lower esophageal sphincter in response to
Brain tumor Organic acidemia swallowing and abnormal, nonperistaltic motor activity
Reye syndrome Galactosemia in the esophageal body.
Rumination Fructose intolerance
Intoxications Tyrosinosis Clinical Findings
Alcohol Scleroderma
Aspirin Epidermolysis bullosa A. SYMPTOMS AND SIGNS
Acetaminophen Achalasia is uncommon in children younger than age
5 years. Typical symptoms include retrosternal pain
and episodes of food “sticking” in the throat or upper
chest. Patients eat slowly and often drink large amounts
of fluid with meals. Dysphagia is relieved by repeated
forceful swallowing or by vomiting. Familial cases have
been described in patients with Allgrove syndrome
 GASTROINTESTINAL TRACT / 627

(alacrima, adrenal insufficiency, and achalasia) and in flammation to coagulative necrosis with ulceration, per-
patients with familial dysautonomia. Chronic cough, foration, and mediastinitis (or peritonitis if the stomach
wheezing, recurrent pneumonitis, anemia, and weight is involved). The severity of the oral or laryngeal lesions
loss may occur. after ingestion does not correlate well with the degree of
esophageal injury. Esophageal or laryngeal obstruction
B. IMAGING AND MANOMETRIC STUDIES secondary to edema and exudate formation occurs
The barium esophagagram shows a dilated esophagus within 24 hours. Pain may be severe. Strictures of the
with a short, tapered “beak” at the distal end. In in- esophagus may develop quickly, or gradually over sev-
fants, esophageal dilation may not be present. Cinefluo- eral months. Esophageal strictures develop in areas of
roscopy may show very disordered esophageal peristal- anatomic narrowing such as the thoracic inlet, the GE
sis. Esophageal manometry may show high resting junction, and at the point where the left bronchus
pressure in the lower esophageal sphincter, failure of crosses the esophagus. Stricture occurs only with full-
the sphincter to relax with swallowing, and abnormal or thickness esophageal necrosis. Short circumferential
absent esophageal peristalsis. The cause is unknown. strictures may occur, or the entire esophagus may be-
Decrease in neuronal nitric oxide synthetase (nNOS) in come twisted and narrowed. Shortening of the esopha-
the area of the lower esophageal sphincter causes a local gus may lead to hiatal hernia.
deficiency of nitric oxide, preventing normal sphincter The lips, mouth, and airway should be carefully ex-
relaxation. It is unclear whether the lack of nNOS is amined in any child with suspected alkali ingestion.
secondary or primary to achalasia. In acquired achalasia Drooling is common. Oral lesions are especially com-
associated with Chagas’ disease, nNOS is also reduced, mon with solid agents. Vomiting should not be in-
and ganglion cells may be decreased or absent in the duced. Give intravenous corticosteroids (eg, methyl-
muscular esophagus near the lower esophageal sphinc- prednisolone, 1–2 mg/kg/d) immediately to reduce oral
ter. cavity swelling and laryngeal edema. Intravenous fluids
may be necessary if dysphagia is present.
Differential Diagnosis Esophagoscopy should be done within 24–48 hours
after ingestion.
Congenital esophageal stricture, esophageal webs, pep- Treatment may be stopped if only first-degree burns
tic stricture secondary to chronic reflux, and esophageal are present. Corticosteroids may be beneficial in first-
masses may mimic esophageal achalasia. Intestinal and second-degree burns, but are not likely to prevent
pseudo-obstruction, multiple endocrine neoplasia IIb, stricture formation from third-degree burns. Repeated
systemic amyloidosis, and postvagotomy syndrome also esophageal dilations may be necessary as a stricture de-
cause esophageal dysmotility and symptoms similar to velops but are not performed acutely. When radi-
achalasia. ographs show erosion into the mediastinum or peri-
toneum, antibiotics are mandatory. Intraluminal
Treatment & Prognosis esophageal stenting may be beneficial during early
Pneumatic dilation of the lower esophageal sphincter is management. Surgical replacement of the esophagus
of value in most cases and can be repeated if symptoms with a segment of colon or with a gastric tube may be
recur. Botulinum toxin injected into the lower esopha- necessary if dilation fails to control stricture.
geal sphincter may be effective temporarily. More de- Although other ingestants (eg, bleach, detergents,
finitive results can be achieved by surgically splitting acids) may cause esophageal irritation, it is rare for any
the lower esophageal sphincter muscle (Heller my- but the strongest acids and detergents to produce full-
otomy), a procedure that can be performed laparoscop- thickness necrosis and stricture.
ically or thoracoscopically. Because of the shorter dura-
tion of esophageal obstruction in children, the Del Rosario JF, Orenstein SR: Common pediatric esophageal dis-
prognosis for return of some normal esophageal motor orders. Gastroenterologist 1998;6:104.
function after surgery is better in pediatric patients than
in adults. HIATAL HERNIA
Hussain SZ et al: A review of achalasia in 33 children. Dig Dis Sci Hiatal hernias are classified as (1) paraesophageal, in
2002;47:2538 [PMID: 12452392]. which the esophagus and GE junction are normally
placed with the gastric cardia herniated beside the
esophagus through the diaphragmatic hiatus; or
CAUSTIC BURNS OF THE ESOPHAGUS (2) sliding, in which the GE junction and a portion of
Ingestion of caustic solids or liquids (pH > 12.0) may the proximal stomach are herniated through the esoph-
produce esophageal lesions ranging from superficial in- ageal hiatus. Paraesophageal hernia is rare in childhood
628 / CHAPTER 20

and presents with pain, esophageal obstruction, or res- Treatment & Prognosis
piratory compromise. The most common situation in
which a paraesophageal hernia occurs is in patients with Pyloromyotomy is the treatment of choice and consists
previous fundoplication. Sliding hernia is common in of incision down to the mucosa along the pyloric
children. GE reflux may accompany sliding hiatal her- length. The procedure can be performed laparoscop-
nia, although many cause no symptoms. Surgical cor- ically. To prevent complications during surgery, it is
rection of paraesophageal or hiatus hernia is indicated if imperative first to resolve hydration and electrolyte ab-
symptoms persist in spite of medical treatment. normalities even if it takes 24–48 hours.
The outlook is excellent following surgery. Patients
often vomit postoperatively as a consequence of gastri-
tis, esophagitis, or associated GE reflux. The postopera-
PYLORIC STENOSIS tive barium radiograph remains abnormal despite relief
The cause of postnatal pyloric circular muscle hypertro- of symptoms.
phy leading to gastric outlet obstruction is unknown.
The incidence is 1–8:1000 births, with a 4:1 male pre-
dominance. A positive family history is present in 13% Fugimoto T et al: Laparoscopic extramucosal pyloromyotomy ver-
of patients. Recent studies suggest that erythromycin sus open pyloromyotomy for infantile hypertrophic pyloric
therapy may be associated with development of pyloric stenosis: Which is better? J Pediatr Surg 1999;34:370.
stenosis in infants younger than 30 days. Mahon BE et al: Maternal and infant use of erythromycin and
other macrolide antibiotics as risk factors for infantile hyper-
trophic pyloric stenosis. J Pediatr 2001;139:380.

Clinical Findings
A. SYMPTOMS AND SIGNS PEPTIC DISEASE
Vomiting usually begins between ages 2 and 4 weeks Peptic ulcers occur at any age but are more common
and rapidly becomes projectile after every feeding; vom- between ages 12 and 18 years. Boys are affected more
iting starts at birth in about 10% of cases. Onset of frequently than girls. Most ulcers in childhood are sec-
symptoms may be delayed in premature infants. The ondary to underlying illness, toxin, or a drug causing
vomitus is rarely bilious but may be blood-streaked. breakdown in normal mucosal defense, permitting acid
The infant is hungry and nurses avidly. Constipation, peptic digestion of gastric or duodenal mucosa. Causes
dehydration, weight loss, fretfulness, and finally apathy include (1) reduced mucosal protective mechanisms
occur. The upper abdomen may be distended after (aspirin, nonsteroidal anti-inflammatory drugs
feeding, and prominent gastric peristaltic waves from [NSAIDs], hypoxia); (2) reduced metabolic activity of
left to right may be seen. An olive-sized mass can be felt the mucosal cell, which allows for diffusion of hydro-
on deep palpation in the right upper abdomen, espe- gen ions into the mucosa (hypoxia, hypotension);
cially after the child has vomited. (3) increased secretion of acid or pepsin (increased pari-
etal cell mass, increased postprandial secretion of gas-
B. LABORATORY FINDINGS trin, increased vagal tone); (4) reflux of bile from duo-
Hypochloremic alkalosis with potassium depletion oc- denum to stomach; and (5) decreased neutralizing
curs. Hemoconcentration is reflected by elevated hemo- activity in duodenal secretions.
globin and hematocrit values. Elevated unconjugated A close association exists between Helicobacter pylori
bilirubin occurs in 2–5% of cases. infection of the gastric antrum and nodular antral gas-
tritis, duodenal ulcer, and gastric ulcer. There is no evi-
dence that H pylori infection causes recurrent abdomi-
C. IMAGING nal pain of childhood or dyspepsia without gastritis. H
An upper GI series reveals gastric retention of contrast pylori antibody positivity is found in 10–20% of
and an elongated narrowed pyloric channel with a dou- healthy North American children. It tends to increase
ble tract of barium. Many normal infants have some with age. The prevalence is higher in areas with poor
delay in gastric emptying during upper GI series due to sanitation and contaminated water supply and is higher
pylorospasm. This by itself is insufficient to make a di- in families with an antibody-positive member. Diagno-
agnosis of pyloric stenosis. The enlarged pyloric muscle sis of H pylori infection is made by seeing organisms in
causes characteristic semilunar impressions on the gas- gastric antral tissue, testing antral tissue for bacterial
tric antrum. Ultrasonography shows a hypoechoic ring urease activity, or using the urease breath test. Serum
with a hyperdense center. Thickness of circular muscle antibody positivity does not prove active H pylori infec-
is greater than 4 mm in pyloric stenosis. tion.
 GASTROINTESTINAL TRACT / 629

Clinical Findings gastric acid secretion. Aspirin and NSAIDs should not
be used.
A. SYMPTOMS AND SIGNS Treatment of the peptic disease associated with H
In children younger than age 6 years, vomiting and pylori infection requires eradication of the organism.
upper GI bleeding are the most common manifesta- The optimal therapeutic regimen is still undetermined.
tions of peptic ulcer disease. Older children are more The combination of amoxicillin, metronidazole, and
likely to complain of abdominal pain. Acute H pylori bismuth subsalicylate for 10–14 days and omeprazole
infection with gastritis is characterized by vomiting and and amoxicillin, are both effective. Clarithromycin for
often by hematemesis. Large ulcers in the pyloric chan- 7 days with a proton pump inhibitor for 6 weeks is also
nel may cause gastric outlet obstruction. Acute illnesses effective.
responsible for secondary ulcers include central nervous
system disease, burns, sepsis, and multiorgan system Chang HY et al: Knowledge, attitudes and practice styles of North
failure. Chronic conditions such as pulmonary insuffi- American pediatric gastroenterologists: Helicobacter pylori in-
ciency, Crohn disease, hepatic cirrhosis, and rheuma- fection. J Pediatr Gastroenterol Nutr 2003;36:235 [PMID:
toid arthritis are associated with peptic disease. Upper 1254860].
GI bleeding requiring transfusion is more commonly Czinn S et al: Research agenda for pediatric gastroenterology, hepa-
seen in secondary ulcers, particularly following inges- tology and nutrition: Acid peptic diseases: Report of the
tion of aspirin, alcohol, and NSAIDs, than in primary North American Society for Gastroenterology, Hepatology,
and Nutrition for the Children’s Digestive Health and Nutri-
ulcer disease. Ulcers may occur throughout the upper tion Foundation. J Pediatr Gastroenterol Nutr 2003;
GI tract secondary to NSAIDs. The use of specific cy- 35(Suppl 3) 250.
clooxygenase-2 (COX-2) inhibitors (celecoxib [Cele- McCarthy DM: Nonsteroidal anti-inflammatory drugs: Reducing
brex], rofecoxib [Vioxx]) instead of the standard the risks to the gastrointestinal tract. Clin Perspect Gastroen-
NSAIDs and aspirin—which inhibit both COX-1 and terol 1999;2:219.
COX-2 enzymes—may result in a decrease in NSAID- Suerbaum S, Michetti P: Helicobacter pylori infection. N Engl
associated complications. COX-1 regulates the produc- J Med 2002;347:1175 [PMID: 12374879].
tion of thromboxane from arachidonic acid and thus
decreases platelet aggregation with a resultant increase CONGENITAL DIAPHRAGMATIC
in bleeding tendency. COX-2, an inducible enzyme
present in many tissues, regulates prostaglandin synthe- HERNIA
sis. COX-2 inhibition has a purer anti-inflammatory Diaphragmatic hernia may be secondary to a postero-
and analgesic effect with a reduced tendency to produce lateral defect in the diaphragm (foramen of Bochdalek)
GI complications. or, in about 5% of cases, to a retrosternal defect (fora-
men of Morgagni). It represents failure of division of
B. IMAGING AND ENDOSCOPY the thoracic and abdominal cavities at the 8th to 10th
week of fetal life. All degrees of protrusion of the ab-
An upper GI radiograph may show an ulcer crater. Soft dominal viscera through the diaphragmatic opening
signs of peptic disease, such as duodenal spasticity and may occur. Eighty percent of posterolateral defects in-
irregularity, which are suggestive of ulcer in adults, are volve the left diaphragm. In eventration of the di-
often seen in healthy children and are not reliable indi- aphragm, a leaf of the diaphragm with hypoplastic
cators of peptic disease. Upper intestinal endoscopy is muscular elements balloons into the chest and leads to
the most accurate diagnostic test for peptic disease. It similar but milder symptoms.
also allows for identification of other causes of peptic Mild to severe respiratory distress is usually present
symptoms such as esophagitis, eosinophilic enteropa- at birth. The abdomen may be scaphoid because of dis-
thy, and celiac disease. placement of the viscera. Breath sounds in the affected
hemithorax are absent, with displacement of the point
of maximal cardiac impulse. Thirty percent of newborn
Treatment infants with diaphragmatic hernia die, mostly from pul-
Acid suppression or neutralization is the mainstay of monary insufficiency. The lung on the affected side and
peptic ulcer therapy. Liquid antacids are usually unac- also on the contralateral side may be hypoplastic, with
ceptable to children in the volumes needed to neutralize decreased generations of airways, lymphatics, and pul-
gastric acid. H2-receptor antagonists and proton pump monary vessels. Pulmonary hypertension is present.
inhibitors are more effective and usually produce endo- Other complications include mediastinal shift with vas-
scopic healing in 4–8 weeks. Bland “ulcer diets” are not cular kinking, pulmonary infection, prematurity, car-
indicated in children. Foods that cause pain should be diac anomalies, and intestinal malrotation. Extracorpo-
avoided. Caffeine should be avoided because it increases real membrane oxygenation may decrease the early
630 / CHAPTER 20

postoperative mortality rate in patients with poor lung that no additional anomalies are present lower in the
compliance. Inhaled nitric oxide reduces pulmonary GI tract. The mortality rate is significantly increased in
vascular hypertension, and it was hoped that its use infants with prematurity, Down syndrome, and associ-
might improve the outcome in patients with diaphrag- ated congenital anomalies. Duodenal dilation and hy-
matic hernia. Results in controlled trials have thus far pomotility resulting from antenatal obstruction may
been disappointing. Occasionally, a diaphragmatic her- cause functional obstructive symptoms even after surgi-
nia is first identified in an older infant or child by an cal treatment.
incidental radiograph or routine physical examination.
These children usually have a more favorable prognosis CONGENITAL INTESTINAL
than diaphragmatic hernias identified at birth.
ATRESIAS & STENOSES
CONGENITAL DUODENAL Excluding anal anomalies, intestinal atresia and stenosis
OBSTRUCTION account for one third of all cases of neonatal intestinal
obstruction. Antenatal ultrasound can identify intesti-
Extrinsic duodenal obstruction is usually due to con- nal atresia in utero, and polyhydramnios occurs in most
genital peritoneal bands associated with intestinal mal- affected pregnancies. Prematurity and other congenital
rotation, annular pancreas, or duodenal duplication. anomalies may be present. The localization and relative
Intrinsic obstruction is a result of stenosis, mucosal di- incidence of atresias and stenoses are listed in Table
aphragm (so-called wind sock deformity), or duodenal 20–2.
atresia. The duodenal lumen may be obliterated by a Failure to pass meconium, bile-stained vomiting,
membrane or completely interrupted with a fibrous and abdominal distention usually begin in the first
cord between the two segments. Atresia is more often 48 hours of life. Atresias, stenoses, and obstructing
distal than proximal to the ampulla of Vater. membranes may affect multiple sites. The small intes-
tine may be shortened significantly. Radiographic fea-
Clinical Findings tures include dilated loops of small bowel and absence
of colonic gas. Barium enema reveals narrow-caliber
A. ATRESIA microcolon if the atresia is in the lower small bowel. In
A history of polyhydramnios is common. Vomiting (usu- over 10% of cases of intestinal atresia, the mesentery is
ally bile-stained) and epigastric distention begin within a absent, and the superior mesenteric artery cannot be
few hours of birth. Meconium may be passed normally. identified beyond the origin of the right colic and ileo-
Duodenal atresia is commonly associated with other con- colic arteries. The ileum coils around one of these two
genital anomalies (30%), including esophageal atresia, arteries, giving rise to the so-called Christmas tree de-
other intestinal atresias, and cardiac and renal anomalies.
Prematurity (25–50%) and Down syndrome (20–30%)
are associated conditions. Abdominal radiographs show Table 20–2. Localization and relative frequency
gaseous distention of the stomach and proximal duode-
num (the “double-bubble” radiologic sign). With pro- of congenital gastrointestinal atresias
tracted vomiting, less air may be in the stomach. Absence and stenoses.
of gas distal to the obstruction suggests atresia or an ex-
trinsic obstruction severe enough to completely occlude Relative
the lumen, whereas air scattered over the lower abdomen Area Involved Type of Lesion Frequency
may indicate a partial duodenal obstruction. A barium Pylorus Atresia; web 1%
enema may be helpful in determining the presence of or diaphragm
malrotation or atresia lower in the GI tract.
Duodenum 80% are distal Atresia, steno- 45%
B. DUODENAL STENOSIS to the ampulla sis; web or dia-
Obvious symptoms of duodenal obstruction may be de- of Vater phragm
layed for weeks or years. Although the stenotic area is Jejunoileal Proximal jeju- Atresia (multi- 50%
usually beyond the ampulla of Vater, the vomitus does num and distal ple in 6–29%);
not always contain bile. ileum stenosis
Colon Left colon and Atresia (usually 5–9%
Treatment & Prognosis rectum associated with
atresias of the
Duodenoduodenostomy is performed to bypass stenosis
small bowel)
or atresia. Thorough exploration is necessary to ensure
 GASTROINTESTINAL TRACT / 631

formity. The tenuous blood supply often compromises B. IMAGING

surgical anastomoses. The differential diagnosis in- An upper GI series shows the duodenojejunal junction
cludes Hirschsprung disease, paralytic ileus secondary on the right side of the spine along with the jejunal
to sepsis, gastroenteritis or pneumonia, midgut volvu- loops. The diagnosis of malrotation can be further con-
lus, and meconium ileus. Surgery is mandatory. Post- firmed by barium enema, which may demonstrate a
operative complications include short bowel syndrome mobile cecum located in the midline, right upper quad-
and hypomotility secondary to antenatal obstruction rant, or left abdomen.
and proximal bowel dilation.
Treatment & Prognosis
ANNULAR PANCREAS
The surgical treatment of malrotation is the Ladd pro-
Annular pancreas results when rotation and fusion of cedure, in which the duodenum is mobilized and the
the dorsal and ventral pancreatic anlagen is incomplete. short mesenteric root is extended. Midgut volvulus is a
The condition presents with symptoms of partial or surgical emergency. Bowel necrosis results from occlu-
complete duodenal obstruction. Down syndrome and sion of the superior mesenteric artery. When necrosis is
congenital anomalies of the GI tract occur frequently. extensive, it is recommended that a first operation in-
Polyhydramnios is common. Clinical manifestations clude only reduction of the volvulus with lysis of
can develop late in childhood when the obstruction is mesenteric bands. Resection of necrotic bowel should
less than complete. Treatment consists of duodenoduo- be delayed if possible until a second-look operation
denostomy or duodenojejunostomy without operative 24–48 hours later can be undertaken in the hope that
dissection or division of the pancreatic annulus. more bowel can be salvaged. The prognosis is guarded
if perforation, peritonitis, or extensive intestinal necro-
INTESTINAL MALROTATION WITH OR sis is present. Treatment of malrotation discovered in
WITHOUT VOLVULUS children older than age 12 months is uncertain. Be-
cause volvulus can occur at any age, surgical repair is
The midgut, which extends from the duodenojejunal usually recommended, even in asymptomatic children.
junction to the mid transverse colon, is supplied by the Laparoscopic repair of malrotation is possible but may
superior mesenteric artery, which runs in the root of the be technically difficult and is never performed in the
mesentery. During gestation, the midgut elongates into presence of volvulus.
the umbilical sac, returning to the intra-abdominal posi-
tion during the tenth week of gestation. The root of the
mesentery rotates in a counterclockwise direction during Complications
retraction. This causes the colon to cross the abdominal If bowel necrosis is extensive, the infant with malrota-
cavity ventrally; the cecum to move from the left to the tion and volvulus may be left with an intestine of insuf-
right lower quadrant, and the duodenum to cross dor- ficient length to support normal absorption and
sally and become partly retroperitoneal. When this rota- growth—the so-called short bowel syndrome. Estimates
tion is incomplete, the dorsal fixation of the mesentery of the small-bowel length of a newborn range from
is defective and shortened, so that the bowel from the 150 to 300 cm. The commonly accepted definition of
ligament of Treitz to the mid transverse colon may neonatal short bowel syndrome is less than 50% of the
twist, causing a volvulus around the narrow mesenteric small intestinal length remaining after resection. In
root and occluding the superior mesenteric artery. these patients, it is almost certain that intravenous nu-
trition will be required for months to years to support
Clinical Findings growth. The most common causes of short bowel syn-
drome in the newborn vary with the patient referral
A. SYMPTOMS AND SIGNS patterns of the institution, but include necrotizing ente-
Malrotation accounts for 10% of neonatal intestinal rocolitis (45%), intestinal atresias (23%), gastroschisis
obstructions. Most infants present with recurrent bile- (15%), volvulus (15%), and, less commonly, entities
stained vomiting or acute small-bowel obstruction in such as congenital short bowel and extensive
the first 3 weeks of life. Intrauterine volvulus has been Hirschsprung disease. Although the remaining intestine
reported. The neonate may present with ascites. Later does not experience a compensatory increase in length,
in life signs of intermittent intestinal obstruction, mal- if nutrition can be maintained, the enterocytes will pro-
absorption, protein-losing enteropathy, or diarrhea may liferate on lengthened villi, and over time, the intestine
be present. Associated congenital anomalies, especially will elongate in proportion to the child’s increasing
cardiac manifestations, occur in over 25% of sympto- height and eventually may be sufficient for the patient’s
matic patients. nutritional needs. Achieving independence from intra-
632 / CHAPTER 20

venous nutrition becomes less likely when the remain- ized peritonitis may occur. Chronic recurrent abdomi-
ing intestine measures less than 30 cm. The presence of nal pain may rarely be the only symptom.
an intact colon is a factor improving the chances of in-
dependence from intravenous nutrition. Liver failure, a B. IMAGING
consequence of intravenous nutrition and recurrent in- Diagnosis of Meckel diverticulum is seldom made on
fection, among other causes, is the most common cause barium radiograph. Radionuclide imaging uses 99mTc
of death in patients with short bowel syndrome. The pertechnetate, which is taken up by the heterotopic gas-
mortality rate among all infants with short bowel syn- tric mucosa in the diverticulum. Stimulation of 99mTc
drome is about 10–15%. pertechnetate uptake and retention of radionuclide by
the heterotopic gastric mucosa by pentagastrin or ci-
Adzick NS, Nance ML: Pediatric surgery: First of two parts. metidine can reduce the number of false-negative re-
N Engl J Med 2000;342:1651. sults. Angiography or tagged red cell scan may be useful
Adzick NS, Nance ML: Pediatric surgery: Second of two parts. when bleeding is brisk.
N Engl J Med 2000;342:1726.
Andorsky DJ et al: Nutritional and other post operative manage- Treatment & Prognosis
ment of neonates with short bowel syndrome correlates with
clinical outcomes. J Pediatr 2001;139:27. Treatment is surgical. At laparoscopy or laparotomy,
Sigalet DL: Short bowel syndrome in infants and children, an the ileum proximal and distal to the diverticulum may
overview. Semin Pediatr Surg 2001;10:49. reveal ulcerations and heterotopic tissue adjacent to the
neck of the diverticulum. The prognosis for Meckel di-
MECKEL DIVERTICULUM verticulum is good. Marked hemorrhage may occur but
is rarely exsanguinating.
& OMPHALOMESENTERIC
DUCT REMNANTS
2. Other Remnants of the
1. Meckel Diverticulum Omphalomesenteric Duct
Meckel diverticulum is the most common of the om- Fecal discharge from the umbilicus is evidence of a
phalomesenteric duct remnants. It is usually found on patent omphalomesenteric duct. The duct may be com-
the antimesenteric border of the mid to distal ileum. It pletely closed, causing a fibrous cord joining ileum and
is present in 1.5% of the population but rarely causes umbilicus and potentially the origin of a volvulus. A
symptoms. In addition to the ileal mucosa, diverticula mucoid umbilical discharge may be indicative of a mu-
may contain gastric, pancreatic, jejunal, or colonic mu- cocele, which can protrude through the umbilicus and
cosa. Familial cases have been reported. Complications be mistaken for an umbilical granuloma because it is
occur three times more frequently in males than in fe- firm and bright red. In all cases, surgical excision of the
males and in 50–60% of cases within the first 2 years of omphalomesenteric remnant is indicated.
life. Acid secreted by heterotopic gastric tissue causes
ulceration and bleeding from adjacent ileal mucosa.
DUPLICATIONS OF THE
GASTROINTESTINAL TRACT
Clinical Findings
Duplications are congenital anomalies of the GI tract.
A. SYMPTOMS AND SIGNS They are fluid-filled, spherical, or tubular structures
In 40–60% of symptomatic patients, painless passage of found anywhere along the GI tract, most commonly in
maroon or melanotic blood per rectum occurs. Acute the ileum. Duplications usually contain fluid and some-
bleeding may cause shock. Occult bleeding is less com- times blood if necrosis has taken place. Most duplica-
mon. Intestinal obstruction occurs in 25% of sympto- tions do not communicate with the intestinal lumen
matic patients as a result of ileocolonic intussusception. but are attached to the mesenteric side of the gut and
Intestinal volvulus may occur around a fibrous remnant share a common muscular coat. The epithelial lining of
of the vitelline duct extending from the tip of the diver- the duplication is usually of the same type as that from
ticulum to the abdominal wall. In some patients, en- which it originates. Some duplications (neuroenteric
trapment of a bowel loop under a band running be- cysts) are attached to the spinal cord and are associated
tween the diverticulum and the base of the mesentery with hemivertebrae and anterior or posterior spina bi-
occurs. The diverticulum may be trapped in an inguinal fida.
hernia (Littre hernia). Diverticulitis occurs in 10–20% Symptoms of vomiting, abdominal distention, col-
of symptomatic patients and is clinically indistinguish- icky pain, rectal bleeding, partial or total intestinal ob-
able from acute appendicitis. Perforation and general- struction, or an abdominal mass may start in infancy.
 GASTROINTESTINAL TRACT / 633

Diarrhea and malabsorption may result from bacterial by fever, explosive diarrhea, and prostration are re-
overgrowth in communicating duplications. Physical ported in about 50% of newborns with this disease.
examination reveals a rounded, smooth, movable mass, These episodes may lead to acute inflammatory and is-
and radiographic films of the abdomen show a noncal- chemic changes in the colon, with perforation (espe-
cified mass displacing the intestines or stomach. Scan- cially cecal) and sepsis. In later infancy, alternating ob-
ning with 99mTc pertechnetate is useful in duplications stipation and diarrhea predominate. The older child is
containing gastric mucosa. Involvement of the terminal more likely to present with constipation. The stools are
small bowel can give rise to an intussusception. Prompt foul-smelling and ribbon-like, the abdomen enlarged,
surgical treatment is indicated. and the veins prominent; peristaltic patterns are readily
visible, and fecal masses are palpable. Intermittent
bouts of intestinal obstruction due to fecal impaction,
CONGENITAL AGANGLIONIC hypochromic anemia, hypoproteinemia, and failure to
MEGACOLON (HIRSCHSPRUNG thrive are common. Encopresis occurs rarely.
DISEASE) On digital examination, the anal canal and rectum
are devoid of fecal material despite fecal impaction ob-
Hirschsprung disease results from an absence of gan- vious on abdominal examination or radiograph. If the
glion cells in the mucosal and muscular layers of the aganglionic segment is short, there may be a gush of fla-
colon. Neural crest cells fail to migrate to the mesoder- tus and stool as the finger is withdrawn.
mal layers, possibly mediated by abnormalities in end-
organ cell surface receptors or local deficiency of nitric B. LABORATORY FINDINGS
oxide synthesis. The rectum alone (30%) or the rec-
tosigmoid (44%) is usually affected. The entire colon is Ganglion cells are absent in both the submucosal and
aganglionic in 8% of patients. Segmental aganglionosis muscular layers of the involved bowel. Special stains
is very rare and may be an acquired lesion. The agan- may show nerve trunk hypertrophy and increased
glionic segment is of normal caliber or slightly nar- acetylcholinesterase activity. Ganglionated bowel above
rowed, with dilation of the normal colon proximal to the aganglionic segment may be characterized by ab-
the aganglionic segment. The mucosa of the dilated normal location and proliferation of ganglion cells.
colonic segment may become thin and inflamed (ente- This finding—intestinal neuronal dysplasia—is some-
rocolitis), resulting in diarrhea, bleeding, and protein times associated with motor dysfunction that may re-
loss. sult in poor motor function of the unresected intestine.
A familial pattern has been described, particularly in A family history of Hirschsprung disease may be pre-
total colonic aganglionosis. The disease is four times sent in 5% of patients.
more common in boys than in girls, and 10–15% of
patients have Down syndrome. Mutations in the ret C. IMAGING
proto-oncogene are recognized in a significant propor- Radiographic examination of the abdomen may reveal
tion of familial and sporadic cases. dilated proximal colon and absence of gas in the pelvic
colon. A barium enema using a catheter with the tip in-
serted barely beyond the anal sphincter usually demon-
Clinical Findings strates the narrowed segment distally with a sharp tran-
A. SYMPTOMS AND SIGNS sition to proximal dilated colon. A transition zone may
Failure of the newborn to pass meconium—followed not be seen in neonates since the normal proximal
by vomiting, abdominal distention, and reluctance to bowel has not had time to become dilated. Retention of
feed—suggests the diagnosis of Hirschsprung disease. barium for 24–48 hours is not diagnostic of
Infants of diabetic mothers may demonstrate symptoms Hirschsprung disease, because it also occurs in retentive
of apparent intestinal obstruction and failure to pass constipation. Retention of barium for 24 hours is a
meconium at birth. In this setting, small left colon syn- more reliable sign in neonates.
drome should be suspected. Meglumine diatrizoate
(Gastrograffin) enema is both diagnostic and therapeu- D. SPECIAL EXAMINATIONS
tic as it reveals a meconium plug in the left colon, Failure of reflex relaxation of the internal anal sphincter
which is often passed during the diagnostic radiograph. muscle after balloon distention of the rectum occurs in
The left colon is narrow but usually functional. In a all patients with Hirschsprung disease, regardless of the
small proportion of these patients, Hirschprung disease length of the aganglionic segment. In occasional pa-
may later be found. In some patients with tients, a nonrelaxing internal anal sphincter is the only
Hirschsprung disease, symptoms of distention and abnormality. This condition is often called “ultrashort
vomiting appear later. Bouts of enterocolitis manifested segment Hirschsprung disease.”
634 / CHAPTER 20

Differential Diagnosis Clinical Findings

Hirschsprung disease accounts for 15–20% of cases of A. SYMPTOMS AND SIGNS
neonatal intestinal obstruction. In childhood, this dis- In both congenital and acquired lymphatic obstruction,
ease must be differentiated from retentive constipation. chylous ascites, diarrhea, and failure to thrive are noted.
In older infants and children it can be confused with The abdomen is distended, with a fluid wave and shift-
celiac disease because of the striking abdominal disten- ing dullness. Unilateral or generalized peripheral edema
tion and failure to thrive. may be present.
B. LABORATORY FINDINGS
Treatment
Laboratory findings include hypoalbuminemia, hy-
Treatment is surgical. Initially, diverting colostomy (or pogammaglobulinemia, and lymphopenia. Ascitic fluid
ileostomy) is performed proximal to the aganglionic contains lymphocytes and has the biochemical compo-
segment. Resection of the aganglionic segment may be sition of chyle if the patient has just been fed; other-
postponed until the infant is at least age 6 months. At wise, it is indistinguishable from ascites secondary to
the time of definitive surgery, the transition zone be- cirrhosis.
tween ganglionated and nonganglionated bowel is iden-
tified. Aganglionic bowel is resected, and a pull-
through of ganglionated bowel to the preanal rectal
Differential Diagnosis
remnant is made. Several surgical techniques, including Chylous ascites must be differentiated from ascites due
laparoscopic pull-through, are in use. In children with to liver failure and, in the older child, from constrictive
ultrashort segment disease, an internal anal sphincter pericarditis and neoplastic, infectious, or inflammatory
myotomy or botulinum toxin injection of the internal diseases causing lymphatic obstruction.
anal sphincter may suffice to control symptoms.
Complications & Sequelae
Prognosis Chylous ascites from intestinal lymphatic obstruction is
Complications following surgery include chronic con- associated with fat malabsorption protein loss. Chronic
stipation, fecal incontinence, anastomotic breakdown, intestinal loss of albumin and γ-globulin may lead to
or anastomotic stricture. Postoperative obstruction may edema and increase the risk of infection. Rapidly accu-
result from inadvertent retention of a distal aganglionic mulating chylous ascites may cause respiratory compli-
colon segment or postoperative destruction of ganglion cations. The primary infections and malignancies caus-
cells secondary to vascular impairment. Neuronal dys- ing chylous ascites may be life-threatening.
plasia of the remaining bowel may result in a pseudo-
obstruction syndrome. Enterocolitis occurs postopera- Treatment & Prognosis
tively in 15% of patients.
Little can be done to correct congenital abnormalities
due to hypoplasia, aplasia, or ectasia of the lymphatics.
Kubota M et al: External anal sphincter dysfunction and postopera- Treatment is supportive, consisting mainly of a very
tive bowel habits in patients with Hirschsprung’s disease. high protein diet and careful attention to infections.
J Pediatr Surg 1997;32:22. Shunting of peritoneal fluid into the venous system is
Wartiovaara K et al: Hirschsprung’s disease genes and the develop- sometimes effective. A fat-free diet supplemented with
ment of the enteric nervous system. Ann Med 1998;30:66. medium-chain triglycerides decreases the formation of
chylous ascitic fluid. Total parenteral nutrition may be
necessary. In the neonate, congenital chylous ascites
CHYLOUS ASCITES may spontaneously disappear following one or more
In the neonate, chylous ascites may be due to congeni- paracenteses and a medium-chain triglyceride diet.
tal infection or developmental abnormality of the lym-
phatic system (intestinal lymphangiectasia). If the tho- Chye JK et al: Neonatal chylosis ascites: Report of 3 cases and re-
racic duct is involved, chylothorax may be present. view of the literature. Pediatr Surg Int 1997;12:296.
Later in life, chylous ascites may result from congenital
lymphangiectasia, retroperitoneal or lymphatic tumors,
peritoneal bands, abdominal trauma, or infection, or it
CONGENITAL ANORECTAL ANOMALIES
may occur after cardiac or abdominal surgery. It may be Anorectal anomalies occur once in every
associated with intestinal malrotation. 3000–4000 births, and most types are more common
 GASTROINTESTINAL TRACT / 635

in males. Inspection of the perianal area is an essential anomalies of the bowel and the urogenital tract can be
part of the newborn physical examination. identified.

Classification & Presentation Treatment & Prognosis

A. ANTERIOR DISPLACEMENT OF THE ANUS Dilation of the anus should be undertaken in cases of
This anomaly is more common in girls than boys. It anal stenosis. Treatment for imperforate anal mem-
may be associated with a posterior rectal shelf and usu- brane consists of excision of the membrane and dila-
ally is characterized by constipation and straining with tion. Diverting colostomy is necessary in anorectal age-
stool. The diagnosis of an anteriorly displaced anus de- nesis. In patients with anal agenesis and a visible
pends on finding the anus located close to the base of perineal fistula of sufficient size to pass meconium,
the scrotum or vaginal fourchette. If the center of the surgery can be deferred. Males without a visible fistula
anus is located less than 33% of the total distance from may have a urethral fistula, and diverting colostomy is
vaginal fourchette (or base of scrotum) to coccyx, there recommended.
is a high likelihood of difficulty with defecation. Of the patients with low imperforate anus, 80–90%
are continent after surgery; of those with high imperfo-
B. ANAL STENOSIS rate anus, only 30% achieve continence. Gracilis mus-
In anal stenosis, the anal aperture may be very small cle transplants may improve continence. Levatorplasty
and filled with a dot of meconium. Defecation is diffi- may also be used as a secondary operation following
cult, and there may be ribbon-like stools, passage of surgery for anorectal agenesis. Antegrade continence
blood and mucus per rectum, fecal impaction, and ab- enema procedures may allow for continence in children
dominal distention. This malformation accounts for without anal sphincter function by facilitating irriga-
about 10% of cases of anorectal anomalies. This anom- tion of the colon via a cecostomy or appendicostomy.
aly may not be apparent at birth and may be discovered
Endo M et al: Analysis of 1992 patients with anorectal malforma-
on rectal examination of the infant who is straining at tions over the past two decades in Japan. J Pediatr Surg
stool. 1999;34:435.
C. IMPERFORATE ANAL MEMBRANE
The infant with an imperforate anal membrane fails to ACUTE ABDOMEN
pass meconium, and a greenish bulging membrane is Entities causing acute abdomen are shown in Table
seen in the anal aperture. After excision, bowel and 20–3. Some of the specific entities are discussed in sub-
sphincter function are normal. sequent sections. Reaching a speedy and accurate diag-
nosis in the patient with an acute abdomen is critical
D. ANAL AGENESIS and requires skill in physical diagnosis, intimate ac-
In the child with anal agenesis, an anal dimple is pre- quaintance with the characteristic symptoms of a large
sent, and stimulation of the perianal area leads to puck- number of conditions, and the judicious selection of
ering, indicating that the external sphincter is present. laboratory and radiologic tests.
If no associated rectoperineal fistula is present, intesti-
nal obstruction occurs. Fistulas may also be vulvar in Gauderer MW: Acute abdomen. When to operate immediately and
the female and urethral in the male. when to observe. Semin Pediatr Surg 1997;6:74.

E. ANORECTAL AGENESIS
PERITONITIS
Anorectal agenesis accounts for 75% of total anorectal
anomalies. Fistulas are almost invariably present. In the Primary bacterial peritonitis accounts for less than 2%
female, they may be vaginal or may enter a urogenital of pediatric cases of peritonitis. The most common or-
sinus, which is a common passageway for the urethra ganisms responsible are Escherichia coli, other enteric
and vagina. In the male, fistulas are rectovesical or rec- organisms, hemolytic streptococci, and pneumococci.
tourethral. Associated major congenital malformations Primary peritonitis occurs in patients with splenec-
are common. Sacral defects and absence of internal and tomy, splenic dysfunction, or ascites (nephrotic syn-
external anal sphincters are common. drome, advanced liver disease, kwashiorkor). It occurs
also in infants with pyelonephritis or pneumonia. Sec-
ondary peritonitis is associated with peritoneal dialysis,
Radiologic Findings penetrating abdominal trauma, or a ruptured viscus.
Careful radiologic evaluation is indicated immediately The organisms associated with secondary peritonitis
so that the anal anomaly and the extent of associated vary depending on the cause. In association with peri-
636 / CHAPTER 20

Table 20–3. Etiologic classification of acute abdomen.

Mechanical Obstruction Inflammatory Diseases and Infections

Intraluminal Extraluminal Gastrointestinal Blunt
Obstruction Obstruction Disease Paralytic Ileus Trauma Miscellaneous
Foreign body Hernia Appendicitis Sepsis Accident Lead poisoning
Bezoar Intussusception Crohn disease Pneumonia Battered child Sickle cell crisis
Fecalith Volvulus Ulcerative colitis Pyelonephritis syndrome Familial Mediterra-
Gallstone Duplication Henoch–Schönlein Peritonitis nean fever
Parasites Stenosis purpura and other Pancreatitis Porphyria
Distal intestinal obstruc- Tumor causes of vasculi- Cholecystitis Diabetic acidosis
tion syndrome of Mesenteric cyst tis Renal and gall- Addisonian crisis
cystic fibrosis bladder stones
Tumor Superior mesenteric Peptic ulcer Pelvic inflammation Torsion of testis
Fecaloma artery syndrome Meckel’s diverticuli- Lymphadenitis due Torsion of ovarian
Pyloric stenosis tis to viral or bacterial pedicle
Acute gastroenteritis infection
Pseudomembranous
enterocolitis
Reproduced, with permission, from Roy CC, Morin CL, Weber AM: Gastrointestinal emergency problems in paediatric practice. Clin Gas-
troenterol 1981;10:225.

toneal dialysis, organisms not commonly pathogenic ACUTE APPENDICITIS

such as Staphylococcus epidermidis and Candida may be
the cause of secondary peritonitis. Multiple enteric or- Acute appendicitis is the most common indication for
ganisms may be isolated after penetrating abdominal emergency abdominal surgery in childhood. The fre-
injury or bowel perforation. Intra-abdominal abscesses quency increases with age and peaks between 15 and
may form in pelvic, subhepatic, or subphrenic areas, 30 years. Obstruction of the appendix by fecaliths
but such localization of infection is less common in (25%) or parasites is a predisposing factor.
young infants than in adults. The incidence of perforation is high (40%) in in-
Symptoms include severe abdominal pain, fever, fants and children. To avoid delay in diagnosis, it is im-
nausea, and vomiting. Respirations are shallow. The ab- portant to maintain close communication with parents,
domen is tender, rigid, and distended, with involuntary perform a thorough physical examination and sequen-
guarding. Bowel sounds may be absent. Diarrhea is tial examinations of the abdomen at frequent intervals
fairly common in primary peritonitis and less so in sec- over several hours, and interpret correctly the evolving
ondary peritonitis. symptoms and signs.
The leukocyte count is high initially (> 20,000/µL),
with a predominance of immature forms, and later may Clinical Findings
fall to neutropenic levels, especially in primary peritoni-
tis. Bacterial peritonitis should be suspected if paracente- A. SYMPTOMS AND SIGNS
sis fluid contains more than 500 leukocytes/µL or more The typical child with appendicitis has fever and peri-
than 32 mg/dL of lactate; if it has a pH less than 7.34; or umbilical abdominal pain, which then localizes to the
if the pH is over 0.1 pH unit less than arterial blood pH. right lower quadrant, accompanied by signs of peri-
Diagnosis is made by Gram stain and culture, preferably toneal irritation. Anorexia, vomiting, constipation, and
of 5–10 mL of fluid for optimal yield. The blood culture diarrhea also occur. The clinical picture is often atypical
is often positive in primary peritonitis. and includes generalized pain and tenderness around
Antibiotic treatment and supportive therapy for de- the umbilicus without leukocytosis. Rectal examination
hydration, shock, and acidosis are indicated. Surgical should always be done and may reveal localized mass or
treatment of the underlying cause of secondary peri- tenderness. Because many conditions give rise to symp-
tonitis is critical. Removal of infected peritoneal dialysis toms mimicking appendicitis and because physical
catheters in patients with secondary peritonitis is some- findings are often inconclusive, it is important to per-
times necessary and almost always required if Candida form repeated examinations of the abdomen over sev-
infection is present. eral hours. In children younger than age 2 years, the
 GASTROINTESTINAL TRACT / 637

pain of appendicitis is poorly localized, and perforation occurs in patients with celiac disease and cystic fibro-
before surgery is common. sis—related to the bulk of stool in the terminal ileum.
Henoch–Schönlein purpura may also cause isolated
B. LABORATORY FINDINGS small-bowel intussusception. In children older than age
White blood cell counts are seldom higher than 6 years, lymphoma is the most common cause. Inter-
15,000/µL. Pyuria, fecal leukocytes, and guaiac-posi- mittent small-bowel intussusception is a rare cause of
tive stool are occasionally found. recurrent abdominal pain.
The usual ileocolic intussusception starts just proxi-
C. IMAGING
mal to the ileocecal valve and extends for varying dis-
A radiopaque fecalith is reportedly present in two thirds tances into the colon. Swelling, hemorrhage, incarcera-
of cases of ruptured appendix. A positive diagnosis of tion, and necrosis of the intussuscepted bowel may
nonperforated appendicitis cannot be made by barium occur. Intestinal perforation and peritonitis occur as a
enema. In experienced hands, ultrasonography of the result of impairment of venous return.
acutely inflamed appendix shows a noncompressible,
thickened appendix in 93% of cases. A localized fluid col-
lection adjacent to or surrounding the appendix may also Clinical Findings
be seen. Abdominal computed tomography scan after in- Characteristically, a thriving infant age 3–12 months
stillation of rectal contrast with thin cuts in the area of the develops recurring paroxysms of abdominal pain with
appendix may be diagnostic. Indium-labeled white blood screaming and drawing up of the knees. Vomiting and
cell scan may localize to an inflamed appendix. Enlarged diarrhea occur soon afterward (90% of cases), and
mesenteric lymph nodes are a nondiagnostic finding. bloody bowel movements with mucus appear within
the next 12 hours (50%). The child is characteristically
Differential Diagnosis lethargic between paroxysms. Prostration and fever su-
pervene. The abdomen is tender and becomes dis-
The presence of intrathoracic infection (eg, pneumo- tended. On palpation, a sausage-shaped mass may be
nia) or urinary tract infection should be kept in mind, found, usually in the upper mid abdomen. An intussus-
along with other medical and surgical conditions lead- ception can persist for several days if obstruction is not
ing to acute abdomen (see Table 20–3). complete, and patients may present with separate at-
tacks of enterocolitis. In older children, sudden attacks
Treatment & Prognosis of abdominal pain may be related to chronic recurrent
Exploratory laparotomy or laparoscopy is indicated intussusception with spontaneous reduction. In July
whenever the diagnosis of appendicitis cannot be ruled 1999, the American Academy of Pediatrics recom-
out after a period of close observation. Postoperative mended suspending oral rotavirus immunization in the
antibiotic therapy is reserved for patients with gan- United States because of an increased occurrence of in-
grenous or perforated appendix. A single intraoperative tussusception among young infants in the weeks fol-
dose of cefoxitin or cefotetan is recommended for all lowing oral immunization.
patients to prevent postoperative complications. The
mortality rate is less than 1% during childhood despite Treatment
the high incidence of perforation. In uncomplicated A. CONSERVATIVE MEASURES
nonruptured appendicitis, laparoscopic approach is as-
sociated with a shortened hospital stay. Barium enema and air enema are both diagnostic and
therapeutic. Reduction by barium enema should not be
Mason JD: The evaluation of acute abdominal pain in children. attempted if signs of strangulated bowel, perforation, or
Emerg Med Clin North Am 1996;14:629. severe toxicity are present. Air insufflation of the colon
under fluoroscopic guidance is a safe alternative to bar-
INTUSSUSCEPTION ium enema with excellent diagnostic sensitivity and
specificity without the risk of contaminating the ab-
Intussusception is the most frequent cause of intestinal dominal cavity with barium. Great care must be taken
obstruction in the first 2 years of life. It is three times in performing either air or barium enema because is-
more common in males than in females. In most cases chemic damage to the colon secondary to vascular com-
(85%) the cause is not apparent, although polyps, promise increases the risk of perforation.
Meckel diverticulum, Henoch–Schönlein purpura,
lymphoma, lipoma, parasites, foreign bodies, and viral B. SURGICAL MEASURES
enteritis with hypertrophy of Peyer patches are predis- In extremely ill patients and in patients who have evi-
posing factors. Intussusception of the small intestine dence of bowel perforation or in whom hydrostatic or
638 / CHAPTER 20

pneumatic reduction has been unsuccessful (25%), can be extracted. Only an experienced radiologist
surgery is required. Surgery has the advantage of identi- should attempt this maneuver.
fying any lead point such as a Meckel diverticulum.
Surgical reduction of intussusception is associated with
a lower recurrence rate than pneumatic reduction.
ANAL FISSURE
Anal fissure is a slit-like tear in the squamous epithe-
lium of the anus, usually secondary to the passage of
Prognosis large, hard fecal masses. Anal stenosis, anal crypt ab-
The prognosis relates directly to the duration of the in- scess, and trauma can be contributory factors. Sexual
tussusception before reduction. The mortality rate with abuse must be considered in children with large, irregu-
treatment is 1–2%. The patient should be observed lar, or multiple anal fissures. Anal fissures may be the
carefully after hydrostatic or pneumatic reduction be- presenting sign of Crohn disease in older children.
cause intussusception recurs within 24 hours in 3–4% The infant or child with anal fissure typically cries
of patients. with defecation and will try to hold back stools. Sparse,
bright red bleeding is seen on the outside of the stool or
on the toilet tissue following defecation. The fissure can
Eshel G et al: Intussusception: A nine year survey. J Pediatr Gas- often be seen if the patient is examined in a knee-chest
troenterol Nutr 1997;24:253.
position with the buttocks spread apart. When a fissure
cannot be identified, it is essential to rule out other
FOREIGN BODIES causes of rectal bleeding such as juvenile polyp, perianal
IN THE ALIMENTARY TRACT inflammation (due to group A streptococcal infection),
or inflammatory bowel disease. Anal fissures should be
Most foreign bodies pass through the GI tract without treated promptly to break the constipation → fissure →
difficulty, although objects longer than 5 cm may have retention → constipation cycle. A stool softener should
difficulty negotiating the ligament of Treitz. Ingested be given. Anal dilation relieves sphincter spasm. Warm
foreign bodies tend to lodge in areas of natural constric- sitz baths after defecation may be helpful. In rare cases,
tion—valleculae, thoracic inlet, GE junction, pylorus, silver nitrate cauterization or surgery is indicated. Anal
ligament of Treitz, and ileocecal junction. Foreign bod- surgery should be avoided in patients with Crohn dis-
ies lodged in the esophagus for more than 24 hours re- ease because of the high risk of recurrence and progres-
quire removal. Smooth foreign bodies in the stomach, sion after surgery.
such as buttons or coins, may be watched without at-
tempting removal for up to several months if the child
is free of symptoms. Straight pins, screws, and nails INGUINAL HERNIA
generally pass without incident. Removal of open safety A peritoneal sac precedes the testicle as it descends from
pins or wooden toothpicks is recommended. Disk- the genital ridge to the scrotum. The lower portion of
shaped batteries lodged in the esophagus should be re- this sac envelops the testis to form the tunica vaginalis,
moved immediately. Disk-shaped batteries in the stom- and the remainder normally atrophies by the time of
ach will generally pass uneventfully. The use of birth. In some cases, peritoneal fluid may become
balanced electrolyte lavage solutions containing poly- trapped in the tunica vaginalis of the testis (noncom-
ethylene glycol may help the passage of small, smooth municating hydrocele). If the processus vaginalis re-
foreign bodies lodged in the stomach or intestine. mains open, peritoneal fluid or an abdominal structure
Lavage is especially useful in hastening the passage of may be forced into it (indirect inguinal hernia).
disk-shaped batteries or ingested tablets that may be Most inguinal hernias are of the indirect type and
toxic. Failure of a smooth foreign body to exit the occur more frequently (9:1) in boys than in girls. Her-
stomach suggests the possibility of gastric outlet ob- nias may be present at birth or may appear at any age
struction. thereafter. The incidence in premature male infants is
Esophagogastroscopy will permit the removal of close to 5%. Inguinal hernia is reported in 30% of male
most foreign bodies lodged in the esophagus and stom- infants weighing 1000 g or less.
ach. A Foley catheter may be used to dislodge smooth,
round esophageal foreign bodies in healthy children
with no previous esophageal disease. The catheter is in-
Clinical Findings
troduced into the esophagus, and the balloon at the dis- No symptoms are associated with an empty processus
tal end is inflated below the foreign body. Careful with- vaginalis. In most cases, a hernia is a painless inguinal
drawal of the catheter under fluoroscopic observation swelling of variable size. The mother of the infant with
will bring the foreign body into the mouth, where it an inguinal hernia may be the only person to see the
 GASTROINTESTINAL TRACT / 639

mass, as it may retract when the infant is active, cold, white infants. Small bowel may incarcerate in small-di-
frightened, or agitated from the physical examination. ameter umbilical hernias. Most umbilical hernias
There may be a history of inguinal fullness associated regress spontaneously if the fascial defect has a diameter
with coughing or long periods of standing, or there of less than 1 cm. Large defects and smaller hernias per-
may be a firm, globular, and tender swelling, sometimes sisting after age 4 years should be treated surgically. Re-
associated with vomiting and abdominal distention. In ducing the hernia and strapping the skin over the ab-
some instances, a herniated loop of intestine may be- dominal wall defect does not accelerate the healing
come partially obstructed, leading to pain and partial process.
intestinal obstruction. Rarely, bowel becomes trapped
in the hernia sac, and complete intestinal obstruction TUMORS OF THE GASTROINTESTINAL
occurs. Gangrene of the hernia contents or testis may
occur. In girls, the ovary may prolapse into the hernia TRACT
sac. Inspection of the two inguinal areas may reveal a 1. Juvenile Polyps
characteristic bulging or mass. Infants should be ob-
served for evidence of swelling after crying, and older Juvenile polyps are usually pedunculated and solitary.
children after bearing down. A suggestive history is The head of the polyp is composed of hyperplastic
often the only criterion for diagnosis, along with the glandular and vascular elements, often with cystic trans-
“silk glove” feel of the rubbing together of the two walls formation. Juvenile polyps are benign, and 80% occur
of the empty hernia sac. in the rectosigmoid. Their incidence is highest between
ages 3 and 5 years, and they are rare before age 1 year
Differential Diagnosis and, because of autoamputation, after age 15 years.
They are more frequent in boys. The painless passage of
Inguinal lymph nodes may be mistaken for a hernia. small amounts of bright red blood on a normal or con-
Nodes are usually multiple with more discrete borders. stipated stool is the most frequent manifestation. Ab-
A hydrocele of the cord should transilluminate. An un- dominal pain is rare, but a juvenile polyp can be the
descended testis is usually mobile in the canal and is as- lead point for an intussusception. Low-lying polyps
sociated with absence of the gonad in the scrotum. may prolapse during defecation.
Rarely, many juvenile polyps may be present in the
Treatment colon, causing anemia, diarrhea, and protein loss. A few
cases of generalized juvenile polyposis involving the
Manual reduction of incarcerated inguinal hernias can be stomach, small bowel, and colon have been reported.
attempted after the sedated infant is placed in the Tren- These cases are associated with a slightly increased risk
delenburg position with an ice bag on the affected side. of cancer.
Manual reduction is contraindicated if incarceration has Colonoscopy is both diagnostic and therapeutic
been present for more than 12 hours or if bloody stools when polyps are suspected. After removal of the polyp
are noted. Surgery is usually indicated if a hernia has ever by electrocautery, nothing further should be done if
incarcerated. Hydroceles frequently resolve by age histologic findings confirm the diagnosis. There is a
2 years. Controversy remains about exploration of the slight risk of developing further juvenile polyps.
opposite side. Exploration of the unaffected groin can Other polyposis syndromes are summarized in
document the patency of the processus vaginalis, but pa- Table 20–4.
tency does not always mean that herniation will occur,
especially in patients older than age 1 year, in whom the
risk of contralateral hernia is about 10%. Incarceration of 2. Cancers of the Esophagus,
an inguinal hernia is more likely to occur in boys and in Small Intestine, & Colon
children younger than 10 months of age.
Esophageal cancer is rare in childhood. Cysts, leiomy-
omas, and hamartomas predominate. Caustic injury of
Gahukamble DB, Khamage AS: Early vs delayed repair of reduced
incarcerated inguinal hernias in the pediatric population.
the esophagus increases the risk of squamous cell carci-
J Pediatr Surg 1996;31:1218 [PMID: 8887087]. noma as a very long term complication. Chronic peptic
Nicholls E: Inguinal scrotal problems in children. Practitioner esophagitis is associated with Barrett esophagus, a pre-
2003;247:226. cancerous lesion. Simple GE reflux in infancy without
esophagitis is not a risk for cancer of the esophagus.
The most common gastric or small-bowel cancer in
UMBILICAL HERNIA children is lymphoma or lymphosarcoma. Intermittent
Umbilical hernias are more common in premature than abdominal pain, abdominal mass, intussusception, or a
in full-term infants and more common in black than in celiac-like picture may be present. Carcinoid tumors are
 Table 20–4. Gastrointestinal polyposis syndromes.

Malignant
Location Number Histology Extraintestinal Findings Potential Recommended Therapy
Juvenile polyps Colon Single (70%) Hyperplastic, None None Remove polyp for continuous
Several (30%) hamartomatous bleeding or prolapse.
Familial juvenile Colon More than Hyperplastic None 10–25%; Remove all polyps. Consider
polyposis colia ten with focal higher if colectomy if very numerous
adenomatous familial or adenomatous.
change
Generalized Stomach, small Multiple Hyperplastic Hydrocephaly, cardiac lesions, mesenteric lymph- 10–25% Colectomy and close
juvenile poly- bowel, colon with focal angioma, malrotation surveillance.
posisa adenomatous
change
640

Familial Colon; less commonly, Multiple Adenomatous None 95–100% Colectomy by age 18 years.
adenomatous stomach and small
polyposisa bowel
Peutz–Jeghers Small bowel, stomach, Multiple Hamartomatous Pigmented cutaneous and oral macules; ovarian 2–3% Remove accessible polyps or
syndromea colon cysts and tumors; bony exostoses those causing obstruction or
bleeding.
Gardner’s Colon; less commonly, Multiple Adenomatous Cysts, tumors, and desmoids of skin and bone; 95–100% Colectomy by age 18 years.
syndrome stomach and small bowel ampullary tumors; other tumors, retinal pigmen- Upper tract surveillance.
tations can be a screening tool in families
Cronkhite–Canada Stomach, colon; less Multiple Hamartomatous Alopecia; onychodystrophy; hyperpigmentation Rare None.
syndrome commonly, esophagus
and small bowel
Turcot’s Colon Multiple Adenomatous Thyroid and brain tumors are the usual presen- Possible Central nervous system
syndromeb tation screening most important
a
Autosomal dominant.
b
Autosomal recessive.
 GASTROINTESTINAL TRACT / 641

usually benign and most often an incidental finding in with at least eight serotypic variants, is the most com-
the appendix following appendectomy. Metastasis is mon. As with most viral pathogens, rotavirus affects the
rare. The carcinoid syndrome (flushing, sweating, hy- small intestine, causing voluminous watery diarrhea
pertension, diarrhea and vomiting), associated with without leukocytes or blood. In the United States, ro-
serotonin secretion, only occurs with metastatic carci- tavirus affects mainly infants between ages 3 and
noid tumors. 15 months. Peak incidence in the United States is in
Adenocarcinoma of the colon is rare in pediatric pa- the winter months. Sporadic cases occur at other times.
tients. The transverse colon and rectosigmoid are the The virus is transmitted via the fecal–oral route and
two most commonly affected sites. The low 5-year sur- survives for hours on hands and for days on environ-
vival rate relates to the nonspecificity of presenting mental fomites.
complaints and the large percentage of undifferentiated
types. Children with a family history of colon cancer, Diagnosis & Treatment
chronic ulcerative colitis, or familial polyposis syn-
dromes are at greater risk.
of Rotavirus Infections
The incubation period for rotavirus is 24–48 hours.
3. Mesenteric Cysts Vomiting is the first symptom in 80–90% of patients,
followed within 24 hours by low-grade fever and volu-
These rare tumors may be small or large and single or minous watery diarrhea. Diarrhea usually lasts 4–8 days
multiloculated. Invariably thin-walled, they contain but may last longer in young infants or immunocom-
serous, chylous, or hemorrhagic fluid. They are com- promised patients. The white blood cell count is rarely
monly located in the mesentery of the small intestine elevated. The stool sodium level is usually less than
but may also be seen in the mesocolon. Most mesen- 40 mEq/L. Thus, as patients become dehydrated from
teric cysts cause no symptoms. Traction on the mesen- unreplaced fecal water loss, they may become hyperna-
tery may lead to colicky abdominal pain, which can be tremic. The stool does not contain blood or white cells.
mild and recurrent but may appear acutely with vomit- Metabolic acidosis results from bicarbonate loss in the
ing. Volvulus may occur around a cyst, and hemor- stool, ketosis from poor intake, and lactic acidemia
rhage into a cyst may be mild or hemodynamically sig- from hypotension and hypoperfusion.
nificant. A rounded mass can occasionally be palpated Replacement of fluid and electrolyte deficits and on-
or seen on radiograph to displace adjacent intestine. going losses is critical, especially in small infants. (Oral
Abdominal ultrasonography is usually diagnostic. Sur- and intravenous therapy are discussed in Chapter 42.)
gical removal is indicated. The use of oral rehydration fluid is appropriate in most
cases. The use of clear liquids or hypocaloric (dilute for-
4. Intestinal Hemangioma mula) diets for more than 48 hours is not advisable in
uncomplicated viral gastroenteritis because starvation
Hemangiomas of the bowel may cause acute or chronic depresses digestive function and prolongs diarrhea.
blood loss. They may also cause intestinal obstruction Intestinal lactase levels are reduced during rotavirus
via intussusception, local stricture, or intramural infection. Brief use of a lactose-free diet is associated
hematoma formation. Thrombocytopenia and con- with a shorter period of diarrhea but is not critical to
sumptive coagulopathy are occasional complications. successful recovery in most healthy infants. Reduced fat
Some lesions are telangiectasias (Rendu–Osler–Weber intake during recovery may reduce nausea and vomit-
syndrome), and others are capillary hemangiomas. The ing.
largest group are cavernous hemangiomas, which are Antidiarrheal medications are ineffective (kaolin–
composed of large, thin-walled vessels arising from the pectin combinations) or even dangerous (loperamide,
submucosal vascular plexus. They may protrude into tincture of opium, diphenoxylate with atropine). Bis-
the lumen as polypoid lesions or may invade the intes- muth subsalicylate preparations may reduce stool vol-
tine from mucosa to serosa. ume but are not critical to recovery. Oral immunoglob-
ulin or specific antiviral agents have occasionally been
ACUTE INFECTIOUS DIARRHEA useful in limiting duration of disease in immunocom-
promised patients.
(Gastroenteritis) Specific identification of rotavirus is not required in
Viruses are the most common cause of acute gastroen- every case, especially in outbreaks. Rotavirus antigens
teritis in developing and developed countries. Bacterial can be identified in stool. False positives (which may
and parasitic enteric infections are discussed in Chap- actually be nonpathogenic rotavirus) are seen in
ters 38 and 39. Of the viral agents causing enteric infec- neonates. Some immunity is imparted by the first
tion, rotavirus, a 67-nm double-stranded RNA virus episode of rotavirus infection. Serum antibodies are
642 / CHAPTER 20

present, but their role in prevention of subsequent at- (4) increase in unabsorbable osmotically active mole-
tacks is unclear. Repeat infections occur but are usually cules in the intestinal lumen; (5) increase in intestinal
less severe. Prevention of rotavirus is mainly by good permeability, leading to increased loss of water and
hygiene and prevention of fecal–oral contamination. In electrolytes; and (6) stimulation of enterocyte secretion
July 1999, the American Academy of Pediatrics recom- by toxins or cytokines.
mended suspending the use of oral rotavirus vaccine in
the United States despite an approximately 75% pro- Noninfectious Causes of Diarrhea
tection rate of vaccinated infants because of its associa-
tion with intussusception in the first 3 weeks following A. ANTIBIOTIC THERAPY
vaccine administration. Diarrhea is reported in up to 60% of children receiving
antibiotics. Eradication of normal gut flora and over-
Diagnosis & Treatment growth of other organisms may cause diarrhea. Most
of Other Viral Infections antibiotic-associated diarrhea is watery in nature, is not
associated with systemic symptoms, and decreases when
Other viral pathogens in stool have been identified by antibiotic therapy is stopped. Pseudomembranous
electron microscopy, special viral cultures, or enzyme- colitis, caused by the toxins produced by Clostridium
linked immunoassays in infants with diarrhea. Depend- difficile, occurs in 0.2–10% of patients taking antibi-
ing on the geographic location, enteric adenoviruses otics, especially clindamycin, cephalosporins, and
(serotypes 40 and 41) or caliciviruses are the next most amoxicillin. Patients develop fever, tenesmus, and ab-
common viral pathogens in infants. The symptoms of dominal pain with diarrhea, which contains leukocytes
enteric adenovirus infection are similar to those pro- and sometimes gross blood up to 8 weeks after antibi-
duced from rotavirus, but infection is not seasonal and otic exposure. Treatment with oral metronidazole
duration of illness may be longer. The Norwalk agent, a (30 mg/kg/d) or oral vancomycin (30–50 mg/kg/d) for
calicivirus, is a small RNA virus that causes chiefly 7 days is recommended. Vancomycin is many times
vomiting but also some diarrhea in older children and more expensive than metronidazole and no more effica-
adults, usually in common source outbreaks (perhaps cious. Relapse occurs after treatment in 10–50% of pa-
water-borne). The duration of symptoms is short, usu- tients because of exsporulation of residual spores in the
ally 24–48 hours. Other potentially pathogenic viruses colon. Retreatment with the same antibiotic regimen is
include astroviruses, corona-like viruses, and other usually effective, but multiple relapses are possible.
small round viruses. Cytomegalovirus rarely causes diar-
rhea in immunocompetent children but may cause ero- B. EXTRAINTESTINAL INFECTIONS
sive colitis or enteritis in immunocompromised hosts. Infections of the urinary tract and upper respiratory
Cytomegalovirus enteritis is particularly common after tract (especially otitis media) are at times associated
bone marrow transplantation and in late stages of HIV with diarrhea. The mechanism remains obscure. An-
infection. tibiotic treatment of the primary infection, toxins re-
leased by infecting organisms, and local irritation of the
Caeiro JP et al: Etiology of outpatient pediatric nondysenteric diar- rectum (in patients with bladder infection) may play a
rhea: A multicenter study in the United States. Pediatr Infect role.
Dis J 1999;18:94.
C. MALNUTRITION
CHRONIC DIARRHEA Malnutrition is associated with an increased frequency
of enteral infections. Decreased bile acid synthesis, pan-
It is difficult to define chronic diarrhea because normal creatic enzyme output, and disaccharidase activity; al-
bowel habits vary greatly. Some infants normally have tered motility; and changes in the intestinal flora all
5–8 soft small stools daily. A gradual or sudden increase may cause diarrhea. Severely malnourished children are
in the number and volume of stools (> 15 g/kg/d) com- at higher risk of enteric infections because of depressed
bined with an increase in fluidity should raise a suspi- immune functions, both cellular and humoral.
cion that an organic cause of chronic diarrhea is pre-
sent. D. DIET
Diarrhea may result from any of the following Overfeeding may cause diarrhea, especially in young in-
pathogenetic mechanisms: (1) interruption of normal fants. Relative deficiency of pancreatic amylase in
cell transport processes for water, electrolytes, or nutri- young infants may produce diarrhea after starchy foods.
ents; (2) decrease in the surface area available for ab- Fruit juices, especially those high in fructose or sorbitol,
sorption, which may be due to shortening of the bowel produce osmotic diarrhea because these osmotically ac-
or mucosal disease; (3) increase in intestinal motility; tive sugars are poorly absorbed by the immature gut.
 GASTROINTESTINAL TRACT / 643

Intestinal irritants (spices and foods high in fiber) and The following measures are helpful: institution of a
histamine-containing or histamine-releasing foods (eg, slightly high-fat (about 40% of total calories), low-car-
citrus fruits, tomatoes, certain cheeses, red wines, and bohydrate, high-fiber diet; avoidance of between-meal
scromboid fish) also cause diarrhea. snacks; and avoidance of chilled fluids, especially fruit
juices. It may be helpful to give loperamide,
E. ALLERGIC DIARRHEA 0.1–0.2 mg/kg/d in two or three divided doses;
Diarrhea caused by allergy to dietary proteins is a fre- cholestyramine, 2–4 g in divided doses; or psyllium
quently entertained but rarely authenticated diagnostic agents, 1–2 tsp twice daily.
entity. Protein allergy is more common in infants
younger than age 12 months, who may experience mild G. SECRETORY DIARRHEA
to severe colitis. A personal or family history of atopy is Certain malignancies of childhood, including neuro-
common in infants with enteric protein allergy. Older blastoma, ganglioneuroma, metastatic carcinoid, and
children may develop a celiac-like syndrome with flat- GI neuroendocrine tumors such as pancreatic VIPoma
tening of small-bowel villi, steatorrhea, hypoproteine- or gastrinoma, may secrete substances such as gastrin
mia, occult blood loss, and chronic diarrhea. Skin test- and vasoactive interstinal polypeptide that promote
ing is not reliable. Double-blind oral challenge with the small-intestine secretion of water and electrolytes.
suspected food under careful observation is necessary to These children present with large volume, watery diar-
confirm intestinal protein allergy. Mild diarrhea with rhea that does not cease when they discontinue oral
blood and mucus may occur in thriving young infants feedings. Fat malabsorption is not characteristic. The
receiving either breast milk or formula. In the breast- serum potassium level is often low because of losses in
fed infant, maternal avoidance of milk protein may be diarrhea. The hallmark of the diarrhea is that, unlike
effective in reducing the signs of colitis. Feeding a pro- osmotic and infectious viral diarrheas, the sodium con-
tein hydrolysate formula may also reduce symptoms. tent of the stool water is high, usually between 90 and
Because allergic colitis in young infants is self-limited, 140 mEq/L of stool. Other specific signs and symptoms
the condition does not absolutely require treatment if are associated with specific tumors. Neuroblastoma and
the infant is thriving and the colitic symptoms are ganglioneuroma lead to elevations in urinary ho-
not severe. Colonoscopy is not required for diagnosis, movanillic acid and vanillylmandelic acid. Metastatic
but rectal biopsies usually show mild lymphonodular carcinoid is associated with characteristic flushing and
hyperplasia, mucosal edema, and slight eosinophilia. sweating. Gastrinoma may be associated with multiple
In infants, the condition usually disappears after duodenal ulcers (Zollinger–Ellison syndrome). In all se-
12 months. Allergies to fish, peanuts, and eggs are more cretory diarrheas, a careful radiologic search for a tumor
likely to be lifelong. Multiple food allergy (more than mass is indicated. Bacterial overgrowth of the small
three) is rare. bowel in patients with short bowel, cancer chemother-
apy, or anatomic abnormalities may lead to the produc-
Khan S, Orenstein S: Eosinophilic gastroenteritis: Epidemiology, tion of enterotoxins, which can promote a secretory di-
diagnosis and management. Paed Drugs 2002;4:563. arrhea without the presence of tumor. Cholera is the
best known bacterial secretory diarrhea. Its enterotoxin
F. CHRONIC NONSPECIFIC DIARRHEA stimulates cyclic adenosine monophosphate in the ente-
Chronic nonspecific diarrhea is the most common rocyte, which promotes salt and water secretion.
cause of loose stools in thriving children. The typical
patient is a healthy child age 6–20 months who was a
colicky baby and who has three to six loose mucoid
THE MALABSORPTION SYNDROMES
stools per day during the waking hours. The diarrhea Malabsorption of ingested food has many causes (Table
worsens with a low-residue, low-fat, or high-carbohy- 20–5). Shortening of the small bowel (usually via surgi-
drate diet and during periods of stress and infection. It cal resection) and mucosal damage (celiac disease) both
clears spontaneously at about age 31⁄2 years (usually co- reduce surface area. Impaired motility of the small in-
incident with toilet training). No organic disease is dis- testine may interfere with normal propulsive move-
coverable. Possible causes include abnormalities of bile ments and mixing of food with pancreatic and biliary
acid absorption in the terminal ileum, incomplete car- secretions. Anaerobic bacteria proliferate under these
bohydrate absorption (excessive fruit juice ingestion conditions and impair fat absorption by deconjugation
seems to worsen the condition or in some cases appears of bile acids (intestinal pseudo-obstruction, post-
to be the primary cause), and abnormal motor func- operative blind loop syndrome). Impaired intestinal
tion. A high familial incidence of functional bowel dis- lymphatic (congenital lymphangiectasis) or venous
ease is observed. Stool tests for blood, white cells, fat, drainage also causes malabsorption. Diseases reducing
parasites, and bacterial pathogens are negative. pancreatic exocrine function (cystic fibrosis, Shwach-
644 / CHAPTER 20

Table 20–5. Malabsorption syndromes.

Intraluminal phase abnormalities Intestinal phase abnormalities (cont’d)

Acid hypersecretion; Zollinger–Ellison syndrome Circulatory disturbances
Gastric resection Cirrhosis
Exocrine pancreatic insufficiency Congestive heart failure
Cystic fibrosis Abnormal structure of gastrointestinal tract
Chronic pancreatitis Dumping syndrome after gastrectomy
Pancreatic pseudocysts Malrotation
Schwachman syndrome Stenosis of jejunum or ileum
Enterokinase deficiency Small bowel resection; short bowel syndrome
Lipase and colipase deficiency Polyposis
Malnutrition Selective inborn absorptive defects
Decreased conjugated bile acids Congenital malabsorption of folic acid
Liver production and excretion Selective malabsorption of vitamin B12
Neonatal hepatitis Cystinuria, methionine malabsorption
Biliary atresia: intrahepatic and extrahepatic Hartnup disease, blue diaper syndrome
Acute and chronic active hepatitis Glucose–galactose malabsorption
Disease of the biliary tract Primary disaccharidase deficiency
Cirrhosis Acrodermatitis enteropathica
Fat malabsorption in the premature infant Abetalipoproteinemia
Intestinal malabsorption of bile acids Congenital chloridorrhea
Short bowel syndrome Primary hypomagnesemia
Bacterial overgrowth Hereditary fructose intolerance
Blind loop Familial hypophosphatemic rickets
Fistula Endocrine diseases
Strictures, regional enteritis Diabetes mellitus
Scleroderma, intestinal pseudo-obstruction Addison disease
Intestinal phase abnormalities Hyperthyroidism
Mucosal diseases Hypoparathyroidism, pseudohypoparathyroidism
Infections, bacterial or viral Neuroblastoma, ganglioneuroma
Infections, parasitic Vascular and lymphatic disorders
Giardia lamblia Whipple disease
Fish tapeworm Intestinal lymphangiectasis
Hookworm Congestive heart failure
Cryptosporidium Regional enteritis with lymphangiectasis
Malnutrition Lymphoma
Marasmus Abetalipoproteinemia
Kwashiorkor Miscellaneous
Dermatitis herpetiformis Renal insufficiency
Folic acid deficiency Carcinoid, mastocytosis
Drugs: methotrexate, antibiotics Immune deficiency disorders
Crohn disease Familial dysautonomia
Cow’s milk and soy protein intolerance Collagen–vascular disease
Secondary disaccharidase deficiency Wolman disease
Secondary monosaccharide intolerance Histiocytosis X
Hirschsprung disease with enterocolitis
Tropical sprue
Celiac disease
Radiation enteritis
Lymphoma
 GASTROINTESTINAL TRACT / 645

man syndrome) or the production and flow of biliary Clinical Findings

secretions cause nutrient malabsorption. Malabsorption
of specific nutrients may be genetically determined (dis- Signs and symptoms are mainly those related to hy-
accharidase deficiency, glucose–galactose malabsorp- poproteinemia, and in some instances to malabsorp-
tion, and abetalipoproteinemia). tion. Edema, ascites, poor weight gain, and, depending
on the underlying condition, signs of specific vitamin
and mineral deficiencies may all be present. Serum al-
Clinical Findings bumin and globulins may be decreased. Fecal α1-anti-
trypsin, a marker for protein loss, is elevated (> 3 mg/g
GI symptoms such as diarrhea, vomiting, anorexia, ab- dry weight stool; slightly higher in breast-fed infants).
dominal pain, failure to thrive, and abdominal disten- Disorders associated with protein-losing enteropathy
sion are common. Observation of the stools for abnor- are listed in Table 20–6.
mal color, consistency, bulkiness, odor, mucus, and
blood is important. Microscopic examination of stools Differential Diagnosis
for neutral fat and fatty acids is helpful because most
malabsorption syndromes involve some fat malabsorp- Hypoalbuminemia may be due to an increased cata-
tion. Pancreatic insufficiency is associated with neutral bolic rate or may be associated with poor protein in-
fat in the stool. Fatty acids are the major fatty material take, impaired hepatic protein synthesis, or congenital
found in the stool of patients with mucosal disease malformations of lymphatics outside the GI tract. Pro-
(celiac disease) and liver disease. teinuria associated with nephritis and nephrotic syn-
Quantitative assessment of fat absorption requires drome may also cause hypoalbuminemia.
measurement of fat excreted in the feces as a proportion
of fat intake for a defined period. Excretion of 5% of
ingested fat is normal for a child older than age 1 year; Table 20–6. Disorders associated with
10–15% is normal in a younger infant. Prothrombin protein-losing enteropathy.
time and serum carotene, vitamin E, and vitamin D
levels may be depressed by long-standing fat malabsorp-
Vascular obstruction
tion. Accurate assessment of protein absorption is diffi-
Congestive heart failure
cult and requires isotopic labeling of amino acids. Loss Constrictive pericarditis
of serum proteins across the intestinal mucosa can be Atrial septal defect
estimated by measurement of fecal α1-antitrypsin. Mal- Primary myocardial disease
absorption of complex carbohydrate is rarely measured. Increased right atrial pressurea
Disaccharide or monosaccharide malabsorption is esti- Stomach
mated by reduction in stool pH, increased breath hy- Giant hypertrophic gastritis (Ménétrier disease), often
drogen after ingestion of carbohydrate, or decreased in- secondary to cytomegalovirus infection
testinal mucosal disaccharidase activity. Polyps
Other tests that may suggest a specific cause of mal- Gastritis secondary to Helicobacter pylori infection
absorption in a child include sweat chloride concentra- Small intestine
tion (cystic fibrosis), intestinal mucosal biopsy (eg, Celiac disease
celiac disease, intestinal lymphangiectasia, giardiasis, in- Intestinal lymphangiectasia
flammatory bowel disease), liver and gallbladder func- Blind loop syndrome
tion tests, and pancreatic secretion of enzymes after Abetalipoproteinemia
stimulation with secretin and cholecystokinin. Some of Chronic mucosal ischemia (eg, from chronic volvulus or
the most common disorders associated with malabsorp- radiation enteritis)
tion in pediatric patients are detailed in the following Allergic enteropathy
sections. Malrotation
Inflammatory bowel disease
Colon
Ulcerative colitis
1. Protein-Losing Enteropathies Hirschsprung disease
Loss of plasma proteins into the GI tract occurs in asso- Pseudomembranous colitis
ciation with inflammatory conditions of the intestine, Polyposis syndromes
intestinal graft-versus-host disease, acute and chronic Villous adenoma
intestinal infections, venous or lymphatic obstruction Solitary rectal ulcer
or malformations, and malignant infiltration of the in- a
Children who undergo Fontan procedure for tricuspid atresia are
testine or its lymphatics and vasculature. especially prone.
646 / CHAPTER 20

Treatment 3. Failure to thrive—The onset of diarrhea is usually

accompanied by loss of appetite, failure to gain weight,
Albumin infusions, diuretics, and a high-protein/low- and irritability. Weight loss is most marked in the limbs
fat diet may control symptoms. Treatment must be di- and buttocks. The abdomen becomes distended sec-
rected toward identifying and treating the underlying ondary to gas and fluid in the intestinal tract. Short
cause of GI protein loss if possible. stature and delayed puberty are characteristic in older
children and may be the only symptoms.
2. Celiac Disease (Gluten Enteropathy) 4. Anemia and vitamin deficiencies—Anemia usu-
Celiac disease results from intestinal sensitivity to the ally responds to iron supplementation and is rarely
gliadin fraction of glutens from wheat, rye, barley, and megaloblastic. Anemia is more likely to be the present-
(possibly) oats. Most pediatric cases present during the ing problem of adult patients with celiac disease. Defi-
second year of life, but the age at onset and the severity ciencies in fat-soluble vitamins are common. Rickets
are both variable. Up-to-date estimates of disease fre- can be seen when growth has not been completely
quency are being revised with the widespread use of halted by the disease. Osteomalacia is more common,
sensitive screening tests such as the tissue transglutami- however, and pathologic fractures may occur. Hy-
nase and endomysial antibodies. Screening with poprothrombinemia secondary to vitamin K malab-
antigliadin antibodies is no longer recommended be- sorption can cause easy bleeding.
cause of the high frequency of false-positive tests. It is 5. Silent celiac disease—Serologic screening among
estimated that the frequency of celiac disease in the pediatric patients with nonspecific GI complaints,
United States is around 1:300, a figure approaching the growth failure, conditions linked to celiac disease (type
high incidence reported in the past from European 1 diabetes, thyroid disease, vitiligo, IgA deficiency,
countries. It is thought that intestinal damage and vil- Down syndrome), and family members of celiac pa-
lous atrophy result from a cell-mediated immune re- tients is widespread. The therapy for a symptom-free
sponse initiated by exposure to a polypeptide fragment child with positive serology is unclear. Intestinal biopsy
of gliadin, the alcohol-soluble fraction of gluten. Ten specimens from children with positive serology are very
percent of first-degree relatives may be affected. The in- often abnormal and consistent with celiac disease. In
heritance is probably polygenic, but it might result these patients, the prudent response is to recommend a
from a single gene in combination with an environ- gluten-free diet. In patients with positive serology but
mental precipitant such as intestinal viral infection. The normal intestinal biopsies, careful follow-up without
increased incidence of celiac disease in children with diet therapy is the most appropriate current recommen-
type I diabetes mellitus, IgA deficiency, and Down syn- dation.
drome is consistent with possible immunologic factors
in the development of celiac disease. Individuals with B. LABORATORY FINDINGS
HLA-DR4 and perhaps DR3 tissue type are at higher 1. Fat content of stools—A 3-day collection of stools
risk. usually reveals excessive fecal fat excretion. A normal
child will excrete 5–10% of ingested fats. The patient
Clinical Findings with untreated celiac disease will excrete more than
15% of daily fat intake. Anorexia may be so severe that
A. SYMPTOMS AND SIGNS steatorrhea may not be present in 10–25% of patients
1. Diarrhea—Affected children present with digestive until normal intake is established.
disturbances starting at age 6–12 months—the age at 2. Impaired carbohydrate absorption—A low oral
which grains are first fed. Initially, the diarrhea may be glucose tolerance curve is seen. Absorption of D-xylose
intermittent; subsequently it is continuous, with bulky, is impaired, with blood levels lower than 20 mg/dL
pale, frothy, greasy, foul-smelling stools. During celiac 60 minutes after ingestion.
crises, dehydration, shock, and acidosis occur. In cases
in which anorexia is severe (about 10%), diarrhea may 3. Hypoproteinemia—Hypoalbuminemia can be se-
be absent. vere enough to lead to edema. There is evidence of in-
creased protein loss in the gut lumen and poor hepatic
2. Constipation, vomiting, and abdominal pain— synthesis secondary to malnutrition.
This triad of symptoms may occasionally dominate the
clinical picture and suggest a diagnosis of intestinal ob- C. IMAGING
struction. Constipation generally results from a combi- A small-bowel series shows a malabsorptive pattern
nation of anorexia, dehydration, muscle weakness, and characterized by segmentation, clumping of the barium
bulky stools. column, and hypersecretion. These changes are nonspe-
 GASTROINTESTINAL TRACT / 647

cific and can be found in patients with other malab- toms of celiac crisis (profound anorexia, malnutrition, di-
sorption states (see Table 20–5). arrhea, edema, abdominal distention, and hypokalemia).
D. BIOPSY FINDINGS
Prognosis
Intestinal biopsy is the most reliable test for celiac dis-
ease. Under the dissecting microscope, the jejunal mu- Clinical and histologic recovery is the rule but may be
cosa lacks the slender, finger-like projections that char- slow. Malignant lymphoma of the small bowel occurs
acterize normal villi. Under the light microscope, the with increased frequency in adults with long-standing
florid celiac mucosa has shortened or absent villi, disease. Dietary treatment seems to decrease the risk of
lengthened crypts of Lieberkühn, intense plasma cell this complication.
infiltration of the lamina propria, and numerous in-
traepithelial lymphocytes. Cerf-Bensussan N: Coeliac disease: An update on facts and ques-
tions based on the 10th international symposium on coeliac
E. SEROLOGIC TESTS disease. J Pediatr Gastroenterol Nutr 2003;37:412.
The false-positive rate for the IgG antigliadin antibody Fasano A et al: The prevalence of celiac disease in at risk and not at
is 10% among healthy individuals. The false-positive risk groups in the United States: A multicenter study. Arch
rate for IgA antigliadin antibodies is lower. Endomysial Int Med 2003;163:286.
or tissue transglutaminase antibody assays have greater
than 95% sensitivity and slightly less specificity for the 3. Disaccharidase Deficiency
diagnosis. Because both of these antibodies are of the
IgA class, screening for them in a patient who is IgA- Starches and the disaccharides sucrose and lactose are
deficient may yield a falsely negative result. The best quantitatively the most important dietary carbohy-
available serologic screening test, therefore, is a quanti- drates. The dietary disaccharides and oligosaccharide
tative IgA level with a transglutaminase antibody assay. products of pancreatic amylase action on starch require
hydrolysis by intestinal brush border disaccharidases be-
fore significant absorption can take place. Disacchari-
Differential Diagnosis dase levels are higher in the jejunum and in the proxi-
The differential diagnosis includes disorders that cause mal ileum than in the distal ileum and duodenum.
malabsorption. Strict adherence to two diagnostic crite- In primary disaccharidase deficiency, a single en-
ria is essential—the characteristic small-bowel micro- zyme is affected, disaccharide intolerance is likely to
scopic changes and clinical improvement on a gluten- persist, intestinal histologic findings are normal, and a
free diet. Repeated mucosal biopsies to prove histologic family history is common.
recovery on gluten-free diet and relapse on gluten chal- Because disaccharidases are located on the luminal
lenge are not critical to the diagnosis in typical patients. surface of intestinal enterocytes, they are susceptible to
mucosal damage. Many conditions cause secondary dis-
Treatment accharidase deficiency, with lactase usually most se-
verely depressed. Histologic examination reveals
A. DIET changes compatible with the underlying disorder.
Treatment consists of dietary gluten restriction for life.
All sources of wheat, rye, and barley must be eliminated Clinical Findings
during the initial treatment. Some patients may be able
to tolerate oats in the diet, but this should be tested A. PRIMARY (CONGENITAL)
only after recovery has occurred. Lactose is poorly toler- 1. Lactase deficiency—Congenital lactase deficiency
ated in the acute stage because extensive mucosal dam- is rare. The ingestion of lactose results in diarrhea, gassy
age causes secondary disaccharidase deficiency. Normal distention, and abdominal pain. The stools are frothy,
amounts of fat are advisable. Supplemental calories, vit- with a pH below 4.5, owing to the presence of organic
amins, and minerals are indicated in the acute phase. acids. Vomiting is common. Severe malnutrition may
Clinical improvement is usually evident within a week, occur. Reducing substances are present in the stools.
and histologic repair is complete after 3–12 months. The blood glucose fails to rise more than 10 mg/dL
Tissue transglutaminase titers may decrease on a after ingestion of 1 g/kg of lactose. A rise in breath hy-
gluten-free diet, but usually do not disappear. drogen after oral administration of lactose (from hydro-
gen produced by normal colon flora during fermenta-
B. CORTICOSTEROIDS tion of unabsorbed carbohydrate) is also diagnostic.
Corticosteroids can hasten clinical improvement but are Patients respond to a reduction of dietary lactose.
indicated only in very ill patients with signs and symp- Tolerance for dietary starch and sucrose is normal. Lac-
648 / CHAPTER 20

tase extracted from Aspergillus and Kluyvera species Baudon JJ et al: Sucrase-isomaltase deficiency: Changing pattern
(Lactaid) can be added to milk products or taken with over 2 decades. J Pediatr Gastroenterol Nutr 1996;22:284
[PMID: 8708882].
meals to enhance lactose hydrolysis. Although all
human racial groups are lactase-sufficient at birth, ge- Treem WR et al: Saccharosidase therapy for congenital sucrase iso-
maltase deficiency. J Pediatr Gastroenterol Nutr 1999;28:
netically determined lactase deficiency may develop 137.
after age 3 to 5 years in some groups. Certain racial
groups are more likely to develop lactase deficiency. In
Asians, genetic lactase deficiency develops in virtually 4. Glucose–Galactose Malabsorption
100% of individuals. In Africans, the incidence in most Glucose–galactose malabsorption is a rare disorder in
tribes is over 80%. In African Americans, the incidence which the sodium–glucose transport protein is defec-
is about 70%, and among European Americans, the in- tive. The gene has been localized to the long arm of
cidence is between 30 and 60%. chromosome 22. Transport of glucose in the intestinal
epithelium and renal tubular epithelium is severely im-
2. Sucrase and isomaltase deficiency—This is a paired. Diarrhea begins with the first feedings, accom-
combined defect that is inherited as an autosomal reces- panied by reducing sugar in the stool and acidosis.
sive trait. Ten percent of Alaskan natives are affected. Small-bowel histologic findings are normal. Glycosuria
The condition is rare in other groups. Abdominal dis- and aminoaciduria may occur. The glucose tolerance
tention, failure to thrive, and chronic diarrhea may be test is flat. Fructose is well tolerated. The diarrhea sub-
the presenting symptoms. Distaste for and avoidance of sides promptly on withdrawal of glucose and galactose
sucrose occurs even in young infants. from the diet. The acquired form of glucose–galactose
Because sucrose is not a reducing sugar, tests for re- malabsorption occurs mainly in infants younger than
ducing substances in the stool may be negative unless age 6 months, usually following acute viral or bacterial
the sucrose in the stool is hydrolyzed by colon bacteria. enteritis.
A sucrose tolerance test (1 g/kg) is likely to be abnor- In the congenital disease, exclusion of glucose and
mal. Breath hydrogen will be elevated after ingestion of galactose from the diet is mandatory. A satisfactory for-
sucrose. Treatment of primary sucrase–isomaltase defi- mula is one with a carbohydrate-free base plus added
ciency requires elimination of most sucrose. A prepara- fructose. The prognosis is good if the disease is diag-
tion of yeast sucrase taken with meals is also effective. nosed early, because tolerance for glucose and galactose
improves with age. In secondary monosaccharide intol-
B. SECONDARY (ACQUIRED) erance, prolonged parenteral nutrition may be required
1. Secondary lactase deficiency—The most common until intestinal transport mechanisms for monosaccha-
mechanism by which secondary lactase deficiency oc- rides return.
curs is small intestinal injury due to viral infection. This
condition is usually self-limited, lasting days or, at Wright EM: Glucose–galactose malabsorption. Am J Physiol
most, weeks after recovery from infection. Celiac dis- 1998;275:G879.
ease, giardiasis, malnutrition, abetalipoproteinemia, im-
munoglobulin deficiencies, and intestinal mucosal in- 5. Intestinal Lymphangiectasia
jury secondary to radiation and cancer chemotherapy
all can decrease intestinal lactase activity. This form of protein-losing enteropathy results from a
congenital ectasia of the bowel lymphatic system, often
2. Secondary sucrase deficiency—Intestinal mucosal associated with abnormalities of the lymphatics in the
damage tends to lower the levels of all disaccharidases. extremities. Obstruction of lymphatic drainage of the
Signs of sucrose intolerance are usually masked by the intestine leads to rupture of the intestinal lacteals with
more striking symptoms of lactose intolerance. Infec- leakage of lymph into the lumen of the bowel. Fat loss
tious diarrhea is the most common cause of secondary may be significant and lead to steatorrhea. Chronic loss
sucrose intolerance. of lymphocytes and immunoglobulins increases the sus-
ceptibility to infections.

Prognosis Clinical Findings

Primary disaccharidase deficiency is a lifelong defect. Peripheral edema, diarrhea, abdominal distention, lym-
However, in both lactase and sucrase deficiencies, toler- phedematous extremities, chylous effusions, and re-
ance for the disaccharide may increase with age. The peated infections are common. Laboratory findings are
prognosis in the secondary or acquired forms of disac- low serum albumin, decreased immunoglobulin levels,
charidase deficiency depends on the underlying illness. lymphocytopenia, and anemia. Fecal fat loss is in-
 GASTROINTESTINAL TRACT / 649

creased. Serum calcium and magnesium are frequently infancy. If the symptoms suggest an anaphylactic re-
depressed as these cations are lost in complex with un- sponse to milk or any other protein, food challenge
absorbed fatty acids. Lymphocytes may be seen in large should be performed only in a setting in which resusci-
numbers on a stool smear. Fecal α1-antitrypsin is ele- tation can be carried out.
vated. Radiographic studies reveal an edematous small- Infants who are solely breast-fed can also develop
bowel mucosal pattern, and biopsy reveals dilated blood-streaked stools and a sigmoidoscopic picture sim-
lacteals in the villi and lamina propria. If only the lym- ilar to that of formula-fed infants with milk protein
phatics of the deeper layers of bowel or intestinal sensitivity. Tiny amounts of intact allergen passed in
mesenterics are involved, laparotomy may be necessary breast milk may be the cause, but other environmental
to establish the diagnosis. allergens may play a role. Elimination of whole milk
from the mother’s diet sometimes resolves bloody diar-
Differential Diagnosis rhea. A switch to a protein hydrolysate formula almost
always results in improvement. Because the blood loss
Other causes of protein-losing enteropathy must be and diarrhea in these breast-fed infants are rarely severe,
considered, although an associated lymphedematous it is not essential that breast feeding be stopped. If
extremity strongly favors this diagnosis. symptoms are severe or prolonged, however, a trial of
semielemental formula is recommended. The colitic
Treatment & Prognosis pattern of milk protein sensitivity and colitis in breast-
fed infants usually clears spontaneously by age
A very high protein diet (up to 6–7 g/kg/d may be 6–12 months.
needed) enriched with medium-chain triglycerides as a Early reports that patients with milk protein allergy
fat source may allow for adequate nutrition and growth have a 30% incidence of sensitivity to soy protein, with
in patients with intestinal mucosal lymphangiectasia. similar symptoms, have not been uniformly confirmed.
Vitamin and calcium supplements should be given. An-
tibiotics are used for specific infections. Total par- 7. Immunologic Deficiency States
enteral nutrition is helpful on a temporary basis.
Surgery is needed when the lesion is localized to a small with Diarrhea or Malabsorption
area of the bowel or in cases of constrictive pericarditis Diarrhea is common in immune deficiency states, but
or obstructing tumors. Intravenous albumin and im- the cause is often obscure. Between 50% and 60% of
mune globulin may also be used to control symptoms. patients with idiopathic acquired hypogammaglobu-
The prognosis is not favorable, although remission may linemia have steatorrhea and intestinal villous atrophy.
occur with age. Malignant degeneration of the abnor- Lymphonodular hyperplasia is a common feature in
mal lymphatics may occur, and intestinal lymphoma of this group of patients. Patients with congenital or Bru-
the B-cell type may be a long-term complication of in- ton-type agammaglobulinemia usually have diarrhea
testinal lymphangiectasia. and abnormal intestinal morphology. Patients with iso-
lated IgA deficiency may also present with chronic diar-
6. Cow’s Milk Protein Intolerance rhea, a celiac-like picture, lymphoid nodular hyperpla-
sia, and giardiasis. Patients with isolated cellular
Milk protein intolerance is more common in males immunity defects, combined cellular and humoral im-
than females and in young infants with a family history mune incompetence, and HIV infection may have se-
of atopy. The estimated prevalence is 0.5–1%. Colic, vere chronic diarrhea leading to malnutrition. The
vomiting, and diarrhea are the major symptoms. Stools cause of diarrhea may be common bacterial, viral, fun-
often contain blood and mucus. Sigmoidoscopic exami- gal, or parasitic pathogens, organisms usually consid-
nation reveals a superficial colitis, often with edema, a ered nonpathogenic (Blastocystis hominis, Candida); or
mild eosinophilic infiltrate, and lymphonodular hyper- unusual organisms (cytomegalovirus, Cryptosporidium,
plasia. Pneumatosis intestinalis may be present on radi- Isospora belli, Mycobacterium species, microsporidia,
ograph. Viral gastroenteritis sometimes precedes the and algal organisms such as cyanobacteria). Often the
onset of symptoms. Less commonly, milk protein may cause is not found. The incidence of disaccharidase de-
induce eosinophilic gastroenteritis with protein-losing ficiency is high. Chronic granulomatous disease may be
enteropathy, hypoalbuminemia, and hypogammaglob- associated with intestinal symptoms suggestive of
ulinemia. A celiac-like syndrome with villous atrophy, chronic inflammatory bowel disease. A rectal biopsy
malabsorption, hypoalbuminemia, occult blood in the may reveal the presence of typical macrophages.
stool, and anemia can occur in older children. IgE-me- Treatment must be directed toward correction of
diated anaphylactic shock is a rare but potentially life- the immunologic defect. Specific treatments are avail-
threatening manifestation of milk protein sensitivity in able or are being developed for many of the unusual
650 / CHAPTER 20

pathogens causing diarrhea in the immunocompro- Clinical Findings

mised host. Thus a vigorous diagnostic search for spe-
cific pathogens is warranted in these individuals. Normal infants younger than age 3 months often
grunt, strain, and turn red in the face while passing
normal stools. This pattern may be viewed erroneously
8. Pancreatic Insufficiency as constipation. Failure to appreciate this normal devel-
opmental pattern may lead to the unwise use of laxa-
The most common cause of pancreatic exocrine insuffi- tives or enemas. Infants and children may gradually de-
ciency in childhood is cystic fibrosis. Decreased secre- velop the ability to ignore the sensation of rectal
tion of pancreatic digestive enzymes is caused by ob- fullness and retain stool. Many factors promote and re-
struction of the exocrine ducts by thick secretions, inforce this behavior, which results in impaction of the
which destroys the pancreatic acinar cells. This destruc- rectum and overflow incontinence or encopresis:
tion of acinar cells may occur antenatally. Some geno- painful defecation; skeletal muscle weakness; psycho-
types of cystic fibrosis have partially or completely pre- logical issues, especially those relating to control and
served pancreatic exocrine function. Other conditions authority; modesty and distaste for school bathrooms;
associated with exocrine pancreatic insufficiency are medications; and others listed in Table 20–7. The di-
discussed in Chapter 21. lated rectum becomes less sensitive to dilation, thus
perpetuating the problem, regardless of the original
cause. As many as 1–2% of healthy primary school chil-
9. Other Genetic Disorders dren have retentive constipation. The ratio of males to
Causing Malabsorption females is 4:1 in some studies.
A. A-β-LIPOPROTEINEMIA
A-β-lipoproteinemia is an autosomal recessive condi- Differential Diagnosis
tion in which the secretion of triglyceride-rich lipopro-
teins from the small intestine (chylomicrons) and liver Features distinguishing retentive constipation from
(very low density lipoproteins) is abnormal. Profound Hirschsprung disease are summarized in Table 20–8.
steatosis of the intestinal enterocytes (and hepatocytes)
and severe fat malabsorption occur. Deficiencies of fat- Treatment of Retentive Constipation
soluble vitamins occur over time, with neurologic com-
plications of vitamin E deficiency and atypical retinitis Increased intake of fluids and high-residue foods such
pigmentosa. The serum cholesterol level is very low, as bran, whole wheat, fruits, and vegetables may be suf-
and the red cell membrane lipids are abnormal, causing ficient therapy in mild constipation. It should be noted
acanthosis of the red blood cells, which sometimes is that the most likely response to increased fluid intake in
the key to diagnosing this rare condition. normally hydrated children is increased urination with
little effect on defecation. The use of a barley malt ex-
B. ACRODERMATITIS ENTEROPATHICA tract (Maltsupex), 1–2 tsp added to feedings two or
three times daily, is helpful in small infants. Polyethyl-
Acrodermatitis enteropathica is an autosomal recessive ene glycol solution is also a safe softener. Stool softeners
condition in which the intestine has a selective inability such as dioctyl sodium sulfosuccinate, 5–10 mg/kg/d,
to absorb zinc. The condition usually becomes clini- prevent excessive drying of the stool but are less effec-
cally obvious at the time of weaning and is character- tive in children with voluntary stool retention. Cathar-
ized by rash on the extremities, rashes around the body tics such as standardized extract of senna fruit (eg,
orifices, eczema, profound failure to thrive, steatorrhea, Senokot syrup), 1–2 tsp twice daily depending on age,
diarrhea, and immune deficiency. Zinc supplementa- can be used for short periods.
tion by mouth results in rapid improvement. If encopresis is present, treatment should start with
relieving fecal impaction. An effective stool softener
should be given as a maintenance medication in doses
CONSTIPATION sufficient to induce two or three loose bowel move-
Constipation is passage of bulky or hard stool at infre- ments per day. Such medications include mineral oil
quent intervals. Retention of feces in the rectum results (2–3 mL/kg/d), a nonabsorbable osmotic agent such as
in encopresis (involuntary fecal leakage) in 60% of af- polyethylene glycol (Miralax, 1 gm/kg/d), and milk of
fected children. Organic causes of constipation are magnesia (1–2 mL/kg/d). After several weeks to months
listed in Table 20–7. Most constipation in childhood is of regular loose stools, the stool softener can be tapered
not organic but a result of voluntary or involuntary re- and stopped. Mineral oil should not be given to non-
tentive behavior. ambulatory infants, physically handicapped or bed-
 GASTROINTESTINAL TRACT / 651

Table 20–7. Causes of constipation.

Functional or retentive causes Abnormalities of myenteric ganglion cells

Dietary causes Hirschsprung disease
Undernutrition, dehydration Waardenburg syndrome
Excessive milk intake Multiple endocrine neoplasia IIa
Lack of bulk Hypo- and hyperganglionosis
Cathartic abuse von Recklinghausen disease
Drugs Multiple endocrine neoplasia IIb
Narcotics Intestinal neuronal dysplasia
Antihistamines Chronic intestinal pseudo-obstruction
Some antidepressants Spinal cord defects
Vincristine Metabolic and endocrine disorders
Structural defects of gastrointestinal tract Hypothyroidism
Anus and rectum Hyperparathyroidism
Fissure, hemorrhoids, abscess Renal tubular acidosis
Anterior ectopic anus Diabetes insipidus (dehydration)
Anal and rectal stenosis Vitamin D intoxication (hypercalcemia)
Presacral teratoma Idiopathic hypercalcemia
Small bowel and colon Skeletal muscle weakness or incoordination
Tumor, stricture Cerebral palsy
Chronic volvulus Muscular dystrophy/myotonia
Intussusception
Smooth muscle diseases
Scleroderma and dermatomyositis
Systemic lupus erythematosus
Chronic intestinal pseudo-obstruction
Modified and reproduced, with permission, from Silverman A, Roy CC: Pediatric Clinical Gastroen-
terology, 3rd ed. Mosby, 1983.

Table 20–8. Differentiation of retentive

constipation and Hirschsprung disease. bound children, or those with GE reflux. Aspiration of
mineral oil may cause lipid pneumonia. Stool softeners
Retentive Hirschsprung help extinguish the tendency to retention and the estab-
Constipation Disease lishment of a regular bowel habit by making defecation
quick, easy, and painless. Recurrence of encopresis
Onset 2–3 years At birth should be treated promptly with a short course of stim-
Abdominal Rare Present ulant laxatives or an enema. A multiple vitamin is rec-
distention ommended while mineral oil is administered. Psychi-
Nutrition and Normal Poor atric consultation may be indicated for patients with
growth resistant symptoms or severe emotional disturbances.
Soiling and reten- Intermittent Rare
tive behavior or constant GASTROINTESTINAL BLEEDING
Rectal examination Ampulla full Ampulla may be empty Vomiting blood and passing blood per rectum are
alarming symptoms. The history is the key to identify-
Rectal biopsy Ganglion cells Ganglion cells absent ing the bleeding source. The following questions
present should be answered:
Rectal manometry Normal Nonrelaxation of inter-
rectoanal nal anal sphincter after 1. Is it really blood, and is it coming from the GI
reflex rectal distention tract? A number of substances simulate hema-
tochezia or melena (Table 20–9). The presence of
Barium enema Distended Narrow distal segment blood should be confirmed chemically. Geni-
rectum with proximal mega- tourinary problems, coughing, tonsillitis, lost
colon
teeth, or epistaxis may cause what appears to be
652 / CHAPTER 20

Table 20–9. Pitfalls in the diagnosis of 10 mm Hg when the patient sits up is also a sensi-
gastrointestinal bleeding in children. tive index of significant volume depletion.
4. Is the child still bleeding? Serial determinations of
Exogenous blood vital signs and hematocrit are essential to assess
Maternal blooda ongoing bleeding. Detection of blood in the gas-
Epistaxis tric aspirate confirms a bleeding site proximal to
Uncooked meat the ligament of Treitz. However, its absence does
Pseudoblood not rule out the duodenum as the source. Testing
Medications in red syrup the stool for occult blood will help in monitoring
Red Kool-Aid, fruit punch, red gelatin ongoing loss of blood.
Tomato skin
Tomato juice
Cranberry juice Treatment
Beets If a hemorrhagic diathesis is detected, vitamin K should
Peach skin be given intravenously. In severe bleeding, the need for
Red diaper syndromeb volume replacement is monitored by measurement of
Red cherries central venous pressure. In less severe cases, vital signs,
Black stools
serial hematocrits, and gastric aspirates are sufficient.
Iron preparationsc,d
Pepto-Bismol
If blood is recovered from the gastric aspirate, gastric
Grape juice lavage with saline should be performed until only a
Purple grapes blood-tinged return is obtained. Upper intestinal en-
Spinach doscopy is then done to identify the bleeding site. En-
Chocolate doscopy is superior to barium contrast study for lesions
a
such as esophageal varices, stress ulcers, and gastritis.
From cracked nipples in a breast-fed baby. Colonoscopy may identify the source of bright red rec-
b
Red pigmentation of soiled diapers due to Serratia marcescens in
stool.
tal bleeding but should be performed as an emergency
c
Ferrous sulfate and ferrous gluconate with guaiac and orthotoli- only if the extent of bleeding warrants immediate inves-
dine-based tests.
d
High false-positive rate with orthotolidine-based tests.
Modified and reproduced, with permission, from Treem WR: Gas- Table 20–10. Identification of sites
trointestinal bleeding in children. Gastrointest Endosc Clin North
Am 1994;4:75. of gastrointestinal bleeding.

Location of
Symptom or Sign Bleeding Lesion
GI bleeding. An adolescent female may be experi- Effortless bright red Nasopharyngeal or oral
encing menarche. blood from the mouth lesions; tonsillitis; esophageal
varices; lacerations of
2. How much blood is there and what is its color
esophageal or gastric mucosa
and character? Table 20–10 lists the sites of GI (Mallory–Weiss syndrome)
bleeding predicted by the appearance of the blood
in the stools. Table 20–11 lists causes of rectal Vomiting of bright red Lesion proximal to ligament of
bleeding. blood or of “coffee Treitz
3. Is the child acutely or chronically ill? The physical grounds”
examination should be thorough. Physical signs of Melanotic stool Lesion proximal to ligament of
portal hypertension, intestinal obstruction, or co- Treitz, upper small bowel. Blood
agulopathy are particularly important. The nasal loss in excess of 50–100 mL/24 h
passages should be inspected for signs of recent Bright red or dark red Lesion in the ileum or colon.
epistaxis, the vagina for menstrual blood, and the blood in stools (Massive upper gastrointestinal
anus for fissures and hemorrhoids. bleeding may also be associ-
A systolic blood pressure below 100 mm Hg ated with bright red blood in
and a pulse rate above 100 beats/min in an older stool.)
child suggest at least a 20% reduction of blood
volume. A pulse rate increase of 20 beats/min or a Streak of blood on outside Lesion in the rectal ampulla or
of a stool anal canal
drop in systolic blood pressure greater than
 GASTROINTESTINAL TRACT / 653

Table 20–11. Differential diagnosis of gastrointestinal bleeding in children by symptoms

and age at presentation.

Infant Child (2–12 years) Adolescent (> 12 years)

Hematemesis Swallowed maternal blood Epistaxis Esophageal ulcer
Peptic esophagitis Peptic esophagitis Peptic esophagitis
Mallory–Weiss tear Caustic ingestion Mallory–Weiss tear
Gastritis Mallory–Weiss tear Esophageal varices
Gastric ulcer Esophageal varices Gastric ulcer
Duodenal ulcer Gastritis Gastritis
Gastric, duodenal ulcer Gastric ulcer Duodenal ulcer
Duodenal ulcer Hereditary hemorrhagic telangiectasia
Hereditary hemorrhagic telangiectasia Hemobilia
Hemobilia Henoch–Schönlein purpura
Henoch–Schönlein purpura
Painless melena Duodenal ulcer Duodenal ulcer Duodenal ulcer
Duodenal duplication Duodenal duplication Leiomyoma (sarcoma)
Ileal duplication Ileal duplication
Meckel diverticulum Meckel diverticulum
Gastric heterotopiaa Gastric heterotopiaa
Melena with pain, Necrotizing enterocolitis Duodenal ulcer Duodenal ulcer
obstruction, Intussusceptionb Hemobiliac Hemobiliac
peritonitis, Volvulus Intussusceptionb Crohn disease (ileal ulcer)
perforation Volvulus
Ileal ulcer (isolated)
Hematochezia Infectious colitis Infectious colitis Infectious colitis
with diarrhea, Pseudomembranous colitis Pseudomembranous colitis Pseudomembranous colitis
crampy ab- Eosinophilic colitis Granulomatous (Crohn) colitis Granulomatous (Crohn) colitis
dominal pain Hirschsprung enterocolitis Hemolytic–uremic syndrome Hemolytic–uremic syndrome
Henoch–Schönlein purpura Henoch–Schönlein purpura
Lymphonodular hyperplasia
Hematochezia Anal fissure Anal fissure Anal fissure
without diarrhea Eosinophilic colitis Solitary rectal ulcer Hemorrhoid
or abdominal Rectal gastric mucosa Juvenile polyp Solitary rectal ulcer
pain heterotopia Lymphonodular hyperplasia Colonic arteriovenous malformation
Colonic hemangiomas
a
Ectopic gastric tissue in jejunum or ileum without Meckel diverticulum.
b
Classically, “currant jelly” stool.
c
Hemobilia often accompanied by vomiting, right upper quadrant pain.
Reproduced, with permission, from Treem WR: Gastrointestinal bleeding in children. Gastrointest Endosc Clin North Am 1994;4:75.

tigation and if plain abdominal radiographs show no intravenous octreotide, 25–30 µ g/m2/h (preferable be-
signs of intestinal obstruction. Colonoscopy on an un- cause of fewer adverse effects). Sustained infusion of oc-
prepped colon is often inadequate for making a diagno- treotide may be used for up to 48 hours if needed.
sis. Bleeding from esophageal varices may be stopped by
Small- or large-bowel lesions that bleed briskly temporary compression with a Sengstaken–Blakemore
(> 0.5 mL/min) may be localized by angiography or ra- tube. Sclerotherapy or banding of bleeding varices is the
dionuclide scanning following injection of labeled red treatment of choice.
cells. If gastric decompression, acid suppressive therapy,
Persistent vascular bleeding (varices, vascular anom- and transfusion are ineffective in stopping ulcer bleed-
alies) may be relieved temporarily using intravenous va- ing, laser therapy, local injection of epinephrine, elec-
sopressin, 20 units/1.73 m2 over a 20-minute period, or trocautery, or emergency surgery may be necessary.
654 / CHAPTER 20

Fox VL: Gastrointestinal bleeding in infants and children. Gas- 20–3. Pinworms, mesenteric lymphadenitis, and
trointest Clin North Am 2000;29:37. chronic appendicitis are improbable causes of recurrent
abdominal pain. Lactose intolerance usually causes ab-
RECURRENT ABDOMINAL PAIN dominal distention, gas, and diarrhea with milk inges-
tion. At times, however, abdominal discomfort may be
About 10% of healthy school children between ages the only symptom. Abdominal migraine and abdomi-
5 and 15 years will at some time experience recurrent nal epilepsy are rare conditions with an episodic charac-
episodes of abdominal pain severe enough to interfere ter often associated with vomiting. The incidence of
with normal activities. An organic cause can be found peptic gastritis, esophagitis, duodenitis, and ulcer dis-
in fewer than 10% of patients. ease is probably underappreciated. Upper intestinal en-
doscopy may be useful.
Clinical Findings
A. SYMPTOMS AND SIGNS Treatment & Prognosis
Attacks of abdominal pain are characteristically of variable Treatment consists of reassurance based on a thorough
duration and intensity. It is not rare for the child or par- physical appraisal and a sympathetic, age-appropriate
ent to report that the pain is constant, all day every day. explanation of the nature of functional pain. The con-
Although the pain is usually located in the periumbilical cept of “visceral hyperalgesia” or increased pain signal-
area, location far from the umbilicus does not rule out re- ing from physiologic stimuli such as gas, acid secretion,
current abdominal pain. Pain may occur both day and or stool is one that parents can understand and helps
night. Weight loss is rare. Pain may be associated with them to respond appropriately to the child’s com-
dramatic reactions—frantic crying, clutching the ab- plaints. Reassurance without education is rarely helpful.
domen, doubling over. Parents may be alarmed, and chil- Regular activity should be resumed, especially school
dren are often taken to emergency departments, where attendance. Therapy for emotional problems is some-
the evaluation is negative for an abdominal crisis. School times required, but drugs should be avoided. In older
attendance may suffer, and enjoyable family events may patients, and in those with what appears to be visceral
be disrupted. The pain may be associated with pallor, hyperalgesia, amitriptyline in low doses may occasion-
nausea, vomiting, and slight temperature elevation. ally be helpful. Antispasmodic medications are rarely
The pain usually bears little relationship to bowel helpful and should be reserved for patients with more
habits and physical activity. However, some patients have typical irritable bowel complaints.
a constellation of symptoms strongly suggesting irritable
bowel syndrome—bloating, postprandial pain, lower ab- Hyams JS, Hyman PE: Recurrent abdominal pain and the biopsy-
dominal discomfort, and erratic stool habits with a sensa- chosocial model of medical practice. J Pediatr 1998;133:472.
tion of obstipation or incomplete evacuation of stool. A Hyams JS et al: Abdominal pain and irritable bowel syndrome in
adolescents: A community based study. J Pediatr 1996;
precipitating or stressful situation in the child’s life at the 129:220.
time the pains began can sometimes be elicited. School Van Ginkel R et al: Alterations in rectal sensitivity and motility in
phobia may be a precipitant. A history of functional GI childhood irritable bowel syndrome. Gastroenterology 2001;
complaints is often found in family members. 120:31.
A thorough physical examination is essential and
usually normal. Complaints of abdominal tenderness
elicited during palpation sometimes seem out of pro-
INFLAMMATORY BOWEL DISEASE
portion to visible signs of distress. Crohn disease and ulcerative colitis are the two major
idiopathic inflammatory bowel diseases of children.
B. LABORATORY FINDINGS They share many features resulting from bowel inflam-
Complete blood count, sedimentation rate, urinalysis, mation, such as diarrhea, pain, fever, and blood loss,
and stool test for occult blood usually suffice. In the but they differ in important aspects, such as distribu-
adolescent female patient, ultrasound of the abdomen tion of disease, histologic findings, incidence and type
may be helpful to detect gallbladder or ovarian pathol- of extraintestinal symptoms, response to medications
ogy. If the pain is atypical, further testing suggested by and surgery, and prognosis. A comparison of these two
symptoms and family history should be done. conditions is shown in Table 20–12. The cause is un-
known but is probably a result of inappropriate activa-
tion of the mucosal immune system fueled by the pres-
Differential Diagnosis ence of normal luminal flora. The aberrant response
Abdominal pain secondary to disorders of the urinary appears to be facilitated by defects in the barrier func-
tract and extra-abdominal sources are listed in Table tion of the intestinal epithelium as well. The single
 GASTROINTESTINAL TRACT / 655

Table 20–12. Features of Crohn’s disease and ulcerative colitis.

Crohn’s Disease Ulcerative Colitis

Age at onset 10–20 years 10–20 years
Incidence 4–6 per 100,000 3–15 per 100,000
Area of bowel affected Oropharynx, esophagus, and stomach, rare; Total colon, 90%; proctitis, 10%
small bowel only, 25–30%; colon and anus
only, 25%; ileocolitis, 40%; diffuse disease, 5%
Distribution Segmental; disease-free skip areas common Continuous; distal to proximal
Pathology Full-thickness, acute, and chronic inflammation; Superficial, acute inflammation of mucosa
noncaseating granulomas (50%), extraintestinal with microscopic crypt abscess
fistulas, abscesses, stricture, and fibrosis may
be present
Radiographic findings Segmental lesions; thickened, circular folds, Superficial colitis; loss of haustra; shortened
cobblestone appearance of bowel wall second- colon and pseudopolyps (islands of normal
ary to longitudinal ulcers and transverse fis- tissue surrounded by denuded mucosa) are
sures; fixation and separation of loops; late findings
narrowed lumen; “string sign”; fistulas
Intestinal symptoms Abdominal pain, diarrhea (usually loose with Abdominal pain, bloody diarrhea, urgency,
blood if colon involved), perianal disease, and tenesmus
enteroenteric or enterocutaneous fistula,
abscess, anorexia
Extraintestinal symptoms
Arthritis/arthralgia 15% 9%
Fever 40–50% 40–50%
Stomatitis 9% 2%
Weight loss 90% (mean 5.7 kg) 68% (mean 4.1 kg)
Delayed growth and sexual 30% 5–10%
development
Uveitis, conjunctivitis 15% (in Crohn colitis) 4%
Sclerosing cholangitis — 4%
Renal stones 6% (oxalate) 6% (urate)
Pyoderma gangrenosum 1–3% 5%
Erythema nodosum 8–15% 4%
Laboratory findings High erythrocyte sedimentation rate; microcytic High erythrocyte sedimentation rate; micro-
anemia; low serum iron and total iron-binding cytic anemia, high white blood cell count
capacity; increased fecal protein loss; low with left shift; antineutrophil cytoplasmic an-
serum albumin; antineutrophil cytoplasmic tibodies present in 80%
antibodies present in 10–20%; Saccharomyces
cerevisiae antibodies positive in 60%.
Reproduced, with permission, from Kirschner BS: Inflammatory bowel disease in children. Pediatr Clin North Am 1988;35:189.
656 / CHAPTER 20

greatest risk factor for inflammatory bowel disease is a disease. These patients may have superficial Crohn coli-
positive family history (found in 15–30% of inflamma- tis or may have ulcerative colitis with relative rectal
tory bowel disease patients). Monozygotic twins have a sparing. The same group of medications are used for its
37% concordance for Crohn disease and a 10% con- treatment.
cordance for ulcerative colitis. Recent genetic studies
have identified an inflammatory bowel disease suscepti- Differential Diagnosis
bility gene on chromosome 16 (CARD15), the product
of which is involved in the activation of the nuclear fac- A. CROHN DISEASE
tor NFκB and also in the responsiveness to bacterial When extraintestinal symptoms predominate, Crohn
lipopolysaccharides. More genetic loci are being identi- disease can be mistaken for rheumatoid arthritis, sys-
fied, giving some hope that basic immune mechanisms temic lupus erythematosus, or hypopituitarism. Fre-
of Crohn disease and perhaps ulcerative colitis will be quently, the acute onset of ileocolitis is mistaken for
soon discovered. There is no indication that emotional acute appendicitis. Symptoms sometimes suggest celiac
factors are a primary cause of these diseases. disease, peptic ulcer, intestinal obstruction, intestinal
lymphoma, anorexia nervosa, or growth failure from
Diagnostic Testing endocrine causes.
A. CROHN DISEASE B. ULCERATIVE COLITIS
Because Crohn disease can occur at any location in the In the acute stage, bacterial pathogens and toxins caus-
GI tract from the mouth to the anus, a complete evalu- ing colitis must be ruled out. These include Shigella,
ation is required. Upper and lower endoscopy allows Salmonella, Yersinia, Campylobacter, Entamoeba his-
investigation of mouth, esophagus, duodenum, colon, tolytica, enteroinvasive Escherichia coli (E coli 0157),
and terminal ileum. Biopsy specimens from all these Aeromonas hydrophila, and Clostridium difficile. Mild
areas may reveal the typical histologic findings. Barium ulcerative colitis sometimes mimics irritable bowel
radiograph of the small intestine is still the best way to symptoms. Crohn disease of the colon is an important
look for small-bowel disease, but capsule video en- differential possibility.
doscopy may soon be a more uniformly available means
to study the small intestine. Computed tomographic Complications (See Table 20–12.)
scan and magnetic resonance imaging of the small
bowel can show mucosal and mural edema but are not A. CROHN DISEASE
specific enough to confirm a diagnosis. Serum antibod- Intestinal obstruction, fistula, and abscess formation are
ies to Saccharomyces cerevisiae are present in 40–60% of common. Perforation and hemorrhage are rare. Malnu-
patients with Crohn disease. This may be helpful for trition is caused by anorexia and compounded by mal-
screening if positive, but it is not sensitive or specific absorption, protein-losing enteropathy, disaccharidase
enough to be diagnostic. Fecal calprotectin is a neu- deficiency, and diarrhea induced by bile salts. Systemic
trophil-associated protein, which, when elevated in complications include perianal disease, pyoderma gan-
stool, suggests the presence of an inflammatory process. grenosum, arthritis, amyloidosis, and growth retarda-
It may be more useful for monitoring therapy in estab- tion. The risk of colon cancer is increased in patients
lished Crohn disease than for diagnosis. with Crohn colitis, although not to the extent seen in
ulcerative colitis.
B. ULCERATIVE COLITIS
Colonoscopy with mucosal biopsy is the best diagnostic B. ULCERATIVE COLITIS
test for ulcerative colitis. Nearly pathognomonic signs Arthritis, uveitis, pyoderma gangrenosum, and malnu-
may be seen on barium enema, but the test is being re- trition all occur. Growth failure and delayed puberty
placed in most instances by colonoscopy. The perinu- are less common than in Crohn disease. Liver disease
clear neutrophil cytoplasmic antigen is positive in (chronic active hepatitis, sclerosing cholangitis) is more
60–70% of patients with ulcerative colitis. Fecal calpro- common. In patients with pancolitis, carcinoma of the
tectin is high in patients with active disease. colon occurs with an incidence of 1–2% per year after
the first 10 years of disease. Cancer risk is a function of
C. INDETERMINATE COLITIS disease duration and not age at onset. The mortality
This poorly defined entity is a diagnostic challenge and rate from colon cancer is high because the usual signs
is generally a diagnosis of exclusion in patients in whom (occult blood in stool, pain, and abnormal radiologic
colonoscopic biopsy specimens do not seem typical of findings) are not specific and may be ignored in a pa-
ulcerative colitis or Crohn disease. More experience is tient with colitis. Routine cancer screening via
needed to determine whether this is indeed a separate colonoscopy, with multiple biopsies and evaluation of
 GASTROINTESTINAL TRACT / 657

specimens by histology for metaplasia and by flow cy- tis. Salicylate polymers for both oral and rectal use (ol-
tometry for aneuploidy, is recommended in pediatric salazine, mesalamine) are available. A variety of pH-
patients after 10 years of pancolitis. Dysplasia that per- sensitive tablet coatings and microencapsulation allow
sists in absence of inflammation is an indication for release of these products at specific locations in the GI
colectomy, as is aneuploidy in multiple biopsies. tract, thereby improving their efficacy. They are no
more effective than sulfasalazine but can be tolerated by
Treatment sulfonamide-sensitive patients and have fewer side ef-
fects.
A. MEDICAL TREATMENT
3. Corticosteroids—With more severe inflammatory
Medical treatment for Crohn disease and ulcerative col-
bowel disease, corticosteroids are used. Methylpred-
itis is similar and includes anti-inflammatory, antidiar-
nisolone, 2 mg/kg/d, or hydrocortisone, 10 mg/kg/d,
rheal, and antibiotic medication. No medical therapy
may be given intravenously when disease is severe.
has proved uniformly effective.
Prednisone, 1–2 mg/kg/d orally in two or three divided
1. Diet—A high-protein, high-carbohydrate diet with doses, is given for 6–8 weeks, followed by a gradual ta-
normal amounts of fat is recommended. Decreased pering. Alternate-day steroids are associated with fewer
amounts of fiber may help decrease symptoms in those side effects as the dosage of drug is tapered. There is no
with colitis or with partial intestinal obstruction. Lac- evidence that corticosteroids prevent relapses. Pred-
tose is poorly tolerated when disease is active. The main nisone is often given in conjunction with sulfasalazine.
concern should be ensuring adequate caloric intake. Re- The patient’s varicella immunity should be confirmed
strictive or bland diets are counterproductive because by history or antibody screen and the parents counseled
they usually result in poor intake. Vitamin and iron appropriately as to risk and therapy after varicella expo-
supplements are recommended. Zinc levels are often sure. Serum titers against E histolytica and stool exami-
low in patients with Crohn disease and should be sup- nation for amebic parasites must be checked before
plemented. Supplemental calories in the form of liquid starting therapy with corticosteroids, because amebic
diets are well tolerated. Total parenteral nutrition for colitis may become generalized with steroid therapy.
periods of 4–6 weeks may induce remission of symp- Hydrocortisone in the form of enema or foam can be
toms and stimulate linear growth and sexual develop- instilled into the rectum in patients with tenesmus or
ment. Enteral administration of low-residue or elemen- ulcerative proctitis. Budesonide, which has “one pass
tal liquid diets is widely used outside of the United metabolism” in the liver, is available in both oral and
States to induce remission in patients with Crohn dis- rectal preparations. These preparations are most useful
ease. It is less effective in ulcerative colitis. Home pro- for treatment of rectal disease (enemas and supposito-
grams of both enteral and parenteral nutritional sup- ries) and right-sided colon disease (oral) and in appro-
port have been especially effective in patients with priate doses have fewer corticoid side effects.
intractable symptoms or growth failure.
4. Azathioprine—Azathioprine (Imuran), 1–2 mg/kg/d
2. Nonabsorbable salicylate derivatives—Sul- orally, or 6-mercaptopurine can be used when a high
fasalazine is effective in mild cases of ulcerative colitis maintenance dose of corticosteroids is necessary to keep
and perhaps in cases of Crohn disease of the colon. It the inflammatory bowel disease under control (espe-
prevents relapse of ulcerative colitis once remission is cially in Crohn disease). The optimal dose of 6-mercap-
induced. The drug is not absorbed in the small intes- topurine depends on the patient’s ability to metabolize
tine. It is hydrolyzed by colon flora into sulfapyridine the compound. Positive results of this therapy may be
and 5-aminosalicylate. The sulfonamide moiety is delayed weeks to months. Side effects include pancre-
probably inactive but is responsible for the allergic side atitis, hepatotoxicity, and bone marrow suppression.
effects of the drug. The salicylate moiety probably has Metabolites of azathioprine should be monitored to
local anti-inflammatory activity in the colon. Side ef- avoid over- and underdosing in patients with variable
fects are common, including skin rash, nausea, metabolizing capacity. Genetic testing is available to
headache, and abdominal pain. More rarely, serum identify individuals with diminished ability to metabo-
sickness, hemolytic anemia, aplastic anemia, and pan- lize azathioprine.
creatitis occur. Response to therapy may be slow. Sul-
fasalazine inhibits folic acid absorption, and supple- 5. Metronidazole—This drug is used in treating
mental folic acid is required. Crohn disease in patients with perianal disease. Disease
The recommended dosage is 2–3 g/d in three divided tends to recur when the drug is discontinued. It may
doses for children over age 10 years or 50 mg/kg/d for also be effective in treating Crohn disease of the colon.
younger children. Half of this dosage is used as a main- The dosage of metronidazole is 15–30 mg/kg/d in three
tenance medication for well-controlled ulcerative coli- divided doses. Peripheral neuropathy may be a side ef-
658 / CHAPTER 20

fect with prolonged use. Ciprofloxacin may have simi- likely within 2 years. The rate of recurrence may be less
lar therapeutic effects. in disease limited to the colon. Surgery performed to
6. Cyclosporine—This powerful immunosuppressant correct growth retardation must be performed before
is effective in severe, steroid-resistant ulcerative colitis, puberty.
but because of side effects and rapid relapse after dis- 2. Ulcerative colitis—Surgery is curative and is rec-
continuation, it is usually used to buy time in severely ommended for those with uncontrolled hemorrhage,
affected patients for whom surgical treatment is toxic megacolon, unrelenting pain and diarrhea, growth
planned but who are too ill to tolerate surgery immedi- failure, high-grade mucosal dysplasia, or malignant tu-
ately. mors. There are now several surgical approaches
7. Methotrexate—There has been recent encouraging (ileoanal anastomosis, Koch-type continent ileostomy)
experience with both oral and subcutaneous methotrex- that allow a near-normal lifestyle after colectomy. Liver
ate in treating Crohn disease. Liver toxicity is a risk disease associated with ulcerative colitis (sclerosing
with prolonged use. cholangitis) is not improved by colectomy.
8. Anticytokines—Tumor necrosis factor alpha
(TNF-α) is a proinflammatory cytokine produced in Prognosis
monocytes, macrophages, and activated T cells, which A. CROHN DISEASE
among other functions stimulates the production of
proinflammatory cytokines such as interleukins IL-1, Although the mortality rate is low (2% in the first
IL-6, IL-8, and granulocyte–macrophage colony-stimu- 7 years), morbidity is high. The disease is progressive in
lating factor. TNF-α levels are increased in intestinal most cases. Over 50% of patients experience symptoms
mucosa of Crohn disease patients. Administration of a that affect the quality of life. About 20% have severe
chimeric human–mouse antibody to TNF-α (inflix- disabling disease, and 20% have so few symptoms that
imab) has been effective in the treatment of Crohn dis- they describe themselves as healthy.
ease, especially in patients with resistant perianal dis- B. ULCERATIVE COLITIS
ease. Relapse is common within 3 months of first
treatment, and most patients require repeated intra- The prognosis is good. About 5% of patients present
venous infusions of the medication at intervals ranging with toxic megacolon—massive colonic dilation sec-
from 4 to 12 weeks in order to remain in remission. ondary to full-thickness enterocolitis accompanied by
Anaphylactic reactions to this medication have been re- shock and fever—and require immediate colectomy.
ported, and infusions should be carried out in a setting Seventy-five percent have a relapsing and remitting
where emergency resuscitation is available. Humanizing course. Between 25% and 40% require colectomy—es-
the antibody and the concomitant use of azathioprine pecially those with pancolitis, anemia, and hypoalbu-
seem to decrease the incidence of severe allergic reac- minemia at the time of presentation.
tions. Treatment with the anti-inflammatory cytokine
IL-10 is in the developmental stage for patients with Baldassano R et al: Infliximab (Remicade) therapy in treatment of
pediatric Crohn’s disease. Am J Gastroenterol 2003;98:833.
Crohn disease. Anticytokine therapy is less effective in
ulcerative colitis. Bariol C et al: Early studies on the safety and effectiveness of
thalidomide for symptomatic inflammatory bowel disease.
9. Thalidomide—Thalidomide has been used in pa- J Gastroenterol Hepatol 2002;217:135 .
tients with inflammatory bowel disease, especially those Bonen DK, Cho J: The genetics of inflammatory bowel disease.
with oral and vaginal ulcers secondary to Crohn disease. Gastroenterology 2003;124:521.
The mechanism of its therapeutic action may be via its Markowitz J et al: A multi center trial of 6 MP and prednisone in
prevention of TNF secretion or its antiangiogenic activ- children with newly diagnosed Crohn’s disease. Gastroen-
ity. This medication must be used under strict supervi- terology 2000;119:895.
sion in postpubescent female patients because of the Ogata H, Hibi T: Cytokine and anticytokine therapies for inflam-
risk of teratogenesis. matory bowel disease. Cur Phar Des 2003;9:1108.
Tamboli CP et al: Fecal calprotectin in Crohn’s disease. Gastroen-
B. SURGICAL TREATMENT terology 2003;124:1972.
1. Crohn disease—Crohn disease is not cured by
surgery. However, 70% of patients eventually require REFERENCES
surgery to relieve obstruction, drain abscess, relieve in-
tractable symptoms, or encourage growth and sexual Websites
maturation. Newer treatment may decrease this figure. [email protected]
The relapse rate 6 years after surgery is 60%. Recur- The website for the North American Society for Pediatric Gas-
rence usually occurs at the site of anastomosis, most troenterology, Hepatology and Nutrition has an excellent se-
 GASTROINTESTINAL TRACT / 659

lection of educational materials on many pediatric gastroen- Suchy FJ (ed): Liver Disease in Children, 2nd ed. Mosby, 2000.
terologic conditions with parent information and recommen- Walker WA et al (eds): Pediatric Gastrointestinal Disease, 4th ed.
dations for evaluation and therapy. BC Decker, 2003.
Wyllie R, Hyams JS (eds): Pediatric Gastrointestinal Disease. WB
General References Saunders, 1993.

Silverman A, Roy CC: Pediatric Clinical Gastroenterology, 4th ed.

Mosby, 1995.
 Liver & Pancreas 21
Ronald J. Sokol, MD, & Michael R. Narkewicz, MD

bilirubin in duodenal aspirates also confirms patency.

LIVER Patency can also be determined by cholangiography
carried out intraoperatively, percutaneously by trans-
hepatic cholecystography, or endoscopic retrograde
PROLONGED NEONATAL cholangiopancreatography (ERCP) using a pediatric-
CHOLESTATIC JAUNDICE size side-viewing endoscope.

The main clinical features of disorders causing pro-

longed neonatal cholestasis are (1) elevated serum con- 1. Perinatal or Neonatal Hepatitis
jugated bilirubin fraction (> 2 mg/dL or > 20% of total Resulting from Infection
bilirubin), (2) elevated serum bile acids (> 10 µmol/L), This diagnosis is considered in infants with jaundice,
(3) variably acholic stools, (4) dark urine, and (5) hepa- hepatomegaly, vomiting, lethargy, fever, and petechiae.
tomegaly. It is important to identify perinatally acquired viral,
Prolonged neonatal cholestasis (conditions with de- bacterial, or protozoal infections (Table 21–3). Infec-
creased bile flow) has intrahepatic and extrahepatic tion may occur transplacentally, by ascent through the
causes. Specific clinical clues (Table 21–1) distinguish cervix into amniotic fluid, from swallowed contami-
these two major categories of jaundice in 85% of cases. nated fluids (maternal blood, urine) during delivery,
Histologic examination of tissue obtained by percuta- from blood transfusions administered in the early
neous liver biopsy increases the accuracy of differentia- neonatal period, or from breast milk or environmental
tion to 95% (Table 21–2). sources. Infectious agents associated with neonatal in-
trahepatic cholestasis include herpes simplex virus
INTRAHEPATIC CHOLESTASIS (HSV), varicella virus, enteroviruses (coxsackievirus and
echovirus), cytomegalovirus (CMV), rubella virus, ade-
novirus, parvovirus, human herpesvirus (HHV) type 6,
ESSENTIALS OF DIAGNOSIS hepatitis B virus (HBV), human immunodeficiency
& TYPICAL FEATURES virus (HIV), Treponema pallidum, and Toxoplasma
gondii. Although hepatitis C may be transmitted verti-
• Elevated total and conjugated bilirubin. cally, it rarely causes neonatal cholestasis. The degree of
liver cell injury caused by these agents is variable, rang-
• Hepatomegaly and dark urine. ing from massive hepatic necrosis (herpes simplex, en-
• Patency of extrahepatic biliary tree. teroviruses) to focal necrosis and mild inflammation
(CMV, HBV). Serum bilirubin, bile acids, alanine
aminotransferase (ALT), aspartate aminotransferase
(AST), and alkaline phosphatase are elevated. The in-
fant is jaundiced and generally appears ill.
General Considerations
Intrahepatic cholestasis is characterized by hepatocyte Clinical Findings
dysfunction and patency of the extrahepatic biliary sys-
tem. A specific cause can be identified in about 25% of A. SYMPTOMS AND SIGNS
cases. Patency of the extrahepatic biliary tract is sug- Clinical symptoms usually appear in the first 2 weeks of
gested by pigmented stools and lack of bile duct pro- life but may appear as late as age 2–3 months. Jaundice
liferation on liver biopsy. It can be confirmed least may be noted in the first 24 hours or may develop later.
invasively by hepatobiliary scintigraphy using tech- Loss of appetite, poor sucking reflex, lethargy, and
netium-99m (99mTc)-diethyliminodiacetic acid (di- vomiting are frequent. Stools may be normal to pale in
ethyl-IDA [DIDA]). Radioactivity in the bowel within color but are seldom acholic. Dark urine stains the dia-
4–24 hours is evidence of bile duct patency. Finding per. Hepatomegaly is present, and the liver has a uni-
660
Copyright © 2005, 2001, by The McGraw-Hill Companies, Inc. Click here for terms of use.
 LIVER & PANCREAS / 661

Table 21–1. Characteristic clinical features of nance imaging scans can identify intracranial calcifica-
intrahepatic and extrahepatic neonatal tions (especially CMV and toxoplasmosis). Hepatobil-
cholestasis. iary scintigraphy shows decreased hepatic clearance of
the circulating isotope with excretion into the gut.
Careful ophthalmologic examination may be useful for
Intrahepatic Extrahepatic
diagnosis of HSV, CMV, toxoplasmosis, and rubella.
Preterm infant, small for gesta- Full-term infant, seems A percutaneous liver biopsy is useful in distinguish-
tional age, appears ill; hepato- well; hepatomegaly (firm ing intrahepatic from extrahepatic cholestasis, but may
splenomegaly, other organ or to hard); complete not identify a specific infectious agent (see Table 21–2).
system involvement; incom- cholestasis (acholic However, typical inclusions of CMV in hepatocytes or
plete cholestasis (stools with stools); polysplenia syn- bile duct epithelial cells, the presence of intranuclear
some color); associated cause drome, equal right and acidophilic inclusions of herpes simplex, or positive im-
identified (infections, meta- left hepatic lobes munohistochemical stains for several viruses can be di-
bolic, familial, etc) agnostic. Variable degrees of lobular disarray character-
ized by focal necrosis, multinucleated giant-cell
transformation, and ballooned pale hepatocytes with
loss of cord-like arrangement of liver cells are usual. In-
form firm consistency. Splenomegaly is variably pre-
trahepatocytic and canalicular cholestasis may be
sent. Macular, papular, vesicular, or petechial rashes
prominent. Portal changes are not striking, but modest
may occur. In less severe cases, failure to thrive may be
neoductular proliferation and mild fibrosis may occur.
the major complaint. Unusual presentations include
Viral cultures or polymerase chain reaction (PCR) test-
liver failure, hypoproteinemia, anasarca (nonhemolytic
ing of biopsy material may be helpful.
hydrops), and hemorrhagic disease of the newborn.
B. DIAGNOSTIC STUDIES Differential Diagnosis
Neutropenia, thrombocytopenia, and signs of mild he- Great care must be taken to distinguish infectious
molysis are common. Mixed hyperbilirubinemia, ele- causes of intrahepatic cholestasis from genetic or meta-
vated aminotransferases with near-normal alkaline bolic disorders because the clinical presentations are
phosphatase, prolongation of clotting studies, mild aci- similar. Galactosemia, congenital fructose intolerance,
dosis, and elevated cord serum IgM suggest congenital and tyrosinemia must be investigated promptly, be-
infection. Nasopharyngeal washings and urine, stool, cause specific dietary therapy is available. α1-Anti-
and cerebrospinal fluid (CSF) should be cultured for trypsin deficiency, cystic fibrosis, and neonatal iron
virus. Specific IgM antibody and nucleic acid tests may storage disease must also be considered. Specific physi-
be useful, as are long-bone radiographs to determine cal features may be helpful when considering Alagille or
the presence of “celery stalking” in the metaphyseal re- Zellweger syndrome. Idiopathic neonatal hepatitis may
gions of the humeri, femurs, and tibias. When indi- be indistinguishable from infectious causes.
cated, computed tomography (CT) and magnetic reso- Patients with intrahepatic cholestasis frequently ap-
pear ill, whereas infants with extrahepatic cholestasis do
not appear ill, have stools that are usually completely
Table 21–2. Characteristic histologic features of acholic, and have an enlarged, firm liver. Histologic
intrahepatic and extrahepatic neonatal findings are shown in Table 21–2.
cholestasis.
Treatment
Intrahepatic Extrahepatic
Most forms of viral neonatal hepatitis are treated symp-
Giant cells +++ + tomatically. However, infections with HSV, varicella,
Lobules Disarray Normal CMV, parvovirus, adenovirus, and toxoplasmosis have
specific treatments. Fluids and adequate calories are en-
Portal reaction Inflammation/ Fibrosis couraged. Intravenous dextrose is needed if feedings are
minimal fibrosis not well tolerated. The consequences of cholestasis are
Neoductular Rare Marked treated as indicated (Table 21–4). Vitamin K orally or
proliferation by injection and vitamins D and E orally should be
provided. Choleretics (cholestyramine or ursodeoxy-
Other Steatosis, extrame- Portal bile duct plug-
cholic acid [UDCA]) are used if cholestasis persists.
dullary hematopoiesis ging, bile lakes
Corticosteroids are contraindicated. Penicillin for sus-
662 / CHAPTER 21

Table 21–3. Infectious causes of neonatal hepatitis.

Infectious Agent Diagnostic Tests Specimens Treatment

Cytomegalovirus Culture and PCR, liver histology, Urine, blood, liver ?Ganciclovir (Foscarnet)b
IgM/aIgG
Herpes simplex PCR and culture, liver histology, Liver, blood, eye, throat, Acyclovir
Ag (skin) rectal, CSF, skin
Rubella Culture, IgM/aIgG Liver, blood, urine Supportive
Varicella Culture, PCR, Ag (skin) Skin, blood, CSF, liver Acyclovir (Foscarnet)b
Parvovirus Serum IgM/aIgG, PCR Blood Supportive, ? IVIG
Enteroviruses Culture and PCR Blood, urine, CSF, throat, Pleconaril (investigative)
rectal, liver
Adenovirus Culture and PCR Nasal/throat, rectal, blood, Cidofovir, ?IVIG
liver, urine
Hepatitis B virus (HBV) HBsAg, HBcAg IgM Serum Supportive for acute infection
Hepatitis C virus (HCV) HCV PCR, HCV-IgG Serum Supportive for acute infection
Treponema pallidum Serology; dark-field exam Serum, CSF Penicillin
a
Toxoplasma gondii IgM/ IgG, PCR, culture Serum, liver Pyrimethamine and sulfadiazine
with folinic acid
Mycobacterium tuberculosis PPD, chest radiograph, liver Serum, liver, gastric aspirate INH, pyrazinamide, rifampin and
tissue histologic stains and streptomycin
culture, gastric aspirate stain
and culture
a
IgG = positive indicates maternal infection and transfer of antibody transplacentally; negative indicates unlikelihood of infection in
mother and infant.
IVIG = intravenous gamma globulin, PCR = polymerase chain reactin test for viral DNA or RNA, Ag = viral antigen testing, INH = isoniazid,
CSF = cerebrospinal fluid, HBsAg = hepatitis B surface antigen, HBC = hepatitis B core antigen, PPD = purified protein derivative.
b
Use for resistant viruses.

pected syphilis or antibiotics for bacterial hepatitis need Specific Infectious Agents
to be administered promptly.
A. NEONATAL HEPATITIS B VIRUS DISEASE
Infection with HBV may occur at any time during peri-
natal life, but the risk is higher when acute maternal
Prognosis disease occurs during the last trimester of pregnancy.
Multiple organ involvement is commonly associated However, most cases of neonatal disease are acquired
with neonatal infectious hepatitis and has a poor out- from mothers who are asymptomatic carriers of hepati-
come. Death from hepatic or cardiac failure, intractable tis B. Although HBV has been found in most body flu-
acidosis, or intracranial hemorrhage may occur, espe- ids, including breast milk, neonatal transmission occurs
cially in herpesvirus or enterovirus infection and occa- occasionally transplacentally and primarily from expo-
sionally in CMV or rubella infection. HBV may rarely sure to maternal blood at delivery. In chronic hepatitis
cause fulminant neonatal viral hepatitis; most infected B surface antigen (HBsAg) carrier mothers, fetal and in-
infants become asymptomatic carriers of hepatitis B. fant acquisition risk is greatest if the mother (1) is also
Persistent liver disease results in mild chronic hepatitis, hepatitis B envelope antigen (HBeAg)-positive and
portal fibrosis, or cirrhosis. Chronic cholestasis, al- hepatitis B envelope antibody (HBeAb)-negative,
though rare following infections, may lead to dental (2) has detectable levels of serum-specific hepatitis B
enamel hypoplasia, failure to thrive, biliary rickets, se- DNA polymerase, or (3) has high serum levels of hepa-
vere pruritus, and xanthoma. titis B core antibody (HBcAb). These findings are
 LIVER & PANCREAS / 663

Table 21–4. Treatment of complications of chronic cholestatic liver disease.

Indication Treatment Dose Toxicity

Intrahepatic Phenobarbital 3–10 mg/kg/d Drowsiness, irritability, interference
cholestasis with vitamin D metabolism
Cholestyramine/colestipol hydro- 250–500 mg/kg/d Constipation, acidosis, binding of
chloride drugs, increased steatorrhea
Ursodeoxycholic acid 15–20 mg/kg/d Transient increase in pruritus
Pruritus Phenobarbital or cholestyramine/ Same as above
colestipol (or both)
Antihistamines: Drowsiness
diphenhydramine hydrochloride 5–10 mg/kg/d
hydroxyzine 2–5 mg/kg/d
Ultraviolet light B Exposure as needed Skin burn
Carbamazepine 20–40 mg/kg/d Hepatotoxicity, marrow
suppression, fluid retention
Rifampin 10 mg/kg/d Hepatotoxicity, marrow suppres-
sion
Ursodeoxycholic acid 15–20 mg/kg/d Transient increase in pruritus
Steatorrhea Formula containing medium-chain 120–150 calories/kg/d for infants Expensive
triglycerides (eg, Pregestimil)
Oil supplement containing 1–2 mL/kg/d Diarrhea, aspiration
medium-chain triglycerides
Malabsorption Vitamin A 10,000–25,000 units/d Hepatitis, pseudotumor cerebri,
of fat-soluble bone lesions
vitamins
Vitamin D 800–5000 units/d Hypercalcemia, hypercalciuria
25-Hydroxycholecalciferol 3–5 µg/kg/d Hypercalcemia, hypercalciuria
(vitamin D)
1,25-Dihydroxycholecalciferol 0.05–0.2 µg/kg/d Hypercalcemia, hypercalciuria
(vitamin D)
Vitamin E (oral) 25–200 IU/kg/d Potentiation of vitamin K deficiency
Vitamin E (oral, TPGSa) 15–25 IU/kg/d Potentiation of vitamin K deficiency
Vitamin E (intramuscular) 1–2 mg/kg/d Muscle calcifications
Vitamin K (oral) 2.5 mg twice per week to
5 mg/d
Vitamin K (intramuscular) 2–5 mg each 4 wk
Malabsorption of Multiple vitamin 1–2 times the standard dose
other nutrients
Calcium 25–100 mg/kg/d Hypercalcemia, hypercalciuria
Phosphorus 25–50 mg/kg/d Gastrointestinal intolerance
Zinc 1 mg/kg/d Interference with copper and iron
absorption
a
D-
-Tocopheryl polyethylene glycol-1000 succinate.
664 / CHAPTER 21

markers for circulating infectious virus; however, hepa- C. NEONATAL JAUNDICE WITH URINARY TRACT
titis B can be transmitted even if HBsAg is the only INFECTION
marker present. Jaundice in affected infants—usually males—typically
Neonatal liver disease resulting from HBV is ex- appears between the second and fourth weeks of life.
tremely variable. The infant has a 70–90% chance of This disorder causes lethargy, fever, poor appetite,
acquiring HBV at birth from an HBsAg-positive jaundice, and hepatomegaly. Except for mixed hyper-
mother if nothing is done to prevent infection. Most bilirubinemia, other liver function tests (LFTs) are
infected infants become prolonged asymptomatic carri- mildly abnormal. Leukocytosis is present, and infection
ers of HBV. Fulminant hepatic necrosis has rarely been is confirmed by culture. The mechanism for the liver
reported. In such cases, progressive jaundice, stupor, impairment is the toxic action of bacterial products (en-
shrinking liver size, and coagulation abnormalities dotoxins) and inflammatory cytokines.
dominate the clinical picture. Respiratory, circulatory, Treatment of the infection leads to prompt resolu-
and renal failure usually follow. Histologically, the liver tion of the cholestasis without hepatic sequelae. Meta-
shows massive hepatocyte necrosis, collapse of the retic- bolic liver diseases, such as galactosemia and tyrosine-
ulum framework, minimal inflammation, and occa- mia, may present with gram-negative bacterial urinary
sional pseudoacinar structures. Survival is rare but is as- tract infection and must be considered.
sociated with reasonable repair of liver architecture.
In less severe cases, focal hepatocyte necrosis occurs Broderick AL, Jonas MM: Hepatitis B in children. Semin Liver Dis
with a mild portal inflammatory response. Cholestasis 2003;23(1):59 [PMID: 12616451].
is intracellular and canalicular. Chronic active hepatitis Kane MA: Hepatitis viruses and the neonate. Clin Perinatol 1997;
may be present for many years, with serologic evidence 24:181 [PMID: 9099509].
of persisting antigenemia (HBsAg) and mildly elevated Kesson AM: Management of neonatal herpes simplex virus infec-
serum aminotransferases. Chronic active hepatitis may tion. Paediatr Drugs 2001;3:81 [PMID: 11269641].
rarely progress to cirrhosis within 1–2 years. Most in- Rosenthal P: Neonatal hepatitis and congenital infections. In Suchy
fected infants have only mild evidence, if any, of liver FJ et al (eds): Liver Disease in Children. Lippincott, Williams
injury. & Wilkins, 2001:239.
To prevent perinatal transmission, all infants of
mothers who are HBsAg-positive (regardless of HBeAg 2. Intrahepatic Cholestasis Resulting
status) should receive hepatitis B immunoglobulin from Inborn Errors of Metabolism,
(HBIG) and hepatitis B vaccine within the first
24 hours after birth and vaccine again at ages 1 and Familial & “Toxic” Causes
6 months (see Chapter 9). This prevents HBV infection These cholestatic syndromes caused by specific enzyme
in 85–95% of infants. HBIG can provide some protec- deficiencies, other genetic disorders, or certain precipi-
tion when given as late as 72 hours after birth. If not tants associated with neonatal liver disease feature intra-
given at birth it can be administered as late as 7 days hepatic cholestasis (ie, jaundice, hepatomegaly, and
postpartum as long as the infant has received vaccine. normal to completely acholic stools). Some of the spe-
cific clinical conditions have characteristic clinical signs.
B. NEONATAL BACTERIAL HEPATITIS
Most bacterial liver infections in newborns are acquired Enzyme Deficiencies
by transplacental invasion from amnionitis with as-
cending spread from maternal vaginal or cervical infec-
& Other Inherited Disorders
tion. Onset is abrupt, usually within 48–72 hours after Early specific diagnosis is important because dietary or
delivery, with signs of sepsis and often shock. Jaundice pharmacologic treatment may be available (Table
appears early and is of the mixed type. The liver en- 21–5). Reversal of liver disease and clinical symptoms is
larges rapidly, and the histologic picture is that of dif- prompt and permanent in several disorders as long as
fuse hepatitis with or without microabscess. The most the diet is maintained. As with other inborn errors of
common organisms involved are Escherichia coli, Liste- metabolism, parents of the affected infant should be of-
ria monocytogenes, and group B streptococci. Isolated fered genetic counseling. For some disorders, prenatal
neonatal liver abscess caused by E coli or Staphylococcus genetic diagnosis is available.
aureus is often associated with omphalitis or umbilical Cholestasis caused by metabolic diseases such as
vein catheterization. Bacterial hepatitis and neonatal galactosemia, fructose intolerance, and tyrosinemia may
liver abscesses require specific antibiotics in large doses be accompanied by vomiting, lethargy, poor feeding,
and, rarely, surgical or radiologic interventional and irritability. Hepatomegaly is a constant finding.
drainage. Deaths are common, but survivors show no The infants often appear septic; gram-negative bacteria
long-term consequences of liver disease. can be cultured from blood in 25–50% of cases, espe-
 LIVER & PANCREAS / 665

Table 21–5. Metabolic and genetic causes of neonatal cholestasis.

Disease Inborn Error Hepatic Pathology Diagnostic Studies

Galactosemia Galactose-1-phosphate Cholestasis, steatosis, necrosis, Galactose-1-phosphate
uridylyltransferase pseudoacini, fibrosis uridylyltransferase assay of red
blood cells
Fructose intolerance Fructose-1-phosphate Steatosis, necrosis, pseudoacini, Liver fructose-1-phosphate
aldolase fibrosis aldolase assay or leukocyte DNA
analysis
Tyrosinemia Fumarylacetoacetase Necrosis, steatosis, pseudoacini, Urinary succinylacetone,
portal fibrosis fumarylacetoacetase assay of
red blood cells
Cystic fibrosis Cystic fibrosis transmem- Cholestasis, neoductular prolifer- Sweat test and leukocyte DNA
brane conductance ation, excess bile duct mucus, analysis
regulator gene portal fibrosis
Hypopituitarism Deficient production of pi- Cholestasis, giant cells Thyroxine, TSH, cortisol levels
tuitary hormones
α1-Antitrypsin deficiency Abnormal α1-antitrypsin Giant cells, cholestasis, steato- Serum α1-antitrypsin phenotype
molecule (Pi ZZ sis, neoductular proliferation, fi-
phenotype) brosis, PAS-diastase-resistant
cytoplasmic granules
Gaucher disease β-Glucosidase Cholestasis, cytoplasmic inclu- β-Glucosidase assay in leuko-
sions in Kupffer’s cells (foam cytes
cells)
Niemann–Pick disease Lysosomal Cholestasis, cytoplasmic inclu- Sphingomyelinase assay of leu-
sphingomyelinase sions in Kupffer’s cells kocytes or liver or fibroblasts
(type C); leukocyte DNA analysis
Glycogen storage disease Branching enzyme Fibrosis, cirrhosis, PAS-diastase- Branching enzyme analysis of
type IV resistant cytoplasmic inclusions leukocytes or liver
Neonatal hemochromatosis Unknown Giant cells, portal fibrosis, Histology, iron stains
hemosiderosis, cirrhosis
Peroxisomal disorders (eg, Deficient peroxisomal en- Cholestasis, necrosis, fibrosis, cir- Plasma very long chain fatty
Zellweger’s syndrome) zymes or assembly rhosis, hemosiderosis acids, qualitative bile acids, plas-
malogen, pipecolic acid, liver
electron microscopy
Abnormalities in bile acid me- Several enzyme deficien- Cholestasis, necrosis, giant cells Urine, serum, duodenal fluid
tabolism cies defined analyzed for bile acids by fast
atom bombardment-mass
spectroscopy
Byler’s disease (familial pro- FIC-1 and BSEP genes Cholestasis, necrosis, giant cells, Histology, family history, normal
gressive intrahepatic cho- fibrosis cholesterol, low or normal
lestasis) γ-glutamyl transpeptidase, DNA
analysis
MDR3 deficiency MDR3 gene Cholestasis, bile duct proliferation, Bile phospholipid level, DNA
portal fibrosis analysis
Alagille’s syndrome (syndro- Jagged 1 gene mutations Cholestasis, paucity of interlobu- Three or more clinical features,
mic paucity of interlobular lar bile ducts, increased copper liver histology, DNA analysis
bile ducts) levels
TSH = thyroid-stimulating hormone, PAS = periodic acid-Schiff.
666 / CHAPTER 21

cially in patients with galactosemia. Neonatal screening in hemolytic disease of the newborn (Rh, ABO) and in
for galactosemia usually detects the disorder before some infants receiving TPN. The same mechanisms
cholestasis develops. Other inherited conditions associ- may cause intrinsic obstruction of the common duct.
ated with neonatal intrahepatic cholestasis are outlined An ischemia–reperfusion injury may also contribute to
in Table 21–5. Treatment of these disorders is dis- cholestasis in Rh incompatibility. In extreme hemolysis,
cussed in Chapter 32. the cholestasis may be seemingly complete, with acholic
stools. Levels of bilirubin may reach 40 mg/dL, primar-
“Toxic” Causes of Neonatal Cholestasis ily conjugated. If inspissation of bile occurs within the
extrahepatic biliary tree, differentiation from biliary
A. NEONATAL ISCHEMIC–HYPOXIC CONDITIONS atresia may be difficult. A trial of choleretics is indi-
Perinatal events that result in hypoperfusion of the gas- cated. Once stools show a return to normal color or
99m
trointestinal system are sometimes followed in Tc-DIDA scanning shows biliary excretion into the
1–2 weeks by cholestasis. This occurs in premature in- duodenum, patency of the extrahepatic biliary tree is
fants with respiratory distress, severe hypoxia, hypo- ensured. Although most cases improve slowly over
glycemia, shock, and acidosis. When these perinatal 2–6 months, persistence of complete cholestasis for
conditions develop in association with gastrointestinal more than 2 weeks requires further studies (ultrasonog-
lesions such as ruptured omphalocele, gastroschisis, or raphy, DIDA scanning, liver biopsy) with possible
necrotizing enterocolitis, a subsequent cholestatic pic- cholangiographic or magnetic resonance imaging of the
ture is common (25–50% of cases). Liver function extrahepatic biliary tree. Irrigation of the common bile
studies reveal mixed hyperbilirubinemia, elevated alka- duct is sometimes necessary to dislodge the obstructing
line phosphatase and γ-glutamyl transpeptidase (GGT) inspissated biliary material.
values, and variable elevation of the aminotransferases.
Stools are seldom persistently acholic.
Andorsky DJ et al: Nutritional and other postoperative manage-
Choleretics (cholestyramine or UDCA), introduc- ment of neonates with short bowel syndrome correlates with
tion of enteral feedings as soon as possible, and nutri- clinical outcomes. J Pediatr 2001;139:27 [PMID:
tional support are the mainstays of treatment until the 11445790].
cholestasis resolves (see Table 21–4). In some cases, this Colomb V et al: Role of lipid emulsions in cholestasis associated
resolution may take 3–6 months. As long as no severe with long-term parenteral nutrition in children. J Parenter
intestinal problem is present (eg, short gut syndrome), Ent Nutr 2000;24:345 [PMID: 11071594].
complete resolution of the hepatic abnormalities is the Heubi JE et al: Tauroursodeoxycholic acid (TUDCA) in the pre-
rule. But portal fibrosis with periportal scarring is occa- vention of total parenteral nutrition-associated liver disease.
J Pediatr 2002;141(2):237 [PMID: 12183720].
sionally found on follow-up biopsy.
Teitelbaum DH, Tracy T: Parenteral nutrition-associated cholesta-
B. PROLONGED PARENTERAL NUTRITION sis. Semin Pediatr Surg 2001;10:72 [PMID: 11329608].
Weinberger B et al: Association of lipid peroxidation with hepato-
Cholestasis may develop after 1–2 weeks in premature cellular injury in preterm infants. Crit Care 2002;6:521
newborns receiving total parenteral nutrition (TPN). [PMID: 12493074
Even full-term infants with significant intestinal disease,
resections, or dysmotility may develop TPN-related
cholestasis. Contributing factors may include toxicity of 3. Idiopathic Neonatal Hepatitis
intravenous amino acids, diminished stimulation of bile (Giant-Cell Hepatitis)
flow from prolonged absence of feedings, translocation
of intestinal bacteria and their cell wall products, miss- This type of cholestatic jaundice of unknown cause pre-
ing nutrients or antioxidants, photooxidation of amino sents with features of cholestasis and a typical liver
acids, infusion of lipid hydroperoxides, and the “physio- biopsy appearance; it accounts for 25–50% of cases of
logic cholestatic” propensity of the premature infant. neonatal intrahepatic cholestasis. The degree of
Histology of the liver may resemble that of extrahepatic cholestasis is variable, and the disorder may be indistin-
biliary obstruction. Early introduction of feedings has guishable from extrahepatic causes in 10% of cases.
reduced the frequency of this disorder. The prognosis is Viral infections, α1-antitrypsin deficiency, Alagille syn-
generally good. Occasional cases of cirrhosis, liver fail- drome, Niemann–Pick type C disease (NPC), progres-
ure, and hepatoma may develop, particularly in infants sive familial intrahepatic cholestasis (PFIC), and bile
with intestinal resections or anomalies. acid synthesis defects may present in a similar clinical
and histologic manner. However, in PFIC and bile acid
C. INSPISSATED BILE SYNDROME synthesis defects the γ-glutamyl transpeptidase levels are
This syndrome is the result of accumulation of bile in normal or low. Electron microscopy of the liver biopsy
canaliculi and in the small- and medium-size bile ducts may help distinguish NPC and PFIC.
 LIVER & PANCREAS / 667

Intrauterine growth retardation, prematurity, poor Yerushalmi B et al: Niemann–Pick disease type C in neonatal
feeding, emesis, poor growth, and partially or intermit- cholestasis at a North American Center. J Pediatr Gastroen-
terol Nutr 2002;35(1):44 [PMID: 12142809].
tently acholic stools are characteristic of intrahepatic
cholestasis. Patients with neonatal lupus erythematosus
may present with giant-cell hepatitis; however, throm-
bocytopenia, skin rash, or congenital heart block is usu-
4. Paucity of Interlobular Bile Ducts
ally also present. Forms of intrahepatic cholestasis caused by decreased
In cases of suspected idiopathic neonatal hepatitis numbers of interlobular bile ducts (< 0.5 bile ducts per
(absence of infectious, metabolic, and toxic causes), pa- portal tract) may be classified according to whether they
tency of the biliary tree should be verified to exclude ex- are associated with other malformations. The gene
trahepatic surgical disorders. DIDA scanning and ultra- (Jagged 1) for the syndromic form, Alagille syndrome
sonography may be helpful in this regard. Some (arteriohepatic dysplasia), is located on chromosome
clinicians have used the enteral string test during DIDA 20p and codes for a ligand of the notch receptor, al-
scanning to confirm bile duct patency. Liver biopsy though the pathogenesis is not understood. Alagille syn-
findings are usually diagnostic after age 6–8 weeks (see drome is sometimes recognized by identification of the
Table 21–2) but may be misleading before age 6 weeks. characteristic facies, which becomes more obvious with
Failure to detect patency of the biliary tree, nondiagnos- age. The forehead is prominent, as is the nasal bridge.
tic liver biopsy findings, or persisting complete cholesta- The eyes are set deep and sometimes widely apart (hy-
sis (acholic stools) are indications for minilaparotomy pertelorism), The chin is small and slightly pointed and
and intraoperative cholangiography performed by an ex- projects forward. The ears are prominent. The stool
perienced surgeon, ERCP, percutaneous cholecystogra- color varies with the severity of cholestasis. Pruritus be-
phy, or magnetic resonance cholangiopancreatography gins by age 3–6 months. Firm, smooth hepatomegaly
(MRCP). Occasionally, a small but patent (hypoplastic) may be present. Cardiac murmurs are present in 95% of
extrahepatic biliary tree is demonstrated and is probably patients, and butterfly vertebrae (incomplete fusion of
the result rather than the cause of diminished bile flow; the vertebral body or anterior arch) are present in 50%.
surgical reconstruction of hypoplastic biliary trees Xanthomas develop later in the disease. Occasionally,
should not be attempted. early cholestasis is mild and not recognized.
Once a patent extrahepatic tree is confirmed, ther- Direct hyperbilirubinemia may be mild to severe
apy should include choleretics, a special formula with (2–15 mg/dL). Serum alkaline phosphatase, GGT, and
medium-chain triglycerides (Pregestimil, Alimentum), cholesterol are markedly elevated, especially early in
and supplemental fat-soluble vitamins in water-miscible life. Serum bile acids are always elevated. Aminotrans-
form (see Table 21–4). This therapy is continued as ferases are mildly increased, but clotting factors and
long as significant cholestasis remains (conjugated other liver proteins are usually normal.
bilirubin > 1 mg/dL). Fat-soluble vitamin levels should The cardiovascular abnormalities include peripheral
be monitored while supplements are given and at least and valvular pulmonary stenoses (most common), atrial
once after their discontinuation. septal defect, coarctation of the aorta, and tetralogy of
Eighty percent of patients recover without signifi- Fallot. Up to 15% of patients develop intracranial hem-
cant hepatic fibrosis. However, in 20% of cases with orrhage early in childhood.
this presentation, the patient has PFIC and is likely to Eye abnormalities (posterior embryotoxon) and
progress to cirrhosis. In general, failure to resolve the renal abnormalities (dysplastic kidneys, renal tubular
cholestatic picture by age 6–12 months is associated ectasia, single kidney, hematuria) can also be present.
with progressive liver disease and evolving cirrhosis. Growth retardation with normal to increased levels of
This may occur with either normal or diminished num- growth hormone is common. Although variable, the in-
bers of interlobular bile ducts (paucity of interlobular telligence quotient is frequently low. Hypogonadism
ducts). Liver transplantation has been successful when with micropenis may be present. A weak, high-pitched
signs of hepatic decompensation are noted (rising voice may develop. Neurologic disorders resulting from
bilirubin, coagulopathy, intractable ascites). vitamin E deficiency (areflexia, ataxia, ophthalmople-
gia) eventually develop in many children.
In the nonsyndromic form, paucity of interlobular
Arora NK et al: Hepatic technetium-99m-mebrofenin iminodiac- bile ducts occurs in the absence of the extrahepatic mal-
etate scans and serum gamma-glutamyl transpeptidase levels
interpreted in series to differentiate between extrahepatic bil-
formations. Paucity of interlobular bile ducts may also
iary atresia and neonatal hepatitis. Acta Paediatr 2001;90(9): occur in α1-antitrypsin deficiency, Zellweger syndrome,
975 [PMID: 11683209]. in association with lymphedema (Aagenaes’ syndrome),
McKiernan PJ: Neonatal cholestasis. Semin Neonatol 2002;7(2): PFIC, cystic fibrosis, CMV or rubella infection, and in-
153 [PMID: 12208100]. born errors of bile acid metabolism.
668 / CHAPTER 21

High doses (250 mg/kg/d) of cholestyramine may caused by mutations in the bile salt export pump
control pruritus, lower cholesterol, and clear xan- (BSEP) gene, which codes for an adenosine triphos-
thomas. Ursodeoxycholic therapy (15–25 mg/kg/d) ap- phate (ATP)-dependent canalicular bile salt transport
pears to be more effective and less toxic than cholestyra- protein. Clinically and biochemically, patients are simi-
mine. Nutritional therapy to prevent wasting and lar to PFIC type I patients, as are their liver histology
deficiencies of fat-soluble vitamins is of particular im- and treatment options. PFIC type III is caused by mu-
portance because of the severity of cholestasis (see Table tations in the MDR3 (multiple drug resistance protein
21–4). type 3) gene, which encodes a canalicular protein that
Prognosis is more favorable in the syndromic than pumps phospholipid into bile. Serum GGT and bile
in the nonsyndromic varieties. In the former, only acid levels are elevated, bile duct proliferation and por-
30–40% of patients have severe complications of dis- tal tract fibrosis are seen in liver biopsies, and bile phos-
ease, whereas over 70% of patients with nonsyndromic pholipid levels are low. Treatment is similar to that for
varieties progress to cirrhosis. Many of this latter group other forms of PFIC. Bile acid synthesis defects are
may have PFIC. In Alagille syndrome, cholestasis may clinically similar to those in PFIC I and PFIC II, with
improve by age 2–4 years, with minimal residual he- low serum levels of GGT and cholesterol; however, the
patic fibrosis. Survival into adulthood despite raised serum level of total bile acids is low and urine bile acid
serum bile acids, aminotransferases, and alkaline phos- analysis may identify a defect.
phatase occurs in about 50% of cases. Several patients
have developed hepatocellular carcinoma. Hypogo- Jacquemin E: Progressive familial intrahepatic cholestasis: Genetic
nadism has been noted; however, fertility is not obvi- basis and treatment. Clin Liver Dis 2000;4(4):753 [PMID:
ously affected. Cardiovascular anomalies may shorten 11232355].
life expectancy. Some patients have persistent, severe Melter M et al: Progressive familial intrahepatic cholestasis: Partial
cholestasis, rendering their quality of life poor; liver biliary diversion normalizes serum lipids and improves
transplantation has been performed under these cir- growth in noncirrhotic patients. Am J Gastroenterol 2000;
cumstances. 95(12):3522 [PMID: 11151888].

Emerick KM et al: Features of Alagille syndrome in 92 patients: EXTRAHEPATIC NEONATAL

Frequency and relation to prognosis. Hepatology 1999;29: CHOLESTASIS
822 [PMID: 10051485].
Lykavieris P et al: Bleeding tendency in children with Alagille syn- Extrahepatic neonatal cholestasis is characterized by
drome. Pediatrics 2003;111(1):167 [PMID: 12509572]. complete and persistent cholestasis (acholic stools) in
McElhinney DB et al: Analysis of cardiovascular phenotype and the first 3 months of life; lack of patency of the extra-
genotype–phenotype correlation in individuals with a hepatic biliary tree proved by intraoperative, percuta-
JAG1 mutation and/or Alagille’s syndrome. Circulation neous, or endoscopic cholangiography; firm to hard
2002;106(20):2567 [PMID: 12417653]
hepatomegaly; and typical features on histologic exami-
nation of liver biopsy tissue (see Table 21–2). Causes
PROGRESSIVE FAMILIAL include biliary atresia, choledochal cyst, spontaneous
INTRAHEPATIC CHOLESTASIS perforation of the extrahepatic ducts, and intrinsic ob-
struction of the common duct.
(Byler Disease)
PFIC is a group of disorders presenting as pruritus, di-
arrhea, jaundice, and failure to thrive in the first
1. Biliary Atresia
6–12 months of life. PFIC type I (Byler disease), caused Biliary atresia is the progressive fibroinflammatory oblit-
by mutations in the FIC1 gene, is associated with low eration of the lumen of all, or part of, the extrahepatic
to normal serum levels of GGT and cholesterol and ele- biliary tree presenting within the first 3 months of life.
vated levels of bilirubin, aminotransferases, and bile In European Americans, biliary atresia occurs in
acids. Diarrhea is common. Liver biopsy results are 1:10,000–1:15,000 births, and the incidence in both
similar to those found with giant-cell hepatitis but sexes is equal. In Asian Americans, the incidence is
sometimes with a paucity of interlobular bile ducts and higher, and the disorder is twice as common in girls.
centrolobular fibrosis that progresses to cirrhosis. Elec- The abnormality found most commonly is complete
tron microscopy shows diagnostic granular “Byler bile” atresia of all extrahepatic biliary structures. There appear
in canaliculi. to be at least two types of biliary atresia: the perinatal
Treatment includes administration of UDCA, par- form (80% of cases) and the fetal–embryonic form
tial biliary diversion if the condition is unresponsive to (20% of cases). In the perinatal form, meconium and
UDCA, and liver transplantation. PFIC type II is first-passed stools are usually normal in color, suggesting
 LIVER & PANCREAS / 669

early patency of the ducts. Evidence obtained from sur- trypsin deficiency), choledochal cyst, or intrinsic bile
gically removed remnants of the extrahepatic biliary tree duct obstruction (stones, bile plugs). Although sponta-
suggests an inflammatory or sclerosing cholangiopathy. neous perforation of extrahepatic bile ducts leads to
Although an infectious cause seems reasonable, no agent jaundice and acholic stools, the infants are usually quite
has been consistently found in such cases. A role for re- ill with chemical peritonitis from biliary ascites, and
ovirus type 3 and rotavirus group C has been suggested. hepatomegaly is not found.
Certain histocompatibility locus antigen (HLA) types If the diagnosis of biliary atresia cannot be excluded
may predispose to biliary atresia. In the fetal–embryonic by the diagnostic evaluation before age 60 days, surgical
type, the bile duct presumably developed abnormally exploration is necessary. Laparotomy must include liver
and is associated with other nonhepatic congenital biopsy and an operative cholangiogram if a gallbladder
anomalies. The strongest association of biliary atresia is is present. The presence of yellow bile in the gallbladder
with the polysplenia syndrome (situs inversus, preduo- implies patency of the proximal extrahepatic duct sys-
denal portal vein, interruption of the inferior vena cava, tem. Radiographic visualization of cholangiographic
polysplenia, midline liver). contrast in the duodenum excludes obstruction to the
Jaundice may be noted in the newborn period but is distal extrahepatic ducts.
more often delayed until age 2–3 weeks. The urine In the absence of surgical correction, the following
stains the diaper; and the stools are often pale yellow, eventually develop: failure to thrive, marked pruritus,
buff-colored, gray, or acholic. Seepage of bilirubin portal hypertension, hypersplenism, bleeding diathesis,
products across the intestinal mucosa may give some rickets, ascites, and cyanosis. Bronchitis and pneumo-
yellow coloration to the stools. Hepatomegaly is com- nia are common. Eventually, hepatic failure and death
mon, and the liver may feel firm to hard; splenomegaly occur, almost always by age 18–24 months.
develops later. Pruritus, digital clubbing, xanthomas, Except for the occasional example of correctable bil-
and a rachitic rosary may be noted in older patients. By iary atresia, in which choledochojejunostomy is feasi-
age 2–6 months, the growth curves reveal poor weight ble, the standard procedure is hepatoportoenterostomy
gain. Late in the course, ascites and bleeding complica- (Kasai procedure). Occasionally, portocholecystostomy
tions occur. (gallbladder Kasai procedure) may be performed if the
No single laboratory test will consistently differenti- gallbladder is present and the passage from it to the
ate biliary atresia from other causes of complete ob- duodenum is patent. These procedures are best done in
structive jaundice. A study of hepatic 2,6-dimethylim- specialized centers where experienced surgical, pedi-
inodiacetic acid (HIDA) excretion performed early in atric, and nursing personnel are available. Surgery
the course of disease and after pretreatment with phe- should be performed as early as possible (before 60 days
nobarbital (3–5 mg/kg/d for 5–7 days) helps to distin- of life); the Kasai procedure should generally not be un-
guish intrahepatic from extrahepatic causes of cholesta- dertaken in infants older than age 4 months, because
sis, though it is not diagnostic. MRCP shows promise the likelihood of bile drainage at this age is very low.
as an imaging study to define biliary atresia. Although Orthotopic liver transplantation is now indicated for
biliary atresia is suggested by persistent elevation of patients who do not undergo the Kasai procedure, who
serum γ-glutamyl transpeptidase or alkaline phos- fail to drain bile after the Kasai procedure, or who
phatase levels, high cholesterol levels, and prolonged progress to end-stage biliary cirrhosis despite surgical
prothrombin times, these findings have also been re- treatment. The 5-year survival rate following transplan-
ported in severe neonatal hepatitis, α1-antitrypsin defi- tation is 70–85%.
ciency, and bile duct paucity. Furthermore, these tests Whether or not the Kasai procedure is performed,
will not differentiate the location of the obstruction supportive medical treatment measures consist of vita-
within the extrahepatic system. Generally, the amino- min and caloric support (vitamins A, D, K, and E and
transferases are elevated only modestly in biliary atresia. formulas containing medium-chain triglycerides
Serum proteins and blood clotting factors are not af- [Pregestimil or Alimentum]) (see Table 21–4). Bacter-
fected early in the disease. Routine chest radiograph ial infections (eg, ascending cholangitis) should be
may reveal abnormalities suggestive of polysplenia syn- treated promptly with broad-spectrum antibiotics, and
drome. Ultrasonography of the biliary system should be signs of bleeding tendency should be corrected with in-
performed to ascertain the presence of choledochal cyst tramuscular vitamin K. Ascites can be managed initially
and intra-abdominal anomalies. Liver biopsy specimens with reduced sodium intake and spironolactone.
can differentiate intrahepatic causes of cholestasis from Choleretics and bile acid-binding products (cholestyra-
biliary atresia in over 90% of cases (see Table 21–2). mine, aluminum hydroxide gel) are of little use. The
The major diagnostic dilemma is distinguishing be- value of UDCA remains to be determined.
tween this entity and neonatal hepatitis, bile duct When bile flow is sustained, the 10-year survival rate
paucity, metabolic liver disease (particularly α1-anti- is 25–35%. Death is usually caused by liver failure, sep-
670 / CHAPTER 21

sis, acidosis, or respiratory failure secondary to in- The prognosis depends on the presence or absence
tractable ascites. Esophageal variceal hemorrhage devel- of associated evidence of atresia and the appearance of
ops in 40% of patients. Surprisingly, terminal hemor- the intrahepatic ducts. If atresia is found, the prognosis
rhage is unusual. Liver transplantation has dramatically is similar to that described in the preceding section. If
changed the outlook for these patients. an isolated extrahepatic cyst is encountered, the out-
come is generally excellent, with resolution of the jaun-
Larrosa-Haro A et al: Duodenal tube test in the diagnosis of biliary
dice and return to normal liver architecture. However,
atresia. J Pediatr Gastroenterol Nutr 2001;32:311 [PMID: bouts of ascending cholangitis, particularly if intrahep-
11345182]. atic cysts are present, or obstruction of the anastomotic
Meyers RL et al: High-dose steroids, ursodeoxycholic acid, and site may occur. The risk of biliary carcinoma develop-
chronic intravenous antibiotics improve bile flow after Kasai ing within the cyst is about 5–15% at adulthood; there-
procedure in infants with biliary atresia. J Pediatr Surg fore, cystectomy or excision of cyst mucosa should be
2003;38(3):406 [PMID: 12632357]. undertaken whenever possible.
Miga D et al: Survival after first esophageal variceal hemorrhage in
patients with biliary atresia. J Pediatr 2001;139:291 [PMID:
11487759]. Bismuth H, Krissat J: Choledochal cyst malignancies. Ann Oncol
1999;10:94 [PMID: 10436795].
Nio M et al: Japanese Biliary Atresia Registry: Five- and 10-year
survival rates after surgery for biliary atresia: A report from He X et al: Congenital choledochal cyst—Report of 56 cases. Chin
the Japanese Biliary Atresia Registry. J Pediatr Surg 2003; Med Sci J 2000;15(1):52 [PMID: 12899402].
38(7):997 [PMID: 12861525]. Mackenzie TC et al: The management of prenatally diagnosed
Ohi R: Biliary atresia: A surgical perspective. Clin Liver Dis choledochal cysts. J Pediatr Surg 2001;36:1241 [PMID:
2001;4:779 [PMID: 11232357]. 11479866].
Sokol RJ et al: Pathogenesis and outcome of biliary atresia: Current
concepts. J Pediatr Gastroenterol Nutr 2003;37:4 [PMID: 3. Spontaneous Perforation
12827000].
Sokol RJ, Mack C: Etiopathogenesis of biliary atresia. Semin Liver
of the Extrahepatic Bile Ducts
Dis 2001;21:517 [PMID: 11745039]. The sudden appearance of obstructive jaundice, acholic
stools, and abdominal enlargement with ascites in a sick
newborn is suggestive of this condition. The liver is
2. Choledochal Cyst usually normal in size, and a yellow-green discoloration
Choledochal cysts cause 2–5% of cases of extrahepatic can often be discerned under the umbilicus or in the
neonatal cholestasis; the incidence is fourfold higher in scrotum. In 24% of cases, stones or sludge obstructs the
girls and higher in patients of Asian descent. In most common bile duct. DIDA scan or ERCP shows leakage
cases, the clinical manifestations, basic laboratory find- from the biliary tree, and ultrasonography confirms as-
ings, and histopathologic features on liver biopsy are in- cites or fluid around the bile duct.
distinguishable from those associated with biliary atre- Treatment is surgical. Simple drainage, without at-
sia. Neonatal symptomatic cysts are usually associated tempts at oversewing the perforation, is sufficient in
with atresia of the distal common duct—accounting for primary perforations. A diversion anastomosis is con-
the diagnostic dilemma—and may simply be part of the structed in cases associated with choledochal cyst or
spectrum of biliary atresia. However, a palpable sub- stenosis. The prognosis is generally good.
hepatic mass and a positive ultrasound scan promptly
resolve the diagnostic question. Discovery of such a Chardot C et al: Spontaneous perforation of the biliary tract in in-
mass eliminates the need for other studies. Immediate fancy: A series of 11 cases. Eur J Pediatr Surg 1996;6:341
operation is indicated once abnormalities in clotting [PMID: 9007467].
factors have been corrected and bacterial cholangitis, if Xanthakos SA et al: Spontaneous perforation of the bile duct in in-
present, has been treated with intravenous antibiotics. fancy: A rare but important cause of irritability and abdomi-
In older children, choledochal cyst presents as recurrent nal distension. J Pediatr Gastroenterol Nutr 2003;36(2):
287 [PMID: 12548069].
episodes of obstructive jaundice, pancreatitis, or right
upper quadrant abdominal pain and vomiting, or as a
right abdominal mass. OTHER NEONATAL
Excision of the cyst and choledocho–Roux-en-Y je- HYPERBILIRUBINEMIC CONDITIONS
junal anastomosis are recommended. In some cases, be-
cause of technical problems, only the mucosa of the
(Noncholestatic Nonhemolytic)
cyst can be removed with jejunal anastomosis to the This group of disorders associated with hyperbiliru-
proximal bile duct. Anastomosis of cyst to jejunum or binemia is of two types: (1) unconjugated hyperbili-
duodenum is not recommended. rubinemia, consisting of breast milk jaundice,
 LIVER & PANCREAS / 671

Lucey–Driscoll syndrome, congenital hypothyroidism, Congenital Hypothyroidism

upper intestinal obstruction, Gilbert disease,
Crigler–Najjar syndrome, and drug-induced hyper- Although the differential diagnosis of indirect hyper-
bilirubinemia; and (2) conjugated noncholestatic hy- bilirubinemia should always include congenital hy-
perbilirubinemia, consisting of Dubin–Johnson syn- pothyroidism, the diagnosis may be obvious from other
drome and Rotor syndrome. clinical and physical clues or from the newborn screen-
ing results. The jaundice clears quickly with replace-
ment thyroid hormone therapy, although the mecha-
1. Unconjugated Hyperbilirubinemia nism is unclear.
Breast Milk Jaundice
Labrune P et al: Bilirubin uridine diphosphate glucuronosyltrans-
Persistent elevation of the indirect bilirubin fraction ferase hepatic activity in jaundice associated with congenital
may occur in up to 36% of breast-fed infants. En- hypothyroidism. J Pediatr Gastroenterol Nutr 1992;14:79
hanced β-glucuronidase activity in breast milk as the [PMID: 1573516].
cause for increased absorption of unconjugated biliru-
bin is controversial. The increased enterohepatic shunt- Upper Intestinal Obstruction
ing of unconjugated bilirubin exceeds the normal con-
jugating capacity in the liver of these infants. The The association of indirect hyperbilirubinemia with
mutation for Gilbert syndrome predisposes to breast high intestinal obstruction (eg, duodenal atresia, annu-
milk jaundice and to more prolonged jaundice. lar pancreas, pyloric stenosis) in the newborn has been
Hyperbilirubinemia does not usually exceed 20 observed repeatedly; the mechanism is unknown. Di-
mg/dL, with most cases in the range of 10–15 mg/dL. minished levels of hepatic glucuronyl transferase have
In patients whose bilirubin levels are above 4–5 mg/dL, been found on liver biopsy in pyloric stenosis, and ge-
the jaundice is noticeable by the fifth to seventh day of netic studies suggest that this indirect hyperbilirubine-
breast-feeding. It may accentuate the underlying physi- mia is an early sign of Gilbert syndrome.
ologic jaundice—especially early, when total fluid in- Treatment is that of the underlying obstructive con-
take may be less than optimal. Except for jaundice, the dition (usually surgical). Jaundice disappears once ade-
physical examination is usually normal; urine does not quate nutrition is achieved.
stain the diaper, and the stools are golden yellow.
The jaundice peaks by the third week of life and Trioche P et al: Jaundice with hypertrophic pyloric stenosis is an
early manifestation of Gilbert’s syndrome. Arch Dis Child
clears before age 3 months in almost all infants, even 1999;81:301 [PMID: 10490432].
when breast-feedings are continued. All infants who re-
main jaundiced past age 2 weeks should have measure-
ments of conjugated bilirubin to exclude hepatobiliary Gilbert Syndrome
disease. Gilbert syndrome is a common form (3–7% of the
Kernicterus has never been reported in association population) of familial hyperbilirubinemia associated
with this condition. In special situations, breast-feeding with a partial reduction of hepatic bilirubin uridine
may be discontinued temporarily and replaced by for- diphosphate (UDP) glucuronyl transferase activity and
mula feedings for 2–3 days until serum bilirubin de- perhaps an abnormality in the function or amount of
creases by 2–8 mg/dL. Cow’s milk formulas inhibit the one or more hepatocyte membrane protein carriers. Ac-
intestinal reabsorption of unconjugated bilirubin. celerated jaundice of the newborn, breast milk jaun-
When breast-feeding is reinstituted, the serum bilirubin dice, and jaundice with intestinal obstruction may be
may increase slightly but not to the previous level. Pho- present in affected infants. During puberty and beyond,
totherapy is not indicated in the healthy full-term in- mild fluctuating jaundice, especially with illness, and
fant with this condition. vague constitutional symptoms are common. Shortened
red blood cell survival time in some patients is thought
Kreamer BL et al: A novel inhibitor of beta-glucuronidase: L-Aspar- to be caused by reduced activity of enzymes involved in
tic acid. Pediatr Res 2001 Oct;50(4):460 [PMID: heme biosynthesis (protoporphyrinogen oxidase).
11568288]. Subsidence of hyperbilirubinemia has been achieved
Mauro Y et al: Prolonged unconjugated hyperbilirubinemia associ- in patients by administration of phenobarbital
ated with breast milk and mutations of the bilirubin uridine
diphosphate-glucuronosyl transferase gene. Pediatrics 2000;
(5–8 mg/kg/d), although this therapy is not justified.
106:E59 [PMID: 11061796]. The disease is inherited as an autosomal recessive ab-
Monaghan G et al: Gilbert’s syndrome is a contributory factor in normality of the promoter region of UDP-glucuronyl
prolonged unconjugated hyperbilirubinemia of the newborn. transferase-1; however, another factor is necessary for
J Pediatr 1999;134:441 [PMID: 10190918]. disease expression. The homozygous (16%) and het-
672 / CHAPTER 21

erozygous states (40%) are common. Males are affected and diconjugated bilirubin in the bile follows pheno-
more often than females (4:1). Serum unconjugated barbital treatment.
bilirubin is generally less than 3–6 mg/dL, although Liver biopsy findings and LFTs are consistently nor-
rare cases may exceed 8 mg/dL. The findings on liver mal in both types.
biopsy and most other LFTs are normal except for pro-
longed indocyanine green and bromosulfophthalein Kadakol A et al: Genetic lesions of bilirubin uridine-diphosphoglu-
(BSP) retention. An increase of 1.4 mg/dL or more in curonate glucuronosyltransferase (UGT1A1) causing
the level of unconjugated bilirubin after a 2-day fast Crigler–Najjar and Gilbert syndromes: Correlation of geno-
(300 kcal/d) is consistent with the diagnosis of Gilbert type to phenotype. Hum Mutat 2000;16:297 [PMID:
11013440].
syndrome. Genetic testing is available but rarely
Schauer R et al: Treatment of Crigler–Najjar type 1 disease: Rele-
needed. No treatment is necessary. vance of early liver transplantation. J Pediatr Surg
2003;38(8):1227 [PMID: 12891498].
Bancroft JD et al: Gilbert syndrome accelerates development of Strom SC et al: Hepatocyte transplantation for the treatment of
neonatal jaundice. J Pediatr 1998;132:656 [PMID: human disease. Semin Liver Dis 1999;19:39 [PMID:
9580766]. 10349682].
Ulgenalp A et al: Analyses of polymorphism for UGT1*1 exon
1 promoter in neonates with pathologic and prolonged jaun-
dice. Biol Neonate 2003;83(4):258 [PMID: 12743455]. Drug-Induced Hyperbilirubinemia
Vajro P et al: Unusual presentation of Gilbert’s syndrome in pedi- Vitamin K3 (menadiol) may elevate indirect bilirubin
atric recipients of liver transplantation. J Pediatr Gastroen- levels by causing hemolysis. Vitamin K1 (phytona-
terol Nutr 2000;31:238 [PMID: 10997365].
dione) can be used safely in neonates. Rifampin and an-
tiretroviral protease inhibitors may cause unconjugated
Crigler–Najjar Syndrome hyperbilirubinemia. Other drugs (eg, ceftriaxone, sul-
Infants with type I Crigler–Najjar syndrome usually de- fonamides) may displace bilirubin from albumin, po-
velop rapid severe elevation of unconjugated bilirubin tentially increasing the risk of kernicterus—especially in
(> 30–40 mg/dL) with neurologic consequences (ker- the sick premature infant.
nicterus). Consanguinity is often present. Prompt
recognition of this entity and treatment with exchange 2. Conjugated Noncholestatic
transfusions are required, followed by phototherapy. Hyperbilirubinemia (Dubin–Johnson
Some patients have no neurologic signs until adoles-
cence or early adulthood, at which time deterioration
Syndrome & Rotor Syndrome)
may occur suddenly. For diagnosis of this condition it These diagnoses are suspected when persistent or recur-
is useful to obtain a duodenal bile specimen, which rent conjugated hyperbilirubinemia and jaundice occur
characteristically will be colorless and contain a pre- and liver function tests are normal. The basic defect in
dominance of unconjugated bilirubin, small amounts Dubin–Johnson syndrome affects the multiple organic
of monoconjugates, and only traces of diconjugated anion transport protein (MRP2) of the bile canaliculus,
bilirubin. Phenobarbital administration in these pa- causing impaired hepatocyte excretion of conjugated
tients does not significantly alter these findings, nor bilirubin into bile. A variable degree of impairment in
does it lower serum bilirubin levels. The glucuronyl uptake and conjugation complicates the clinical pic-
transferase deficiency is inherited in an autosomal reces- ture. Transmission is autosomal recessive, so a positive
sive pattern. A combination of phototherapy and family history is occasionally obtained. In Rotor syn-
cholestyramine may keep bilirubin levels below drome, the defect lies in hepatic uptake and storage of
25 mg/dL. The use of tin protoporphyrin or tin meso- bilirubin. Bile acids are metabolized normally, so that
porphyrin remains experimental. Liver transplantation cholestasis does not occur. Bilirubin values range from
is curative and may prevent kernicterus if performed 2 to 5 mg/dL, and other LFTs are normal.
early. An auxiliary orthotopic transplantation also re- In Rotor syndrome, the liver is normal; in
lieves the jaundice while the patient retains native liver. Dubin–Johnson syndrome, it is darkly pigmented on
Hepatocyte transplantation is experimental. gross inspection and may be enlarged. Microscopic ex-
A milder form (type II) with both autosomal domi- amination reveals numerous dark-brown pigment gran-
nant and recessive inheritance is rarely associated with ules consisting of polymers of epinephrine metabolites,
neurologic complications. Hyperbilirubinemia is less especially in the centrilobular regions. However, the
severe, and the bile is pigmented and contains bilirubin amount of pigment varies within families, and some
mono- and diglucuronide. Patients with this form re- jaundiced family members may have no demonstrable
spond to phenobarbital with lowering of serum biliru- pigmentation in the liver. Otherwise, the liver is histo-
bin levels. An increased proportion of monoconjugated logically normal. Oral cholecystography fails to visual-
 LIVER & PANCREAS / 673

ize the gallbladder in Dubin–Johnson syndrome but is • Abnormal LFTs.

normal in Rotor syndrome. Differences in the excretion • Local epidemic of the hepatitis A infection.
patterns of BSP, in results of DIDA cholescintigraphy, • Positive Anti-HAV IgM antibody.
in urinary coproporphyrin I and III levels, and in the
serum pattern of monoglucuronide and diglucuronide
conjugates of bilirubin can help distinguish between
these two conditions.
The prognosis is excellent, and no treatment is
needed. General Considerations
Hepatitis A virus (HAV) infection occurs in both epi-
Kaplan M et al: Bilirubin genetics for the nongeneticist: Hereditary demic and sporadic fashion (Table 21–6). Transmis-
defects of neonatal bilirubin conjugation. Pediatrics sion by the fecal–oral route explains epidemic outbreaks
2003;111(4 Pt 1):886 [PMID: 12671128]. from contaminated food or water supplies, including by
Regev RH et al: Treatment of severe cholestasis in neonatal food handlers. Viral particles 27 nm in diameter have
Dubin–Johnson syndrome with ursodeoxycholic acid. J Peri-
nat Med 2002;30(2):185 [PMID: 12012642].
been found in stools during the acute phase of hepatitis
A infection and are similar in appearance to the en-
teroviruses. Sporadic cases usually result from contact
HEPATITIS A with an affected individual. Transmission through
blood products obtained during the viremic phase is a
rare event, although it has occurred in a newborn nurs-
ESSENTIALS OF DIAGNOSIS ery. The overt form of the disease is easily recognized
& TYPICAL FEATURES by the clinical manifestations. However, two thirds of
children are asymptomatic, and two thirds of sympto-
matic children are anicteric. Lifelong immunity to
• Gastrointestinal upset (anorexia, vomiting, diar-
HAV follows infection. In developing countries, most
rhea). children are exposed to HAV by age 10 years, while
• Jaundice. only 20% are exposed by age 20 years in developed
• Liver tenderness and enlargement. countries.

Table 21–6. Hepatitis viruses.

HAV HBV HCV HDV HEV

Type of virus Enterovirus (RNA) Hepadnavirus (DNA) Flavivirus (RNA) Incomplete (RNA) Calicivirus (RNA)
Transmission Fecal–oral Parenteral, sexual, Parenteral, sexual, Parenteral, sexual Fecal-oral
routes vertical vertical
Incubation period (days) 15–40 50–150 30–150 20–90 14–65
Diagnostic test Anti-HAV IgM HBsAg, anti-HBc IgM Anti-HCV, Anti-HDV Anti-HEV
PCR–RNA test
Mortality rate (acute) 0.1–0.2% 0.5–2% 1–2% 2–20% 1–2% (in pregnant
women, 20%)
Carrier state No Yes Yes Yes No
Vaccine available Yes Yes No Yes (HBV) No
Treatment None Interferon-
or Interferon-
plus Treatment for HBV None
lamivudine ribavirin
Pegylated
interferon
(adults)
PCR = polymerase chain reaction; HAV = hepatitis A virus; HBsAg = hepatitis B surface antigen; HBc = hepatitis B core; HDV = hepatitis D
(delta) virus; HBV = hepatitis B virus.
674 / CHAPTER 21

Antibody to HAV appears within 1–4 weeks of clin- glycemia, and marked prolongation of prothrombin
ical symptoms. Although the great majority of children time are serious prognostic findings. Diagnosis is made
with infectious hepatitis are asymptomatic or have mild by serology. A positive anti-HAV IgM indicates acute
disease and recover completely, some will develop ful- disease, whereas IgG anti-HAV persists after recovery.
minant hepatitis. Percutaneous liver biopsy is rarely indicated but may
be performed safely in most children provided that the
partial thromboplastin time and platelet count are nor-
mal and the prothrombin time is prolonged less than
HEPATITIS VIRUS ABBREVIATIONS
4–5 seconds. The presence of ascites may increase the
risk of percutaneous liver biopsy. “Balloon cells” and
acidophilic bodies are characteristic histologic findings.
HAV Hepatitis A virus
Liver cell necrosis may be diffuse or focal, with accom-
Anti-HAV IgM IgM antibody to HAV
HBV Hepatitis B virus
panying infiltration of inflammatory cells containing
HBsAg HBV surface antigen polymorphonuclear leukocytes, lymphocytes, macro-
HBcAg HBV core antigen phages, and plasma cells, particularly in portal areas.
HBeAg HBV envelope antigen Some bile duct proliferation may be seen in the perilob-
Anti-HBs Antibody to HBsAg ular portal areas alongside areas of bile stasis. Regenera-
Anti-HBc Antibody to HBcAg tive liver cells and proliferation of reticuloendothelial
Anti-HBc IgM IgM antibody to HBcAg cells are present. Occasionally massive hepatocyte
Anti-HBe Antibody to HBeAg necrosis occurs, portending a bad prognosis.
HCV Hepatitis C virus
Anti-HCV Antibody to HCV
HDV Hepatitis D (delta) virus
Differential Diagnosis
Anti-HDV Antibody to HDV Before jaundice appears, the symptoms are those of a
HEV Hepatitis E virus nonspecific viral enteritis. Other diseases with some-
Anti-HEV Antibody to HEV what similar onset include pancreatitis, infectious
NANBNC Non-A, non-B, non-C hepatitis virus mononucleosis, leptospirosis, drug-induced hepatitis,
Wilson disease, autoimmune hepatitis, and, most often,
other hepatitis viruses. Acquired CMV disease may also
Clinical Findings mimic HAV, although lymphadenopathy is usually
present in the former.
A. HISTORY
Features of the patient’s history elicit direct exposure to a Prevention
previously jaundiced individual, consumption of seafood
or contaminated water, or recent travel to an area of en- Some attempt at isolation of the patient during initial
demic infection. Following an incubation period of phases of illness is indicated, although most patients
15–40 days, the initial nonspecific symptoms usually with hepatitis A are noninfectious by the time the dis-
precede the development of jaundice by 5–10 days. ease becomes overt. Stool, diapers, and other fecally
stained clothing should be handled with care for 1 week
B. SYMPTOMS AND SIGNS after the appearance of jaundice.
Fever, anorexia, vomiting, headache, and abdominal Passive–active immunization of exposed susceptible
pain are the usual symptoms. Darkening of the urine persons can be achieved by giving standard immune
precedes jaundice, which peaks in 1–2 weeks and then globulin, 0.02–0.04 mL/kg intramuscularly. Illness is
begins to subside. The stools may become light or clay- prevented in 80–90% of individuals if immune globu-
colored during this time. Clinical improvement can lin is given within 1–2 weeks of exposure. Individuals
occur as jaundice develops. Tender hepatomegaly and traveling to endemic disease areas should receive HAV
jaundice are typically present; splenomegaly is variable. vaccine or 0.02–0.06 mL/kg of immune globulin as
prophylaxis if there is insufficient time (< 2 weeks) for
C. LABORATORY FINDINGS the initial dose of vaccine. All children older than age
Aminotransferases and conjugated and unconjugated 2 years with chronic liver diseases should receive two
bilirubin levels are elevated. The leukocyte count is doses of HAV vaccine 6 months apart. It is currently
normal to low; the sedimentation rate is elevated. recommended that universal childhood immunization
Serum proteins are generally normal, but an elevation for HAV be implemented in states in the United States
of the γ-globulin fraction (> 2.5 g/dL) can occur and with 20 or more cases per 100,000 population per year,
indicates a worse prognosis. Hypoalbuminemia, hypo- and in local areas with a high prevalence.
 LIVER & PANCREAS / 675

Treatment (see Table 21–5). The disease is caused by a DNA virus

that is usually acquired perinatally from a carrier
There are no specific measures. Sedatives and cortico- mother, or later in life from blood products, shared
steroids should be avoided. At the start of the illness, a needles, needle sticks, skin piercing, or tattoos; or
light diet is preferable. During the icteric phase, lower- through sexual transmission. Transmission via blood
fat foods may diminish gastrointestinal symptoms but products has been almost eliminated by anti-HBc anti-
do not affect overall outcome. Drugs and elective body donor-screening protocols. The complete HBV
surgery should be avoided. particle is composed of a core (28-nm particle) that is
found in the nucleus of infected liver cells and a double
Prognosis outer shell (surface antigen). The surface antigen in
Ninety-nine percent of children recover without seque- blood is termed HBsAg. The antibody to it is anti-HBs.
lae. In rare cases of fulminant hepatitis, the patient may The core antigen is termed HBcAg and its antibody is
die in 5 days or may survive as long as 1–2 months anti-HBc. A specific anti-HBc IgM antibody occurs
without liver transplantation. The prognosis is poor if during primary viral replication.
the signs and symptoms of hepatic coma develop, with Another important antigen–antibody system associ-
deepening of jaundice and development of ascites; or- ated with HBV disease is the “e” (envelope) antigen sys-
thotopic liver transplantation is indicated under these tem. HBeAg, a truncated soluble form of HBcAg, ap-
circumstances. Incomplete resolution leads to pro- pears in the serum of infected patients early and
longed hepatitis or chronic cholestatic hepatitis but not correlates with active virus replication. Persistence of
to cirrhosis. Rare cases of aplastic anemia following HBeAg is a marker of infectivity, whereas the appear-
acute infectious hepatitis have been reported. A benign ance of anti-HBe generally implies termination of viral
relapse of symptoms may occur in 10–15% of cases replication. However, HBV mutant viruses (precore
after 6–10 weeks of apparent resolution. mutant) may replicate with negative HBeAg tests for
and positive tests for anti-HBe antibody. Other sero-
Advisory Committee on Immunization Practices: Prevention of logic markers indicating viral replication include the
hepatitis A through active or passive immunization: Recom- presence of DNA polymerase and circulating HBV
mendation of the Advisory Committee on Immunization DNA.
Practices (ACIP). MMWR 1999;48:1 [PMID: 10543657].
Jacobs R et al: The cost-effectiveness of adolescent hepatitis A vac-
cination in states with the high disease rates. Arch Pediatr Clinical Findings
Adolesc Med 2000;154:763 [PMID: 10922291].
A. SYMPTOMS AND SIGNS
Demicheli V, Tiberti D: The effectiveness and safety of hepatitis A
vaccine: A systematic review. Vaccine 2003;21(19–20): The symptoms are nonspecific, consisting only of slight
2242 [PMID: 12744850]. fever (which may be absent) and mild gastrointestinal
upset. Visible jaundice is usually the first significant
HEPATITIS B finding. It is accompanied by darkening of the urine
and pale or clay-colored stools. Hepatomegaly is pre-
sent. Occasionally a symptom complex (caused by anti-
ESSENTIALS OF DIAGNOSIS gen–antibody complexes) of macular rash, urticarial le-
& TYPICAL FEATURES sions, and arthritis antedates the appearance of icterus.
Occasionally, HBV infection presents as a glomeru-
• Gastrointestinal upset, anorexia, vomiting, diar- lonephritis or nephrotic syndrome. When acquired ver-
rhea.
tically at birth, chronic disease is frequently completely
asymptomatic despite ongoing liver injury.
• Jaundice, tender hepatomegaly, abnormal LFTs.
• Serologic evidence of hepatitis B disease: HBsAg, B. LABORATORY FINDINGS
HBeAg, anti-HBc IgM. To diagnose acute HBV infection, the HBsAg and anti-
• History of parenteral, sexual, or household expo- HBc IgM are the only tests needed. To document re-
sure or maternal HBsAg carriage. covery, immunity, or response to the HBV vaccine, the
anti-HBs is useful. If HBsAg persists after 8 weeks in
acute infections, it may signify a chronic infection, al-
though chronic infection is defined as lasting 6 months
or more. Vertical transmission to newborns is docu-
General Considerations mented by positive HBsAg.
In contrast to hepatitis A, hepatitis B virus (HBV) in- LFT results are similar to those discussed earlier for
fection has a longer incubation period of 21–135 days hepatitis A. Liver histology is similar for HAV and
676 / CHAPTER 21

HBV disease, although specific stains may detect units/m2 body surface area injected subcutaneously three
HBcAg or HBsAg in the liver. times a week for 4–6 months) inhibits viral replication in
Renal involvement may be suspected on the basis of 30–40% of patients, normalizes the ALT level, and leads
urinary findings suggesting glomerulonephritis or to the disappearance of HBeAg and the appearance of
nephrotic syndrome. anti-HBe. Side effects are common. Younger children
may respond better than older children. Orally adminis-
Differential Diagnosis tered lamivudine therapy (3 mg/kg/day up to 100 mg
per day for 12 months) leads to a successful response in
The differentiation between HAV and HBV disease is 25% of treated children, with minimal side effects. How-
made easier by a history of parenteral exposure, an ever, resistant organisms can emerge. Asymptomatic
HBsAg-positive parent, or an unusually long period of HBsAg carriers (normal serum ALT, no hepatomegaly)
incubation. HBV and hepatitis C virus (HCV) infec- do not respond to either therapy. Liver transplantation is
tion or EBV infection are differentiated serologically. successful in acute fulminant hepatitis B; however, rein-
The history may suggest a drug-induced hepatitis, espe- fection is common following liver transplantation for
cially if a serum sickness prodrome is reported. Autoim- chronic hepatitis B. Chronic HBIG therapy or lamivu-
mune hepatitis, Wilson disease, hemochromatosis, non- dine therapy reduces recurrence after transplantation.
alcoholic steatohepatitis, and α1-antitrypsin deficiency
should also be considered.
Non-A non-B non-C (NANBNC) hepatitis is diag-
Prognosis
nosed when test results for the serologic markers of HAV, The prognosis is good, although fulminant hepatitis or
HBV, HCV and EBV are negative; drug-induced hepati- chronic hepatitis and cirrhosis may supervene in up to
tis if there is a history of drug exposure; autoimmune hep- 10% of patients. The course of the disease is variable,
atitis if autoimmune markers are present; Wilson disease but jaundice seldom persists for more than 2 weeks.
if ceruloplasmin levels are abnormal; hemochromatosis if HBsAg disappears in 95% of cases at the time of clini-
transferrin saturation is high; α1-antitrypsin deficiency if cal recovery. Persistent asymptomatic antigenemia may
serum concentration is decreased, and steatohepatitis if occur, particularly in children with vertical transmis-
liver biopsy findings are suggestive. sion, Down syndrome, or leukemia and in those under-
going chronic hemodialysis. Persistence of neonatally
Prevention acquired HBsAg occurs in 70–90% of infants without
immunoprophylaxis or vaccination, and the presence of
Control of hepatitis B in the population is based on e antigen in the HBsAg carrier indicates ongoing viral
screening of blood donors and pregnant women, use of replication. If HBV infection is acquired later in child-
properly sterilized needles and surgical equipment, hood, HBV is cleared and recovery occurs in 90–95%
avoidance of sexual contact with carriers, and vaccina- of patients. Chronic hepatitis B disease predisposes the
tion of all infants and adolescents, as well as household patient to development of hepatocellular carcinoma.
contacts, sexual partners, medical personnel, and those Once chronic HBV infection is established, surveillance
at high risk. Universal immunization of all infants born for development of hepatocellular carcinoma with he-
in the United States and of adolescents is now recom- patic ultrasonography and serum α-fetoprotein is per-
mended, as it is in most other countries. When ac- formed annually. Routine HBV vaccination of new-
quired vertically at birth, chronic disease is frequently borns in endemic countries has reduced the incidence
asymptomatic despite ongoing liver injury or a benign of hepatocellular carcinoma in children.
carrier state. The vaccine is highly effective for preexpo-
sure prophylaxis (see Chapter 9). Postexposure admin- Broderick AL, Jonas MM: Hepatitis B in children. Semin Liver Dis
istration of HBIG (0.06 mL/kg intramuscularly, given 2003;23(1):59 [PMID: 12616451].
as soon as possible after exposure, up to 7 days) and ini- Chang MH et al: Hepatitis B vaccination and hepatocellular carci-
tiation of vaccination are also effective. noma rates in boys and girls. JAMA 2000;284:3040 [PMID:
11122592].
Comanor L et al: Impact of chronic hepatitis B and interferon-
Treatment alpha therapy on growth of children. J Viral Hepat
2001;8:139 [PMID: 11264734].
Supportive measures such as bed rest and a nutritious
diet are used during the active stage of disease. Corticos- Jonas MM et al; International Pediatric Lamivudine Investigator
Group: Clinical trial of lamivudine in children with chronic
teroids are contraindicated. No other treatment is needed hepatitis B. N Engl J Med 200219;347(12):955 PMID:
for acute HBV infection. For patients with progressive [12037150].
disease (chronic active hepatitis), there are two treatment Schwarz KB: Pediatric issues in new therapies for hepatitis B and C.
options. Treatment with α-interferon (5–6 million Curr Gastroenterol Rep 2003;5(3):233 [PMID: 12734046].
 LIVER & PANCREAS / 677

HEPATITIS C HCV infection. Diagnosis is established by the pres-

ence of anti-HCV (second-generation ELISA) con-
General Considerations firmed by the radioimmunoblot assay (RIBA) or HCV
Hepatitis C virus (HCV) virus is the most common RNA by PCR. Anti-HCV is acquired passively at birth
cause of most non-B chronic hepatitis (90% of post- from infected mothers and cannot be used to confirm
transfusion hepatitis cases) (see Table 21–6). Risk fac- disease in the neonate for the first 15 months. HCV
tors include illicit use of intravenous drugs (40%), oc- RNA testing should be performed in suspicious cases.
cupational or sexual exposure (10%), and transfusions Results of this test may be negative in the first month of
(10%); 30% of cases have no known risk factors. In life, but become positive by 4 months.
children, most cases are associated with blood or blood Percutaneous liver biopsy should be considered in
product transfusions, transmission from an infected chronic cases. Histologic examination shows portal tria-
mother, or other household transmission. In the past, ditis with chronic inflammatory cells, occasional lym-
children with hemophilia or on chronic hemodialysis phocyte nodules in portal tracts, mild macrovesicular
were at significant risk. The risk from transfused blood steatosis, and variable bridging necrosis, fibrosis, and
products has diminished greatly (from 1–2:100 to cirrhosis. Cirrhosis in adults generally requires
1:100,000 units of blood) since the advent of blood 10–30 years of chronic HCV infection, but it has occa-
testing for ALT and anti-HCV. HCV infection has sionally developed sooner in children.
been caused by contaminated immune serum globulin
preparations. Vertical transmission from HCV-infected Differential Diagnosis
mothers occurs more commonly with mothers who are
HIV-positive (10–20%) compared with those who are HCV hepatitis should be distinguished from HAV,
HIV-negative (5–6%). About 0.4% of adolescents and HBV, and NANBNC hepatitis by serologic testing.
1.5% of adults in the United States are infected. In- Other causes of cirrhosis in children should be consid-
fected infants have elevated ALT levels, but do not ap- ered in cases of chronic illness, such as Wilson disease
pear ill; long-term outcome is unknown. Transmission or α1-antitrypsin deficiency. Chronic hepatitis may also
of the virus from breast milk is probably rare. HCV be caused by drug reactions, autoimmune disease, or
rarely causes fulminant hepatitis in children or adults in steatohepatitis.
Western countries, but different serotypes do so in Asia.
HCV is a single-stranded RNA virus in the fla- Treatment
vivirus family. At least seven genotypes of HCV exist.
Several well-defined HCV antigens are the basis for Treatment of acute HCV hepatitis is supportive. Indi-
serologic antibody tests. The third-generation enzyme- cations for treatment of chronic infection will be deter-
linked immunosorbent assay (ELISA) test for anti- mined by current clinical trials. Chronic infection re-
HCV is highly accurate. Anti-HCV is generally present sponds to interferon-α (3 million units/m2 three times
when symptoms occur; however, test results may be a week for 6–12 months) in 30–50% of cases. Relapses
negative in the first few months of infection. HCV are common and appear to depend on genotype of the
RNA, which can be detected in serum by PCR and virus. Overall only 10–20% are sustained responders,
branched-DNA test, indicates active infection. and the response is poorer with infections with geno-
type 1a or 1b. Combined interferon plus ribavirin is
more successful in adults and is being tested in chil-
Clinical Findings dren. Long-acting (pegylated) interferon (with or with-
A. SYMPTOMS AND SIGNS out ribavirin) is effective in adults and is being tested in
children. End-stage liver disease secondary to HCV re-
The incubation period is 1–5 months, with insidious sponds well to liver transplantation, although reinfec-
onset of symptoms. Many childhood cases, especially tion is common and gradually progressive. There is no
those acquired vertically, are asymptomatic despite de- vaccine, and no benefit from using immune globulin in
velopment of chronic hepatitis. Flu-like prodromal infants born to infected mothers. Elective C-section of
symptoms and jaundice occur in less than 25% of cases. HCV-infected pregnant women with a high titer of cir-
Hepatosplenomegaly may or may not be evident in culating virus may lessen the likelihood for transmis-
chronic hepatitis. Ascites, clubbing, palmar erythema, sion.
or spider angiomas indicate progression to cirrhosis.

B. LABORATORY FINDINGS Prognosis

Fluctuating mild to moderate elevations of aminotrans- In adults, 70–80% of HCV cases develop chronic hepa-
ferases over long periods are characteristic of chronic titis, and cirrhosis develops in 20% of those with
678 / CHAPTER 21

chronic infection for 10–30 years. Alcohol intake in- Dalekos GN et al: Interferon-alpha treatment of children with
creases this risk. HCV is now the leading indication for chronic hepatitis D virus infection: The Greek experience.
Hepatogastroenterology 2001;47:1072.
liver transplantation in adults. A strong association ex-
ists between chronic HCV disease and the development Kelly D, Skidmore S: Hepatitis C-Z: Recent advances. Arch Dis
Child 2002;86(5):339 [PMID: 11970925].
of hepatocellular carcinoma after as little as 15 years.
The outcome in children is less well defined, although
cirrhosis may develop rapidly or after decades. About HEPATITIS E
50% of children infected by transfusion in the first few General Considerations
years of life develop chronic infection. Infants infected
at birth often have concomitant HIV infection; their Hepatitis E virus (HEV) infection is a cause of enteri-
outcome is unknown at present. In adults, chronic cally transmitted, epidemic non-A, non-B hepatitis (see
HCV infection has been associated with mixed cryo- Table 21–6). It is rare in the United States. HEV is a
globulinemia, polyarteritis nodosa, a sicca-like syn- calicivirus-like agent that is transmitted via the
drome, and membranoproliferative glomerulonephritis. fecal–oral route. It occurs predominantly in developing
countries in association with water-borne epidemics,
Alter MJ et al: The prevalence of hepatitis C virus infection in the and has only a 3% secondary attack rate in household
United States 1988 through 1994. N Engl J Med 1999;19: contacts. Areas reporting epidemics include southeast
341 [PMID: 10451460]. Asia, China, the Indian subcontinent, the Middle East,
Bortolotti F et al: An epidemiological survey of hepatitis C virus in- northern and western Africa, Mexico, and Central
fection in Italian children in the decade 1990–1999. J Pediatr America. Its clinical manifestations are similar to those
Gastroenterol Nutr 2001;32:562 [PMID: 11419517]. of HAV infection except that symptomatic disease is
Di Ciommo V et al: Interferon alpha in the treatment of chronic rare in children, more common in adolescents and
hepatitis C in children: A meta-analysis. J Viral Hepat 2003;
10(3):210 [PMID: 12753340].
adults, and is associated with a high mortality
(10–20%) in pregnant women, particularly in the third
European Pediatric Hepatitis C Virus Network: Effects of mode of
delivery and infant feeding on the risk of mother-to-child trimester. Diagnosis is established by detecting anti-
transmission of hepatitis C virus. BJOG 2001;108:371 HEV antibody. The outcome in nonpregnant individu-
[PMID: 11305543]. als is benign, with no chronic hepatitis or chronic car-
Gibb DM et al: Mother-to-child transmission of hepatitis C virus: rier state reported. There is no effective treatment.
Evidence for preventable peripartum transmission. Lancet
2000;356:904 [PMID: 11036896]. Aggarwal R et al: Hepatitis E: An overview and recent advances in
Resti M et al: Hepatitis C virus infection in children coinfected clinical and laboratory research. J Gastroenterol Hepatol
with HIV: Epidemiology and management. Paediatr Drugs 2000;15:9 [PMID: 10719741].
2002;4(9):571 [PMID: 12175272]. Arora NK et al: Hepatitis E infection in children: Study of an out-
Schwarz KB, Balistreri W: Viral hepatitis. J Pediatr Gastroenterol break. J Gastroenterol Hepatol 1999;14:572 [PMID:
Nutr 2002;35 (Suppl 1):S29 [PMID: 12151818]. 10385067].
Arora NK et al: Acute liver failure. Indian J Pediatr 2003;70(1):
73 [PMID: 12619956].
HEPATITIS D (Delta Agent) Piper-Jenks N et al: Risk of hepatitis E infection to travelers.
General Considerations J Travel Med 2000;7:1949 [PMID: 11003732].

The hepatitis D virus (HDV) is a 35-nm defective virus

that requires a coat of HBsAg to be infectious (see
OTHER HEPATITIS VIRUSES
Table 21–6). HDV infection thus can occur only in the The recently discovered hepatitis G virus (HGV), also
presence of HBV infection. In developing countries, called the GB virus, is relatively common and parenter-
transmission is by intimate contact; in Western coun- ally and vertically transmitted, but it has not been
tries, by parenteral exposure. HDV is rare in North shown to produce acute or chronic liver disease. Coin-
America. HDV can infect simultaneously with HBV, fection appears to improve the prognosis of HIV dis-
causing acute hepatitis, or can superinfect a patient ease. TT virus is also commonly transmitted, but is not
with chronic HBV infection, predisposing the individ- a significant cause of hepatitis.
ual to chronic hepatitis or fulminant hepatitis. In chil- Other undiscovered NANBNC viruses probably
dren, the association between chronic HDV coinfec- cause the majority of cases of fulminant hepatitis in
tion with HBV and chronic hepatitis and cirrhosis is a children. Infection with these uncharacterized agents is
strong. Vertical HDV transmission is rare. The diagno- associated with the development of aplastic anemia in a
sis of HDV is made by anti-HDV IgM. Treatment is small proportion of patients recovering from hepatitis
directed at therapy for HBV infection (eg, interferon- and in 15–20% of those undergoing liver transplanta-
α) or for fulminant hepatic failure. tion for fulminant hepatitis. Parvovirus has been associ-
 LIVER & PANCREAS / 679

ated with fulminant hepatitis; the prognosis is relatively ease, acute fatty liver of pregnancy, Reye syndrome, au-
good in children. toimmune hepatitis, drugs (eg, acetaminophen, anes-
Infectious mononucleosis (Epstein–Barr virus) is thetic agents) or toxins (eg, poisonous mushrooms,
commonly associated with acute hepatitis. CMV, aden- herbs), leukemia, and cardiac dysfunction must also be
ovirus, and leptospirosis are other infectious causes of considered.
acute hepatitis.
Clinical Findings
Howard CR: Hepatitis viruses: A Pandora’s box? J Gastroenterol
Hepatol 2002;17 (Suppl):S464-7 [PMID: 12534779]. In some patients, the disease proceeds in a rapidly ful-
Sokal EM et al: Acute parvovirus B19 infection associated with ful- minant course with deepening jaundice, coagulopathy,
minant hepatitis of favorable prognosis in young children. hyperammonemia, ascites, a rapidly shrinking liver, and
Lancet 1998;352:1739 [PMID: 9848349]. progressive coma. Terminally, AST and ALT, which
Tillmann HL et al: Infection with GB virus C and reduced mortal- were greatly elevated (2000–10,000 units/L), may im-
ity among HIV-infected patients. N Engl J Med 2001;345: prove at the time when the liver is getting smaller and
715 [PMID: 11547740].
undergoing massive necrosis and collapse. Some pa-
tients start with a course typical of benign hepatitis and
FULMINANT HEPATIC FAILURE then suddenly become severely ill during the second
(Acute Massive Hepatic Necrosis, week of the disease. Fever, anorexia, vomiting, and ab-
Acute Liver Failure) dominal pain may be noted, and worsening of LFTs
parallels changes in sensorium or impending coma. Hy-
perreflexia and a positive extensor plantar response are
ESSENTIALS OF DIAGNOSIS seen. A characteristic breath odor (fetor hepaticus) is
& TYPICAL FEATURES present. A generalized bleeding tendency occurs at this
time. Impairment of renal function, manifested by ei-
ther oliguria or anuria, is an ominous sign. The striking
• Acute hepatitis with deepening jaundice. laboratory findings include elevated serum bilirubin
• Extreme elevation of AST and ALT. levels (usually > 20 mg/dL), high AST and ALT (>
• Prolonged prothrombin time. 3000 units/L) that may decrease terminally, low serum
• Encephalopathy and cerebral edema. albumin, hypoglycemia, and prolonged prothrombin
time. Blood ammonia levels may be elevated, whereas
• Asterixis and fetor hepaticus. blood urea nitrogen is often very low. Hyperpnea is fre-
quent, and mixed respiratory alkalosis and metabolic
acidosis are present.

General Considerations Differential Diagnosis

Fulminant hepatic failure is defined as acute liver dys- Infectious, metabolic, and drug/toxin causes are most
function resulting in hepatic coma and coagulopathy common. Patients with Reye syndrome or urea cycle
within 6 weeks after onset. Mortality is 60–80% in defects are typically anicteric. Wilson disease, autoim-
children (without liver transplantation). An unusually mune hepatitis, acute leukemia, cardiomyopathy, and
virulent infectious agent or peculiar host susceptibility Budd–Chiari syndrome should be considered. Aceta-
is postulated in many cases. In the first few weeks of minophen, herbal remedies and other toxins (eg, “Ec-
life, fulminant hepatic failure can be caused by herpes stasy”) need to be considered even if there is a negative
simplex, enteroviruses, adenovirus, galactosemia, fruc- history.
tose intolerance, tyrosinemia, neonatal iron storage dis-
ease, respiratory chain and fatty acid oxidation defects,
familial erythrophagocytic histiocytosis, bile acid syn-
Complications
thesis defects, and peroxisomal diseases. In older infants The development and depth of hepatic coma determine
and children, HBV, NANBNC hepatitis, parvovirus, the prognosis. Patients in grade 3 or 4 coma (unrespon-
and HEV are sometimes causative. HAV rarely is re- siveness to verbal stimuli, decorticate or decerebrate func-
sponsible. Patients with immunologic deficiency dis- tion) rarely survive without transplantation, and may
eases and those receiving immunosuppressive drugs are have residual CNS deficits. Cerebral edema, which usu-
vulnerable to herpes viruses. In children with HIV in- ally accompanies coma, is frequently the cause of death.
fection, nucleoside analogues have triggered lactic aci- Extreme prolongation of prothrombin time or interna-
dosis and liver failure. In older children, Wilson dis- tional normalized ratio (INR) predicts poor recovery. Ac-
680 / CHAPTER 21

etaminophen overdose is the exception. Sepsis, hemor- nial pressure in patients awaiting liver transplantation is
rhage, renal failure, or cardiorespiratory arrest is a com- advocated. Artificial hepatic support devices are being
mon terminal event. The rare survivor without transplan- developed, although continuous venous–venous dialysis
tation may have residual fibrosis or even cirrhosis. may be helpful. Prophylactic immune globulin,
0.02 mL/kg intramuscularly, should be given to close
contacts of patients who have HAV infection.
Treatment
Many regimens have been tried, but controlled evalua- Prognosis
tion of therapy remains difficult. Exchange transfusion
(with fresh heparinized blood) temporarily repairs both The overall prognosis remains poor without liver trans-
the chemical and hematologic abnormalities. Plasma- plantation. Exchange transfusions or other modes of
pheresis with plasma exchange, total body washout, heroic therapy do not improve survival figures. The
charcoal hemoperfusion, and hemodialysis using a spe- presence of nests of liver cells seen on liver biopsy
cial high-permeability membrane have been used in the amounting to more than 25% of the total cells and ris-
treatment of fulminant hepatic failure. Removal of cir- ing levels of clotting factors V and VII coupled with ris-
culating toxins may be of greater benefit to extrahepatic ing levels of serum α-fetoprotein may signify a more fa-
organ function (brain) than to the liver itself. Reversal vorable prognosis for survival. The survival rate in
of hepatic encephalopathy may follow any of these patients who undergo liver transplantation (60–85%)
therapeutic modalities, but without improving the final exceeds that of those who do not (20–40%).
prognosis. Extracorporeal hepatic support devices are in
development. Orthotopic liver transplantation is suc- Church JA et al: Mitochondrial DNA depletion, near-fatal meta-
cessful in 60–85% of cases; however, patients in grade bolic acidosis, and liver failure in an HIV-infected child
treated with combination antiretroviral therapy. J Pediatr
4 coma may not always recover cerebral function. 2001;138:748 [PMID: 11343055].
Therefore, patients in hepatic failure should be trans- Ee LC et al: Acute liver failure in children: A regional experience.
ferred early to centers where liver transplantation can be J Paediatr Child Health 2003;39(2):107 [PMID: 12603798].
performed. Criteria for deciding when to perform Kjaergard LL et al: Artificial and bioartificial support systems for
transplantation are not firmly established; however, acute and acute-on-chronic liver failure: A systematic review.
serum bilirubin over 20 mg/dL, prothrombin time over JAMA 2003;289(2):217 [PMID: 12517233].
30 seconds, and factor V levels less than 20% indicate a Ostapowicz G et al; U.S. Acute Liver Failure Study Group: Results
poor prognosis. Living related donors may be required of a prospective study of acute liver failure at 17 tertiary care
for transplantation in a timely fashion. The prognosis is centers in the United States. Ann Intern Med 2002;
better for acetaminophen ingestion, particularly when 137(12):947 [PMID: 12484709].
N-acetylcysteine treatment is given. Singer AL et al: Role of plasmapheresis in the management of acute
hepatic failure in children. Ann Surg 2001;234:418 [PMID:
Corticosteroids may be harmful, unless autoimmune 11524594].
hepatitis is the cause. Sterilization of the colon with oral
antibiotics such as metronidazole, neomycin, or genta-
micin is recommended. An alternative is acidification AUTOIMMUNE HEPATITIS
of the colon with lactulose, 1–2 mL/kg three or four (LUPOID HEPATITIS)
times daily, which reduces blood ammonia levels and
traps ammonia in the colon. Some centers use N-acetyl-
cysteine in all patients. ESSENTIALS OF DIAGNOSIS
Close monitoring of fluid and electrolytes is manda- & TYPICAL FEATURES
tory and requires a central venous line. Ten percent
dextrose solutions should be infused (6–8 mg/kg/min) • Acute or chronic hepatitis
to maintain normal blood glucose. Diuretics, sedatives,
• Hypergammaglobulinemia
and tranquilizers are to be used sparingly. Early signs of
cerebral edema are treated with infusions of mannitol • Positive ANA, ASMA, or anti-LKM
(0.5–1 g/kg).
Comatose patients are intubated, given mechanical
ventilatory support, and monitored for signs of infec-
tion. Coagulopathy is treated with fresh-frozen plasma,
other clotting factor concentrates, platelet infusions, or
General Considerations
exchange transfusion. Plasmapheresis and hemodialysis Autoimmune hepatitis (AIH) is most common in ado-
may help maintain a patient while awaiting liver trans- lescent girls, although it occurs at all ages and in either
plantation. Epidural monitoring for increased intracra- sex. Chronic hepatitis may also follow HBV, HCV, and
 LIVER & PANCREAS / 681

HDV infections. Rarely, chronic hepatitis evolves from infection; steatohepatitis; Wilson disease; α1-antitrypsin
drug-induced hepatitis (eg, pemoline) or may develop deficiency; primary sclerosing cholangitis). Primary scle-
in conjunction with such diseases as ulcerative colitis, rosing cholangitis occasionally presents in a manner sim-
Sjögren syndrome, or autoimmune hemolytic anemia. ilar to AIH, including the presence of autoantibodies.
Wilson disease, α1-antitrypsin deficiency, and bile acid Wilson disease and α1-antitrypsin deficiency must be
synthesis defects may also present as chronic hepatitis. excluded if HBV and HCV studies are negative. Drug-
A positive HBsAg test implicates HBV, and anti-HCV induced (isoniazid, methyldopa, pemoline) chronic hep-
and anti-HDV suggest HCV and HDV, respectively. atitis should be ruled out. In acute, severe viral hepatitis,
Positive antinuclear antibodies, smooth muscle anti- histologic examination may also show an “aggressive” le-
bodies (type I AIH) or liver–kidney microsomal (LKM) sion early in the disease (< 3 months).
antibodies (type II AIH), elevated serum IgG, and sys-
temic manifestations (eg, arthralgia, weight loss, acne,
amenorrhea) are characteristic of AIH.
Complications
A genetic susceptibility to development of this entity Untreated disease that continues for months to years
is suggested by the increased incidence of the histocom- eventually results in postnecrotic cirrhosis, with compli-
patibility antigens HLA-A1 and HLA-B8. These histo- cations of portal hypertension. Persistent malaise, fa-
compatibility antigens may be related to a defect in tigue, amenorrhea, and anorexia parallel disease activ-
suppressor T-cell function noted in patients with ity. Bleeding from esophageal varices and development
chronic hepatitis. Increased autoimmune disease in of ascites usually usher in hepatic failure.
families of patients and a high prevalence of seroim-
munologic abnormalities in relatives have been noted.
Occasionally patients have an “overlap syndrome” of
Treatment
AIH and primary sclerosing cholangitis. Corticosteroids (prednisone, 2 mg/kg/d) decrease the
mortality rate during the early active phase of the dis-
Clinical Findings ease. Azathioprine, 1–2 mg/kg/d, is of value in decreas-
ing the side effects of long-term corticosteroid therapy
Fever, malaise, recurrent or persistent jaundice, skin
but should not be used alone during the induction
rash, arthritis, amenorrhea, gynecomastia, acne,
phase of treatment. Steroids are reduced over a 6- to
pleurisy, pericarditis, or ulcerative colitis may be found
12-month period, and azathioprine is continued for
in the history of these patients, or asymptomatic hepa-
1–2 years if AST and ALT are normal. Liver biopsy is
tomegaly or splenomegaly may be found on examina-
performed before stopping azathioprine therapy; if in-
tion. Occasionally patients present in acute liver failure.
flammation persists, then azathioprine is continued.
Cutaneous signs of chronic liver disease may be noted
Relapses are treated similarly. Many patients require
(eg, spider angiomas, liver palms, digital clubbing). He-
chronic azathioprine therapy. UCDA, cyclosporine,
patosplenomegaly is frequently present.
tacrolimus, or methotrexate may be helpful in poorly
LFTs reveal moderate elevations of serum bilirubin,
responsive cases. Use of mycophenolate mofetil instead
AST, ALT, and serum alkaline phosphatase. Serum al-
of azathioprine is under study. Liver transplantation is
bumin may be low. Serum IgG levels are strikingly ele-
indicated when disease progresses to decompensated
vated (in the range of 2–6 g/dL). Low levels of C3 com-
cirrhosis despite therapy or in unresponsive cases pre-
plement have been reported. Three subtypes have been
senting in acute liver failure. Steroid therapy may be
described based on autoantibodies present: type 1: anti-
life-saving in those presenting in acute liver failure.
smooth muscle (antiactin), type 2: anti-LKM (anticy-
tochrome P-450), and type 3: antisoluble liver antigen.
Histologic examination of liver biopsy specimens Prognosis
shows loss of the lobular limiting plate, and interface
The overall prognosis for AIH is improved significantly
hepatitis (“piecemeal” necrosis). Portal fibrosis, an in-
with early therapy. Some studies report cures (normal
flammatory reaction of lymphocytes and plasma cells in
histologic findings) in 15–20% of patients. Relapses
the portal areas and perivascularly, and some bile duct
(seen clinically and histologically) occur in 40–50% of
and Kupffer cell proliferation and pseudolobule forma-
patients after cessation of therapy; remissions follow re-
tion may be present. Cirrhosis may exist at diagnosis in
peat treatment. Survival for 10 years is common despite
up to 50% of patients.
residual cirrhosis. Of children with AIH, 20–50%
eventually require liver transplantation. Complications
Differential Diagnosis of portal hypertension (bleeding varices, ascites) require
Laboratory and histologic findings differentiate other specific therapy. Liver transplantation is successful
types of chronic hepatitis (eg, HBV, HCV, and HDV 70–90% of the time. Disease recurrence after trans-
682 / CHAPTER 21

plantation occurs 10–50% of the time and is treated α1-ANTITRYPSIN DEFICIENCY

similarly to pretransplant disease. LIVER DISEASE
Alvarez F, Schwarz K: Immune diseases of the liver and biliary
tract. J Pediatr Gastroenterol Nutr 2002;35 (Suppl ESSENTIALS OF DIAGNOSIS
1):S39 [PMID: 12151820].
Bahar RJ et al: Orthotopic liver transplantation for autoimmune
& TYPICAL FEATURES
hepatitis and cryptogenic chronic hepatitis in children.
Transplantation 2001;72:829 [PMID: 11571445]. • Serum α1-antitrypsin level less than 50–80 mg/dL.
Czaja AJ: Treatment of autoimmune hepatitis. Semin Liver Dis • Identification of a specific protease inhibitor (Pi)
2002;22(4):365 [PMID: 12447708].
system phenotype (ZZ, SZ).
Mieli-Vergani G, Vergani D: Autoimmune liver disease in children.
Ann Acad Med Singapore 2003;32(2):239 [PMID: • Detection of diastase-resistant glycoprotein de-
12772529]. posits in periportal hepatocytes.
• Histologic evidence of liver disease.
STEATOHEPATITIS • Family history of early-onset pulmonary disease
Patients with steatohepatitis present with asymptomatic or liver disease.
soft hepatomegaly or mild to moderately elevated
aminotransferases (2 to 10 times the upper limit of nor-
mal). ALT is frequently higher than AST. Alkaline
phosphatase and GGT may be mildly elevated, but General Considerations
bilirubin is normal. Liver biopsy shows macrovesicular
steatosis, mild portal inflammation, normal bile ducts, The disease is caused by a deficiency in α1-antitrypsin,
and variable degrees of portal fibrosis to cirrhosis. Ul- a protease inhibitor (Pi) system, predisposing patients
trasonography or CT scanning indicates fat density in to chronic liver disease and an early onset of pulmonary
the liver. Most cases are associated with obesity or type emphysema. It is most often associated with the Pi phe-
II diabetes mellitus. One to three percent of adolescents notype ZZ. The other phenotype associated with possi-
may have steatohepatitis, based on the observation that ble liver disease is SZ. Heterozygotes may have a
15–25% of American adolescents are overweight or slightly higher incidence of liver disease. The exact rela-
obese and that roughly 10% of these will have tionship between low levels of serum α1-antitrypsin and
steatohepatitis. Steatohepatitis is also associated with the development of liver disease is unclear. Emphysema
Wilson disease, hereditary fructose intolerance, ty- develops because of a lack of inhibition of neutrophil
rosinemia, HCV hepatitis, cystic fibrosis, fatty acid oxi- elastase, which destroys pulmonary connective tissue.
dation defects, kwashiorkor, Reye syndrome, respira- Although all patients with the ZZ genotype eventually
tory chain defects, and toxic hepatopathy (ethanol and have antitrypsin inclusions in hepatocytes, only about
others). Treatment is weight reduction and exercise for 10–20% develop significant liver disease. An associated
obesity or treatment for the other causes. A pilot trial abnormality in the microsomal disposal of accumulated
suggests that vitamin E may be of value. A similar en- aggregates may be necessary for the liver disease pheno-
tity, termed nonalcoholic steatohepatitis, occurs in type.
adults. Cirrhosis and liver failure have been described in About 20% of affected individuals present with
adults with this disease. neonatal cholestasis. About 10% of individuals with α1-
antitrypsin deficiency have or have had clinically signif-
Lavine JE: Vitamin E treatment of nonalcoholic steatohepatitis in icant liver injury by age 18 years. Very few children
children: A pilot study. J Pediatr 2000;136:734 [PMID: have significant pulmonary involvement. Most children
10839868]. are asymptomatic, with no laboratory or clinical evi-
Molleston JP et al: Obese children with steatohepatitis can develop dence of liver disease.
cirrhosis in childhood. Am J Gastroenterol 2002;97(9):
2460 [PMID: 12358273].
Clinical Findings
Neuschwander-Tetri BA, Caldwell SH: Nonalcoholic steatohepati-
tis: Summary of an AASLD Single Topic Conference. Hepa- A. SYMPTOMS AND SIGNS
tology 2003;37(5):1202 [PMID: 12717402].
Roberts EA: Nonalcoholic steatohepatitis in children. Curr Gas-
α1-Antitrypsin deficiency should be considered in all
troenterol Rep 2003;5(3):253 [PMID: 12734049]. infants with neonatal cholestasis. Serum GGT is usually
Strauss RS et al: Prevalence of abnormal serum transaminase values elevated. Jaundice, acholic stools, and malabsorption
in overweight and obese adolescents. J Pediatr 2000;136: suggest neonatal hepatitis but are not pathognomonic
727 [PMID: 10839867]. of any one cause. Infants are often small for gestational
 LIVER & PANCREAS / 683

age, and hepatosplenomegaly may be present. The fam- Table 21–4). UCDA may reduce AST, ALT, and
ily history may be positive for emphysema or cirrhosis. GGT, but its effect on outcome is unknown. Portal hy-
In older children, hepatomegaly or physical findings pertension, esophageal bleeding, ascites, and other
suggestive of cirrhosis, especially in the face of a nega- complications are treated as described elsewhere. He-
tive history of liver disease, should always lead one to patitis A and B vaccines should be given to children
consider α1-antitrypsin deficiency. Recurrent pul- with α1-antitrypsin deficiency. Genetic counseling is
monary disease (bronchitis, pneumonia) may be pre- indicated whenever the diagnosis is made. Diagnosis by
sent in a few children. prenatal screening is possible. Liver transplantation
cures the deficiency. Cigarette smoke exposure should
B. LABORATORY FINDINGS be eliminated to help prevent pulmonary manifesta-
Levels of the α1-globulin fraction may be less than tions.
0.2 mg/dL on serum protein electrophoresis. α1-Anti-
trypsin levels are low (< 50–80 mg/dL) in homozygotes
(ZZ). Specific Pi phenotyping should be done to con- Prognosis
firm the diagnosis. LFTs often reflect underlying he- Of those patients presenting with neonatal cholestasis,
patic pathologic changes. Hyperbilirubinemia (mixed) approximately 10–25% will need liver transplantation
and elevated aminotransferases, alkaline phosphatase, in the first 5 years of life, 15–25% during childhood or
and GGT are present early. Hyperbilirubinemia gener- adolescence, and 50–75% will survive into adulthood
ally resolves, while aminotransferase elevation may per- with variable degrees of liver fibrosis. A correlation be-
sist. Signs of cirrhosis and portal hypertension may de- tween histologic patterns and clinical course has been
velop. documented in the infantile form of the disease. Liver
Liver biopsy after age 6 months shows diastase-resis- failure can be expected 5–15 years after development of
tant, periodic acid-Schiff staining intracellular granules, cirrhosis. Recurrence or persistence of hyperbilirubine-
with hyaline masses, particularly in periportal zones. mia along with worsening coagulation studies indicates
These may be absent prior to age 6 months. the need for evaluation for possible liver transplanta-
tion. Decompensated cirrhosis caused by this disease is
Differential Diagnosis an excellent indication for liver transplantation; the sur-
vival rate should reach 80–90%.
In newborns, other specific causes of neonatal cholesta-
sis need to be considered. In older children, other
causes of insidious cirrhosis (eg, HBV or HCV infec- Francavilla R et al: Prognosis of alpha-1-antitrypsin deficiency-re-
lated liver disease in the era of paediatric liver transplantation.
tion, autoimmune hepatitis, Wilson disease, cystic fi- J Hepatol 2000;32:986 [PMID: 10898319].
brosis, hemochromatosis, glycogen storage disease) Primahak RA, Tanner MS: Alpha-1 antitrypsin deficiency. Arch
should be considered. Dis Child 2001;85:2 [PMID: 11420185].
Piitulainen E, Sveger T: Respiratory symptoms and lung function
Complications in young adults with severe alpha(1)-antitrypsin deficiency
(PiZZ). Thorax 2002;57(8):705 [PMID: 12149531].
Of all infants with Pi ZZ α1-antitrypsin deficiency, Sveger T, Eriksson S: The liver in adolescents with α1-antitrypsin
only 20% develop liver disease in childhood. The com- deficiency. Hepatology 1995;22:514 [PMID: 7635419].
plications of portal hypertension, cirrhosis, and chronic Volpert D et al: Alpha 1-antitrypsin deficiency-associated liver dis-
cholestasis predominate in affected children. Occasion- ease progresses slowly in some children. J Pediatr Gastroen-
ally, children develop paucity of interlobular bile ducts. terol Nutr 2000;31:258 [PMID: 10997369].
Early-onset pulmonary emphysema occurs in young
adults (age 30–40 years), particularly in smokers. An
increased susceptibility to hepatocellular carcinoma has WILSON DISEASE
been noted in cirrhosis associated with α1-antitrypsin (Hepatolenticular Degeneration)
deficiency.

Treatment
ESSENTIALS OF DIAGNOSIS
& TYPICAL FEATURES
There is no specific treatment for the liver disease of
this disorder. Replacement of the protein by transfusion • Acute or chronic liver disease.
therapy is successful in preventing pulmonary disease in
affected adults. The neonatal cholestatic condition is • Deteriorating neurologic status.
treated with choleretics, medium-chain triglyceride- • Kayser–Fleischer rings.
containing formula, and water-miscible vitamins (see • Elevated liver copper.
684 / CHAPTER 21

• Abnormalities in levels of ceruloplasmin and are elevated markedly owing to hepatic necrosis and re-
serum and urine copper. lease of copper. The presence of anemia, hemolysis,
very high serum bilirubin levels (> 20–30 mg/dL), and
low alkaline phosphatase are characteristic of acute Wil-
son disease. Urine copper excretion in children older
than age 3 years is normally less than 30 µg/d; in Wil-
General Considerations son disease, it is greater than 150 µg/d. Finally, the tis-
Wilson disease is caused by a mutation in the gene on sue content of copper from a liver biopsy, normally less
chromosome 13 coding for a specific P-type ATPase in- than 50 µg/g dry tissue, is greater than 250 µg/g in
volved in copper transport. This results in impaired bile Wilson disease.
excretion of copper and incorporation of copper into Glycosuria, aminoaciduria, and depressed serum
ceruloplasmin by the liver. The accumulated hepatic uric acid levels have been reported. Hemolysis and gall-
copper causes oxidant (free-radical) damage to the liver. stones may be present; bone lesions simulating those of
Subsequently, copper accumulates in the basal ganglia osteochondritis dissecans have also been found.
and other tissues. The disease should be considered in The coarse nodular cirrhosis, steatosis, and glyco-
all children older than 4 years old with evidence of liver genated nuclei seen on liver biopsy may distinguish
disease (especially with hemolysis) or with suggestive Wilson disease from other types of cirrhosis. Early in
neurologic signs. A family history is often present, and the disease, vacuolation of liver cells, steatosis, and lipo-
25% of patients are identified by screening asympto- fuscin granules can be seen, as well as Mallory bodies.
matic homozygous family members. The disease is au- The presence of Mallory bodies in a child is strongly
tosomal recessive and occurs in 1:30,000 live births in suggestive of Wilson disease. Stains for copper may
all populations. sometimes be negative despite high copper content in
the liver. Therefore, liver copper levels must be deter-
mined biochemically on biopsy specimens. Electron
Clinical Findings microscopy findings may be helpful.
A. SYMPTOMS AND SIGNS
Hepatic involvement may be fulminant, present as an Differential Diagnosis
acute hepatitis, may masquerade as chronic liver dis- During the icteric phase, acute viral hepatitis, α1-anti-
ease, or may progress insidiously to postnecrotic cirrho- trypsin deficiency, autoimmune hepatitis, Indian child-
sis. Findings include jaundice; hepatomegaly early in hood cirrhosis, and drug-induced hepatitis are the usual
childhood; splenomegaly; Kayser–Fleischer rings; and diagnostic possibilities. Later, other causes of cirrhosis
later onset of neurologic manifestations such as tremor, and portal hypertension require consideration. Labora-
dysarthria, and drooling beginning after age 10 years. tory testing for serum ceruloplasmin, 24-hour urine
Deterioration in school performance is often the earliest copper excretion, liver copper concentration, and a slit-
neurologic expression of disease. Psychiatric symptoms lamp examination of the cornea will differentiate Wil-
may also occur. The Kayser–Fleischer rings can some- son disease from the others. The radiocopper cerulo-
times be detected by unaided visual inspection as a plasmin incorporation test is sometimes needed to
brown band at the junction of the iris and cornea, but differentiate Wilson disease with a normal ceruloplas-
slitlamp examination is always necessary. Absence of min level from other liver disease with increased liver
Kayser–Fleischer rings does not exclude this diagnosis. and urine copper values. Urinary copper excretion dur-
ing penicillamine challenge may help differentiate Wil-
B. LABORATORY FINDINGS son disease from other causes. Genetic testing may be
The laboratory diagnosis is sometimes difficult. Serum necessary in confusing cases. Other copper storage dis-
ceruloplasmin levels (measured by the oxidase method) eases that occur in early childhood include Indian
are usually less than 20 mg/dL. (Normal values are childhood cirrhosis, Tyrolean childhood cirrhosis, and
23–43 mg/dL.) Low values, however, occur normally in idiopathic copper toxicosis. However, ceruloplasmin
infants younger than age 3 months, and in at least concentrations are normal in these conditions.
5–10% of homozygotes the levels may be within the
lower end of the normal range (20–30 mg/dL), particu- Complications
larly if immunoassays are used for ceruloplasmin. Rare
patients with higher ceruloplasmin levels have been re- Progressive liver disease, postnecrotic cirrhosis, hepatic
ported. Serum copper levels are low, but the overlap coma, and death are common in the untreated patient.
with normal is too great for satisfactory discrimination. The complications of portal hypertension (variceal he-
In acute fulminant Wilson disease, serum copper levels morrhage, ascites) are poorly tolerated by these pa-
 LIVER & PANCREAS / 685

tients. Progressive degenerating central nervous system Sutcliffe RP et al: Liver transplantation for Wilson’s disease: Long-
disease and terminal aspiration pneumonia are com- term results and quality-of-life assessment. Transplantation
200315;75(7):1003 [PMID: 12698088].
mon in untreated older people. Acute hemolytic disease
may result in renal impairment and profound jaundice Wilson DC et al: Severe hepatic Wilson’s disease in preschool-aged
children. J Pediatr 2000;137:719 [PMID: 11060541].
as part of the presentation of fulminant hepatitis.

Treatment REYE SYNDROME

(Encephalopathy with Fatty
Copper chelation with D-penicillamine or trientine hy-
drochloride, 1000–2000 mg/d orally, is the treatment Degeneration of the Viscera)
of choice in all cases, whether or not the patient is
symptomatic. It is best to begin with 250 mg/d and in-
crease the dose weekly by 250 mg increments. The tar- ESSENTIALS OF DIAGNOSIS
get dose is 20 mg/kg/d. Strict dietary restriction of cop- & TYPICAL FEATURES
per intake is not practical. Supplementation with zinc
acetate (25–50 mg orally, three times daily) may reduce • Prodromal upper respiratory tract infection, in-
copper absorption. Copper chelation is continued for fluenza A or B illness, or varicella.
life, although doses may be reduced transiently at the
time of surgery or early in pregnancy. Vitamin B6 • Vomiting.
(25 mg) is given daily while on penicillamine to prevent • Lethargy, drowsiness progressing to semicoma.
optic neuritis. In some countries, after a clinical re- • Elevated AST, hyperammonemia, normal or
sponse to penicillamine or trientine, zinc therapy is slightly elevated bilirubin, prolonged prothrom-
substituted and continued for life. Tetrathiomolybdate bin time.
is being tested as an alternative therapy. Noncompli- • Microvesicular steatosis of the liver, kidneys,
ance with the drug regimen can lead to fulminant liver
brain.
failure and death.
General treatment measures for acute hepatitis are as • Absence of other metabolic diseases.
outlined for infectious hepatitis. Liver transplantation is
indicated for all cases of acute fulminant disease, pro-
gressive hepatic decompensation despite several months
of penicillamine, and severe progressive hepatic insuffi-
ciency in patients who unadvisedly discontinue penicil- General Considerations
lamine therapy. The number of reported cases of Reye syndrome is de-
creasing, perhaps because of a decline in the use of sali-
Prognosis cylates among younger children, who seem to be at
greater risk. Varicella, influenza A and B, echovirus 2,
The prognosis of untreated Wilson disease is poor. coxsackievirus A, and Epstein–Barr virus infection are
Without transplantation, all patients with the fulmi- associated. Salicylate use is associated with Reye syn-
nant presentation succumb. Copper chelation reduces drome. Many apparent cases are actually caused by de-
hepatic copper content, reverses many of the liver le- fects in fatty acid oxidation and other newly discovered
sions, and can stabilize the clinical course of established metabolic diseases.
cirrhosis. Neurologic symptoms generally respond to The pathogenesis is thought to be damage to mito-
therapy. All siblings should be immediately screened chondria caused by salicylate metabolites or some other
and homozygotes given treatment with copper chela- toxin or chemical in the milieu of a viral infection or
tion or zinc acetate therapy, even if asymptomatic. Ge- underlying polymorphism in mitochondrial function.
netic testing (haplotype analysis or genotyping) is avail- Mitochondrial dysfunction leads to elevated short-
able at a few centers for family members. chain fatty acids and hyperammonemia as well as di-
rectly to cerebral edema.
Brewer GJ et al: Treatment of Wilson’s disease with zinc: XVI.
Treatment during the pediatric years. J Lab Clin Med 2001;
137:191 [PMID: 11241029]. Clinical Findings
Loudianos G, Gitlin JD: Wilson’s disease. Semin Liver Dis 2000;
20:353 [PMID: 11076401].
A. SYMPTOMS AND SIGNS
Roberts EA, Schilsky ML: A practice guideline on Wilson disease. Varicella, influenza, or minor upper respiratory tract ill-
Hepatology 2003;37(6):1475 [PMID: 12774027]. ness precedes the development of vomiting, irrational
Scheinberg IH, Sternlieb I: Wilson’s Disease. WB Saunders, 1984. behavior, progressive stupor, and coma. Restlessness
686 / CHAPTER 21

and convulsions may also occur. Striking physical find- should be monitored directly and kept below
ings are hyperpnea, irregular respirations, and dilated, 15–20 mm Hg, and systemic blood pressure should be
sluggishly reacting pupils. Jaundice is minimal or ab- kept high enough to maintain cerebral perfusion pres-
sent. The liver may be normal or enlarged. sure above 45–50 mm Hg. Hyperventilation, mannitol
Splenomegaly is absent. A positive Babinski sign, hy- infusions (0.5–1 g/kg every 4 hours), barbiturates, or
perreflexia, and decorticate and decerebrate posturing ventricular drainage is used to lower intracranial pres-
are consistent with increased intracranial pressure. sure. Maintenance fluids using 10% glucose should be
given at a rate sufficient to produce a urine flow of
B. LABORATORY FINDINGS 1–1.5 mL/kg/h. Vitamin K, 3–5 mg intramuscularly,
CSF is acellular, and CSF glucose may be low in should be administered. Hypothermia and pentobarbi-
younger patients who have hypoglycemia. CSF pressure tal coma have been used to decrease body (brain) meta-
is increased. Moderate to severe elevations of AST, bolic needs during the period of uncontrolled intracra-
ALT, and lactate dehydrogenase and normal serum nial pressure.
bilirubin and alkaline phosphatase values are character-
istic. The prothrombin time is usually prolonged, and Prognosis
the blood ammonia is elevated to varying degrees. A
mixed respiratory alkalosis and metabolic acidosis is At least 70% of patients with Reye syndrome survive.
typical. Hyperaminoacidemia (glutamine, alanine, ly- The prognosis is related to the depth of coma and the
sine) and hypocitrullinemia are present. peak ammonia level on admission. Because Reye syn-
Histology of the liver shows diffuse microvesicular drome is less common now, many patients are diag-
steatosis with minimal inflammatory changes. Glyco- nosed only when in deep coma. All patients should be
gen is virtually absent from the hepatocytes in biopsy screened for fatty acid oxidation and other metabolic
specimens taken before administration of hypertonic defects. Survivors should not be given aspirin.
glucose. Mitochondria are large, pleomorphic, and have
decreased matriceal density on electron microscopy. Auret-Leca E et al: Incidence of Reye syndrome in France: A hospi-
The kidney changes include swelling and fatty de- tal-based survey. J Clin Epidemiol 2001;54:857 [PMID:
11470397].
generation of the proximal lobules.
Casteels-Van Daele M et al: Reye syndrome revisited: A descriptive
C. ELECTROENCEPHALOGRAPHY term covering a group of heterogeneous disorders. Eur J Pedi-
atr 2000;159:641 [PMID: 11014461].
The electroencephalogram shows diffuse slow wave ac- da Silveira EB et al: Reye’s syndrome in a 17-year-old male: Is this
tivity. disease really disappearing? Dig Dis Sci 2002;47(9):1959
[PMID: 12353836].
Differential Diagnosis Orlowski JP et al: Is aspirin a cause of Reye’s syndrome? A case
against. Drug Saf 2002;25(4):225 [PMID: 11994026].
Differentiation of Reye syndrome from encephalitis,
acute toxic encephalopathy, hepatic coma, or fulminant CIRRHOSIS
hepatitis can be made on clinical and laboratory
grounds. A negative history and urine screen for inges- Cirrhosis is a histologically defined condition of the
tion of poisons and drugs, absence of cells in the CSF, liver characterized by diffuse hepatocyte injury and re-
and absence of jaundice favor a diagnosis of Reye syn- generation, an increase in connective tissue (bridging fi-
drome. The fatty acid oxidation defects (eg, medium- brosis), and disorganization of the lobular and vascular
chain acyl-CoA dehydrogenase deficiency) and other architecture (regenerative nodules). It may be micron-
metabolic disorders may resemble Reye syndrome; gas odular or macronodular in appearance. It is the vascula-
chromatographic analysis of urine and serum acyl-car- ture distortion that leads to increased resistance to
nitine levels will help differentiate them. Liver biopsy blood flow, producing portal hypertension and its con-
and electron microscopy can be diagnostic and are indi- sequences.
cated in atypical cases. Many liver diseases may progress to cirrhosis. In
children, the two most common forms of cirrhosis are
postnecrotic and biliary—with different causes, symp-
Treatment tomatology, and treatment requirements. Both forms
Treatment in an intensive care unit is mainly support- can eventually lead to liver failure and death.
ive. If cerebral edema can be minimized, the liver In the pediatric population, postnecrotic cirrhosis is
makes a full recovery. Mechanical ventilation may be- often a result of acute or chronic liver disease (eg, idio-
come necessary if the patient reaches grade 3 coma (agi- pathic neonatal giant-cell hepatitis; viral hepatitis
tated delirium, combativeness). Intracranial pressure [HBV, HCV, or NANBNC hepatitis]; autoimmune or
 LIVER & PANCREAS / 687

drug-induced hepatitis); or certain inborn errors of me- min K administration. Burr and target red cells may be
tabolism (see Table 21–5). Cirrhosis is an exceptional noted on the peripheral blood smear. Anemia, throm-
outcome of HAV infection and only follows massive bocytopenia, and leukopenia are present if hyper-
hepatic necrosis. The evolution to cirrhosis may be in- splenism exists. However, cirrhosis may be present de-
sidious, with no recognized icteric phase, as in some spite normal blood tests.
cases of HBV or HCV infection, Wilson disease, he- In biliary cirrhosis, elevated conjugated bilirubin,
mochromatosis, or α1-antitrypsin deficiency. At the bile acids, GGT, alkaline phosphatase, and cholesterol
time of diagnosis of cirrhosis, the underlying liver dis- are common.
ease may be active, with abnormal LFT results; or it
may be quiescent, with normal LFTs. Most cases of bil- C. IMAGING
iary cirrhosis result from congenital abnormalities of Hepatic ultrasound or CT examination may demon-
the bile ducts (biliary atresia, choledochal cyst, com- strate abnormal hepatic texture and nodules. In biliary
mon duct stenosis), tumors of the bile duct, Caroli dis- cirrhosis, abnormalities of the biliary tree may be appar-
ease, Byler disease, primary sclerosing cholangitis, ent by ultrasonography, CT, hepatobiliary scintigraphy,
paucity of the intrahepatic bile ducts, and cystic fibro- or cholangiography.
sis.
Occasionally, cirrhosis may follow a hypersensitivity D. PATHOLOGIC FINDINGS
reaction to certain drugs such as phenytoin. Parasites Liver biopsy findings of regenerating nodules and sur-
(Opisthorchis sinensis, Fasciola, Ascaris) may be causative rounding fibrosis are hallmarks of cirrhosis. Pathologic
in children living in endemic areas. features of biliary cirrhosis also include canalicular and
hepatocyte cholestasis, as well as plugging of bile ducts.
Clinical Findings The interlobular bile ducts may be increased or de-
creased, depending on the cause and the stage of the
A. SYMPTOMS AND SIGNS disease process.
General malaise, loss of appetite, failure to thrive, and
nausea are frequent complaints, especially in anicteric Complications & Treatment
varieties. Easy bruising may be reported. Jaundice may
or may not be present. The first indication of underly- Major complications of cirrhosis in childhood include
ing liver disease may be ascites, gastrointestinal hemor- progressive nutritional disturbances and hormonal dis-
rhage, or hepatic encephalopathy. Variable he- turbances and the evolution of portal hypertension and
patosplenomegaly, spider angiomas, warm skin, palmar its complications. Hepatocellular carcinoma occurs
erythema, or digital clubbing may be present. A small, with increased frequency in the cirrhotic liver, espe-
shrunken liver may be detected by percussion over the cially in patients with the chronic form of hereditary ty-
right chest wall that reveals resonance rather than ex- rosinemia or after long-standing HBV or HCV disease.
pected dullness. Most often, the liver is enlarged At present, there is no proven medical treatment for cir-
slightly, especially in the subxiphoid region, where it rhosis, but whenever a treatable condition is identified
has a firm to hard quality and an irregular edge. Ascites (eg, Wilson disease, galactosemia, congenital fructose
may be detected as shifting dullness or a fluid wave. intolerance) or an offending agent eliminated (HBV,
Gynecomastia may be noted in males. Digital clubbing HCV, drugs, toxins), disease progression can be altered;
occurs in 10–15% of cases. Pretibial edema often oc- occasionally regression of fibrosis has been noted. Im-
curs, reflecting underlying hypoproteinemia. In adoles- munosuppressive treatment in autoimmune hepatitis
cent girls, irregularities of menstruation and amenor- can halt the progression of cirrhosis. Surgical correction
rhea may be early complaints. of biliary tree abnormalities can stabilize the disease
In biliary cirrhosis, patients often have jaundice, process or lead to a reversal in some situations. Chil-
dark urine, pruritus, hepatomegaly, and sometimes dren with cirrhosis should receive the hepatitis A and B
xanthoma in addition to the previously mentioned clin- vaccines. Liver transplantation may be appropriate in
ical findings. Undernutrition and failure to thrive be- patients with cirrhosis whose disease is continuing to
cause of steatorrhea may be more apparent in this form progress or in whom the complications of cirrhosis are
of cirrhosis. no longer manageable.
B. LABORATORY FINDINGS
Prognosis
Mild abnormalities of aminotransferases (AST, ALT)
are often present, with a decreased level of albumin and Postnecrotic cirrhosis has an unpredictable course.
a variable increase in the level of γ-globulins. Prothrom- Without transplantation, affected patients may die
bin time is prolonged and may be unresponsive to vita- from liver failure within 10–15 years. Patients with a
688 / CHAPTER 21

rising bilirubin or a vitamin K-resistant coagulopathy made until age 3–5 years. Patients with a positive
along with diuretic refractory ascites usually survive less neonatal history tend to be symptomatic earlier.
than 1–2 years. The terminal event in some patients A variety of portal or splenic vein malformations,
may be generalized hemorrhage, sepsis, or cardiorespi- some of which may be congenital, have been described,
ratory arrest. For patients with biliary cirrhosis, the including defects in valves and atretic segments. Cav-
prognosis is similar, except for those with surgically cor- ernous transformation is probably the result of at-
rected lesions that result in regression or stabilization of tempted collateralization around the thrombosed portal
the underlying liver condition. With liver transplanta- vein rather than a congenital malformation. The site of
tion, the long-term survival rate is 70–80%. the venous obstruction may be anywhere from the
hilum of the liver to the hilum of the spleen.
Friedman SL: Hepatic fibrosis. In Schiff ER, Sorrell MF, Maddrey
WC (eds): Schiff’s Diseases of the Liver. Lippincott-Raven, B. SUPRAHEPATIC VEIN OCCLUSION OR THROMBOSIS
1999. (BUDD–CHIARI SYNDROME)
Hardy SC, Kleinman RE: Cirrhosis and chronic liver failure. In In most instances, no cause can be demonstrated. Sug-
Suchy FJ, Sokol RJ, Balistreri WF (eds): Liver Disease in
Children. Lippincott Williams & Wilkins, 2001.
gested causes include endothelial injury to hepatic veins
by bacterial endotoxins, which has been demonstrated
Reddy SI, Grace ND: Liver imaging: A hepatologist’s perspective.
Clin Liver Dis 2002;6:297 [PMID: 11933595]. experimentally. The occasional association of hepatic
vein thrombosis in inflammatory bowel disease favors
the presence of endogenous toxins traversing the liver.
PORTAL HYPERTENSION Allergic vasculitis leading to endophlebitis of the he-
patic veins has been described occasionally. In addition,
hepatic vein obstruction may be secondary to tumor,
ESSENTIALS OF DIAGNOSIS abdominal trauma, hyperthermia, or sepsis, or it may
& TYPICAL FEATURES occur following the repair of an omphalocele or gas-
troschisis. Congenital vena caval bands, webs, a mem-
• Splenomegaly. brane, or strictures above the hepatic veins are some-
• Recurrent ascites. times causative. Hepatic vein thrombosis may be a
complication of oral contraceptive medications. Under-
• Variceal hemorrhage.
lying thrombotic conditions (deficiency of antithrom-
• Hypersplenism. bin III, protein C or protein S, factor V Leiden; an-
tiphospholipid antibodies; or mutations of the
prothrombin gene) should be evaluated.
C. INTRAHEPATIC PORTAL HYPERTENSION
General Considerations
1. Cirrhosis (see previous section).
Portal hypertension is defined as an increase in the por-
2. Veno-occlusive disease (acute stage)—This now
tal venous pressure to more than 5 mm Hg greater than occurs most frequently in bone marrow transplant pa-
the inferior vena caval pressure. Portal hypertension is tients. It may also develop after chemotherapy for acute
most commonly a result of cirrhosis. However, portal leukemia, particularly with thioguanine. Additional
hypertension without cirrhosis may be divided into pre- causes include the ingestion of pyrrolizidine alkaloids
hepatic, suprahepatic, and intrahepatic causes. Al- (“bush tea”) or other herbal teas and a familial form of
though the specific lesions vary somewhat in their clini- the disease occurring in congenital immunodeficiency
cal signs and symptoms, the consequences of portal
states.
hypertension are common to all. The acute form of the disease generally occurs in the
A. PREHEPATIC PORTAL HYPERTENSION first month after bone marrow transplantation and is
Prehepatic portal hypertension from acquired abnor- heralded by the triad of weight gain (ascites), tender
malities of the portal and splenic veins accounts for hepatomegaly, and jaundice.
5–8% of cases of gastrointestinal bleeding in children. 3. Congenital hepatic fibrosis—This is a rare autoso-
A history of neonatal omphalitis, sepsis, dehydration, or mal recessive cause of intrahepatic presinusoidal portal
umbilical vein catheterization is present in 30–50% of hypertension (Table 21–7). Liver biopsy is generally di-
patients. Less common causes in older children include agnostic, demonstrating Meyenburg complexes. On an-
local trauma, peritonitis (pyelophlebitis), hypercoagula- giography, the intrahepatic branches of the portal vein
ble states, and pancreatitis. Symptoms may occur be- may be duplicated. Renal abnormalities (microcystic
fore age 1 year, but in most cases the diagnosis is not disease) are often associated with the hepatic lesion;
 Table 21–7. Biliary tract diseases of childhood.

Acute Hydrops Caroli Diseasee

Transient Dilatation Choledochal Cystc Acalculous (Idiopathic Intrahepatic Congenital Hepatic
of Gallbladdera,b (See Figure 20–1.) Cholecystitisd Bile Duct Dilation) Fibrosisf
Predisposing or Premature infants with Congenital lesion. Female Systemic illness, sepsis (Strep- Congenital lesion. Also found Familial (autosomal-recessive)
associated prolonged fasting or sys- sex. Asians. Rarely with tococcus, Salmonella, Kleb- in congenital hepatic fibrosis 25% with autosomal-recessive
conditions temic illness. Hepatitis. Caroli disease or congenital siella, etc), HIV infection. Gall- or with choledochal cyst. polycystic kidney disease. Cho-
Abnormalities of cystic hepatic fibrosis. bladder stasis, obstruction of Female sex. Autosomal-re- ledochal cyst. Caroli’s disease.
duct. Kawasaki disease. cystic duct (stones, nodes, cessive polycystic kidney Meckel–Gruber, Ivemark’s, or
Bacterial sepsis, EBV. tumor). disease. Jeune’s syndrome.
Symptoms Absent in premature Abdominal pain, vomiting, Acute severe abdominal pain, Recurrent abdominal pain, Hematemesis, melena from
infants. Vomiting, abdo- jaundice. vomiting, fever. vomiting. Fever, jaundice bleeding esophageal varices.
minal pain in older chil- when cholangitis occurs.
dren.
Signs Right upper quadrant ab- Icterus, acholic stools, dark Tenderness in mid and right Icterus, hepatomegaly. Hepatosplenomegaly.
dominal mass. Tender- urine in neonatal period. upper abdomen. Occasional
ness in some. Right upper quadrant abdo- palpable mass in right upper
minal mass or tenderness quadrant.
689

in older children.
Laboratory Most are normal. In- Conjugated hyperbilirubine- Elevated WBC count, normal Abnormal LFTs. Increased Low platelet and WBC count (hy-
abnormalities creased WBC count in mia, elevated GGT, slightly or slight abnormality of LFTs. WBC count with cholangitis. persplenism), slight elevation of
sepsis (may be de- increased AST. Elevated Urine abnormalities if asso- AST, GGT. Inability to concen-
creased in premature in- pancreatic serum amylase if ciated with congential hepatic trate urine.
fants). Abnormal LFTs in ampulla hepatopancreatica fibrosis.
hepatitis. is involved.
Diagnostic studies Gallbladder ultrason- Gallbladder ultrasonography Scintigraphy to confirm non- Transhepatic cholangiography, Liver biopsy. Ultrasonography
most useful ography. hepatobiliary scintigraphy, function of gallbladder. Ultra- ERCP, MRCP, scintigraphy, of the liver and kidneys. Upper
ERCP, or MRCP. sonography or abdominal CT ultrasonography, intravenous endoscopy.
scan to rule out other neigh- pyelography.
boring disease.
Treatment Treatment of associated Surgical resection and cho- Broad-spectrum antibiotic Antibiotics and surgical or Treatment of portal hyperten-
condition. Needle or ledochojejunostomy coverage, then cholecystec- endoscopic drainage for sion. Liver/kidney transplanta-
tube cystostomy rarely tomy or cholecystostomy cholangitis. Liver trans- tion for some.
required. Cholecystec- drainage and definitive plantation for some. Lobec-
tomy seldom indicated. surgery 3–4 weeks later. tomy for localized disease.
(continued)
 Table 21–7. Biliary tract diseases of childhood. (continued)

Acute Hydrops Caroli Diseasee

c
Transient Dilatation Choledochal Cyst Acalculous (Idiopathic Intrahepatic Congenital Hepatic
of Gallbladdera,b (See Figure 20–1.) Cholecystitisd Bile Duct Dilation) Fibrosisf
Complications Perforation with bile peri- Progressive biliary cirrhosis. Perforation and bile peritonitis, Sepsis with episodes of cho- Bleeding from varices. Splenic
tonitis rare. Increased incidence of cho- sepsis, abscess or fistula for- langitis, biliary cirrhosis, por- rupture, severe thrombocyto-
langiocarcinoma. Cholangitis mation. Pancreatitis. tal hypertension. Intraductal penia. Progressive renal failure.
in some. stones. Cholangiocarcinoma.
Prognosis Excellent with resolution Depends on anatomic type Good with early diagnosis and Poor, with gradual deteriora- Good in absence of serious renal
of underlying condition. of cyst, associated condition, treatment. tion of liver function. Multiple involvement and with control of
690

Consider cystic duct ob- and success of surgery. Liver surgical drainage procedures portal hypertension. Slightly in-
struction if disorder fails transplantation required in expected. Liver transplanta- creased risk of cholangiocarci-
to resolve. some. tion should alter long-term noma.
prognosis.
Ultrasonography = liver and biliary tract scanning; scintigraphy = hepatobiliary scan using radiolabeled 99mtechnetium; AST = aspartate aminotransferase (SGOT); CT = computed tomogra-
phy; ERCP = endoscopic retrograde cholangiopancreatography; GGT = γ-glutamyl transpeptidase; LFT = liver function tests; MRCP = magnetic resonance cholangiopancreatography; WBC =
white blood count.
a
Crankson S et al: Acute hydrops of the gallbladder in childhood. Eur J Pediatr 1992;151:318 [PMID 9788647].
b
Zulian F et al: Acute surgical abdomen as presenting manifestation of Kawasaki disease. J Pediatr 2003;142:731 [PMID 12838207].
c
deVries JS et al: Choledochal cysts: Age of presentation, symptoms and late complications related to Todani’s classification. J Pediatr Surg 2002;37:1568 [PMID 12407541].
d
Imamoglu M et al: Acute acalculous cholecystitis in children: Diagnosis and treatment, J Pediatr Surg 2002;37:36 [PMID 11781983].
e
Levy AD et al: Careli’s disease: Radiologic spectrum and pathologic correlation. Am J Roentgenol 2002;179:1053 [PMID 12239064].
f
Perisic VN: Long term studies on congenital hepatic fibrosis in children. Acta Paediatr 1995;85:695 [PMID 7670259].
 LIVER & PANCREAS / 691

therefore, renal ultrasonography and urography should sible, confirmation of a normal liver is best obtained by
be routinely performed. liver biopsy.
Doppler-assisted ultrasound scanning of the liver,
4. Other rare causes—Hepatoportal sclerosis (idio- portal vein, splenic vein, inferior vena cava, and hepatic
pathic portal hypertension, noncirrhotic portal fibro- veins may assist in defining the vascular anatomy. In
sis), noncirrhotic nodular transformation of the liver, prehepatic portal hypertension, abnormalities of the
and schistosomal hepatic fibrosis are also rare causes of portal or splenic vein may be apparent, whereas the he-
intrahepatic presinusoidal portal hypertension. patic veins are normal. When noncirrhotic portal hy-
pertension is suspected, angiography often is diagnostic.
Clinical Findings Selective arteriography of the superior mesenteric artery
is recommended prior to surgical shunting to deter-
A. SYMPTOMS AND SIGNS mine the patency of the superior mesenteric vein.
For prehepatic portal hypertension, splenomegaly in an For suprahepatic portal hypertension, an inferior ve-
otherwise well child is the most constant physical sign. nacavogram using catheters from above or below the
Recurrent episodes of abdominal distention resulting suspected obstruction may reveal an intrinsic filling de-
from ascites may also be noted. The usual presenting fect, an infiltrating tumor, or extrinsic compression of
symptoms are hematemesis and melena. the inferior vena cava by an adjacent lesion. A large cau-
The presence of prehepatic portal hypertension is date lobe of the liver suggests Budd–Chiari syndrome.
suggested by the following: (1) an episode of severe Care must be taken in interpreting extrinsic pressure
infection in the newborn period or early infancy—espe- defects of the subdiaphragmatic inferior vena cava if as-
cially omphalitis, sepsis, gastroenteritis, severe dehydra- cites is significant.
tion, or prolonged or difficult umbilical vein catheteri- Simultaneous wedged hepatic vein pressure and he-
zations; (2) no previous evidence of liver disease; (3) a patic venography are useful to demonstrate obstruction
history of well-being prior to onset or recognition of to major hepatic vein ostia and smaller vessels. In the
symptoms; and (4) normal liver size and tests with absence of obstruction, reflux across the sinusoids into
splenomegaly. the portal vein branches can be accomplished. Pressures
Most patients with suprahepatic portal hypertension should also be taken from the right heart and supradi-
present with abdominal pain, tender hepatomegaly of aphragmatic portion of the inferior vena cava to elimi-
acute onset, and abdominal enlargement caused by as- nate constrictive pericarditis and pulmonary hyperten-
cites. Jaundice is present in only 25% of patients. Vom- sion from the differential diagnosis.
iting, hematemesis, and diarrhea are less common. Cu-
taneous signs of chronic liver disease are often absent, as
the obstruction is usually acute. Distended superficial Differential Diagnosis
veins on the back and the anterior abdomen, along with All causes of splenomegaly must be included in the dif-
dependent edema, are seen when inferior vena cava ob- ferential diagnosis. The most common ones are infec-
struction affects hepatic vein outflow. Absence of hepa- tions, immune thrombocytopenic purpura, blood
tojugular reflux (jugular distention when pressure is ap- dyscrasias, lipidosis, reticuloendotheliosis, cirrhosis of
plied to the liver) is a helpful clinical sign. the liver, and cysts or hemangiomas of the spleen.
The symptoms and signs of intrahepatic portal hy- When hematemesis or melena occurs, other causes of
pertension are generally those of cirrhosis (see section gastrointestinal bleeding are possible, such as gastric or
on Cirrhosis). duodenal ulcers, tumors, duplications, and inflammatory
bowel disease.
B. LABORATORY FINDINGS AND IMAGING Because ascites is almost always present in suprahe-
Most other common causes of splenomegaly or he- patic portal hypertension, cirrhosis resulting from any
patosplenomegaly may be excluded by proper labora- cause must be excluded. Other suprahepatic (cardiac,
tory tests. Cultures, Epstein–Barr virus titers, hepatitis pulmonary) causes of portal hypertension must also be
serologies, blood smear examination, bone marrow ruled out. Although ascites may occur in prehepatic
studies, and LFTs may be necessary. In prehepatic por- portal hypertension, it is uncommon.
tal hypertension, LFTs are generally normal. In
Budd–Chiari syndrome and veno-occlusive disease, Complications
mild to moderate hyperbilirubinemia with modest ele-
vations of aminotransferases and prothrombin time are The major manifestation and complication of portal
often present. Hypersplenism with mild leukopenia and hypertension is bleeding esophageal varices. Fatal
thrombocytopenia is often present. Upper endoscopy exsanguination is uncommon, but hypovolemic shock
may reveal varices in symptomatic patients. When pos- or resulting anemia may require prompt treatment. Hy-
692 / CHAPTER 21

persplenism with leukopenia and thrombocytopenia graphic relief of obstruction should be attempted if a
occurs but seldom causes major symptoms. Rupture of defined obstruction of the vessels is apparent. Liver
the enlarged spleen secondary to trauma is always a transplantation should be considered early in the course
threat. Retroperitoneal edema has been reported (Clat- if direct correction is not possible. In most cases, man-
worthy sign). agement of portal hypertension is directed at manage-
Without treatment, complete and persistent hepatic ment of the complications (Table 21–8).
vein obstruction leads to liver failure, coma, and death.
A nonportal type of cirrhosis may develop in the Prognosis
chronic form of hepatic veno-occlusive disease in which
small- and medium-sized hepatic veins are affected. For prehepatic portal hypertension, the prognosis de-
Death from renal failure may occur in rare cases of con- pends on the site of the block, the effectiveness of
genital hepatic fibrosis. variceal eradication, the availability of suitable vessels
for shunting procedures, and the experience of the sur-
geon. Each unsuccessful surgical procedure worsens the
Treatment prognosis. In patients treated by medical means, bleed-
Definitive treatment of noncirrhotic portal hyperten- ing episodes seem to diminish with adolescence.
sion is generally lacking. In prehepatic portal hyperten- The prognosis in patients treated by medical and
sion, the experience with surgical portosystemic shunts supportive therapy may be better than in the surgically
is complicated by a lack of sustained patency in most treated group, especially when surgery is performed at
children younger than age 10 years. Aggressive medical an early age. Portacaval encephalopathy is unusual after
treatment of the complications of prehepatic portal hy- shunting except when protein intake is excessive, but
pertension is the preferred option. Some centers have neurologic outcome may be better in patients who re-
reported good results with shunting procedures, and ceive a mesenterico-left portal bypass when compared
the mesorex shunt is preferred when possible. Veno-oc- with medical management alone.
clusive disease may be prevented somewhat by the pro- The mortality rate of hepatic vein obstruction is very
phylactic use of UCDA prior to conditioning for bone high (95%). In veno-occlusive disease, the prognosis is
marrow transplantation. Withdrawal of the suspected better, with complete recovery possible in 50% of acute
offending agent, if possible, may increase the chance of forms and 5–10% of subacute forms.
recovery. For suprahepatic portal hypertension, efforts
should be directed at determining the underlying cause Brown RS Jr, Lake JR: Transjugular intrahepatic portosystemic
and correction, if possible. Either surgical or angio- shunt as a form of treatment for portal hypertension: Indica-

Table 21–8. Treatment of complications of portal hypertension.

Complication Diagnosis Treatment

Bleeding esophageal varices Endoscopic verification Endosclerosis or variceal band ligation. Octreotide, 30 µg/m2/h intra-
of variceal bleeding venous. Pediatric Sengstaken–Blakemore tube. Surgical variceal liga-
tion, selective venous embolization, TIPS, OLT. Propranolol may be
useful to prevent recurrent bleeding.
Ascites Clinical examination Sodium restriction (1–2 mEq/kg/d), spironolactone (3–5 mg/kg/d), fur-
(fluid wave, shifting osemide (1–2 mg/kg/d), intravenous albumin (0.5–1 g/kg per dose),
dullness), abdominal paracentesis, peritoneovenous (LeVeen) shunt, TIPS, surgical porto-
ultrasonography systemic shunt, OLT.a
Hepatic encephalopathy Abnormal neurologic Protein restriction (0.5–1 g/kg/d), intravenous glucose (6–8 mg/kg/min),
examination, elevated neomycin (2–4 g/m2 BSA PO in 4 doses), lactulose (1 mL/kg per dose [up
plasma ammonia to 30 mL] every 4–6 h PO), plasmapheresis, hemodialysis, OLT.a
Hypersplenism Low WBC count, plate- No intervention, partial splenic embolization, TIPS, surgical portosys-
lets, and/or hemoglobin. temic shunt, OLT. Splenectomy may worsen variceal bleeding.
Splenomegaly.
a
In order of sequential management.
TIPS = transjugular intrahepatic portosystemic shunt, OLT = orthotopic liver transplantation, BSA = body surface area, WBC = white blood
cell.
 LIVER & PANCREAS / 693

tions and contraindications. Adv Intern Med 1997;42: patients, gallbladder dysfunction is associated with bil-
485 [PMID: 9048128]. iary sludge formation, which may evolve into “sludge
Carreras E et al: Hepatic veno-occlusive disease after bone marrow balls” or tumefaction bile and then into gallstones. The
transplant. Blood Rev 1993;7:43[PMID: 8467232]. process is reversible in many patients.
Dhiman RK et al: Non-cirrhotic portal fibrosis (idiopathic portal
hypertension): Experience with 151 patients and a review of
the literature. J Gastroenterol Hepatol 2002;17:6 [PMID Clinical Findings
11895549].
Dilawari JB et al: Hepatic outflow obstruction (Budd–Chiari syn-
A. HISTORY
drome): Experience with 177 patients and a review of the lit- Most symptomatic gallstones are associated with acute
erature. Medicine 1994;73:21[PMID: 8309360]. or recurrent episodes of moderate to severe, sharp right
Fuchs J et al: Mesenterico-left portal vein bypass in children with upper quadrant or epigastric pain. The pain may radi-
congenital extrahepatic portal vein thrombosis: A unique cu- ate substernally or to the right shoulder. On rare occa-
rative approach. J Pediatr Gastroenterol Nutr 2003;36:213 sions, the presentation may include a history of jaun-
[PMID 12548056].
dice, back pain, or generalized abdominal discomfort,
Hassall E: Nonsurgical treatments for portal hypertension in chil-
dren. Gastrointest Endosc Clin North Am 1994;4:223
when it is associated with pancreatitis, suggesting stone
[PMID: 8137016]. impaction in the common duct or ampulla hepatopan-
McKiernan PJ: Treatment of variceal bleeding. Gastrointest Endosc creatica. Nausea and vomiting may occur during at-
Clin North Am 2001;11:789 [PMID 11689366]. tacks. Pain episodes often occur postprandially, espe-
Price MR et al: Management of esophageal varices in children by cially after ingestion of fatty foods. The groups at risk
endoscopic variceal ligation. J Pediatr Surg 1996;31: for gallstones include patients with known or suspected
1056[PMID: 8863233]. hemolytic disease; females; teenagers with prior preg-
Ryckman FC, Alonso MH: Causes and management of portal hy- nancy; obese individuals; certain racial or ethnic
pertension in the pediatric population. Clin Liver Dis groups, particularly Native Americans (Pima Indians)
2001;5:789 [PMID 11565141]. and Hispanics; infants and children with ileal disease
Shun A et al: Portosystemic shunting for paediatric portal hyper- (Crohn disease) or prior ileal resection; and patients
tension. J Pediatr Surg 1997;32:489[PMID: 9094025].
with cystic fibrosis or Wilson disease. Infants on pro-
Vogelsang GB, Dalal J: Hepatic venoocclusive disease in blood and longed parenteral hyperalimentation are at particular
bone marrow transplantation in children: Incidence, risk fac-
tors and outcome. J Pediatr Hematol Oncol 2002;24:746 risk for gallstone formation. Other, less certain risk fac-
[PMID 12468908]. tors include a positive family history, use of birth con-
trol pills, and diabetes mellitus.
BILIARY TRACT DISEASE B. SYMPTOMS AND SIGNS
During acute episodes of pain, tenderness is present in
1. Cholelithiasis the right upper quadrant or epigastrium, with a positive
inspiratory arrest (Murphy sign), usually without peri-
ESSENTIALS OF DIAGNOSIS toneal signs. If present, scleral icterus is helpful. Evi-
dence of underlying hemolytic disease in addition to
& TYPICAL FEATURES icterus may include pallor (anemia), splenomegaly,
tachycardia, and high-output cardiac murmur. Fever is
• Episodic right upper quadrant abdominal pain. unusual in uncomplicated cases.
• Elevated bilirubin, alkaline phosphatase, and GGT
C. LABORATORY FINDINGS
• Stones or sludge seen on abdominal ultrasound.
Laboratory tests are usually normal unless calculi have
lodged in the extrahepatic biliary system, in which case
the serum bilirubin and GGT (or alkaline phosphatase)
may be elevated. Amylase and lipase levels may be in-
General Considerations creased if stone obstruction occurs at the ampulla he-
patopancreatica.
Gallstones may develop at all ages in the pediatric pop-
ulation and in utero. Gallstones may be divided into D. IMAGING
cholesterol stones, which contain more than 50% cho- Ultrasound evaluation is the best imaging technique,
lesterol, and pigment stones, black (sterile bile) and showing abnormal intraluminal contents (stones,
brown (infected bile). Pigment stones predominate in sludge) as well as anatomic alterations of the gallbladder
the first decade of life, while cholesterol stones account or dilation of the biliary ductal system. The presence of
for up to 90% of gallstones in adolescence. For some an anechoic acoustic shadow differentiates calculi from
694 / CHAPTER 21

intraluminal sludge or sludge balls. Ceftriaxone may Prognosis

cause similar findings. Plain abdominal radiographs will
show calculi with a high calcium content in the region The prognosis is excellent in uncomplicated cases that
of the gallbladder in up to 15% of patients. Lack of vi- come to standard cholecystectomy.
sualization of the gallbladder with hepatobiliary scintig-
Burch Bruch SW et al: The management of nonpigmented gall-
raphy suggests chronic cholecystitis. In selected cases, stones in children. J Pediatr Surg 2000;35:729 [PMID:
ERCP or MRCP may be helpful in defining subtle ab- 10813336].
normalities of the bile ducts and locating intraductal Holcomb GW III et al; Laparoscopic cholecystectomy in children:
stones. Lessons learned from the first 100 patients. J Pediatr Surg
1999;34:1236 [PMID: 10466603].
Lobe, TE: Cholelithiasis and cholecystitis in children. Semin Pedi-
Differential Diagnosis atr Surg 2000;9:170 [PMID: 11112834].
Miltenburg DM et al: Changing indications for pediatric cholecys-
Other abnormal conditions of the biliary system with tectomy. Pediatrics 2000;105:1250 [PMID: 10835065].
similar presentation are summarized in Table 21–7. Zitsman JL: Current concepts in minimal access surgery for chil-
Liver disease (hepatitis, abscess, tumor) can cause simi- dren. Pediatrics 2003;111:1239 [PMID: 12777537].
lar symptoms or signs. Peptic disease, reflux esophagitis,
paraesophageal hiatal hernia, cardiac disease, and pneu- 2. Primary Sclerosing Cholangitis
momediastinum must be considered when the pain is
epigastric or substernal in location. Renal or pancreatic
disease is a possible explanation if the pain is localized ESSENTIALS OF DIAGNOSIS
to the right flank or mid back. Subcapsular or supra- & TYPICAL FEATURES
capsular lesions of the liver (abscess, tumor, hematoma)
or right lower lobe infiltrate may also be a cause of non-
traumatic right shoulder pain. • Pruritus and jaundice.
• Elevated GGT.
• Associated with inflammatory bowel disease.
Complications • Abnormal ERCP or MRCP.
Major problems are related to stone impaction in either
the cystic or common duct and lead to stricture forma-
tion or perforation. Acute distention and subsequent
perforation of the gallbladder may occur when gall- General Considerations
stones cause obstruction of the cystic duct. Stones im-
pacted at the level of the ampulla hepatopancreatica Primary sclerosing cholangitis (PSC) is a progressive liver
often cause gallstone pancreatitis. disease of unknown cause, characterized by chronic in-
flammation and fibrosis of the intra- or extrahepatic bile
ducts (or both), with eventual obliteration of peripheral
Treatment bile ducts, cholangiographic evidence of strictures, and
dilation of all or parts of the biliary tree. PSC is more
Symptomatic cholelithiasis is best treated by either common in males with inflammatory bowel disease, par-
open or laparoscopic cholecystectomy. Intraoperative ticularly ulcerative colitis. It can also be seen with histio-
cholangiography via the cystic duct is required so that cytosis X, sicca syndromes, congenital and acquired im-
the physician can be certain the ductal system is free of munodeficiency syndromes, and cystic fibrosis.
retained stones. Calculi in the extrahepatic bile ducts
may be removed by ERCP, sphincterotomy, and bal- Clinical Findings
loon extraction.
Gallstones developing in premature infants on total A. SYMPTOMS AND SIGNS
parenteral nutrition can be followed by ultrasound ex- PSC often has an insidious onset. Clinical symptoms may
amination. Most of the infants are asymptomatic, and include abdominal pain, fatigue, pruritus, and jaundice.
the stones will resolve in 3–36 months. Gallstone disso- Acholic stools and steatorrhea can occur. Physical find-
lution using cholelitholytics (UCDA) or mechanical ings include hepatomegaly, splenomegaly, and jaundice.
means (lithotripsy) has not been approved for use in
children. Asymptomatic gallstones do not usually re- B. LABORATORY FINDINGS
quire treatment, as less than 20% will eventually cause The earliest finding may be asymptomatic elevation of
problems. the GGT. Subsequent laboratory abnormalities include
 LIVER & PANCREAS / 695

elevated levels of alkaline phosphatase and bile acids. Wilschanske M et al: Primary sclerosing cholangitis in 32 children:
Later, cholestatic jaundice and elevated AST and ALT Clinical, laboratory, and radiographic features, with survival
analysis. Hepatology 1995;22:1415 [PMID: 7590657].
may occur. Patients with associated inflammatory
bowel disease often test positive for perinuclear anti-
neutrophil cytoplasmic antibodies (pANCA). Other 3. Other Biliary Tract Disorders
markers of autoimmune liver disease (antinuclear anti-
bodies and antismooth muscle antibody) are often For a schematic representation of the various types of
found but are not specific for PSC. Sclerosing cholangi- choledochal cysts, see Figure 21–1. For summary infor-
tis due to cryptosporidia is common in immunodefi- mation on acute hydrops, choledochal cyst, acalculous
ciency syndromes. cholecystitis, Caroli disease, and congenital hepatic fi-
brosis, see Table 21–7.
C. RADIOLOGIC FINDINGS
Ultrasound may show dilated intrahepatic bile ducts
behind strictures. ERCP or MRCP is the diagnostic PYOGENIC & AMEBIC LIVER ABSCESS
study of choice, demonstrating irregularities of the bil-
iary tree. ESSENTIALS OF DIAGNOSIS
& TYPICAL FEATURES
Differential Diagnosis
The differential diagnosis includes infectious hepatitis, • Fever and painful enlarged liver.
secondary cholangitis, autoimmune hepatitis, metabolic • Ultrasound of liver demonstrating an abscess.
liver disease, cystic fibrosis, choledochal cyst, or other
anomalies of the biliary tree, including Caroli disease • Positive serum ameba antigen titer or positive
and congenital hepatic fibrosis. bacterial culture of abscess fluid.

Complications
Complications include secondary bacterial cholangitis,
pancreatitis, biliary fibrosis, and cirrhosis. Progression
TYPE FINDINGS
to liver failure is common and the risk of cholangiocar-
cinoma is higher in PSC. l Spherical dilatation of the common duct
GB
Treatment CBD

No completely effective treatment is available. Patients ll Congenital diverticulum of the common

with early disease may benefit from high-dose UCDA bile duct
(20 mg/kg/d). Patients with autoimmune markers may
benefit from treatment with corticosteroids and aza-
thioprine. Antibiotic treatment of cholangitis and dila- lll Intraduodenal diverticulum of the
tion and stenting of dominant bile duct strictures can common bile duct
reduce symptoms. (choledochocele)

Prognosis lVa Multiple intrahepatic communicating

cysts
The majority of patients will eventually require liver (Caroli disease)
transplantation; however, the course of the disease may
be 10–20 years.
lVb Mixed extrahepatic and intrahepatic
fusiform or cystic dilation (possibly
Gilger MA et al: Efficacy of ursodeoxycholic acid in the treatment variants of Caroli disease, congenital
of primary sclerosing cholangitis in children. J Pediatr Gas- hepatic fibrosis)
troenterol Nutr 2000;31:136 [PMID: 10941964].
Gregorio GV et al: Autoimmune hepatitis/sclerosing cholangitis Figure 21–1. Classification of cystic dilation of the
overlap syndrome in childhood: A 16-year prospective study.
Hepatology 2001;33:544 [PMID: 11230733]. bile ducts. Types I, II, and III are extrahepatic chole-
Mieli-Vergani G, Vergani D: Sclerosing cholangitis in the paedi- dochal cysts. Type IVa is solely intrahepatic, and type
atric patient. Best Pract Res Clin Gastroenterol 2001;15:681 IVb is both intrahepatic and extrahepatic. GB = gall-
[PMID: 11492976]. bladder; CBD = common bile duct.
696 / CHAPTER 21

General Considerations amebic liver disease) and the prompt response of the
latter to antiamebic therapy (metronidazole). Examina-
Pyogenic liver abscesses are often caused by intestinal tion of material obtained by needle aspiration of the ab-
bacteria seeded via the portal vein from infected viscera scess using ultrasound guidance is often diagnostic.
and occasionally from ascending cholangitis or gan-
grenous cholecystitis. Blood cultures are positive in up
to 60% of patients. The resulting lesion tends to be Differential Diagnosis
solitary and located in the right hepatic lobe. Bacterial Hepatitis, hepatoma, hydatid cyst, gallbladder disease,
seeding may also occur from infected burns, pyoder- or biliary tract infections can mimic liver abscess. Sub-
mas, and osteomyelitis. Unusual causes include om- phrenic abscesses, empyema, and pneumonia may give
phalitis, subacute infective endocarditis, pyelonephritis, a similar picture. Inflammatory disease of the intestines
Crohn disease, and perinephric abscess. In immuno- or of the biliary system may be complicated by liver ab-
compromised patients, S aureus, gram-negative organ- scess.
isms, and fungi may seed the liver from the arterial sys-
tem. Multiple pyogenic liver abscesses are associated Complications
with severe sepsis. Children receiving anti-inflammato-
ry and immunosuppressive agents and children with Spontaneous rupture of the abscess may occur with ex-
defects in white blood cell function (chronic granulo- tension of infection into the subphrenic space, thorax,
matous disease) are prone to pyogenic hepatic abscesses, peritoneal cavity, and, occasionally, the pericardium.
especially those caused by S aureus. Bronchopleural fistula with large sputum production
Amebic liver abscess is rare in children. An increased and hemoptysis can develop in severe cases. Simultane-
risk is associated with travel through areas of endemic ously, the amebic liver abscess may be secondarily in-
infection (Mexico, Southeast Asia). Entamoeba histolyt- fected with bacteria (in 10–20% of patients). Metasta-
ica invasion occurs via the large bowel, although a his- tic hematogenous spread to the lungs and the brain has
tory of diarrhea (colitis-like picture) is not always ob- been reported.
tained.
Treatment
Clinical Findings Ultrasound- or CT-guided percutaneous needle aspira-
tion for aerobic and anaerobic culture with simultane-
With pyogenic liver abscess, nonspecific complaints of ous placement of a catheter for drainage, combined
fever, chills, malaise, and abdominal pain are frequent. with appropriate antibiotic therapy, is the treatment of
Weight loss is very common, especially in delayed diag- choice for solitary pyogenic liver abscess. Multiple liver
nosis. A few patients have shaking chills and jaundice. abscesses may also be treated successfully by this
The dominant complaint is a constant dull pain over an method. Surgical intervention may be indicated if rup-
enlarged liver that is tender to palpation. An elevated ture occurs outside the capsule of the liver or if entero-
hemidiaphragm with reduced or absent respiratory ex- hepatic fistulae are suspected.
cursion may be demonstrated on physical examination Amebic abscesses in uncomplicated cases should be
and confirmed by fluoroscopy. Laboratory studies show treated promptly with oral metronidazole, 35–50
leukocytosis and, at times, anemia. LFTs may be nor- mg/kg/d, in three divided doses for 10 days. Intra-
mal or reveal mild elevation of transaminases and alka- venous metronidazole can be used for patients unable
line phosphatase. Amebic liver abscesses are usually her- to take oral medication. Failure to improve after
alded by an acute illness with high fever, chills, and 72 hours of drug therapy suggests superimposed bacter-
leukocytosis. Early in the course, liver tests may suggest ial infection or an incorrect diagnosis. At this point,
mild hepatitis. An occasional prodrome may include needle aspiration or surgical drainage is indicated. Once
cough, dyspnea, and shoulder pain as rupture of the ab- oral feedings can be tolerated, a 20-day course of
scess into the right chest occurs. Consolidation of the iodoquinol (30 mg/kg/d in three doses) is started as a
right lower lobe is common (10–30% of patients). luminal amebicide. Resolution of the abscess cavity oc-
Ultrasound liver scan is the most useful diagnostic curs over 3–6 months.
aid in evaluating pyogenic and amebic abscesses, detect-
ing lesions as small as 1–2 cm. Nuclear scanning with Prognosis
gallium or technetium sulfur colloid or CT imaging
may be useful in differentiating tumor or hydatid cyst. An unrecognized and untreated pyogenic liver abscess is
The distinction between pyogenic and amebic ab- universally fatal. With drainage and antibiotics, the
scesses is best made by indirect hemagglutination test cure rate is about 90%. Most amebic abscesses are
(which is positive in more than 95% of patients with cured with conservative medical management; the mor-
 LIVER & PANCREAS / 697

tality rate is less than 3%. If extrahepatic complications patients receiving androgens for treatment of Fanconi
occur (empyema, bronchopleural fistula, pericardial syndrome and aplastic anemia must also be kept in
complications), 10–15% of patients will succumb. mind. The use of anabolic steroids by body-conscious
adolescents poses a risk of hepatic neoplasia. An inter-
Kumar A et al: Pyogenic liver abscess in children—South Indian esting aspect of primary epithelial neoplasms of the
experiences. J Pediatr Surg 1998;33:417 [PMID 9537550]. liver has been the increased incidence of associated
Moazam F, Nazir Z: Amebic liver abscess: Spare the knife but save anomalies and endocrine abnormalities. Virilization has
the child. J Pediatr Surg 1998;33:119 [PMID: 9473115]. been reported as a consequence of gonadotropin activ-
Rajak CL et al: Percutaneous drainage of liver abscesses: Needle as- ity of the tumor. Feminization with bilateral gyneco-
piration versus catheter drainage. AJR Am J Roentgenol mastia may occur in association with high estradiol lev-
1998;170:1035 [PMID 9530055]. els in the blood, the latter a consequence of increased
Stanley SL: Amoebiasis. Lancet 2003;361:1025 [PMID 12700377]. aromatization of circulating androgens by the liver.
Leydig cell hyperplasia without spermatogenesis is
HEPATOMA found on testicular biopsy. Hemihypertrophy, congeni-
tal absence of the kidney, macroglossia, and Meckel di-
verticulum have been found in association with hepato-
ESSENTIALS OF DIAGNOSIS carcinoma.
& TYPICAL FEATURES
Clinical Findings
• Abdominal enlargement and pain, weight loss, A noticeable increase in abdominal girth with or with-
anemia. out pain is the most constant feature of the history. A
• Hepatomegaly with or without a definable mass. parent may note a bulge in the upper abdomen or re-
port feeling a hard mass. Constitutional symptoms (eg,
• Mass lesion on imaging studies.
anorexia, fatigue, fever, chills) may be present. Teenage
• Laparotomy and tissue biopsy. boys may complain of gynecomastia.
A. SYMPTOMS AND SIGNS
Weight loss, pallor, and abdominal pain associated with
a large abdomen are common. Physical examination re-
General Considerations veals hepatomegaly with or without a definite tumor
Primary epithelial neoplasms of the liver represent mass, usually to the right of the midline. In the absence
0.2–5.8% of all malignant conditions in children. After of cirrhosis, signs of chronic liver disease are usually ab-
Wilms’ tumor and neuroblastoma, hepatomas are the sent. However, evidence of virilization or feminization
third most common intra-abdominal cancer. The inci- in prepubertal children may be noted.
dence is higher in Southeast Asia, where childhood cir- B. LABORATORY FINDINGS
rhosis is more common. There are two basic morpho- Normal LFTs are the rule. Anemia frequently occurs,
logic types with certain clinical and prognostic especially in cases of hepatoblastoma. Cystathioninuria
differences. Hepatoblastoma predominates in male in- has been reported. α-Fetoprotein levels are often ele-
fants and children and accounts for 79% of liver cancer vated, especially in hepatoblastoma. Estradiol levels are
in children, with most cases appearing before age sometimes elevated. Final tissue diagnosis is best ob-
5 years. There is an increased risk of hepatoblastoma in tained at laparotomy, although ultrasound- or CT-
Beckwith–Wiedemann syndrome, hemihypertrophy, guided needle biopsy of the liver mass can be used.
familial adenomatosis polyposis coli, and in premature
or low-birth-weight infants. Most lesions are found in C. IMAGING
the right lobe of the liver. Pathologic differentiation Ultrasonography, CT, and MRI are useful for diagnosis
from hepatocarcinoma may be difficult. Hepatocarci- and for following tumor response to therapy. A scinti-
noma, the other major malignant tumor of the liver, graphic study of bone and lung and selective angiogra-
occurs more frequently after age 3 years. This type of phy are generally part of the preoperative work-up to
neoplasm carries a poorer prognosis than hepatoblas- evaluate metastatic disease.
toma and causes more abdominal discomfort. Patients
with chronic HBV or HCV infection, cirrhosis, glyco-
gen storage disease type I, tyrosinemia, or α1-anti-
Differential Diagnosis
trypsin deficiency have an increased risk for hepatocel- In the absence of a palpable mass, the differential diag-
lular carcinoma. The late development of hepatoma in nosis is that of hepatomegaly with or without anemia or
698 / CHAPTER 21

jaundice. Hematologic and nutritional conditions Dower NA, Smith LJ: Liver transplantation for malignant liver tu-
should be ruled out, as well as HBV and HCV infec- mors in children. Med Pediatr Oncol 2000;34:136 PMID
10657876.
tion, α1-antitrypsin deficiency disease, lipid storage dis-
eases, histiocytosis X, glycogen storage disease, tyrosine- Herzog CE et al: Childhood cancers: Hepatoblastoma. Oncologist
2000;5:445 [PMID 11110595].
mia, congenital hepatic fibrosis, cysts, adenoma, focal
Newman KD: Hepatic tumors in children. Semin Pediatr Surg
nodular hyperplasia, inflammatory pseudotumor, and 1997;6:38 [PMID:9117273 ].
hemangiomas. If fever is present, hepatic abscess (pyo- Raney B: Hepatoblastoma in children: A review. J Pediatr Hematol
genic or amebic) must be considered. Veno-occlusive Oncol 1997;19:418 [PMID: 9329462].
disease and hepatic vein thrombosis are rare possibili- Reynolds M: Pediatric liver tumors. Semin Surg Oncol 1999;16:
ties. Tumors in the left lobe may be mistaken for pan- 159.
creatic pseudocysts. Stringer MD: Liver tumors. Semin Pediatr Surg 2000;9:196
[PMID 11112837].
Complications
Progressive enlargement of the tumor, abdominal dis- LIVER TRANSPLANTATION
comfort, ascites, respiratory difficulty, and widespread Orthotopic liver transplantation is no longer experi-
metastases (especially to the lungs and the abdominal mental. Children with end-stage liver disease, acute ful-
lymph nodes) are the rule. Rupture of the neoplastic minant hepatic failure, or complications from meta-
liver and intraperitoneal hemorrhage have been re- bolic liver disorders should be considered for liver
ported. Progressive anemia and emaciation predispose transplantation. Recent advances in immunosuppres-
the patient to an early septic death. sion (eg, cyclosporine and tacrolimus, use of mono-
clonal antibodies against T cells, introduction of my-
Treatment cophenolate mofetil and sirolimus), better candidate
selection, improvements in surgical techniques, and ex-
An aggressive surgical approach has resulted in the only
perience in postoperative management have con-
long-term survivals. Complete resection of the lesion
tributed to improved results.
offers the only chance for cure. It appears that every iso-
The major indications for childhood transplantation
lated lung metastasis should also be surgically resected.
are
Radiotherapy and chemotherapy have been disappoint-
ing in the treatment of primary liver neoplasms, al- 1. A failed Kasai operation or decompensated cirrho-
though new combinations of drugs are continually sis caused by biliary atresia
being evaluated. These modalities are also used for ini- 2. α1-Antitrypsin deficiency
tial cytoreduction of tumors found to be unresectable at
3. Posthepatitic (autoimmune chronic active hepati-
the time of primary surgery. Second-look celiotomy
tis, hepatitis B or C disease) cirrhosis
has, in some cases, allowed resection of the tumor, re-
sulting in a reduced mortality rate. Liver transplanta- 4. Tyrosinemia
tion has been disappointing but continues to be per- 5. Crigler–Najjar syndrome type I
formed in selected patients. The survival rate may be 6. Wilson disease
better for those patients in whom the tumor is inciden- 7. Acute fulminant hepatic failure when recovery is
tal to another disorder (tyrosinemia, biliary atresia, cir- unlikely
rhosis). In HBV-endemic areas, childhood HBV vacci- 8. Primary sclerosing cholangitis
nation has reduced the incidence of hepatocellular
carcinoma. 9. Hepatic-based malignancies
10. Cases in which the consequences of chronic
Prognosis cholestasis severely impair the patient’s quality of
life.
The survival rate if the tumor is completely removed is
90% for hepatoblastoma and 33% for hepatocellular Children should be referred early for evaluation be-
carcinoma. Fibrolamellar oncocytic hepatocarcinoma cause the limiting factor for success is the small donor
has a more favorable prognosis. The overall survival and pool. Pared-down adult livers, organs from living re-
cure rate is less than 20%. If metastases are present, sur- lated donors, and split adult donor livers are being used
vival is reduced to 30% for hepatoblastoma. in children in many centers. Ten percent of recipients
require retransplantation. In general, 75–85% of chil-
Chang MH et al: Universal hepatitis B vaccination in Taiwan and dren survive at least 2–5 years after transplantation,
the incidence of hepatocellular carcinoma in children. N Engl with long-term survival expected to be comparable.
J Med 1997;336:1855 [PMID: 9197213]. Lifetime immunosuppression therapy using combina-
 LIVER & PANCREAS / 699

tions of cyclosporine, tacrolimus, prednisone, or aza- stones, choledochal cyst, tumors of the duodenum,
thioprine, with its incumbent risks, is necessary to pre- pancreas divisum, and ascariasis. Acute pancreatitis has
vent rejection. The overall quality of life for children been seen following treatment with sulfasalazine, thi-
with a transplanted liver appears to be excellent. The azides, valproic acid, azathioprine, mercaptopurine, as-
lifelong risk of Epstein–Barr virus-induced lymphopro- paraginase, antiretroviral drugs (especially ddI), high-
liferative disease is approximately 5% and is related to dose corticosteroids, and other drugs. It may also occur
age and EBV exposure status at time of transplant and in cystic fibrosis, systemic lupus erythematosus, α1-an-
intensity of immunosuppression. Various protocols are titrypsin deficiency, diabetes mellitus, Crohn disease,
being tested for prevention and treatment of lympho- glycogen storage disease type I, hyperlipidemia types I
proliferative disease. and V, hyperparathyroidism, Henoch–Schönlein pur-
pura, Reye syndrome, organic acidopathies, Kawasaki
Bucuvalas JC et al: Health-related quality of life in pediatric liver disease, or chronic renal failure; during rapid refeeding
transplant recipients: A single-center study. Liver Transpl in cases of malnutrition; and in familial cases. Alcohol-
2003;9(1):62 [PMID: 12514775]. induced pancreatitis should be considered in the
Diem HV et al: Pediatric liver transplantation for biliary atresia: teenage patient.
Results of primary grafts in 328 recipients. Transplantation
2003;75(10):1692 [PMID: 12777858].
Holmes RD, Sokol RJ: Epstein–Barr virus and post-transplant lym- Clinical Findings
phoproliferative disease. Pediatr Transplant 2002;6(6):456 A. SYMPTOMS AND SIGNS
[PMID: 12453197].
Inomata Y et al: Living donor liver transplantation: An 8-year expe- An acute onset of persistent (hours to days), moderate
rience with 379 consecutive cases. Transplant Proc 1999;31: to severe upper abdominal and midabdominal pain oc-
381 [PMID: 10083152]. casionally referred to the back, and vomiting, is the
Krull K et al: Neurocognitive outcome in pediatric liver transplant common presenting picture. The abdomen is tender
recipients. Pediatr Transplant 2003;7(2):111 [PMID: but not rigid, and bowel sounds are diminished, sug-
12654051] gesting peritoneal irritation. Abdominal distention is
Miller CM et al: One hundred nine living donor liver transplants common in infants and younger children. Jaundice is
in adults and children: A single center experience. Ann Surg unusual. Ascites may be noted, and a left-sided pleural
2001;234:301 [PMID: 11524583].
effusion is present in some patients. Periumbilical and
flank bruising indicate hemorrhagic pancreatitis.
B. LABORATORY FINDINGS
PANCREAS
Leukocytosis and an elevated serum amylase (>3 times
normal) should be expected early, except in infants
ACUTE PANCREATITIS younger than age 6 months who may have hypoamy-
lasemia. Serum lipase is elevated and persists longer
than serum amylase. The immunoreactive trypsinogen
ESSENTIALS OF DIAGNOSIS test may also be of value. Pancreatic amylase isoenzyme
determination can help differentiate nonpancreatic
& TYPICAL FEATURES causes (eg, salivary, intestinal, tubo-ovarian) of serum
amylase elevation. Hyperglycemia (serum glucose >
• Epigastric abdominal pain radiating to the back. 300 mg/dL), hypocalcemia, falling hematocrit, rising
• Nausea and vomiting. blood urea nitrogen, hypoxemia, and acidosis may all
• Elevated serum amylase and lipase. occur in severe cases and imply a poor prognosis.
• Evidence of pancreatic inflammation by CT or ul- C. IMAGING
trasound. Plain radiographic films of the abdomen may show a
localized ileus (sentinel loop). Ultrasonography shows
decreased echodensity of the gland in comparison with
the left lobe of the liver. Pseudocyst formation can also
be seen early in the course. CT scanning is better for
General Considerations detecting pancreatic phlegmon, or abscess formation.
Most cases of acute pancreatitis are the result of drugs, ERCP or MRCP may be useful in confirming patency
viral infections, systemic diseases, abdominal trauma, or of the main pancreatic duct in cases of abdominal
obstruction of pancreatic flow. More than 20% are id- trauma; in recurrent acute pancreatitis; or in revealing
iopathic. Causes of pancreatic obstruction include stones, ductal strictures, and pancreas divisum.
700 / CHAPTER 21

Differential Diagnosis rate is 5–10% in patients treated by operation and 1%

in those treated medically. The morbidity rate is high
Other causes of acute upper abdominal pain include le- with surgery as a result of fistula formation.
sions of the stomach, duodenum, liver, and biliary sys-
tem; acute gastroenteritis or atypical appendicitis; Jackson WD: Pancreatitis: Etiology, diagnosis, and management.
pneumonia; volvulus; intussusception; and nonacciden- Curr Opin Pediatr 2001;13:447 [PMID: 11801891].
tal trauma. Pietzak MM, Thomas DW: Pancreatitis in childhood. Pediatr Rev
2000;21:406 [PMID: 11121497].
Complications
Complications early in the disease include shock, fluid CHRONIC PANCREATITIS
and electrolyte disturbances, ileus, acute respiratory dis- Chronic pancreatitis is differentiated from acute pan-
tress syndrome, and hypocalcemic tetany. Hyperv- creatitis in that the pancreas remains structurally or
olemia is seen between the third and fifth days, at functionally abnormal after an attack.
which time renal tubular necrosis may occur. The gas- The causes are multiple and can be divided into
trointestinal, neurologic, musculoskeletal, hepatobil- toxic-metabolic (eg, alcohol, chronic renal failure, hy-
iary, dermatologic, and hematologic systems may also percalcemia), idiopathic, genetic, autoimmune, recur-
be involved. rent and severe acute pancreatitis, and obstructive pan-
Later, 5–20% of patients develop a pseudocyst her- creatitis (eg, pancreas divisum, choledochal cyst).
alded by recurrence of abdominal pain and rise in the
serum amylase. Up to 60–70% of these pseudocysts will Clinical Findings
resolve spontaneously. Infection, hemorrhage, rupture,
or fistulization may occur. Phlegmon formation is com- The diagnosis often is delayed by the nonspecific symp-
mon and may extend from the gland into the retroperi- toms and the lack of persistent laboratory abnormali-
toneum or into the lesser sac. Most regress, but some re- ties.
quire drainage. Infection in this inflammatory mass is a
constant threat. Pancreatic abscess formation is rare A. SYMPTOMS AND SIGNS
(3–5%) and develops 2–3 weeks after the initial insult. There is usually a history of recurrent upper abdominal
Fever, leukocytosis, and pain suggest this complication; pain of variable severity but prolonged duration. Radia-
diagnosis is made by ultrasound or CT scanning. tion of the pain into the back is a frequent complaint.
Chronic pancreatitis, exocrine or endocrine pancre- Fever and vomiting are not common. Steatorrhea and
atic insufficiency, and pancreatic lithiasis are rare seque- symptoms of diabetes may develop later in the course,
lae of acute pancreatitis. and malnutrition secondary to failure of pancreatic ex-
ocrine secretions may also occur.
Treatment B. LABORATORY FINDINGS
Medical management includes rest, gastric suction, flu- Serum amylase and lipase levels are usually elevated
ids, electrolyte replacement, and blood or colloid as during early acute attacks but are often normal later.
needed. Pain should be controlled with opioids. Oxy- Pancreatic insufficiency and reduced volume and bicar-
gen may be required if desaturation occurs. Acid sup- bonate response may be found at pancreatic stimulation
pression may be helpful. Nutrition is provided by the testing or by determination of fecal pancreatic elastase
parenteral or enteral (jejunal) route. Broad-spectrum 1. Mutations of the cationic trypsinogen gene, the pan-
antibiotic coverage is useful only in necrotizing pancre- creatic secretory trypsin inhibitor, and the cystic fibrosis
atitis. Drugs known to produce acute pancreatitis transmembrane conductance regulator gene (CFTR)
should be discontinued. are associated with recurrent acute and chronic pancre-
Surgical treatment is reserved for traumatic disrup- atitis. Elevated blood glucose and glycohemoglobin lev-
tion of the gland, intraductal stone, other anatomic ob- els and glycosuria frequently occur in protracted dis-
structive lesions, and unresolved or infected pseudocysts ease. Sweat chloride should be checked for cystic
or abscesses. Early endoscopic decompression of the bil- fibrosis and serum calcium for hyperparathyroidism.
iary system reduces the morbidity associated with pan-
creatitis caused by obstruction of the common bile duct.
C. IMAGING
Radiographs of the abdomen may show pancreatic cal-
Prognosis cifications in up to 30% of patients. Ultrasound or CT
examination demonstrates pancreatic enlargement,
In the pediatric age group, the prognosis is surprisingly ductal dilation, and calculi in up to 80%. CT is the ini-
good with conservative management. The mortality tial imaging procedure of choice. ERCP can show duc-
 LIVER & PANCREAS / 701

tal dilation, stones, strictures, or stenotic segments. The GASTROINTESTINAL & HEPATOBILIARY
use of endoscopic ultrasound and MRCP in the diag- MANIFESTATIONS OF CYSTIC FIBROSIS
nosis and staging of chronic pancreatitis is being evalu-
ated. Cystic fibrosis is a disease with protean manifestations.
Although pulmonary and pancreatic involvement dom-
inate the clinical picture for most patients (see Chapter
Differential Diagnosis 18), a variety of other organs can be involved. Table
21–9 lists the important gastrointestinal, pancreatic,
Other causes of recurrent abdominal pain must be con- and hepatobiliary conditions that may affect cystic fi-
sidered. Specific causes of pancreatitis such as hyper- brosis patients along with their clinical findings, inci-
parathyroidism; systemic lupus erythematosus; infec- dence, most useful diagnostic studies, and preferred
tious disease; and ductal obstruction by tumors, stones, treatment.
or helminths must be excluded by appropriate tests.

Diwakar V et al: Liver disease in children with cystic fibrosis. Paedi-

Complications atr Respir Rev 2001;2:340 [PMID: 12052306].
Dodge JA, Macpherson C: Colonic strictures in cystic fibrosis. J R
Disabling abdominal pain, steatorrhea, nutritional de- Soc Med 1995;88(Suppl 25):3 [PMID: 7776325].
privation, pancreatic pseudocysts, and diabetes are the Ratjen F, Doring G: Cystic fibrosis. Lancet 2003;361:681 [PMID
most frequent long-term complications. Pancreatic car- 12606185].
cinoma occurs more frequently in chronic pancreatitis, Riedel BD: Gastrointestinal manifestations of cystic fibrosis. Pedi-
and in up to 40% of patients with hereditary pancreati- atr Ann 1997;26:235 [PMID: 9114442].
tis by age 70. Sokol RJ, Durie PR: Recommendations for management of liver
and biliary tract disease in cystic fibrosis: Cystic Fibrosis
Foundation Hepatobiliary Disease Consensus Group. J Pedi-
Treatment atr Gastroenterol Nutr 1999;28(Suppl 1):S1 [PMID:
9934970].
Medical management of acute attacks is indicated (see Taylor CJ, Aswani N: The pancreas in cystic fibrosis. Paediatr
Acute Pancreatitis section). If ductal obstruction is Respir Rev 2002;3:77 [PMID: 12065186].
strongly suspected, endoscopic therapy (balloon dila-
tion, stenting, stone removal, sphincterotomy) should
be pursued. Relapses seem to occur in most patients. SYNDROMES WITH PANCREATIC
Orally ingested non–enteric-coated pancreatic enzymes EXOCRINE INSUFFICIENCY
at mealtime may reduce pain episodes in some patients.
Antioxidant therapy is being investigated. Pseudocysts Several syndromes are associated with exocrine pancre-
may be marsupialized to the surface or drained into the atic insufficiency. Clinically the patients present with a
stomach or into a loop of jejunum if they fail to regress history of failure to thrive, diarrhea, fatty stools, and an
spontaneously. Experience in pediatric patients indi- absence of respiratory symptoms. Laboratory findings
cates that lateral pancreaticojejunostomy can reduce include a normal sweat chloride; low fecal pancreatic
pain in patients with a dilated pancreatic duct and may elastase 1; and low to absent pancreatic lipase, amylase,
prevent or delay progression of functional pancreatic and trypsin levels on duodenal intubation. Each disor-
impairment. der has several associated clinical features that aid in the
differential diagnosis. In Shwachman syndrome, pan-
creatic exocrine hypoplasia with widespread fatty re-
Prognosis placement of the glandular acinar tissue is associated
with neutropenia because of maturational arrest of the
In the absence of a correctable lesion, the prognosis is granulocyte series. Metaphyseal dysostosis and an ele-
not good. Disabling episodes of pain, pancreatic insuf- vated fetal hemoglobin are common, but immunoglob-
ficiency, diabetes, and pancreatic cancer may ensue. ulin deficiency and hepatic dysfunction are also re-
Narcotic addiction and suicide are risks in teenagers ported. CT examination of the pancreas demonstrates
with disabling disease. the widespread fatty replacement. Serum immunoreac-
tive trypsinogen levels are extremely low.
Etemad B, Whitcomb DC: Chronic pancreatitis: Diagnosis, classi-
Other associations of exocrine pancreatic insuffi-
fication, and new genetic developments. Gastroenterology ciency include (1) aplastic alae, aplasia cutis, deafness
2001;120:682 [PMID: 11179244]. (Johanson–Blizzard syndrome); (2) sideroblastic ane-
Witt H: Gene mutations in children with chronic pancreatitis. mia, developmental delay, seizures, and liver dysfunc-
Pancreatology 2001;1:432 [PMID: 12120220]. tion (Pearson bone marrow pancreas syndrome);
 Table 21–9. Gastrointestinal and hepatobiliary manifestations of cystic fibrosis.

Incidence
Organ Condition Symptoms Age at Presentation (%) Diagnostic Evaluation Management
Esophagus Gastroesophageal reflux, Pyrosis, dysphagia, epigas- All ages 10–20 Endoscopy and biopsy, over- H blockers, antacids, carafate,
2

esophagitis tric pain, hematemesis. night pH study PPIs, surgical antireflux

procedure.
Varices Hematemesis, melena. Childhood and adolescents 3–10 Endoscopy Endosclerosis, band ligation,
drugs (see text), TIPS liver
transplantation. (see
Table 21–8)
Stomach Gastritis Upper abdominal pain, vomit- School age and older 10–25 Endoscopy and biopsy H blockers, antacids, cara-
2

ing, hematemesis. fate, PPIs.

Hiatal hernia Reflux symptoms (see School age and older 3–5 Endoscopy; barium swallow As above. Surgery in some.
above), epigastric pain.
Intestine Meconium ileus Abdominal distention, bilious Neonate 10–15 Radiologic studies, plain Dislodgement of obstruction
emesis. abdominal films; contrast with Gastrografin enema. Sur-
enema shows microcolon gery if unsuccessful or if case
702

complicated by atresia, perfo-

ration, or volvulus.
Distal intestinal obstruc- Abdominal pain, acute and re- Any age, usually school age 10–15 Palpable mass in right lower Gastrografin enema, intesti-
tion syndrome current; distention; occa- through adolescence quadrant, radiologic studies nal lavage solution, diet, bulk
sional vomiting. laxatives, adjustment of pan-
creatic enzyme intake.
Fibrosing colonopathy As above. History of high >3 years <1 Barium enema or Reduce pancreatic enzyme
enzyme dosage. UGI/SBFT, abdominal ultra- dose to < 2000 units of lipase/
sound, or CT kg per dose if indicated.
Surgical resection may be
necessary.
Intussusception Acute, intermittent abdominal Infants through adolescence 1–3 X-ray studies, barium enema Reduction by barium or air
pain; distention; emesis. enema or surgery if needed.
Diet. Bulk laxatives. Adjust-
ment of pancreatic enzyme
intake.
Rectal prolapse Anal discomfort, rectal bleed- Infants and children to age 15–25 Visual mass protruding from Manual reduction, adjust-
ing. 4–5 years anus ment of pancreatic enzyme
dosage, reassurance as prob-
lem resolves by age 3–5 years.
 Intestine Carbohydrate intolerance Abdominal pain, flatulence, Any age 10–25 Intestinal mucosal biopsy and Reduce lactose intake; reduc-
(cont’d) continued diarrhea with ade- disaccharidase analysis. tion of gastric hyperacidity if
quate replacement therapy. Breath hydrogen after lactose mucosa shows partial villous
load. atrophy. Beware concurrent
celiac disease or Giardia in-
fection.
Pancreas Total exocrine insuffi- Diarrhea, steatorrhea, malnu- Neonate through infancy 85–90 72-h fecal fat evaluation, Pancreatic enzyme replace-
ciency trition, failure to thrive. Spe- fecal pancreatic elastase ment, may need elemental
cific fat-soluble vitamin formula, fat-soluble vitamin
deficiency states. and vitamin E supplements.
Pancreatic sufficiency Occasional diarrhea, mild Any age 10–15 72-hour fecal fat evaluation, Pancreatic enzyme replace-
(partial exocrine growth delay. direct pancreatic function ment in selected patients.
insufficiency) tests Fat-soluble vitamin supple-
ments as indicated by bio-
chemical evaluation.
Pancreatitis Recurrent abdominal pain, Older children through 0.1 Increased serum lipase and Addition of pancreatic en-
vomiting. adolescence. Primarily in amylase, pancreatic provoca- zymes to feeds, endoscopic
patients with partial tive test, endoscopic removal of sludge or stones
pancreatic sufficiency. pancreatogram if present, endoscopic papil-
lotomy.
703

Diabetes Weight loss, polyuria, polydip- Older children through 5–7 Glucose tolerance test and Diet, insulin.
sia. adolescence insulin levels
Liver Steatosis Hepatomegaly. Neonates and infants, but 20–60 Liver biopsy Improved nutrition, replace-
can be seen at all ment of pancreatic enzymes
ages and vitamins.
Focal biliary cirrhosis Hepatomegaly. Infants and older patients 10–70 Liver biopsy As above. Taurine supple-
Prevalence increases with ments (still experimental),
age. ursodeoxycholic acid.
Multilobular biliary Hepatosplenomegaly, School age through adoles- 5–15 Liver biopsy, endoscopy Improved nutrition, ursode-
cirrhosis hematemesis from esopha- cence oxycholic acid, endosclero-
geal varices; hypersplenism, sis or band ligation of varices,
jaundice, ascites late in or partial splenic emboliza-
course. tion, liver transplantation.
(continued)
 Table 21–9. Gastrointestinal and hepatobiliary manifestations of cystic fibrosis. (continued)

Incidence
Organ Condition Symptoms Age at Presentation (%) Diagnostic Evaluation Management
Liver Neonatal jaundice Cholestatic jaundice Neonates 0.1–1 Sweat chloride test, liver bi- Nutritional support, special
(cont’d) hepatomegaly; often seen opsy formula with medium-chain
with meconium ileus. triglyceride-containing oil,
pancreatic enzyme replace-
ment, vitamin supplements.
Gallbladder Microgallbladder None. Congenital—present at any 30 Ultrasound or hepatobili- None needed.
age ary scintigraphy
704

Cholelithiasis Recurrent abdominal pain, School age through adoles- 1–10 Ultrasound Surgery if symptomatic and
rarely jaundice. cence low risk, trial of cholelitholy-
tics in others.
Extrahepatic Intraluminal obstruction Jaundice, hepatomegaly, ab- Neonates, then older children Rare in Ultrasound and hepatobiliary Surgery in neonates, endo-
bile ducts (sludge, stones, tumor) dominal pain. through adolescence neonates scintigraphy, endoscopic scopic intervention in older
(< 0.1) cholangiography patients or surgery.
Extraluminal obstruction As above. Older children to adults Rare As above Surgical biliary drainage pro-
(intrapancreatic (< 1) cedure or biliary stent place-
compression, tumor) ment vs. balloon dilation
endoscopically.
PPI = proton pump inhibitor; CT = computed tomography; TIPS = transjugular intrahepatic portosystemic shunt; UGI/SBFT = upper gastrointestinal/small bowel follow-through radiologic
series.
 LIVER & PANCREAS / 705

(3) duodenal atresia or stenosis; (4) malnutrition; and Sarles J, Guys JM, Sauniere JF: Pancreatic function and congenital
(5) pancreatic hypoplasia or agenesis. duodenal abnormalities. J Pediatr Gastroenterol Nutr 1993;
16:284 [PMID 8492257].
The complications and sequelae of deficient pancre-
atic enzyme secretion are malnutrition, diarrhea, and Seneca S et al: Pearson marrow pancreas syndrome: A molecular
study and clinical management. Clin Genet 1997;51:338
growth failure. The degree of steatorrhea may lessen [PMID: 9212183].
with age. Intragastric lipolysis primarily caused by lin- Wright NM et al: Permanent neonatal diabetes mellitus and pan-
gual lipase may compensate in patients with low or ab- creatic exocrine insufficiency resulting from congenital pan-
sent pancreatic function. In Shwachman syndrome, the creatic agenesis. Am J Dis Child 1993;147:607 [PMID:
major sequela is short stature. Increased numbers of in- 8506821].
fections may result from chronic neutropenia. Neu-
trophil mobility is also impaired in many patients. In ISOLATED EXOCRINE PANCREATIC
addition, an increased incidence of leukemia has been
noted in these patients. ENZYME DEFECT
Pancreatic enzyme and fat-soluble vitamin replace- Normal premature infants and most newborns produce
ment are required therapy in most patients. The prog- little, if any, pancreatic amylase following meals or ex-
nosis appears to be good for those able to survive the in- ogenous hormonal stimulation. This temporary physio-
creased number of bacterial infections early in life and logic insufficiency may persist for the first 3–6 months
those patients without severe associated defects. of life and be responsible for diarrhea when complex
carbohydrates (cereals) are introduced into the diet.
Congenital pancreatic lipase deficiency and congeni-
Durie PR: Pancreatic aspects of cystic fibrosis and other inherited tal colipase deficiency are extremely rare disorders,
causes of pancreatic dysfunction. Med Clin North Am 2000;
84:609 [PMID: 10872418].
causing diarrhea and variable malnutrition with malab-
Dror Y, Freedman MH: Shwachman–Diamond syndrome. Br
sorption of dietary fat and fat-soluble vitamins. The
J Haematol 2002;118:701 [PMID: 12181037]. sweat chloride level is normal, and neutropenia is ab-
Rothbaum R et al: Shwachman–Diamond syndrome: Report from sent. Treatment is oral replacement of pancreatic en-
an international conference. J Pediatr 2002;141:266-70 zymes and a low-fat diet or formula containing
[PMID: 12183725]. medium-chain triglycerides.

Table 21–10. Pancreatic tumors.

Associated
Age Major Findings Diagnosis Treatment Conditions
Insulinoma Any age Hypoglycemia, seizures; Ultrasound, CT scan, Surgery
high serum insulin; MRI, EUS
abdominal pain and
mass infrequent
Adenocarcinoma Any age Epigastric pain, mass Ultrasound, CT scan, Surgery Chronic pancreatitis
weight loss, anemia, bil- MRI, EUS
iary obstruction
Gastrinoma Older Male sex, gastric hyper- Elevated fasting gastrin H2 blockers, Zollinger–Ellison
than age secretion, peptic symp- and postsecretin sup- omeprazole, sur- syndrome, multiple
5–8 toms, multiple ulcers, pression test (> 300 pg/ gical resection, total endocrine neopla-
years gastrointestinal bleeding, mL), CT scan, MRI, EUS gastrectomy sia syndrome type I,
anemia, diarrhea laparotomy neurofibromatosis
VIPoma Any age Secretory diarrhea, Elevated vasoactive in- Surgery, octreotide
hypokalemia, weight testinal polypeptide (VIP)
loss levels; sometimes, eleva-
ted serum gastrin and
pancreatic polypeptide
Glucagonoma Older Necrolytic rash, diarrhea, Elevated glucagon, gas- Surgery
patients anemia, thrombotic events trin, VIP
CT = computed tomography, MRI = magnetic resonance imaging, EUS = endoscopic ultrasound.
706 / CHAPTER 21

Exocrine pancreatic insufficiency of proteolytic en- glucagonoma). These malignant lesions produce diverse
zymes (eg, trypsinogen, trypsin, chymotrypsin) is symptoms, because they release biologically active
caused by enterokinase deficiency, a duodenal mucosal polypeptides from this ectopic location. The clinical
enzyme required for activation of the pancreatic proen- features of these tumors are summarized in Table
zymes. These patients present with malnutrition associ- 21–10. The differential diagnosis of these abdominal
ated with hypoproteinemia and edema but are free of tumors includes Wilms’ tumor, neuroblastoma, and
respiratory symptoms and have a normal sweat test. malignant lymphoma. In older children, endoscopic ul-
They respond to pancreatic enzyme replacement ther- trasonography can aid in localizing these tumors.
apy and feeding formulas that contain a casein hy-
drolysate (eg, Nutramigen, Pregestimil).
Jaksic T et al: A 20-year review of pediatric pancreatic tumors. J Pe-
diatr Surg 1992;27:1315 [PMID: 1328584].
Durie PR: Pancreatic aspects of cystic fibrosis and other inherited
causes of pancreatic dysfunction. Med Clin North Am 2000; Johnson PRV, Spitz L: Cysts and tumors of the pancreas. Semin
84:609 [PMID: 10872418]. Pediatr Surg 2000;9:209 [PMID 11112838].
Mann NS, Mann SK: Enterokinase. Proc Soc Exp Biol Med 1994; Vossen S et al: Therapeutic management of rare malignant pancre-
206:114 [PMID: 8208733]. atic tumors in children. World J Surg 1998;22:879 [PMID:
9673563].
McKenna LL: Pancreatic disorders in the newborn. Neonatal Netw
2000;19:13 [PMID: 11949098].
Stormon MO, Durie PR: Pathophysiologic basis of exocrine pan-
creatic dysfunction in childhood. J Pediatr Gastroenterol REFERENCES
Nutr 2002;35:8 [PMID: 12142803].
Roy CC et al (eds): Pediatric Clinical Gastroenterology, 4th ed.
Mosby-Year Book, 1995.
PANCREATIC TUMORS Sokol RJ, Feranchak AM: Genetic and metabolic basis of pediatric
liver disease. Semin Liver Dis 2001;21:469.
Pancreatic tumors, whether benign or malignant, are
Suchy FJ et al (eds): Liver Disease in Children, 2nd ed. Lippincott,
rare lesions. They most often arise from ductal or acinar Williams & Wilkins, 2001.
epithelium (malignant adenocarcinoma) or from islet Walker WA et al (eds): Pediatric Gastrointestinal Disease: Pathophys-
(endocrine) components within the gland, such as the iology, Diagnosis, Management, 2nd ed. Mosby-Year Book,
benign insulinoma (adenoma) derived from β cells. 1996.
Other pancreatic tumors also originate from these Wyllie R, Hyams JS (eds): Pediatric Gastrointestinal Disease. Saun-
pluripotential endocrine cells (gastrinoma, VIPoma, ders, 1999.
 Kidney & Urinary Tract 22
Gary M. Lum, MD

LABORATORY EVALUATION
EVALUATION OF THE KIDNEY OF RENAL FUNCTION
& URINARY TRACT Urinalysis
Commercially available dipsticks can be used to screen
HISTORY for the presence of red blood cells, hemoglobin, leuko-
cytes, nitrites, and protein and to approximate pH.
When renal disease is suspected, the history should in- Positive results for blood should always be confirmed
clude by microscopy, as should any suspicion of crystalluria.
Significant proteinuria (> 150 mg/dL) detected by dip-
1. Family history of cystic disease, hereditary nephri- stick should be confirmed by quantitation either with a
tis, deafness, dialysis, or renal transplantation 24-hour collection or by the protein/creatinine ratio
2. Preceding acute or chronic illnesses (eg, UTI, (see following section) of a random specimen.
pharyngitis, impetigo, endocarditis)
3. Rashes or joint pains
Serum Analysis
4. Growth delay or failure to thrive
5. Polyuria, polydipsia, enuresis, urinary frequency, The standard indicators of renal function are serum lev-
or dysuria els of urea nitrogen and creatinine; their ratio is nor-
mally about 10:1. This ratio may increase when renal
6. Documentation of hematuria, proteinuria, or dis-
perfusion or urine flow is decreased, as in urinary tract
colored urine
obstruction or dehydration. Because serum urea nitro-
7. Pain (abdominal, costovertebral angle, or flank) gen levels are more affected by these and other factors
or trauma (eg, nitrogen intake, catabolism, use of corticosteroids)
8. Sudden weight gain or edema than are creatinine levels, the most reliable single indi-
9. Drug or toxin exposure cator of glomerular function is the serum level of creati-
nine. For example, serum creatinine increasing from
For the newborn or small infant, the physician 0.5 mg/dL to 1.0 mg/dL represents a 50% decrease in
should obtain birth history and information regarding glomerular filtration rate. Small children should have
prenatal ultrasonographic studies, birth asphyxia, Apgar serum creatinine levels well under 0.8 mg/dL, and only
scores, oligohydramnios, dysmorphic features, abdomi- larger adolescents should have levels exceeding
nal masses, voiding patterns, anomalous development, 1 mg/dL. Less precise but nonetheless important indi-
and umbilical artery catheterization. cators of the possible presence of renal disease are ab-
normalities of serum electrolytes, pH, calcium, phos-
phorus, magnesium, albumin, or complement.
PHYSICAL EXAMINATION
Important aspects of the physical examination include Measurement of Glomerular
the height, weight, skin lesions (café-au-lait or ash leaf
spots), pallor, edema, or skeletal deformities. Anomalies
Filtration Rate
of the ears, eyes, or external genitalia may be associated The endogenous creatinine clearance (Ccr) in milliliters
with renal disease. The blood pressure should be mea- per minute estimates the glomerular filtration rate
sured in a quiet setting. The cuff should cover two (GFR). A 24-hour urine collection is usually obtained;
thirds of the child’s upper arm, and peripheral pulses however, in small children from whom collection is dif-
should be noted. An ultrasonic device is useful for mea- ficult, a 12-hour daytime specimen, collected when
surements in infants. The abdomen should be palpated, urine flow rate is greatest, is acceptable. The procedure
with attention to the kidneys, abdominal masses, mus- for collecting a timed urine specimen should be ex-
culature, and the presence of ascites. plained carefully so that the parent or patient under-
707
Copyright © 2005, 2001, by The McGraw-Hill Companies, Inc. Click here for terms of use.
708 / CHAPTER 22

stands fully the rationale of (1) first emptying the blad- sign of chronic renal failure. The first morning void
der (discarding that urine) and noting the time; and should be concentrated. Evaluation of other abnormali-
(2) putting all urine subsequently voided into the col- ties of urinary concentration or dilution is discussed
lection receptacle, including the last void, 12 or later in the sections on specific disease entities, such as
24 hours later. Reliability of the 24-hour collection can diabetes insipidus.
be checked by measuring the total 24-hour creatinine
excretion in the specimen. Total daily creatinine excre-
tion (creatinine index) should be in the range of
Microhematuria or Isolated Proteinuria
14–20 mg/kg. Creatinine indices on either side of this In children with asymptomatic hematuria or protein-
range suggest collections that were either inadequate or uria, the search for renal origins will yield the most re-
excessive. Calculation by the following formula requires sults. Isolated proteinuria may reflect urologic abnor-
measurements of plasma creatinine (Pcr) in mg/mL, malities, benign excretion, or glomerular alterations.
urine creatinine (Ucr) in mg/mL, and urine volume (V) The presence of red cell casts suggests glomerulonephri-
expressed as mL/min: tis (GN), but the absence of casts does not rule out this
disease. Anatomic abnormalities such as cystic disease
may be a source of hematuria.
UCr V
CCr = Benign hematuria, including benign familial hema-
PCr turia, is diagnosed by exclusion. In this group are chil-
dren whose hematuria is caused by asymptomatic hy-
Creatinine is a reflection of body muscle mass. Be- percalciuria. Figure 22–1 suggests an approach to the
cause accepted ranges of normal creatinine clearance are renal work-up of hematuria. GN is discussed in more
based on adult parameters, correction for size is needed detail later in this chapter.
to determine normal ranges in children. Clearance is The association of proteinuria with hematuria is
corrected to a standard body surface area of 1.73 m2 in characteristic of more significant glomerular disease.
the formula: Quantitation of the proteinuria is customarily accom-
plished by a time collection (eg, over a 24-hour period).
However, an assessment of the degree of proteinuria
Patient‘s CCr × 1.73m2 may be made with the performance of the urine pro-
“Corrected” CCr = tein/creatinine ratio in a random urine sample. A pro-
Patient‘s body surface area
tein-to-creatinine ratio of more than 0.2 is abnormal. A
timed urine collection is performed as described previ-
Although 80–125 mL/min/1.73 m2 is the normal ously for creatinine clearance. In the evaluation of
range for creatinine clearance, estimates at the lower asymptomatic proteinuria, orthostatic or postural pro-
end of this range may indicate problems. teinuria should be ruled out. The protein present in
A simple and tested formula for quick approxima- urine voided on arising in the morning is compared
tion of creatinine clearance incorporates use of the with that in urine formed in the upright position dur-
plasma creatinine level and the child’s length in cen- ing the rest of the day. This can be accomplished more
timeters: simply by comparing the protein/creatinine ratios. If
the quantitation is accomplished by separation of the
0.55 × Height in cm “upright” and “supine” portions of a 24-hour collec-
CCr (mL / min /1.73m2 ) = tion, if the upright collection contains 80–100% of the
PCr in mg / dL entire 24-hour measured protein, and if there are no
other markers of renal disease, the diagnosis of benign
Note: Because this formula takes into account the postural proteinuria is acceptable.
body surface area, further correction is not necessary. An approach to the work-up of isolated proteinuria
Use 0.45 × length in centimeters for newborns and for is shown in Figure 22–2. Note that corticosteroid ther-
infants younger than age 1 year. This method of calcu- apy is indicated in the algorithm because this may be
lation is not meant to detract from the importance of initiated prior to referral. Other renal lesions with pro-
clearance determinations but is useful when a suspi- teinuric manifestations are discussed later in this chap-
cious plasma creatinine needs to be checked. ter.

Urine Concentrating Ability Special Tests of Renal Function

Inability to concentrate urine is associated with Measurements of urinary sodium, creatinine, and os-
polyuria, polydipsia, or enuresis and is often the first molality are useful in differentiating prerenal causes of
 KIDNEY & URINARY TRACT / 709

Initial data: history of prior acute infection?

Family history: dialysis, transplant, SLE, familial hematuria
Physical examination: BP, edema, rashes, arthralgia
Lab tests: U/A, RBC casts, protein, serum BUN, Cr,
electrolytes, urine Ca/Cr ratio (ASO, C3, ANA)

Microhematuria Gross hematuria

(tea-colored/smoky, RBC casts)

Acute
Abnormal Normal glomerulonephritis
initial data initial data

Ultrasound Follow; No history of History of prior infection

Refer if indicated prior infection (e.g., streptococcal)

Abnormal Normal “Medical renal

disease”

Surgical Non-surgical ASO titer, streptozyme, complement (C3)*,

intervention intervention urine protein/creatinine, or 24-hour urine
protein if U/A > 3+

Urology referral/ Follow

intervention Atypical course: suspect
more complicated disease; Typical course/
obtain ANA, IgA, CBC resolution
Follow-up ↑BP, ↑hematuria
↑creatinine, ↑proteinura

Treat ↑BP; hospitalize if ↑BP severe

or if significant ↓renal function

Nephrology consultation
(Treat and/or renal biopsy)

Figure 22–1. Approach to the renal work-up of hematuria. (Exclude UTI, lithiasis, trauma, bleeding disorders, sickle
cell disease.) ANA = antinuclear antibody; ASO = antistreptolysin antibody; BP = blood pressure; BUN = blood urea
nitrogen; C3 = complement; Ca = calcium; Cr = creatinine; GN = glomerulonephritis; IgA = immunoglobulin A; PSGN
= poststreptococcal glomerulonephritis; RBC = red blood cell; SLE = systemic lupus erythematosus; U/A = urinalysis.

renal insufficiency from renal causes such as acute tubu- tion of a 24-hour urine specimen and evaluation of
lar necrosis. The physiologic response to decreased tubular reabsorption of phosphorus (TRP) will help
renal perfusion is decreased urinary output, increased document renal tubular diseases as well as hyper-
urine osmolality, increased urinary solutes (eg, creati- parathyroid states. TRP (expressed as percentage of re-
nine), and decreased urinary sodium (usually < absorption) is calculated as follows:
20 mEq/L). Prolonged underperfusion results in vary-
ing increases in the serum creatinine and blood urea ni-
trogen (BUN) concentrations, prompting the need to ⎡ S × UPO4 ⎤
TRP = 100 ⎢1 − Cr ⎥
differentiate between this state and acute tubular necro- ⎢⎣ SPO4 × UCr ⎥⎦
sis (see Acute Renal Failure section).
The presence of certain substances in urine may sug-
gest tubular dysfunction. For example, urine glucose where Scr = serum creatinine; Ucr = urine creatinine;
should be less than 5 mg/dL. Hyperphosphaturia oc- SPO4 = serum phosphate; and UPO4 = urine phosphate.
curs with significant tubular abnormalities (eg, Fanconi All values for creatinine and phosphate are expressed in
syndrome). Measurement of the phosphate concentra- milligrams per deciliter for purposes of calculation. A
710 / CHAPTER 22

Initial data: history of renal or urological disease or exercise-induced

Physical examination: BP, edema >20 RBC/hpf or
Lab tests: Serum BUN, Cr, electrolytes, U/A, 24-hour urinary RBC casts
protein excretion or protein/creatinine ratio (if (see Fig 21–1)
nephrotic syndrome: albumin, cholesterol, triglycerides)

Nonnephrotic Nephrotic syndrome

Abnormal Normal Congenital Idiopathic

initial data initial data

Nonorthostatic Orthostatic
proteinuria proteinuria

Degree of
Ultrasound
proteinuria

Abnormal Normal "Medical > 1.5 g < 1.5 g Corticosteroid

anatomy renal Treatment
disease"
Follow
Follow-up
Surgical Nonsurgical

Nephrology referral
Reflux: Obstruction:
Obtain VCUG Obtain renal scan
with "washout"

Course alters (eg,

Urology referral/ proteinuria
intervention Follow-up
renal function
BP)

Figure 22–2. Approach to the work-up of isolated proteinuria. BP = blood pressure; Cr = creatinine; hpf = high-
power field; RBC = red blood cell; U/A = urinalysis; VCUG = voiding cystourethrogram. *Complement is depressed in
acute poststreptococcal glomerulonephritis, chronic glomerulonephritis, and lupus. Will normalize within a month
in poststreptococcal glomerulonephritis.

TRP value of 80% or more is considered normal, al- LABORATORY EVALUATION

though it depends somewhat on the value of SPO4. OF IMMUNOLOGIC FUNCTION
The urinary excretion of amino acids in generalized
tubular disease reflects a quantitative increase rather Many parenchymal renal diseases are thought to have
than a qualitative change. Diseases affecting proximal immune causation, although the mechanisms are
tubular reabsorption of bicarbonate—including iso- largely unknown. Examples of mechanisms in the kid-
lated renal tubular acidosis, Fanconi syndrome (which ney include (1) deposition of circulating antigen–anti-
occurs in diseases such as cystinosis), and chronic renal body complexes that are themselves injurious or incite
failure—are discussed later in the chapter. injurious responses and (2) formation of antibody di-
 KIDNEY & URINARY TRACT / 711

rected against the glomerular basement membrane itself

(rare in children). CONGENITAL ANOMALIES
Total serum complement and the C3 and C4 com-
plement components should be measured when im- OF THE URINARY TRACT
mune-mediated renal injury or chronic GN is sus-
pected. Where clinically indicated, antinuclear
antibodies, hepatitis B surface antigen, and rheumatoid RENAL PARENCHYMAL ANOMALIES
factor should be obtained. In rare cases the presence About 10% of children have congenital anomalies of
of cold-precipitable proteins (cryoglobulins), C3 the genitourinary tract, which range in severity from
“nephritic” factor, or antiglomerular basement mem- asymptomatic to lethal. Some asymptomatic abnormal-
brane (anti-GBM) antibody may be helpful in deter- ities may have significant complications. For example,
mining a specific diagnosis. At some point in the work- patients with “horseshoe” kidney (kidneys fused in their
up, the diagnosis may be supported or confirmed by lower poles) have a higher incidence of renal calculi.
the description of renal histology. Unilateral agenesis is usually accompanied by com-
pensatory hypertrophy of the contralateral kidney
and thus should be compatible with normal renal func-
tion. Supernumerary and ectopic kidneys are usually of
RADIOGRAPHIC EVALUATION no significance. Abnormal genitourinary development
Renal ultrasonography is a useful noninvasive tool in can result in varying degrees of renal maldevelopment
the evaluation of renal parenchymal disease, urinary and function, of which complete renal agenesis is the
tract abnormalities, or renal blood flow. Excretory most severe. When the agenesis is bilateral, it causes
urography is used to assess the anatomy and function early death. Severe oligohydramnios is present and can
of the kidney, collecting system, and bladder. Radio- result in pulmonary hypoplasia and peculiar (Potter) fa-
isotope studies provide valuable information con- cies.
cerning renal anatomy, blood flow, and integrity and
function of the glomerular, tubular, and collecting sys-
tems.
Evaluation of the lower urinary tract (voiding cys- Renal Dysgenesis
tourethrography or cystoscopy) is indicated when vesi-
Renal dysgenesis represents a spectrum of anomalies. In
coureteral reflux or bladder outlet obstruction is sus-
simple hypoplasia, which may be unilateral or bilateral,
pected. Cystoscopy is rarely useful in the evaluation of
the affected organs are smaller than normal. In the vari-
asymptomatic hematuria or proteinuria in children.
ous forms of dysplasia, immature, undifferentiated
Renal arteriography or venography is indicated to
renal tissue persists. In some of the dysplasias, the num-
define vascular abnormalities (eg, renal artery stenosis)
ber of normal nephrons is insufficient to sustain life
prior to surgical intervention. Less invasive measures
once the child reaches a critical body size. Such lack of
such as ultrasonography and Doppler studies can
renal tissue may not be readily discernible in the new-
demonstrate renal blood flow or thromboses.
born period because the infant’s urine production,
though poor in concentration, may be adequate in vol-
ume. Often, the search for renal insufficiency is initi-
ated only when growth fails or chronic renal failure de-
RENAL BIOPSY velops.
Histologic information is valuable for diagnosis, treat- Other forms of renal dysplasia include oligomega-
ment, and prognosis. Satisfactory evaluation of renal nephronia (characterized by the presence of only a few
tissue requires examination by light, immunofluores- large glomeruli) and the cystic dysplasias (characterized
cence, and electron microscopy. by the presence of renal cysts). This group includes mi-
When a biopsy is anticipated, a pediatric nephrolo- crocystic disease (congenital nephrosis). A simple cyst
gist should be consulted. In children, percutaneous within a kidney may be clinically unimportant because
renal biopsy with a biopsy needle is an acceptable low- it does not predispose to progressive polycystic develop-
risk procedure—avoiding the risks of general anesthe- ment. An entire kidney lost to multicystic development
sia—when performed by an experienced physician. A with concomitant hypertrophy and normal function of
surgeon should perform the biopsy procedure if opera- the contralateral side may also be of little clinical conse-
tive exposure of the kidney is necessary, if an increased quence. Nonetheless, even a simple cyst could pose
risk factor (eg, bleeding disorder) is present, or if a problems if it becomes a site for lithiasis, infection, or
“wedge” biopsy is preferred. hematuria.
712 / CHAPTER 22

Polycystic Kidney Disease Severe bladder malformations such as exstrophy are

clinically obvious and provide a surgical challenge.
Autosomal recessive polycystic kidney disease (ARPKD) More subtle—but urgent in terms of diagnosis—is ob-
is increasingly diagnosed by prenatal ultrasound. In its struction of urine flow from vestigial posterior urethral
most severe form the cystic kidneys are nonfunctional valves. This anomaly, which occurs almost exclusively
in utero, and, therefore, newborns can have Potter fa- in males, usually presents as anuria or a poor voiding
cies and other complications of oligohydramnios. In in- stream in the newborn period, with severe obstruction
fancy and childhood, kidney enlargement by cysts may of urine flow. Ascites may occur, and the kidneys and
initially be recognized by abdominal palpation of the bladder may be easily palpable. Surgical drainage of
renal masses. Hypertension is an early problem. The urine is urgently required to prevent irreversible dam-
rate of the progression of renal insufficiency varies, as age, if possible.
does growth failure and other complications of chronic
renal failure. Two genes (ADPKD-1 and ADPKD-2) ac-
count for 80% and 10% of cases of the autosomal
dominant polycystic kidney disease, respectively. Sus- Complex Anomalies
ceptibility of members in ADPKD families is detected Prune belly syndrome is an association of urinary tract
by gene linkage studies. Renal ultrasound identifies anomalies with cryptorchidism and absent abdominal
cysts in about 80% of affected children by age 5 years. musculature. Although complex anomalies, especially
Children with this diagnosis need close monitoring for renal dysplasia, usually cause early death or the need for
the development and treatment of hypertension, and dialysis or transplantation, some patients have lived
their families should be offered genetic counseling. into the third decade with varying degrees of renal in-
Management of end-stage renal failure is by dialysis or sufficiency. Early urinary diversion is essential to sus-
renal transplantation. tain renal function. A renal biopsy at the time of this
surgery may predict subsequent renal function.
Gabow PA: Utility of ultrasonography in the diagnosis of autoso- Other complex malformations and external genital
mal dominant polycystic kidney disease in children. J Am Soc anomalies such as hypospadias are beyond the scope of
Nephrol 1997;8:105. this text. Overall, urologic abnormalities resulting in se-
Murcia NS, Sweeney WE Jr. Avner ED: New insights into the vere compromise and destruction of renal tissue provide
molecular pathophysiology of polycystic kidney disease. Kid-
ney Int 1999;55:1187.
therapeutic and management challenges aimed at pre-
serving all remaining function and treating the compli-
cations of progressive chronic renal failure.
Medullary Cystic Disease
(Juvenile Nephronophthisis)
Medullary cystic disease is characterized by varying sizes
of cysts in the renal medulla and is associated with HEMATURIA & GLOMERULAR
tubular and interstitial nephritis. Children present with
renal failure and signs of tubular dysfunction (decreased DISEASE
concentrating ability, Fanconi syndrome). This lesion
should not be confused with medullary sponge kidney Children with painful hematuria should be investigated
(renal tubular ectasia), a frequently asymptomatic dis- for urinary tract infection (UTI) or direct injury to the
ease occurring in adults. urinary tract. Dysuria commonly suggests cystitis or
urethritis; back pain may support the presence of
DISTAL URINARY TRACT ANOMALIES pyelonephritis; and colicky flank pain may mean the
passage of a stone. Bright red blood or clots in the urine
Obstruction at the ureteropelvic junction may be the are associated with bleeding disorders, trauma, and ar-
result of intrinsic muscle abnormalities, aberrant ves- teriovenous malformations. Abdominal masses suggest
sels, or fibrous bands. The lesion can cause hy- the presence of urinary tract obstruction, cystic disease,
dronephrosis and usually presents as an abdominal mass or tumors involving the renal or perirenal structures.
in the newborn. Obstruction can occur in other parts of Asymptomatic hematuria is a challenge because clin-
the ureter, especially at its entrance into the bladder, ical and diagnostic data are required to decide whether
with resulting proximal hydroureter and hydronephro- to refer the child to a nephrologist. Figure 22–1 delin-
sis. Whether intrinsic or extrinsic, urinary tract obstruc- eates the outpatient approach to renal hematuria. The
tion should be relieved surgically as soon as possible to concern regarding the differential diagnosis is the possi-
minimize damage to the kidneys. ble presence of glomerular disease.
 KIDNEY & URINARY TRACT / 713

GLOMERULONEPHRITIS IgA Nephropathy

Poststreptococcal Glomerulonephritis When asymptomatic gross hematuria appears to ac-
company a minor acute febrile illness or other stressful
Acute poststreptococcal GN is the most common form
occurrence, the diagnosis of IgA nephropathy may be
of “postinfectious” GN. The epidemiologic relationship
entertained. In contrast to postinfection GN, in IgA
between certain strains of streptococci and GN is well
nephropathy there is no evidence of prior infection,
recognized. Antigen–antibody complexes are formed in
complement is not depressed, and serum immunoglo-
the bloodstream and deposited in the glomeruli. These
bin A is elevated in 50% of all cases. Often there are no
deposited complexes may incite glomerular inflamma-
associated clinical factors. The gross hematuria resolves
tion and activate the complement system.
within days, and there are no serious sequelae in 85%
The diagnosis of poststreptococcal disease is sup-
of cases of IgA neprhopathy. Treatment is not indi-
ported by a recent history (7–14 days previously) of
cated, and the prognosis is good in most cases. Progno-
group A β-hemolytic streptococcal infection. If a posi-
sis is guarded, however, if severe proteinuria, hyperten-
tive culture is not available, recent infection may be
sion, or renal insufficiency is present or ensues. In such
supported by an elevated antistreptolysin O titer or by
instances, treatment is usually attempted. Although no
high titers of other antistreptococcal antibodies. Other
treatment is universally accepted, corticosteroids and
infections can cause similar glomerular injury; thus,
other immunosupressive drugs are used. Omega-3 fatty
“postinfection GN” may be a better term for this type
acids present in fish oils are thought to be helpful.
of acute GN. In most cases recovery is expected and
usually complete within weeks. In cases when the diag-
nosis is in some question, or in patients whose renal Henoch–Schönlein Purpura
function progressively deteriorates, a renal biopsy
should be performed. The diagnosis of Henoch–Schönlein purpura rests on the
The clinical presentation of GN is usually with gross presence of a typical maculopapular rash found primar-
hematuria (coffee-colored or tea-colored urine), with or ily, but not exclusively, on the dorsal surfaces of lower ex-
without edema (eg, periorbital), which in mild cases oc- tremities and buttocks. Most children have abdominal
curs secondary to the alteration in glomerular function, pain and bloody diarrhea. Joint pain is common, and,
resulting in sodium and water retention. Symptoms are depending on the extent of renal involvement, hyperten-
usually nonspecific. In cases accompanied by hyperten- sion may be present. Joint and abdominal pain responds
sion (a common finding), headache may be present. to treatment with corticosteroids. Renal involvement
Fever is uncommon. Severe glomerular injury (which ranges from mild GN with microhematuria to severe
usually occurs in severe, acute presentations of the more GN and varying degrees of renal insufficiency. GN with
chronic or destructive forms of GN) may be accompa- massive proteinuria and renal insufficiency carries the
nied by massive proteinuria (nephrotic syndrome), worst prognosis. Twenty percent of such cases result in
anasarca or ascites, and severe compromise of renal end-stage renal failure. There is no universally accepted
function. treatment, but corticosteroids are often administered.
Typical poststreptococcal GN has no specific treat-
ment. Appropriate antibiotic therapy is indicated if an Membranoproliferative
infection is still present. The disturbances in renal func- Glomerulonephritis
tion and resulting hypertension may require close fol-
low-up and management, with reduction in salt intake, The most common “chronic” form of GN occurring in
treatment with diuretics, or antihypertensive drugs. In children is membranoproliferative GN. The diagnosis
severe cases, with profound renal failure, hemodialysis is established from the histologic appearance of the
or peritoneal dialysis may be necessary; corticosteroids glomeruli. The discussion of the various types of this
may also be administered in an attempt to influence the form of GN is complex. Clinically, type II carries the
course of the infection. worse prognosis, as end-stage renal failure develops in
The acute abnormalities generally resolve in most cases. Type I more often responds to treatment
2–3 weeks; serum complement (C3) may be normal as with corticosteroids. C3 is depressed (in both types)
early as 3 days or as late as 30 days after onset. Al- and may be useful as a marker of response to treatment.
though microscopic hematuria may persist for as long The various types of GN have similar manifesta-
as a year, most children recover completely. Persistent tions. Table 22–1 lists the most commonly encoun-
deterioration in renal function, urinary abnormalities tered entities in the differential diagnosis of GN in
beyond 18 months, persistent hypocomplementemia, childhood and their clinical and histopathologic de-
and nephrotic syndrome are ominous signs. If any one scriptions. Severe glomerular histopathologic and clini-
of these is present, a renal biopsy is indicated. cal entities, such as anti-GBM antibody disease (Good-
714 / CHAPTER 22

Table 22–1. Glomerular diseases encountered in childhood.

Entity Clinical Course Prognosis

Postinfection glomerulonephritis. Acute phase is usually over in 2 weeks. Excellent. Chronic disease is rare.
Onset occurs 10–14 days after acute ill- There is complete resolution in 95% of Severe proteinuria, atypical
ness, commonly streptococcal. Charac- cases. Severity of renal failure and hyper- presentation or course, or persistent
teristics include acute onset, tea- tension varies. Microhematuria hypocomplementemia suggest another
colored urine, mild to severe renal may persist to 18 months. Hypocom- entity.
insufficiency, and edema. plementemia resolves in 1–30 d.
Membranoproliferative glomerulone- Course can be mild to severe (rapid Type I may respond to corticosteroids.
phritis. Presentation ranges from mild deterioration in renal function); may Type II (dense deposit disease) is less
microhematuria to acute GN syndrome. mimic postinfection GN. Proteinuria can treatable; function decrease varies from
Diagnosis is made by renal biopsy. be severe. Complement depression is immediate to as long as 15 y
Etiology is unknown. Type I and intermittent to persistent. Hypertension is in 30–50% of untreated cases.
type II are most common. Lesion is usually significant.
chronic.
IgA nephropathy. Classic presentation 90% of cases resolve in 1–5 y. Gross Generally good. Small percentage de-
consists of asymptomatic gross hema- hematuric episodes resolve with recovery velop chronic renal failure. Proteinuria
turia during acute unrelated illness, with from acute illness. Severity of renal insuf- in the nephrotic range is a poor sign.
microhematuria between episodes. ficiency and hypertension varies. Protein- There is no universally accepted medi-
There are occasional instances of acute uria occurs in more severe, atypical cation. (Corticosteroids may be useful
GN syndrome. Etiology is unknown. cases. in severe cases.)
Diagnosis is made by biopsy.
Henoch–Schönlein purpura glomerulo- Presentation varies with severity of renal Overall, prognosis is good. Patients pre-
nephritis. Degree of renal involvement lesion. In rare cases, may progress rapidly senting with greater than 50% reduc-
varies. Asymptomatic microhematuria is to serious renal failure. Hypertension tion in function or proteinuria
most common, but GN syndrome can varies. Proteinuria in the nephrotic exceeding 1 g/24 h may develop
occur. Renal biopsy is recommended range and severe decline in func- chronic renal failure. Severity of renal
in severe cases; it can provide tion can occur. biopsy picture can best guide
prognostic information. approach in such cases. There is no
universally accepted medication.
Glomerulonephritis of systemic lupus Renal involvement is mild to severe. Clin- Renal involvement accounts for most
erythematosus (SLE). Microhematuria ical complexity depends on degree of re- significant morbidity in SLE. Control
and proteinuria are rarely first signs of nal insufficiency and other systems in- of hypertension affects renal progno-
this systemic disease. Renal involve- volved. Hypertension is significant. Mani- sis. Medication is guided by symptoms,
ment varies. GN often causes the most festations of the severity of the renal serology, and renal lesion. End-stage
concern. lesion guide therapeutic intervention. renal failure can occur.
Hereditary glomerulonephritis (eg, Al- There is no acute syndrome. Females Progressive proteinuria and hyperten-
port syndrome). Transmission is auto- are generally less affected but are carri- sion occur early, with gradual decline
somal-dominant/X-linked, with family ers. Hypertension and increasing protein- in renal function in those most severely
history marked by end-stage renal fail- uria occur with advancing renal failure. affected. Disease progresses to
ure, especially in young males. Deafness There is no known treatment. end-stage renal failure in most males.
and eye abnormalities are associated.

pasture syndrome), Wegener granulomatosis, and idio- and secondary involvement of the tubules. It seems to
pathic, rapidly progressive GN, may be considered in be related most often to drugs (eg, β-lactam-containing
the differential diagnosis of acute GN. But these disor- antibiotics, such as methicillin).
ders are exceedingly rare in children. Fever, rigor, abdominal or flank pain, and rashes
may occur in drug-associated cases. Urinalysis should
ACUTE INTERSTITIAL NEPHRITIS reveal leukocyturia and hematuria. Hansel staining of
the urinary sediment is helpful in demonstrating the
Acute interstitial nephritis is characterized by diffuse or presence of eosinophils. The inflammation can be se-
focal inflammation and edema of the renal interstitium vere enough to cause significant deterioration of renal
 KIDNEY & URINARY TRACT / 715

function. If the diagnosis is unclear from a history of occur as a result of any form of glomerular disease and
drug or toxin exposure or the presence of eosinophils in may rarely be associated with a variety of extrarenal
the urine, a renal biopsy may be performed to demon- conditions. In young children, the disease usually takes
strate the characteristic tubular and interstitial inflam- the form of idiopathic nephrotic syndrome of child-
mation. Immediate identification and removal of the hood (nil disease, lipoid nephrosis, minimal change dis-
causative agent is imperative and may be all that is nec- ease), which has characteristic clinical and laboratory
essary. Treatment with corticosteroids is helpful in findings, but no well-understood cause.
cases with progressive renal insufficiency or nephrotic
syndrome. Severe renal failure requires supportive dial-
ysis.
Clinical Findings
Affected patients are generally younger than age 6 years
PROTEINURIA & RENAL DISEASE at the time of their first episode. Often following an in-
fluenza-like syndrome, periorbital swelling and perhaps
Urine is not normally completely protein-free, but the oliguria are noticed. Within a few days, increasing
average excretion is well below 150 mg/24 h. Small in- edema—even anasarca—becomes evident. Other than
creases in urinary protein can accompany febrile ill- vague malaise and occasionally abdominal pain, com-
nesses or exertion and in some cases are produced while plaints are few. With significant “third spacing” of
in the upright posture (discussed earlier). plasma volume, however, some children may present
An algorithm for investigation of isolated protein- with hypotension. With marked edema, dyspnea due to
uria is presented in Figure 22–2. In idiopathic pleural effusions may also occur.
nephrotic syndrome without associated features of GN, Despite heavy proteinuria, the urine sediment is
treatment with corticosteroids may be initiated as de- usually normal, although microscopic hematuria (<
scribed later in this chapter. Nephrologic advice or fol- 20 RBC/high-power field) may be present. Plasma al-
low-up should be sought, especially in difficult or fre- bumin levels are low, and lipid levels are increased.
quently relapsing cases. When azotemia occurs, it is usually secondary to in-
travascular volume depletion rather than to impairment
CONGENITAL NEPHROSIS of function.
Glomerular morphology is unremarkable except for
Congenital nephrosis is a rare autosomal recessive dis- fusion of foot processes of the glomerular basement
order. The kidneys are pale and large and may show membrane. This finding, however, is nonspecific and is
microcystic dilations (microcystic disease) of the proxi- associated with many proteinuric states. Changes in the
mal tubules and glomerular changes. The latter consist glomerular mesangium may be minimal, with unre-
of proliferation, crescent formation, and thickening of markable findings on immunofluorescence and electron
capillary walls. The pathogenesis is not well under- microscopic examination.
stood.
Infants with congenital nephrosis commonly have
low birth weight, a large placenta, wide cranial sutures, Complications
and delayed ossification. Mild edema may be seen after Infections (eg, peritonitis) sometimes occur, and pneu-
the first few weeks of life. Anasarca follows, and the ab- mococci are frequently the cause. Hypercoagulability
domen can become greatly distended by ascites. Mas- may be present, and thromboembolic phenomena are
sive proteinuria associated with typical-appearing commonly reported. Hypertension and varying degrees
nephrotic syndrome and hyperlipidemia is the rule. of renal insufficiency are often encountered. In cases of
Hematuria is common. If the patient lives long enough, minimal-change disease (no significant glomerular le-
progressive renal failure occurs. Most affected infants sions are demonstrated), hypertension can still be noted
succumb to infections at the age of a few months. and renal insufficiency is primarily due to decreased
Treatment prior to dialysis and transplantation has renal perfusion.
little to offer other than nutritional support and man-
agement of the chronic renal failure.
Treatment & Prognosis
IDIOPATHIC NEPHROTIC SYNDROME As soon as the diagnosis of idiopathic nephrotic syn-
OF CHILDHOOD (Nil Disease, Lipoid drome is made, corticosteroid treatment should be
started. Prednisone, 2 mg/kg/d (maximum, 60 mg/d),
Nephrosis, Minimal Change Disease) is given as a single daily dose until the urine protein
Nephrotic syndrome is characterized by proteinuria, falls to trace or negative levels for a maximum of
hypoproteinemia, edema, and hyperlipidemia. It may 8 weeks. The same dose is then administered on an al-
716 / CHAPTER 22

ternate-day schedule for 6 weeks; thereafter, the dose is MESANGIAL NEPHROPATHY

tapered gradually and discontinued over the ensuing (Mesangial Glomerulonephritis)
2 months. If remission is achieved, only to be followed
by relapse, the treatment course may be repeated. If at Mesangial nephropathy is another form of corticoster-
any time the nephrosis becomes refractory to treatment oid-resistant nephrotic syndrome. The renal biopsy
or if three relapses occur within 1 year, renal biopsy shows a distinct increase in the mesangial matrix of the
may be considered. A renal biopsy is also often consid- glomeruli. Very often the expanded mesangium con-
ered when there is little or no response to treatment. tains deposits of IgM demonstrable on immunofluores-
One should take into account that the histologic find- cent staining. The cause is unknown. Corticosteroid
ings may not alter the treatment plan, which is more therapy may induce remission, but relapses are com-
often influenced by the need to eliminate the nephrotic mon. Choices for treating this type of nephrotic syn-
syndrome regardless of underlying renal histology. drome are the same as noted earlier.
Unless the edema is symptomatic (eg, respiratory
compromise due to ascites), diuretics should be used
with extreme care; patients may have decreased circulat-
MEMBRANOUS NEPHROPATHY
ing volume and are also at risk for intravenous throm- (Membranous Glomerulonephritis)
bosis. However, careful restoration of compromised cir- Although largely idiopathic in nature, membranous
culating volume with intravenous albumin infusion and nephropathy can be found in association with diseases
administration of diuretics is helpful in mobilizing such as hepatitis B antigenemia, systemic lupus erythe-
edema. Infections (eg, acute peritonitis) should be matosus, congenital and secondary syphilis, and renal
treated promptly to reduce morbidity. Immunization vein thrombosis; with immunologic disorders such as
with pneumoccoccal vaccine is advised. autoimmune thyroiditis; and with administration of
The initial response to corticosteroids is a guide to drugs such as penicillamine. The pathogenesis is un-
prognosis. A prompt remission lasting for over 1 year is known, but the glomerular lesion is thought to be the
almost always permanent. Failure to respond or early result of prolonged deposition of circulating
relapse usually heralds a prolonged series of relapses. antigen–antibody complexes.
This not only may indicate the presence of more serious The onset of membranous nephropathy may be in-
nephropathy, but it presents a challenge in choosing fu- sidious or may resemble that of idiopathic nephrotic
ture therapy. Chlorambucil or cyclophosphamide drug syndrome of childhood (see preceding section). It oc-
therapy is predictably successful only in children who curs more often in older children and adults. The pro-
respond to corticosteroids. Patients who do not re- teinuria of membranous nephropathy responds little if
spond to corticosteroids or who relapse frequently at all to corticosteroid therapy. Low-dose corticosteroid
should be referred to a pediatric nephrologist. Intra- therapy, however, has been shown to reduce or delay
venous solumedrol in more refractory cases has been development of chronic renal insufficiency. The diag-
shown to be helpful. In some cases, when the continued nosis is made by renal biopsy.
usage of corticostersoids alone is unsuccessful and raises
concerns of toxicity, concomitant treatment with either
cyclosporin A or tacrolimus appears to be helpful.
DISEASES OF THE RENAL
Chesney RW: The idiopathic nephrotic syndrome. Curr Opin Pe- VESSELS
diatr 1999;11:158.

RENAL VEIN THROMBOSIS

FOCAL GLOMERULAR SCLEROSIS In the newborn period, renal vein thrombosis may
Focal glomerular sclerosis is one cause of corticosteroid- complicate sepsis or dehydration. It may be observed in
resistant or frequent relapsing nephrotic syndrome. The an infant of a diabetic mother, or it may be the result of
cause is unknown. The diagnosis is made by renal umbilical vein catheterization. It may result from any
biopsy, which shows normal-appearing glomeruli as condition that produces a hypercoagulable state (eg,
well as some partially or completely sclerosed glomeruli. clotting factor deficiency, systemic lupus erythemato-
The lesion has serious prognostic implications because sus, or thrombocytosis). Renal vein thrombosis is less
as many as 15–20% of cases can progress to end-stage common in older children and adolescents; it may de-
renal failure. The clinical response to corticosteroid velop following trauma or without any apparent predis-
treatment is variable. In difficult cases, cyclosporin A or posing factors. Nephrotic syndrome may either cause or
tacrolimus has been used in addition to corticosteroids. result from renal vein thrombosis. Spontaneous renal
 KIDNEY & URINARY TRACT / 717

vein thrombosis has been associated with membranous sociation with hyperviscosity or umbilical artery
glomerulonephropathy. catheterization). Early diagnosis and treatment (eg, he-
parin) provides the best chance of reestablishing renal
Clinical Findings blood flow.
Renal vein thrombosis in newborns is generally charac-
terized by the sudden development of an abdominal HEMOLYTIC–UREMIC SYNDROME
mass. If the thrombosis is bilateral, oliguria may be pre- Hemolytic–uremic syndrome is the most common
sent; urine output may be normal with a unilateral glomerular vascular cause of acute renal failure in child-
thrombus. In older children, flank pain, sometimes hood. It is usually the result of infection with Shiga-
with a palpable mass, is a common presentation. toxin-producing (also called verotoxin-producing)
No single laboratory test is diagnostic of renal vein strains of Shigella or Escherichia coli. There are many
thrombosis. Hematuria usually is present. Proteinuria is serotypes, but the most common pathogen in the
less constant. In the newborn, thrombocytopenia may United States is E coli 0157:H7. Bloody diarrhea is the
be found; this is rare in older children. The diagnosis is usual presenting complaint, followed by hemolysis and
made by ultrasonography and Doppler flow studies. renal failure. Circulating verotoxin causes endothelial
damage, which leads to platelet deposition, microvascu-
Treatment lar occlusion with subsequent hemolysis, and thrombo-
Anticoagulation with heparin is the treatment of choice cytopenia. Ingestion of undercooked ground beef or
both in newborns and in older children. In the new- unpasteurized foods is a common cause. Such mi-
born, a course of heparin combined with treatment of crovascular endothelial activation may also be triggered
the underlying problem is usually all that is required. by some drugs (eg, cyclosporin A); by viruses (human
Management in other cases is less straightforward. The immunodeficiency virus [HIV]); and by pneumococcal
tendency for recurrence and embolization has led some infections, in which bacterial neuraminidase exposes
to recommend long-term anticoagulation. If an under- the Thomsen–Friedenrich antigen on red cells,
lying membranous GN is suspected, biopsy should be platelets, and endothelial cells, thereby causing platelet
performed. aggregation, endothelial damage, and hemolysis. Rare
cases are caused by predisposing genetic factors (eg,
congenitally depressed C3 complement and factor H
Course & Prognosis deficiency).
The mortality rate in newborns from renal vein throm-
bosis depends on the underlying cause. With unilateral Clinical Findings
thromboses, the prognosis for adequate renal function
is good. Renal vein thrombosis may rarely recur in the The epidemic form begins with a prodrome of abdomi-
same kidney or occur in the other kidney years after the nal pain, diarrhea, and vomiting. Oliguria, pallor, and
original episode of thrombus formation. Extension into bleeding manifestations, principally gastrointestinal,
the vena cava, with pulmonary emboli, is possible. occur next. Hypertension and seizures develop in some
children—especially those who develop severe renal fail-
RENAL ARTERIAL DISEASE ure and fluid overload. There may also be significant di-
rect involvement of the central nervous system (CNS).
Arterial disease (eg, fibromuscular hyperplasia and con- Anemia is profound, and red blood cell fragments are
genital stenosis) is a rare cause of hypertension in chil- seen on blood smears. A high reticulocyte count con-
dren. Although there are few clinical clues to underly- firms the hemolytic nature of the anemia, but may not
ing arterial lesions, arterial lesions should be suspected be noted in the presence of renal failure. Thrombocy-
in children whose hypertension is severe, with onset at topenia is profound, but other coagulation abnormali-
or before age 10 years, or associated with delayed visu- ties are less consistent. Serum fibrin split products are
alization with nuclear medicine scan. The diagnosis is often present, but fulminant disseminated intravascular
established by renal arteriography with selective renal coagulation is rare. Hematuria and proteinuria are often
vein renin measurements. Some of these lesions may be present. The serum complement level is normal except
approached by transluminal angioplasty or surgery (see in those cases related to congenital predisposition.
Renal Hypertension section), but repair may be techni-
cally impossible in many small children. Although Complications
thrombosis of renal arteries is rare, it should be consid-
ered in a patient experiencing acute onset of hyperten- These usually result from renal failure. Neurologic
sion and hematuria in an appropriate setting (eg, in as- problems, particularly seizures, may result from elec-
718 / CHAPTER 22

trolyte abnormalities such as hyponatremia, hyperten-

sion, or from CNS vascular disease. Severe bleeding, RENAL FAILURE
transfusion requirements, and hospital-acquired infec-
tions must be anticipated.
ACUTE RENAL FAILURE
Treatment Acute renal failure is the sudden inability to excrete urine
of sufficient quantity or adequate composition to main-
Meticulous attention to fluid and electrolyte status is tain body fluid homeostasis. The most common cause in
crucial. The use of antimotility agents and antibiotics is children is dehydration. However, encountering signs of
believed to worsen the disease. Antibiotics may up-reg- acute renal insufficiency in a hospitalized patient raises
ulate and cause the release of large amounts of bacterial many other possibilities: impaired renal perfusion or renal
Shiga toxin. Early dialysis improves the prognosis; the ischemia, acute renal disease, renal vascular compromise,
patient’s size will usually dictate peritoneal dialysis as acute tubular necrosis, or obstructive uropathy. Table
the technique of choice. Seizures usually respond to 22–2 lists such prerenal, renal, and postrenal causes.
control of hypertension and electrolyte abnormalities.
It has been suggested that the plasma in some cases
lacks a prostacyclin-stimulating factor that is a potent
Clinical Findings
inhibitor of platelet aggregation. Therefore, plasma in- The hallmark of early renal failure is oliguria. Although
fusion or plasmapheresis has been advocated in severe an exact etiologic diagnosis may be unclear at the onset,
cases. Platelet inhibitors have also been tried, but the
results have not been impressive, especially late in the
disease. Nonetheless, it appears that using a platelet in- Table 22–2. Classification of renal failure.
hibitor early in the disease in an attempt to halt platelet
consumption and microvascular occlusion may obviate Prerenal
the need for platelet transfusion and reduce the progres- Dehydration due to gastroenteritis, malnutrition, or
sion of renal failure. Red cell and platelet transfusions diarrhea
may be necessary; although the risk of volume overload Hemorrhage, aortic or renal vessel injury, trauma, cardiac
is significant, it can be minimized by dialysis. Erythro- disease and/or surgery, renal arterial thrombosis
poietin (epoetin alfa) treatment may reduce red cell Diabetic acidosis
transfusion needs. Although no therapy is universally Hypovolemia associated with capillary leak or nephrotic
accepted for patients with this syndrome, the strict con- syndrome
trol of hypertension and nutrition and the timely use of Shock
dialysis reduce morbidity and mortality. If renal failure Heart failure
is “nonoliguric,” and thus output is sufficient to ensure Renal
against fluid overload and electrolyte abnormalities, Hemolytic-uremic syndrome
management of renal failure without dialysis is possible. Acute glomerulonephritis
Prolonged renal hypoperfusion
Nephrotoxins
Acute tubular necrosis or vascular nephropathy
Course & Prognosis Renal (cortical) necrosis
Most commonly, children recover from the acute Intravascular coagulation—septic shock, hemorrhage
episode within 2–3 weeks. Some form of residual renal Diseases of renal vessels
disease (including hypertension) occurs in about 30%, Iatrogenic disorders
and end-stage renal failure in about 15%. Thus follow- Severe infections
up of children recovering from hemolytic–uremic syn- Drowning, especially fresh water
drome should include serial determinations of renal Crystalluria: sulfonamide or uric acid
function for 1–2 years and meticulous attention to Hyperuricacidemia from cancer treatment
blood pressure for 5 years. Mortality (about 3–5%) is of Hepatic failure
Postrenal
greatest concern in the early phase, primarily resulting
Obstruction due to tumor, hematoma, posterior urethral
from CNS complications. valves, ureteropelvic junction stricture, ureterovesical
junction stricture, ureterocele
Stones
Trachtman H, Christen E: Pathogenesis, treatment, and therapeu- Trauma to a solitary kidney or collecting system
tic trials in hemolytic uremic syndrome. Curr Opin Pediatr
1999;11:162.
Renal vein thrombosis
 KIDNEY & URINARY TRACT / 719

classifying the oliguria as outlined in Table 22–2 is relieved by insertion of a urethral catheter followed by
helpful in determining if any immediately reversible surgical correction. Timely intervention may prevent ir-
causes are present. reversible renal injury and chronic renal failure. De-
If the cause of an elevation in serum BUN and crea- layed voiding in the newborn period, anuria, or poor
tinine or oliguria is unclear, entities that can be quickly urinary stream usually suggests obstruction. Uretero-
addressed and corrected (eg, volume depletion) should pelvic junctional obstruction usually presents as an ab-
be considered first. Once normal renal perfusion is en- dominal mass.
sured and no clinical evidence for de novo renal disease
is present, a diagnosis of acute tubular necrosis (vaso-
motor nephropathy, ischemic injury) may be enter- Complications
tained.
The clinical severity of the complications depends on
A. PRERENAL CAUSES the degree of renal functional impairment and oliguria.
Common complications include (1) fluid overload (hy-
The most common cause of decreased renal function in pertension, congestive heart failure, pulmonary edema),
children is compromised renal perfusion. It is usually (2) electrolyte disturbances (hyperkalemia), (3) meta-
secondary to dehydration, although abnormalities of bolic acidosis, (4) hyperphosphatemia, and (5) uremia.
renal vasculature and poor cardiac performance may
also be considered. Such causes should be sought and, if
present, corrected to determine if true renal functional Treatment
disturbances are present. Table 22–3 lists the urinary
indices helpful in distinguishing these “prerenal” condi- An indwelling bladder catheter is inserted to ascertain
tions from true renal parenchymal diseases, such as urine output. If urine volume is insignificant and renal
acute tubular necrosis. failure is established, the catheter should be removed to
minimize infection risks. Prerenal or postrenal factors
B. RENAL CAUSES should be excluded or rectified, and normal circulating
Causes of renal failure intrinsic to the kidney include volume established and maintained with appropriate
acute glomerulonephritides, hemolytic–uremic syn- fluids. Strict measurements of volume input and output
drome, acute interstitial nephritis, and nephrotoxic in- must be maintained, and adjustments made to reduce
jury. The diagnosis of acute tubular necrosis (vasomo- input as reduction in output dictates. The patient’s re-
tor nephropathy)—which is reserved for those cases in sponse is assessed by physical examination and mea-
which renal ischemic insult is believed to be the likely surement of urinary output. Measurement of central
cause—should be considered when correction of prere- venous pressure may be indicated. If diuresis does not
nal or postrenal problems does not improve renal func- occur in response to these measures, furosemide
tion. (1–5 mg/kg, per dose, intravenously, maximum of
200 mg) may be used. The effective dose will depend
C. POSTRENAL CAUSES on the amount of functional compromise (if < 50%
Postrenal failure, usually found in newborns with uro- function, initiate attempt at diuresis with maximum
logic anatomic abnormalities, is accompanied by vary- dose). If a response does not occur within 1 hour (ie,
ing degrees of renal insufficiency. Obstruction of the the urine output remains low [< 0.5 mL/kg/h]), the
bladder outlet, as in posterior urethral valves, should be furosemide dose, if not already at maximum, should be
increased up to 5 mg/kg. In some cases the addition of
a long-acting thiazide diuretic, such as metolazone, may
be useful. If no diuresis occurs with maximum dosing,
Table 22–3. Urine studies. further administration of diuretics will not be helpful.
If these maneuvers stimulate some urine flow but
Prerenal Failure Acute Tubular Necrosis biochemical evidence of acute renal failure persists, the
resulting nonoliguric acute renal failure should be more
Urine osmolality 50 mOsm/kg Urine osmolality equal to or
manageable. Fluid overload and dialysis may be
greater than plasma osmo- less than plasma osmolality
lality
averted. However, if the medications and nutrients re-
quired exceed the urinary output, dialysis is indicated.
Urine sodium < 10 mEq/L Urinary sodium > 20 mEq/L Institution of dialysis before the early complications of
Ratio of urine creatinine to Ratio of urine creatinine to acute renal failure develop is likely to improve clinical
plasma creatinine > 14:1 plasma creatinine < 14:1 management and outcome. It is important to adjust
medication dosage according to the degree of renal
Specific gravity > 1.020 Specific gravity 1.012–1.018 function.
720 / CHAPTER 22

Acute Dialysis quate, hypophosphatemia must be addressed. High

dextrose concentrations (maximum 4.25%) can correct
A. INDICATIONS FOR DIALYSIS fluid overload rapidly at the risk of causing hyper-
Immediate indications for dialysis are (1) severe hyper- glycemia. Fluid removal may be increased with more
kalemia; (2) unrelenting metabolic acidosis (usually in a frequent exchanges of the dialysate, but rapid osmotic
situation where fluid overload prevents sodium bicar- transfer of water may result in hypernatremia.
bonate administration); (3) fluid overload with or with- Even in small infants, hemodialysis can rapidly cor-
out severe hypertension or congestive heart failure (a rect major metabolic and electrolyte disturbances, as
situation that would seriously compromise nutrition or well as volume overload. The process is highly efficient,
drug administration); and (4) symptoms of uremia, but the speed of the changes can cause problems such as
usually manifested in children by CNS depression. The hemodynamic instability. Anticoagulation is usually re-
rate of rise of both urea nitrogen and creatinine levels quired. Careful monitoring of the appropriate bio-
may indicate the need for dialysis; it is generally ac- chemical parameters is important. Note that during or
cepted that the urea nitrogen level should not be al- immediately following the procedure, blood sampling
lowed to exceed 100 mg/dL (keeping in mind nonrenal will produce misleading results because equilibration
functional factors contributing to excessive BUN) in between extravascular compartments and the blood will
small children. not yet have been completed. Vascular access must be
obtained and carefully monitored.
B. METHODS OF DIALYSIS
The choice between peritoneal dialysis and hemodialy- Course & Prognosis
sis may be dictated by their availability. Peritoneal dial-
ysis is generally preferred in children because of the ease The period of severe oliguria, if it occurs, usually lasts
of performance and patient tolerance. Although peri- about 10 days. Oliguria lasting longer than 3 weeks, or
toneal dialysis is technically less efficient than he- anuria, makes a diagnosis of acute tubular necrosis very
modialysis, hemodynamic stability and metabolic con- unlikely and favors vascular injury, severe ischemia
trol can be better sustained because this technique can (cortical necrosis), GN, or obstruction. The diuretic
be applied on a relatively continuous basis. However, phase begins with an increase in urinary output to pas-
hemodialysis should be considered (1) if rapid removal sage of large volumes of isosthenuric urine containing
of toxins is desired, (2) if the size of the patient makes sodium levels of 80–150 mEq/L. During the recovery
hemodialysis less technically cumbersome and hemody- phase, signs and symptoms subside rapidly, although
namically well tolerated, or (3) if impediments to effi- polyuria may persist for several days or weeks. Urinary
cient peritoneal dialysis are present (eg, ileus). Further- abnormalities usually disappear completely within a few
more, if vascular access and usage of anticoagulation are months. If renal recovery does not ensue, arrangements
not impediments, a slow, continuous hemodialytic are made for chronic dialysis and eventual renal trans-
process (continuous renal replacement treatment) may plantation.
be applied, if the technical expertise is available.
C. COMPLICATIONS OF DIALYSIS CHRONIC RENAL FAILURE
Complications of peritoneal dialysis include peritonitis, Chronic renal failure in children most commonly re-
volume depletion, and technical complications such as sults from developmental abnormalities of the kidneys
dialysate leakage and respiratory compromise from intra- or urinary tract. The kidneys may develop poorly (dys-
abdominal dialysate fluid. Peritonitis can be avoided by genesis) or not at all (agenesis). Cystic development
strict observance of aseptic technique. Peritoneal fluid may result in immediate or progressive insufficiency.
cultures are obtained as clinically indicated. Dialysate Abnormal development of the urinary tract may not
can leak around the dialysis catheter or through tissue permit normal renal development. Obstructive uropa-
planes, causing dissection. Leakage is reduced by good thy or severe vesicoureteral reflux nephropathy, without
catheter placement technique and appropriate intra-ab- (or despite) surgical intervention, continues to cause a
dominal dialysate volumes. Technical problems causing significant amount of progressive renal insufficiency in
abnormal flow of dialysate in and out of the peritoneal children. In older children, the chronic glomeru-
cavity require help from a nephrologist. Dialysis is use- lonephritides and nephropathies, irreversible nephro-
ful in maintaining electrolyte balance. Potassium (ab- toxic injury, or hemolytic–uremic syndrome may also
sent from standard dialysate solutions) can be added to result in chronic renal failure.
the dialysate as required. Phosphate is also absent be- When chronic renal failure is the result of an inade-
cause hyperphosphatemia is an expected problem in quate amount of normally functioning renal tissue, the
renal failure. Nonetheless, if phosphate intake is inade- inability to concentrate urine results in polyuria, poly-
 KIDNEY & URINARY TRACT / 721

dipsia, or enuresis. Affected patients often fail to thrive. normocytic from decreased renal erythropoietin synthe-
Without medical care, children with long-standing sis) is usual. Platelet dysfunction and other abnormali-
chronic renal failure may present with complications ties of the coagulation system may be present. Bleeding
such as rickets or anemia. phenomena—especially gastrointestinal bleeding—may
Chronic renal failure may follow acute GN or de- be a problem. Cardiovascular manifestations may be
velop with chronic GN in the absence of an obvious life-threatening. Uremic pericarditis, congestive heart
acute episode. Presentations range from hypertension to failure, or hypertension may occur.
overt uremic symptoms. Growth failure depends on age
at presentation and the rapidity of functional decline.
Some of the chronic glomerulonephritides (eg, mem-
branoproliferative GN) can progress unnoticed if subtle
Treatment
abnormalities of the urinary sediment are undetected or Treatment of chronic renal failure before dialysis is
ignored. Any child with a history of chronic GN or sig- done to preserve remaining renal function and to avoid
nificant renal injury needs close follow-up and moni- complications. Controlling hypertension (see Renal
toring of renal function. Angiotensin-converting en- Hypertension section) and hyperphosphatemia and
zyme (ACE) inhibitors decrease the glomerulosclerosis preventing UTI are important. Acidosis may be treated
that follows glomerular injury and are often used to with sodium citrate solutions, as long as the added
treat the associated hypertension. sodium will not aggravate hypertension. Sodium re-
striction is advisable when hypertension is present. Hy-
perphosphatemia is controlled by dietary restriction
Complications and dietary phosphate binders (eg, calcium carbonate).
The kidney can compensate for gradual loss of func- Vitamin D should be given to maintain normal serum
tioning nephrons in progressive chronic renal failure calcium. When the BUN level exceeds approximately
until the GFR falls below 15 mL/min/1.73 m2. Com- 50 mg/dL, or if the child is lethargic or anorexic, di-
plications appear as compensatory power is lost. In chil- etary protein should be restricted. Potassium restriction
dren who have developmentally reduced function but will be necessary as the GFR falls to a level where uri-
are unable to concentrate the urine, polyuria and thus nary output decreases sharply. Meanwhile, the diet
dehydration is more likely to be a problem than fluid must continue to provide the child’s specific daily re-
overload. Output may be expected to gradually dimin- quirements.
ish with time as renal failure progresses to end stage; Renal function must be monitored regularly (creati-
however, some children can continue to produce gener- nine and BUN), and serum electrolytes, calcium, phos-
ous quantities of urine (but not of good quality) even phorus, alkaline phosphatase, and hemoglobin and
though they require dialysis. Moreover, a salt-wasting hematocrit levels must be checked. Results guide
state can occur. In contrast, children who develop changes in fluid and dietary management as well as
chronic renal failure due to the glomerular disease or dosages of phosphate binder, citrate buffer, vitamin D,
renal injury will characteristically retain sodium and and blood pressure medications. Anemia may be
water so that hypertension occurs relatively early. treated with epoetin alfa. These treatment areas require
Metabolic acidosis and growth retardation occur careful monitoring to minimize symptoms while the
early in chronic renal failure. Disturbances in calcium, child’s need for chronic dialysis and transplantation
phosphorus, and vitamin D metabolism leading to continues to be assessed.
renal osteodystrophy require prompt attention. Al- Care must be taken to avoid medications that aggra-
though renal compensation and increased parathyroid vate hypertension; increase the body burden of sodium,
hormone can maintain a normal serum phosphate level potassium, or phosphate; or increase production of
early in the course, secondary hyperparathyroidism BUN. Successful management relies greatly on educa-
with resulting skeletal abnormalities will occur. This tion of the patient and family.
physiologic response to hyperphosphatemia can be re- Attention must also be directed toward the psy-
flected by an increase in serum alkaline phosphatase, chosocial needs of the patient and family during adjust-
but measurement of intact parathyroid hormone is ment to chronic illness. The strategy for patient man-
more clinically specific. agement—and the need for family education and
Uremic symptoms occur late in chronic renal failure adjustment—changes when a plan for chronic dialysis
and include anorexia, nausea, and malaise. CNS fea- and possible renal transplantation is initiated. These
tures range from confusion, apathy, and lethargy to stu- changes may include a reduction in medications or di-
por and coma. Associated electrolyte abnormalities may etary limitations, with the potential for improving
precipitate seizures (more commonly, a result of un- growth. Some uremic children will grow significantly
treated hypertension). Anemia (normochromic and when given human recombinant growth hormone.
722 / CHAPTER 22

Dialysis & Transplantation creased understanding of the roles of water and salt re-
tention on the one hand and overactivity of the
The best tolerated treatment of end-stage renal disease renin–angiotensin system on the other has done much
in a child is a successful and uncomplicated renal trans- to guide therapy; nevertheless, not all forms of hyper-
plant. The North American Pediatric Renal Transplant tension can be explained by these two mechanisms.
Collaborative Study reports a 1-year graft survival rate The causes of renal hypertension in the newborn pe-
of living-related kidney transplants of 90%, with 85% riod include (1) congenital anomalies of the kidneys or
at 2 years and 75% at 5 years. With cadaveric trans- renal vasculature, (2) obstruction of the urinary tract,
plantation, percentages of graft survivals are 76%, 71%, (3) thrombosis of renal vasculature or kidneys, and
and 62%, respectively. Overall, the mortality rate is 4% (4) volume overload. Some instances of apparent para-
for recipients of living-related donors and 6.8% for re- doxic elevations of blood pressure have been reported in
cipients of cadaver organs. These percentages are af- clinical situations in which chronic diuretic therapy is
fected by the increased mortality, reported to be as high used, such as in bronchopulmonary dysplasia. Hyperten-
as 75% in infants younger than age 1 year, primarily sive infants should also be examined for renal, vascular,
due to technical issues and complications of immuno- or aortic abnormalities (eg, thrombosis, neurofibromato-
suppression. Therefore, most transplantation centers sis, coarctation) as well as some endocrine disorders.
are waiting until infants reach a body weight of about
15 kg. This body weight appears to be associated with a
significantly improved survival rate. Adequate growth Diagnosis
and well-being are directly related to acceptance of the A child is normotensive if the average recorded systolic
graft, the degree of normal function, and the side ef- and diastolic blood pressures are lower than the 90th
fects of medications. percentile for age and sex. The 90th percentile in the
Great advances have also been made in peritoneal newborn period is approximately 85–90/55–65 mm Hg
dialysis and hemodialysis, both in technique and in our for both sexes. In the first year of life, the acceptable lev-
understanding of the specialized approach required. He- els are 90–100/60–67 mm Hg. Incremental increases
modialysis is now performed in major centers that de- with growth occur, gradually approaching young adult
vote their entire effort to the treatment of pediatric pa- ranges of 100–120/65–75 mm Hg in the late teens.
tients and is regarded as a reasonable long-range method Careful measurement of blood pressure includes ensur-
of treating the older child with end-stage renal disease. ing correct cuff size and reliable equipment. The cuff
The demonstrated feasibility of chronic peritoneal dialy- should be wide enough to cover two thirds of the upper
sis in children, however, has made it the primary choice arm and should encircle the arm completely without
of dialysis therapy, especially for small children. It is well causing an overlap in the inflatable bladder. Although
accepted and can be performed in the home. an anxious child may have an elevation in blood pres-
The best measure of the success of chronic dialysis sure, abnormal readings must not be too hastily attrib-
in children is the level of physical and psychosocial re- uted to this cause. Repeat measurement is helpful, espe-
habilitation achieved. Patients continue to participate cially after the child has been consoled.
in day-to-day activities and attend school. Although Routine laboratory studies include a complete blood
catch-up growth rarely occurs, patients can grow at an count, urinalysis, and urine culture. Radiography and
acceptable rate even though they may remain in the ultrasonography are used to study the anatomy of the
lower percentiles. Use of epoetin alfa, growth hormone, urinary tract, the blood flow to the kidneys, and their
and better control of renal osteodystrophy contribute to function. A renal biopsy (which rarely reveals the cause
improved outcome. of hypertension unless clinical evidence of renal disease
is present) should always be undertaken with special
Neu AM, Warady BA: Dialysis and renal transplantation in infants care in the hypertensive patient and preferably after
with irreversible renal failure. Adv Ren Replace Ther pressures have been controlled by therapy. Figure
1996;3:48. 22–3 presents a suggested approach to the outpatient
Warady BA et al: Optimal care of the pediatric end-stage renal dis- work-up of hypertension.
ease patient on dialysis. Am J Kidney Dis 1999;33:567.
Treatment
RENAL HYPERTENSION A. TREATMENT OF ACUTE EMERGENT HYPERTENSION
Hypertension in children is commonly of renal origin. A hypertensive emergency exists when CNS signs of hy-
It is anticipated as a complication of known renal pertension appear, such as papilledema or encephalopa-
parenchymal disease, but it may be found on routine thy. Retinal hemorrhages or exudates indicate a need
physical examination in an otherwise normal child. In- for prompt and effective control. In children, however,
 KIDNEY & URINARY TRACT / 723

Initial data: Physical examination,including BP (for extremity

history, UA, BUN, Cr, electrolytes, peripheral renin
(electrocardiogram, chest x-ray, urine
metanephrines, catechols)

Normal Abnormal
initial data initial data

Renal
Mild BP, Sever or
older age child, difficult to control BP C3, ANA, Nonrenal
and family history (suspected renovascular renal ultrasound
hypertension)
Treat and Appropriate diagnostic
follow steps and referral

Renal ultrasound with Nephrology

Doppler study referral
Difficult
Treatment Captopril enhanced scan
or mRA

Normal anatomy Abnormal renal anatomy Vascular flow discrepancy

Treat BP and follow (eg, scarring, atrophy, cysts)

Digital subtraction angiography or

Repeat initial workup, arteriography, +_ renal vein renins
Surgical Nonsurgical
renal vein renin, or
arteriography
(digital subtraction
angiography) Normal Abnormal
Resolved Persistent
BP
Transluminal
Abnormal
angioplasty
or vascular
Continue treatment surgery
Normal Continued BP
and follow

Reevaluate? Follow-up Resolution

Figure 22–3. Approach to the outpatient work-up of hypertension. ANA = antinuclear antibody; BUN = blood urea
nitrogen; Cr = creatinine.

end-organ abnormalities secondary to hypertension the 95th percentile for age may be treated with oral an-
commonly are not present. Treatment varies with the tihypertensives, aiming for progressive improvement
clinical presentation. The primary classes of useful anti- and control within 48 hours.
hypertensive drugs are (1) diuretics, (2) α- and β-
adrenergic blockers, (3) ACE inhibitors, (4) calcium 1. Sublingual nifedipine—This calcium channel
channel blockers, and (5) vasodilators. blocker is rapid acting, and, in appropriate doses,
Whatever method is used to control emergent hy- should not result in hypotensive blood pressure levels.
pertension, medications for sustained control should The liquid from a 10-mg capsule can be drawn into a
also be initiated so that the effect will be maintained syringe and the dosage approximated. The exact dosage
when the emergent measures are discontinued (Table for children who weigh less than 10–30 kg is difficult
22–4). Acute elevations of blood pressure not exceeding to ascertain by this method, but 5 mg is a safe starting
724 / CHAPTER 22

Table 22–4. Antihypertensive drugs for Table 22–5. Antihypertensive drugs

emergent treatment. for ambulatory treatment.

Major Side Drug Oral Dose Major Side Effectsa

Drug Oral Dose Effectsa
Hydrochloro- 2–4 mg/kg/24 h as Potassium depletion,
Nifedipine 0.25–0.5 mg/kg/ Flushing, tachycardia thiazide single dose or in 2 hyperuricemia
SL individual doses
Labetalol 1–3 mg/kg/h IV Secondary to β-block- Furosemide 1–5 mg/kg/dose, Potassium and volume
ing activity 2–3 doses per day depletion
Sodium 0.5–10 mg/kg/min Cyanide toxicity, so- Hydralazine 0.75 mg/kg/24 h in Lupus erythematosus,
nitroprusside IV drip dium and water reten- 4–6 divided doses tachycardia, headache
tion
Amlodipine 0.2 to 0.5 mg/kg/d Fatigue, headache, facial
Furosemide 1–5 mg/kg IV Secondary to severe in 2 divided doses flushing
volume contraction,
Propranolol 0.2–5 mg/kg/dose, Syncope, cardiac failure,
hypokalemia
2–3 doses per day hypoglycemia
Diazoxide 2–10 mg/kg IV Hyperglycemia, hyper-
Minoxidil 0.15 mg/kg/dose, Tachycardia, angina,
bolus uricemia, sodium and
2–3 doses per day fluid retention, hir-
water retention
sutism
Hydralazine 0.1–0.2 mg/kg IV Sodium and water re-
Captopril 0.3–2 mg/kg/dose, Rash, hyperkalemia,
tention, tachycardia,
2–3 doses per day glomerulopathy
flushing
a
Many more side effects than those listed have been reported.
Enalapril 0.2–0.5 mg/kg/d in Proteinuria, cough,
2 divided doses hyperkalemia
Nifedipine 0.5–1 mg/kg/d, 3 Flushing, tachycardia
point. Because the treatment is given for rising blood doses per day
pressure, it is unlikely that the effects will be greater Verapamil 3–7 mg/kg/d in AV conduction dis-
than desired. Larger children with malignant hyperten- 2 or 3 divided doses turbance
sion require 10 mg. In such cases, the capsule may sim- a
Many more side effects than those listed have been reported.
ply be pierced and the medication squeezed under the
patient’s tongue.
2. Intravenous hydralazine—This vasodilator is
sometimes effective. Dosage varies according to the ciency, but disadvantages of possible electrolyte imbal-
severity of the hypertension and should begin at about ance must be considered. Single-drug therapy with an
0.15 mg/kg. ACE inhibitor is useful, especially because most hyper-
tension in children has renal causes. Calcium channel
3. Sodium nitroprusside—In an intensive care set- blockers are increasingly useful, and appear well toler-
ting, this powerful vasodilator is very effective for reduc- ated in children. The use of the vasodilator type of anti-
ing severely elevated blood pressure. Intravenous admin- hypertensive drug requires concomitant administration
istration of 0.5–10 mg/kg/min will reduce blood of a diuretic to counter the effect of vasodilation on in-
pressure in seconds, and the dose must be monitored creasing renal sodium and water retention and a β-
carefully. Metabolism of the drug results in thiocyanate; blocker to counter reflex tachycardia. Minoxidil, con-
thus, with prolonged usage, levels of thiocyanate must sidered the most powerful of the orally administered
be monitored, especially in renal insufficiency. vasodilators, can be extremely efficacious in the treat-
4. Furosemide—Administered at 1–5 mg/kg, intra- ment of severe, sustained hypertension, but its effect is
venously, this diuretic will reduce blood volume and greatly offset by the other effects described. Hirsutism
enhance the effectiveness of antihypertensive drugs. is a significant side effect. Hydralazine hydrochloride
may still be the most common vasodilator in pediatric
B. TREATMENT OF SUSTAINED HYPERTENSION use—but, again, the necessity of using two additional
Several choices are available (Table 22–5). A single drugs for maximum benefit keeps vasodilators in re-
drug such as a β-blocker (unless contraindicated, eg, in serve for those severe situations calling for management
reactive airway disease) may be adequate to treat mild with three or four drugs. The advice of a pediatric
hypertension. Diuretics are useful to treat renal insuffi- nephrologist should be sought.
 KIDNEY & URINARY TRACT / 725

Bartosh SM, Aronson AJ: Childhood hypertension. An update on tubular dysfunction, and chronic renal failure. Table
etiology, diagnosis and treatment. Pediatr Clin North Am 22–6 lists some of the major entities; discussion of the
1999;46:235.
rarer conditions is beyond the scope of this book.

DISORDERS OF THE RENAL TUBULES

INHERITED OR Three subtypes of renal tubular acidosis are well recog-
DEVELOPMENTAL DEFECTS nized: (1) the classic form, called type I or distal renal
OF THE URINARY TRACT tubular acidosis; (2) the bicarbonate-wasting form,
called type II or proximal renal tubular acidosis; and
(3) type IV, or hyperkalemic renal tubular acidosis (rare
There are many developmental, hereditary, or meta- in children), which is associated with hyporeninemic
bolic defects of the kidneys and collecting system. The hypoaldosteronism. Type I and type II and their vari-
clinical consequences include metabolic abnormalities, ants are encountered most frequently in children. Type
failure to thrive, nephrolithiasis, renal glomerular or III is a combination of types I and II.

Table 22–6. Inherited or developmental defects of the urinary tract.

Cystic diseases of genetic origin sis, Hurler syndrome, Niemann-Pick disease, familial
Polycystic disease metachromatic leukodystrophy, glycogenosis type I [von
Autosomal-recessive form (infantile) Gierke disease], glycogenosis type II [Pompe disease])
Autosomal-dominant form (adult) Hereditary amyloidosis (familial Mediterranean fever, here-
Other syndromes that include either form dofamilial urticaria with deafness and neuropathy, pri-
Cortical cysts mary familial amyloidosis with polyneuropathy)
Several syndromes are known to have various renal cys- Hereditary renal diseases associated with tubular
tic manifestations, including “simple” cysts; may not transport defects
have significant effect on renal functional status or Hartnup disease
be associated with progressive disease Fanconi’s anemia
Medullary cysts Oculocerebrorenal syndrome of Lowe
Medullary sponge kidney Cystinosis (infantile, adolescent, adult types)
Medullary cystic disease (nephronophthisis) Wilson’s disease
Hereditary and familial cystic dysplasia Galactosemia
Congenital nephrosis Hereditary fructose intolerance
“Finnish” disease Renal tubular acidosis (many types)
Dysplastic renal diseases Hereditary tyrosinemia
Renal aplasia (unilateral, bilateral) Renal glycosuria
Renal hypoplasia (unilateral, bilateral, total, segmental) Vitamin D-resistant rickets
Multicystic renal dysplasia (unilateral, bilateral, multilocular, Pseudohypoparathyroidism
postobstructive) Vasopressin-resistant diabetes insipidus
Familial and hereditary renal dysplasias Hypouricemia
Oligomeganephronia Hereditary diseases associated
Hereditary diseases associated with nephritis with lithiasis
Hereditary nephritis with deafness and ocular defects Hyperoxaluria
(Alport’s syndrome) L-Glyceric aciduria
Nail-patella syndrome Xanthinuria
Familial hyperprolinemia Lesch-Nyhan syndrome and variants, gout
Hereditary nephrotic syndrome Nephropathy due to familial hyperparathyroidism
Hereditary osteolysis with nephropathy Cystinuria (types I, II, III)
Hereditary nephritis with thoracic asphyxiant dystrophy Glycinuria
syndrome Miscellaneous
Hereditary diseases associated with intrarenal deposition Hereditary intestinal vitamin B12 malabsorption
of metabolites Total and partial lipodystrophy
Angiokeratoma corporis diffusum (Fabry disease) Sickle cell anemia
Heredopathia atactica polyneuritiformis (Refsum disease) Bartter syndrome
Various storage diseases (eg, GM1 monosialogangliosido-
726 / CHAPTER 22

Primary tubular disorders in childhood, such as threshold, that is, the concentration of serum bicarbon-
glycinuria, hypouricemia, or renal glycosuria, may re- ate above which bicarbonate appears in the urine. With
sult from a defect in a single tubular transport pathway more severe acidosis, the concentration of serum bicar-
(see Table 22–6). bonate drops and bicarbonate disappears from the
urine; these changes reflect normal distal tubular acidi-
1. Distal Renal Tubular Acidosis (Type I) fication.
Proximal renal tubular acidosis is the most common
The most common form of distal renal tubular acidosis type encountered in children. It is often an isolated de-
in childhood is the hereditary form. The clinical pre- fect, and in the newborn infant it can be considered an
sentation is one of failure to thrive, anorexia, vomiting, aspect of renal immaturity. Onset in infants is accom-
and dehydration. Hyperchloremic metabolic acidosis panied by failure to thrive, hyperchloremic acidosis, hy-
occurs, with hypokalemia and a urinary pH exceeding pokalemia, and, rarely, nephrocalcinosis. Secondary
6.5. The acidosis is more severe in the presence of a bi- forms result from reflux or obstructive uropathy and
carbonate “leak.” This variant of distal renal tubular occur in association with other tubular disorders (see
acidosis with bicarbonate wasting has been called type Table 22–6). Proximal renal tubular acidosis requires
III, but for clinical purposes need not be considered as a greater than 3 mEq/kg of alkali per day to correct the
distinct entity. Concomitant hypercalciuria may lead to acidosis. Serum bicarbonate should be monitored
rickets, nephrocalcinosis, nephrolithiasis, and renal fail- weekly until a level of at least 20 mEq/L is attained.
ure. Citrate solutions (eg, Bicitra, Polycitra) are some-
Other situations that may be responsible for distal what more easily tolerated than sodium bicarbonate.
renal tubular acidosis are found in some of the entities Bicitra contains 1 mEq of Na+ and citrate per milliliter.
listed in Table 22–6. Polycitra contains 2 mEq per milliliter of citrate and
Distal renal tubular acidosis results from a defect in 1 mEq each of Na+ and K+. The required daily dosage is
the distal nephron, in the tubular transport of hydrogen given in three divided doses. Potassium supplementa-
ion, or in the maintenance of a steep enough gradient tion may be required, because the added sodium load
for proper excretion of hydrogen ion. This defect can presented to the distal tubule may exaggerate potassium
be accompanied by degrees of bicarbonate wasting. losses.
The classic test for distal renal tubular acidosis is an The prognosis is excellent in cases of isolated de-
acid load from NH4Cl. The test is cumbersome and fects, especially when the problem is related to renal
can produce severe acidosis. A clinical trial of alkali ad- immaturity. Alkali therapy can usually be discontinued
ministration should be used to rule out proximal (type after several months to 2 years. Growth should be nor-
II) renal tubular acidosis. The dose of alkali required to mal, and the gradual increase in the serum bicarbonate
achieve a normal plasma bicarbonate concentration in level to above 22 mEq/L heralds the presence of a raised
patients with distal renal tubular acidosis is low (seldom bicarbonate threshold in the tubules. If the defect is
exceeding 2–3 mEq/kg/24 h)—in contrast to that re- part of a more complex tubular abnormality (Fanconi
quired in proximal renal tubular acidosis (> syndrome with attendant phosphaturia, glycosuria, and
10 mEq/kg/24 h). Higher doses are needed, however, if amino aciduria), the prognosis depends on the underly-
distal renal tubular acidosis is accompanied by bicar- ing disorder or syndrome.
bonate wasting. Correction of acidosis can result in re-
duced complications and improved growth. OCULOCEREBRORENAL SYNDROME
Distal renal tubular acidosis is usually permanent,
although it sometimes occurs as a secondary complica- (Lowe Syndrome)
tion. If the defect is not caused by a greater tubular dis- Lowe syndrome results from a range of mutations in
order and renal damage is prevented, the prognosis is the ORCL1 gene that codes for a Golgi apparatus phos-
good. phatase. Affected males have anomalies involving the
eyes, brain, and kidneys. The physical stigmas and the
2. Proximal Renal Tubular degree of mental retardation are variable and depend on
the location of the mutation. In addition to congenital
Acidosis (Type II) cataracts and buphthalmos, the typical facies includes
Proximal renal tubular acidosis is characterized by an prominent epicanthal folds, frontal prominence, and a
alkaline urine pH, loss of bicarbonate in the urine, and tendency to scaphocephaly. Muscle hypotonia is a
mildly reduced serum bicarbonate concentrations. prominent finding. The renal abnormalities are of
About 85–90% of bicarbonate reabsorption occurs in tubule function and include hypophosphatemic rickets
the proximal tubules. The lesion in proximal renal with low serum phosphorus levels, low to normal serum
tubular acidosis is a lowering of the renal bicarbonate calcium levels, elevated serum alkaline phosphatase lev-
 KIDNEY & URINARY TRACT / 727

els, renal tubular acidosis, and aminoaciduria. Treat- mal recessive. Cystine is stored in cellular lysosomes in
ment includes alkali therapy, phosphate replacement, virtually all tissues. Eventually, cystine accumulation re-
and vitamin D. Antenatal diagnosis is possible. sults in cell damage and cell death, particularly in the
renal tubules. Renal failure between ages 6 and 12 years
Satre et al: Characterization of a germline mosaicism in families is common.
with Lowe syndrome, and identification of seven novel muta- Whenever the diagnosis of cystinosis is suspected,
tions in the ORCL1 gene. Am J Hum Genet 1999;65:68. slitlamp examination of the corneas by an ophthalmol-
ogist should be performed, because cystine crystal de-
CONGENITAL HYPOKALEMIC position causes an almost pathognomonic ground-glass
ALKALOSIS (Bartter Syndrome “dazzle” appearance. Increased white cell cystine levels
are diagnostic. Hypothyroidism is common.
and Gitelman Syndrome) Cystagon therapy is helpful in the treatment of
Bartter syndrome is characterized by severe hy- cystinosis. Depending on the progression of chronic
pokalemic, hypochloremic metabolic alkalosis, ex- renal failure, management is directed toward all side ef-
tremely high levels of circulating renin and aldosterone, fects of renal failure, with particular attention paid to
and a paradoxic absence of hypertension. On renal the control of renal osteodystrophy. Dialysis and trans-
biopsy, a striking juxtaglomerular hyperplasia is seen. plantation may be needed.
A neonatal form of Bartter syndrome is thought to
result from mutations in two genes affecting either Anikster Y et al: Identification and detection of the common 65-kb
Na+–K+ or K+ transport. These patients have life-threat- deletion breakpoint in the nephropathic cystinosis gene. Mol
Genet Metab 1999;66:111.
ening episodes of fever and dehydration with hypercal-
ciuria and early-onset nephrocalcinosis. Classic Bartter http://www.cystinosisfoundation.org
syndrome presenting in infancy with polyuria and
growth retardation (but not nephrocalcinosis) is PHOSPHATE-LOSING RENAL
thought to result from mutations in a chloride channel TUBULAR SYNDROMES & OTHER
gene. Gitelman syndrome occurs in older children and FORMS OF RICKETS
features episodes of muscle weakness, tetany, hy-
pokalemia, and hypomagnesemia. These children have Recent investigation of the metabolic products of vita-
hypocalciuria. min D3 has done much to clarify the causes of various
Treatment with prostaglandin inhibitors and potas- forms of rickets. Those forms due primarily to a lack of
sium-conserving diuretics (eg, amiloride combined with available calcium are described in Chapter 10. They in-
magnesium supplements) and potassium may be bene- clude idiopathic hypercalciuria, in which there is exces-
ficial. Although the prognosis is guarded, a few patients sive urinary calcium loss not responsive to reduction in
seem to have less severe forms of the disease that are calcium intake, lack of vitamin D3 because of low di-
compatible with long survival times. etary intake or from steatorrhea, and vitamin D depen-
dency and azotemic rickets. In vitamin D3 dependency,
Rodriguez-Soriano J: Bartter’s syndrome comes of age. Pediatrics there is an inborn or acquired inability to synthesize
1999;103:663. 1,25-dihydroxycholecalciferol (the calcium transport
stimulating factor, type I), or there may be end-organ
insensitivity to this factor (type II). Treatment consists
CYSTINOSIS of giving supplementary calcium or vitamin D in ap-
Three types of cystinosis have been identified: adult, propriate doses.
adolescent, and infantile. In children the adolescent Diseases associated with decreased availability of
type is characterized by cystine deposition and, if left phosphorus also cause rickets. Excessive use of antacids
untreated with phosphocysteamine (Cystagon), is ac- may be responsible. Most commonly the defect is an
companied by the development of the renal Fanconi inherited or acquired one in which a defect of phospho-
syndrome and varying degrees of renal failure; growth is rus reabsorption is variably associated with other trans-
usually normal. The infantile type is both the most port defects (eg, Fanconi syndrome). Certain general-
common and the most severe. Characteristically, chil- ized metabolic diseases—notably Wilson disease,
dren present in the first or second year of life with Fan- galactosemia, fructose intolerance, and cystinosis—may
coni syndrome and, without the metabolic benefit of cause similar tubular damage. Treatment of the primary
Cystagon treatment, progress to end-stage renal failure. type includes giving extra phosphorus. Acquired forms
Cystinosis results from mutations in the CTNS gene are treated in the same manner as the basic disease.
that codes for a cystine transporter. About 50% of pa- Familial hypophosphatemic vitamin D-resistant
tients share an identical deletion. Inheritance is autoso- rickets is an example of a tubular nephropathy in which
728 / CHAPTER 22

only phosphorus transport is affected. Most patients Clinically, the diagnosis can be made on the basis of
present during the second year of life, but some condi- a history of polydipsia and polyuria that are not sensi-
tions have onset in the first 6 months. tive to the administration of vasopressin, desmopressin
Clinical features vary. Changes may be only bio- acetate, or lypressin. It is wise to confirm this diagnosis
chemical, with a strikingly low serum phosphorus and by performing a vasopressin test. Carefully monitored
an elevated alkaline phosphatase level. Muscle hypoto- water restriction does not increase the tubular reabsorp-
nia may be severe; growth failure, bowing of the legs, tion of water (TcH2O) to above 3 mL/min/m2. Urine
and enlargement of the wrists, knees, and costochon- osmolality will remain lower than 450 mOsm/kg,
dral junctions are often associated with spinal deformi- whereas serum osmolality rises and total body weight
ties. Craniosynostosis has been described in infants falls. Before weight reduction greater than 5% occurs or
with this disease. Pathologic fractures may be seen on before serum osmolality exceeds 320 mOsm/kg, vaso-
radiograph as well as certain unique findings consisting pressin should be administered. Urine concentrating
of an irregular mosaic formation of the haversian sys- ability is impaired in a number of conditions—sickle
tem and trabecular “halos” of low-density bone. cell anemia, pyelonephritis, potassium depletion, hy-
In most cases, the serum phosphorus level is less than percalcemia, cystinosis and other renal tubular disor-
2 mg/dL. The urinary calcium level is low, and the serum ders and obstructive uropathy—and as a result of
calcium level may be normal or slightly low. Serum levels nephrotoxic drugs.
of 1,25-dihydroxycholecalciferol are low, probably be- In infants, it is usually best to allow water as de-
cause high levels of phosphate in the tubule cell shut off manded and to restrict salt. Serum sodium levels should
the 1α-hydroxylase activity. Aminoaciduria is rare. be evaluated at intervals to avoid hyperosmolality from
Treatment consists of giving 1–3 g of phosphorus inadvertent water restriction. In later childhood,
daily, either as a buffered monosodium and disodium sodium intake should continue to be restricted to
hydrogen phosphate solution at pH 7.4 or as Fleet’s 2–2.5 mEq/kg/24 h.
Phospho-Soda. Magnesium oxide, 10–15 mg/kg/d by Treatment with hydrochlorothiazide is helpful, and
mouth, may be of value. Supplementary calcitriol, up many patients show improvement with administration
to 40 mg/kg/d, should be given if the serum calcium of prostaglandin inhibitors such as indomethacin or tol-
levels remain below normal. metin.
Normal growth is never achieved unless every effort
is made to keep the serum phosphorus level over Wilden RS, Cogdell DE: Clinical utility of direct mutation testing
3 mg/dL. for congenital nephrogenic diabetes insipidus in families. Pe-
diatrics 1999;103:632.
Gregory MJ, Schwartz GJ: Diagnosis and treatment of renal tubu-
lar disorders. Semin Nephrol 1998;18:317.
NEPHROLITHIASIS
NEPHROGENIC DIABETES INSIPIDUS Renal calculi in children may result from certain inborn
errors of metabolism, such as cystine in cystinosis,
In the normal kidney, the interstitial fluid of the papilla glycine in hyperglycinuria, urates in Lesch–Nyhan syn-
is hyperosmolar to the fluid in the collecting duct. The drome, and oxalates in oxalosis. Stones may occur sec-
luminal cells have a specific receptor for antidiuretic ondary to hypercalciuria in distal tubular acidosis, and
hormone (ADH), which, acting via cyclic adenosine large stones are quite often seen in children with spina
monophosphate, permits water to move across the cell bifida who have paralyzed lower limbs. Treatment is
membrane in response to the osmotic gradient. The limited to that of the primary condition, if possible.
congenital X-linked recessive form of nephrogenic dia- Surgical removal of stones should be considered only
betes insipidus results from mutations in the vaso- for obstruction, intractable severe pain, and chronic in-
pressin receptor, AVPR2. Autosomal (recessive and fection.
dominant) forms of nephrogenic diabetes insipidus are
caused by mutations of the AQP2 gene that codes for a Cystinuria
water channel protein, aquaporin-2. Genetic counseling
and mutation testing are available. Cystinuria, like Hartnup disease and a number of other
The symptoms are limited to polyuria, polydipsia, disorders, is primarily an abnormality of amino acid
and failure to thrive. In some children, particularly if transport across both the enteric and proximal renal
the solute intake is unrestricted, adjustment to an ele- tubular epithelium. There appear to be at least three
vated serum osmolality may develop. These children are biochemical types. In the first type, the bowel transport
particularly susceptible to episodes of dehydration, of basic amino acids and cystine is impaired, but trans-
fever, vomiting, and convulsions. port of cysteine is not impaired. In the renal tubule,
 KIDNEY & URINARY TRACT / 729

basic amino acids are again rejected by the tubule, but than age 6 months have UTIs far more commonly than
cystine absorption appears to be normal. The reasons boys, whereas uncircumcised boys younger than
for the cystinuria are, therefore, still obscure. Heterozy- 3 months of age have more UTIs than girls. Circumci-
gous individuals have no aminoaciduria. The second sion reduces the likelihood of UTI in boys tenfold. The
type is similar to the first except that heterozygous indi- protective effect of circumcision is mediated by a reduc-
viduals excrete excess cystine and lysine in the urine, tion in the density of distal urethral and periurethral
and cystine transport in the bowel is normal. In the bacterial colonization. Similarly, the density of urethral
third type, only the nephron is involved. The only clin- and periurethral colonization with uropathogenic bac-
ical manifestations are related to stone formation: teria is correlated to the risk of UTI in girls.
ureteral colic, dysuria, hematuria, proteinuria, and sec- Dysfunctional voiding, which is uncoordinated re-
ondary UTI. Urinary excretion of cystine, lysine, argi- laxation of the urethral sphincter during voiding lead-
nine, and ornithine is increased. ing to incomplete emptying of the bladder, may cause
The most reliable way to prevent stone formation is frequent UTI. Similarly, any condition that interferes
to maintain a constantly high free-water clearance. This with complete emptying of the bladder, such as consti-
involves generous fluid intake. Alkalinization of the pation or a neurogenic bladder, is associated with an in-
urine is helpful. If these measures do not prevent signif- creased risk of UTI. Poor perineal hygiene, structural
icant renal lithiasis, the use of tiopronin (Thiloa) is rec- abnormalities of the urinary tract, catheterization, and
ommended. instrumentation of the urinary tract are all associated
with UTI. In sexually active teenagers, intercourse may
Primary Hyperoxaluria introduce bacteria into the urethra and bladder, result-
ing in acute cystitis.
Oxalate production in humans is derived from the ox- Most UTIs are ascending infections. Specific ad-
idative deamination of glycine to glyoxylate, from the hesins present on the fimbria of uropathogenic bacteria
serine-glycolate pathway, and from ascorbic acid. allow colonization of the uroepithelium in the urethra
At least two enzymatic blocks have been described. and bladder and increase the likelihood of UTI.
Type 1 is a deficiency of liver-specific peroxisomal ala- The inflammatory response to infection during
nine:glyoxylate aminotransferase. Type 2 is glyoxylate pyelonephritis may result in renal parenchymal scars. It
reductase deficiency. is hypothesized that renal parenchymal scars in infancy
Excess oxalate combines with calcium to form insol- and childhood may contribute to hypertension, renal
uble deposits in the kidneys, lungs, and other tissues. disease, and renal failure later in life. Unfortunately,
The onset is during childhood. The joints are occasion- long-term outcome studies of the natural history of
ally involved, but the main effect is on the kidneys, pyelonephritis and the effect of medical intervention on
where progressive oxalate deposition leads to fibrosis the development of adult renal diseases are not avail-
and eventual renal failure. able.
Pyridoxine supplementation and a low-oxalate diet The organisms responsible for UTI are normal fecal
have been tried as therapy, but the overall prognosis is flora, most commonly E coli (> 85%), Klebsiella, Pro-
poor, and most patients succumb to uremia by early teus, other gram-negative bacteria, and, less frequently,
adulthood. Renal transplantation is not very successful Enterococcus or coagulase-negative staphylococci.
because of destruction of the transplant kidney. How-
ever, encouraging results have been obtained with con-
comitant liver transplantation, correcting the metabolic A. SYMPTOMS AND SIGNS
defect. Newborns and infants demonstrate nonspecific signs,
Hyperoxaluria may also occur secondary to ileal dis- including fever, hypothermia, jaundice, poor feeding,
ease or after ileal resection. irritability, vomiting, failure to thrive, and sepsis.
Strong, foul-smelling or cloudy urine may be noted.
Broyer M et al: Management of oxalosis. Kidney Int 1996;53:593. Preschool children may have abdominal or flank pain,
Cochat P: Primary hyperoxaluria type 1. Kidney Int 1999;55:2533. vomiting, fever, urinary frequency, dysuria, urgency, or
enuresis. School-age children commonly have classic
signs of cystitis (frequency, dysuria, urgency) or
URINARY TRACT INFECTIONS pyelonephritis (fever, vomiting, flank pain). Costover-
tebral tenderness is unusual in young children, but may
be demonstrated by school-age children.
UTI is common in children, but the frequency de- Physical examination should include attention to
creases with age. It is estimated that 8% of girls and 2% blood pressure determination, abdominal exam, and a
of boys will acquire UTIs in childhood. Girls older genitourinary exam. Urethritis, poor perineal hygiene,
730 / CHAPTER 22

herpes simplex virus, or other genitourinary infections because differentiating asymptomatic bacteriuria (eg,
may be apparent on examination. detected at the time of a febrile viral infection) from
true UTI with no or minimal signs of inflammation in
B. LABORATORY TESTS the urine can be difficult. Repeated urine cultures are
Collection of urine for urinalysis and culture is difficult often helpful in differentiating asymptomatic bacteri-
in children due to frequent contamination of the sam- uria from contamination of the culture versus true
ple. In toilet-trained, cooperative, older children, a UTI.
midstream, clean-catch method is satisfactory. Al- In children with pyelonephritis, a serum creatinine
though cleaning of the perineum does not improve should be determined.
specimen quality, straddling of the toilet to separate the
labia in girls, retraction of the foreskin in boys, and col- C. TREATMENT
lecting midstream urine significantly reduce contami- Management of UTI requires an assessment of toxicity,
nation. hydration, ability to tolerate oral intake, and signs of
In infants and young children, bladder catheteriza- sepsis. Very young children (younger than 3 months)
tion or suprapubic collection is necessary in most cases and children with dehydration, toxicity, or sepsis
to avoid contaminated samples. Bagged urine speci- should be admitted to the hospital and treated with
mens are helpful only if negative. parenteral antimicrobials.
Screening urinalysis indicates pyuria (>5 WBC/hpf) Older infants and children who are not seriously ill
in most children with UTI, but many children with can be treated as outpatients. Initial antimicrobial ther-
pyuria do not have UTI. White cells may be present in apy is based on prior history of infection and antimi-
urine from the urethra or vagina or be present because crobial use, as well as location of the infection in the
of a systemic infection. The leukocyte esterase test cor- urinary tract. Uncomplicated cystitis can be treated
relates well with the presence of pyuria, but has a simi- with amoxicillin, trimethoprim–sulfamethoxazole, or a
lar false-positive rate. The detection of urinary nitrite first-generation cephalosporin. Each of these antimicro-
by dipstick is highly correlated with urine culture posi- bials is concentrated in the lower urinary tract, and
tive for enteric organisms. Most young children (70%) high cure rates are common. There are significant dif-
with UTI have negative nitrite tests because they empty ferences in the rates of antimicrobial resistance, so
their bladder frequently, and several hours is required knowledge of the rates in the local community is im-
for bacteria to convert ingested nitrates to nitrite in the portant. More seriously ill children are treated parenter-
bladder. The sensitivity of nitrite detection is highest ally initially with a third-generation cephalosporin or
on a first morning void. Gram stain of unspun urine parenteral aminoglycoside. The initial antimicrobial
correlates well with culture recovery of 105 cfu/mL or choice is adjusted after culture and susceptibility are
more, but is infrequently available outside of the hospi- known. For sexually mature teenagers, fluoro-
tal. quinolones such as ciprofloxacin and levofloxacin given
The gold standard for diagnosis remains the prop- for 3 days for cystitis are usually cost-effective.
erly collected urine specimen. Specimens that are not The recommended duration of antimicrobial ther-
immediately cultured should be refrigerated and kept apy for uncomplicated cystitis is 7–10 days. Short-
cold during transport. Any growth is considered signifi- course therapy of cystitis is not recommended in chil-
cant from a suprapubic culture. Quantitative recovery dren, because differentiating upper and lower tract
of 105 cfu/mL or more is considered significant on disease may be difficult, and higher failure rates are re-
clean-catch specimens, and 104–105 is considered sig- ported in most studies of short-course therapy.
nificant on catheterized specimens. Usually the recov- Acute pyelonephritis is usually treated for 10 days,
ery of multiple organisms indicates contamination; although some very severe infections may require
however, some contaminated specimens will yield only longer therapy. The duration of parenteral therapy in
a single species. uncomplicated pyelonephritis is not well defined, but
Asymptomatic bacteriuria is detected in 0.5–1.0% most children can complete therapy orally once symp-
of children who are screened with urine culture. tomatic improvement has occurred. A repeat urine cul-
Asymptomatic bacteriuria is believed to represent colo- ture 24–48 hours after beginning therapy is not needed
nization of the urinary tract with nonuropathogenic if the child is improving and doing well.
bacteria. Treatment may increase the risk of sympto-
matic UTI by eliminating nonpathogenic colonization. D. RADIOLOGIC EVALUATION
Screening urine cultures in nonsymptomatic children Because congenital urologic abnormalities increase the
are, therefore, generally discouraged. The treatment of risk of UTI, radiologic evaluation of first UTI has been
children with fever, normal urinalysis, and significant routinely recommended. These recommendations usu-
growth on quantitative urine culture is controversial, ally include routine ultrasound of the kidneys and void-
 KIDNEY & URINARY TRACT / 731

ing cystourethrogram (VCUG). These recommenda- with grades I–III, IV and V VUR, prophylactic antimi-
tions are controversial because no good data are avail- crobials may be beneficial in reducing UTI, as an alter-
able to support the theory that the detection and man- native to surgical correction, or in the interval prior to
agement of vesicourethral reflux (VUR), the most surgical therapy. Many experts recommend surgical
commonly detected abnormality, improves the long- correction of higher grade reflux, particularly grade V.
term renal health of most children. Trimethoprim–sulfamethoxazole and nitrofurantoin
VUR is a congenital abnormality present in about are approved for prophylaxis. Use of broader spectrum
1% of the population. VUR is graded using the inter- antimicrobials leads to colonization and infection with
national scale (I—reflux into ureter; II—reflux to the resistant strains.
kidney; III—reflux to kidney with dilation of ureter Children with dysfunctional voiding generally do
only; IV—reflux with dilation of ureter and mild blunt- not benefit from prophylactic antimicrobials; rather,
ing of renal calyces; V—reflux with dilation of ureter addressing the underlying dysfunctional voiding is most
and blunting of renal calyces). Reflux is detected in important.
30–50% of children 1 year of age and younger. The In some children, erroneous diagnosis based on con-
natural history of reflux is to improve, and 80% of re- taminated urine specimens leads to recovery of gram-
flux of grades I, II, or III will resolve or significantly negative rods with increasing antimicrobial resistance.
improve within 3 years following detection. Prophylactic antimicrobials are not helpful—catheter-
VCUG should be done selectively on children with ized or suprapubic urine specimens are often helpful in
first UTI. Children with suspected urologic abnormal- clarifying the underlying contamination.
ity due to weak stream, dribbling, or perineal abnor-
malities should be studied with VCUG. Boys with first Baker PC et al: The addition of ceftriaxone to oral therapy does not
UTI should be studied to detect posterior urethral improve outcome in febrile children with urinary tract infec-
valves, an important congenital abnormality that re- tions. Arch Pediatr Adolesc Med 2001;155(2):133 [PMID:
quires surgery. Children older than 3 years who are oth- 11177086].
erwise healthy and growing well usually can be followed Hoberman A et al: Imaging studies after a first febrile urinary tract
infection in young children. N Engl J Med 2003;348(3):
clinically and do not need VCUG with first UTI. The 195 [PMID: 12529459].
yield in sexually active teenagers is also very low.
Huicho L et al: Meta-analysis of urine screening tests for determin-
Ultrasonographic examination of kidneys should be ing the risk of urinary tract infection in children. Pediatr In-
done in children with acute pyelonephritis who have fect Dis J 2002;21(1):1 [PMID: 11791090].
not improved after 3–5 days of antimicrobial treatment Smellie JM et al: Outcome at 10 years of severe vesicoureteric reflux
adjusted for the susceptibility of the organism. The ex- managed medically: Report of the international reflux study
amination is done to detect renal or perirenal abscesses in children. J Pediatr 2001;139(5):656 [PMID: 11713442].
or obstruction of the kidney. The yield of routine ultra- Subcommittee on Urinary Tract Infection, American Academy of
sound examination of first-time UTI in children who Pediatrics: Practice parameter: The diagnosis, treatment, and
are improving on therapy is low in recent studies. Most evaluation of the initial urinary tract infection in febrile in-
fants and young children. Pediatrics 1999;103(4):843
obstructing lesions of the urinary system are detected [PMID:10103321].
prenatally by in utero ultrasound.
E. FOLLOW-UP REFERENCES
Children with UTI should be followed with screening Barratt TM et al: Pediatric Nephrology, 5th ed. Lippincott Williams
urinalysis 1 and 2 months after resolution of UTI. Dip- & Wilkins, 2003.
stick nitrate determination can be used at home by par- Webb N, Postlethwaite R: Clinical Paediatric Nephrology, 3rd ed.
ents on first morning voided urine in children with fre- Oxford University Press, 2003.
quently recurring UTI.
F. PROPHYLACTIC ANTIMICROBIALS
Selected children with frequently recurring UTI may
benefit from prophylactic antimicrobials. In children
 Neurologic & Muscular Disorders 23
Paul G. Moe, MD, & Tim A. Benke, MD, PhD

such as hemangiomas, ash-leaf depigmented patches, or

NEUROLOGIC ASSESSMENT café au lait spots present? Is the fontanel open or closed,
too big or too small? A more detailed mental status ex-
& NEURODIAGNOSTIC amination may be appropriate for school-age children
PROCEDURES (Table 23–2). The child should be observed for truncal
sway or loss of balance (Romberg test). Testing for vi-
bratory appreciation requires that the child be old
NEUROLOGIC HISTORY enough to report whether he or she can feel the vibra-
& EXAMINATION tions of a tuning fork applied to the digits or bony
prominences. Muscle mass, consistency, tone, and
Despite recent advances in neurodiagnostic testing and strength should be assessed in all four limbs, across
neuroimaging, a thorough history remains the most im- multiple joints, and in the neck and trunk. Muscle
portant tool in accurately diagnosing neurologic disor- stretch reflexes can be elicited normally from infancy to
ders. The chief complaint(s) and present illness should adulthood at the biceps, triceps, knees, and ankles. The
clearly delineate the temporal profile and sequence of presence, absence, or asymmetry of automatic infantile
neurologic symptoms. From a detailed history, the clin- movements and reflexes (automatisms) should be noted
ician will determine if the neurologic symptoms are (see Table 23–1).
acute or chronic, static or progressive, recurrent or The examiner should then proceed with a systematic
monophasic, periodic or randomly intermittent, short neurologic examination, including an assessment of cra-
or prolonged. The patient’s description of his or her nial nerves II through XII, funduscopy, and testing of
symptoms will provide clues as to the anatomic local- eye movements and pupillary light and near-vision re-
ization of the disturbance and possible pathogenic flexes. Cerebellar control of body and extremity pos-
mechanisms. The history should also include what pre- ture, ambulation, and fine coordinated movements can
cipitates, palliates, or changes the symptoms. usually be evaluated by watching the child walk, run,
The history and review of systems provide essential play with or reach for toys, sit, and stand still. Re-
background information about the patient and may sponses to light touch and mildly painful stimulation
provide evidence for a more generalized disorder or for can be assessed by tickling or touching the child and
associated or predisposing conditions. Similarly, the lightly pinching toes or fingers and observing facial ex-
family history and social history frequently provide pression and withdrawal and avoidance movements.
clues for underlying genetic, hereditary, environmental, Position sensation can be assessed in older children by
or psychological conditions that are the basis of the pa- having them stand with eyes closed. The clinician
tient’s complaints. The social history also provides in- should construct a differential diagnostic list of disor-
sight into how the symptoms affect the child’s and fam- ders that could account for the patient’s symptoms and
ily’s day-to-day living, school performance, and quality develop a systematic approach to neurodiagnostic test-
of life. A developmental history may provide the earliest ing and neuroimaging procedures.
clues of a degenerative disorder. Some developmental
milestones are summarized in Table 23–1.
The physical examination should include the child’s LUMBAR PUNCTURE
height, weight, head circumference, blood pressure, Spinal fluid is usually obtained by inserting a small-
pulse rate, general appearance, and level of alertness and gauge needle (eg, No. 22) through the L3–L4 interver-
attentiveness. It is important to observe the child’s tebral space into the thecal sack while the patient is
spontaneous activity, behavior and responses to light, lying on his or her side. After an opening pressure is
noise, and touch. Is the child abnormally irritable or measured, a small amount of fluid is removed most fre-
demonstrating odd behavior for his or her age? Are quently to examine for evidence of infection or inflam-
there dysmorphic features of the face, head, ears, trunk, mation (Table 23–3). Fluid is sent for red and white
extremities, or digits? Are any discolored patches of skin cell counts, for determination of the concentrations of
732
Copyright © 2005, 2001, by The McGraw-Hill Companies, Inc. Click here for terms of use.
 NEUROLOGIC & MUSCULAR DISORDERS / 733

Table 23–1. Neurologic developmental milestones.

Birth 3 Months 6 Months 9 Months 12–15 Months 24 Months

Motor Flexor posture, Sits: head for- Rolls both ways, Creeps, pulls up Walks with one Walks and runs well,
lifts head prone, ward, bobbing, begins to sit standing, pincer or both hands walks downstairs,
hands grasped lifts head supine, alone, supports grasp, sits well held, stands turns pages singly
hands open, re- (erect), bounces alone briefly,
tains briefly releases on
command
Special Regards (vision), Looks at hands, Discriminates Picks up raisin, Localizes Towers six or seven
senses may follow 45 follows 90–180 voices, localizes “bye-bye” noises, localizes cubes, imitates
degrees degrees sounds pain scribble
Adaptive Startles to Smiles socially, Holds cube, pal- Bangs toys to- Assists in dress- Asks for toilet, pulls
sound, delayed vocalizes so- mar grasp, re- gether, pat-a- ing, attempts on garments, spoon-
nociceptive re- cially, follows trieves toy, cake spoon feeding, feeds well, parallel
sponse vertically transfers and tries two-cube play
rakes raisin tower
Language Throaty noises Coos, chuckles, Babbles (poly- “Ma-ma, Da-da,” Understands Speaks in phrases,
vocal social re- syllables), one other “word” simple com- names three to five
sponse “mmm-mmm” mand, speaks pictures, pronouns:
one to three “I, me, you”
words
Reflex Tonic neck, pal- Disappearing Begins volun- Parachute re-
mar grasp tonic neck, tary stepping sponse
Moro reflex
Automatisms Moro reflex, Landau re- Neck righting,
sucks, roots, sponse, traction: blinks to threat
stepping, sup- no head lag
porting, traction:
head lag

protein and glucose, and for viral and bacterial cultures.

In some cases, additional information is obtained with
special staining techniques for mycobacteria and fun-
Table 23–2. Mental status examination gus. Additional fluid may be sent for polymerase chain
for school-age children. reaction (PCR) testing for specific viral agents, anti-
body titer determinations, cytopathologic study, lactate
Orientation: Time, place, situation, name, date, year. and pyruvate concentrations, and amino acid and neu-
Memory: Recent and remote, eg, “What did you have for rotransmitter analysis. Lumbar puncture is imperative
lunch?” “What did you do on your birthday?” Remember when bacterial meningitis is suspected. Caution must
(for 10 min): “Red flag, Washington’s birthday, be exercised, however, when signs of increased intracra-
Christmas presents.” nial pressure (eg, papilledema) or focal neurologic signs
Calculation: Depends on educational background. Example: are present that might indicate a substantial risk of pre-
Subtract serial sevens. cipitating tentorial or tonsillar herniation.
Proverbs: Interpret: “Too many cooks spoil the broth.” “A
rolling stone gathers no moss.”
Situation: “What would you do if you saw a fire?” ELECTROENCEPHALOGRAPHY
Aphasia: “What’s this?” (chalk). “Stick out your tongue.” “Put Electroencephalography (EEG), a widely used noninva-
your right finger on your left ear.” Sample speech, reading, sive electrophysiologic method for recording cerebral
and writing.
activity, has its greatest clinical applicability in the
 Table 23–3. Characteristics of cerebrospinal fluid in the normal child and in central nervous system infections and inflammatory
conditions.

Initial Pressure Protein Glucose

Condition (mm H2O) Appearance Cells/µL (mg/dL) (mg/dL) Other Tests Comments
Normal < 160 Clear 0–5 lymphocytes; first 15–35 (lumbar), 50–80 (two CSF-IgG index CSF protein in first month
3 months, 1–3 PMNs; 5–15 (ventricular); thirds of blood < 0.7a; LDH 2–27 may be up to 170 mg/dL
neonates, up to 30 up to 150 (lumbar) glucose); may units/L in small-for-date or pre-
lymphocytes, 20–50 for short time after be increased mature infants. No in-
RBCs birth; to 6 months after seizure crease in WBCs due to
up to 65 seizure.
Bloody tap Normal or low Bloody (some- One additional WBC/700 One additional milli- Normal RBC number should Spin down fluid, super-
times with clot) RBCsb; RBCs not crenated gram per 800 RBCsb fall between first and natant will be clear and
third tubes; wait 5 min colorless.c
between tubes
Bacterial men- 200–750+ Opalescent to Up to thousands, mostly Up to hundreds Decreased; may Smear and culture man- Very early, glucose may
ingitis, acute purulent PMNs; early, few cells be none datory; LDH > 24 U/L; be normal. PCR (meningo-
lactate, IL-8, TNF elevated, and pneumococcus)
734

correlate with prognosis plasma, CSF may aid

diagnosis
Bacterial men- Usually Clear or opal- Usually increased; PMNs Elevated Normal or de- LDH usually > 24 U/L; Smear and culture may
ingitis, par- increased escent usually predominate creased PCR be negative if antibio-
tially treated tics have been in use.
Tuberculous 150–750+ Opalescent; 250–500, mostly lympho- 45–500; parallels cell Decreased; may Smear for acid-fast or- Consider AIDS.
meningitis fibrin web or cytes; early, more PMNs. count; increases over be none ganism: CSF culture and
pellicle time inoculation; PCR
Fungal men- Increased Variable; often 10–500; early, more PMNs; Elevated and in- Decreased India ink preparations, Often superimposed in
ingitis clear then mostly lymphocytes creasing cryptococcal antigen, PCR, patients who are debil-
culture, inoculations, itated or on immunosup-
immunofluorescence tests pressive therapy.
Aseptic men- Normal or Clear unless None to a few hundred, 20–125 Normal; may be CSF, stool, blood, throat Acute and convalescent
ingoencepha- slightly in- cell count mostly lymphocytes; low in mumps, washings for viral cul- antibody titers for some
litis (viral men- creased > 300/µL PMNs predominate herpes, or other tures; LDH < 28 U/L; viruses. In mumps, up to
ingitis, or para- early viral infections PCR for HSV, CMV, EBV, 1000 lymphocytes; serum
meningeal enterovirus, etc. amylase often elevated.
disease) Rarely, a thousand
cells present in enterovi-
ral infection.
 Parainfectious 80–450, usually Usually clear 0–50+, mostly lymphocytes 15–75 Normal CSF-IgG index may be in- No organisms. Fulminant
encephalomy- increased creased; oligoclonal cases resemble bacterial
elitis (ADEM) bands variable meningitis.
Polyneuritis Normal and Early: normal; Normal; occasionally Early: normal; late: Normal CSF-IgG index may be in- Try to find cause (viral
occasionally late: xantho- slight increase 45–1500 creased; oligoclonal infections, toxins, lupus,
increased chromic if pro- bands variable. diabetes, etc).
tein high
Meningeal car- Often elevated Clear to opal- Cytologic identification Often mildly to mod- Often depres- Cytology Seen with leukemia, med-
cinomatosis escent of tumor cells erately elevated sed ulloblastoma, meningeal
melanosis, histiocytosis X.
Notes: May mimic menin-
gitis.
Brain abscess Normal or in- Usually clear 5–500 in 80%; mostly Usually slightly in- Normal; occa- Imaging study of brain Cell count related to
creased PMNs creased sionally de- (MRI) proximity to meninges;
creased findings as in purulent
meningitis if abscess
perforates.
a
CSF-IgG index = CSF IgG/serum IgG ÷ CSF albumin/serum albumin.
b
Many studies document pitfalls in using these ratios due to WBC lysis. Clinical judgment and repeat taps may be necessary to rule out meningitis in this situation.
c
CSF WBC (predicted) = CSF RBC × (blood WBC/blood RBC). O:P ratio = observed CSF WBC ÷ predicted CSF WBC. Also, do WBC: RBC ratio. If O:P ratio ≤ 0.01, and WBC:RBC ratio ≤ 1:100, menin-
735

gitis is absent.
PMN = polymorphonuclear neutrophil; CSF = cerebrospinal fluid; WBC = white blood cell; RBC = red blood cell; LDH = lactate dehydrogenase; AIDS = acquired immunodeficiency syndrome;
PCR = polymerase chain reaction; HSV = herpes simplex virus; CMV = cytomegalovirus; EBV = Epstein–Barr virus; ADEM = acute disseminated encephalomyelitis; IL-8 = interleukin 8; TNF =
tumor necrosis factor.
736 / CHAPTER 23

study of seizure disorders. Activation techniques to ac- short-latency somatosensory evoked potentials (see
centuate abnormalities or disclose latent abnormalities Short-Latency Somatosensory Evoked Potentials sec-
include photic stimulation, sustained hyperventilation tion) indicate the level of function of the relevant sen-
for 3 minutes, and sleep deprivation, the last of which sory pathway or system and identify the site of anatom-
is an excellent, though less widely used, activation ic disruption. Although results of these tests alone are
method. usually not diagnostic, the tests are noninvasive, sensi-
EEG is also used in the evaluation of tumors, cere- tive, objective, and relatively inexpensive extensions of
brovascular accidents, neurodegenerative diseases, and the clinical neurologic examination. Because the audi-
other neurologic disorders causing brain dysfunction. tory and somatosensory tests and one type of visual test
Recordings over a 24-hour period or all-night record- are completely passive, requiring only that the patient
ings are invaluable in the diagnosis of sleep disturbances remain still, they are particularly useful in the evalua-
and narcolepsy. EEG with telemetry or simultaneous tion of neonates, young children, and patients unable
monitoring of behavior on videotape has great useful- to cooperate. Knowledge of normal values and experi-
ness in selected cases. The EEG can be helpful in deter- ence in testing are mandatory.
mining a possible cause or mechanism of coma and is
frequently used to help determine whether coma is irre-
versible and brain death has occurred.
Brainstem Auditory Evoked Potentials
The limitations of EEG are considerable. In most A brief auditory stimulus (click) of varying intensity
cases, the duration of the actual tracing is about and frequency is delivered to the ear to activate the au-
45 minutes and reflects only surface cortical function. ditory nerve (nerve VIII) and sequentially activate the
Many drugs, especially barbiturates and benzodi- cochlear nucleus, tracts and nuclei of the lateral lemnis-
azepines, have considerable effects on the EEG and may cus, and inferior colliculus. Thus this technique assesses
confuse interpretation. Moreover, about 15% of hearing and function of the brainstem auditory tracts.
nonepileptic individuals, especially children, may have Hearing in the neonate or uncooperative patient can
an abnormal EEG. EEG findings such as those occa- be assessed objectively, making the technique particu-
sionally seen in migraine, learning disabilities, or behav- larly useful in high-risk infants and in mentally retarded
ior disorders are often nonspecific and do not reflect or autistic patients. Brainstem auditory evoked poten-
permanent brain damage. A major usefulness of EEG is tials are used to judge brainstem dysfunction in sleep
to show epileptiform activity in children with seizure apnea, Arnold–Chiari malformation, and achondropla-
disorders. Sometimes the findings are diagnostic, as in sia. Because high doses of anesthetic agents or barbitu-
the hypsarrhythmia EEG of infantile spasms or the pro- rates do not seriously affect results, the test is used to as-
longed 3/s spike-wave of absence seizures. sess and monitor brainstem function of surgical patients
At present, computed tomography (CT) scans, (in the operating room) and those in hypoxic–ischemic
evoked potentials, positron emission tomography coma or coma following head injury. Absence of evoked
(PET), regional cerebral blood flow studies, single-pho- potential waves beyond the first wave from the auditory
ton emission computed tomography (SPECT), and nerve usually signifies brain death. Brainstem auditory
magnetic resonance imaging (MRI) supplement the evoked potentials are also useful in the early evaluation
EEG as a diagnostic and prognostic tool. of diseases affecting myelin, that is, the leukodystrophies
and multiple sclerosis, although auditory evoked poten-
tials are less valuable than visual evoked potentials in the
EVOKED POTENTIALS evaluation of multiple sclerosis. Intrinsic brainstem
Cortical auditory, visual, or somatosensory evoked po- gliomas can also be evaluated with auditory evoked po-
tentials (evoked responses) may be recorded from the tentials. They are sometimes useful in evaluation of
scalp surface over the temporal, occipital, or frontopari- hereditary ataxias, Wilson disease, and other degenera-
etal cortex after repetitive stimulation of the retina by tive disorders of the brainstem.
light flashes, the cochlea by sounds, or a nerve by gal-
vanic stimuli of varying frequency and intensity, respec- Pattern-Shift Visual Evoked Potentials
tively. Computer averaging is used to recognize and en-
hance these responses while subtracting or suppressing The preferred stimulus is a shift (reversal) of a checker-
the asynchronous background EEG activity. The pres- board pattern, and the response is a single wave (called
ence or absence of evoked potential waves and their la- P-100) generated in the striate and parastriate visual
tencies (time from stimulus to wave peak or time be- cortex. The absolute latency of P-100 (time from stim-
tween peaks) figures in the clinical interpretation. ulus to wave peak) and the difference in latency be-
The reproducible and quantifiable results obtained tween the two eyes are sensitive indicators of disease.
from brainstem auditory, pattern-shift visual, and The amplitude of response is affected by any process re-
 NEUROLOGIC & MUSCULAR DISORDERS / 737

sulting in poor fixation on the stimulus screen or affect- and brain death, somatosensory evoked potentials sup-
ing visual acuity. Ability to focus on a checkerboard plement the results of auditory evoked potentials.
pattern is necessary. An LED (light-emitting diode),
goggles, or bright flash stimulus can be used in younger
and uncooperative children, but the norms are less stan- PEDIATRIC NEURORADIOLOGIC
dardized. Normal evoked potentials in infants age PROCEDURES
6–7 months suggest that visual acuity is normal. Sedation for Procedures
Clinical applications of the test include detection
and monitoring of strabismus (eg, in amblyopia ex Oral chloral hydrate, 30–60 mg/kg/dose, is safest.
anopsia), optic neuritis, and lesions near the optic nerve Many radiology departments, however, use intra-
and chiasm such as optic gliomas and craniopharyn- venously administered agents because of the risks of
giomas. Degenerative and immunologic diseases that vomiting and aspiration. One favorite is pentobarbital,
affect visual transmission may be detected early and fol- 6 mg/kg for children weighing less than 15 kg and
lowed by serial evaluations. Examples of such diseases 5 mg/kg for larger children (up to a maximum of
include adrenoleukodystrophy, Pelizaeus–Merzbacher 200 mg) given intramuscularly or rectally (at least
disease, some spinocerebellar degenerations, sarcoidosis, 20 minutes before a procedure) or 2–4 mg/kg given in-
and even multiple sclerosis. Flash visual evoked poten- travenously. Equipment to support blood pressure and
tials are used to monitor function during surgery on the respiration must be available. This dosage usually
eyes or optic nerve, to assess cortical or hysterical blind- achieves sedation for up to 2 hours. If, however, seda-
ness, and to evaluate patients with photosensitive tion is inadequate 30 minutes after injection, and if the
epilepsy, who may have exaggerated responses. child’s condition permits a second dose of pentobarbi-
tal, 2 mg/kg is given. General anesthesia may be indi-
Short-Latency Somatosensory cated, especially if the child is to undergo surgery im-
mediately on completion of a radiologic examination.
Evoked Potentials
Responses are commonly produced by electrical stimu- Computed Tomography
lation of peripheral sensory nerves, because this evokes
potentials of greatest amplitude and clarity. Finger tap- CT scanning consists of a series of cross-sectional
ping and muscle stretching may also be used to stimu- (axial) roentgenograms. Radiation exposure is approxi-
late somatosensory potentials. The function of this test mately the same as that from a skull radiographic series.
is similar to that of the auditory test in closely correlat- The images can be viewed on a television screen, as the
ing wave forms with function of the sensory pathways scan is being done, and later examined on films. Both
and permitting localization of conduction defects. record variations in tissue density. CT scanning is of
Short-latency somatosensory evoked potentials are high sensitivity (88–96% of lesions larger than 1–2 cm
used in the assessment of a wide variety of lesions of the can be seen) but low specificity (tumor, infection, or in-
peripheral nerve, root, spinal cord, and central nervous farct may look the same).
system (CNS) following trauma, neuropathies (eg, in The CT scan is often repeated after intravenous in-
diabetes mellitus or Guillain–Barré syndrome), jection of iodized contrast for enhancement, which re-
myelodysplasias, cerebral palsy, and many other disor- flects the vascularity of a lesion or its surrounding tis-
ders. The procedure is often performed on an outpa- sues. Precautions should be taken to ensure that the
tient basis. One method is stimulation of the median patient is not sensitive to iodinated dyes and that aller-
nerve at the wrist with small (nonpainful) electrical gic reactions can be managed promptly. Sufficient in-
shocks and recording of responses from the brachial formation is often obtained from a nonenhanced scan,
plexus above the clavicle, the neck (cervical cord), and thus reducing both cost and risk.
the opposite scalp area overlying the sensorimotor cor-
tex. After stimulation from the knee (peroneal nerve) or Magnetic Resonance Imaging
ankle (tibial nerve), impulses are recorded from the
lower lumbar spinal cord, cervical cord, and sensorimo- MRI is a noninvasive technique that uses the magnetic
tor cortex. Such potentials are used to monitor spinal properties of certain nuclei to produce diagnostically
cord sensory functioning during surgery for scoliosis, useful signals. Currently the technique is based on de-
myelodysplasias, tumors, and other lesions of the spinal tecting the response (resonance) of hydrogen proton
cord or its blood vessels. The technique is also used in nuclei to applied radiofrequency electromagnetic radia-
leukodystrophies involving peripheral nerves, in multi- tion. These nuclei are abundant in the body and more
ple sclerosis, and in the evaluation of hysteria and ma- sensitive to MRI than other nuclei. The strength of
lingering (anesthetic limbs). In the diagnosis of coma MRI signals varies with the relationship of water to
738 / CHAPTER 23

protein and the amount of lipid in the tissue. The MRI Positron Emission Tomography
image displayed provides high-resolution contrast of
soft tissues. MRI can provide information about the PET is an imaging technique that measures the meta-
histologic, physiologic, and biochemical status of tissues bolic rate at a given site by CT scanning. For measure-
in addition to gross anatomic data. ment of local cerebral metabolism, the radiolabeled
MRI has been used to delineate brain tumors, substrate most frequently used has been intravenously
edema, ischemic and hemorrhagic lesions, hydro- administered fluorodeoxyglucose (18F). Gray matter
cephalus, vascular disorders, inflammatory and infec- and white matter are clearly distinguishable; the skull
tious lesions, and degenerative processes. MRI can be and air- or fluid-filled cavities are least active metaboli-
used to study myelination and demyelination and, cally.
through the demonstration of changes in relaxation PET has been used to study the cerebral metabolism
time, metabolic disorders of the brain, muscles, and of neonates and brain activation by visual or auditory
glands. Because bone causes no artifact in the images, stimuli. Pathologic states that have been studied in-
the posterior fossa and its contents can be studied far clude epilepsy, brain infarcts, brain tumors, and de-
better using MRI than with CT scans. Even blood ves- mentias. This functional test of brain metabolism is
sels and the cranial nerves can be imaged. In contrast, useful in preoperative evaluation for epilepsy surgery.
the inability of MRI to detect calcification limits its The epileptogenic zone will often be hypermetabolic
usefulness in the investigation of calcified lesions such during seizures and hypoactive during the time between
as craniopharyngioma and leptomeningeal angiomatosis. seizures. The information from PET scan complements
Magnetic resonance angiography (MRA) is a nonin- EEG and MRI findings to aid in the decision about tis-
vasive (no arterial or venous puncture or dye injection) sue removal. In infants with infantile spasms, PET scan
technique to show large extra- and intracranial blood has occasionally detected focal lesions, thereby leading
vessels. It often replaces the more hazardous intra-arter- to successful surgical removal. Clinical application is
ial injection angiogram. limited by the cost of the procedure and the clinician’s
Perfusion imaging using a paramagnetic contrast need for access to a nearby cyclotron for preparation of
agent is used in stroke patients to evaluate brain is- the radiopharmaceuticals.
chemic penumbra. Similarly, diffusion imaging (mea-
suring random motion of water molecules) may show
reduced diffusion in areas of cytoxic edema, useful in
Ultrasonography
acute strokes, and toxic or metabolic brain injuries. The Ultrasonography offers a pictorial display of the varying
area of involvement often exceeds the T1 hypodense or densities of tissues in a given anatomic region by
T2 hyperdense stroke area, and possibly reflects recov- recording the echoes of ultrasonic waves reflected from
erable tissue injury as compared with totally infarcted it. These waves, modulated by pulsations, are intro-
tissue, cell death, or apoptosis (programmed cell death) duced into the tissue by means of a piezoelectric trans-
in the center of the stroke. ducer. The many advantages of ultrasonography in-
Another new MRI technique, proton MR spec- clude the ability to assess a structure and its positioning
troscopy, measures signals of increased cellular (neu- quickly with easily portable equipment, without ioniz-
ronal?) activity, and oxidative metabolism: neuronal ing radiation, and at about one fourth the cost of CT
acetyl aspartate (NAA), phosphocreatinine (PCR), and scanning. Sedation is usually not necessary, and the
phosphomonoester (PME) are increased. Ratios are procedure can be repeated as often as needed without
often calculated to choline and Pi (inorganic phos- risk to the patient. In brain imaging, B-mode and real-
phate). Or increased lactate (anaerobic metabolism), time sector scanners are usually used, permitting excel-
choline, and creatinine, reflecting increased cell sur- lent detail in the coronal and sagittal planes. Contigu-
face—as in gliosis or scarring—can be assessed in a cho- ous structures can be studied by a continuous sweep
sen voxel or tiny area of interest. An epileptic focus in and reviewed on videotape.
the medial temporal lobe is an example: an active Ultrasonography has been used for in utero diagno-
seizure site might show increased metabolism. Sclerosis sis of hydrocephalus and other anomalies. In neonates,
and gliosis (“scar”) would show the converse. the thin skull and the open anterior fontanelle have fa-
Functional MRI (fMRI) can be performed at the cilitated imaging of the brain, and ultrasonography is
same time as an ongoing regular MRI. Blood oxygena- used to screen and follow infants of less than 32 weeks’
tion changes in an area of interest (eg, an area of lan- gestation or weighing less than 1500 g for intracranial
guage acquisition) during rest and then during a verbal hemorrhage. Other uses in neonates include detection
work paradigm can identify and lateralize the language of hydrocephalus, major brain and spine malforma-
cortex. A change in ratio of oxyhemoglobin to deoxyhe- tions, and calcifications from intrauterine infection
moglobin results in a detectable MRI signal. with cytomegalovirus (CMV) or Toxoplasma.
 NEUROLOGIC & MUSCULAR DISORDERS / 739

Cerebral Angiography
Arteriography remains a useful procedure in the diag- DISORDERS AFFECTING THE
nosis of many cerebrovascular disorders, particularly in NERVOUS SYSTEM IN INFANTS
cerebrovascular accidents or in potentially operable vas-
cular malformations. In some brain tumors, arteriogra- & CHILDREN
phy may be necessary to define the precise location or
vascular bed, to differentiate among tumors, or to dis-
tinguish tumor from abscess or infarction. Noninvasive
ALTERED STATES OF CONSCIOUSNESS
CTs, MRIs, and MRAs can diagnose many cases of sta-
tic or flowing blood disorders (eg, sinus thromboses). If ESSENTIALS OF DIAGNOSIS
necessary, invasive arteriography is usually done via
femoral artery–aorta catheterization.
& TYPICAL FEATURES

Myelography • Reduction or alteration in cognitive and affective

mental functioning and in arousability or atten-
Radiographic examination of the spine may be indi- tiveness.
cated in cases of spinal cord tumors or various forms of • Acute onset.
spinal dysraphism and in the rare instance of herniated
disks in children. MRI has largely replaced sonography
and CT.

Aydin K et al.: Utility of electroencephalography in the evaluation General Considerations

of common neurologic conditions in children. J Child Neu-
rol 2003;18:394 [PMID: 128896973]. Many terms are used to describe the continuum from
Dooley JM et al: The utility of the physical examination and inves- full alertness to complete unresponsiveness and deep
tigations in the pediatric neurology consultation. Pediatr coma, including clouding, obtundation, somnolence or
Neurol 2003;28:96 [PMID: 12699858]. stupor, semicoma or light coma, and deep coma. Sev-
Halsted HJ, Jones BV: Pediatric neuroimaging for the pediatrician. eral scales have been used to grade the depth of uncon-
Pediatr Ann 2002;31:661 [PMID: 12389370].
sciousness (Table 23–4). The commonly used Glasgow
Kim YO et al: Diagnostic capability of CSF ferritin in children Coma Scale is summarized in Table 11–5. Physicians
with meningitis. Pediatr Neurol 2003;28:271 [PMID:
12849879]. should use one of these tables and provide further de-
Kleine TO et al: New and old diagnostic markers of meningitis in
scriptions in case narratives. These descriptions help
cerebrospinal fluid (CSF). Brain Res Bull 2003;61:287 subsequent observers quantify unconsciousness and
[PMID: 12909299]. evaluate changes in the patient’s condition.
Krishnamoorthy KS et al: Diffusion-weighted imaging in neonatal The neurologic substrate for consciousness is the
cerebral infarction: Clinical utility and follow-up. J Child reticular activating system in the brainstem, up to and
Neurol 2000;15:592 [PMID: 11019790]. including the thalamus and paraventricular hypothala-
Mazor SS et al: Interpretation of traumatic lumbar punctures: Who mus. Large lesions of the cortex, especially of the left
can go home? Pediatrics 2003;111:525 [PMID: 12612231]. hemisphere, can also cause coma. The term “locked-in
Straussberg R et al: Absolute neutrophil count in aseptic and bacte- syndrome” describes patients who are conscious but
rial meningitis related to time of lumbar puncture. Pediatr have no access to motor or verbal expression because of
Neurol 2003;28:365 [PMID: 12878298].
massive loss of motor function of the brainstem. Coma
Tang RB et al: Interleukin-1 beta and tumor necrosis factor-alpha
in cerebrospinal fluid of children with bacterial meningitis.
vigil refers to patients who seem comatose but have
Childs Nerv Syst 2001;17:453 [PMID: 11508533]. some spontaneous motor behavior, such as eye opening
or eye tracking, almost always at a reflex level. Persis-
tent vegetative state denotes a chronic condition in
which there is preservation of the sleep–wake cycle but
no awareness and no recovery of mental function.

Emergency Measures
The clinician’s first response is to ensure that the pa-
tient will survive. The ABCs of resuscitation are perti-
nent: Airway must be kept open with positioning or
even endotracheal intubation. Breathing and adequate
740 / CHAPTER 23

Table 23–4. Gradation of coma.

Deep Coma Light Coma

Grade 4 Grade 3 Grade 2 Grade 1 Stupor
Response to pain 0 + Avoidance Avoidance Arousal
unsustained
Tone/posture Flaccid Decerebrate Variable Variable Normal
Tendon reflexes 0 +/− + + +
Pupil response 0 + + + +
Response to verbal stimuli 0 0 0 0 +
Other corneal reflex 0 + + + +
Gag reflex 0 + + + +

air exchange can be assessed by auscultation; hand by Reye syndrome or viral or bacterial meningitis. A
bag respiratory assistance with oxygen may be needed. combination of viral illness, especially varicella or in-
Circulation must be ensured by assessing pulse and fluenza, followed by 1–3 days of intractable vomiting
blood pressure. An intravenous line is always necessary. invariably precedes the coma of Reye syndrome.
Fluids, plasma, blood, or even a dopamine drip Trauma is a common cause of coma. Lack of a history
(1–20 µg/kg/min) may be required in cases of hypoten- of trauma, especially in infants, does not rule it out.
sion. An extremely hypothermic or febrile child may re- Nonaccidental trauma or a fall not witnessed by care-
quire vigorous cooling or warming to save life. The as- givers may have occurred. In coma of unknown cause,
sessment of vital signs may signal the diagnosis. Slow, poisoning is always a possibility. Absence of a history of
insufficient respirations suggest poisoning by hypnotic ingestion of a toxic substance or of medication in the
drugs; apnea may indicate diphenoxylate hydrochloride home does not rule out poisoning as a cause.
poisoning. Rapid, deep respirations suggest acidosis, Often the history is obtained concurrently with a
possibly metabolic, as with diabetic coma; toxic, such as brief pediatric and neurologic screening examination.
that due to aspirin; or neurogenic, as in Reye syn- After the assessment of vital signs, the general examina-
drome. Hyperthermia may indicate infection or heat tion proceeds with a trauma assessment. Palpation of
stroke; hypothermia may indicate cold exposure, the head and fontanelle, inspection of the ears for infec-
ethanol poisoning, or hypoglycemia (especially in in- tion or hemorrhage, and a careful examination for neck
fancy). stiffness are indicated. If circumstances suggest head or
The signs of impending brain herniation are another neck trauma, the head and neck must be immobilized
priority of the initial assessment. Bradycardia, high so that any fracture or dislocation will not be aggra-
blood pressure, irregular breathing, increased extensor vated. The skin must be inspected for petechiae or pur-
tone, and third nerve palsy with the eye deviated out- pura that might suggest bacteremia, infection, bleeding
ward and the pupil dilated are possible signs of impend- disorder, or traumatic bruising. Examination of the
ing temporal lobe or brainstem herniation. These signs chest, abdomen, and limbs is important to exclude en-
suggest a need for hyperventilation, reducing cerebral closed hemorrhage or traumatic fractures.
edema, prompt neurosurgical consultation, and possi- Neurologic examination quantifies the stimulus re-
bly, in an infant with a bulging fontanelle, subdural or sponse and depth of coma, such as responsiveness to
ventricular tap (or both). Initial intravenous fluids verbal or painful stimuli. Examination of the pupils,
should contain glucose until further assessment dis- optic fundi, and eye movements is important. Are the
proves hypoglycemia as a cause. eye movements spontaneous, or is it necessary to do the
A history obtained from parents or witnesses is de- doll’s-eye maneuver (rotating the head rapidly to see
sirable. Sometimes the only history will be obtained whether the eyes follow)? Motor and sensory examina-
from ambulance attendants. An important point is tions assess reflex asymmetries, Babinski sign, and evi-
whether the child is known to have a chronic illness, dence of spontaneous posturing or posturing induced
such as diabetes, hemophilia, epilepsy, or cystic fibrosis. by noxious stimuli (eg, decorticate or decerebrate pos-
Recent acute illness raises the possibility of coma caused turing).
 NEUROLOGIC & MUSCULAR DISORDERS / 741

If the cause of the coma is not obvious, emergency tric suction is initially important. The bladder should
laboratory tests must be obtained. Table 23–5 lists be catheterized for monitoring urine output and for
some of the causes of coma in children. An immediate urinalysis.
blood glucose (or Dextrostix), complete blood count,
urine obtained by catheterization if necessary, pH and B. SEIZURES
electrolytes (including bicarbonate), serum urea nitro- An EEG should be ordered if seizures are suspected. If
gen, and aspartate aminotransferase (AST) are initial obvious motor seizures have occurred, treatment for
screens. Urine, blood, and even gastric contents must status epilepticus is given with intravenous drugs (see
be saved for toxin screen if the underlying cause is not section on Seizure Disorders). If brainstem herniation
obvious. Spinal tap is often necessary to rule out CNS or increased pressure is possible, an intracranial moni-
infection. Papilledema is a relative contraindication to tor may be necessary. This procedure is described in
lumbar puncture. Occasionally, blood culture is ob- more detail in Chapter 13. Initial treatment of impend-
tained, antibiotics started, and imaging study of the ing herniation includes keeping the patient’s head up
brain done prior to a diagnostic spinal tap. If meningi- (15–30 degrees) and providing hyperventilation. The
tis is suspected and a tap is believed to be hazardous, use of mannitol, diuretics, corticosteroids, and drainage
antibiotics should be started and the diagnostic spinal of cerebrospinal fluid (CSF) are more heroic measures
puncture done later. Tests that are helpful in obscure covered in detail in Chapter 13.
cases of coma include PO2, PCO2, ammonia levels,
serum and urine osmolality, porphyrins, lead levels, and Prognosis
urine and serum amino acids and urine organic acids.
If head trauma or increased pressure is suspected, an About 50% of children with nontraumatic causes of
emergency CT scan or MRI is necessary. Bone win- coma have a good outcome. In studies of adults assessed
dows on the former study or skull radiographs can be on admission or within the first days after the onset of
done at the same sitting. The absence of skull fracture coma, an analysis of multiple variables was most helpful
does not rule out coma caused by closed head trauma. in assessing prognosis. Abnormal neurophthalmologic
Injury that results from shaking a child is one example. signs (eg, the absence of pupillary reaction or of eye
In a child with an open fontanelle, a real-time ultra- movement in response to the doll’s-eye maneuver or ice
sound may be substituted for the other, more definitive water calorics and the absence of corneal responses)
imaging studies if there is good local expertise. were unfavorable. Delay in the return of motor re-
Rarely, an emergency EEG aids in diagnosing the sponses, tone, or eye opening was also unfavorable. In
cause of coma. A nonconvulsive status epilepticus or children, the assessment done on admission is about as
focal finding seen with herpes encephalitis (periodic lat- predictive as one done in succeeding days. Approxi-
eralized epileptiform discharges) and focal slowing as mately two thirds of outcomes can be successfully pre-
seen with stroke or cerebritis are cases in which the dicted at an early stage on the basis of coma severity, ex-
EEG might be helpful. The EEG also may correlate traocular movements, pupillary reactions, motor
with the stage of coma (eg, in Reye syndrome) and add patterns, blood pressure, temperature, and seizure type.
prognostic information. Other characteristics, such as the need for assisted respi-
ration, the presence of increased intracranial pressure,
and the duration of coma, are not significantly predic-
Treatment tive. Published reports suggest that an anoxic (in con-
trast to traumatic, metabolic, or toxic) coma, such as
A. GENERAL MEASURES that caused by near drowning, has a much grimmer
Vital signs must be monitored and maintained. Most outlook.
emergency rooms and intensive care units have flow
sheets that provide space for repeated monitoring of the
coma; one of the coma scales (described earlier) can be
BRAIN DEATH
a useful tool for this purpose. The patient’s response to Many medical and law associations have endorsed the
vocal or painful stimuli and orientation to time, place, following definition of death: An individual who has
and situation are monitored. Posture and movements sustained either (1) irreversible cessation of circulatory
of the limbs, either spontaneously or in response to and respiratory functions or (2) irreversible cessation of
pain, are serially noted. Pupillary size, equality, and re- all functions of the entire brain, including the brain-
action to light and movement of the eyes to the doll’s- stem, is dead. A determination of death must be made
eye maneuver or ice-water calorics should be recorded. in accordance with accepted medical standards. Repre-
Intravenous fluids can be tailored to the situation, as for sentatives from several pediatric and neurologic associa-
treatment of acidosis, shock, or hypovolemia. Nasogas- tions have endorsed the Guidelines for the Determina-
Table 23–5. Some causes of coma in childhood.

Likely Cause
Mechanism of Coma Newborn Infant Older Child

Anoxia
Asphyxia Birth asphyxia CO poisoning
Respiratory Meconium aspiration, infection (especially res- Croup, epiglottitis
obstruction piratory syncytial virus)
Severe anemia Hydrops fetalis Hemolysis, blood loss

Ischemia
Cardiac Shunting lesions, hypoplastic left heart Shunting lesions, aortic stenosis, myocarditis
Shock Asphyxia, sepsis Blood loss, infection

Head trauma Birth contusion, hemorrhage, nonaccidental Falls, auto accidents, athletic injuries
trauma

Infection Gram-negative meningitis, herpes encephali- Bacterial meningitis, viral encephalitis, postinfec-
tis, sepsis tious encephalitis

Vascular Intraventricular hemorrhage, sinus Arterial or venous occlusion with congenital heart
thrombosis disease

Neoplasm “Unknown” Brain stem glioma, increased pressure with poste-

rior fossa tumors

Drugs Maternal sedatives, injected analgesics Overdose, many drugs

Epilepsy Constant minor motor seizures; electrical Constant minor motor seizures, petit mal status,
seizure without motor manifestations postictal state; drugs given to stop seizures

Toxins Maternal sedatives or injections Arsenic, alcohol, drugs, pesticides

Hypoglycemia Birth injury, diabetic progeny, toxemic progeny Diabetes, “prediabetes,” hypoglycemic
agents

Increased intracranial Anoxic brain damage, hydrocephalus, meta- Toxic encephalopathy, Reye syndrome, head
pressure bolic disorders (urea cycle; amino-, organic trauma, tumor of posterior fossa
acidurias)

Hepatic causes Hepatic failure, inborn metabolic errors in bili- Hepatic failure
rubin conjugation

Renal causes Hypoplastic kidneys Nephritis, acute and chronic

Hypertensive encepha- Acute nephritis, vasculitis

lopathy Reversible posterior leucoencephelopathy
Hypercapnia Congenital lung anomalies, bronchopulmonary Cystic fibrosis
dysplasia

Electrolyte abnormalities
Hypernatremia Iatrogenic (NaHCO3 use), salt poisoning Diarrhea, dehydration
Hyponatremia Inappropriate antidiuretic hormone, Diarrhea, dehydration
adrenogenital syndrome, dialysis (iatrogenic)
Severe acidosis Septicemia, cold injury, metabolic errors Infection, diabetic coma, poisoning (eg, aspirin)
Hyperkalemia Renal failure, adrenogenital syndrome Poisoning (aspirin)

Purpuric Disseminated intravascular coagulation, Disseminated intravascular coagulation, leukemia,

hemolytic-uremic syndrome thrombotic purpura (rare)
Modified and reproduced, with permission, from Lewis J, Moe PG: The unconscious child. In: Conn H, Conn R (eds). Current Diagnosis, 5th
ed. WB Saunders, 1977.
742
 NEUROLOGIC & MUSCULAR DISORDERS / 743

tion of Brain Death in Children. The criteria in full- respirator. The recommended observation period to
term infants (ie, born at greater than 38 weeks’ gesta- confirm brain death (repeated examinations) is
tion) were applicable 1 week after the neurologic insult. 12–24 hours (longer in infants); reversible causes must
Difficulties in assessing premature infants and full-term be ruled out. If an irreversible cause is documented,
infants shortly after birth were acknowledged. laboratory testing is not essential. Helpful tests to sup-
port the clinical assertion of brain death include EEG
Prerequisites and angiography. Electrocerebral silence on EEG
should persist for 30 minutes, and drug concentrations
In assessment of brain death, the history is important. must be insufficient to suppress EEG activity. Absence
The physician must determine proximate causes to of intracerebral arterial blood flow can be confirmed by
make sure no remediable or reversible conditions are carotid angiography and cerebral radionuclide angiog-
present. Examples of such causes are metabolic condi- raphy. Persistence of dural sinus flow does not invali-
tions, toxic agents, sedative–hypnotic drugs, surgically date the diagnosis of brain death.
remediable conditions, hypothermia, and paralytic Cerebral evoked potentials, intracranial blood pulsa-
agents. tions on ultrasound, and xenon-enhanced CT have not
been sufficiently studied to be considered definitive in
Physical Examination Criteria the diagnosis of brain death. In rare cases, preserved in-
tracranial perfusion in the presence of EEG silence has
(See also Chapter 13) been documented, and the converse has also been re-
The following criteria are those established by the ported.
Task Force on Brain Death in Children:
1. Coexistence of coma and apnea—The patient Alfonso I et al: Evaluation of the comatose full term neonate. Int
must exhibit complete loss of consciousness, vocaliza- Pediatr 1997;12:74.
tion, and volitional activity. Lazar NM et al: Bioethics for clinicians: 24. Brain death. CMAJ
2001;164:833 [PMID: 11276553].
2. Absence of brainstem function—As defined by
Ruiz-Garcia M et al: Brain death in children: Clinical, neurophysi-
the following: (a) Midposition or fully dilated pupils ological and radioisotopic angiography findings in 125 pa-
that do not respond to light. Drugs may influence and tients. Childs Nerv Syst 2000;16:40 [PMID: 10672428].
invalidate pupillary assessment. (b) Absence of sponta- Shewmon DA: Coma prognosis in children. Part II: Clinical applica-
neous eye movements and those induced by side-to-side tion. J Clin Neurophysiol 2000;17:467 [PMID: 11085550].
passive head movements (oculocephalic reflex) and ice Singhi P et al: Reversible brain lesions in childhood hypertension.
water instillation in the external auditory canal (ice Acta Paediatr 2002:91:1005 [PMID: 12412881].
water calorics). (c) Absence of movement of bulbar Wijdicks EFM: Brain death worldwide: Accepted fact but no global
musculature, including facial and oropharyngeal mus- consensus in diagnostic criteria. Neurology 2002;58:20
cles. The corneal, gag, cough, sucking, and rooting re- [PMID: 11781400].
flexes are absent. (d) Absence of respiratory movements Yager JY et al: Coma scales in pediatric practice. Am J Dis Child
when the patient is off the respirator. Apnea testing 1990;144:1088 [PMID: 2403089].
using standardized methods can be performed but is
done after other criteria are met. SEIZURE DISORDERS (Epilepsies)
3. Temperature and blood pressure—The patient
must not be significantly hypothermic or hypotensive
for age. ESSENTIALS OF DIAGNOSIS
& TYPICAL FEATURES
4. Tone—Tone is flaccid, and spontaneous or induced
movements are absent, excluding spinal cord events
such as reflex withdrawal or spinal myoclonus. • Recurrent nonfebrile seizures.
5. General examination findings—The examination • Often, interictal electroencephalographic changes.
should remain consistent with brain death throughout
the observation and testing period.

Confirmation General Considerations

Apnea testing should be carried out at a PCO2 level A seizure is a sudden, transient disturbance of brain
greater than 60 mm Hg, and with normal oxygenation function, manifested by involuntary motor, sensory,
maintained throughout the test period. This level may autonomic, or psychic phenomena, alone or in any
be reached 3–15 minutes after taking the patient off the combination, often accompanied by alteration or loss
744 / CHAPTER 23

of consciousness. A seizure may occur after a metabolic, Events after the seizure can be helpful in diagnosis. Was
traumatic, anoxic, or infectious insult to the brain. there loss of speech? Was the patient able to respond ac-
Repeated seizures without evident cause justify the curately before going to sleep? All the events prior to,
label of epilepsy. Seizures and epilepsy occur most com- during, and after the seizure can help to classify the
monly at the extremes of life. The incidence is highest seizure and, indeed, may help to determine if the event
in the newborn period and higher in childhood than in actually was an epileptic seizure or a pseudoseizure (a
later life. Epilepsy in childhood often remits. Prevalence nonepileptic phenomenon mimicking a seizure). Classi-
flattens out after age 10–15 years. The chance of having fying the seizure may aid in diagnosis or prognosis and
a second seizure after an initial unprovoked episode is may suggest appropriate laboratory tests and medica-
30%. The chance of remission from epilepsy in child- tions (Tables 23–6 and 23–7).
hood is 50%. The recurrence rate after the withdrawal
of drugs is about 30%. Factors adversely influencing re- B. STATUS EPILEPTICUS
currence include (1) difficulty in getting the seizures Status epilepticus is a clinical or electrical seizure lasting
under control (ie, the number of seizures occurring be- at least 30 minutes, or a series of seizures without com-
fore control is achieved), (2) neurologic dysfunction or plete recovery over the same period of time. After
mental retardation, (3) age at onset younger than 30 minutes of seizure activity, hypoxia and acidosis
2 years, and (4) abnormal EEG at the time of discon- occur, with depletion of energy stores, cerebral edema,
tinuing medication. The type of seizure also often de- and structural damage. Eventually, high fever, hypoten-
termines prognosis. sion, respiratory depression, and even death may occur.
Seizures are caused by any factor that disturbs brain Status epilepticus is a medical emergency.
function. Seizures and epilepsy are often classified as Status epilepticus is classified as (1) convulsive (the
symptomatic (the cause is identified or presumed) or common tonic–clonic, or grand mal, status epilepticus)
idiopathic (the cause is unknown or presumed to be ge- or (2) nonconvulsive (characterized by altered mental
netic). The younger the infant or child, the more likely status or behavior with subtle or absent motor compo-
it is the cause can be identified. Idiopathic or genetic nents). Absence status, or spike-wave stupor, and (very
epilepsy most often appears between ages 4 and rare) partial complex status epilepticus are examples of
16 years. A seizure disorder or epilepsy should not be the nonconvulsive type (Table 23–8). An EEG may be
considered idiopathic unless thorough history, exami- necessary to aid in diagnosing nonconvulsive status, be-
nation, and laboratory tests have revealed no apparent cause these patients sometimes appear merely stuporous
cause. and lack typical convulsive movements.
A child with status epilepticus may have a high fever
with or without intracranial infection. Studies show
Clinical Findings that 25–75% of children with status epilepticus experi-
ence it as their initial seizure. Often it is a reflection of a
A. SYMPTOMS AND SIGNS remote insult (eg, anoxic or traumatic). Tumor, stroke,
The key to the diagnosis of epilepsy is the history. An or head trauma, which are common causes of status
aura sometimes precedes the seizure itself. The patient epilepticus in adults, are uncommon causes in child-
describes a feeling of fear, numbness or tingling in the hood. Fifty percent of cases are symptomatic of acute
fingers, or bright lights in one visual field. Sometimes (25%) or chronic (25%) CNS disorders. Infection and
the patient recalls nothing because there has been no metabolic disorders are the most common causes of sta-
aura or warning. The parent might report that the pa- tus epilepticus in children. The cause is unknown in
tient’s eyes deviated to one side or that pallor, trismus, 50% of patients, but many of these patients will be
or body stiffening occurred first. Occasionally there is a febrile. Status epilepticus occurs most commonly in
prodrome. For example, the patient may experience a children age 5 years and younger (85%). The most
feeling of unwellness, a premonition that something is common age is 1 year or younger (37%), and the distri-
about to happen, or a recurrent thought for minutes or bution is even for each year thereafter (approximately
hours prior to the aura and seizure itself. 12% per year). For treatment options, see Table 23–9.
Minute details of the seizure can help determine the
site of onset and aid in classification. Did the patient C. FEBRILE SEIZURES
become extremely pale before falling? Was the patient Criteria for febrile seizures are (1) ages 3 months to
able to respond to queries during the episode? Did the 5 years (most occur between ages 6 and 18 months),
patient become completely unconscious? Did the pa- (2) fever of greater than 38.8°C, and (3) non-CNS in-
tient fall stiffly or gradually slump to the floor? Was fection. More than 90% of febrile seizures are general-
there an injury? How long did the stiffening or jerking ized, last less than 5 minutes, and occur early in the ill-
last? Where in the body did the jerking take place? ness causing the fever. Febrile seizures occur in 2–3%
 Table 23–6. Seizures by age at onset, pattern, and preferred treatment.

Treatment and Comments

Age Group and Age Clinical Causative Electroencephalographic Other Diagnostic (Anticonvulsants
Seizure Type at Onset Manifestations Factors Pattern Studies by Order of Choice)
Neonatal Birth to 2 Often atypical; sudden Neurologic insults (hypoxia/ May correlate poorly with Lumbar puncture; Phenobarbital, IV or IM; if sei-
seizures wk limpness or tonic post- ischemia; intracranial hemor- clinical seizures. Focal CSF PCR for herpes, zures not controlled, add pheny-
uring, brief apnea, and rhage) present more in first spikes or slow rhythms; enterovirus; serum toin IV (loading dose 20 mg/kg
cyanosis; odd cry; eyes 3 d or after eighth day; multifocal discharges. Ca2+, PO43−, glucose, each). Diazepam 0.3 mg/kg.
rolling up; blinking or metabolic disturbances Electroclinical dissocia- MG2+; BUN, amino Treat underlying disorder. Sei-
mouthing or chewing alone between third and tion may occur: EEG- acid screen, blood zures due to brain damage often
movements; nystagmus, eighth days; hypoglycemia, electrical seizure with- ammonia, organic resistant to anticonvulsants.
twitchiness or clinic move- hypocalcemia, hyper- and out clinical manifesta- acid screen, TOR- When cause in doubt, stop pro-
ments—focal, multifocal, hyponatremia. Drug with- tions and vice versa. CHESa IgM. Ultra- tein feedings until enzyme defi-
or generalized. Some sei- drawal. Pyridoxine depend- sound or CT scan ciencies of urea cycle or amino
zures are nonepileptic- cency and other metabolic for suspected in- acid metabolism ruled out.
decerebrate, or other causes. CNS infections and tracranial hemor-
posturings, release from structural abnormalities. rhage and struc-
745

forebrain inhibition; poor tural abnormalities

response to drugs.
West syndrome 3–18 Sudden, usually symme- Pre- or perinatal brain dam- Hypsarrhythmia; chaotic Funduscopic and ACTH preferred (2–4 U/kg/d)
infantile mos; tric adduction and flexion age or malformation in ap- high-voltage slow waves, skin examination, IM Acthar gel once daily, then
spasms. occasion- of limbs with concomitant proximately one third; bio- random spikes, all leads trial of pyridoxine. slow withdrawal. Some prefer
(See also ally up to flexion of head and trunk; chemical, infectious, degen- (90%); other abnormalities Amino and organ- oral corticosteroids. Clonazepam,
Lennox– 4y also abduction and exten- erative causes in approxi- in 10%. Rarely normal. EEG ic acid screen. valproic acid, vigabatrin, B6 pyri-
Gastaut sor movements like Moro mately one third; unknown normalization usually Chronic inflamma- doxine trial (Japan). In resistant
syndrome, reflex. Tendency for in approximately one third. early in course correlates tory disease. TOR- cases, ketogenic or medium-
below.) spasms to occur in clusters, With early onset, pyridoxine with reduction of seizures; CHESa screen, CT, chain triglyceride diet (see text).
on waking or falling asleep, deficiency, amino- or organ- not helpful prognostically or MRI scan should New drugs: zonisamide, topira-
or when fatigued, or may ic aciduria. Tuberous sclerosis regarding mental develop- be done to (1) es- mate, lamotrigine.
be noted particularly when in 5–10%. Chronic inflamma- ment. tablish definite Retardation of varying degree in
the infant is being handled, tory disease, eg, TORCHESa, diagnosis, (2) aid approximately 90% of cases.
is ill, or is otherwise irri- homeobox gene mutations. in genetic counse- Occasionally, surgical extirpation
table. Tendency for each ling. SPECT or PET of focal lesion may be curative.
patient to have own scan may identify
stereotyped pattern. focal lesion.

(continued)
 Table 23–6. Seizures by age at onset, pattern, and preferred treatment. (continued)

Treatment and Comments

Age Group and Age Clinical Causative Electroencephalographic Other Diagnostic (Anticonvulsants
Seizure Type at Onset Manifestations Factors Pattern Studies by Order of Choice)
Febrile convul- 3 mos Usually generalized seizures, Nonneurologic febrile illness Normal interictal EEG, es- Lumbar puncture Treat underlying illness, fever.
sions to 5 y less than 15 mins; rarely (temperature rises to 39°C pecially when obtatined in infants or when- Diazepam orally or rectally as
(maximum focal in onset. May lead to or higher); positive family 8–10 d after seizure. ever suspicion of needed, 0.3–0.5 mg/kg tid dur-
6–18 mos) status epilepticus. Latter history, day care, slow devel- In older infants, 3/s gen- meningitis exists. ing illness or for prolonged
Most com- usually benign. Recurrence opment, prolonged neonatal eralized spike waves often (>5–15 mins) seizure. Prophylaxis
mon child- risk of second febrile seizure hospitalization are other risk seen. with phenobarbital or valproic
hood sei- 30%; 50% if under 1 y of factors. acid rarely needed: maybe with
zure: inci- age; recurrence risk is same neurologic deficits, prolonged
dence 2% after status. seizures, family anxiety.
746

Myoclonic-astatic Any time Shock-like violent contrac- Multiple causes, usually re- Atypical slow (1–2.5 Hz) As dictated by in- Difficult to treat. Valproic acid,
(akinetic, aton- in child- tions of one or more muscle sulting in diffuse neuronal spike-wave complexes dex of suspicion. clonazepam, ethosuximide.
ic) seizures, for- hood; nor- groups, singly or irregularly damage. History of West’s (petit mal variant) and Nerve conduction Felbamate. Diazepam. Ketogen-
merly atypical mally 2– repetitive; may fling patient syndrome; prenatal or peri- bursts of high-voltage studies. Skin or ic or medium-chain triglyceride
absence. When 7y suddently to side, forward, natal brain damage; viral generalized spikes, often conjunctival biopsy diet. ACTH or corticosteroids as
mental retarda- or backward. Usually no or meningoencephalitides; with diffusely slow back- for electron micro- in West syndrome. Perhaps la-
tion is presen- only brief loss of conscious- CNS degenerative disorders; ground frequencies. See scopy, MRI scan, motrigine, topiramate, zoniso-
ted, this is cal- ness. Half of patients or lead or other encephalo- text. WBC lysosomal mide. Protect head with helmet
led Lennox– more also have generalized pathies; structural cerebral enzymes if metab- and chin padding.
Gastaut syn- grand mal seizures. abnormalities; eg, migrational olic degenerative
drome. abnormalities. disease suspected.
Absence (petit 3–15 y Lapses of consciousness or Unknown. Genetic compo- 3/s bilaterally synchro- Hyperventilation Valproic acid or ethosuximide;
mal). Also ju- vacant stares, lasting about nent: probably an autosomal nous, symmetric, high-vol- when patient on with latter, add phenobarbital
venile and myo- 10 s, often in “clusters.” dominant gene. tage spikes and waves. inadequate or no or valproate if major motor sei-
clonic absence. Automatisms of face and EEG normalization corre- medication often zures. In resistant cases, keto-
hands; clonic activity in lates closely with control provokes attacks. genic diet, lamotrigine, topira-
30–45%. Often confused of seizures. CT scan is rarely mate, acetazolamide.
with complex partial sei- of value.
zures but no aura or postic-
tal confusion.
 Simple partial or Any age Seizure may involve any Often secondary to birth Focal spikes or slow waves If seizures are diffi- Carbamazepine, phenytoin.
focal seizures part of body; may spread in trauma, inflammatory pro- in appropriate cortical re- cult to control or Valproic acid useful adjunct.
(motor/sen- fixed pattern (jacksonian cess, vascular accidents, gion; sometimes diffusely progressive deficits Also used: lamotrigine, gaba-
sory/jack- march), becoming genera- meningoencephalitis, etc. abnormal or even normal. occur, neuroradio- pentin, topiramate, and levetira-
sonian). lized. In children, epilepto- If seizures are coupled with “Rolandic spikes” one typi- diagnostic studies, cetam
genic focus often “shifts,” new or progressive neurolo- cal (often benign) pattern. particularly MRI
and epileptic manifestations gic deficits, a structural lesion brain scan, impera-
may change concomitantly. (eg, brain tumor) is likely tive (see text).
Complex partial Any age Aura may be a sensation of As above. Temporal lobes As above, but occurring in MRI when struc- Carbamazepine, phenytoin.
seizures (psy- fear, eigastric discomfort, especially sensitive to hy- temporal lobe and its con- tural lesions sus- More than one drug may be
chomotor, tem- odd smell or taste (usually poxia; thus, this seizure type nections, eg, frontotemp- pected. PCR of necessary. Valproic acid may be
poral lobe, or unpleasant), visual or audi- may be a sequela of birth oral, temporoparietal, cerebrospinal fluid useful. In cases uncontrolled
limbic seizures tory hallucination (either trauma, febrile convulsions, temporo-occipital regions. in acute febrile sit- by drugs and where a primary
are older terms). vague and “unformed” or etc. Also especially vulner- uation for herpes; epileptogenic focus is identifi-
well-formed image, words, able to certain viral infec- rarely, temporal able, excision of anterior third
music). Aura and seizure tions, especially herpes sim- lobe biopsy. Caro- of temporal lobe. Gabapentin,
stereotyped for each pa- plex. Remediable other tid amobarbital in- topiramate, lamotrigine, leve-
tient. Seizure may consist of causes are small cryptic tu- jection when later- tiracetam, and tiagabine (for
vague stare; facial, tongue, mors or vascular malforma- alization of speech > 16-year-olds).
or swallowing movements tions. dominance in ques-
and throaty sounds; or var- tion and surgical
747

ious complex automatisms. extirpation of epi-

Unlike absences, complex leptogenic area is
partial seizures tend not to contemplated.
occur in clusters but singly
and to last longer (1 min
or more), followed by
confusion. History of aura
(eg, child running to adult
from “vague fear”) and of
automatisms involving
more than face and hands
establish diagnosis.
(continued)
 Table 23–6. Seizures by age at onset, pattern, and preferred treatment. (continued)

Treatment and Comments

Age Group and Age Clinical Causative Electroencephalographic Other Diagnostic (Anticonvulsants
Seizure Type at Onset Manifestations Factors Pattern Studies by Order of Choice)
Benign epilepsy 5–16 y Partial motor or generalized Seizure history or abnormal Centrotemporal spikes or Seldom need CT or Carbamazepine or phenytoin.
of childhood seizures. Similar seizure pat- EEG findings in relatives of sharp waves (“rolandic dis- MRI scan. (See simple, complex partial
(with centro- terns may be observed in 40% of affected probands charges”) appearing par- seizures.) Often no medication
temporal or patients with focal cortical and 18–20% of parents and oxysmally against a nor- is necessary, especially if seizure
rolandic foci) lesions. Usually nocturnal siblings, suggesting trans- mal EEG background. is exclusively nocturnal and in-
simple partial seizures of mission by a single autoso- frequent. Lamotrigine, topira-
face, tongue, hand. mal-dominant gene, possibly mate.
with age-dependent pene-
trance.
Juvenile myoclo- Late child- Mild myoclonic jerks of 40% of relatives have myo- Interictal EEG shows variety Differentiate from Valproic acid. Lamotrigine. topir-
nic epilepsy (of hood and neck and shoulder flexor clonias, especially in females; of spike-and-wave se- progressive myo- amate ?Levetiracetam.
Janz) adoles- muscles after awakening. 15% have the abnormal EEG quences or 4- to 6-Hz clonic encephalo-
748

cence, Intelligence usually normal. pattern with clinical attacks. multispike and wave com- pathy of Unverricht–
peaking at Often absence seizures, plexes (“fast spikes”) Lafora and other
13 y and GTCS as well. degenerative dis-
orders by appropri-
ate biopsies (mus-
cles, liver, etc).
Generalized Any age Loss of consciousness; Often unknown. Genetic Bilaterally synchronous, As above Phenobarbital in infants; carba-
tonic–clonic tonic–clonic movements, component. May be seen symmetrical multiple high- mazepine or valproic acid;
seizures (grand often preceded by vague with metabolic disturbances, voltage spikes, spikes and phenytoin; topiramate, oxcar-
mal) (GTCS) aura or cry. Bladder and trauma, infection, intoxica- waves, mixed patterns. bazepine. Combinations may be
bowel incontinence in tion, degnerative disorders, Often normal younger than necessary.
approximately 15%. Post- brain tumors. age 4.
ictal confusion; sleep.
Often mixed with or mask-
ing other seizure patterns.
a
TORCHES is a mnemonic formula for toxoplasmosis, rubella, cytomegalovirus, herpes simplex, and syphilis.
ACTH = adrenocorticotropic hormone; BUN = blood urea nitrogen; CNS = central nervous system; CT = computed tomography; EEG = electroencephalogram; IM = intramuscularly; IV = intra-
venously; MRI = magnetic resonance imaging; PCR = polymerase chain reaction; PET = positron emission tomography; SPECT = single photon emission computed tomography; WBC = white
blood cell.
 NEUROLOGIC & MUSCULAR DISORDERS / 749

Table 23–7. Benign childhood epileptic Table 23–8. Status epilepticus: clinical types.
syndromes.
Generalized seizure (common)
Syndrome Characteristics Convulsive (tonic, clonic, myoclonic); 90%
Nonconvulsive (absence, atypical absence, atonic); 10%
Benign idiopathic 6% of neonatal convulsions; 97% have Focal (partial) seizures (rare)
neonatal con- onset on 3rd to 7th day of life (so-called Simple partial
vulsions (BINC) 5th day fits); clonic; multifocal; usually Complex partial
brief; occasional status epilepticus Neonatal
Benign familial Autosomal-dominant; onset in 2–90 d; Many clinical varieties
neonatal con- 20% have linkage to chromosome May be electrical (ie, on electroencephalogram) status only
vulsions 20q13; clonic; 86% recover with no visible clinical findings; called electroclinical dis-
(BFNC) sociation
Generalized Age at onset, 3–11 y; may have
tonic–clonic family or personal history of febrile con-
seizures vulsions; 50% have 3/s spike-wave EEG;
(GTCS) may have concurrent absence seizures
Childhood Incidence higher in girls than in boys; age febrile seizures have complex features, such as a dura-
absence sei- at onset, 3–12 y (peak 6–7 years); tion of longer 15 minutes, more than one seizure in the
zures 10–200 seizures per day; 3/s spike– same day, or focal features. Other adverse factors are an
wave EEG; 40% have GTCS; most abnormal neurologic status preceding the seizures (eg,
remit at puberty cerebral palsy or mental retardation), early onset of
Juvenile absence Incidence higher in boys than in girls; age febrile seizure (before age 1 year), and a family history
seizures at onset, 10–12 y; uncommon; less fre- of epilepsy. Even with adverse factors, the risk of
quent seizures; 3–4/s general spike- epilepsy after febrile seizures is low, in the range of
wave EEG; most have GTCS; some remit 15–20%. Recurrent febrile seizures occur in 30–50% of
Juvenile myo- Age at onset, 12–18 y (average, 15 y); cases but, in general, do not worsen the long-term out-
clonic epilepsy myoclonic jerks upper limbs, seldom look.
(Janz syn- fall; 4–6/s general spike–wave EEG; The child with a febrile seizure must be examined.
drome) untreated, 90% have GTCS, mostly on Routine studies such as serum electrolytes, glucose, cal-
waking; 20–30% have absence seizures; cium, skull radiographs, or brain imaging studies are
25–40% are photosensitive; 10% remis- seldom helpful. A white count above 20,000/µL or an
sion rate
extreme left shift may correlate with bacteremia. Com-
Benign epilepsy Autosomal-dominant; age at onset
with centro- 3–13 y (most at 4–10 y); 80% have
plete blood count and blood cultures may be appropri-
temporal brief, 2–5 min sleep seizures only; ate studies. Serum sodium is often slightly low but not
spikes (BECTS); usually simple partial seizures (face, low enough to require treatment or to cause the seizure.
rolandic tongue, cheek, hand) sensory or Meningitis must be ruled out. Patients with bacterial
epilepsy motor; occasionally have GTCS; bilat- meningitis can present with a fever and seizure. Signs of
eral spikes on EEG; may not need med- meningitis (eg, bulging fontanelle, stiff neck, stupor,
ication if seizures infrequent; remits at and irritability) may all be absent, especially in a child
puberty younger than age 18 months.
After controlling the fever and stopping an ongoing
EEG = electroencephalogram.
seizure, the physician must decide whether to do a
spinal tap. The fact that the child has had a previous
febrile seizure does not rule out meningitis as the cause
of children. Acute respiratory illnesses are most com- of the current episode. The younger the child, the more
monly associated with febrile seizures. Gastroenteritis, important the tap, because physical findings are less re-
especially when caused by Shigella or Campylobacter, liable in diagnosing meningitis. Although the yield is
and urinary tract infections are less common causes. low, a tap should probably be done if the child is
Roseola infantum is a rare but classic cause. One study younger than age 2 years, if recovery is slow, if no other
implicated viral causes in 86% of cases. Immunizations cause for the fever is found, or if close follow-up will
may be a cause. not be possible. Occasionally observation in the emer-
Rarely status epilepticus may occur during a febrile gency room for several hours obviates the need for a
seizure. Febrile seizures rarely (1–2.4%) lead to epilepsy tap. A negative tap does not rule out the emergence of
or recurrent nonfebrile seizures in later childhood and meningitis during the same febrile illness. Sometimes a
adult life. The chance of later epilepsy is higher if the second tap must be done.
750 / CHAPTER 23

Table 23–9. Status epilepticus treatment. tion of the febrile illness (0.5 mg/kg two or three times
per day orally or rectally). Diastat is an expensive rectal
1. ABCs diazepam preparation. Phenobarbital, 3–5 mg/kg/d as a
a. Airway: Maintain oral airway; intubation may be neces- single bedtime dose, is an inexpensive and safe prophy-
sary. laxis. Often, increasing the dosage gradually (eg, start-
b. Breathing: Oxygen. ing with 2 mg/kg/d the first week, increasing to
c. Circulation: Assess pulse, blood pressure; support with 3 mg/kg/d the second week, and so on) decreases side
IV fluids, drugs. Monitor vital signs. effects and noncompliance. A plasma phenobarbital
2. Start glucose-containing IV; evaluate serum glucose; elec- level in the range of 15–40 mg/mL is desirable. Val-
trolytes, HCO3−, CBC, BUN, anticonvulsant levels. proate sodium is more hazardous. In infants, the com-
3. May need arterial blood gases, pH. monly used liquid suspension has a short half-life and
4. Give 50% glucose if dextrose low (1–2 mL/kg). causes more gastrointestinal upset than do the sprinkle
5. Begin IV drug therapy; goal is to control status epilepticus capsules. The dosage is 15–60 mg/kg/d in two three or
in 20–60 min. four divided doses. Precautionary laboratory studies are
a. Diazepam 0.3–0.5 mg/kg over 1–5 min (20 mg maxi- necessary. Phenytoin and carbamazepine have not
mum); may repeat in 5–20 min; or, lorazepam 0.05–0.2 shown effectiveness in the prophylaxis of febrile seizures
mg/kg (less effective with repeated doses, longer-act- (see Table 23–9). Measures to control fever such as
ing than diazepam). Midazolam IM or IV: 0.1–0.3
sponging or tepid baths, antipyretics, and the adminis-
mg/kg; intranasally, 0.2 mg/kg.
b. Phenytoin 10–20 mg/kg IV (not IM) over 5–20 min;
tration of antibiotics for proven bacterial illness are rea-
1000 mg maximum); monitor with blood pressure and sonable but unproven to prevent recurrent febrile
ECG. Fosphenytoin may be given more rapidly—even seizures.
IM—in the same dosage; order 10–20 mg/kg of Simple febrile seizures do not have any long-term
“phenytoin equivalent.” adverse consequences. An EEG should be performed if
c. Phenobarbital 5–20 mg/kg (sometimes higher in new- the febrile seizure is complicated or unusual. In uncom-
borns or refractory status in intubated patients). plicated febrile seizures, the EEG is usually normal.
6. Correct metabolic perturbations (eg, low-sodium, acidosis). About 22% of patients will show slowing or epilepti-
7. Other drug approaches in refractory status: form abnormalities. Ideally the EEG should be done at
a. Repeat phenytoin, phenobarbital (10 mg/kg). Monitor least a week after the illness to avoid transient changes
blood levels. Support respiration, blood pressure as due to fever or the seizure itself. In older children, 3/s
necessary. spike-wave discharge, suggestive of a genetic propensity
b. Midazolam drip: 1-5 µg/kg/min (even to 20 kgm/min). to epilepsy, may occur. In the young infant, EEG find-
Valproate sodium (Depacon), available as 100 mg/mL ings seldom aid in assessing the chance of recurrence of
for IV use; give 15–30 mg/kg over 5–20 min. febrile seizures or in long-term prognosis.
c. Pentobarb coma. Propofol. General anesthetic.
8. Consider underlying causes: D. LABORATORY FINDINGS AND IMAGING
a. Structural disorders or trauma. Consider CT scan. Ordering of laboratory tests depends on the child’s age,
b. Infection: Spinal tap, blood culture, antibiotics. the severity and type of seizure, whether the child is ill
c. Metabolic disorders: Consider lactic acidosis, toxins,
or injured, and the clinician’s suspicion about the un-
uremia. May need to evaluate medication levels, toxin
screen, judicious fluid administration.
derlying cause. Every case of suspected seizure disorder
9. Give maintenance drug (if diazepam only was sufficient warrants an EEG. Other studies are used selectively.
to halt status epilepticus): phenytoin 10 mg/kg, pheno- Seizures in early infancy are often symptomatic. There-
barbital 5 mg/kg, daily dose IV (or by mouth) divided fore, the younger the child, the more careful must be
every 12 hours. the laboratory assessment (Table 23–10).
Metabolic abnormalities are seldom found in the
BUN = blood urea nitrogen; CBC = complete blood count; CT = well child with seizures. Unless there is a high clinical
computed tomography; ECG = electrocardiogram; IM = intramus-
cularly; IV = intravenously.
suspicion of uremia, hyponatremia, or other serious
conditions, laboratory tests are not necessary. Special
studies may be necessary in unusual circumstances, for
Prophylactic anticonvulsants are not required after example, when hemolytic–uremic syndrome or lead
the uncomplicated febrile seizure. If febrile seizures are poisoning is a suspected cause. CT scans are overused
complicated or prolonged, or if medical reassurance in patients with seizures. The youngster with a routine
fails to relieve family anxiety, anticonvulsant prophy- febrile seizure, a nonfebrile generalized seizure with
laxis may be indicated and can reduce the incidence of normal examination and normal EEG, or an absence
recurrent febrile or nonfebrile seizures. One remedy is seizure does not need a CT or MRI scan. The yield in a
to use diazepam at the first onset of fever for the dura- child with normal neurologic examination and EEG is
 NEUROLOGIC & MUSCULAR DISORDERS / 751

Table 23–10. Laboratory studies after first eases anxiety and rules out the remote possibility of
seizure (nonneonatal). tumor or vascular malformation. Other indications for
MRI scan (the superior study) scan include difficulty in
Well infant EEG, calcium, BUN, or urinalysis, and per- controlling seizures, progressive neurologic findings on
haps CT or MRI. (Abnormal examination or serial examinations, worsening focal findings on the
focally abnormal EEG: do imaging study.) EEG, suspicion of increased pressure, and, of course,
Rule out nonaccidental trauma. any case in which surgery is being considered. A previ-
ous normal scan does not rule out an emerging tumor;
Well older child EEG; consider CT or MRI if the course is unsatisfactory, repeating the scan may be
Ill infant Calcium, magnesium, CBC, BUN, glucose, necessary. A neoplasm or other unexpected treatable le-
electrolytes, blood culture, lumbar punc- sion is found in a small number, perhaps 2–3%, of
ture, EEG, possibly CT or MRI scans.
Ill older child CBC, BUN, lumbar puncture, EEG, CT or MRI
Generalized Calcium, glucose, CBC, BUN, electro- E. ELECTROENCEPHALOGRAPHY
tonic–clonic lytes, lumbar puncture (may omit if afebrile, The limitations of EEG—even with epilepsy, for which
seizure looks well) it is most useful—are considerable. A seizure is a clini-
Generalized EEG only
cal phenomenon; an EEG showing epileptiform activ-
absence ity may confirm and even extend the clinical diagnosis,
but it cannot make the diagnosis.
Atypical EEG, MRI: Consider studies for mental The EEG need not be abnormal in the epileptic
absence retardation: serum and urine amino and or- child. Normal EEGs are seen following a first general-
ganic acids and chromosomes, including ized seizure in one third of children younger than age
fragile X. If there is progressive worsening, 4 years. The initial EEG is normal in about 20% of
consider lysosomal enzymes, lumbar punc- older epileptic children and in about 10% of epileptic
ture (protein, enzymes, IgG), long-chain adults. These percentages are reduced when serial trac-
fatty acids, skin or conjunctival biopsies.
ings are obtained. Focal spikes and generalized spike-
Infantile spasms See Atypical absence wave discharges are seen in 30% of close nonepileptic
Myoclonic pro- See Atypical absence relatives of patients with epilepsy.
gressive sei-
zure with 1. Diagnostic value—The greatest value of the EEG
mental retar- in convulsive disorders is to help classify seizure types
dation and select appropriate therapy (see Table 23–6). Petit
Focal EEG. In cases of mental retardation, positive mal absences and partial complex or psychomotor
neurologic examination, EEG focal slow seizures are sometimes difficult to distinguish, especially
wave, or poorly controlled seizures, do MRI. when the physician must rely on the history and cannot
In refractory cases, consider surgical evalua- observe the seizure. The differing EEG patterns of these
tion. seizures will then prove most helpful. Finding a mixed
seizure EEG pattern in a child who clinically has only
BUN = blood urea nitrogen; CBC = complete blood count; major motor seizures or only focal seizures will help the
CT = computed tomography; EEG = electroencephalogram;
MRI = magnetic resonance imaging.
clinician select anticonvulsants effective for both seizure
types identified by the EEG. The EEG may help in di-
agnosing neonatal seizures with minimal or atypical
clinical manifestations; it may show hypsarrhythmia
less than 5%. Conversely, in children with sympto- (high-amplitude spikes and slow waves with a disorga-
matic epileptic syndromes, the EEG will be abnormal nized background) in infantile spasms or 1–4/s slow
in as many as 60–80% of patients. Examples include spike-wave pattern of the Lennox–Gastaut syndrome.
infantile spasms, Lennox–Gastaut syndrome, and pro- Both are expressions of diffuse brain dysfunction and
gressive myoclonic epilepsy. generally of grave significance. The EEG may show
In focal seizures, children with benign rolandic focal slowing that, if constant, particularly when corre-
epilepsy do not need a CT scan; it will invariably be sponding focal seizure manifestations and abnormal
normal. The yield with other focal seizures is 15–30%, neurologic findings are present, will alert the physician
with most of the findings unimportant in relation to di- to the presence of a structural lesion. In this case, brain
agnosis and prognosis (eg, a mildly dilated single ventri- imaging may establish the cause and help determine
cle, superficial atrophy). Nonetheless, an imaging study further investigation and treatment.
752 / CHAPTER 23

2. Prognostic value—A normal EEG following a first Pseudoretardation may occur in children with
convulsion suggests (but does not guarantee) a favor- poorly controlled epilepsy because their seizures (or the
able prognosis. Markedly abnormal EEGs may become subclinical paroxysms sustained) interfere with their
normal with treatment (1) immediately following intra- learning ability. Anticonvulsants are less likely to cause
venous injection of 50 mg of vitamin B6 in pyridoxine such interference but may do so when given in toxic
dependency or deficiency; (2) in infantile spasms and amounts. Phenobarbital is particularly implicated. True
sometimes the Lennox–Gastaut syndrome (with the use mental retardation is most commonly part of the same
of adrenocorticotropic hormone [ACTH] or cortico- pathologic process that causes the seizures but may oc-
steroids); (3) in absence (appropriate anticonvulsants); casionally be worsened when seizures are frequent, pro-
and (4) in akinetic and other minor motor seizures, in- longed, and accompanied by hypoxia.
cluding the Lennox–Gastaut syndrome (ketogenic Physical injuries, especially lacerations of the fore-
diet). If so, it is likely that seizure control will be head and chin, are frequent in astatic or akinetic
achieved (although this offers no clues to the ultimate seizures (so-called drop attacks), necessitating protective
developmental status of the patient). headgear. In all other seizure disorders in childhood, in-
Electroencephalography should be repeated when juries as a direct result of an attack are rare.
the severity and frequency of seizures increase despite
adequate anticonvulsant therapy, when the clinical Treatment
seizure pattern changes significantly, or when progres-
sive neurologic deficits develop. Emergence of new The ideal treatment of seizures is the correction of spe-
focal or diffuse slowing may indicate a progressive le- cific causes. However, even when a biochemical disor-
sion. A normalized tracing may help confirm remission der, a tumor, meningitis, or another specific cause is
of absence seizures. being treated, anticonvulsant drugs are often still re-
The EEG may be helpful in determining when to quired.
discontinue anticonvulsant therapy. The presence or
absence of epileptiform activity on the EEG prior to A. PRECAUTIONARY MANAGEMENT
withdrawal of anticonvulsants after a seizure-free period OF INDIVIDUAL BRIEF SEIZURES
of several years on the medications has been shown to Caregivers should be intstructed to protect the patient
be correlated with the degree of risk of recurrence of against self-injury and aspiration of vomitus; beyond
seizures. that, no specific therapy is necessary. The less done to
the patient during a brief seizure of less than 15 min-
utes, the better. Thrusting a spoon handle or tongue
Differential Diagnosis depressor into the clenched mouth of a convulsing pa-
It is extremely important to be accurate in the diagnosis tient or trying to restrain tonic–clonic movements may
of epilepsy and not to make the diagnosis without cause worse injuries than a bitten tongue or bruised
ample proof. To the layperson, epilepsy often has con- limb. Mouth-to-mouth resuscitation is rarely necessary.
notations of brain damage and limitation of activity. A
person so diagnosed may be excluded from certain oc- B. GENERAL MANAGEMENT
cupations in later life. It is often very difficult to change OF THE YOUNG EPILEPTIC PATIENT
an inaccurate diagnosis of many years’ standing. Some 1. Education—The patient and parents must be
of the common nonepileptic events that mimic seizure helped to understand the problem of seizures and their
disorder are listed in Table 23–11. management. Many children—some even as young as
age 3 years—are capable of cooperating with the physi-
cian in problems of seizure control.
Complications All bottles containing antiepileptic drugs should be
Emotional disturbances—notably anxiety, depression, labeled. The parents should know the names and
anger, and feelings of guilt and inadequacy—often dosage of the anticonvulsants being administered.
occur not only in the patient but also in the parents of Materials on epilepsy—including pamphlets, mono-
the child with seizures. The seizures, particularly the graphs, films, and videotapes suitable for children and
hallucinatory auras and psychomotor attacks, fre- teenagers, parents, teachers, and medical profession-
quently set off in the prepubescent and adolescent pa- als—may be purchased through the Epilepsy Founda-
tient fantasies (and sometimes obsessive ruminations) tion of America, Materials Service Center, 4351 Gar-
about dying and death that may become so strong that den City Drive, Landover, MD 20785. The
they lead to suicidal behavior. The limitations many Foundation’s local chapter and other community orga-
school systems place on epileptic children add to the nizations are eager to provide guidance and other ser-
problem. Some children may react by acting out. vices. Support groups exist in many cities for older chil-
 NEUROLOGIC & MUSCULAR DISORDERS / 753

Table 23–11. Nonepileptic paroxysmal events.

Breath-holding attacks Benign nocturnal myoclonus

Age 6 mo to 3 y. Always precipitated by trauma and fright. Common in infants and may last even up to school age.
Cyanosis; sometimes stiffening, tonic (or jerking-clonic) Focal or generalized jerks (the latter also called hypnic or
convulsion (anoxic seizure). Patient may sleep following at- sleep jerks) may persist from onset of sleep on and off all
tack. Family history positive in 30%. Electroencephalogram night. A video record for physician review can aid in diag-
(EEG) normal. Treatment is interpretation and reassurance. nosis. EEG taken during jerks is normal, proving that these
Infantile syncope (pallid breath holding) jerks are not epilepsy. Treatment is reassurance.
No external precipitant (perhaps internal pain, cramp, or Shuddering
fear?). Pallor may be followed by seizure (anoxic–ischemic). Shuddering or shivering attacks can occur in infancy and
Vagally (heart-slowing) mediated, like adult syncope. EEG be a forerunner of essential tremor in later life. Often, the
normal; may see cardiac slowing with vagal stimulation family history is positive for tremor. The shivering may be
(cold cloth on face) during EEG. very frequent. EEG is normal. There is no clouding or loss of
Tics or Tourette syndrome consciousness.
Simple or complex stereotyped (the same time after time) Gastroesophageal reflux
jerks or movements, coughs, grunts, sniffs. Worse at repose Seen more commonly in children with cerebral palsy or
or with stress. May be suppressed during physician visit. brain damage; reflux of acid gastric contents may cause
Family history often positive. EEG negative. Nonanticonvul- pain that cannot be described by the child. At times, there
sant drugs may benefit. may be unusual posturings (dystonic or other) of the head
Night terrors, sleep talking, walking, “sit-ups” and neck or trunk, an apparent attempt to stretch the
Age 3–10. Usually occur in first sleep cycle (30–90 min after esophagus or close the opening. There is no loss of con-
going to sleep), with crying, screaming, and “autonomic sciousness, but there may be eye rolling, apnea, occasional
discharge” (pupils dilated, perspiring, etc). Lasts minutes. vomiting that may simulate a seizure. An upper gastroin-
Child goes back to sleep and has no recall of event next testinal series, cine of swallowing, sometimes even an EEG
day. Sleep studies (polysomnogram and EEG) are normal. (which is always normal) may be necessary to distinguish
Disappears with maturation. Sleep talking and walking and this from seizures.
short “sit-ups” in bed are fragmentary arousals. If a spell is Masturbation
recorded, EEG shows arousal from deep sleep, but the be- Rarely in infants, repetitive rocking or rubbing motions may
havior seems wakeful. The youngster needs to be pro- simulate seizures. The youngster may look out of contact,
tected from injury and gradually settled down and taken be poorly responsive to the environment, and have auto-
back to bed. nomic expressions (eg, perspiration, dilated pupils) that
Nightmares may be confused with seizures. Observation by a skilled in-
Nightmares or vivid dreams occur in subsequent cycles of dividual, sometimes even in a hospital situation, may be
sleep, often in the early morning hours, and generally are necessary to distinguish this from seizures. EEG is of course
partially recalled the next day. The bizarre and frightening normal between or during attacks. Interpretation and reas-
behavior may sometimes be confused with complex partial surance are the only necessary treatment.
seizures. These occur during REM (rapid eye movement) Conversion reaction/pseudoseizures
sleep; epilepsy usually does not occur during that phase of As many as 50% of patients with pseudoseizures have
sleep. In extreme or difficult cases, an all-night sleep EEG epilepsy. Episodes may be writhing, intercourse-like move-
may help to differentiate seizures from nightmares. ments, tonic episodes, bizarre jerking and thrashing
Migraine around, or even apparently sudden unresponsiveness.
One variant of migraine can be associated with an acute Often, there is ongoing psychological trauma. Often, but
confusional state. There may be the usual migraine pro- not invariably, the patients are developmentally delayed.
drome with spots before the eyes, dizziness, visual field de- The spells must often be seen or recorded on videotape in
fects, and then agitated confusion. A history of other, more a controlled situation to distinguish them from epilepsy. A
typical migraine with severe headache and vomiting but normal EEG during a spell is a key diagnostic feature. Often,
without confusion may aid in the diagnosis. The severe the spells are so bizarre that they are easily distinguished.
headache with vomiting as the youngster comes out of the Sometimes, pseudoseizures can be precipitated by sugges-
spell may aid in distinguishing the attack from epilepsy. tion with injection of normal saline in a controlled situa-
Other seizure manifestations are practically never seen, eg, tion. Combativeness is common; self-injury and inconti-
tonic–clonic movements, falling, and complete loss of con- nence rare.
sciousness. The EEG in migraine is usually normal and sel- Temper tantrums and rage attacks
dom has epileptiform abnormalities often seen in patients These are sometimes confused with epilepsy. The young-
with epilepsy. Lastly, migraine and epilepsy are sometimes ster is often amnesic or at least claims amnesia for events
linked: migraine-caused ischemia on the brain surface during the spell. The attacks are usually precipitated by
sometimes leads to later epilepsy. frustration or anger and are often directed either verbally
(continued)
754 / CHAPTER 23

Table 23–11. Nonepileptic paroxysmal events. (continued)

or physically and subside with behavior modification and in this age group), abnormalities with hypofunction of one
isolation. EEGs are generally normal but unfortunately sel- side are sometimes seen. Medications are usually not desir-
dom obtained during an attack. Anterior temporal leads able or necessary.
may be helpful in ruling out temporal or lateral frontal ab- Staring spells
normalities, the latter sometimes seen in partial complex Teachers often make referral for absence or petit mal
seizures. Improvement of the attacks with psychotherapy, seizures in youngsters who stare or seem preoccupied at
milieu therapy, or behavioral modification helps rule out school. Helpful in the history is the lack of these spells at
epilepsy. home, eg, before breakfast, a common time for absence
Benign paroxysmal vertigo seizures. A lack of other epilepsy in the child or family his-
These are brief attacks of vertigo in which the youngster tory often is helpful. Sometimes, these children have diffi-
often appears frightened and pale and clutches the parent. culties with school and a cognitive or learning disability.
The attacks last 5–30 s. Sometimes, nystagmus is identified. The child can generally be brought out of this spell by a
There is no loss of consciousness. Usually, the child is well firm command. An EEG is sometimes necessary to confirm
and returns to play immediately afterward. The attacks may that absence seizures are not occurring. A 24-hour ambula-
occur in clusters, then disappear for months. Attacks are tory EEG to record attacks during the child’s everyday
usually seen in infants and preschoolers age 2–5. EEG is school activities is occasionally necessary.
normal. If caloric tests can be obtained (often very difficult

dren and adolescents and for their parents and others or basic neurologic problem does not interfere with the
concerned. ability to drive. A guide to this and other legal matters
2. Privileges and precautions in daily life—Encour- pertaining to persons with epilepsy is published by the
age normal living within reasonable bounds. Children Epilepsy Foundation of America, whose legal depart-
should engage in physical activities appropriate to their ment may be able to provide additional information
age and social group. After seizure control is estab- (see reference at the end of this section).
lished, swimming is generally permissible with a buddy 4. Pregnancy—In the pregnant teenager with epilepsy,
system or adequate lifeguard coverage. High diving and the possibility of teratogenic effects of anticonvulsants,
high climbing should not be permitted. Physical train- such as facial clefts (two to three times increased risk),
ing and sports are usually to be welcomed rather than must be weighed against the risks from seizures. Such
restricted. Driving is discussed in the next section. malformations occur in the infants of about 2.5% of
Loss of sleep should be avoided. Emotional distur- mothers with untreated epilepsy.
bances may need to be treated. Alcohol intake should
C. PRINCIPLES OF ANTICONVULSANT THERAPY
be avoided because it may precipitate seizures. Prompt
attention should be given to infections. Further neuro- 1. Drug selection—Treat with the drug appropriate
logic disturbances should be brought to the physician’s to the clinical situation, as outlined in Table 23–12.
attention promptly. 2. Treatment strategy—Start with one drug in con-
Although every effort should be made to control ventional dosage, and increase the dosage until seizures
seizures, this must not interfere with a child’s ability to are controlled. If seizures are not controlled on the tol-
function. Sometimes a child is better off having an oc- erated maximal dosage of one major anticonvulsant,
casional mild seizure than being so heavily sedated that gradually switch to another before using two-drug ther-
function at home, in school, or at play is impaired. apy. The dosages and usually effective blood levels are
Therapy and medication adjustment often require listed in Table 23–12. Individual variations must be ex-
much art and fortitude on the physician’s part. Some pected. The therapeutic range may also vary somewhat
patients with infrequent seizures, especially if only noc- with the method used to determine levels.
turnal partial seizures (eg, Rolandic seizures) may not 3. Counseling—Advise the parents and the patient
need anticonvulsant medications. that the prolonged use of anticonvulsant drugs will not
3. Driving—Driving becomes important to most produce significant or permanent mental slowing (al-
young people at age 15 or 16 years. Restrictions vary though the underlying cause of the seizures might) and
from state to state. In most states, a learner’s permit or that prevention of seizures for 1–2 years substantially
driver’s license will be issued to an epileptic individual reduces the chances of recurrence. Advise them also
if he or she has been under a physician’s care and free of that anticonvulsants are given to prevent further
seizures for at least 1 year, provided that the treatment seizures and that they should be taken as prescribed.
Table 23–12. Guide to pediatric anticonvulsant drug therapy.a

Average Total
Dosage Steady Effective Side Effects Directions
Drug (mg/kg/d) State Blood Levelsb and Precautions and Remarks
Primary anticonvulsant
Carbamazepine 15–25 mg/kg/d 3–6 d 4–12 µg/mL (> 15) Dizziness, ataxia, diplo- Monitor CBC, platelet count, liver
(Tegretol) in 2–4 divided pia, drowsiness, nausea, function tests periodically. Blood
(Carbatrol, doses rash. Rare: hepato- effects usually early and trans-
Tegretol XR toxicity, bone marrow ient. Drug interactions: ↑ by flu-
are sustained depression, dystonia, oxetine, propoxyphene, erythro-
release inappropriate ADH mycin, cimetidine; ↓ by felba-
formulations) secretion, bizarre mate, phenobarbital, phenytoin.
behaviors, tics.
Valproic acid 15–60 mg/kg/d 2–4 d 50–120 µg/mL Weight gain, occa- For prophylaxis in febrile convul-
(Depakene, in 2–4 divided (> 140) sional gastric discom- sions, see text. Monitor CBC,
Depakote) doses fort, constipation. Tre- platelets, liver function tests
(Depacon) mor, hair loss in 5%. closely in first 6 months, then
Rare: hepatotoxicity, periodically. Can be given
hyperammonemia, rectally (suspension: 250 mg/
leukopenia, polycystic 5 mL). Depacon is an IV prepa-
ovaries (more toxic ration, 100 mg/mL. Drug interac-
in infants younger tions: ↓ by phenobarbital,
than 2 years) phenytoin, carbamazepine, ↑ by
lamotrigine felbamate.
Phenytoin 5–10 mg/kg/d 5–10 d 5–20 µg/mL Gum hypertrophy, hir- Good dental hygiene reduces
(Dilantin) in 1 or 2 doses (>25) sutism, ataxia, nys- gum hyperplasia. May aggravate
tagmus, diplopia, rash, absence and myoclonic seizures.
anorexia, nausea, Poorly absorbed by neonatal gut.
osteomalacia. Rare: Use 50 mg Infant tabs in infants
macrocytic anemia, (may be crushed to adjust dos-
lymph node involve- age). Suspension not recom-
ment, exfoliative mended. Drug interactions: ↑ by
dermatitis, peripheral felbamate; ↓ by carbamazepine,
neuropathy. phenobarbital, antacids.
Phenobarbital 3–5 mg/kg/d 10–21 d 15–40 µg/mL Irritability and overac- Overall, the safest drug. Bitter
as single daily (> 45) tivity in many children; taste. Higher blood levels some-
dose sedative effects in times required and tolerated in
others. Mild ataxia, severe chronic epileptics. Useful
depression, skin rash. in neonatal seizures and status
May interfere with epilepticus. Valproate increases
learning. unbound phenobarbital levels.
Primidone 10–25 mg/kg/d 1–5 d 4–12 µg/mL Drowsiness, ataxia, Start slowly with 25–35% of ex-
(Mysoline) in 3 or 4 (> 15) vertigo, anorexia, nau- pected maintenance dose; in-
divided doses sea, vomiting, rash. (Like crease every other day until full
phenobarbital.) dose reached.
Ethosuximide 10–40 mg/kg/d 5–6 d 40–100 µg/mL Nausea, gastric dis- May aggravate generalized sei-
(Zarontin) in 1 or 2 doses (> 150) comfort, hiccups, zures. Combine with valproic acid
blood dyscrasias. in refractory absence seizures.
Clonazepam 0.01–0.1 mg/ 5–10 d 15–80 ng/mL Drowsiness (> 50%): Start slowly with 25% of expect-
(Klonopin) kg/dose 1–2 (> 80) soporific effects great- ed maintenance dosage; increase
times/day est drawback. Behav- every 2 or 3 d. Useful with re-
ior problems in 25%. fractory minor motor seizures (as-
Slurred speech, ataxia, tatic, myoclonic, infantile spasms;
salivation. absences). Tolerance may occur.
(continued)
756 / CHAPTER 23

Table 23–12. Guide to pediatric anticonvulsant drug therapy.a (continued)

Average Total
Dosage Steady Effective Side Effects Directions
Drug (mg/kg/d) State Blood Levelsb and Precautions and Remarks
Adjunctive or secondary drug
Acetazolamide 5–20 mg/kg/d 1–2 d 10–14 µg/mL Anorexia; numbness Supplement to other medications,
(Diamox) in 2 or 3 divided and tingling. Urinary especially in absence and com-
doses frequency, so do not plex partial seizures. Also in fe-
give in evening. Renal males 4 days prior to and in the
stones. first 2 or 3 days of menstrual pe-
riod for catamenial seizures.
Levetiracetam 10–20 mg/kg/d. 1–3 d 20–40 µg/mL Somnolence, dizziness, Complex partial seizures, myo-
(Keppra) To maximal headache, asthenia. clonic. Little effect on other drugs.
40–60 over Rare: decWBC
2–6 weeks
Oxcarbazepine 8–10 mg/kg/d 1–3d MHD (breakdown Dizziness, fatigue, Partial, generalized seizures. Little
(Trileptal) initial, 20–50 product) 12–30 somnolence, nausea, effect on other drug levels. No
mg/kg/d maint µg/mL ataxia, headache, hypo- need for lab (CBC, LFTs).
in 2 doses natremia, rash
Felbamate 15–45 mg/kg/d 5–7 d 22–137 µg/mL Anorexia, vomiting, in- A dangerous drug. Used in
(Felbatol) in 3 or 4 somnia, headache, children with Lennox–Gastaut
divided doses somnolence. Rash in syndrome; in adults with com-
1%. Aplastic anemia plex partial seizures. Obtain
and hepatic failure are informed consent. Drug interac-
significant hazards. tions: ↓ by phenytoin, carba-
mazepine.
Vigabatrin 20–100 mg/ Not Not known Drowsiness, confusion, Infantile spasms, especially tub-
(Sabril) kg/d in 2–3 known weight gain, retinal erous sclerosis. Add-on drug for
divided doses changes, visual loss partial seizures. Not licensed by
FDA in United States as of 1999
Gabapentin 30–60 mg/kg/d 1–2 d 12–25 µg/mL Drowsiness, dizziness, Add-on drug for partial seizures;
(Neurontin) in 3 divided ataxia. no effect on other anticonvulsant
> 12 years doses (900– drug levels.
4800 mg total
per day)
Topiramate Start 0.5–1 mg/ Not 8–25 µg/mL Somnolence, slowed Adjunctive drug for complex
(Topomax) kg/d to 10 mg/ known mentation, dizziness, partial seizures. Minimal effect
kg/d) in 2 di- language problems, on other drug levels. Lennox–
vided doses kidney stones (rarely, Gastaut, West syndrome.
(maximum, metabolic acidosis, Broad-spectrum drug.
400 mg/d) anorexia).
Tiagabine 0.1–1.5 mg/ 1–2 d 20–70 µg/mL Dizziness, tremor, Adjunctive drug for partial
(Gabitril) kg/d in 2 abnormal thinking seizures.
divided doses
Zonisamide 1–2 mg/kg/d 5–7 d 20–30 µg/mL Drowsiness, anorexia, Effects in multi seizure types. A
(Zonegran) to maximum GI symptoms, weight sulfonamide (don’t use if allegic
8–12 mg/kg/d loss, behavior changes, to sulfa drugs). Hazard: oligohy-
in 1 or 2 divided renal stones (0.2–2%), drosis-fever syndrome. Widely
doses hypohidrosis. Rash used in Japan.
(continued)
 NEUROLOGIC & MUSCULAR DISORDERS / 757

Table 23–12. Guide to pediatric anticonvulsant drug therapy.a (continued)

Average Total
Dosage Steady Effective Side Effects Directions
Drug (mg/kg/d) State Blood Levelsb and Precautions and Remarks
Lamotrigine 5–15 mg/kg/d 8–15 d 10–20 µg/mL Dizziness, headaches, Add-on drug for children older
(Lamictal) in 2 divided diplopia, ataxia, nausea. than 16 y with complex partial sei-
doses (1–5 mg/ Rash in 5–10%. 1% zures, Lennox–Gastaut syndrome,
kg if taking val- Stevens–Johnson absence seizures. Valproate in-
proic acid); 5–400 usually in first creases drug half-life. Increase
mg/d total 4–8 wk. dose slowly over 2 mos.
Treatment of status epilepticusa
Diazepam 0.3 mg/kg IV. Repeat dose: 0.1–0.3 mg/kg IV. Administer slowly. May need to be repeated every
(Valium) Monitor pulse and 3–4 h. Follow with phenytoin
blood pressure. May or phenobarbital for long-range
cause respiratory control. Note: Intramuscular
depression in pres- administration for status epilep-
ence of phenobarbital. ticus ineffective.
Phenobarbital 5–20 mg/kg IV initially. Repeat dose: See above. Rule out pyridoxine deficiency.
5–10 mg/kg IV. In neonatal seizures, load with
15–20 mg/kg IV.
Phenytoin 10–20 mg/kg IV initially. Repeat dose: Administer IV over a Adjunct in neonatal seizures (20
(Dilantin); 5–10 mg/kg IV. 5-min period. Administer mg/kg IV) if phenobarbital alone
(Fospheny- fosphenytoin IM only if fails. Fosphenytoin, new safe
toin newer, no IV access. Monitor preparation. Same dose. May
safer) blood levels. give rapidly IV, over 5 min.
Lorazepam 0.05–0.2 mg/kg IV. May repeat. Mild respiratory May be more effective than
(Ativan) depression. diazepam. Longer-acting.
Midazolam 0.1–0.3 mg/kg IM or IV; 0.2 mg/kg as nasal See other benzodia- Short-acting.
(Versed) spray. IV drip 1–5++ µg/kg/min pines.
Valproate 5–60 mg/kg IV (20 mg/min). Administer slowly. Half-life 16 h. Useful when child
sodium (Dep- Depacon rapid injection form (see Table 23–9) Dizziness, nausea, and can’t take valproate orally, or for
acon) injection-site pain. status epilepticus
a
Treatment of infantile spasms: See text regarding use of corticotropin or corticosteroids. See also clonazepam or valproic acid, especially
with recurrences. ADH = antidiuretic hormone; CBC = complete blood count; IM = intramuscularly; IV = intravenously; MHD = mono hy-
droxy metabolite; LFT = liver function tests.
b
In parentheses are shown the levels at which clinical toxicity becomes manifest in monotherapy.
c
General anesthesia if other measures fail.

Changes in medications or dosages should not be made riodic neurologic reevaluation is important. Repeat
without the physician’s knowledge. Unsupervised sud- EEGs are not needed to achieve seizure control. Indica-
den withdrawal of anticonvulsant drugs may precipitate tions for repeat EEGs are discussed earlier.
severe seizures or even status epilepticus. Anticonvul-
sants must be kept where they cannot be ingested by 5. Long-term management—Continue anticonvul-
small children or suicidal patients. sant treatment until the patient is free of seizures for at
least 1–2 years or, in some cases, until the patient
4. Follow-up—Check the patient at intervals, depend- reaches adolescence. In about 75% of patients, seizures
ing on the underlying cause of the seizures, the degree may not recur. Variables such as younger age at onset,
of control, and the toxic properties of the anticonvul- normal EEG, and ease of controlling seizures carry a fa-
sant drug or drugs used. Blood counts and liver func- vorable prognosis, whereas later onset, epileptiform
tion tests must be obtained periodically in the case of spikes on EEG, difficulty in controlling the seizures,
some anticonvulsants, as indicated in Table 23–12. Pe- polytherapy, generalized tonic–clonic or myoclonic
758 / CHAPTER 23

seizures, and an abnormal neurologic examination are tient. Blood level monitoring is useful also when ex-
associated with a higher risk of recurrence. pected control on a “usual” dosage has not been
6. Withdrawal of treatment—In general, there is no achieved either with a single drug or after adding an-
need to withdraw anticonvulsants before taking an other, when seizures recur in a patient with previously
EEG. Discontinue anticonvulsants gradually. If it be- well-controlled seizures, or when control is poor in a
comes necessary to withdraw anticonvulsants abruptly, patient taking anticonvulsants who is being seen for the
the patient should be under close medical surveillance. first time. A low level may indicate inadequate dosage,
If seizures recur during or after withdrawal, anticonvul- drug interaction, or noncompliance with the prescribed
sant therapy should be reinstituted and again main- regimen. A high level may indicate slowed metabolism
tained for at least 1–2 years. or excretion or drug interaction.
Blood levels are mandatory when signs and symp-
D. BLOOD LEVELS OF ANTIEPILEPTIC DRUGS toms of toxicity are present, especially when more than
1. General comments—Most anticonvulsants take one drug is being used or when the dosage of a single
two or three times the length of their half-life to reach drug has been changed. Blood levels may be the only
the steady states indicated in Table 23–12. This must means of detecting intoxication in a comatose patient
be considered when blood levels are assessed after anti- or very young child. Toxic levels also occur with drug
convulsants are started or dosages are changed. Individ- abuse and liver or renal disease. Blood levels of anticon-
uals vary in their metabolism and their particular phar- vulsants are unnecessary when the patient’s seizure con-
macokinetic characteristics. These and external factors, trol is satisfactory and he or she is free of toxic signs or
including, for example, food intake or illness, also affect symptoms.
the blood level. Thus the level reached on a milligram E. SIDE EFFECTS OF ANTIEPILEPTIC DRUGS
per kilogram basis varies among patients. Experience
and clinical research in the determination of antiepilep- (See also Table 23–12.)
tic blood levels have shown that there is some correla- 1. Allergic reactions—Serious allergic reactions usu-
tion between (1) drug dose and blood level, (2) blood ally necessitate discontinuance of a drug. However, not
level and therapeutic effect, and (3) blood level and every rash in a child receiving an anticonvulsant is
some toxic effects. drug-related. If a useful antiepileptic drug is discontin-
2. Effective levels—The ranges given in Table ued and the rash disappears, restarting the drug in a
23–12 are those within which seizure control without smaller dosage may be warranted to see if the rash re-
toxicity will be achieved in most patients. The level for curs.
any given individual will vary not only with metabolic 2. Drug toxicity—Signs of drug toxicity often disap-
makeup (including biochemical defects) but also with pear when the daily dosage is reduced by 25–30%.
the nature and severity of the seizures and their under- 3. Avoiding sedation—The sedative effect of many of
lying cause, and with other medications being taken, the anticonvulsants may be avoided by slowly working
among other factors. Seizure control may be achieved at up to the usual therapeutic dose—for example, over
lower levels in some patients, and higher levels may be 3–4 weeks for phenobarbital.
reached without toxicity in others. When control is
achieved at a lower level, the dosage should not be in- 4. Avoiding side effects—Gingival hyperplasia sec-
creased merely to get the level into the therapeutic ondary to phenytoin is best minimized through good
range. Likewise, toxic side effects will be experienced at dental hygiene but occasionally requires gingivectomy.
different levels even within the therapeutic range. Low- This condition may recede within about 6 months after
ering the dosage usually resolves the problem, but the drug is discontinued. The hypertrichosis associated
sometimes the drug must be withdrawn or another with phenytoin does not regress when the drug is dis-
added (or both). Some serious toxic effects, including continued.
allergic reactions and bone marrow or liver toxicity, are F. ADRENOCORTICOTROPIC HORMONE
independent of dosage. AND CORTICOSTEROIDS
3. Interaction of antiepileptic drugs—Blood levels 1. Indications—These drugs are indicated for infantile
of anticonvulsants may be affected by other drugs. Indi- spasms not due to causes amenable to specific therapy
vidual variations occur; adjustment of dosages may be and in the Lennox–Gastaut syndrome, which cannot be
required. (See Table 23–12.) controlled by anticonvulsant drugs. Duration of ther-
4. Indications for determination of blood levels— apy is guided by cessation of clinical seizures and nor-
Drug blood levels should be measured after a new drug malization of the EEG. ACTH or oral corticosteroids
is introduced and seizure control without toxicity is are usually continued in full doses for 2 weeks and
achieved to determine the effective level for that pa- then, if seizures have ceased, tapered over 1 week. Oth-
 NEUROLOGIC & MUSCULAR DISORDERS / 759

ers use a total treatment period of about 2 months. If amounts of) anticonvulsants, and parental and patient
seizures recur, the dosage is increased to the last effec- satisfaction is most gratifying.
tive level and repeated for 2–4 weeks, or switching to or
from prednisone is tried. Some clinicians keep the pa- H. SURGERY
tient at this dosage for up to 6 months before attempt- In seizure disorders intractable to anticonvulsant ther-
ing withdrawal. There is no strong evidence, however, apy and primarily of focal origin, neurosurgery should
that longer courses of treatment are more beneficial. be considered. Useful procedures, depending on the le-
2. Dosages— sion, include corticectomy, hemispherectomy, anterior
temporal lobectomy (for complex partial seizures), cal-
a. ACTH gel—Start with 2–4 units/kg/d intramus- losotomy (or commissurotomy), and stereotactic abla-
cularly in a single morning dose. Parents can be taught tion. Vagal nerve stimulation with an implanted elec-
to give injections. trode is another new, expensive surgical approach for
b. Prednisone—Start with 2–4 mg/kg/d orally in intractable epilepsy.
two or three divided doses.
3. Precautions—Give additional potassium, guard Avoli M et al: Generalized epileptic disorders: An update. Epilepsia
2001;42:445 [PMID: 11440339].
against infections, follow for possible hypertension, and
discuss the cushingoid appearance and its disappear- Berg AT et al: How long does it take for partial epilepsy to become
intractable? Neurology 2003;60:186 [PMID: 12552028].
ance. Do not withdraw oral corticosteroids suddenly.
Berg AT et al: Neuroimaging in children with newly diagnosed
Side effects in some series occur in up to 40% of pa- epilepsy: A community based study. Pediatrics 2000;106:
tients, especially with higher dosages than those listed 527 [PMID: 10969098].
here (used by some authorities). With long-term use, Bourgeois BFD: .Chronic management of seizures in the syn-
prophylaxis against Pneumocystis infection may be re- dromes of idiopathic generalized epilepsy. Epilepsia 2003;44:
quired. 27 [PMID: 12752459].
Browne TR, Holmes GL: Epilepsy. N Engl J Med 2001;344:
G. KETOGENIC OR MEDIUM-CHAIN TRIGLYCERIDE 1145 [PMID: 11297707].
Diet in Treatment of Epilepsy Buchhalter JR, Jarrar RG: Therapeutics in pediatric epilepsy, Part
2: Epilepsy surgery and vagus nerve stimulation. Mayo Clin
A ketogenic diet should be recommended in astatic and Proc 2003;78:371 [PMID: 12630591].
myoclonic seizures and absence seizures not responsive Camfield P, Camfield C: Childhood epilepsy: What is the evidence
to drug therapy. It is occasionally recommended for in- for what we think and what we do? J Child Neurol 2003;
fantile spasms that do not respond to ACTH or corti- 18:272 [PMID: 12760431].
costeroids. Ketosis is induced by a diet high in fats and Capovilla G et al: Short-term nonhormonal and nonsteroid treat-
very limited in carbohydrates with sufficient protein for ment in West syndrome. Epilepsia 2003;44:1085 [PMID:
body maintenance and growth. The ratio of fat calories 12887441].
to carbohydrate calories may range from 2.5:1 up to Claassen J et al: Treatment of refractory status epilepticus with pen-
tobarbital, propofol, or midazolam: A systematic review.
4:1. Adding medium-chain triglycerides to the diet in- Epilepsia 2002;43:146 [PMID: 11903960].
duces ketosis more readily than does a high level of di- Daulin M et al: Reduction of seizures with low-dose Clonazepam
etary fats and thus requires less carbohydrate restriction. in children with epilepsy. Pediatr Neurol 2003;28:48
The mechanism for the anticonvulsant action of the ke- [PMID: 12657920].
togenic diet is not understood. It is, however, the keto- DeViro DC: Metabolic determinants of infant epilepsy. J Child
sis, not the acidosis, that raises the seizure threshold. Neurol 2002;17 (Suppl 3):351.
The diet is most effective in children younger than age Glauser TA, Pellock JM: Zonisamide in pediatric epilepsy: Review
8 years. of the Japanese experience. J Child Neurol 2002;17:87
The ketogenic diet is difficult and expensive, tends [PMID: 119952083].
to be monotonous, and depends on the caregiver’s abil- Hancock E et al: The treatment of West syndrome: A Cochrane re-
ity to weigh out the foods as well as on absolute adher- view of the literature to December 2000. Brain & Dev
2001;23:624 [PMID: 11701267].
ence to the diet prescribed. Whether the ketosis is
achieved by high-fat meals or by adding medium-chain Hawash KY, Rosman P: Do partial seizures predict an increased
risk of seizure recurrence after antiepilepsy drugs are with-
triglycerides to the diet is often a matter of the physi- drawn? J Child Neurol 2003;18:331 [PMID: 12822817].
cian’s, the dietitian’s, or the patient’s preference. The Hill A: Neonatal seizures. Pediatr Rev 2000;21:117 [PMID:
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760 / CHAPTER 23

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SYNCOPE & FAINTING
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Pavone P et al: Neuropsychological assessment in children with of children (age birth–20 years) will faint at some time.
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Philippi H et al: Topiramate and metabolic acidosis in infants and
toddlers. Epilepsia 2002;43;744 [PMID: 12102678].
falling, many children stiffen or have jerking motions
when unconscious, a tonic–clonic, anoxic–ischemic
Prasad A et al: Evolving antiepileptic drug treatment in juvenile
myoclonic epilepsy. Arch Neurol 2003;60:1100 [PMID: seizure mimicking epilepsy. Watching or undergoing a
12925366]. venipuncture is a common precipitant of fainting, as is
Sahin M, Riviello JJ: Prolonged treatment of refractory status prolonged standing, fatigue, illness, overheating and
epilepticus in a child. J Child Neurol 2001;16:147 [PMID: sweating, dehydration, hunger, and athleticism with
11292225]. slow baseline pulse. The family history is positive for
Sahin M et al: Prolonged treatment for acute symptomatic refrac- similar episodes in 90% of patients.
tory status epilepticus. Neurology 2003;61:398 [PMID:
12913208].
Shinnar S, Glauser TA: Febrile Seizures. J Child Neurol 2002; Classification
17:S44 [PMID: 11918463]. Ninety-five percent of cases of syncope are of the vaso-
Shinnar S et al: Short-term outcomes of children with febrile status vagal–vasodepressive or neurocardiogenic type (Table
epilepticus. Epilepsia 2001;42:47 [PMID: 211207784].
23–13). Vasodilation, cardiac slowing, and hypotension
Sinclair DB: Prednisone therapy in pediatric epilepsy. Pediatr Neu-
rol 2003:28:194 [PMID: 12770672].
Singhi S et al: Continuous midazolam versus diazepam infusion for
refractory convulsive status epilepticus. J Child Neurol
2002:17:106 [PMID: 11952069].
Table 23–13. Classification of syncope
Snodgrass SR: Ambulatory management of children with epilepsy. in childhood.
Pediatr Ann 1999;28:246 [PMID: 10224618].
Snodgrass SR, Parks BR: Anticonvulsant blood levels: Historical re- Vasovagal, neurocardiogenic (neurally mediated)
view with a pediatric focus. J Child Neurol 2000; Orthostatic
15:734 [PMID: 11108507]. Athleticism
Stromme P et al: Infantile spasms, dystonia, and other X-linked Pallid breath-holding
phenotypes caused by mutations in Arista-less related home- Situational (stress, blood drawing)
obox gene, ARX. Brain Dev 2002;24:266 [PMID: Cardiac
12142061].
Obstructive
Tromp SC et al: Relative influence of epileptic seizures and of Arrhythmia
epilepsy syndrome on cognitive function. J Child Neurol
2003;18:407 [PMID: 12886976].
Prolonged QTc
Hypercyanotic (eg, in tetralogy of Fallot)
Uneri A, Turkdogan D: Evaluation of vestibular functions in chil-
dren with vertigo attacks. Arch Dis Child 2003;88:510
Nonsyncope mimicker
[PMID: 12765917]. Migraine with confusion or stupor
Valente KD et al: The diagnostic role of short duration outpatient
Seizure
V-EEG monitoring in children. Pediatr Neurol 2003;28: Hypoglycemia
285 [PMID: 12829881]. Hysteria
VanNess PC: therapy for the epilepsies. Arch Neurol 2002;59:732 Hyperventilation
[PMID: 12020253]. Vertigo
 NEUROLOGIC & MUSCULAR DISORDERS / 761

cause transient (1–2 minutes) cerebral ischemia and re- tating situations. The patient should be cautioned to lie
sult in the patient passing out. The patient arouses in down if prodromal symptoms occur. Good hydration
1–2 minutes, but full recovery may take an hour or and reasonable salt intake are advisable. In some cases
more. Besides those already listed, rare precipitants in- β-blockers and rarely fludrocortisone may have a role.
clude hair grooming, cough, micturition, neck stretch-
ing, and emotional stress. More ominous is cardiac syn- Kapoor WN: Syncope. N Engl J Med 2000;343:1856 [PMID:
cope, which often occurs during exercise. Angina or 11117979].
palpitations may occur. An obstructive lesion such as Narchi H: The child who passes out. Pediatr Rev 2000;21:384
aortic stenosis, cardiomyopathy, coronary disease, or [PMID: 11077022].
dysrhythmia may be the cause. Other spells that may Sateriades ES et al: Incidence and prognosis of syncope. N Engl
mimic syncope are listed in Table 23–13. J Med 2002;347:878 [PMID: 12239256].
Willis J: Syncope. Pediatr Rev 2000;21:201 [PMID: 10854315].
Clinical Findings
HEADACHES
A. SYMPTOMS AND SIGNS
The work-up of fainting includes the history and a Headache is one of the most common complaints in pe-
physical examination with emphasis on blood pressure diatric neurology clinics, accounting for 25–30% of all
and cardiac and neurologic features. In the adolescent, referrals. Epidemiologic studies indicate that headache
a blood pressure drop of more than 30 mm Hg after occurs in 37% of children by age 7 years and in 69% of
standing for 5–10 minutes or a baseline systolic pres- children by age 14 years. Migraine headache occurs in
sure of less than 80 mm Hg suggests orthostasis. 5% and 15%, respectively, of children at these ages.
Successful treatment requires an accurate diagnosis and
B. LABORATORY FINDINGS AND IMAGING proper classification of headache. Based on the patient’s
Hemoglobin should be checked if anemia is suggested history, a simplified initial categorization as summarized
by the history. Electrocardiography should be done. in Table 23–14 can be made. A more exhaustive classifi-
Consider Holter monitoring and echocardiography if cation scheme has been developed by the International
cardiac causes seem likely. Tilt testing (though norms Headache Society and modified for use in children.
are vague) may have a role in frequent recurrent syn- Muscle contraction, tension headaches are common in
cope to confirm a vasodepressive cause and avoid more older children and adolescents. They are frequently gen-
expensive diagnostic investigations. eralized over the head with a “hat band” pressure or
squeezing quality. Although appetite may be dimin-
ished, nausea and vomiting are usually not present.
Treatment Symptoms specifically referable to the CNS are absent.
Treatment consists mostly of giving advice about the If this type of headache becomes very frequent (3 or
benign nature of fainting and about avoiding precipi- more days per week) consideration should be given to

Table 23–14. Differential features of headaches in children.

Muscle Contraction Vascular Traction and Inflammatory

(Tension/Psychogenic) (Migraine) (Increased Intracranial Pressure)
Time course Chronic, recurrent Acute, paroxysmal, recurrent Chronic or intermittent but increas-
ingly frequent; progressive severity
Prodromes No Yes (sometimes in children) No
Description Diffuse, band-like, tight Intense, pulsatile, unilateral in older Diffuse; more occipital with infraten-
child (70%); usually forehead in or torial mass, more frontal with supra-
behind one or both eyes. tentorial mass
Characteristic findings Feelings of inadequacy, Neurologic symptoms and signs Positive neurologic signs, especially
depression, or anxiety usually transient papilledema
Predisposing factors Problems at home or Positive family history (75%); trivial No
school or socially (sexually) head trauma may precipitate
762 / CHAPTER 23

drug (analgesic) overuse or misuse, depression, or sleep frequently accompanied by nausea, vomiting, photo-
disorder. The neurologic examination is normal, neu- phobia, sensitivity to sound, vertigo, lightheadedness,
roimaging tests are generally not needed, and treatment fatigue, and mood alterations. Occasionally children
is judicious use of ibuprofen with or without a limited may have loss of speech, hemiparesis, ataxia, confu-
trial of amitriptyline. If simple measures are not satisfac- sional states, and bizarre visual distortions (so-called
tory, biofeedback may be useful. Alice in Wonderland syndrome). Very young children
Between 65% and 75% of children referred to neurol- may experience recurrent or cyclical vomiting, abdomi-
ogy clinics for consultation regarding headaches have mi- nal pain, or recurrent self-limited bouts of ataxia or ver-
graine. Many of these children are referred after they have tigo as the early manifestations of migraine.
seen ophthalmologists for “eye strain” or otolaryngologists Occasionally the frequency of migraine may sponta-
to rule out sinusitis. Approximately 30% of children are neously increase and become almost daily, a condition
referred after already undergoing one or more neuroimag- referred to as transformed migraine. When this change
ing tests, the vast majority of which are normal. in frequency happens, it should at least raise suspicion
of medication overuse with development of rebound
Clinical Findings headache; successful treatment of which requires med-
ication withdrawal for 6–12 weeks or longer.
The diagnosis and proper classification of migraine de- In contrast to tension and migraine headaches,
pends primarily on a thorough and detailed history headaches caused by intracranial disorders or increased
(Table 23–15). Migraine headaches are paroxysmal, re- intracranial pressure rarely occur in children who are
current events separated by symptom-free intervals in a otherwise healthy and well and who have completely
child with normal growth and development and whose normal examinations.
neurologic examination is normal. Migraine affects Laboratory studies and neuroimaging tests are rarely
children of all ages but is difficult to diagnose before needed if a thorough history has been taken and the
age 4 years. The family history is positive for vascular, neurologic examination is normal. If the progression of
migrainous headaches in 75% of patients. The headache is atypical for migraine or tension-type
headaches have a pulsatile quality and are located uni- headaches or if the neurologic examination is abnormal,
laterally or bilaterally in the frontal or temporal regions, an MRI scan should be considered. When papilledema
or commonly in the retro-orbital and cheek regions. is present but the MRI is normal, a lumbar puncture
The headaches last from 2 to more than 24 hours. A may be needed to diagnose pseudomotor cerebri.
nonspecific prodrome of decreased or increased ap-
petite and change in mood and temperament may pre-
cede the headache by hours or days. Headaches may be
Treatment
triggered by specific foods, minor head injuries, sleep Successful treatment of migraine is usually achieved
deprivation, or irregular eating patterns, but more often with the systematic use of simple analgesics such as
no precipitant can be identified. An aura such as visual ibuprofen. The key to successful results is to take
scotomata is uncommon in children. The headache is enough early enough to do the job. As soon as possible

Table 23–15. Proposed Revised IHS Classification

Pediatric Migraine Without Aura (Common) Pediatric Migraine With Auraa (Rare)
Diagnostic Criteria Diagnostic Criteria
A. At least five attacks fulfilling B-D A. At least two atacks fulfilling B
B. Headache attack lasting 1-48 hours B. At least three of the following:
C. Headache has at least two of the following: 1. One or more fully reversible aura aymptoms
1. Bilateral location (frontal/temporal) or unilateral location indicating focal cortical and/or brain stem dys-
2. Pulsating quality function
3. Moderate to severe intensity 2. At least one aura developing gradually over
4. Aggravation by routine physical acitivity more than 4 minutes or 2 or more symptoms oc-
D. During headache, at least one of the following curring in succession
1. Nausea and/or vomiting 3. No auras lasting more than 60 minutes
2. Photophobia and/or phonophobia 4. Headache follows less than 60 minutes
a
Idiopathic recurring disorder; headache usually lasts 1–48 hours.
IHS = International Headache Society.
Adapted from: Winner P et al: Classification of pediatric migraine: Proposed revisions of the IHS criteria. Headache 1995; 35:407.
 NEUROLOGIC & MUSCULAR DISORDERS / 763

after the headache starts, the child is given ibuprofen during sleep and frequent awakenings in an older child
10 mg/kg followed in 45 minutes by 5 mg/kg if who shows poor school performance associated with ex-
needed. Additional doses of analgesics rarely provide cessive daytime sleepiness or irritability and hyperactiv-
additional benefit. The addition of 40–65 mg of caf- ity. Children with these problems frequently have hy-
feine, caffeine–ergotamine combinations, or 65 mg of pertrophied tonsils or adenoids, causing partial airway
isometheptene (Midrin) to ibuprofen may provide obstruction. Sleep apnea may be associated with facial
more reliable relief for some patients. Nausea and vom- dysmorphism; neuromuscular disorders with poor pha-
iting can be treated with metoclopramide (Reglan), ryngeal muscle control; and conditions with swelling of
taken 10–20 minutes before other medications. For fre- soft tissue in pharynx and neck such as myxedema,
quently recurring migraine, prophylaxis with propra- Hodgkin disease, and massive obesity (Pickwickian syn-
nolol, amitriptyline, cyproheptadine, valproate, or cal- drome). Evaluation includes soft tissue radiographs of
cium channel blockers should be considered. At this the lateral neck; chest radiograph; electrocardiogram
time experience with using triptan and dihydroergota- (ECG) to rule out cardiomegaly, sinus dysrhythmias,
mine (nasal spray) in children is limited, but some stud- and right-sided heart failure; arterial blood gas determi-
ies show sumatriptan, rizatriptan, naratriptan, and di- nations while awake and during sleep; and
hydroergotamine to be effective. Biofeedback, polysomnography. Therapy is generally surgical, rang-
relaxation therapy, and other nonpharmacologic ap- ing from tonsillectomy and adenoidectomy when ap-
proaches to managing headache may be useful in chil- propriate, to tracheostomy when medical measures fail.
dren, and they provide an alternative method of treat-
ment that avoids medication-related side effects.
2. Narcolepsy
Narcolepsy, a primary disorder of sleep, is characterized
Andrasik F et al: Brief neurologist-administered behavioral treat- by chronic, excessive daytime sleeping that occurs re-
ment of pediatric episodic tension-type headache. Neurology
2003;60:1215 [PMID: 12682344]. gardless of activity or surroundings and is not relieved
Hering-Hanit R et al: Successful withdrawal from analgesic abuse
by increased sleep at night. Onset occurs as early as age
in a group of youngsters with chronic daily headache. J Child 3 years. Of children with narcolepsy, 18% are younger
Neurol 2001;16:448 [PMID: 11417614]. than age 10, and 60% are between puberty and their
Just U et al: Emotional and behavioral problems in children and late teens. Narcolepsy usually interferes severely with
adolescents with primary headache. Cephalalgia 2003; normal living. Months to years after onset, there may
23:206 [PMID: 12662188]. also be cataplexy (transient partial or total loss of muscle
Lewis DW et al: Practice parameter: Evaluation of children and tone, often triggered by laughter, anger, or other emo-
adolescents with recurrent headaches. Neurology 2002;59: tional upsurge), hypnagogic hallucinations (visual or au-
490 [PMID: 12196640]. ditory), and sensations of paralysis on falling asleep.
Linder SL, Winner P: Pediatric headache. Med Clin North Am Studies have shown that rapid eye movement (REM)
2001;85:1037 [PMID: 11480257].
sleep, with loss of muscle tone and an EEG low-ampli-
Medina LS et al: Children with headache suspected of having a
brain tumor: A cost-effectiveness analysis of diagnostic strate-
tude mixed frequency pattern, occurs soon after sleep
gies. Pediatrics 2001;108:255 [PMID: 11483785]. onset in patients with cataplexy, whereas normal sub-
Millichap JG, Yee MM: The diet factor in pediatric and adolescent jects experience 80–100 minutes or longer of non-REM
migraine. Pediatr Neurol 2003;28:9 [PMID: 12657413]. (NREM) sleep before the initial REM period.
Powers SW et al: A pilot study of one-session biofeedback training Recent research suggests absence of a hypothalamic
in pediatric headache. Neurology 2001;56:133 [PMID: neuropeptide, hypocretin (from autoimmune injury?),
11148256]. causes narcolepsy and cataplexy. Spinal fluid (but not
Wasiewski WW: Preventive therapy in pediatric migraine. J Child plasma) levels of hypocretin-1 (also called orexin) are
Neurol 2001;16:71 [PMID: 11292228]. diagnostic (level will be nil or zero).
Zwijnenburg PJG, et al: Alice in wonderland syndrome: A clinical Narcolepsy is treated with a CNS stimulant (dex-
presentation of frontal lobe epilepsy. Neuropediatrics 2002; troamphetamine or long-acting methylphenidate is pre-
33:53 [PMID: 11930280]. ferred). Cataplexy responds to venlafaxine, fluoxetine,
or clomipramine. Modafinil is a new effective treatment
for excessive daytime sleepiness. The condition persists
SLEEP DISORDERS throughout life.
1. Sleep Apnea Syndrome
in Older Children 3. Somnambulism
Sleep apnea syndrome should be considered if there is a Somnambulism is one of a group of sleep disturbances
history of restless sleep with snoring or respiratory noise known as disorders of arousal. The onset is abrupt, usu-
764 / CHAPTER 23

ally early in the night. It is characterized by coordinated Table 23–16. Signs of increased intracranial
activity (eg, walking, sometimes moving objects with- pressure.
out seeming purpose) in a state of veiled consciousness.
The episode is relatively brief and ceases spontaneously. Acute
There is poor recall of the event on waking in the Macrocephaly
morning. Somnambulism may be related to mental ac- Excessive rate of head growth
tivities occurring in stages 3 and 4 of NREM sleep. In- Altered behavior
cidence has been estimated at only 2–3%, but up to Decreased level of consciousness
15% of cases are reported in children age 6–16 years. Vomiting
Boys are affected more often than girls, and many have Blurred vision
recurrent episodes. Psychopathologic features are rarely Double vision
demonstrated, but a strong association (30%) between Optic disk swelling
childhood migraine and somnambulism has been Abducens nerve paresis
noted. Episodes of somnambulism may be triggered in Chronic
predisposed children by stresses, including febrile ill- Macrocephaly
nesses. No treatment of somnambulism is required, and Growth impairment
it is not necessary to seek psychiatric consultation. Developmental delay
Optic atrophy
Visual field loss
4. Night Terrors
Night terrors (pavor nocturnus) are a disorder of
arousal from NREM sleep. Most cases occur in chil- pressure as outlined in Table 23–16. The cause is usu-
dren age 3–8 years, and the disorder rarely occurs after ally unknown, but pseudotumor cerebri has been de-
adolescence. It is characterized by sudden (but only par- scribed in association with a variety of inflammatory,
tial) waking, with the severely frightened child unable metabolic, toxic, and connective tissue disorders (Table
to be fully roused or comforted. Concomitant auto- 23–17). The diagnosis of pseudotumor cerebri is one of
nomic symptoms include rapid breathing, tachycardia, exclusion. CT or MRI scans of the head are needed to
and perspiring. The child has no recall of any night- exclude hydrocephalus and intracranial masses. These
mare. Psychopathologic mechanisms are unclear, but studies demonstrate ventricles of small or normal size
falling asleep after watching scenes of violence on televi- but no other structural abnormalities. Venus thrombo-
sion or hearing frightening stories may play a role.
Elimination of such causes and administration of a
mild antianxiety agent such as chlordiazepoxide may be Table 23–17. Conditions associated
helpful. It is important to differentiate these episodes with pseudotumor cerebri.
from complex partial (psychomotor) seizures. (See also
Chapter 2.)
Metabolic-toxic disorders
Hypervitaminosis A
Guilleminault C, Pelayo R: Narcolepsy in children: A practical
guide to its diagnosis, treatment and follow-up. Paediatr
Hypovitaminosis A
Drugs 2000;2:1. Review [PMID: 10937454]. Prolonged steroid therapy
Scammell TE: The neurobiology, diagnosis, and treatment of nar-
Steroid withdrawal
colepsy. Ann Neurol 2003;53:154 [PMID: 12557281]. Tetracycline therapy
Silber MH et al: Solving the mysteries of narcolepsy. Neurology
Nalidixic acid therapy
2001;56:1616 [PMID: 11425923]. Iron deficiency
Thiedke CC: Sleep disorders and sleep problems in childhood. Am
Lead poisoning
Fam Physician 2001;63:277 [PMID: 11201693]. Hypocalcemia
Tsukamoto H et al: Undetectable levels of CSF hypocretin-
Hyperparathyroidism
1 (orexin-A) in two prepubertal boys with narcolepsy. Neuro- Adrenal insufficiency
pediatrics 2002;33:51 [PMID: 11930279]. Lupus erythematosus
Chronic CO2 retention
Infectious and parainfectious disorders
PSEUDOTUMOR CEREBRI Chronic otitis media
Pseudotumor cerebri is characterized by increased in- Poliomyelitis
tracranial pressure in the absence of an identifiable in- Guillain–Barré syndrome
tracranial mass or hydrocephalus. Manifestations of Dural sinus thrombosis
pseudotumor cerebri are those of increased intracranial Minor head injury
 NEUROLOGIC & MUSCULAR DISORDERS / 765

sis, an underrecognized cause, must be ruled out by diac, vascular, or hematologic disease and intracranial
MRV (magnetic resonance venogram) or even injected disorders should be undertaken (Table 23–18). Though
venograms of cerebral sinuses. Lumbar puncture should most strokes are not associated with underlying sys-
be performed to document elevated CSF pressure. Ex- temic disorders, previously diagnosed congenital heart
amination of CSF reveals normal findings except for el- disease followed by hematologic and neoplastic disor-
evated pressure. In some inflammatory and connective ders are the most common predisposing to stroke. In
tissue diseases, however, the CSF protein concentration many instances the origin is multifactorial, necessitating
may be increased. a thorough investigation even when the cause may seem
Treatment of pseudotumor cerebri is aimed at cor- obvious. As a result, the cause of childhood stroke is
recting the identifiable predisposing condition. In addi- often determined whereas in past studies up to 30% re-
tion, some patients may benefit from the use of mained idiopathic. This is particularly important when
furosemide or acetazolamide to decrease the volume considering that recurrence risk may be as high as 35%.
and pressure of CSF within the CNS. These drugs may
be used in combination with repeated lumbar punc- Clinical Findings
tures to remove CSF. If a program of repeated CSF re-
moval and medical management is not successful or if A. SYMPTOMS AND SIGNS
central vision or visual field loss is detected despite Manifestations of stroke in childhood vary according to
these measures, lumboperitoneal shunt or another sur- the vascular distribution to the brain structure that is
gical decompression procedure may be necessary to pre- involved. Because many conditions leading to child-
vent irreparable visual loss and damage to the optic hood stroke result in emboli, multifocal neurologic in-
nerves. volvement is common. Children may present with
acute hemiplegia similar to stroke in adults. Symptoms
Friedman DI, Jacobson DM: Diagnostic criteria for idiopathic in- of unilateral weakness, sensory disturbance, dysarthria,
tracranial hypertension. Neurology 2002;59:1492 [PMID: and dysphagia may develop over a period of minutes,
12455560]. but at times progressive worsening of symptoms may
Kesler A, Fattall-Valevski A: Idiopathic intracranial hypertension in evolve over several hours. Bilateral hemispheric involve-
the pediatric population. J Child Neurol 2002;17:745
[PMID: 12546428].
ment may lead to a depressed level of consciousness.
Mckiernan SP, Difazio M: Case 3. Diagnosis: Pseudotumor cere-
The patient may also demonstrate disturbances of
bri. Pediatr Rev 2001;22:211 [PMID: 11436223]. mood and behavior and experience focal or multifocal
Salman MS et al: Idiopathic “benign” intracranial hypertension: seizures. Physical examination of the patient is aimed
Case series and review. J Child Neurol 2001;16:465 [PMID: not only at identifying the specific deficits related to
11453440]. impaired cerebral blood flow but also at seeking evi-
dence for any predisposing disorder. Retinal hemor-
CEREBROVASCULAR DISEASE rhages, splinter hemorrhages in the nail beds, cardiac
murmurs, and signs of trauma are especially important
Cerebrovascular disorders leading to vascular blockage, findings.
or stroke, occur with an age-related incidence in the pe-
diatric population of approximately 28–93:100,000 per B. LABORATORY FINDINGS
year in infancy and 1–8:100,000 per year in childhood. In the acute phase, certain investigations should be car-
This excludes primary disorders involving vascular he- ried out emergently with consideration of treatment
morrhage, whose incidence is greatest among prema- options. This should include complete blood count,
ture infants. The initial approach to the patient should erythrocyte sedimentation rate, basic chemistries, blood
recognize that the timing of presentation represents a urea nitrogen, creatinine, prothrombin time/partial
neurologic emergency, for which promptness in diag- thromboplastin time, chest radiograph, ECG, urine
nosis can affect treatment considerations and outcome. toxicology, and imaging (see following section). Subse-
Unfortunately, most pediatric stroke is not recognized quent studies can be carried out systemically, with par-
until 24–36 hours after onset, when treatment consid- ticular attention to disorders involving the heart, blood
erations matter most. Following this, one should take vessels, platelets, red cells, hemoglobin, and coagulation
into account the patient’s age and any underlying sys- proteins. Additional laboratory tests for systemic disor-
temic or neurologic illness. This should include a thor- ders such as systemic lupus erythematosus and poly-
ough history of prior illnesses, especially those associ- arteritis nodosa are usually indicated. Neonatal infarc-
ated with varicella (even in the prior 1–2 years), tions require pathological examination of the placenta.
mycoplasma, human immunodeficiency virus (HIV), Examination of CSF is indicated in patients with
minor trauma to the head and neck, and familial clot- fever, nuchal rigidity, or obtundation when the diagno-
ting tendencies. A systematic search for evidence of car- sis of intracranial infection requires exclusion. Lumbar
766 / CHAPTER 23

Table 23–18. Etiologic risk factors for stroke puncture, however, may be deferred until a neuroimag-
in children. ing scan excluding brain abscess or a space-occupying
lesion that might contraindicate lumbar puncture has
Cardiac disorders been obtained. In the absence of infection and frank in-
Cyanotic heart disease tracranial subarachnoid hemorrhage, CSF examination
Valvular disease is rarely helpful in defining the cause of the cerebrovas-
Rheumatic cular disorder.
Endocarditis
Cardiomyopathy C. IMAGING
Cardiac dysrhythmia CT and MRI scans of the brain are often helpful in
Vascular occlusive disorders defining the extent of cerebral involvement with is-
Arterial trauma (carotid dissections) chemia or hemorrhage. CT scans, however, may be
Homocystinuria/homocysteinemia normal within the first 12–24 hours of an ischemic
Vasculitis stroke and may need to be repeated several hours later.
Meningitis A CT scan early after the onset of neurologic deficits is
Polyarteritis nodosa valuable in excluding intracranial hemorrhage. This in-
Systemic lupus erythematosus formation may be helpful in the early stages of manage-
Drug abuse (amphetamines) ment and in the decision to treat with anticoagulants.
Varicella State-of-the-art management of stroke in the adult pop-
Mycoplasma ulation omits CT scanning but proceeds directly to ur-
HIV
gent MRI, magnetic resonance angiography (MRA),
Fibromuscular dysplasia
Moyamoya disease
and diffusion weighted imaging since these modalities
Diabetes are sensitive to acute stroke in the initial 3 hours when
Nephrotic syndrome intravenous thrombolytics might be indicated. In con-
Systemic hypertension sideration of venous occlusion either CT scan with con-
Dural sinus and cerebral venous thrombosis trast or MRV is indicated.
Cortical venous thrombosis Except in cases where trauma resulting in arterial
Hematologic disorders dissection is suspected, cerebral angiography (CA) is
Iron deficiency anemia usually not urgently needed but may be needed to con-
Polycythemia firm disorders such as fibromuscular dysplasia and cere-
Thrombotic thrombocytopenia bral arteritis. If CA is done, all major vessels should be
Thrombocytopenic purpura studied from the aortic arch. If evidence of fibromuscu-
Hemoglobinopathies lar dysplasia is present in the intracranial or extracranial
Sickle cell disease vessels, renal arteriography is indicated. In studies
Coagulation defects where both MRA or CA have been used, nearly 80% of
Hemophilia patients with ischemic stroke demonstrated a cere-
Vitamin K deficiency brovascular abnormality.
Hypercoagulable states When seizures are prominent, an EEG may be used
Prothrombin gene mutation as an adjunct in the patient’s evaluation. An EEG and
Lipoprotein (a) sequential EEG monitoring may help in patients with
Factor V Leiden
severely depressed consciousness.
Antiphospholipid antibodies
Hypercholesterolemia
ECG and echocardiography are useful both in the
Hypertriglyceridemia diagnostic approach to the patient and in ongoing
Factor VIII deficiency monitoring and management, particularly when hy-
Pregnancy potension or cardiac arrhythmias complicate the clini-
Systemic lupus erythematosus cal course.
Use of oral contraceptives
Antithrombin III deficiency Differential Diagnosis
Protein C and S deficiencies
Leukemia Patients with an acute onset of neurologic deficits must
Intracranial vascular anomalies be evaluated for other disorders that can cause focal
Arteriovenous malformation neurologic deficits. Hypoglycemia, prolonged focal
Arterial aneurysm seizures, a prolonged postictal paresis (Todd paralysis),
Carotid-cavernous fistula meningitis, encephalitis, and brain abscess should all be
considered. Migraine with focal neurologic deficits may
 NEUROLOGIC & MUSCULAR DISORDERS / 767

be difficult to differentiate initially from ischemic Chronic problems with learning, behavior, and activity
stroke. Occasionally the onset of a neurodegenerative are common.
disorder (eg, adrenoleukodystrophy or mitochondrial
disorder) may begin with the abrupt onset of seizures Delsing BJ et al: Early prognostic indicators of outcome in ischemic
and focal neurologic deficits. The possibility of drug childhood stroke. Pediatr Neurol 2001;24:283 [PMID:
abuse (particularly cocaine) and other toxic exposures 11377103].
must be investigated diligently. deVeber, G: Stroke and the child’s brain: An overview of epidemi-
ology, syndromes and risk factors. Curr Opin Neurol
2002;15:133 [PMID: 11923625].
Treatment Gabis LV et al: Time lag to diagnosis of stroke in children. Pedi-
atrics 2002;110:924 [PMID: 12415031].
The initial management of stroke in a child is aimed at Ganesan V et al: Investigation of risk factors in children with arter-
providing support for pulmonary, cardiovascular, and ial ischemic stroke. Ann Neurol 2003;53:167 [PMID:
renal function. Appropriate fluid and electrolyte infu- 12557282].
sions should be started, and careful monitoring of heart Gordon AL et al: Functional outcome following stroke in children.
rate and rhythm and blood pressure is required. Typi- J Child Neurol 2002;17:429 [PMID: 12174963].
cally, maintenance fluids without added glucose are in- Gruber A et al: Intra-arterial thrombolysis for the treatment of peri-
dicated to augment vascular volume. Specific treatment operative childhood cardioembolic stroke. Neurology
of stroke depends partly on the underlying pathogenesis 2000;54:1684 [PMID: 10762516].
and the specific predisposing disorder. Generally, as- Husson B et al: Magnetic resonance angiography in childhood arte-
pirin 1–2 mg/kg daily is indicated to begin as soon as rial brain infarcts: A comparative study with contrast angiog-
raphy. Stroke 2002;33:1280 [PMID: 11988604].
diagnosis is made. As clinical trials progress, aspirin use
appears safe and has not been associated with Reye syn- Nestoridi E et al: Arterial ischemic stroke in childhood: The role of
plasma-phase risk factors. Curr Opin Neurol 2002;15:139
drome. In some situations, emergent heparinization for [PMID: 11923626].
arterial dissection, emboli, and consumptive coagu- Nowak-Gottl U et al: Antithrombotic drug treatment of pediatric
lopathies is indicated. In adults with cerebrovascular patients with ischemic stroke. Pediatr Drugs 2003;5:167
thrombosis, thrombolytic agents (tissue plasminogen [PMID: 12608881].
activator) used systemically or delivered directly to a
vascular thrombotic lesion using interventional radio- CONGENITAL MALFORMATIONS
logic techniques has been shown to improve outcome;
although case reports exist, studies in children have not OF THE NERVOUS SYSTEM
been completed. Exchange transfusion is indicated in Malformations of the nervous system occur in 1–3% of
cases of sickle cell disease. living neonates and are present in 40% of infants who
Long-term management requires intensive rehabili- die. Developmental anomalies of the CNS may result
tation efforts and therapy aimed at improving the from a variety of causes, including infectious, toxic,
child’s language, educational, and psychologic perfor- metabolic, and vascular insults that affect the fetus. The
mance. Length of treatment with various agents is still specific type of malformation that results from such in-
being studied and depends on etiology. sults, however, may depend more on the gestational pe-
riod during which the insult occurs than on the specific
Prognosis cause. The period of induction, days 0–28 of gestation, is
the period during which the neural plate appears and the
The outcome of stroke in infants and children is vari- neural tube forms and closes. Insults during this phase
able. Roughly, 40% may have minimal deficits, 30% can result in a major absence of neural structures, such as
are moderately affected, and 30% are severely affected. anencephaly, or in a defect of neural tube closure, such as
Underlying predisposing conditions and the vascular spina bifida, meningomyelocele, or encephalocele.
territory involved all play a role in dictating the out- Cellular proliferation and migration characterize neural
come for an individual patient. When the stroke in- development that occurs after 28 days’ gestation.
volves extremely large portions of one hemisphere or Lissencephaly, pachygyria, agyria, and agenesis of the
large portions of both hemispheres and cerebral edema corpus callosum may be the result of disruptions (ge-
develops, the patient’s level of consciousness may dete- netic, toxic, infectious, or metabolic) that can occur dur-
riorate rapidly, and death may occur within the first ing the period of cellular proliferation and migration.
few days. Some patients may achieve almost complete
recovery of neurologic function within several days if
the cerebral territory is small. Seizures, either focal or
1. Abnormalities of Neural Tube Closure
generalized, may occur in 30–50% of patients at some Defects of neural tube closure constitute some of the
point in the course of their cerebrovascular disorder. most common congenital malformations affecting the
768 / CHAPTER 23

nervous system. Spina bifida with associated meningo- the amniotic fluid. All women of childbearing age
myelocele or meningocele is commonly found in the should take prophylactic folate, which can prevent
lumbar region. Depending on the extent and severity of these defects and decrease the risk of recurrence by
the involvement of the spinal cord and peripheral 70%.
nerves, lower extremity weakness, bowel and bladder
dysfunction, and hip dislocation may be present. Deliv-
ery via cesarean section followed by early surgical clo- 2. Disorders of Cellular Proliferation
sure of meningoceles and meningomyeloceles is usually and Migration
indicated. Additional treatment is necessary to manage
chronic abnormalities of the urinary tract, orthopedic
Lissencephaly
abnormalities such as kyphosis and scoliosis, and paresis Lissencephaly is a severe malformation of the brain
of the lower extremities. Hydrocephalus associated with characterized by an extremely smooth cortical surface
meningomyelocele usually requires ventriculoperitoneal with minimal sulcal and gyral development. Such a
shunting. smooth surface is characteristic of fetal brain at the end
of the first trimester. In addition, lissencephalic brains
Arnold–Chiari Malformations have a primitive cytoarchitectural construction with a
four-layered cerebral mantle instead of the mature six-
Arnold–Chiari malformation type I consists of elonga- layered mantle. Pachygyria (thick gyri) and agyria (ab-
tion and displacement of the caudal end of the brain- sence of gyri) may vary in an anterior to posterior gradi-
stem into the spinal canal with protrusion of the cere- ent, which can be suggestive of the underlying genetic
bellar tonsils through the foramen magnum. In defect. Patients with lissencephaly usually have severe
association with this hindbrain malformation, minor to neurodevelopmental delay, microcephaly, and seizures
moderate abnormalities of the base of the skull often (including infantile spasms); however, there is signifi-
occur, including basilar impression (platybasia) and cant phenotypic heterogeneity, which can depend on
small foramen magnum. Arnold–Chiari malformation the specific mutation. These disorders are autosomal re-
type I may remain asymptomatic for years, but in older cessive, except for the X-linked disorders. LIS1 muta-
children and young adults it may cause progressive tions on chromosome 17 are associated with dysmor-
ataxia, paresis of the lower cranial nerves, and progres- phic features (Miller–Dieker syndrome). X-linked
sive vertigo. Posterior cervical laminectomy may be syndromes involving mutations in DCX (double cortin)
necessary to provide relief from cervical cord compres- and ARX (associated with ambiguous genitalia) affect
sion. Ventriculoperitoneal shunting is required for hy- males with lissencephaly and females with band hetero-
drocephalus. topias or agenesis of the corpus callosum. Lissencephaly
Arnold–Chiari malformation type II consists of the in association with hydrocephalus, cerebellar malforma-
malformations found in Arnold–Chiari type I plus an tions, and muscular dystrophy may occur in Walker–
associated lumbar meningomyelocele. Hydrocephalus Warburg syndrome (POMT1 mutation), Fukuyama
develops in approximately 90% of children with muscular dystrophy (fukutin mutation), and muscle–
Arnold–Chiari malformation type II. These patients eye–brain disease (POMGnT1 mutation). It is particu-
may also have aqueductal stenosis, hydromyelia or sy- larly important to identify these syndromes not only
ringomyelia, and cortical dysplasias. The clinical mani- because clinical tests are available but also because of
festations of Arnold–Chiari malformation type II are their genetic implications. Lissencephaly may also be a
most commonly caused by the associated hydro- component of Zellweger syndrome, a metabolic peroxi-
cephalus and meningomyelocele. In addition, dysfunc- somal abnormality associated with the presence of ele-
tion of the lower cranial nerves may be present. Up to vated concentrations of very long-chain fatty acids in
25% may have epilepsy, likely secondary to the cortical plasma. No specific treatment for lissencephaly is avail-
dysplasias. With the advent of “aggressive-selective” able and seizures are often difficult to control with stan-
therapy, mortality is 14%; of survivors 74% are ambu- dard medications.
latory and 73% have a normal IQ. MRI scans have helped to define a number of pre-
Arnold–Chiari malformation type III is character- sumed migrational defects that are similar to but ana-
ized by occipital encephalocele, a closure defect of the tomically more restricted than lissencephaly. A distinc-
rostral end of the neural tube. Hydrocephalus is ex- tive example is bilateral perisylvian cortical dysplasia.
tremely common with this malformation. Patients with this disorder have pseudobulbar palsy,
In general, the diagnosis of neural tube defects is ob- variable cognitive deficits, facial diplegia, dysarthria, de-
vious at the time of birth. Diagnosis may be strongly velopmental delay, and epilepsy. Seizures are often dif-
suspected prenatally on the basis of ultrasonographic ficult to control with antiepileptic drugs; some patients
findings and the presence of elevated α-fetoprotein in have benefited from corpus callosotomy. The cause of
 NEUROLOGIC & MUSCULAR DISORDERS / 769

this syndrome is as yet unknown, though intrauterine neurologic dysfunction. An ataxic syndrome occurs in
cerebral ischemic injury has been postulated. Therapy is fewer than 20% of patients and is usually late in ap-
aimed at improving speech and oromotor functions and pearing. Many long-term neurologic deficits result di-
controlling seizures. rectly from hydrocephalus. Diagnosis of
Dandy–Walker malformation is confirmed by CT or
MRI scanning of the head. Treatment is directed at the
Agenesis of the Corpus Callosum management of hydrocephalus.
Agenesis of the corpus callosum, once thought to be a
rare cerebral malformation, is more frequently diag-
nosed with modern neuroimaging techniques. The
3. Craniosynostosis
cause of this malformation is unknown. Occasionally it Craniosynostosis, or premature closure of cranial su-
appears to be inherited in either an autosomal domi- tures, is usually sporadic and idiopathic. However,
nant or recessive pattern. X-linked recessive patterns some patients have hereditary disorders, such as Apert
have also been described (ARX as mentioned earlier). syndrome and Crouzon disease, that are associated with
Agenesis of the corpus callosum has been found in abnormalities of the digits, extremities, and heart. Oc-
some patients with pyruvate dehydrogenase deficiency casionally craniosynostosis may be associated with an
and in others with nonketotic hyperglycinemia. Most underlying metabolic disturbance such as hyperthy-
cases are sporadic. Maldevelopment of the corpus callo- roidism and hypophosphatasia. The most common
sum may be partial or complete. No specific syndrome form of craniosynostosis involves the sagittal suture and
is typical of agenesis of the corpus callosum, although results in scaphocephaly, an elongation of the head in
many patients have seizures, developmental delay, mi- the anterior to posterior direction. Premature closure of
crocephaly, or mental retardation. Neurologic abnor- the coronal sutures causes brachycephaly, an increase in
malities may be related to microscopic cytoarchitectural cranial growth from left to right. Unless many or all
abnormalities of the brain that occur in association with cranial sutures close prematurely, intracranial volume
agenesis of the corpus callosum. The malformation may will not be compromised, and the brain’s growth will
be found coincidentally by neuroimaging studies in not be impaired. Closure of only one or a few sutures
otherwise normal patients and has been described as a will not cause impaired brain growth or neurologic dys-
coincidental finding at autopsy in neurologically nor- function. Management of craniosynostosis is directed at
mal individuals. A special form of agenesis of the cor- preserving normal skull shape and consists of excising
pus callosum occurs in Aicardi syndrome. In this X- the fused suture and applying material to the edge of
linked disorder, agenesis of the corpus callosum is the craniectomy to prevent reossification of the bone
associated with other cystic intracerebral abnormalities, edges. The best cosmetic effect on the skull is achieved
infantile spasms, mental retardation, lacunar chori- when surgery is done during the first 6 months of life.
oretinopathy, and vertebral body abnormalities.
4. Hydrocephalus
Dandy–Walker Malformation Hydrocephalus is characterized by an increased volume
Despite being described nearly a century ago, the exact of CSF in association with progressive ventricular dila-
definition of the Dandy–Walker malformation is in de- tion. In communicating hydrocephalus, CSF circulates
bate. Classically, it is characterized by aplasia of the ver- through the ventricular system and into the subarach-
mis, cystic enlargement of the fourth ventricle, rostral noid space without obstruction. In noncommunicating
displacement of the tentorium, and absence or atresia hydrocephalus, an obstruction blocks the flow of CSF
of the foramina of Magendie and Luschka. Although within the ventricular system or blocks the egress of
hydrocephalus is usually not present congenitally, it de- CSF from the ventricular system into the subarachnoid
velops within the first few months of life. Ninety per- space. A wide variety of disorders, such as hemorrhage,
cent of patients who develop hydrocephalus do so by infection, tumors, and congenital malformations, may
age 1 year. “Variants” have cerebellar hypoplasia with- play a causal role in the development of hydrocephalus.
out dilatation of the fourth ventricle and hydrocephalus Attention to an X-linked inheritance pattern, the
and may suggest other subtle cortical abnormalities not presence of radialized thumbs and aqueductal stenosis,
classically present and could be confused with other dis- is suggestive of X-linked hydrocephalus due to the
orders such as Joubert syndrome and its variants. On clinically testable neural cell adhesion molecule
physical examination, a rounded protuberance or exag- (NCAM)–L1 deficiency.
geration of the cranial occiput often exists. In the ab- Clinical features of hydrocephalus include macro-
sence of hydrocephalus and increased intracranial pres- cephaly, an excessive rate of head growth, irritability,
sure, few physical findings may be present to suggest vomiting, loss of appetite, impaired upgaze, impaired
770 / CHAPTER 23

extraocular movements, hypertonia of the lower ex- paired the brain’s capacity to grow. The causes of mi-
tremities, and generalized hyperreflexia. Without treat- crocephaly are numerous. Some examples are listed in
ment, optic atrophy may occur. In infants, papilledema Table 23–19.
may not be present, whereas older children with closed
cranial sutures can eventually develop swelling of the Clinical Findings
optic disk. Hydrocephalus can be diagnosed on the
basis of the clinical course, findings on physical exami- A. SYMPTOMS AND SIGNS
nation, and CT or MRI scan. Microcephaly may be suspected in the full-term new-
Treatment of hydrocephalus is directed at providing born and in infants up to age 6 months whose chest cir-
an alternative outlet for CSF from the intracranial com- cumference exceeds the head circumference (unless the
partment. The most common method is ventriculoperi- child is very obese). Microcephaly may be discovered
toneal shunting. Other treatment should be directed, if when the child is examined because of delayed develop-
possible, at the underlying cause of the hydrocephalus. mental milestones or neurologic problems, such as
For genetic testing, see www.genetests.org seizures or spasticity. There may be a marked backward
slope of the forehead (as in familial microcephaly) with
Barkovich AJ et al: Radiologic classification of malformations of narrowing of the bitemporal diameter. The fontanelle
cortical development. Curr Opin Neurobiol 2001;12:145 may close earlier than expected, and sutures may be
[PMID: 11262727]. prominent.
Kato M, Dobyns WB: Lissencephaly and the molecular basis of
neuronal migration. Hum Mol Gen 2003;12:R89 [PMID: B. LABORATORY FINDINGS
12668601].
Laboratory findings vary with the cause. Abnormal der-
Leventer RJ et al: LIS1 missense mutations cause milder
lissencephaly phenotypes including a child with normal IQ.
matoglyphics may be present when the injury occurred
Neurology 2001;57:416 [PMID: 11502906].
Patel S, Barkovich AJ: Analysis and classification of cerebellar mal-
formations. AJNR Am J Neuroradiol 2002;23:1074 [PMID: Table 23–19. Microcephaly.
12169461].
Satran D et al: Cerebello–Oculo–Renal syndromes including
Arima, Senior-Loken and COACH syndromes: More than Causes Examples
just variants of Joubert Syndrome. Am J Med Genetics Chromosomal Trisomy 13, 18, 21
1999;86:459 [PMID: 10508989].
Malformation Lissencephaly, schizencephaly
ABNORMAL HEAD SIZE Syndromes Rubenstein–Taybi, Cornelia de
Lange
Bone plates of the skull have almost no intrinsic capac-
ity to enlarge or grow. Unlike long bones, they depend Toxins Alcohol, anticonvulsants (?),
on extrinsic forces to stimulate new bone formation at maternal phenylketonuria
the suture lines. Although gravity and traction on bone Infections (intrauterine) TORCHESa
by muscle and scalp probably stimulate some growth, Radiation Maternal pelvis, first and second
the single most important stimulus for head growth trimester
during infancy and childhood is brain growth. There-
fore, accurate assessment of head growth is one of the Placental insufficiency Toxemia, infection
most important aspects of the neurologic examination Familial Autosomal-dominant, autosomal-
of young children. A head circumference that is 2 SD recessive
above or below the mean for age requires investigation
and explanation. Perinatal hypoxia, trauma Birth asphyxia, injury
Infections (perinatal) Bacterial meningitis (especially
group B streptococci)
1. Microcephaly Viral encephalitis (enterovirus
A head circumference more than 2 SD below the mean herpes simplex)
for age and sex is by definition microcephaly. More im- Metabolic Hypoglycemia, phenylketonuria,
portant, however, than a single head circumference maple syrup urine disease
measurement is the rate or pattern of head growth
through time. Head circumference measurements that Degenerative disease Tay–Sachs, Krabbe
progressively drop to lower percentiles with increasing a
TORCHES is a mnemonic formula for toxoplasmosis, rubella,
age are indicative of a process or condition that has im- cytomegalovirus, herpes simplex, and syphilis.
 NEUROLOGIC & MUSCULAR DISORDERS / 771

before 19 weeks’ gestation. In the newborn, IgM anti- Vargas JE et al: Congenital microcephaly: Phenotypic features in a
body titers for toxoplasmosis, rubella, CMV, herpes consecutive sample of newborn infants. J Pediatr 2001;139:
210 [PMID: 11487745].
simplex virus, and syphilis must be assessed. Elevated
specific IgM titer is indicative of congenital infection. Watemberg N et al: Significance of microcephaly among children
with developmental disabilities. J Child Neurol 2002;17:117
The urine culture for CMV will be positive at birth [PMID: 11952071].
when this virus is the cause of microcephaly. Eye, car-
diac, and bone abnormalities may also be clues to con-
genital infection. The child’s serum and urine amino 2. Macrocephaly
and organic acid determinations are occasionally diag-
nostic. The mother may require screening for phenylke- A head circumference more than 2 SD above the mean
tonuria. Karyotyping, including for fragile X syndrome, for age and sex denotes macrocephaly. Excessive head
should be considered. growth rate through time suggests increased intracranial
pressure most likely caused by hydrocephalus, extra-
C. IMAGING axial fluid collections, or neoplasms. Macrocephaly
with normal head growth rate suggests familial macro-
CT or MRI scans may aid in diagnosis and prognosis.
cephaly or true megalencephaly, as might occur in neu-
These studies may demonstrate calcifications, malfor-
rofibromatosis. Other causes and examples of macro-
mations, or atrophic patterns that suggest specific con-
cephaly are listed in Table 23–20.
genital infections or genetic syndromes. Plain skull ra-
diographs may show closed sutures, but these studies
are of limited value in diagnosis and have been replaced
by more sensitive and more informative scanning pro-
cedures. Genetic counseling should be offered to the
family of any infant with significant microcephaly. Table 23–20. Macrocephaly.

Differential Diagnosis Causes Examples

Congenital craniosynostosis involving multiple sutures Pseudomacrocephaly, Growing premature infant;
is easily differentiated by inspection of the head, his- pseudohydrocephalus, recovery from malnutrition,
tory, identification of syndromes, hereditary pattern, catch-up growth cross- congenital heart disease,
and sometimes signs and symptoms of increased in- ing percentiles postsurgical correction
tracranial pressure. Common forms of craniosynostosis Increased intracranial pres-
involving sagittal, coronal, and lambdoidal sutures are sure
associated with abnormally shaped heads but do not With dilated ventricles Progressive hydrocephalus,
cause microcephaly. Recognizing treatable causes of un- subdural effusion
dergrowth of the brain such as hypopituitarism, hy- With other mass Arachnoid cyst, porence-
pothyroidism, and severe protein-calorie undernutri- phalic cyst, brain tumor
tion is critical so that therapy can be initiated as early as Benign familial macroceph- External hydrocephalus,
possible. aly (idiopathic external hy- benign enlargement of
drocephalus) the subarachnoid spaces,
Treatment & Prognosis benign subdural collections
of infancy (synonyms)
Except for the treatable disorders already noted, treat-
Megalencephaly (large brain)
ment is usually supportive and directed at the multiple
With neurocutaneous dis- Neurofibromatosis, tuberous
neurologic and sensory deficits, endocrine disturbances order sclerosis, etc
(eg, diabetes insipidus), and seizures. Many children With gigantism Sotos’ syndrome
but not all with microcephaly who are developmentally With dwarfism Achondroplasia
delayed, with head circumferences more than 2 SD Metabolic Mucopolysaccharidoses
below the mean, show variable degrees of mental retar- Lysosomal Metachromatic
dation. The notable exceptions are found in cases of hy- leukodystrophy
popituitarism (rare) or familial autosomal dominant Other leukodystrophy Canavan spongy degenera-
microcephaly. tion
Thickened skull Fibrous dysplasia (bone), he-
Mochida GH, Walsh CA: Molecular genetics of human micro- molytic anemia (marrow),
cephaly. Curr Opin Neurol 2001;14:151 [PMID: sicklemia, thalassemia
11262728].
772 / CHAPTER 23

Clinical Findings derm. Birthmarks and skin growths appearing later

often suggest a need to look for brain, spinal cord, and
Clinical and laboratory findings vary with the underly- eye disease. Hamartomas (histologically normal tissue
ing process. In infants, transillumination of the skull growing abnormally rapidly or in aberrant sites) are
with an intensely bright light in a completely darkened common. The most common dysplasias are dominantly
room may disclose subdural effusions, hydrocephalus, inherited. Benign and even malignant tumors may de-
hydranencephaly, and cystic defects. A surgically or velop.
medically treatable condition must be ruled out. Thus
the first decision is whether and when to perform an
Dahan D et al: Neurocutaneous syndromes. Adolesc Med 2002;
imaging study. 13:495 [PMID: 12270797].
A. IMAGING STUDY DEFERRED Kandt RS: Tuberous sclerosis complex and neurofibromatosis type
1: The two most common neurocutaneous diseases. Neruol
1. Catch-up growth—Catch-up growth may be evi- Clin 2002;20:941 [PMID: 12616676].
dent, as it is in the thriving, neurologically intact pre-
mature infant whose rapid head enlargement is most
marked in the first weeks of life, or the infant in the 1. Neurofibromatosis
early phase of recovery from deprivation dwarfism. As (von Recklinghausen Disease)
the expected “normal” is reached, head growth slows
and then resumes a normal growth pattern. If the
fontanelle is open, cranial ultrasonography can assess ESSENTIALS OF DIAGNOSIS
ventricular size and diagnose or exclude hydrocephalus. & TYPICAL FEATURES
2. Familial macrocephaly—This condition may exist
when another family member has an unusually large • More than six café au lait spots 5 mm in greatest
head with no signs or symptoms referable to such disor- diameter in prepubertal individuals and over
ders as neurocutaneous dysplasias (especially neurofi- 15 mm in greatest diameter in postpubertal indi-
bromatosis) or cerebral gigantism (Sotos syndrome), or viduals.
when there is no significant mental or neurologic ab- • Two or more neurofibromas of any type or one
normalities in the child. plexiform neurofibroma.
B. IMAGING STUDY • Freckling in the axillary or inguinal regions.
CT or MRI scans (or ultrasonography, if the anterior • Optic glioma.
fontanelle is open) are used to define any structural • Two or more Lisch nodules (iris hamartomas).
cause of macrocephaly and to identify an operable disor- • Distinctive osseous lesions, such as sphenoid dys-
der. Even when the condition is untreatable (or does not plasia or thinning of long bone with or without
require treatment), the information gained may permit pseudarthroses.
more accurate diagnosis and prognosis, guide manage-
ment and genetic counseling, and serve as a basis for • First-degree relative (parent, sibling, offspring)
comparison should future abnormal cranial growth or with neurofibromatosis type 1 by above criteria.
neurologic changes necessitate a repeat study. An imag-
ing study is necessary if signs or symptoms of increased
intracranial pressure are present (see Table 23–15).

Cutting LE et al: Megalencephaly in NF1. Neurology 2002;59:

General Considerations
1388 [PMID: 12427889]. Neurofibromatosis is a multisystem disorder with a
Piatt JH Jr: Monozygotic twins discordant for external hydro- prevalence of 1:4000. Fifty percent of cases are due to
cephalus. Pediatr Neurosurg 2001;35:211 [PMID: 11694799]. new mutations in the NF1 gene. Forty percent of pa-
Ravid S, Maytal J: External hydrocephalus: A probable cause for tients will develop medical complications of the disor-
subdural hematoma in infancy. Pediatr Neurol 2003;28:139
[PMID: 12699866].
der in their lifetime.
Suara RO et al: Benign subarachnoid space enlargement of infancy.
J Natl Med Assoc 2001;93:70 [PMID: 12653385]. Clinical Findings
A. SYMPTOMS AND SIGNS
NEUROCUTANEOUS DYSPLASIAS The most common presenting symptoms are cognitive
Neurocutaneous dysplasias are diseases of the neuroec- or psychomotor problems; 40% of patients have learn-
toderm and sometimes involve endoderm and meso- ing disabilities, and mental retardation occurs in 8%.
 NEUROLOGIC & MUSCULAR DISORDERS / 773

The family history is important in identifying domi- mation for laypeople and physicians is available from
nant gene manifestations in parents. Parents should be the National Neurofibromatosis Foundation, Inc.,
examined in detail. The history should focus on lumps 70 West 40th Street, New York, NY 10018.
or masses causing disfigurement, functional problems,
or pain. The clinician should ask about visual prob- Baser ME et al: Evaluation of clinical diagnostic criteria for neurofi-
lems. Strabismus or amblyopia dictates a search for bromatosis 2. Neurology 2002;59:1759 [PMID: 12473765].
optic glioma, a common tumor in neurofibromatosis. Friedman JM: Neurofibromatosis 1: Clinical manifestations and
Any progressive neurologic deficit calls for studies to diagnostic criteria. J Child Neurol 2002;17:548 [PMID:
rule out tumor of the spinal cord or CNS. Tumors of 12403552].
cranial nerve VIII virtually never occur in neurofibro- Korf BR: Clinical features and pathobiology of neurofibromatosis
1. J Child Neurol 2002;17:573 [PMID: 12403555].
matosis type 1 but are the rule in neurofibromatosis
Lynch TM, Gutmann DH: Neurofibromatosis 1. Neurol Clin
type 2, a rare autosomal dominant disease. 2002;20:841 [PMID: 12432832].
The physician should check blood pressure and ex-
Ruggieri M, Huson SM: The clinical and diagnostic implications
amine the spine for scoliosis and the limbs for of mosaicism in the neurofibromatosis. Neurology 2001;56:
pseudarthroses. Head measurement often shows macro- 1433 [PMID: 11409413].
cephaly. Hearing and vision need to be assessed. The Tekin M et al: Café au lait spots: The pediatrician’s perspective. Pe-
eye examination should include a check for proptosis diatr Rev 2001;22:82 [PMID: 11230626].
and iris Lisch nodules. The optic disk should be exam- Vivarelli R et al: Epilepsy in neurofibromatosis 1. J Child Neurol
ined for atrophy or papilledema. Short stature and pre- 2003;18:338 [PMID: 12822818].
cocious puberty are occasional findings. An examina-
tion for neurologic manifestations of tumors (eg, 2. Tuberous Sclerosis
asymmetrical reflexes, spasticity) is important.
(Bourneville Disease)
B. LABORATORY FINDINGS
Laboratory tests are not likely to be of value in asymp- ESSENTIALS OF DIAGNOSIS
tomatic patients. Selected patients require brain MRI & TYPICAL FEATURES
or CT scans with special cuts through the optic nerves
to rule out optic glioma. Hypertension necessitates
evaluation of renal arteries for dysplasia and stenosis. • Facial angiofibromas or subungual fibromas.
Cognitive and school achievement testing may be indi- • Often hypomelanotic macules, gingival fibromas.
cated. Scoliosis or limb abnormalities should be studied • Retinal hamartomas.
by appropriate roentgenograms such as an MRI scan of • Cortical tubers or subependymal glial nodules,
the spinal cord and roots. often calcified.
• Renal angiomyolipomas.
Differential Diagnosis
Patients with Albright syndrome often have larger café
au lait spots with precocious puberty. One or two café
au lait spots are often seen in normal children. General Considerations
Tuberous sclerosis is a dominantly inherited disease. Al-
Treatment most all patients have deletions on chromosome
Genetic counseling is important. The risk to siblings is 9 (TSC1 gene) or 16 (TSC2 gene). The gene products
up to 50%. The disease may be progressive, with seri- hamartin and tuberin have tumor-suppressing effects. A
ous complications occasionally seen. Patients some- triad of seizures, mental retardation, and adenoma se-
times worsen during puberty or pregnancy. Genetic baceum occurs in only 33% of patients. The disease
screening of family members is required. Annual or was earlier thought to have a high rate of mutation. As
semiannual visits are important in the early detection of a result of more sophisticated techniques such as MRI,
school problems or bony or neurologic abnormalities. parents formerly thought not to harbor the gene are
Multidisciplinary clinics at medical centers around now being diagnosed as asymptomatic carriers.
the United States are excellent resources. Prenatal diag- Like neurofibromatosis, tuberous sclerosis is associ-
nosis is probably on the horizon, but the variability of ated with a wide variety of symptoms. The patient may
manifestations (trivial to severe) will make therapeutic be asymptomatic except for skin findings or may be
abortion an unlikely option. Chromosomal linkage devastated by severe infantile spasms in early infancy,
studies are under way (chromosome 17q11.2). Infor- by continuing epilepsy, and by mental retardation.
774 / CHAPTER 23

Seizures in early infancy correlate with later mental re- tion, conduction difficulties, and death. Chest radi-
tardation. ographs and echocardiograms can detect these rare
manifestations. Cardiac rhabdomyoma may be detected
Clinical Findings on prenatal ultrasound examination.
6. Eye involvement—Retinal hamartomas are often
A. SYMPTOMS AND SIGNS near the disk.
1. Dermatologic features—Skin findings bring most 7. Skeletal involvement—Findings sometimes helpful
patients to the physician’s attention. Ninety-six percent in diagnosis are cystic rarefactions of the bones of the
of patients have one or more hypomelanotic macules, fingers or toes.
facial angiofibromas, ungual fibromas, or shagreen
patches. Adenoma sebaceum, the facial skin hamar- B. DIAGNOSTIC STUDIES
tomas, may first appear in early childhood, often on the Plain radiographs may detect areas of thickening within
cheek, chin, and dry sites of the skin where acne is not the skull, spine, and pelvis, and cystic lesions in the
usually seen. They often have a reddish hue. The off- hands and feet. Chest radiographs may show lung hon-
white hypomelanotic macules are seen more easily in eycombing. More helpful is CT scanning, which can
tanned or dark-skinned individuals than in those with show the virtually pathognomonic subependymal
lighter skin. The macules often are oval or “ash leaf” in nodular calcifications and sometimes widened gyri or
shape and follow dermatomes. A Wood lamp (ultravio- tubers and brain tumors. Contrast material may show
let light) shows the macules more clearly, a great help in the often classically located tumors near the foramen
the light-skinned patient. In the scalp, poliosis interventriculare. Hypomyelinated lesions may be seen
(whitened hair) is the equivalent. In infancy, the pres- with MRI. EEG is helpful in delineating the presence
ence of these macules accompanied by seizures is virtu- of seizure discharges.
ally diagnostic of the disease. Subungual or periungual
fibromas are more common in the toes. Leathery, or- Treatment
ange peel-like shagreen patches support the diagnosis.
Café au lait spots are occasionally seen. Fibrous or Therapy is as indicated by underlying disease (eg,
raised plaques may resemble coalescent angiofibromas. seizures and tumors of the brain, kidney, and heart).
Skin lesions on the face may need dermabrasion or laser
2. Neurologic features—Seizures are the most com- treatment. Genetic counseling emphasizes identifica-
mon presenting symptom. Five percent of patients with tion of the carrier. The risk of appearance in offspring if
infantile spasms (a serious epileptic syndrome) have either parent is a carrier is 50%. The patient should be
tuberous sclerosis. Thus any patient presenting with in- seen annually for counseling and reexamination in
fantile spasms (and the parents as well) should be evalu- childhood. Identification of the chromosomes (9,16;
ated for this disorder. An imaging study of the CNS, TSCI and TSC2 genes) may in the future make in-
such as a CT scan, may show calcified subependymal trauterine diagnosis possible.
nodules; MRI may show dysmyelinating white matter
lesions or cortical tubers. Virtually any kind of sympto- Curatolo P et al: Tuberous sclerosis complex: A review of neurolog-
matic seizure (eg, atypical absence, partial complex, and ical aspects. Eur J Paediatr Neurol 2002;6:15 [PMID:
generalized tonic–clonic seizures) may occur. 11993952].
Harris-Stith R, Elston DM: Tuberous sclerosis. Cutis 2002;69: 103
3. Mental retardation—Mental retardation occurs in [PMID: 11868973].
up to 50% of patients referred to tertiary care centers;
Jozwiak S et al: Usefulness of diagnostic criteria of tuberous sclero-
the incidence is probably much lower in randomly se- sis complex in pediatric patients. J Child Neurol 2000;15:
lected patients. Patients with seizures are more prone to 652 [PMID: 11063078].
mental retardation or learning disabilities. MacCollin M, Kwiatkowski D: Molecular genetic aspects of the
4. Renal lesions—Renal cysts or angiomyolipomas phakomatoses: Tuberous sclerosis complex and neurofibro-
matosis 1. Curr Opin Neurol 2001;14:163 [PMID: 11262730].
may be asymptomatic. Hematuria or obstruction of
urine flow sometimes occurs; the latter requires opera- Roach ES et al: Tuberous sclerosis complex consensus conference:
Revised clinical diagnostic criteria. J Child Neurol
tion. Ultrasonography of the kidneys should be done in 1998;13:624 [PMID: 9881533].
any patient suspected of tuberous sclerosis, both to aid
in diagnosis if lesions are found and to rule out renal
obstructive disease. 3. Encephalofacial Angiomatosis
5. Cardiopulmonary involvement—Rarely cystic
(Sturge–Weber Disease)
lung disease may occur. Rhabdomyomas of the heart Sturge–Weber disease consists of a facial port wine
may be asymptomatic but can lead to outflow obstruc- nevus involving the upper part of the face (in the first
 NEUROLOGIC & MUSCULAR DISORDERS / 775

division of cranial nerve V), a venous angioma of the 4. Von Hippel–Lindau Disease
meninges in the occipitoparietal regions, and choroidal (Retinocerebellar Angiomatosis)
angioma. The syndrome has been described without
the facial nevus. Von Hippel–Lindau disease is a rare, dominantly inher-
ited condition with retinal and cerebellar heman-
Clinical Findings gioblastomas; cysts of the kidneys, pancreas, and epi-
didymis; and sometimes renal cancers. The patient may
In infancy, the eye may show congenital glaucoma, or present with ataxia, slurred speech, and nystagmus due
buphthalmos, with a cloudy, enlarged cornea. In early to a hemangioblastoma of the cerebellum or with a
stages, the facial nevus may be the only indication, with medullary spinal cord cystic hemangioblastoma. Retinal
no findings in the brain even on radiologic studies. The detachment may occur from hemorrhage or exudate in
characteristic cortical atrophy, calcifications of the cor- the retinal vascular malformation. Rarely a pancreatic
tex, and meningeal angiomatosis may appear with time, cyst or renal tumor may be the presenting symptom.
solidifying the diagnosis. The diagnostic criteria for the disease are a retinal or
Physical examination may show focal seizures or cerebellar hemangioblastoma with or without a positive
hemiparesis on the side opposite the cerebral lesion. family history, intra-abdominal cyst, or renal cancer.
The facial nevus may be much more extensive than the
first division of cranial nerve V; it can involve the lower
Choyke PL et al: Von Hippel–Lindau disease: Genetic, clinical,
face, mouth, lip, neck, and even torso. Hemiatrophy of and imaging features. Radiology 1995;194:629 [PMID:
the opposite limbs may occur. Mental handicap may re- 7862955].
sult from poorly controlled seizures. Late-appearing Roach ES: Von Hippel–Lindau disease: How does one gene cause
glaucoma and, rarely, CNS hemorrhage occur. multiple tumors? Neurology 1999;53:7 [PMID: 10408528].
Radiologic studies may show calcification of the cor-
tex; CT scanning may show this much earlier than
plain radiographic studies. MRI often shows underlying CENTRAL NERVOUS SYSTEM
brain involvement. DEGENERATIVE DISORDERS
The EEG often shows depression of voltage over the OF INFANCY & CHILDHOOD
involved area in early stages; later, epileptiform abnor-
malities may be present focally. The CNS degenerative disorders of infancy and child-
hood are characterized by arrest of psychomotor devel-
Treatment opment and loss, usually progressive but at variable
rates, of mental and motor functioning and often of vi-
Sturge–Weber disease is sporadic. Early control of sion as well. Seizures are common in some disorders.
seizures is important to avoid consequent developmen- Symptoms and signs vary with age at onset and primary
tal setback. If seizures do not occur, normal develop- sites of involvement of specific types.
ment can be anticipated. Careful examination of the These disorders are fortunately rare. An early clinical
newborn, with ophthalmologic assessment to detect pattern of decline often follows normal early develop-
early glaucoma, is indicated. Rarely, surgical removal of ment. Referral for sophisticated biochemical testing is
the involved meninges and the involved portion of the usually necessary before a definitive diagnosis can be
brain may be indicated, even hemispherectomy. made (Tables 23–21 and 23–22).
Chapieski L, Friedman A, Lachar D: Psychological functioning in
children and adolescents with Sturge–Weber syndrome. DeLonlay P et al: A broad spectrum of clinical presentations in
J Child Neurol 2000;15:660 [PMID: 11063079]. congenital disorders of glycosylation. I: A series of 26 cases.
J Med Genet 2001;38:14 [PMID: 11134235].
Comi AM et al: Encephalofacial anigomatosis sparing the occipital
lobe and without facial nevus: On the spectrum of Goebel H et al: Neurodegenerative diseases. Neuroimaging Clin
Sturge–Weber syndrome variants? J Child Neurol 2003; North Am 2001;11:37 [PMID: 11331227].
18:35 [PMID: 12661936]. Kaye EM: Update on genetic disorders affecting white matter. Pe-
Kossoff EH et al: Outcomes of 32 hemispherectomies for diatr Neurol 2001;24:11 [PMID: 11182276].
Sturge–Weber syndrome worldwide. Neurology 2002;59: Kristjansdottir R, Uvebrant P, Wiklund LM: Clinical characteris-
1735 [PMID: 12473761]. tics of children with cerebral white matter abnormalities. Eu-
Pfund Z et al: Quantitative analysis of gray- and white-matter vol- rope J Paediatr Neurol 2000;4:17 [PMID: 10701100].
umes and glucose metabolism in Sturge–Weber syndrome. Shahbazian MD, Zoghbi HY: Molecular genetic of Rett syndrome
J Child Neurol 2003;18:119 [PMID: 12693779]. and clinical spectrum of MECP2 mutations. Curr Opin Neu-
Sujansky E, Conradi S: Sturge–Weber syndrome: Age of onset of rol 2001;14:171 [PMID: 11262731].
seizures and glaucoma and the prognosis for affected children. Vargas AP: Unusual early-onset Huntington’s disease. J Child Neu-
J Child Neurol 1995;10:49 [PMID: 7769179]. rol 2003;18:429 [PMID: 12886981].
Table 23–21. Central nervous system degenerative disorders of infancy.

Enzyme Defect Early Vision and Somatic

Disease and Genetics Onset Manifestations Hearing Findings
WHITE MATTER
Globoid (Krabbe) Recessive galacto- First 6 mos; Feeding difficulties. Optic atrophy, mid- Head often small.
leukodystrophy cerebroside β-galac- late-onset form Shrill cry. Irritability. course to late. Hyper- Often under-
tosidase deficiency. 2–6 y Arching of back. acusis occasionally. weight.
Chromosome 14.

Metachromatic Recessive. Arylsul- Second year; Incoordination, es- Optic atrophy, usually Head enlarged
leukodystrophy fatase A deficiency. less often, later pecially gait distur- late. Hearing normal. late. No change
22q13. childhood or bance; then general in juvenile form.
adult regression. Reverse
in juveniles.
Neuroaxonal Familial, (?) reces- 6 mos to 2 y Arrest of develop- Nystagmus occasional; Early, may lie in
dystrophy sive. More common ment and dementia. optic atrophy, blind- “frog position.”
in girls than boys; Loss of motor func- ness; abnormal VER.
defect unknown. tions. Occasionally
hypesthesia over
trunk and legs.
Hallervorden– Unknown; may be By age 10 y Rigidity, dystonia, Optic atrophy. None
Spatz syndrome familial. gait disturbance,
tremor.
Pelizaeus– X-linked recessive; (?) Birth to 2 y Eye rolling often Slowly developing op- Head and body
Merzbacher rare female. Proteo- shortly after birth. tic atrophy. Hearing normal
disease lipid protein (myelin) Head bobbing. Slow normal. Nystagmus.
decreased. Xq22 loss of intellect.
DIFFUSE, BUT PRIMARILY GRAY MATTER
Poliodystrophy Occasionally familial, Infancy to ado- Variable: loss of in- Cortical blindness and Head normal
(Alpers’s disease) recessive. Possibly lescence tellect, seizures, in- deafness initially; may
viral. Metabolic forms. coordination. Vom- fail to grow
iting, hepatic failure.
Tay–Sachs disease Recessive. Hexo- Tay–Sachs, and Variable: shrill cry, Cherry-red macula, Head enlarged
and GM2 gan- saminidase deficien- Sandhoff; 3–6 loss of vision, infan- early blindness. Hyper- late. Liver occa-
gliosidosis var- cies. Tay–Sachs (93% mos; others tile spasms, arrest acusis early. Strabis- sionally enlarged.
iants: Sandhoff East European Jew- 2–6 y or of development. In mus in juvenile form, None in juvenile
disease; juvenile; ish), hexosaminidase later. juvenile and chronic blindness late. chronic forms.
chronic-adult A deficiency. Sand- forms: motor difficul-
hoff-hexosaminidase ties; later, mental
A and B deficiency. difficulties.
Juvenile-partial
hexosaminidase A
Niemann–Pick dis- 50% Jewish. Reces- First 6 mos. Slow development. Cherry-red macula in Head usually nor-
ease and variants sive. Sphingomyeli- In variants, later Protruding belly. 35–50%. Blindness mal. Spleen en-
nase deficiency in onset: often late. Deafness larged more than
types A and C in- non-Jewish. occasionally. liver. Occasional
volving the CNS. xanthomas of
skin.
Infantile Gaucher Recessive. Glucocere- First 6 mos; Stridor or hoarse cry; Occasional cherry-red Head usually nor-
disease (gluco- brosidase deficiency. rarely, late in- retraction; feeding macula. Convergent mal. Liver and
sylceramide lipi- fancy difficulties squint. Deafness spleen equally
dosis) occasionally. enlarged.

776
Table 23–21. Central nervous system degenerative disorders of infancy. (continued)

Motor System Seizures Laboratory and Tissue Studies Course

WHITE MATTER
Early spasticity, occasion- Early. Myoclonic CSF protein elevated; usually normal in late-onset Rapid. Death usually by 11⁄2–
ally preceded by hy- and generalized, forms. Sural nerve; nonspecific myelin breakdown. 2 y. Late-onset cases
potonia. Prolonged decerebrate Enzyme deficiency in leukocytes, cultured skin may live 5–10 y.
nerve conduction. posturing fibroblasts. Demyelination, gliosis with low-signal
CT scan, high-signal T2-weighted MRI.
Combined upper and Infrequent, usually Metachromatic cells in urine: negative sulfatase Moderately slow. Death in
lower motor neuron late and gener- A test. CSF protein elevated. Urine sulfatide in- infantile form by 3–8 y,
signs. Ataxia. Pro- alized creased. Sural nerve biopsy; metachromasia. En- in juvenile form by 10–15 y.
longed nerve zyme deficiency in leukocytes, cultured skin fibro-
conduction. blasts. Imaging: Same as globoid leukodystrophy.
Combined upper and Variable, but Denervation on EMG. Increased iron uptake in Progressive, with death
lower motor neuron usually not a region of basal ganglia. Brain and sural nerve: ax- early in second decade
lesions. Hypotonia, prominent fea- onal swellings or “spheroids” Cerebellar atrophy. or earlier.
extrapyramidal mani- ture Cause unknown. Conjunctival biopsy may yield
festations. nerves with “spheroids.”

Extrapyramidal signs, Variable, EEG may Seablue histiocytes in bone marrow. Iron deposits Progressive mental/motor
dysarthria, increased be abnormal in basal ganglia on MRI. deterioration
deep tendon reflexes.
Cerebellar signs early, Usually only late None specific. Brain biopsy: extensive demyelina- Very slow, often seemingly
hyperactive deep re- tion with small perivascular islands of intact mye- stationary.
flexes. Spasticity. lin. Exon abnormalities in PLP gene in 10–25%.

DIFFUSE, BUT PRIMARILY GRAY MATTER

Variable: incoordination, Often initial mani- Nonspecific, CSF protein normal or slightly eleva- Usually rapid, with death
spasticity festation: myo- ted. Extensive neuronal loss in cortex: may occur within 1–3 y after onset.
clinic, akinetic, very late. Variably increased serum pryuvate, lac-
and generalized tate; liver steatosis, cirrhosis late.
Initially floppy. Eventual Frequent, in mid- Blood smears: vacuolated lymphocytes; baso- Moderately rapid. Death
decerebrate rigidity. course and late. phillic hypergranulation. Enzyme deficiencies in usually by 2–5 y. In
In juvenile and chro- Infantile spasms serum, leukocytes, culture skin fibroblasts. High- juvenile form, 5–15 y.
nic forms: dysarthria, and generalized density thalami on CT scan, low-density white
ataxia, spasticity. matter.

Initially floppy. Eventually Rare and late Blood: vacuolated lymphocytes; increased lipids. Moderately slow. Death
spastic. Occasionally X-rays: “mottled” lungs, decalcified bones. “Foam usually by 3–5 y.
extrapyramidal signs. cells” in bone marrow, spleen, lymph nodes. WBC,
Ataxia, dystonia. fibroblast enzyme studies are diagnostic.

Opisthotonos early, fol- Rare and late Anemia. Increased acid phosphatase. X-rays: Very rapid
lowed rapidly by de- thinned cortex, trabeculation of bones. “Gaucher
cerebrate rigidity cells” in bone marrow, spleen. Enzyme deficiency
in leukocytes or cultured skin fibroblasts.
(continued)
777
778 / CHAPTER 23

Table 23–21. Central nervous system degenerative disorders of infancy. (continued)

Enzyme Defect Early Vision and Somatic

Disease and Genetics Onset Manifestations Hearing Findings
DIFFUSE, BUT PRIMARILY GRAY MATTER
Lipogranulomato- Ceramidase defi- Early in infancy Hoarseness, irritabi- Usually normal Painful nodular
sis (Farber ciency lity, restricted joint swelling of joints;
disease) movements subcutaneous
nodules
Generalized gang- Recessive; β-galacto- First year; less Arrest of develop- 50% “cherry-red spot.” Head enlarged
liosidosis and ju- sidase deficiency often, second ment. Protruding Hearing usually nor- early: liver en-
venile type (Gm1 year belly. Coarse facies mal. In juvenile type. larged more than
gangliosidoses) in infantile (genera- occasionally retinitis spleen
lized) form. pigmentosa.
Subacute necro- Recessive or variable. Infancy to late Difficulties in feed- Optic atrophy, often Head usually nor-
tizing encepha- May have deficiency childhood ing; feeble or absent early. Roving eye mal, occasionally
lomyelopathy of pyruvate carboxy- cry; floppiness movements. Ophthal- small; cardiac and
(Leigh disease) lase, pyruvate dehy- moplegia. renal tubular dys-
drogenase, cyto- function occa-
chrome enzymes. sionally
Menkes disease X-linked recessive; Infancy Peculiar facies; sec- May show optic disk Normal to small
(kinky hair defect in copper ondary hair white, pallor and microcysts
disease) absorption twisted, split; hypo- of pigment epithelium
thermia
Carbohydrate- Recessive glycopro- Infancy Failure to thrive, Strabismus Dysmorphic
deficient glyco- tein abnormality; retardation Retinopathy facies. Prominent
protein syn- glycosolation faulty fat pads.
drome
Abetalipopro- Recessive; primary Early childhood Diarrhea in infancy Retinitis pigmentosa; None
teinemia (Bas- defect unknown late ophthalmoplegia
sen–Kornzweig
disease)

Wisniewski KE et al: Neuronal ceroid lipofuscinoses: Classification Clinical Findings

and diagnosis. Adv Genet 2001;45:1 [PMID: 11332767].
A. SYMPTOMS AND SIGNS
Ataxia of the trunk and extremities may be so severe
ATAXIAS OF CHILDHOOD that the child exhibits a staggering, reeling gait and in-
ability to sit without support or to reach for objects; or
1. Acute Cerebellar Ataxia he or she may show only mild unsteadiness. Hypotonia,
tremor of the extremities, and horizontal nystagmus
Acute cerebellar ataxia occurs most commonly in chil- may be present. Speech may be slurred. The child is fre-
dren age 2–6 years. The onset is abrupt, and the evolu- quently irritable, and vomiting may occur.
tion of symptoms is rapid. In about 50% of patients, a There are no clinical signs of increased intracranial
prodromal illness occurs with fever, respiratory or gas- pressure. Sensory and reflex testing usually shows no
trointestinal symptoms, or an exanthem within 3 weeks abnormalities.
of onset. Associated viral infections include varicella,
rubeola, mumps, rubella, echovirus infections, po-
liomyelitis, infectious mononucleosis, and influenza. B. LABORATORY FINDINGS
Bacterial infections such as scarlet fever and salmonel- CSF pressure and protein and glucose levels are normal;
losis have also been incriminated. slight lymphocytosis (≤ 30/mL) may be present. At-
 NEUROLOGIC & MUSCULAR DISORDERS / 779

Table 23–21. Central nervous system degenerative disorders of infancy. (continued)

Motor System Seizures Laboratory and Tissue Studies Course

DIFFUSE, BUT PRIMARILY GRAY MATTER
Psychomotor retardation Usually none Chest radiographs may show pulmonary infil- Rapid: death usually in 1–2 y.
and progressive paraly- trates. Nodules: granulomatous lesions, resem-
sis bling those in reticuloendotheliosis. Multiple
infarcts on CNS imaging.
Initially floppy, eventually Usually late Blood: vacuolated lymphocytes. X-rays: dorsolum- Very rapid. Death within a
spastic bar kyphosis, “beaking” of vertebrae. “Foam cells” few years. Slower in juvenile
similar to those in Niemann–Pick disease. type (to 10 y).

Flaccid and immobile; Rare and late Increased CSF and blood lactate and pyruvate. Usually rapid in infants, but
may become spastic. High-signal MRI T2 foci in thalami; globus pallidus, may be slow with death after
Spinocerebellar forms; subthalamic nuclei. several years. Central hypo-
ataxia. ventilation a frequent cause
of death.

Variable: floppy to spastic Myoclonic infan- Defective absorption of copper. Cerebral angio- Moderately rapid. Death
tile spasms, status graphy shows elongated arteries. Hair shows pili usually by 3–4 ys.
epilepticus torti, split shafts. Copper and ceruloplasmin low.

Variable hypotonia Rare Normal transferrin decreased. Carbohydrate- Cardiomyopathy, throm-

Neuropathy deficient transferrin increased. Liver steatosis. bosis
Cerebellar hypoplasia.

Ataxia, late extrapyra- None Abetalipoproteinemia: acanthocytosis, low serum Progression arrested with
midal movement dis- vitamin E; cerebellar atrophy on imaging. vitamin E
order

CSF = cerebrospinal fluid; CT = computed tomography; EEG = electroencephalogram; EMG = electromyelogram; MRI = magnetic reso-
nance imaging; VER = visual evoked potential; WBC = white blood cell.

tempts should be made to identify the etiologic viral section.) Papilledema, anemia, basophilic stippling of
agent. erythrocytes, proteinuria, typical radiographs, and ele-
vated CSF protein are clinical clues to lead intoxication,
C. IMAGING which is confirmed by serum, urine, or hair lead levels.
CT scans are normal; MRI may show cerebellar postin- An occult neuroblastoma, usually seen with the
fectious demyelinating lesions. The EEG may be nor- polymyoclonus–opsoclonus syndrome (see following
mal or may show nonspecific slowing. section) occasionally begins as acute cerebellar ataxia.
In rare cases, acute cerebellar ataxia may be the pre-
Differential Diagnosis senting sign of acute bacterial meningitis or may be
mimicked by corticosteroid withdrawal, vasculitides
Acute cerebellar ataxia must be differentiated from such as in polyarteritis nodosa, trauma, the first attack
acute cerebellar syndromes due to phenytoin, pheno- of ataxia in a metabolic disorder such as Hartnup dis-
barbital, primidone, or lead intoxication. For pheny- ease, or the onset of acute disseminated en-
toin, the toxic level in serum is usually above cephalomyelitis or of multiple sclerosis. The history and
25 µg/mL; for phenobarbital, above 50 µg/mL; for physical findings may differentiate these disturbances,
primidone, above 14 µg/mL. (See Seizure Disorders but appropriate laboratory studies are often necessary.
 Table 23–22. Central nervous system degenerative disorders of childhood.a

Enzyme Defect Early Vision and

Disease and Genetics Onset Manifestations Hearing Motor System Seizures Laboatory and Tissue Studies Course
Adrenoleukodystrophy X-linked reces- 5–10 years Impaired intel- Cortical Ataxia, spasticity; Occasionally Hyperpigmentation and adreno- Fairly rapid.
780

and variants sive. Neonatal May also lect; behavioral blindness motor deficits may cortical insufficiency. ACTH ele- Death usually
form recessive present as problems and deaf- be asymmetrical or vated. Accumulation of very long within 2–3 y
Xq28. Acyl-CoA newborn, ness one-sided initially; chain fatty acids in plasma. after onset.
synthetase de- adolescent adrenomyeloneu-
ficiency. or adult. ropathy in adults
Neuronal ceroid lipo- Recessive; mul- 6–24 Ataxia; visual Pigmentary Ataxia; spasticity Often early: Blood: vacuolated lymphocytes. Moderately slow.
fuscinosis (NCL; tiple gene mu- months difficulties; ar- degeneration progressing to myoclonus Biopsy, EM of skin, conjunctiva; Death in 3–8 y.
cerebromacular tations, poly- INCL: 2–4 y rested intellec- of macula; decerebrate rig- and later WBC: “curvilinear bodies, finger-
degeneration); in- morphisms. LINCL; tual develop- optic atrophy; idity generalized; print profiles.” Molecular testing
fantile NCL (INCL); (See Ref. Gene 4–8 y JNCL ment. Seizures ERG, VER refractory of CLN1, CLN2, CLN3. Protein
late infantile (LINCL); Reviews.) abnormal gene product testing for CLN1
juvenile NCL (JNCL; and CLN2.
Batten disease)
Subacute sclerosing None. Measles 3–22 years; Impaired intel- Occasionally Ataxia; slurred Myoclonic CSF protein normal to moder- Variable, death
panencephalitis “slow virus” in- rarely earl- lect; emotional chorioretinitis speech; occasion- and akinetic ately elevated. High CSF IgG;b in months to
(Dawson disease) fection. Also re- ier or later lability; incoor- or optic atro- ally involuntary seizures rel- oligoclonal bands. Elevated CSF years. Remis-
ported as result dination phy; hearing movements; atively early; (and serum) measles (or rubella) sions of variable
of rubella. normal spasticity progres- later, focal antibody titers. Characteristic duration may
sing to decere- and general- EEG. Brain biopsy; inclusion body occur.
brate rigidity ized encephalitis; culturing of measles
virus, perhaps rubella virus.
 Multiple sclerosis None. Diagnosis Adoles- Highly variable: Optic neuritis; Motor weakness; Rare: focal CSF may show slight pleocytosis, Variable: com-
difficult in child- cent; rare may strike one diplopia, ny- spasticity; ataxia; or general- elevation of protein and gamma plete remission
hood. in child- or more sites stagmus at sphincter distur- ized globulin;b oligoclonal bands possible. Recur-
hood of CNS; pares- some time; bances; slurred present. CT scan may show areas rent attacks and
thesias common vestibuloco- speech; mental of demyelination. Auditory, vis- involvement of
chlear nerves difficulties. ual, and somatosensory evoked multiple sites are
occasionally responses often show lesions in prerequisites for
affected respective pathways. Changes in diagnosis.
T-cell subsets.
Cerebrotendinous ?Recessive. Ab- Late child- Xanthomas in Cataracts; Cerebellar defects; Myoclonus Xanthomas may appear in lungs. Very slowly pro-
xanthomatosis normal accu- hood to tendons; mental xanthelasma bulbar paralysis Xanthomas in tendons (espec- gressive into
mulation of adoles- deterioration late ially Achilles). middle life. Re-
cholesterol. cence place deficient
bile acid.
Huntington disease Dominant. Chro- 10% child- Rigidity; de- Ophthalmo- Rigidity; chorea 50% with CT scan may show “butterfly” Moderately
mosome 4p hood on- mentia plegia late frequently absent major motor atrophy of caudate and putamen rapid with death
CAG repeat. set in children seizures in 15 y
Refsum disease Recessive. Phy- 5–10 y Ataxia; ichthyo- Retinitis pig- Ataxia; neuro- None Serum phytanic acid elevated. Treat with low
tanic acid oxi- sis; cardiomyo- mentosa; pathy; tendon Slow nerve conduction velocity. phytanic acid
dase deficiency. pathy nystagmus reflexes absent Elevated CSF protein. Peroxiso- diet
781

mal disease.
a
For late infantile metachromatic leukodystrophy, Pelizaeus-Merzbacher disease, poliodystrophy, Gaucher’s disease of later onset, and subacute necrotizing encephalomyelopathy, see
Table 22–22.
b
CSF γ-globulin (IgG) is considered elevated in children when > 9% of total protein (possibly even > 8.3%); definitively elevated when > 14%.
ACTH = adrenocorticotropic hormone; CSF = cerebrospinal fluid; CT = computed tomography; EEG = electroencephalogram; ERG = electroretinogram; VER = visual evoked response; CLN =
ceroid lipofuscinosis.
782 / CHAPTER 23

For ataxias with more chronic onset and course, see the The symptoms respond (often dramatically) to large
sections on spinocerebellar degeneration and the other doses of corticotropin. Plasmapheresis has been success-
degenerative disorders. ful. When a neural crest (or other) tumor is found, sur-
gical excision should be followed by irradiation and
Treatment & Prognosis chemotherapy. Life span is determined by the biologic
behavior of the tumor. The syndrome is usually self-
Treatment is supportive. The use of corticosteroids has limited but may be characterized by exacerbations and
no rational justification. Between 80% and 90% of remissions. Even after removal of a neural crest tumor
children with acute cerebellar ataxia not secondary to and without other evidence of its recurrence, symptoms
drug toxicity recover without sequelae within may reappear. Mild mental retardation may be a se-
6–8 weeks. In the remainder, neurologic disturbances, quela.
including disorders of behavior and of learning, ataxia,
abnormal eye movements, and speech impairment, may Krolczyk S: Opsoclonus: An early sign of neonatal herpes en-
persist for months or years, and recovery may remain cephalitis. J Child Neurol 2003;18:356 [PMID: 12822821].
incomplete. Pranzatelli MR et al: Screening for autoantibodies in children with
opsoclonus–myoclonus-ataxia. Pediatr Neurol 2002;27:384
Go T: Intravenous immunoglobulin therapy for acute cerebellar [PMID: 12504207].
ataxia. Acta Paediatr 2003;92:504 [PMID: 12801122]. Yiu VWY et al: Plasmapheresis as an effective treatment for opso-
Dinolfo E: Evaluation of ataxia. Pediatr Rev 2001;22:177 [PMID: clonus–myoclonus syndrome. Pediatr Neurol 2001;24:72
11331741]. [PMID: 11182286].
Lamperti C et al: Cerebellar ataxia and coenzyme Q10 deficiency.
Neurology 2003;60:1206 [PMID: 12682339]. 3. Spinocerebellar Degeneration
Ryan MM, Engle EC: Acute ataxia I childhood. J Child Neurol Disorders
2003;18:309 [PMID: 12822814].
Spinocerebellar degeneration disorders may be heredi-
2. Polymyoclonia–Opsoclonus tary or may occur in sporadic distribution. Hereditary
disorders include Friedreich ataxia, dominant heredi-
Syndrome of Childhood (Infantile tary ataxia, and a group of miscellaneous diseases.
Myoclonic Encephalopathy, “Dancing
Eyes–Dancing Feet” Syndrome) Friedreich Ataxia
The symptoms and signs of this syndrome are at first This is a recessive disorder characterized by onset of gait
similar to those of acute cerebellar ataxia. Often of sud- ataxia or scoliosis before puberty that becomes progres-
den onset, polymyoclonus–opsoclonus syndrome is sively worse. Reflexes, light touch, and position sensa-
characterized by severe incoordination of the trunk and tion are reduced. Dysarthria becomes progressively
extremities with lightning-like jerking or flinging more severe. Cardiomyopathy usually develops, and di-
movements of a group of muscles, causing the child to abetes mellitus occurs in 40% of patients, half of whom
be in constant motion while awake. Extraocular muscle require insulin. Pes cavus typically is found. The GAA
involvement results in sudden irregular eye movements trinucleotide repeats on chromosome 9 can be used for
(opsoclonus). Irritability and vomiting are often pre- laboratory diagnosis.
sent, but there is no depression of level of conscious- Treatment includes surgery for scoliosis and inter-
ness. This syndrome occurs in association with viral in- vention as needed for cardiac disease and diabetes. Pa-
fections and tumors of neural crest origin among other tients are usually confined to a wheelchair after age
disorders. Immunologic mechanisms have been postu- 20 years. Death occurs, usually from heart failure or
lated. Usually no signs of increased intracranial pressure dysrhythmias, in the third or fourth decade; some pa-
are present. CSF may show normal or mildly increased tients survive longer.
protein levels. Special techniques show increased CSF
levels of plasmacytes and abnormal immunoglobulins. Dominant Ataxia
The EEG may be slightly slow, but when performed to-
gether with EMG, it shows no evidence of association These diseases (in the past known as olivopontocerebel-
between cortical discharges and the muscle movements. lar atrophy, Holmes ataxia, Marie ataxia, and the like)
An assiduous search must be made to rule out tumor of occur with varying manifestations, even among mem-
neural crest origin by chest radiographs and CT scan or bers of the same family. Ataxia occurs at onset, and pro-
ultrasound (or both) of the adrenal area as well as by as- gression continues with ophthalmoplegias (in some pa-
says of urinary catecholamine metabolites (vanillylman- tients), extrapyramidal syndromes, polyneuropathy,
delic acid and so on) and cystathionine. and dementia. Several types have been found to be
 NEUROLOGIC & MUSCULAR DISORDERS / 783

caused by CAG trinucleotide repeats. Levodopa may tion velocities may be reduced. The entire nervous sys-
ameliorate rigidity and bradykinesia, but no other ther- tem may be affected in late stages of the disease. A spec-
apy is available. Only 10% of patients experience onset trum of involvement may be seen in the same family.
in childhood, and the course in these patients is often Immunodeficiencies of IgA and IgE are common (see
more rapid. Chapter 29), and the incidence of certain cancers is
high. Elevated serum α-fetoprotein is a screen for this
Miscellaneous Hereditary Ataxias disease.

Associated findings permit identification of these reces- Cabana MD et al: Consequences of the delayed diagnosis of
sive disorders. These include ataxia–telangiectasia ataxia–telangiectasia. Pediatrics 1998;102:98 [PMID:
(telangiectasia, immune defects; see below); Wilson dis- 9651420].
ease (Kayser–Fleischer rings); Refsum disease Crawford TO: Ataxia–telangiectasia. Semin Pediatr Neurol
(ichthyosis, cardiomyopathy, retinitis pigmentosa, large 1998;5:287 [PMID: 9874856].
nerves); Rett syndrome (regression to autism at age Sandoval C, Swift M: Hodgkin disease in ataxia–telangiectasia pa-
tients with poor outcomes. Med Pediatr Oncol 2003;40:
7–18 months in girls, loss of use of hands, progressive 162 [PMID: 12518345].
failure of brain growth); and abetalipoproteinemia (in-
Tavani F et al: Ataxia–telangiectasia: The pattern of cerebellar atro-
fantile diarrhea, acanthocytosis, retinitis pigmentosa). phy on MRI. Neuroradiology 2003;45:315 [PMID:
Gluten sensitivity may cause ataxia. Patients with juve- 12740724].
nile and chronic gangliosidoses and some hemolytic
anemias and long-term survivors of Chédiak–Higashi
disease may develop spinocerebellar degeneration. Idio- EXTRAPYRAMIDAL DISORDERS
pathic familial ataxia is called Behr syndrome. Neu- Extrapyramidal disorders are characterized by the pres-
ropathies such as Charcot–Marie–Tooth disease pro- ence in the waking state of one or more of the following
duce ataxia. features: dyskinesias, athetosis, ballismus, tremors,
rigidity, and dystonias.
Alper G, Narayanan V: Friedreich’s ataxia. Pediatr Neurol 2003;2 For the most part, the precise pathologic and ana-
8:335 [PMID: 12878293]. tomic localization of these disorders is not understood.
Babovic-Vuksanovic D et al: Spinocerebellar ataxia type 2 (SCA 2) Motor pathways synapsing in the striatum (putamen
in an infant with extreme CAG repeat expansion. Am J Med and caudate nucleus), globus pallidus, red nucleus, sub-
Genet 1998;79:383 [PMID: 9779806]. stantia nigra, and the body of Luys are involved; this
Hadjivassiliou M: Gluten ataxia I perspective: Epidemiology, ge- system is modulated by pathways originating in the
netic susceptibility and clinical characteristics. Brain thalamus, cerebellum, and reticular formation.
2003;126:685 [PMID: 12566288].
Macpherson J et al: Observation of an excess of fragile-X permuta-
tions in a population of males referred with spinocerebellar 1. Sydenham Postrheumatic Chorea
ataxia. Hum Genet 2003;112:619 [PMID: 12612802].
Sydenham chorea is characterized by an acute onset of
Parmeggiani A et al: Epilepsy, intelligence and psychiatric disorders
in patients with cerebellar hypoplasia. J Child Neurol choreiform movements and variable degrees of psycho-
2003;18:1 [PMID: 12661930]. logical disturbance. It is frequently associated with
Tranebjaerg L et al: Genome-wide homozygosity mapping localizes rheumatic endocarditis and arthritis. Although the dis-
a gene for autosomal recessive non-progressive infantile order follows infections with group A β-hemolytic
ataxia to 20q11–q13. Hum Genet 2003;113:293 [PMID: streptococci, the interval between infection and chorea
12811539]. may be greatly prolonged; throat cultures and antistrep-
tolysin O (ASO) titers may therefore be negative.
ATAXIA–TELANGIECTASIA Chorea has also been associated with hypocalcemia;
with vascular lupus erythematosus; and with toxic,
(Louis-Bar Syndrome) viral, infectious, parainfectious, and degenerative en-
Ataxia–telangiectasia is a multisystem disorder inherited cephalopathies.
as an autosomal recessive trait. It is characterized by
progressive ataxia; telangiectasia of the bulbar conjunc- Clinical Findings
tiva, external ears, nares, and (later) other body surfaces,
appearing in the third to sixth year; and recurrent respi- A. SYMPTOMS AND SIGNS
ratory, sinus, and ear infections. Ocular dyspraxia, Chorea, or rapid involuntary movements of the limbs
slurred speech, choreoathetosis, hypotonia and are- and face, is the hallmark physical finding. In addition
flexia, and psychomotor and growth retardation may be to the jerky incoordinate movements, the following are
present. Endocrinopathies are common. Nerve conduc- noted: emotional lability, waxing and waning (“milk-
784 / CHAPTER 23

maid’s”) grip, darting tongue, “spooning” of the ex- more times, but the ultimate outcome does not appear
tended hands and their tendency to pronate, and knee to be worse in those with recurrences. In older studies,
jerks slow to return from the extended to their prestim- valvular heart disease occurs in about one third of pa-
ulus position (“hung up”). Seizures, while uncommon, tients, particularly if other rheumatic manifestations ap-
may be masked by choreic jerks. pear. Psychoneurotic disturbances occur in a significant
percentage of patients.
B. LABORATORY FINDINGS
Anemia, leukocytosis, and an increased erythrocyte sed- Church AJ et al: Anti-basal ganglia antibodies in acute and persis-
imentation rate may be present. The ASO titer may be tent Sydenham’s chorea. Neurology 2002;59:227 [PMID:
elevated and C-reactive protein present. Throat culture 12316062].
is sometimes positive for group A-hemolytic strepto- Garvey MA, Giedd J, Swedo SE: PANDAS: The search for envi-
cocci. ronmental triggers of pediatric neuropsychiatric disorders:
ECG and echocardiography are often essential to Lessons from rheumatic fever. J Child Neurol 1998;13:
413 [PMID: 9733286].
detect cardiac involvement. Antineuronal antibodies are
Lee PH et al: Serial brain SPECT images in a case of Sydenham
present in most patients but are not specific for this dis- chorea. Arch Neurol 1999;56:237 [PMID: 10025430].
ease. Specialized radiologic procedures (MRI, SPECT) Murphy ML, Pichichero ME: Prospective identification and treat-
may show basal ganglia abnormalities. ment of children with pediatric autoimmune neuropsychi-
atric disorder associated with group A streptococcal infection
Differential Diagnosis (PANDAS). Arch Pediatr Adolesc Med 2002;156:
356 [PMID: 11929370].
The diagnosis of Sydenham chorea is usually not diffi- Pranzatelli MR: Movement disorders in childhood. Pediatr Rev
cult. Tics, drug-induced extrapyramidal syndromes, 1996;17:388 [PMID: 8937171].
Huntington chorea, and hepatolenticular degeneration Schlaggar BL, Mink JW: Movement disorders in children. Pediatr
(Wilson disease), as well as other rare movement disor- Rev 2003;24:39 [PMID: 12563038].
ders, can usually be ruled out on historical and clinical
grounds. Immunologic linkages among chorea, tics, 2. Tics (Habit Spasms)
and obsessive–compulsive disorder are being studied in
pediatric patients. Other causes of chorea can be ruled Clinical Findings
out by laboratory tests, such as antinuclear antibody for Tics, or habit spasms, are quick repetitive but irregular
lupus, thyroid screening tests, serum calcium for movements, often stereotyped, and briefly suppressible.
hypocalcemia, and immunologic tests for Epstein–Barr Coordination and muscle tone are not affected. A psy-
virus infection. chogenic basis is seldom discernible. Transient tics of
childhood (12–24% incidence in school-age children)
Treatment last from 1 month to 1 year and seldom need treat-
There is no specific treatment. Dopaminergic blockers ment. Many children with tics have a history of en-
such as haloperidol, 0.5 mg to 3–6 mg/d, and pi- cephalopathic past events, neurologic soft signs, and
mozide, 4–12 mg/d, have been used. Parkinsonian side school problems. Facial tics such as grimaces, twitches,
effects such as rigidity and masked facies and, with high and blinking predominate, but the trunk and extremi-
doses, tardive dyskinesia rarely occur in childhood. A ties are often involved and twisting or flinging move-
variety of other drugs have been used with success in in- ments may be present. Vocal tics are less common.
dividual cases, such as the anticonvulsant sodium val- Tourette syndrome is characterized by multiple fluc-
proate, 50–60 mg/kg/d in divided doses; or prednisone, tuating motor and vocal tics with no obvious cause last-
0.5–2 mg/kg/d in divided doses. Emotional lability and ing more than 1 year. Tics evolve slowly, new ones
depression sometimes warrant administration of antide- being added to or replacing old ones. Coprolalia and
pressants such as amitriptyline. All patients should be echolalia are relatively infrequent. Partial forms are
given antistreptococcal rheumatic fever prophylaxis, common. The usual age at onset is 2–15 years, and the
possibly through child-bearing age. familial incidence is 35–50%. The disorder occurs in all
ethnic groups. Tourette syndrome may be triggered by
stimulants such as methylphenidate and dextroamphet-
Prognosis amine. An imbalance of neurotransmitters, especially
Sydenham chorea is a self-limited disease that may last dopamine and serotonin, has been hypothesized.
from a few weeks to months. Relapse of chorea may In mild cases, tics are self-limited and, when disre-
occur with nonspecific stress or illness—or with break- garded, disappear. When attention is paid to one tic, it
through streptococcus infections (if penicillin prophy- may disappear only to be replaced by another that is
laxis is not done). Two thirds of patients relapse one or often worse. If the tic and its underlying anxiety or
 NEUROLOGIC & MUSCULAR DISORDERS / 785

compulsive neuroses are severe, psychiatric evaluation tic agents used most often are pimozide and risperidone.
and treatment are needed. Sleepiness and weight gain are the most common side
Important comorbidities are attention-deficit/hyper- effects; rare are prolonged QT interval (ECG), akathisia,
activity disorder and obsessive–compulsive disorder. and tardive dyskinesia. Clonidine, clonazepam, and cal-
Learning disabilities, sleep difficulties, anxiety states, cium channel blockers have been used in individual pa-
and mood swings are also common. Medications such tients with some success. Sometimes these agents are
as methylphenidate and dextroamphetamine should be used in combination (eg, clonidine with pimozide).
carefully titrated to treat attention-deficit/hyperactivity Sydenham chorea is a well-documented pediatric
disorder and avoid worsening tics. Fluoxetine and autoimmune disorder associated with streptococcal in-
clomipramine may be useful for obsessive–compulsive fections (PANDAS). Patients with tic disorders occa-
disorder and rage episodes in patients with tics. sionally have obsessive–compulsive disorder precipi-
tated or exacerbated by streptococcal infections. Less
Treatment definite (much less frequent) are tic flare-ups with
streptococcal infection. Active prospective antibody
The most effective medications for treating Tourette (antineuronal and antistreptococcal) and clinical studies
syndrome are dopamine blockers; however, many pedi- are in progress. Research centers have used experimen-
atric patients can manage without drug treatment. Med- tal treatments (IVIG, plasmapharesis, steroids) in severe
ications are generally reserved for patients with disabling cases. At present, most patients with a tic do not
symptoms; treatment may be relaxed or discontinued worsen with group A streptococcal infections; with rare
when the symptoms abate (Table 23–23). Nonpharma- exceptions, penicillin prophylaxis is not generally neces-
cologic treatment of Tourette syndrome includes educa- sary for the majority of patients with tic disorders.
tion of patients, family members, and school personnel.
In some cases, restructuring the school environment to Burd L et al: Long-term follow-up of an epidemiologically defined
prevent tension and teasing may be necessary. Support- cohort of patients with Tourette syndrome. Neurology
ive counseling, either at or outside school, should be 2001;16:431 [PMID: 11417610].
provided. Medications usually do not eradicate the tics. Jankovic J: Tourette’s syndrome. N Engl J Med 2001;345:1184
The goal of treatment should be to reduce the tics to [PMID: 11642235].
tolerable levels without inducing undesirable side ef- Kossoff EH, Singer HS: Tourette syndrome: Clinical characteristics
fects. Medication dosage should be increased at weekly and current management strategies. Paediatr Drugs
intervals until a satisfactory response is obtained. Often 2001;3:355 [PMID: 11393328].
a single dose at bedtime is sufficient. The two neurolep- Kurlan R et al: The behavioral spectrum of tic disorders: A commu-
nity based study. Neurology 2002;59:414 [PMID:
12177376].
Table 23–23. Medications for Tourette syndrome Leckman JF: Tourette’s syndrome. Lancet 2002;360:1577 [PMID:
and tics. 12443611].
Loiselle CR et al: Antistreptococcal, neuronal, and nuclear antibod-
ies in Tourette syndrome. Pediatr Neurol 2003;28:119
Dopamine blockers (many are antipsychotics) [PMID: 12699862].
Haloperidol (Haldol) Murphy ML, Pichichero ME: Prospective identification and treat-
Pimozide (Orap) ment of children with pediatric autoimmune neuropsychi-
Fluphenazine (Prolixin) atric disorder associated with a group A streptococcal infec-
Olanzapine (Zyprexa) tion (PANDAS). Arch Pediatr Adolesc Med 2002;156:356
Risperidone (Resperdal) [PMID: 11929370].
Serotonergic drugsa Singer HS et al: Baclofen treatment in Tourette syndrome: A dou-
Fluoxetine (Prozac) ble blind, placebo-controlled, crossover trial. Neurology
Paroxetine (Paxil) 2001;56:599 [PMID:11245709].
Sertraline (Zoloft) Snider LA et al: Tics and problem behavior in school children:
Anafranil (Clomipromine) Prevalence, characterization, and associations. Pediatrics
Fluvoxamine (Luvox) 2002;110:331 [PMID: 12165586].
Noradrenergic drugsb Zinner SH: Tourette disorder. Pediatr Rev 2000;21:372 [PMID:
Clonidine (Catapres) 11077021].
Guanfacine (Tenex)
Other 3. Paroxysmal Dyskinesias/Chronic
Clonazepam (Klonopin)
Baclofen (Lioresal) Dystonia
a
Useful for obsessive-compulsive disorder. Sudden-onset, short-duration choreoathetosis or dysto-
b
Useful for attention-deficit/hyperactivity disorder. nia episodes occur in childhood. Most often these
786 / CHAPTER 23

episodes are familial and genetic. Episodes may occur tential for causing catastrophic destruction of the ner-
spontaneously or be set off by actions (“kinesiogenic,” vous system. It is imperative for the clinician to recog-
or movement-induced) such as rising from a chair, nize infections early in order to treat and prevent mas-
reaching for a glass, or walking. Sometimes only hard sive tissue destruction.
sustained exercise will induce the dyskinesia. (Noctur-
nal dyskinesia/dystonic episodes are currently thought Clinical Findings
to be frontal lobe seizures.)
The diagnosis is clinical. Onset is usually in child- A. SYMPTOMS AND SIGNS
hood (1.5–14 years). The patient is alert and often dis- Patients with CNS infections, whether caused by bacte-
concerted during an episode. ria, viruses, or other microorganisms, present with simi-
Episodes may last seconds to 5–20 minutes and lar manifestations. Systemic signs of infection include
occur several times daily or monthly. Laboratory work fever; malaise; and impaired heart, lung, liver, or kidney
is normal. EEG is normal between or during an attack; function. General features suggesting CNS infection in-
brain imaging is normal. Inheritance is usually autoso- clude headache, stiff neck, fever or hypothermia,
mal dominant. Anticonvulsants (eg, carbamazepine) changes in mental status (including hyperirritability
usually prevent further attacks. Patients often grow out evolving into lethargy and coma), seizures, and focal
of this disease in one or two decades. sensory and motor deficits. Meningeal irritation is man-
Nonkinesiogenic dyskinesia is often secondary to an ifested by the presence of Kernig and Brudzinski signs.
identifiable brain lesion, less or not responsive to med- In very young infants, signs of meningeal irritation may
ications, and nongenetic. be absent, and temperature instability and hypothermia
Disorders of ion channels underlie many of the ge- are often more prominent than fever. In young infants,
netic cases; some cases are linked to epilepsy and hemi- a bulging fontanelle and an increased head circumfer-
plegic migraine. Chromosome loci are known. ence are common. Papilledema may eventually develop,
The diagnosis of chronic persistent dystonia (some- particularly in older children and adolescents. Cranial
times Ldopa-responsive) may be aided by spinal fluid nerve palsies may develop acutely or gradually during
neurotransmitter and genetic chromosome studies. the course of neurologic infections. No specific clinical
Rarely, dyskinesia (e.g., dystonia) may be precipitated sign or symptom is reliable in distinguishing bacterial
by fever. And, chorea (rarely) may be a benign life-long infections from infections caused by other microbes.
genetic disease. During the initial clinical assessment, conditions
that predispose the patient to infection of the CNS
Anca MH et al: Natural of Oppenheim’s dystonia (DYT1) in Is- should be sought. Infections involving the sinuses or
rael. J Child Neurol 2003;18:325 [PMID: 12822816]. other structures in the head and neck region can result
Bandmann O, Wood NW: Dopa-response dystonia—The story so in direct extension of infection into the intracranial
far. Neuropediatrics 2002;33:1 [PMID: 11930268]. compartment. Open head injuries, recent neurosurgical
Dooley JM et al: Fever-induced dystonia. Pediatr Neurol 2003;28: procedures, immunodeficiency, and the presence of a
149 [PMID: 12699869]. mechanical shunt may predispose to intracranial infec-
Kleiner-Fisman G et al: Benign hereditary chorea: Clinical, genetic tion.
and pathological findings. Ann Neurol 2003:54:244 [PMID:
12891678]. B. LABORATORY FINDINGS
MGrath TM, Dure LS: Paroxysmal dyskinesias in children. Curr When CNS infections are suspected, blood should be
Treat Options Neurol 2003;5:275 [PMID: 12791193]. obtained for a complete blood count, general chemistry
Zorzi G et al: Paroxysmal dyskinesias in childhood. Pediatr Neurol panel, and culture. Most important, however, is obtain-
2003;28:168 [PMID: 12770667].
ing CSF. In the absence of focal neurologic deficits or
signs of increased intracranial pressure, CSF should be
obtained immediately from any patient in whom serious
CNS infection is suspected. When papilledema or focal
INFECTIONS & INFLAMMATORY motor signs are present, a lumbar puncture may be de-
DISORDERS OF THE CENTRAL layed until a neuroimaging procedure has been done to
NERVOUS SYSTEM exclude brain abscess or other space-occupying lesion. It
is generally safe to obtain spinal fluid from infants with
nonfocal neurologic examination even if the fontanelle
Infections of the CNS are among the most common is bulging. Spinal fluid should be examined for the pres-
neurologic disorders encountered by pediatricians. Al- ence of red and white blood cells, protein concentration,
though infections are among the CNS disorders most glucose concentration, bacteria, and other microorgan-
amenable to treatment, they also have a very high po- isms; a sample should be cultured. In addition, sero-
 NEUROLOGIC & MUSCULAR DISORDERS / 787

logic, immunologic, and nucleic acid detection (PCR) cutely (symptoms evolving over 1–7 days), or chroni-
tests may be performed on the spinal fluid in an attempt cally (symptoms evolving over more than 1 week). Dif-
to identify the specific organism. As a general rule, fuse bacterial infections involve the leptomeninges, su-
spinal fluid that contains a high proportion of polymor- perficial cortical structures, and blood vessels. Although
phonuclear leukocytes, a high protein concentration, the term “meningitis” is used to describe these infec-
and a low glucose concentration strongly suggests bacte- tions, it should not be forgotten that the brain
rial infection (see Chapter 38). CSF containing predom- parenchyma is also inflamed and that blood vessel walls
inantly lymphocytes, a high protein concentration, and may be infiltrated by inflammatory cells that result in
a low glucose concentration suggests infection with my- endothelial cell injury, vessel stenosis, and secondary is-
cobacteria, fungi, uncommon bacteria, and some viruses chemia and infarction.
such as lymphocytic choriomeningitis virus, herpes sim- Pathologically, the inflammatory process involves all
plex virus, mumps virus, and arboviruses (see Chapters intracranial structures to some degree. Acutely, this in-
36 and 39). CSF that contains a high proportion of flammatory process may result in cerebral edema or im-
lymphocytes, normal or only slightly elevated protein paired CSF flow through and out of the ventricular sys-
concentration, and a normal glucose concentration is tem, resulting in hydrocephalus.
most suggestive of viral infections, although partially
treated bacterial meningitis and parameningeal infec- Treatment
tions may also result in this type of CSF formula. Typi-
cal CSF findings in a variety of infectious and inflam- A. SPECIFIC MEASURES
matory disorders are shown in Table 23–3. (See also Chapter 35 and the Haemophilus influenzae
In some cases, brain biopsy may be needed to identify Type B Infections section in Chapter 38.)
the presence of specific organisms and clarify the diagno- While awaiting the results of diagnostic tests, the
sis. Herpes simplex virus infections can be confirmed physician should start broad-spectrum antibiotic cover-
using the PCR test to assay for herpes DNA in spinal age as noted in the following discussion. After specific
fluid. This test has a 95% sensitivity and 99% specificity. organisms are identified, antibiotic therapy can be tai-
Brain biopsy may be needed to detect the rare PCR-neg- lored based on antibiotic sensitivity patterns. Bacterial
ative case of herpes simplex and various parasitic infec- meningitis in children younger than age 3 months is
tions, brain tumors, and other structural abnormalities. treated initially with cefotaxime (or ceftriaxone if the
child is older than age 1 month) and ampicillin; the lat-
C. IMAGING ter agent is used to treat Listeria and enterococci infec-
Neuroimaging with CT and MRI scans may be helpful tions, which rarely affect older children. Children older
in demonstrating the presence of brain abscess, than age 3 months are given ceftriaxone, cefotaxime, or
meningeal inflammation, or secondary problems such ampicillin plus gentamicin. If Streptococcus pneumoniae
as venous and arterial infarctions, hemorrhages, and cannot be ruled out by the initial Gram stain, van-
subdural effusions when these are expected. In addi- comycin or rifampin is added until cultures are re-
tion, these procedures may identify sinus or other focal ported, because penicillin-resistant pneumococci are
infections in the head or neck region that are related to common in the United States. Therapy may be nar-
the CNS infection. CT scanning may demonstrate rowed when organism sensitivity allows. Duration of
bony abnormalities, such as basilar fractures. therapy is 7 days for meningococcal infections, 10 days
EEGs may be helpful in the assessment of patients for H influenzae or pneumococcal infection, and
who have had seizures at the time of presentation. The 14–21 days for other organisms. Slow clinical response
changes are often nonspecific and characterized by gen- or the occurrence of complications may prolong the
eralized slowing. In some instances, such as herpes sim- need for therapy. Although therapy for 7 days has
plex virus infection, focal electronegative activity may proved successful in many children with H influenzae
be seen early in the course and may be one of the earli- infection, it cannot be recommended without further
est laboratory abnormalities to suggest the diagnosis. study if steroids are also used (see following discussion).
EEGs may also show focal slowing over regions of ab-
scesses. Unusual but characteristic electroencephalo- B. GENERAL AND SUPPORTIVE MEASURES
graphic patterns are seen in some patients with suba- Children with bacterial meningitis are often systemically
cute sclerosing panencephalitis. ill. The following complications should be looked for
and treated aggressively: hypovolemia, hypoglycemia,
hyponatremia, acidosis, septic shock, increased intracra-
BACTERIAL MENINGITIS nial pressure, seizures, disseminated intravascular coagu-
Bacterial infections of the CNS may present acutely lation, and metastatic infection (eg, pericarditis, arthri-
(symptoms evolving rapidly over 1–24 hours), suba- tis, pneumonia). Children should initially be monitored
788 / CHAPTER 23

closely (cardiorespiratory monitor, strict fluid balance the infecting organism is H influenzae, Meningococcus, or
and frequent urine specific gravity assessment, daily Pneumococcus. These are usually sterilized with the stan-
weights, neurologic assessment every few hours), not fed dard treatment duration, and slowly waning fever during
until neurologically very stable, isolated until the organ- an otherwise uncomplicated recovery may be followed
ism is known, rehydrated with isotonic solutions until clinically. Under any other circumstance, however, aspi-
euvolemic, and then given intravenous fluids containing ration of the fluid for documentation of sterilization or
dextrose and sodium at no more than maintenance rate for relief of pressure should be considered.
(assuming no unusual losses occur). Cerebral edema can participate in the production of
increased intracranial pressure, requiring treatment
Complications with dexamethasone, osmotic agents, diuretics, or hy-
perventilation; continuous pressure monitoring may be
Abnormalities of water and electrolyte balance result needed.
from either excessive or insufficient production of an- Long-term sequelae of meningitis result from direct
tidiuretic hormone and require careful monitoring and inflammatory destruction of brain cells, vascular in-
appropriate adjustments in fluid administration. Moni- juries, or secondary gliosis. Focal motor and sensory
toring serum sodium every 8–12 hours during the first deficits, visual impairment, hearing loss, seizures, hy-
1–2 days, and urine sodium if the inappropriate secre- drocephalus, and a variety of cranial nerve deficits can
tion of antidiuretic hormone is suspected, usually un- result from meningitis. Sensorineural hearing loss in H
covers significant problems. influenzae meningitis occurs in approximately 5–10%
Seizures occur in up to 30% of children with bacter- of patients during long-term follow-up. Recent studies
ial meningitis. Seizures tend to be most common in have suggested that early addition of dexamethasone to
neonates and less common in older children. Persistent the antibiotic regimen may modestly decrease the risk
focal seizures or focal seizures associated with focal neu- of hearing loss in some children with H influenzae
rologic deficits strongly suggest subdural effusion, ab- meningitis (see Chapter 38).
scess, or vascular lesions such as arterial infarct, cortical In addition to the variety of disorders mentioned
venous infarcts, or dural sinus thrombosis. Because gen- earlier in this section, some patients with meningitis
eralized seizures in a metabolically compromised child have mental retardation and severe behavioral disorders
may have severe sequelae, early recognition and therapy that limit their function at school and later perfor-
are critical; some practitioners prefer phenytoin for mance in life. Table 23–24 lists the overall mortality
acute management because it is less sedating than phe- and morbidity figures for the most common organisms
nobarbital. associated with acute bacterial meningitis in childhood.
Subdural effusions occur in as many as 50% of young
children with H influenzae meningitis. Subdural effu-
sions are often seen on CT scans of the head during the BRAIN ABSCESS
course of meningitis. They do not require treatment un-
less they are producing increased intracranial pressure or
Clinical Findings
progressive mass effect. Although subdural effusions may Patients with brain abscess often appear to have systemic
be detected in children who have persistent fever, such illness similar to patients with bacterial meningitis, but
effusions do not usually have to be sampled or drained if in addition they show signs of focal neurologic deficits,

Table 23–24. Outcome of acute bacterial meningitis by organism.

Motor Handicap (%) Intellect (%)

Severe Mental
Organism Mortality (%) None Severe Normal Retardation
Escherichia coli, other coliforms 20–50 62 25 75 25
Haemophilus influenzae 5–10 87 3 82 5
Streptococcus pneumoniae 10–30 96 0 83 0
Neisseria meningitidis 5–10 100 0 93 0
Group B streptococci 20 85 10–15 100 0
Overall total 10–25 85 5 82 6
 NEUROLOGIC & MUSCULAR DISORDERS / 789

papilledema, and other evidence of increased intracra- lead to irreversible tissue destruction and may rupture
nial pressure or a mass lesion. Symptoms may be present into the ventricle, producing catastrophic deterioration
for a week or more; children with bacterial meningitis in neurologic function and death. Because brain ab-
usually present within a few days. Conditions predispos- scesses are often associated with systemic illness and sys-
ing to development of brain abscess include penetrating temic infections, the death rate is frequently high in
head trauma; chronic infection of the middle ear, mas- these patients.
toid, or sinuses (especially the frontal sinus); chronic
dental or pulmonary infection; cardiovascular lesions al-
lowing right-to-left shunting of blood (including arteri-
VIRAL INFECTIONS
ovenous malformations); and endocarditis. Viral infections of the CNS can involve primarily
When brain abscess is strongly suspected, a neu- meninges (meningitis) (see Chapter 36) or cerebral
roimaging procedure such as CT or MRI scans should parenchyma (encephalitis). All patients, however, have
be done prior to lumbar puncture. If a brain abscess is some degree of involvement of both the meninges and
identified, lumbar puncture may be dangerous and cerebral parenchyma (meningoencephalitis). Many viral
rarely alters the choice of antibiotic or clinical manage- infections are generalized and diffuse, but some viruses,
ment since the CSF abnormalities usually reflect only notably herpes simplex and some arboviruses, charac-
parameningeal inflammation. With spread from conta- teristically cause prominent focal disease. Focal cerebral
gious septic foci, streptococci and anaerobic bacteria are involvement is clearly evident on neuroimaging proce-
most common. Staphylococci most often enter from dures. Some viruses have an affinity for specific CNS
trauma or from infections. Enteric organisms may form cell populations. Poliovirus and other enteroviruses can
an abscess from chronic otitis. Unfortunately, cultures selectively infect anterior horn cells (poliomyelitis) and
from a large number of brain abscesses remain negative. some intracranial motor neurons.
The diagnosis of brain abscess is based primarily on Although most viral infections of the nervous system
a strong clinical suspicion and confirmed by a neu- have an acute or subacute course in childhood, chronic
roimaging procedure. EEG changes are nonspecific but infections can occur. Subacute sclerosing panencephali-
frequently demonstrate focal slowing in the region of tis, for example, represents a chronic indolent infection
brain abscess. caused by measles virus and is characterized clinically
by progressive neurodegeneration and seizures.
Treatment Inflammatory reactions within the nervous system
may occur during the convalescent stage of systemic
Initial therapy for infection from presumed contagious viral infections. Parainfectious or postinfectious inflam-
foci uses penicillin and metronidazole. Cefotaxime is a mation of the CNS results in several well-recognized
good alternative to penicillin, especially if enteric organ- disorders: acute disseminated encephalomyelitis (25%
isms are suspected. Enteric organisms are also often sus- of encephalitis), transverse myelitis, optic neuritis,
ceptible to trimethoprim–sulfamethoxazole. Suspicion polyneuritis, and Guillain–Barré syndrome.
of infection by staphylococci, or their recovery from an Congenital viral infections can also affect the CNS.
aspirate, should be treated with nafcillin or vancomycin. CMV, herpes simplex virus, and rubella virus are the
Treatment may include neurologic consultation and an- most notable causes of viral brain injury in utero.
ticonvulsant and edema therapy if necessary. In their Treatment of CNS viral infections is usually limited
early stages, brain abscesses are areas of focal cerebritis to symptomatic and supportive measures, except for
and can be “cured” with antibiotic treatment alone. herpes simplex virus. Acyclovir is the treatment in sus-
Well-developed abscesses require surgical drainage. pected or proved cases of herpes simplex virus en-
cephalitis. Acyclovir is also useful in some patients with
Differential Diagnosis varicella-zoster virus infections of the CNS. West Nile
virus, new in the United States, is an arthropod-borne
Differential diagnosis of brain abscess includes any con- flavivirus. It is found in mosquitoes, birds, and horses,
dition that produces focal neurologic deficits and in- and accounts for 27% of hospitalized patients in New
creased intracranial pressure, such as neoplasms, subdural York (1991) with encephalitis and muscle weakness.
effusions, cerebral infarctions, and certain infections Fourteen percent had encephalitis alone, and 6% had
(herpes simplex, cysticercosis, and toxocariasis). aseptic meningitis. CSF antibody studies and PCR
(57% positive for viral RNA) were diagnostic aids. The
infection is now endemic as far as the western United
Prognosis States, particularly in Colorado. Recent studies have
The surgical mortality rate in the treatment of brain ab- suggested spread of the infection to mosquitoes further
scess is lower than 5%. Untreated cerebral abscesses south along the Atlantic seaboard.
790 / CHAPTER 23

Encephalopathy of HIV Infection direct CNS inflammation or infection. Reye syndrome

is a prominent example of this type of encephalopathy
Neurologic syndromes associated directly with HIV in- that often occurs in association with varicella virus or
fection include subacute encephalitis, meningitis, other respiratory or systemic viral infections. In Reye
myelopathy, polyneuropathy, and myositis. In addi- syndrome, cerebral edema and cerebral dysfunction
tion, secondary opportunistic infections of the CNS occur, but there is no evidence of any direct involve-
occur in patients with HIV-induced immunosuppres- ment of the nervous system by the associated microor-
sion. Toxoplasma and CMV infections are particularly ganism or inflammation. Cerebral edema in Reye syn-
common. Progressive multifocal leukoencephalopathy, drome is accompanied by liver dysfunction and fatty
a secondary papillomavirus infection, and herpes sim- infiltration of the liver. As a result of efforts to discour-
plex and varicella-zoster infections also occur frequently age use of aspirin in childhood febrile illnesses, the
in patients with HIV infection. A variety of fungal (es- number of patients with Reye syndrome has markedly
pecially cryptococcal), mycobacterial, and bacterial in- decreased. The precise relationship, however, between
fections have been described. aspirin and Reye syndrome is unclear.
Neurologic abnormalities in these patients can also
be the result of noninfectious neoplastic disorders. Pri-
Aronin SI, Quagliarello VJ: New perspectives on pneumococcal
mary CNS lymphoma and metastatic lymphoma to the meningitis. Hosp Pract (Off Ed):36:43,49,51 [PMID:
nervous system are the most frequent neoplasms of the 11220360].
nervous system in these patients. See Chapters 29, 35, De Tiege X et al: Herpes simplex encephalitis relapses in children.
and 37 for diagnosis and management of HIV infec- Neurology 2003;61:241 [PMID: 12874408].
tion. Hunson JL et al: Clinical and neuroradiologic features of acute dis-
seminated encephalomyelitis in children. Neurology
2001;56:1308 [PMID: 11376179].
OTHER INFECTIONS Kimberlin DW et al: Natural history of neonatal herpes simplex
A wide variety of other microorganisms, including Tox- virus infections in the acyclovir era. Pediatrics 2001;108:223
oplasma, mycobacteria, spirochetes, rickettsiae, amoe- [PMID: 11484781].
bae, and mycoplasmas, can cause CNS infections. CNS Krshna Murthy SN et al: Acute disseminated encephalomyelitis in
children. Pediatrics 2002;110:e21 [PMID: 12165620].
involvement in these infections is usually secondary to
systemic infection or other predisposing factors. Appro- Nolan MA et al: Survival after pulmonary edema due to enterovirus
71 encephalitis. Neurology 2003;60:1651 [PMID: 12771257].
priate cultures and serologic testing are required to con-
Redington JJ, Tyler KL: Viral infections of the nervous system,
firm infections by these organisms. Parenteral antimi- 2002. Arch Neurol 2002;59:712 [PMID: 12020250].
crobial treatment for these infections is discussed in Sazgar M et al: Influenza B acute necrotizing encephalopathy: A
Chapter 35. case report and literature review. Pediatr Neurol
2003;28:396 [PMID: 12878304].
NONINFECTIOUS INFLAMMATORY Sejvar JJ et al: Neurologic manifestations and outcome of west Nile
virus infection. JAMA 2003;290:511 [PMID: 12876094].
DISORDERS OF THE CENTRAL Straussberg R et al: Improvement of atypical acute disseminated en-
NERVOUS SYSTEM cephalomyelitis with steroids and intravenous immunoglobu-
lins. Pediatr Neurol 2001;24:139 [PMID: 11275464].
The differential diagnosis of bacterial, viral, and other
Tenembaum S et al: Acute disseminated encephalomyelitis. Neu-
microbial infections of the CNS includes disorders that rology 2002;59:1224 [PMID: 12391351].
cause inflammation but for which no specific causal or- Toth C et al: Neonatal herpes encephalitis: A case series and review
ganism has been identified. Sarcoidosis, Behçet disease, of clinical presentations. Can J Neurol Sci 2003;30:36
systemic lupus erythematosus, other collagen–vascular [PMID: 12619782].
disorders, and Kawasaki disease are examples. In these Tyler KL: West Nile virus encephalitis in America (editorial).
disorders, CNS inflammation usually occurs in associa- N Engl J Med 2001;344:1858 [PMID: 11407349].
tion with characteristic systemic manifestations that
allow proper diagnosis. Management of CNS involve- SYNDROMES PRESENTING AS ACUTE
ment in these disorders is the same as the treatment of
the systemic illness. FLACCID PARALYSIS
Flaccid paralysis evolving over hours or a few days sug-
OTHER PARAINFECTIOUS gests involvement of the lower motor neuron complex
(see Floppy Infant Syndrome section). Anterior horn
ENCEPHALOPATHIES cells (spinal cord) may be involved by viral infection
In association with systemic infections or other ill- (paralytic poliomyelitis) or by paraviral or postviral im-
nesses, CNS dysfunction may occur in the absence of munologically mediated disease (acute transverse
 NEUROLOGIC & MUSCULAR DISORDERS / 791

myelitis). The nerve trunks (polyneuritis) may be dis- venous drug abuse can lead to myelitis and paralysis.
eased as in Guillain–Barré syndrome or affected by tox- Furthermore, chronic myelopathy occurs with two
ins (diphtheria, porphyria). The neuromuscular junc- human immunodeficiency virus infections: HTLV-I
tion may be blocked by tick toxin or botulinum toxin. and HTLV-III (now called HIV-1).
The paralysis rarely will be due to metabolic (periodic
paralysis) or inflammatory muscle disease (myositis). A Complications
lesion compressing the spinal cord must be ruled out.
A. RESPIRATORY PARALYSIS
Clinical Findings Early and careful attention to oxygenation is essential. Ad-
ministration of oxygen, intubation, mechanical respiratory
A. SYMPTOMS AND SIGNS assistance, and careful suctioning of secretions may be re-
Features assisting diagnosis are age, a history of preced- quired. Increasing anxiety and a rise in diastolic and sys-
ing or waning illness, the presence (at time of paralysis) tolic blood pressures are early signs of hypoxia. Cyanosis is
of fever, rapidity of progression, cranial nerve findings, a late sign. Deteriorating spirometric findings (forced ex-
and sensory findings (Table 23–25). The examination piratory volume in 1 second [FEV1] and total vital capac-
may show long tract findings (pyramidal tract), causing ity) may indicate the need for controlled intubation and
increased reflexes and a positive Babinski sign. The respiratory support. Blood gases (usually late changes with
spinothalamic tract may be interrupted, causing loss of increased CO2, decreased O2) can aid decisions.
pain and temperature. Back pain, even tenderness to
percussion, may occur, as well as bowel and bladder in- B. INFECTIONS
continence. Often the paralysis is ascending, symmet- Pneumonia is common, especially in patients with res-
ric, and painful (muscle tenderness or myalgia). Labora- piratory paralysis. Antibiotic therapy is best guided by
tory findings occasionally are diagnostic. results of cultures. Bladder infections occur when an in-
dwelling catheter is required because of bladder paraly-
B. LABORATORY FINDINGS (SEE TABLE 23–25) sis. Recovery from myelitis may be delayed by urinary
Examination of CSF is helpful. Imaging studies of the tract infection.
spinal column (plain radiographs) and spinal cord
(MRI, myelogram) are occasionally essential. Viral cul- C. AUTONOMIC CRISIS
tures (CSF, throat, stool) and titers aid in diagnosing This may be a cause of death in Guillain–Barré syn-
poliomyelitis. A high sedimentation rate may suggest drome. Strict attention to vital signs to detect and treat
tumor or abscess; the presence of antinuclear antibody hypotension or hypertension and cardiac arrhythmias
may suggest lupus arteritis. in an intensive care setting is advisable, at least early in
EMG and nerve conduction velocity can be helpful in the course and in severely ill patients.
diagnosing polyneuropathy. Nerve conduction is usually
slowed after 7–10 days. Findings in botulism and tick- Treatment
bite paralysis can be specific and diagnostic. Rarely, eleva-
tion of muscle enzymes or even myoglobinuria may aid in Most of these syndromes have no specific treatment.
diagnosis of myopathic paralysis. Porphyrin urine studies Ticks causing paralysis must be removed. Other thera-
and heavy-metal assays (arsenic, thallium, lead) can reveal pies include the use of erythromycin in Mycoplasma in-
those rare toxic causes of polyneuropathic paralysis. fections and botulism equine antitoxin in wound botu-
lism. Recognized associated disorders (eg, endocrine,
Differential Diagnosis neoplastic, toxic) should be treated by appropriate
means. Supportive care also involves pulmonary toilet,
The child who has been well and becomes paralyzed adequate fluids and nutrition, bladder and bowel care,
often has polyneuritis. Acute transverse myelitis some- prevention of decubiti, and, in many cases, psychiatric
times occurs in an afebrile child. The child who is ill support.
and febrile at the time of paralysis often has acute trans-
verse myelitis or poliomyelitis. Acute epidural spinal A. CORTICOSTEROIDS
cord abscess (or other compressive lesion) must be ruled These agents are believed by most to be of no benefit in
out. Poliomyelitis is very rare in our immunized popu- Guillain–Barré syndrome. Autonomic symptoms (eg,
lation. Paralysis due to tick bites occurs seasonally hypertension) in polyneuritis may require treatment.
(spring and summer). The tick is usually found in the
occipital hair. Removal is curative. B. PLASMAPHERESIS
Paralysis due to botulinum toxin occurs most com- Plasma exchange or intravenous IgG has been beneficial
monly younger than age 1 year (see Chapter 38). Intra- in severe cases of Guillain–Barré syndrome.
Table 23–25. Acute flaccid paralysis in children.

Poliomyelitis
(Paralytic, Spinal, Landry-Guillain-Barré Transverse
and Bulbar), With Syndrome (“Acute Myelitis and
or Without Idiopathic Tick-Bite Neuromyelitis
Encephalitis Polyneuritis”) Botulism Paralysis Optica
Etiology Poliovirus types I, II, Likely delayed hyper- Clostridium botuli- Probable interfer- Usually unknown;
and III; other en- sensitivity—with T-cell- num toxin. Block at ence with trans- multiple viruses
teroviruses; entero- mediated anti- neuromuscular mission of nerve (herpes, EBV, var-
viruses, eg EV71; ganglioside antibodies. junction. Under impulse caused by icella, hepatitis A)
vaccine strain polio Mycoplasmal and viral age 1, toxin syn- toxin in tick saliva often postviral (see
virus (rare); infections (EBV, CMV), thesized in bowel Guillain–Barré
West Nile virus: Campylobacter jejuni, by organisms in in- syndrome)
epidemic in birds. Hepatitis B. jested dust or hon-
Mosquitoes infect ey. At older ages
horses, humans toxin injested in
food. Rarely from
wound infection.
History None, or inadequate Nonspecific respiratory Infancy: dusty en- Exposure to ticks Rarely symptoms
polio immunization. or gastrointestinal vironment (eg, (dog tick in eastern compatible with
Upper respiratory or symptoms in preceding construction area), United States; multiple sclerosis or
gastrointestinal 5–14 d common. honey. Older: food wood ticks). Irrita- optic neuritis. Pro-
symptoms followed Any season, though poisoning. Multiple bility 12–24 h gression from onset
by brief respite. Bul- slightly lower incidence cases hours to before onset of a to paraplegia often
bar paralysis more in summer. days after ingest- rapidly progres- rapid, usually with-
frequent after tonsil- ing contaminated sive ascending out a history of
lectomy. Often in epi- food. paralysis. bacterial infection.
demics, in summer
and early fall.
Presenting Febrile at time of pa- Symmetrical weakness of Infancy: constipa- Rapid onset and Root and back pain
complaints ralysis. Meningeal lower extremities, which tion, poor suck progression of as- in about one-third to
signs, muscle tender- may ascend rapidly to and cry. “Floppy.” cending flaccid pa- one-half of cases.
ness, and spasm. arms, trunk, and face. Apnea. Lethargy. ralysis; often Sensory loss below
Asymmetrical weak- Verbal child may com- Choking (cause of accompanied by level of lesion ac-
ness widespread or plain of paresthesias. SIDS?). Older: pain and paresthe- companying rapidly
segmental (cervical, Fever uncommon. Fa- blurred vision, dip- sias. Paralysis of developing paraly-
thoracic, lumbar). cial weakness early. lopia, ptosis, chok- upper extremities sis. Sphincter diffi-
Bulbar symptoms Miller–Fisher variant ing, weakness. usually occurs on culties common.
early or before ex- presents as ataxia and second day after
tremity weakness; ophthalmoplegia (rare). onset.
anxiety; delirium.
Findings Flaccid weakness, Flaccid weakness, sym- Infants: Flaccid Flaccid, symmetric Paraplegia with
usually asymmetrical. metric, usually greater weakness. Alert. paralysis. Cranial areflexia below level
Cord level: proximally, but may be Eye, pupil, facial nerve and bulbar of lesion early; later,
Lumbar: legs, lower more distal or equal in weakness. Deep (respiratory) paral- may have hyperre-
abdomen distribution. Rarely tendon reflexes ysis, ataxia, sphinc- flexia. Sensory loss
Cervical: shoulder, cranial nerves IX–XI, III– decreased. ter disturbances, below and hyperes-
arm, neck, dia- VI. Miller–Fisher variant: Absent suck, gag. and sensory defi- thesia or normal
phragm ophthalmoplegia, ataxia. Constipation. cits may occur. sensation above
Bulbar: respiratory, Bulbar involvement may Older: paralysis ac- Some fever. Diag- level of lesion.
lower cranial occur. Slight distal im- commodation, eye nosis rests on find- Paralysis of bladder
nerves pairment of position, vi- movements. Weak ing tick, which is and rectum. Optic
Encephalopathy bration, touch; difficult swallow. Respira- especially likely to neuritis rarely may
accompanies para- to assess in young tory paralysis. be on occipital be present.
lysis in West Nile. children. scalp.

792
 NEUROLOGIC & MUSCULAR DISORDERS / 793

Table 23–25. Acute flaccid paralysis in children. (continued)

Poliomyelitis
(Paralytic, Spinal, Landry-Guillain-Barré Transverse
and Bulbar), With Syndrome (“Acute Myelitis and
or Without Idiopathic Tick-Bite Neuromyelitis
Encephalitis Polyneuritis”) Botulism Paralysis Optica
CSF Pleocytosis (20– Cytoalbuminologic dis- Normal Normal Usually no mano-
500+ cells) with PMN sociation; ten or fewer metric block; CSF
predominance in first mononuclear cells with may show increased
few days, later mono- high protein after first protein, pleocytosis
cytic preponderance. week. Normal glucose. with predominantly
Protein frequently IgG may be elevated. mononuclear cells,
elevated (50–150 West Nile will have cells; increased IgG
mg/dL). CSF IgM + in nerves can be involved
West Nile in a myeloradiculitis

Electromyo- Denervation after 10– Nerve conduction ve- EMG distinctive: Nerve conduction Normal early. De-
gram (EMG) 21 days. Nerve con- locities markedly BSAP (brief small slowed; returns nervation at level
duction normal. decreased; may be abundant poten- rapidly to normal of lesion after 10–
Amplitude reduced normal early, or if axon tials). after removal of 21 d.
in West Nile only damage. tick
Other studies Virus in stool and Search for specific Infancy: stool cul- Leukocytosis, Normal spine x-rays
throat. Serial serolo- cause such as infection, ture, toxin. Rare often with moder- do not exclude spi-
gic titers IgG, IgM in intoxication, auto- serum toxin pos- ate eosinophilia nal epidural ab-
West Nile Hyponatre- immune disease. Anti- itive. Older: serum scess. MRI to rule
mia 30% in West Nile. ganglioside antibodies (or wound) toxin. out cord-com-
to GM1 (GQ1b in Miller– pressive lesions.
Fisher) Cord may be
swollen in myelitis.
Course and Paralysis usually Course progressive Infancy: support- Total removal of Large degree of
prognosis maximal 3–5 d after over a few days to ive. Penicillin. tick is followed by functional recovery
onset. Transient about 2 weeks. Note: Botulism immune rapid improve- possible. Cortico-
bladder paralysis Threat greatest from globulin intrave- ment and recovery. steroids are of con-
may occur. Outlook respiratory failure (10%), nous (BIG-IV). Otherwise, mor- troversial benefit in
varies with extent autonomic crises Respiratory support, tality rate due to shortening dura-
and severity of in- (eg, widely variable gavage feeding. respiratory paral- tion of acute attack
volvement. Note: blood pressure, Avoid aminoglyco- ysis is very high. or altering the
Mortality greatest arrhythmia), and super- sides. Older: peni- overall course.
from respiratory infection. Majority cillin, antitoxin,
failure and super- recover completely. prolonged respira-
infection. West Nile Plasmapheresis may tory support. Prog-
paralysis may be have a role. Intravenous nosis: excellent
permanent IgG. Relapses Fatality 3%
occasionally occur.
CMV = cytomegalovirus; CSF = cerebrospinal fluid; EBV = Ebstein–Barr virus; PMN = polymorphonuclear neutrophil; SIDS = sudden infant
death syndrome.
794 / CHAPTER 23

C. PHYSICAL THERAPY Electromyography

Rehabilitative measures are best instituted when acute EMG is often helpful in grossly differentiating myo-
symptoms have subsided and the patient is stable. pathic from neurogenic processes. Fibrillations occur in
D. ANTIBIOTICS both. In the myopathies, very low spikes are more typi-
cal, and the motor unit action potentials seen during
Appropriate antibiotics and drainage are required for
contraction characteristically are of short duration, are
epidural abscess.
polyphasic, and are increased in number for the
Ahmed S et al: Guillain–Barré syndrome: An unusual presentation strength of the contraction (increased interference pat-
of West Nile virus infection. Neurology 2000;55:144 tern). Neurogenic findings include decreased numbers
[PMID: 10891928]. of motor units, which may be polyphasic, larger than
Ammache Z et al: Childhood Guillain–Barré syndrome: Clinical normal, or both. The interference pattern is decreased.
and electrophysiologic features predictive of outcome. J Child In myotonic dystrophy, the EMG is characterized by
Neurol 2001;16:477 [PMID: 11453442]. prolonged discharge of electrical activity on movement
Cheng TL: Infant botulism. Pediatr Rev 2000;21:427 [PMID: of the probing needle (so-called dive bomber sound).
11121502].
Concepcion K: Guillain–Barré. Pediatr Rev 2001;22:22 [PMID:
11229324].
Defresne P et al: Acute transverse myelitis in children: Clinical
Muscle Biopsy
course and prognostic factors. J Child Neurol 2003;18:401 Properly executed (by open biopsy or by using the
[PMID: 12886975].
Bergstrom muscle biopsy needle), this procedure is usu-
Graf WD et al: Outcome in severe pediatric Guillain–Barré syn- ally helpful. Histochemical techniques, histogram
drome after immunotherapy or supportive care. Neurology
1999;52:1494 [PMID: 10227643]. analysis of muscle fiber types and sizes, and electron
Green DM, Ropper AH: Mild Guillain–Barré syndrome. Arch
microscopy are offering new classifications of the my-
Neurology 2001;58:1098 [PMID: 11448299]. opathies. Findings common to the muscular dystro-
Jeha LE et al: West Nile virus infection: A new acute paralytic ill- phies include variation in the size and shape of muscle
ness. Neurology 2003;61:55 [PMID:12847156]. fibers, increase in connective tissue, interstitial infiltra-
Mori M et al: Clinical features and prognosis of Miller–Fisher syn- tion of fatty tissue, degenerative changes in muscle
drome. Neurology 2001;56:1104 [PMID: 11320188]. fibers, and central location of nuclei.
MMWR, CDC: Infant botulism—New York City, 2001–2002. Dystrophin is a normal intracellular plasma mem-
MMWR 2003;52:21 [PMID: 12608714]. brane protein in muscle, the gene product missing in
Tekgul H et al: Outcome of axonal and demyelinating forms of Duchenne and Becker muscular dystrophies. Staining
Guillain–Barré syndrome in children. Pediatr Neurol the muscle for dystrophin aids in differentiating
2003;28:295 [PMID: 12849884]. Duchenne and Becker muscular dystrophies; dys-
Vedanarayanan VV et al: Tick paralysis in children: Electrophysiol- trophin is absent in Duchenne muscular dystrophy and
ogy and possibility of misdiagnosis. Neurology 2002;59: reduced in Becker muscular dystrophy. Electrophoresis
1088 [PMID: 12370471].
can confirm whether the dystrophin is absent or present
Vriesendorp FJ et al: Prognostic factors of Guillain–Barré syn-
drome after intravenous immunoglobulin or plasma ex-
in small amounts and whether there is a qualitative dif-
change. Neurology 1999;53:598 [PMID: 10449126]. ference from normal dystrophin, the latter two patterns
being characteristic of Becker muscular dystrophy.

DISORDERS OF CHILDHOOD Genetic Testing & Carrier Detection

AFFECTING MUSCLES (Table Previously, detection of carriers for Duchenne muscular
23–26) dystrophy (mothers and sisters of affected boys) rested
on creatine kinase elevations (two thirds of patients will
have this finding); physical findings of mild dystrophy
DIAGNOSTIC STUDIES (large calves, muscle weakness); abnormal muscle
EMGs; or biopsy results. All are unreliable for diagnos-
Serum Enzymes tic purposes.
Creatine kinase reflects muscle damage or “leaks” from DNA probes are now available for carrier detection
muscle into plasma. Blood should be drawn before and prenatal diagnosis of Duchenne and Becker muscu-
EMG or muscle biopsy, which may lead to release of the lar dystrophies. Deletions are often (60%) found on the
enzyme. Corticosteroids may suppress levels despite very short arm of the X chromosome; it is postulated that all
active muscle disease, for example, as in polymyositis. patients and most mothers will show deletions when
 NEUROLOGIC & MUSCULAR DISORDERS / 795

sufficient probes are developed to search the whole Mathrew KD, Moore SA: Limb-girdle muscular dystrophy. Curr
Duchenne genome (perhaps 4000 kb in length). Neurol Neurosci Rep 2003;3:78 [PMID: 12507416].
Amplification of DNA by the PCR test can detect Mendell JR: Congenital muscular dystrophy (editorial). Neurology
the deletion. Moreover, this technique plus Southern 2001;56:993 [PMID: 11320168].
blot analysis can detect abnormal DNA base repeats. Mercuri E et al: Phenotypic spectrum associated with mutations in
the fukutin-related protein gene. Ann Neurol 2003;53:537
For example, in myotonic dystrophy, a GCT triplet ex- [PMID: 12666124].
cess is currently the most sensitive test for that disease. Muntoni F et al: Sixth International congenital muscular dystrophy
The tests can be used for intrauterine diagnosis and workshop. Neuromuscul Disord 2002;12:69 [PMID:
prediction of whether the triplet is within the normal or 11731288].
mutant range. Thus, in many cases, the greater the Muntoni F: Cardiac complications of childhood myopathies.
number of repeats, the more severely involved the fetus J Child Neurol 2003;18:191 [PMID: 12731645].
or patient. Muntoni F et al: Defective glycosylation in muscular dystrophy.
Mutations (especially deletions) of survivor motor Lancet 2002;360:1419 [PMID: 12424008].
neuron (SMN) and neuronal apoptosis inhibitory pro- Palmucci L et al: Dystrophinopathy expressing as either cardiomy-
tein (NAIP) genes on chromosome 5q13 are present in opathy or Becker dystrophy in the same family. Neurology
95% of patients with spinal muscular atrophy. 2000;54:529 [PMID: 10668737].
Finally, Kearns–Sayre progressive external ophthal- Roland EH: Muscular dystrophy. Pediatr Rev 2000;21:233
moplegia with retinopathy is inherited via maternal cy- [PMID: 10878185].
toplasmic mitochondria. Assay of mutations and dele- Skuk D et al: Experimental and therapeutic approaches to muscular
dystrophies. Curr Opin Neurol 2002;15:563 [PMID:
tions from blood or muscle samples are now 12352000].
commercially available. Strober JB: Genetics of pediatric neuromuscular disease. Curr Opin
Therapy for Duchenne muscular dystrophy contin- Pediatr 2000 Dec;12(6):549 [PMID: 11106273].
ues to be frustrating. Prednisone in low doses has in- Tubridy N et al: Congenital myopathies and congenital muscular
creased muscle strength and prolonged ambulation. Re- dystrophies. Curr Opin Neurol 2001;14:575 [PMID:
search emphasis is on gene therapy, but there is great 11562568].
difficulty in finding viral vectors able to carry the very Zatz M et al: The 10 autosomal recessive limb-girdle muscular dys-
large dystrophin gene into muscle cells. trophies. Neuromuscul Disord 2003;13:532 [PMID:
12921790].
Zhang W et al: Enzymatic diagnostic test for muscle-eye-brain type
congenital muscular dystrophy using commercially available
Apkon SD: Osteoporosis in children who have disabilities. Phys reagents. Clin Biochem 2003;36:339 [PMID: 12849864].
Med Rehabil Clin North Am 2002;13:839 [PMID:
12465563].
Berven S, Bradford DS: Neuromuscular scoliosis: Causes of defor- BENIGN ACUTE CHILDHOOD MYOSITIS
mity and principles for evaluation and management. Semin
Neurol 2002;22:167 [PMID: 12524562]. Benign acute childhood myositis (myalgia cruris epi-
Bianchi ML et al: Bone mineral density and bone metabolism in demica) is characterized by transient severe muscle pain
Duchenne muscular dystrophy. Osteporos Int 2003;12:761 and weakness affecting mainly the calves and occurring
[PMID: 12897980]. 1–2 days following an upper respiratory tract infection.
Bonifati MD et al: A multicenter, double-blind, randomized trial of Although symptoms involve mainly the gastrocnemius
deflazacort versus prednisone in Duchenne muscular dystro- muscles, all skeletal muscles appear to be invaded di-
phy. Muscle Nerve 2000;23:1344 [PMID: 10951436]. rectly by virus; recurrent episodes are due to different
Bonnemann CG: Limb-girdle muscular dystrophies: An overview. viral types. By seroconversion or isolation of the virus,
J Child Neurology 1999;14:31 [PMID: 10223847]. acute myositis has been shown to be largely due to in-
Gendron NH, MacKenzie AE: Spinal muscular atrophy: Molecular fluenza types B and A and occasionally due to parain-
pathophysiology. Curr Opin Neurol 1999;12:137 [PMID:
10226744].
fluenza and adenovirus.
Grewal PK, Hewitt JE: Glycosylation defects: A new mechanism
for muscular dystrophy? Hum Mol Genet 2003; 12 Spec No MYASTHENIA GRAVIS
2:R259-64 [PMID: 12925572].
Kapsa R et al: Novel therapies for Duchenne muscular dystrophy.
Lancet Neurol 2003;2:299 [PMID: 12849184]. ESSENTIALS OF DIAGNOSIS
Komura K et al: Effectiveness of creatine monohydrate in mito- & TYPICAL FEATURES
chondrial encephalomyopathies. Pediatr Neurol 2003;28:53
[PMID: 12657421].
Lois M et al: Beneficial effects of creatine supplementation in dys- • Weakness, chiefly of muscles innervated by the
trophic patients. Muscle Nerve 2003;27:604 [PMID: brainstem, usually coming on or increasing with
12707981]. use (fatigue).
796 / CHAPTER 23

Table 23–26. Muscular dystrophies and myotonias of childhood.

Early
Disease Genetic Pattern Age at Onset Manifestations Involved Muscles Reflexes
Muscular dystrophies X-linked recessive; 2–6 y; rarely Clumsiness, easy fa- Axial and proximal Knee jerks ±
Duchenne muscu- autosomal-recessive in infancy tigability on walking, before distal. Pelvic or 0; ankle
lar dystrophy unusual. 30–50% running, and climb- girdle; pseudophy- jerks + to ++
(pseudohypertrophic have no family ing stairs. Walking pertrophy of gastroc-
infantile) history. on toes; waddling nemius (90%),
gait. Lordosis. triceps brachii, and
(Climbing up on legs vastus lateralis.
rising from supine Shoulder girdle usu-
position—Gower ally later, also articu-
maneuver.) lation difficulties.
Eventually cardiomy-
opathy (50%).
Becker muscular dys- X-linked recessive. Childhood (usu- Similar to Similar to Similar to
trophy (late onset) (Allele at Xp21) ally later than in Duchenne. Duchenne Duchenne
Duchenne)
Limb-girdle muscular Autosomal-recessive Variable; early Weakness, with dis- A. Pelvic girdle usu- Usually
dystrophy in 60%; high spo- childhood to tribution according to ally involved first and present
radic incidence. adulthood type. Waddling gait, to greater extent. B.
A. Pelvifemoral A. Relatively difficulty climbing Shoulder girdle often
(Leyden–Möbius) common stairs. Lordosis. asymmetric. Quadri-
B. Scapulohumeral B. Rare ceps and hamstrings
(Erb juvenile) may be weakest.
Facioscapulohumeral Autosomal-dominant; Usually late in Diminished facial Facial muscles fol- Present
muscular dystrophy sporadic cases not childhood and movements with in- lowed by shoulder
(Landouzy–Déjérine) uncommon: Linkage adolescence; ability to close eyes, girdle, with occa-
scapuloperoneal to 4q35 rare in infancy; smile, or whistle. sional spread to hips
variant (rare) not uncommon Face may be flat; un- or distal legs
in 20s lined. Difficulty in rais- (scapuloperoneal
ing arms over head. variant)
Lordosis. Tripping in
scapuloperoneal
type.
Spinal muscular atro- Autosomal-reces- 0–2 y Floppy infant Pelvic and shoulder 0 or nearly
phy (SMA) sive girdle. Tongue. In- so
Infantile SMA tercostals. Fingers and
(Werdnig–Hoffman toes spared.
disease)
Juvenile SMA Autosomal-reces- Onset after age Weakness. “Fascicu- Same Same
(Kugelburg–Welan- sive 2 usually (age lations” 50%. Rarely
der disease) 5–15 typical) a cause of floppy in-
fant.
Metabolic myopathies Genetics variable, Infancy to ado- Fasting hypoglyce- Weakness variable; Normal to
Carnitine deficiency often recessive lescence mia and coma; less may be precipitated decreased
(lipid storage ketosis than ex- by exercise (with re-
myopathy) pected. Myopathy. sultant myoglobulinu-
Primary (rare) Cardiomyopathy. ria) or fasting
Secondary: multiple Fatty liver. Don’t con-
forms fuse with Reye,
SIDS.
 NEUROLOGIC & MUSCULAR DISORDERS / 797

Muscle Biopsy Findings Other Diagnostic Tests Treatment Prognosis

Degeneration and variation in EMG myopathic. CK (4000– Physical therapy, braces, Ten percent show nonprogres-
fiber size; proliferation of 5000 IU) very high with de- wheelchair eventually, sive mental retardation. Osteo-
connective tissue. crease toward normal over weight control. Prednisone, porosis, scoliosis common.
Basophilia, phagocytosis. the years. 60% have C- deflazacort improve motor Death from cardiac or respira-
Poor differentiation of fiber terminal Xp21 deletion on function temporarily. Creatine, tory failure 10–15 y after diag-
types on ATPase reaction; blood, amniotic fluid or chor- Some benefit. Gene transfer nosis with 75% of patients dead
deficiency of type IIB fibers. ionic villi. Positive test minidystrophin by viral by age 20.
Dystrophin absent. obviates need for muscle vectors. Utrophin.
biopsy

Similar to above, except type Similar to above, although As above. Wheelchair in late Slower progression than
IIB fibers present. Reduced muscle enzymes may not be childhood or early adult life. Duchenne’s, with death usu-
or abnormal size dystrophin. as elevated ally in adulthood
Dystrophic muscle changes EMG myopathic. CK variable; Physical therapy, weight Mildly progressive: spread
(see Duchenne). Dystrophin many severe cases have sar- control from lower to upper limbs may
normal. Special stains for coglycan deficiency (severe take 15–20 y. Life expectancy
sarcoglycan (dystrophin autosomal recessive type). mid to late adulthood.
associated glycoprotein– Must exclude dystrophino-
DAG deficiency. pathy and SMA.

Predominantly large fibers with EMG myopathic. Muscle en- Physical therapy where indi- Very slowly progressive, often
scattered tiny atrophic fi- zymes usually normal. 4q35ter cated. Wheelchair in 20%. with plateaus, except in infan-
bers, “moth-eaten” and deletion. If blood test positive, Forty percent of biopsies tile form where there may be
whorled fibers. Inflammatory biopsy unnecessary show inflammation; steroids difficulties in walking by ado-
response. Little or no fiber ineffective, however. lescence. Usually normal life
splitting, fibrosis, or type 1 span.
fiber predominance.

Small, group atrophy. Twin EMG neuropathic. Nerve Supportive: respiratory care, 80–95% of patients 0–4 y
peak fiber size. Fiber type conduction, CSF, muscle en- positioning, secretion man- die of pneumonia and respira-
grouping. Minimal fibrosis. zymes normal. 90–95% have agement. Genetic coun- tory failure.
deletions or abnormalities seling.
in SMN (survival motor
neuron) or other genes at
Physical therapy, wheelchair Fairly normal life expectancy.
band 5q13.
Same positioning to avoid scoliosis. 4–40+ y.
May walk, usually later lose
this.
Lipid droplets ± or ragged red Muscle biochemistry (carni- Avoid fasting and mitochon- Variable: occasionally fatal in
fibers may be present. tine, CPT enzyme). Urine or- drial toxins, eg, ASA, valproic infants. Progressive weak-
ganic acids (at time of illness). acid. Carbohydrate. Treat aci- ness, developmental delay,
Plasma carnitine: deficiency dosis. Carnitine orally. cardiomyopathy may occur.
may be in blood alone or
blood and muscle.

(continued)
798 / CHAPTER 23

Table 23–26. Muscular dystrophies and myotonias of childhood. (continued)

Early
Disease Genetic Pattern Age at Onset Manifestations Involved Muscles Reflexes
“Oculocraniosomatic Mitochondrial DNA Variable; from Ptosis and limitation Extraocular muscles, Depressed
syndrome” (ophthal- deletion; other here- infancy to adult of eye movements; often asymmetric. to ± or 0
moplegia and “rag- ditary neurologic life; most at hearing and visual Variable involvement
ged reds”; progres- disorders may be about 10 y loss (retinitis of axial muscles; car-
sive external oph- found in patient or of age pigmentosa); intellec- diac muscles, with
thalmoplegia) family tual loss; cerebellar conduction defect.
Kearns–Sayre disturbance (ataxia)
Myasthenia gravis Variable At birth Difficulty sucking, Somatic and cranial Normal to
Transient neonatal swallowing; trouble muscles decreased
with secretions

Myasthenia gravis Variable Variable: birth, Same as transient Same as transient Same as
Persistent neonatal neonatal, in- form. form. transient
fancy form.
Congenital myopa- Autosomal-dominant At birth Same as myasthe- Cranial and somatic, Decreased
thies nia. Ptosis. Facial di- pharyngeal. to 0
Myotonic dystrophy plegia. Arthrogyposis,
(Neonatal onset) club feet, thin ribs.

“Other” myopathies Dominant or rarely Severe variants Severe variant, new- Similar to myotonic Decreased
Central core autosomal-recessive present at birth; borns with severe dystrophy to 0
Nemaline (rod x-linked recessive milder variants hypotonia and respira-
body) in neonatal form (more common) tory failure is rare.
Myotubular (cen- infancy, child- Later presentation—
tronuclear) hood facial weakness, mild
to moderate weak-
ness, even “toe walk-
ing” only.
Congenital muscu- Genetic; recessive. Birth to 9 mos. Hypotonia, joint con- Heterogenous. Fa- Variable
lar dystrophy chromosome tractures, mental re- cial (cranial) and so-
(Fukayama) 9q31–33. fuKutin tardation. matic. Contracture
(FCMD) mutations common.
Congenital muscu- Unknown; usually Birth (or early in- As above. Normal IQ. Same Same
lar dystrophy (oc- not familial; merosin- fancy) (merosin negative may
cidental) deficient variant 6q2 involve heart, nerves,
Many variants (8) and brain).
Benign congenital Variable Variable Hypotonia only. Somatic muscles Normal to
hypotonia (Op- Deep tendon reflexes (respiratory muscles decreased
penheim) positive. Laboratory spared)
tests, biopsy normal.
Myotonias Autosomal-dominant Early infancy to Difficulty in relaxing Hands especially; Normal
Myotonia congenita (autosomal-recessive late childhood muscles after con- muscles may be dif-
(Thomsen) cases reported) tracting them, espe- fusely enlarged, giv-
cially after sleep; ing patient herculean
aggravated by cold, appearance.
excitement.
 NEUROLOGIC & MUSCULAR DISORDERS / 799

Muscle Biopsy Findings Other Diagnostic Tests Treatment Prognosis

Mitochondrial abnormalities. CK usually normal. ECG with Plastic retraction of eyelids. Dysphagia may develop
“Ragged red” fibers. conduction block. CSF protein Cardiac support. Anticipate (50%) as well as generalized
Changes in fiber size, usu- elevated. Nerve conduction diabetes mellitus. muscle weakness. Prognosis
ally due to type 2 fiber atro- slowed. MRI of brain and Coenzyme Q? poor. In severe cases,
phy. brain stem auditory evoked re- spongy vacuolization of brain
sponse may be abnormal. Mi- and brain stem.
tochondrial deletions.
Unnecessary Edrophonium or neostigmine Supportive. Anticholinergic Usually transient (< 2 months)
tests. Acetylcholine receptor drugs.
(AChR) antibodies. Repetitive
nerve stimulation, EMG.
Sophisticated end plate, nerve May be similar to above. May not respond to ACh-ase Variable, may have long-term
terminal ultrastructural stud- AChR antibodies negative. drugs, steroids, or immuno- severe course.
ies may be necessary. suppressants
Generalized fiber hypertrophy, EMG myotonic in some Supportive, even respiratory Severely involved infant may
delay in maturation. Type I (waning amplitude and pitch). support. Genetic counseling. improve dramatically over
atrophy. Internal nuclei. Test mother. CK often normal. months; expect mental retar-
DNA testing (chromosome 19) dation in this same variant.
for GCT repeat.
Distinctive diagnostic histo- Myopathic EMG. Supportive. Genetic coun- Variable. May shorten life.
chemistry, eg, “central seling. Death in infancy or severe
cores,” “nemaline rods,” handicap in severe neonatal
myotubes type II–I fibers of form. Scoliosis prominent.
unequal size.

“Dystrophic” changes. Fibro- Myopathic EMG. CK in- Supportive. Physical and mental handicap
sis. Necrotic fibers. Internal creased. Positive CT, MRI lifelong. Virtually all are of
nuclei. ? regenerative fibers. scans: white matter low Japanese ancestry.
density, etc.
Same. Evaluate for merosin Brain imaging normal in pure Supportive. May improve, walk. Scoliosis.
(α-laminen-2 deficiency). form. Merosin-deficient form
may have white matter
abnormalities.
Normal with sophisticated Use of this diagnosis is shrink- Supportive Good (by definition). (Few
studies (histochemistry, ing with increasingly sophisti- documented long-term
electron microscopy, even cated biochemical (eg, studies.)
metabolic studies). cytochrome oxidase) studies.
Nonspecific and minor EMG myotonic. Usually none. Phenytoin, es- Normal life expectancy, with
changes; type IIB fibers pecially in cold weather, may only mild disability.
may be absent. improve muscle functioning.

(continued)
800 / CHAPTER 23

Table 23–26. Muscular dystrophies and myotonias of childhood. (continued)

Early
Disease Genetic Pattern Age at Onset Manifestations Involved Muscles Reflexes
Myotonic dystrophy I Autosomal-dominant Late childhood Myotonia of grasp, Wasting, weakness of In infantile
(Steinert) (child- to adolescence; tongue; worsened by facial muscles, (masti- form, marked
hood and adult neonatal and in- cold, emotions. cation); sternocleido- hyporeflexia
form) fantile forms in- “Hatchet-face.” Nasal mastoids, hands.
Myotonic dystrophy II creasingly voice. Weakness and Myotonic phenomena:
[Proximal myotonic recognized easy fatigability. Mild “bunching up” of
myopathy (PROMM)] (see above) to moderate mental muscles of tongue,
retardation noted. thenar eminance, fin-
ger extensors after
tapping with percus-
sion hammer.

• Positive response to neostigmine and edropho- rarely have myasthenia gravis, but other relatives may. Sex
nium. distribution is equal. Symptoms are often subtle and not
• Acetylcholine receptor antibodies in serum (ex- recognized initially. Differential diagnosis includes many
cept in congenital form). other causes of the “floppy infant” syndrome, such as in-
fant botulism, ocular myopathy, congenital ptosis, and
Möbius syndrome (facial nuclear aplasia and other anom-
alies). Congenital myasthenia gravis is not caused by re-
ceptor antibodies and often responds poorly to therapy. It
General Considerations may result from a genetic abnormality of the acetyl-
Myasthenia gravis is characterized by easy fatigability of choline receptor protein, postsynaptic membrane struc-
muscles, particularly the extraocular muscles and those ture, or other myoneural transmission defects.
of mastication, swallowing, and respiration. In the 3. Juvenile myasthenia gravis—In this autoimmune
neonatal period, however, or in early infancy, the weak- form, the symptoms and signs are similar to those in
ness may be so constant and general that an affected in- adults. Receptor antibodies are usually present. The pa-
fant may present nonspecifically as a “floppy infant.” tient may be first seen by an otolaryngologist or psychia-
Girls are affected more frequently than boys. The age at trist. The more prominent signs are difficulty in chew-
onset is older than 10 years in 75% of patients, often ing, dysphagia, a nasal voice, ptosis, and
shortly after menarche. If diagnosed before age ophthalmoplegia. Pathologic fatigability of limbs,
10 years, congenital myasthenia should be considered chiefly involving the proximal limb and neck muscles,
in retrospect. Thyrotoxicosis is found in almost 10% of may be more prominent than the bulbar signs and may
affected female patients. The essential abnormality is a lead to an initial diagnosis of conversion hysteria, mus-
circulating antibody that binds to the acetylcholine re- cular dystrophy, or polymyositis. Weakness may be lim-
ceptor protein and thus reduces the number of motor ited to ocular muscles only. Associated disorders include
end plates for binding by acetylcholine. autoimmune conditions, especially thyroid disease.
An acute fulminant form of myasthenia gravis has
Clinical Findings been reported in children age 2–10 years, who present
with rapidly progressive respiratory difficulties. Bulbar
A. SYMPTOMS AND SIGNS paralysis may evolve within 24 hours. There is no his-
1. Neonatal (transient) myasthenia gravis—This tory of myasthenia. The differential diagnosis includes
disorder occurs in 12% of infants born to myasthenic Guillain–Barré syndrome and bulbar poliomyelitis. Ad-
mothers. The condition is due to maternal acetyl- ministration of anticholinesterase agents establishes the
choline receptor antibody transferred across the pla- diagnosis and is lifesaving.
centa; a thymic factor in the infant may also be in-
volved. B. LABORATORY FINDINGS
2. Congenital (persistent) myasthenia gravis—In this 1. Neostigmine test—In newborns and very young
form of the disease, the mothers of the affected infants infants, the neostigmine test may be preferable to the
 NEUROLOGIC & MUSCULAR DISORDERS / 801

Table 23–26. (continued)

Muscle Biopsy Findings Other Diagnostic Tests Treatment Prognosis

Type I fiber atrophy, type II EMG markedly myotonic. Procainamide, 250 mg tid Frontal baldness, cataracts
hypertrophy, sarcoplasmic Glucose tolerance test, thy- orally, increased to tolerance; (85%), gonadal atrophy (85%
masses, internal nuclei, roid tests. ECG. Chest radio- phenytoin 5–7 mg/kg/d of males), thyroid dysfunction,
phagocytosis, fibrosis, and graph and pulmonary function orally. (Drugs usually little diabetes mellitus (20%). Car-
cellular reaction. tests. Immunoglobulins. PCR role.) diac conduction defects; im-
amplification of GCT repeat paired pulmonary function.
on chromosome 19q13 to dis- Low IgG. Life expectancy de-
tinguish normal from mutant creased.
alleles. CCTG repeat in zinc Type II—slowly progressive
finger protein gene. weakening; good outlook

ASA = acetyl salicyclic acid; CK = creatine kinase; CPT = carnitine palmityl transferase; CSF = cerebrospinal fluid; ECG = electrocardiogram;
EMG = electromyogram; PCR = polymerase chain reaction; SIDS = sudden infant death syndrome.

edrophonium (Tensilon) test because the longer dura- Treatment

tion of its response permits better observation, espe-
cially of sucking and swallowing movements. The test A. GENERAL AND SUPPORTIVE CARE
dose of neostigmine is 0.02 mg/kg subcutaneously, usu- In the newborn or in a child in myasthenic or choliner-
ally given with atropine, 0.01 mg/kg subcutaneously. gic crisis (see item 5 in the following section), suction-
There is a delay of about 10 minutes before the effect ing of secretions is essential. Respiratory assistance may
may be manifest. The physician should be prepared to be required. Treatment should be conducted by physi-
suction secretions. cians with experience in this disorder.
2. Edrophonium test—Testing with edrophonium is B. ANTICHOLINESTERASE DRUG THERAPY
used in older children who are capable of cooperating
in certain tasks, such as raising and lowering their eye- 1. Pyridostigmine bromide—The dosage must be
lids and squeezing a sphygmomanometer bulb or the adjusted for each patient. A frequent starting dosage is
examiner’s hands. The test dose is 0.1–1 mL intra- 15–30 mg orally every 6 hours.
venously, depending on the size of the child. Maximum 2. Neostigmine—Fifteen milligrams of neostigmine
improvement occurs within 2 minutes. are roughly equivalent to 60 mg of pyridostigmine bro-
3. Other laboratory tests—Serum acetylcholine re- mide. Neostigmine often causes gastric hypermotility
ceptor antibodies are often found in the neonatal and with diarrhea, but it is the drug of choice in newborns,
juvenile forms. Ophthalmologic tests of ocular motility in whom prompt treatment may be lifesaving. It may
with edrophonium are often positive in patients able to be given parenterally.
cooperate. In juveniles, thyroid studies are appropriate. 3. Atropine—Atropine may be added on a mainte-
C. ELECTRICAL STUDIES OF MUSCLE nance basis to control mild cholinergic side effects such
as hypersecretion, abdominal cramps, and nausea and
Repetitive stimulation of a motor nerve at slow rates vomiting.
(3/s) with recording over the appropriate muscle reveals
a progressive fall in amplitude of the muscle potential 4. Immunologic intervention—Such intervention is
in myasthenic patients. A maximal stimulus must be achieved primarily with prednisone. Plasmapheresis is
given. At higher rates of stimulation (50/s), there may effective in removing acetylcholine receptor antibody in
be a transient repair of this defect before the progressive severely affected patients.
decline is seen. If this study is negative, single-fiber 5. Myasthenic crisis—Relatively sudden difficulties in
EMG may be helpful diagnostically. swallowing and respiration may be observed in myas-
thenic patients. Edrophonium results in dramatic but
D. IMAGING brief improvement; this may make evaluation of the
Chest radiograph and CT scanning in older children condition of the small child difficult. Suctioning, tra-
may disclose benign thymus enlargement. Thymus tu- cheostomy, respiratory assistance, and fluid and elec-
mors are rare in children. trolyte maintenance may be required.
802 / CHAPTER 23

6. Cholinergic crisis—Cholinergic crisis may result bilaterally. Nuclear or peripheral involvement of the fa-
from overdosage of anticholinesterase drugs. The result- cial nerves results in sagging or drooping of the mouth
ing weakness may be similar to that of myasthenia, and and inability to close one or both eyes, particularly
the muscarinic effects (diarrhea, sweating, lacrimation, when newborns and infants cry. Inability to wrinkle the
miosis, bradycardia, hypotension) are often absent or forehead may be demonstrated in infants and young
difficult to evaluate. The edrophonium test may help to children by getting them to follow a light moved verti-
determine whether the patient is receiving too little of cally above the forehead. Loss of taste of the anterior
the drug or is manifesting toxic symptoms due to over- two thirds of the tongue on the involved side may be
dosage. Improvement after the drugs are withdrawn sug- demonstrated in cooperative children by age 4 or
gests cholinergic crisis. A respirator should be available. 5 years. Playing with a younger child and the judicious
The patient may require atropine and tracheostomy. use of a tongue blade may enable the physician to note
whether the child’s face puckers up when something
C. SURGICAL MEASURES sour (eg, lemon juice) is applied with a swab to the an-
Early thymectomy is beneficial in many patients whose terior tongue. Ability to wrinkle the forehead is pre-
disease is not confined to ocular symptoms; the effects served, owing to bilateral innervation, in supranuclear
may be delayed. Experienced surgical and postsurgical facial paralysis.
care are prerequisites. Injuries to the facial nerve at birth occur in
0.25–6.5% of consecutive live births. Forceps delivery
Prognosis is the cause in some cases; in others, the side of the face
Neonatal (transient) myasthenia presents a great threat affected may have abutted in utero against the sacral
to life, primarily because of secretion aspiration. With prominence. Often, no cause can be established.
proper treatment, the symptoms usually begin to disap- Acquired peripheral facial weakness (Bell’s palsy) of
pear within a few days to 2–3 weeks, after which the sudden onset and unknown cause is common in chil-
child usually requires no further treatment. In the con- dren. It often follows a viral illness (postinfectious) or
genital (persistent) form, the symptoms may initially be physical trauma (eg, cold). It may be a presenting sign
as acute as in the transient variety. More commonly, of tumor, Lyme disease, infectious mononucleosis, her-
however, they are relatively benign and constant, with pes simplex, or Guillain–Barré syndrome and is usually
gradual worsening as the child grows older. Fatal cases diagnosable by the history, physical examination, and
occur. In the juvenile form, patients may become resis- appropriate laboratory tests.
tant or unresponsive to anticholinesterase compounds Bilateral facial weakness in early life may be due to
and require corticosteroids or treatment in a hospital agenesis of the affected muscles or to nuclear causes
where respiratory assistance can be given. The overall (part of Möbius syndrome) or may even be familial.
prognosis for survival, for remission, and for improve- Myasthenia gravis, polyneuritis, and myotonic dystro-
ment after therapy with prednisone and thymectomy is phy must be considered.
favorable. Death in myasthenic or cholinergic crisis Asymmetrical crying facies, in which one side of the
may occur unless prompt treatment is given. lower lip depresses with crying (this is the normal side)
and the other does not, is a common innocent form of
Gajdos P et al: Clinical trial of plasma exchange and high dose in-
autosomal dominant inherited congenital malforma-
travenous immunoglobulin in myasthenia gravis. Ann Neurol tion. The defect in the parent (the asymmetry often im-
1997;41:789 [PMID: 9668320]. proves with age) may be almost inapparent. EMG sug-
Linduer A et al: Outcome in juvenile onset myasthenia gravis: A gests congenital absence of the depressor anguli oris
retrospective study with long-term follow-up of 79 patients. muscle of the lower lip. Forceps pressure is often erro-
J Neurol 1997;244:515 [PMID: 9309559]. neously incriminated as a cause of this innocent con-
Sommer N et al: Ocular myasthenia gravis: Response to long-term genital anomaly. Occasionally other major (eg, cardiac
immunosuppressive therapy. J Neurol Neurosurg Psychiatry septal defects) congenital defects accompany the palsy.
1997;62:156 [PMID: 9048716]. In the vast majority of cases of isolated peripheral fa-
Tsao CY et al: Myasthenia gravis and associated autoimmune dis- cial palsy—both those present at birth and those ac-
eases in children. J Child Neurol 2000;15:767 [PMID:
11108515].
quired later—improvement begins within 1–2 weeks,
and near or total recovery of function is observed
within 2 months. Methylcellulose drops, 1%, should be
PERIPHERAL NERVE PALSIES instilled into the eyes to protect the cornea during the
day; at night, the lid should be taped down with cello-
1. Facial Weakness phane tape. Upward massage of the face for 5–10 min-
Facial asymmetry may be present at birth or may de- utes three or four times a day may help maintain mus-
velop later, either suddenly or gradually, unilaterally or cle tone. Prednisone therapy likely does not aid
 NEUROLOGIC & MUSCULAR DISORDERS / 803

recovery. Acyclovir (herpes antiviral agent) therapy may mediated and may have a relapsing course. Sometimes
have a role in Bell’s palsy. facial weakness occurs. CSF protein levels are elevated.
In the few children with permanent and cosmeti- Nerve conduction is slowed, and nerve biopsies are ab-
cally disfiguring facial weakness, plastic surgical inter- normal. Immunologic abnormalities are seldom
vention at age 6 years or older may be of benefit. New demonstrated, although nerve biopsies may show round
procedures, such as attachment of facial muscles to the cell infiltration. Corticosteroids and other immunosup-
temporal muscle and transplantation of cranial nerve pressants may give long-term benefit.
XI, are being developed. Of the four defined hereditary sensory neu-
ropathies, one rarer variant is familial dysautonomia,
Gimino V, Kamat B: Lyme disease. Pediatr Rev 2001;22:23,28. also called Riley–Day syndrome. Transmitted as an au-
Peitersen E: Bell’s palsy: The spontaneous course of 2,500 periph-
tosomal recessive trait and occurring mostly in Jewish
eral facial nerve palsies of different etiologies. Acta Otolaryn- children, this disorder has its onset in infancy. It is
gol (Suppl) 2002;549:4 [PMID: 12482166]. characterized by vomiting and difficulties in feeding
Wilson C, Grant CC: Facial nerve palsy secondary to Epstein–Barr that are due to abnormal esophageal motility, pul-
virus infection. Arch Pediatr Adolesc Med 1997;151:739 monary infections, decreased or absent tearing, indif-
[PMID: 9232052]. ference to pain, diminished or absent tendon reflexes,
absence of fungiform papillae of the tongue, emotional
lability, abnormal temperature control with excessive
CHRONIC POLYNEUROPATHY sweating, labile blood pressure, abnormal intradermal
Polyneuropathy, usually insidious in onset and slowly histamine responses, and other evidences of autonomic
progressive, occurs in children of any age. The present- dysfunction.
ing complaints are chiefly disturbances of gait and easy Rarely, a careful genetic history (pedigree) and ex-
fatigability in walking or running and, slightly less amination and electrical testing (motor and sensory
often, weakness or clumsiness of the hands. Pain, ten- nerve conduction, EMG) of relatives are keys to diag-
derness, or paresthesias are mentioned less frequently. nosis of hereditary neuropathy. This is the most com-
Neurologic examination discloses muscular weakness, mon cause of chronic neuropathy in children. Other
greatest in the distal portions of the extremities, with hereditary neuropathies may have ataxia as a prominent
steppage gait and depressed or absent deep tendon re- finding often overshadowing the neuropathy. Examples
flexes. Cranial nerves are sometimes affected. Sensory are Friedreich ataxia, dominant cerebellar ataxia, and
deficits occur in a stocking and glove distribution. The Marinesco–Sjögren syndrome. Finally, some hereditary
muscles may be tender, and trophic changes such as neuropathies are associated with identifiable and occa-
glassy or parchment skin and absent sweating may sionally treatable metabolic errors. (see Table 23–22).
occur. Thickening of the ulnar and peroneal nerves These disorders are described in more detail in Chapter
may be felt. Pure sensory neuropathies show up as 32 (see also Table 23–21).
chronic trauma. That is, the patient does not feel minor Laboratory diagnosis of chronic polyneuropathy is
trauma or burns, and thus allows trauma to occur. made by measurement of motor and sensory nerve con-
Known causes include (1) toxins (lead, arsenic, mer- duction velocities. EMG may show a neurogenic
curials, vincristine, and benzene); (2) systemic disorders polyphasic pattern. CSF protein levels are often ele-
(diabetes mellitus, chronic uremia, recurrent hypo- vated, sometimes with an increased IgG index. Nerve
glycemia, porphyria, polyarteritis nodosa, and lupus biopsy, with teasing of the fibers and staining for
erythematosus); (3) inflammatory states (chronic or re- metachromasia, may demonstrate loss of myelin and, to
current Guillain–Barré syndrome and neuritis associ- a lesser degree, loss of axons and increased connective
ated with mumps or diphtheria); (4) hereditary, often tissue or concentric lamellas (so-called onion skin ap-
degenerative conditions, which in some classifications pearance) around the nerve fiber. Muscle biopsy may
include certain storage diseases, leukodystrophies, spin- show the pattern associated with denervation. Other
ocerebellar degenerations with neurogenic components, laboratory studies directed toward specific causes men-
and Bassen–Kornzweig syndrome; and (5) hereditary tioned above include screening for heavy metals and for
sensory or combined motor and sensory neuropathies metabolic, renal, or vascular disorders. Chronic lead in-
(Table 23–27). Polyneuropathies associated with carci- toxication, which rarely causes neuropathy in child-
nomas, beriberi or other vitamin deficiencies, or exces- hood, may escape detection until the child is given ede-
sive vitamin B6 intake are not reported or are exceed- tate calcium disodium and lead levels are determined in
ingly rare in children. timed urine samples.
The most common chronic neuropathy of insidious Therapy is directed at specific disorders whenever
onset often has no identifiable cause. This chronic idio- possible. Occasionally the weakness is profound and in-
pathic neuropathy is assumed to be immunologically volves bulbar nerves, in which case tracheostomy and
804 / CHAPTER 23

Table 23–27. Hereditary motor and sensory neuropathies; metabolic error unknown.

Name Prototype Inheritance Clinical Features Nerve Biopsy

Sensory and auto- Familial dysau- Autosomal-recessive See text Decreased unmyelinated
nomic neuropathy tonomia fibers posterior column
and cord
HMSN I (if tremor is “Classic” Charcot– Autosomal-dominant Onset 0–15 y. Weakness, Segmental demyelination
present, Roussy– Marie–Tooth (CMT) atrophy of feet, calves
Lévy syndrome) type I (pes cavus, “stork legs”),
(60–90% of HMSN (1) CMT 1A 17p11.2 hands. Sensory loss 0 or
are type I) (CMT I) (2) CMT 1B 1g22 variable. Deep tendon
(3) CMT 1C Connexin 32 reflexes 0. Motor nerve
(4) X-linked conduction velocities
(5) Type 4 slowed. 10% have hyper-
trophic (palpable) nerves.
Type 1B is linked to
Duffy blood group.
HMSN II (10–30% Neuronal, axonal Autosomal-dominant Less severe; onset 10– Axonal loss, secondary
of cases) (CMT 2) type 2 Multiple gene sites y. Leg cramps, numbness, demyelination
motor nerve conduction
velocities normal or slightly
slow. CSF protein often
normal.
HMSN III (CMT 3) Hypertrophic CMT Autosomal-recessive Onset in infancy. Severe. Hypertrophic (“onion bulb”)
disease; Déjérine– (or AD, sporadic) CSF protein increased. interstitial changes
Sottas disease Very slow MNCV. Slowly
progressive.
HMSN IV (CMT 4) Refsum disease Autosonal-recessive Severe sensory, mild motor. See HMSN III
demyelinating, or Thick nerves. CSF protein
axonal elevated. Ichthyosis, retini-
tis pigmentosa, ataxia, deaf-
ness. Urine phytanic acid.
HMSN V CMT disease with Abnormal pyramidal tract Defined in pedigrees. Rule
spastic paraparesis findings. Rule out adreno- out adrenomyelopathy with
myelopathy. long-chain fatty acids.
HNPP Hereditary neuro- Autosomal -dominant Adolescent onset. Episodic Occasional “tomaculous
pathy with PMP22 17p11.2 numbness, peroneal palsy, sausage” nerve formations.
pressure palsies deletion carpal tunnel syndrome.
1
CSF = cerebrospinal fluid; MNCV = motor nerve conduction velocity; HMSN = hereditary motor and sensory neuropathy; HNPP = heredi-
tary neuropathy (with ability to) pressure palsies; PMP = peripheral myelin protein; MPZ/PO = myelin protein zero.

respiratory assistance are required. Corticosteroid ther- of hereditary neuropathy. In all cases considered for
apy may be of considerable benefit in cases where the corticosteroid therapy, the risks and benefits should be
cause is unknown or neuropathy is considered to be carefully weighed. When treatment is available, symp-
due to chronic inflammation (this is not the case in toms regress and may disappear altogether over a period
acute Guillain–Barré syndrome). Prednisone is recom- of months.
mended, 1–2.5 mg/kg/d orally, with tapering to the The long-term prognosis varies with the cause and
lowest effective dose—discontinued if the process seems the ability to offer specific therapy. In the corticoster-
to be arresting and reinstituted when symptoms recur. oid-dependent group, residual deficits and deaths
Prednisone should probably not be used for treatment within a few years are more frequent.
 NEUROLOGIC & MUSCULAR DISORDERS / 805

Burns TM et al: Current therapeutic strategies for patients with ing stairs or motor difficulties and lack of endurance.
polyneuropathies secondary to inherited metabolic disorders. Hypotonia or decreased motor activity is a frequent
Mayo Clin Proc 2003;78:858 [PMID: 12839082].
presenting complaint in neuromuscular disorders but
Connolly AM: Chronic inflammatory demyelinating polyneuropa- may also accompany a variety of systemic conditions or
thy in childhood. Pediatr Neurol 2001;24:177 [PMID:
11301217]. may be due to certain disorders of connective tissue.
Donofrio PD: Immunotherapy of idiopathic inflammatory neu-
ropathies. Muscle Nerve 2003;28:273 [PMID: 12929187].
Hughes R et al: Randomized controlled trial of intravenous immu-
1. Paralytic Group
noglobulin versus oral prednisone in chronic inflammatory The hypotonic infant who is weak (appearing para-
demyelinating polyradiculoneuropathy. Ann Neurol
2001;50:195 [PMID: 11506402].
lyzed) usually has a lesion of the lower motor neuron
complex (Table 23–28). The child has significant lack
Ropper AH: Current treatments for CIDP. Neurology 2003;60
(Suppl 3):S16 [PMID: 12707418]. of movement against gravity (eg, fails to kick the legs,
Sander HW, Hedley-Whyte ET: Case records of the Massachusetts
hold up the arms, or attempt to stand when held) or in
General Hospital. Weekly clinicopathological exercises: Case response to stimuli such as tickling or slight pain. In-
6-2003: A nine-year-old girl with progressive weakness and fantile progressive spinal muscular atrophy (Werd-
areflexia. N Engl J Med 2003;348:735 [PMID: 12594319]. nig–Hoffman disease) is the most common cause. Neu-
ropathy is rare. Botulism and myasthenia gravis (rare)
are neuromuscular junction causes. Myotonic dystro-
phy and rare myopathies (eg, central core myopathy)
MISCELLANEOUS are muscle disease entities.
NEUROMUSCULAR DISORDERS In anterior horn cell or muscle disease, weakness is
proximal (ie, in shoulders and hips); finger movement
is preserved. Tendon reflexes are absent or depressed;
FLOPPY INFANT SYNDROME strength (to noxious stimuli) is decreased (paralytic).
Intelligence is preserved. Fine motor, language, and
personal and social milestones are normal, as measured,
ESSENTIALS OF DIAGNOSIS for example, on a Denver Developmental Screening
& TYPICAL FEATURES Test (DDST, or Denver II) (see Chapter 2).

• In early infancy, decreased muscular activity, Myopathies

both spontaneous and in response to postural re-
flex testing and to passive motion. The congenital, relatively nonprogressive myopathies,
muscular dystrophy, myotonic dystrophy, polymyositis,
• In young infants, “frog posture” or other unusual
and periodic paralysis were discussed earlier in this
positions at rest.
chapter. Most cases of congenital or early infantile mus-
• In older infants, delay in motor milestones. cular dystrophy reported in the past probably repre-
sented congenital myopathies (see Table 23–28). Con-
genital muscular dystrophy, diagnosed by muscle
biopsy, occurs in two forms: (1) a benign form, with
gradual improvement in strength; and (2) a severe
General Considerations form, in which either weakness progresses rapidly and
In the young infant, ventral suspension (ie, supporting death occurs in the first months or year of life or severe
the infant with a hand under the chest) normally results disability is present with little or no progression but
in the infant’s holding its head slightly up (45 degrees or lifelong marked limitation of activity.
less), the back straight or nearly so, the arms flexed at the
elbows and slightly abducted, and the knees partly flexed. Glycogenosis with Muscle Involvement
The “floppy” infant droops over the hand like an inverted
U. The normal newborn attempts to keep the head in the Glycogen storage diseases are described in Chapter 32.
same plane as the body when pulled up from supine to Patients with type II disease (Pompe disease, due to a
sitting by the hands (traction response). Marked head lag deficiency of acid maltase) are most likely to present as
is characteristic of the floppy infant. Hyperextensibility of floppy infants. Muscle cramps on exertion or easy fati-
the joints is not a dependable criterion. gability, rather than floppiness in infancy, is the pre-
The usual reasons for seeking medical evaluation in senting complaint in type V disease (McArdle phospho-
older infants are delays in walking, running, or climb- rylase deficiency) or in the glycogenosis due to
806 / CHAPTER 23

Table 23–28. Floppy infant: paralytic causes.

Disease Genetic Early Manifestations

IPSMA AR In utero movements decreased by one third. Gradual weakness, delay
(Infantile progressive in gross motor milestones. Weak cry. Abdominal breathing. Poor limb
spinal muscular atro- motion (“no kicking”). No deep tendon reflexes. Fasciculations of ton-
phy) “Malignant” form gue. Normal personal-social behavior.
“Intermediate” form AR Onset under age 1 year usual. Progression slower: may be impossible to
predict early course of IPSMA. Hand tremors common.
Infantile botulism Acquired younger than Poor feeding. Constipation. Weak cry. Failure to thrive. Lethargy. Facial
age 1 y (mostly under weakness, ptosis, ocular muscle palsy. Inability to suck, swallow. Apnea.
6 mos); botulism spore Source: soil dust (outdoor construction workers or family gardeners
in stool makes toxin may bring it home on clothes), honey.
Myasthenia gravis 12% of infants born from Floppiness. Poor sucking and feeding; choking. Respiratory distress.
Neonatal transient a myasthenia mother Weak cry.
Congenital persistent Mother normal. Rare As above; may improve and later exacerbate.
AR (AD)
Myotonic dystrophy AD 99%—mother Polyhydramnios; failure of suck, respirations. Facial diplegia. Ptosis.
transmits gene Arthrogryposis. Thin ribs. Later, developmental delay. Examine mother
for myotonia, physiognomy.
Neonatal “rare myopathy,” AR, AD Virtually all of the rare myopathies may have a severe (even fatal) neo-
severe variant natal or early infant form. Clinical features similar in infancy to infantile
Nemaline, central core, myotonic dystrophy.
“minimal change,” etc
Congenital muscular Genetic Early onset. Facial weakness. Joint contractures. Severe mental retarda-
dystrophy tion. Seizures. Brain structural abnormalities.
Fukayama (FCMD)
Other Severe or benign. No mental retardation (see text).
Infantile neuropathy HSMN most common Demyelinating or axonal; a rare cause of floppy infant. Rule out
cause mimicking IPSMA (deletion study). EMG, NCV are key studies.
Benign congenital Unknown Diagnosis of exclusion. Family history variable. Mild to moderate
hypotonia cause hypotonia with weakness. (This term being used less with increasing
genetic, microscopy advances)
AD = autosomal dominant; AR = autosomal recessive; HSMN = hereditary sensory motor neuropathy; EMG = electromyelogram; NCV =
nerve conduction velocity.

phosphofructokinase deficiency or phosphohexose iso- both) and may be associated with a variety of other
merase inhibition. anomalies. Orthopedic aspects are discussed in Chapter
24.
Myasthenia Gravis
Neonatal transient and congenital persistent myasthe- Spinal Cord Lesions
nia gravis, with patients presenting as paralytic floppy
infants, is described earlier in this chapter. Severe limpness in newborns following breech extraction
with stretching or actual tearing of the lower cervical to
Arthrogryposis Multiplex (Congenital upper thoracic spinal cord is rarely seen today, owing to
improved obstetric delivery. Klumpke lower brachial
Deformities About Multiple Joints) plexus paralysis may be present; the abdomen is usually
This symptom complex, sometimes associated with hy- exceedingly soft, and the lower extremities are flaccid.
potonia, may be of neurogenic or myopathic origin (or Urinary retention is present initially; later, the bladder
 NEUROLOGIC & MUSCULAR DISORDERS / 807

may function autonomously. Myelography or MRI scan- potonia may occur at varying times in the same infant.
ning may define the lesion. After a few weeks, spasticity Choreoathetoid or ataxic movements and developmen-
of the lower limbs becomes obvious. Treatment is symp- tal delay can clarify the diagnosis. Reflexes are often in-
tomatic and consists of bladder and skin care and even- creased; pathologic reflexes (Babinski, tonic neck) may
tual mobilization on crutches or in a wheelchair. persist or worsen.
The creatine kinase level and the EMG are usually
normal. Prolonged nerve conduction velocities point to
2. Nonparalytic Group polyneuritis or leukodystrophy. Muscle biopsies, using
The nonparalytic hypotonic infant often has a damaged special stains and histographic analysis, often show a re-
brain (Table 23–29). Deep tendon reflexes may be de- markable reduction in size of type II fibers associated
pressed or absent in this group. Brisk reflexes with hy- with decreased voluntary motor activity.
potonia point to suprasegmental or general cerebral Limpness in the neonatal period and early infancy
dysfunction. Intrauterine or perinatal insults to brain or and subsequent delay in achieving motor milestones are
spinal cord, while sometimes difficult to document, are the presenting features in a large number of children
major causes. (Occasionally, severe congenital my- with a variety of CNS disorders, including mental re-
opathies presenting in the newborn period simulate tardation, as in trisomy 21. In many such cases, no spe-
nonparalytic hypotonia.) Persisting severe hypotonia is cific diagnosis can be made. Close observation and scor-
ominous. Tone will often vary. Spasticity and other ing of motor patterns and adaptive behavior, as by the
forms of cerebral palsy may emerge; hypertonia and hy- DDST, are helpful.

Table 23–29. Floppy infant: nonparalytic causes.

Causes Manifestations
Central nervous system disorders
Atonic diplegia (prespastic diplegia) Intrauterine, perinatal Limpness, stupor; poor suck, cry, Moro reflex, grasp; later,
asphyxia, cord injury irritability, increased tone and reflexes
Choreoathetosis As above; kernicterus Hypotonic early; movement disorder emerges later
(6–18 mos)
Ataxic cerebral palsy Same as choreoathetosis Same as choreoathetosis
Syndromes with hypotonia (CNS origin)
Trisomy 21 Genetic All have hypotonia early
Prader–Willi syndrome Genetic deletion 15q11 Hypotonia, hypomentia, hypogonadism, obesity (“H3O”)
Marfan syndrome Autosomal-dominant Arachnodactyly
Dysautonomia Autosomal-recessive Respiratory infections, corneal anesthesia
Turner syndrome 45X, or mosaic Somatic stigmata (see Chapter 32)
Degenerative disorders
Tay–Sachs disease Autosomal-recessive Cherry-red spot on macula
Metachromatic leukodystrophy Autosomal-recessive Deep tendon reflexes increased early, polyneuropathy
late; mental retardation
Systemic diseasesa Deprivation, cystic fibrosis, celiac disease
Malnutrition
Chronic illness Congenital heart disease; chronic pulmonary disease (eg, bronchopulmonary dys-
plasia); uremia, renal acidosis
Metabolic disease Hypercalcemia, Lowe disease
Endocrinopathy Hypothyroid
a
See elsewhere in text for manifestations.
808 / CHAPTER 23

CDC MMWR: Infant botulism—New York City 2001–2002. ataxia, and involuntary movements. Microcephaly is
JAMA 2003;52:21 [PMID: 12608714]. frequently present. In patients with hemiplegia, the af-
Castrodale V: The hypotonic infant: Case study of central core dis- fected arm and leg may be smaller and shorter than the
ease. Neonatal Netw 2003;22:53 [PMID: 12597091]. unaffected limbs. Cataracts, retinopathy, and congeni-
Dua T et al: Spectrum of floppy children in Indian scenario. Indian tal heart defects may be indicative of congenital infec-
Pediatr 2001;38:1236 [PMID: 11721063].
tions such as CMV and rubella.
Johnston HM: The floppy weak infant revisited. Brain Dev
2003;25:155 [PMID: 12689691].
Appropriate laboratory studies depend on the his-
tory and physical findings. MRI scans may be helpful
Ogino S, Wilson RB: Genetic testing and risk assessment for spinal
muscular atrophy (SMA). Hum Genet 2002;111:477 [PMID: in understanding the full extent of cerebral injury, and
12436240]. occasionally neuroimaging results suggest specific eti-
Richer LP et al: Diagnostic profile of neonatal hypotonia: An ologies (eg, periventricular calcifications in congenital
11-year study. Pediatr Neurol 2001;25:32 [PMID: CMV infections). Other diagnostic tests that may be
11483393]. considered include IgG and IgM antibody determina-
Rick JR et al: Infantile botulism: An atypical case of an uncommon tions for specific infective agents; urine amino acids and
disease. Pediatrics 1999;103:1038 [PMID: 10224186]. organic acids; blood amino acids, lactate, pyruvate, and
Wilmshurst JM et al: Peripheral neuropathies of infancy. Dev Med ammonia concentrations.
Child Neurol 2003;45:408 [PMID: 12785442]. The determination that a child has cerebral palsy is
based in part on excluding other neurologic disorders
and following the child for a sufficient amount of time
CEREBRAL PALSY to ascertain the static, nonprogressive nature of the dis-
The term “cerebral palsy” is a nonspecific term used to order.
describe a chronic, static impairment of muscle tone, Treatment and management are directed at assisting
strength, coordination, or movements. The term im- the child to attain maximal physical functioning and
plies that the condition is nonprogressive and origi- potential physical, occupational, and speech therapy;
nated from some type of cerebral insult or injury before orthopedic monitoring and intervention and special ed-
birth, during delivery, or in the perinatal period. There ucational assistance may all contribute to an improved
is no implication in the use of this term about the outcome. Medications for spasticity and seizures are
child’s intellect or whether other neurologic deficits or needed in many children. Also important is the general
disorders (eg, blindness, deafness, epilepsy) exist. Some support of the parents and family with counseling, edu-
form of cerebral palsy occurs in about 0.2% of neonatal cational programs, and support groups.
survivors. The fundamental course, severity, precise The prognosis for patients with cerebral palsy de-
manifestations, and prognosis vary widely. pends greatly on the severity of the motor deficits and
The most common forms of cerebral palsy (75% of the degree of incapacity the patients ultimately experi-
cases) involve spasticity of the limbs. A variety of terms ence. In severe cases, life span is greatly shortened to
denote the specific limb or combination of limbs af- 10 years or less. Aspiration, pneumonia, or other inter-
fected: monoplegia (one limb); hemiplegia (arm and leg current infections are the most common causes of
on same side of body, but arm more affected than leg); death.
diplegia (leg affected more than arms); paraplegia (both In contrast, patients with mild cerebral palsy may
legs affected with arms unaffected); quadriplegia (all improve with age. Some patients experience resolution
four limbs affected equally). of their motor deficits by age 7 years. Many children
Ataxia is the second most common form of cerebral with normal intellect have normal life spans and are
palsy, accounting for about 15% of cases. The ataxia able to lead productive, satisfying lives.
frequently affects fine coordinated movements of the The cause is often obscure or multifactorial. No def-
upper extremities, but may also involve lower extremi- inite etiologic diagnosis is possible in over one third of
ties and trunk. An involuntary movement disorder usu- cases. The incidence is high among infants small for
ally in the form of choreoathetosis accounts for 5% of gestational age. Intrauterine hypoxia is a frequent cause.
cases and persistent hypertonia without spasticity 1%. Other known causes are intrauterine bleeding, infec-
Depending on the type and severity of the motor tions, toxins, congenital malformations, obstetric com-
deficits, associated neurologic deficits or disorders may plications (including birth hypoxia), neonatal infec-
occur: seizure in up to 50%, mild mental retardation in tions, kernicterus, neonatal hypoglycemia, acidosis, and
26%, and severe retardation in up to 27%. Disorders of a small number of genetic syndromes.
language, speech, vision, hearing, and sensory percep-
tion are found in varying degrees and combinations. Albright AL et al: Long-term intrathecal baclofen therapy for severe
The findings on physical examination are variable spasticity of cerebral origin. J Neurosurg 2003;98:291
and are predominately those of spasticity, hyperreflexia, [PMID: 12593613].
 NEUROLOGIC & MUSCULAR DISORDERS / 809

Awaad V et al: Functional assessment following intrathecal ba- Child Neurology Foundation
clofen therapy in children with spastic cerebral palsy. J Child http://www.childneurologyfoundation.org/index.html
Neurol 2003;18:26 [PMID: 12661935]. Describes sites, resources, tests, related to child neurology.
Collet JP et al: Hyperbaric oxygen for children with cerebral palsy: E-Medicine
A randomised multicentre trial. Lancet
2001;357:582 [PMID: 11558483] http://www.emedicine.com/neuro/PEDIATRIC
NEUROLOGY.htm
Gibson CS et al: Antenatal causes of cerebral palsy: Associations be-
tween inherited thrombophilias, viral and bacterial infection, This contains a list of various topics within pediatric neurology.
and inherited susceptibility to infection. Obstet Gynecol Surv American Association of Child and Adolescent Psychiatry
2003;58:209 [PMID: 12612461]. http://www.aacp.org
Perlman JM: Intrapartum hypoxic–ischemic cerebral injury and Contains practice parameters and other information.
subsequent cerebral palsy: Medicolegal issues. Pediatrics National Institute of Neurological Disorders and Stroke
1997;99:851 [PMID: 9164779].
http://www.ninds.nih.gov
Petersen MC, Palmer FB: Advances in prevention and treatment of
Brief descriptions of neurological disorders.
cerebral palsy. Ment Retard Dev Disabil Res Rev
2001;7:30 [PMID: 11241880]. Gene Tests
Rosenbaum PL et al: Prognosis for gross motor function in cerebral http://www.genetests.org
palsy: Creation of motor development curves. JAMA Lengthy descriptions of many of the genetic disorders.
2002;288:1357 [PMID: 12234229]. Epilepsy Foundation of America
Shevell MI et al: Etiologic yield of cerebral palsy: A contemporary http://www.epilepsyfoundation.org
case series. Pediatr Neurol 2003;28:352 [PMID: 12878296]. Describes epilepsy research and some basics about epilepsy
Singhi P et al: Epilepsy in children with cerebral palsy. J Child American Epilepsy Society
Neurol 2003;18:174 [PMID: 12731642].
http://www.aesnet.org
Gives in formation about the society and general in formation
about epilepsy. A good section on drugs given.
Internet References Neurofibromatosis Foundation
Child Neurology Society http://www.nf.org
http://www.childneurologysociety.org Neurofibromatosis information
This site contains information about new developments, research Tuberous Sclerosis Association
and has practice parameters. http://www.tsalliance.org
 Orthopedics 24
Robert E. Eilert, MD

Orthopedics is the medical discipline that deals with instilling an accustomed pattern of proper length and
disorders of the neuromuscular and skeletal systems. bimanual manipulation. Although myoelectric prosthe-
Patients with orthopedic problems present with one or ses have a technologic appeal, the majority of patients
more of the following complaints: pain, loss of func- use the simplest construct in the long run.
tion, or deformity. Although review of the history re- Children quickly learn how to function with their
veals the patient’s expectation, physical examination is prostheses and can lead active lives, even participating
the most important feature of orthopedic diagnosis. in sports with peers.

Kant P et al: Treatment of longitudinal deficiency affecting the

femur: Comparing patient mobility and satisfaction out-
DISTURBANCES OF PRENATAL comes of Syme amputation against extension prosthesis. J Pe-
diatr Orthop 2003;23(2):236 [PMID: 12604957].
ORIGIN McCarthy JJ et al: Fibular hemimelia: Comparison of outcome
measurements after amputation and lengthening. J Bone
Joint Surg Am 2000;82-A(12):1732 [PMID: 11139646].
CONGENITAL AMPUTATIONS
AND LIMB DEFICIENCIES
DEFORMITIES OF THE EXTREMITIES
Congenital amputations may be due to teratogens (eg,
drugs or viruses), amniotic bands, or metabolic diseases 1. Metatarsus Varus
(eg, diabetes in the mother). The incidence of multiple Metatarsus varus is a common congenital foot defor-
limb involvement is 30%. mity characterized by inward deviation of the forefoot.
Children with congenital limb deficiencies, such as A vertical crease in the arch occurs when the deformity
absence of the femur, tibia, or fibula, also have a high is more rigid. The angulation is at the level of the base
incidence of associated congenital anomalies, including of the fifth metatarsal, and this bone will be prominent.
genitourinary and cardiac defects and cleft palate. A Most flexible deformities are secondary to intrauterine
limb deficiency usually consists of partial absence of posture and usually resolve spontaneously. Several in-
structures in the extremity along one side or the other. vestigators have noticed that 10–15% of children with
For example, in radial clubhand, the entire radius is ab- metatarsus varus have hip dysplasia; therefore, a careful
sent, but the thumb may be either hypoplastic or com- hip examination is necessary. If the deformity is rigid
pletely absent; that is, the effect on structures distal to and cannot be manipulated past the midline, it is
the amputation varies. Complex tissue defects are worthwhile to use a cast changed at intervals of 2 weeks
nearly always associated with longitudinal bone defi- to correct the deformity. So-called corrective shoes do
ciency in that the associated nerves and muscles are not not live up to their name, although they can be used to
completely represented when a bone is absent. maintain correction obtained by casting.
Terminal amputations are treated by prosthesis, for
example, to compensate for shortness of one leg. For Lincoln TL, Suen PW: Common rotational variations in children.
certain types of severe anomalies, operative treatment is J Am Acad Orthop Surg 2003;11(5):312 [PMID: 14565753].
indicated to remove a portion of the malformed ex-
tremity (eg, foot) so that a prosthesis can be fitted early.
An extension prosthesis fitted over the foot to equalize
2. Clubfoot (Talipes Equinovarus)
limb length is a reasonable nonsurgical alternative. The diagnosis of classic talipes equinovarus, or club-
Lower extremity prostheses are best fitted between foot, requires three features: (1) plantar flexion of the
ages 12 and 15 months, when walking starts. They are foot at the ankle joint (equinus), (2) inversion defor-
consistently well accepted, because they are necessary mity of the heel (varus), and (3) medial deviation of the
for balancing and walking. For a unilateral upper ex- forefoot (varus). The incidence of clubfoot is approxi-
tremity amputation, fitting the child with dummy-type mately 1:1000 live births. There are three major cate-
prosthesis as early as age 6 months has the advantage of gories of clubfoot: (1) idiopathic, (2) neurogenic, and
810
Copyright © 2005, 2001, by The McGraw-Hill Companies, Inc. Click here for terms of use.
 ORTHOPEDICS / 811

(3) those associated with syndromes such as arthrogry- Clinical Findings

posis and Larsen syndrome. Any infant with a clubfoot
should be examined carefully for associated anomalies, The diagnosis of hip dislocation in the newborn de-
especially of the spine. Idiopathic clubfeet may be pends on demonstrating instability of the joint by plac-
hereditary. ing the infant on its back and obtaining complete relax-
Treatment consists of manipulation of the foot to ation by feeding with a bottle if necessary. The
stretch the contracted tissues on the medial and posteri- examiner’s long finger is then placed over the greater
or aspects, followed by splinting to hold the correction. trochanter and the thumb over the inner side of the
When this treatment is instituted shortly after birth, thigh. Both hips are flexed 90 degrees and then slowly
correction is rapid. When treatment is delayed, the foot abducted from the midline, one hip at a time. With
tends to become more rigid within a matter of days. gentle pressure, an attempt is made to lift the greater
After full correction is obtained, a night brace is neces- trochanter forward. A feeling of slipping as the head re-
sary for long-term maintenance of correction. Treat- locates is a sign of instability (Ortolani sign). When the
ment by means of casting requires patience and experi- joint is more stable, the deformity must be provoked by
ence, but fewer patients require surgery when attention applying slight pressure with the thumb on the medial
is paid to details of the Ponsetti technique. If the foot is side of the thigh as the thigh is adducted, thus slipping
rigid and resistant to cast treatment, surgical release and the hip posteriorly and eliciting a jerk as the hip dislo-
correction are appropriate. Fifteen percent to 50% re- cates (Barlow sign). The signs of instability are more re-
quire a surgical release. liable than a radiograph for diagnosing congenital dislo-
cation of the hip in the newborn. Ultrasonography can
be used but tends to result in overdiagnosis in the new-
Colburn M, Williams M: Evaluation of the treatment of idiopathic born. Asymmetrical skinfolds are present in about 40%
clubfoot by using the Ponsetti method. J Foot Ankle Surg of newborns and therefore are not particularly helpful.
2003;42(5):259 [PMID: 14566717].
After the first month of life, the signs of instability
Tredwell SJ et al: Review of the effect of early amniocentesis on
foot deformity in the neonate. J Pediatr Orthop
become less evident. Contractures begin to develop
2001;21:636 [PMID: 11521033]. about the hip joint, limiting abduction to less than
90 degrees. It is important to hold the pelvis level to de-
tect asymmetry of abduction. If the knees are at un-
3. Infantile Dysplasia of the Hip Joint equal heights when the hips and knees are flexed, the
dislocated hip will be on the side with the lower knee.
The definition of dysplasia is abnormal growth or de- After the first 6 weeks of life, radiologic examination
velopment. Dysplasia of the hip encompasses a spec- becomes more valuable, with lateral displacement of the
trum of conditions in which an abnormal relationship femoral head being the most reliable sign. In mild cases,
exists between the proximal femur and the acetabulum. the only abnormality may be increased steepness of ac-
In the most severe condition, the femoral head is not in etabular alignment, so that the acetabular angle is
contact with the acetabulum and is classified as a dislo- greater than 35 degrees.
cated hip. A dislocatable hip is one in which the hip is If dysplasia of the hip has not been diagnosed dur-
within the acetabulum but can be dislocated with a ing the first year of life and the child begins to walk,
provocative maneuver. A subluxatable hip is one in there will be a painless limp and a lurch to the affected
which the femoral head comes partially out of the joint side. When the child stands on the affected leg, a dip of
with a provocative maneuver. Acetabular dysplasia is the pelvis will be evident on the opposite side, owing to
the term used to denote insufficient acetabular develop- weakness of the gluteus medius muscle. This is called
ment on radiograph. the Trendelenburg sign and accounts for the unusual
Congenital dislocation of the hip occurs in approxi- swaying gait. In children with bilateral dislocations, the
mately 1:1000 live births. At birth, both the acetabu- loss of abduction is almost symmetrical and may be de-
lum and femur are underdeveloped. The dysplasia is ceiving. A radiograph of the pelvis is indicated in chil-
progressive with growth unless the dislocation is cor- dren with incomplete abduction in the first few months
rected. If the dislocation is corrected in the first few of life. As a child with bilateral dislocation of the hips
days or weeks of life, the dysplasia is completely re- begins to walk, the gait is waddling. The perineum is
versible and a normal hip will develop. As the child be- widened as a result of lateral displacement of the hips,
comes older and the dislocation or subluxation persists, and there is flexion contracture as a result of posterior
the deformity will worsen to the point where it will not displacement of the hips. This flexion contracture con-
be completely reversible, especially after the walking tributes to marked lumbar lordosis, and the greater
age. For this reason, it is important to diagnose the de- trochanters are easily palpable in their elevated position.
formity early. Treatment is still possible in the first 2 years of life, but
812 / CHAPTER 24

the results are not nearly as effective as in children re- spine are indicated in all cases. In addition, there is a
ceiving treatment in the nursery. 20% incidence of hip dysplasia.
Acute torticollis may follow upper respiratory infec-
tion or mild trauma in children. Rotatory subluxation
Treatment of the upper cervical spine requires computed tomogra-
Dislocation or dysplasia diagnosed in the first few phy for accurate imaging. Traction or a cervical collar
weeks or months of life can easily be treated by splint- usually results in resolution of the symptoms within
ing, with the hip maintained in flexion and abduction. 1 or 2 days. Other causes of torticollis include spinal
Forced abduction is contraindicated, because this can cord or cerebellar tumors, syringomyelia, and rheuma-
lead to avascular necrosis of the femoral head. The use toid arthritis.
of double or triple diapers is never indicated because di-
apers are not adequate to obtain proper positioning of Fernandez Cornejo VJ et al: Inflammatory atlanto-axial subluxation
the hip. An orthopedic surgeon with experience manag- (Grisel’s syndrome) in children: Clinical diagnosis and man-
ing the problem is best to supervise treatment of chil- agement. Childs Nerv Syst 2003;19(5-6):342 [PMID:
dren requiring splints. 12783261].
In the first 4 months of life, reduction can be ob-
tained by simply flexing and abducting the hip; no GENERALIZED DISORDERS
other manipulation is usually necessary. In late cases, OF SKELETAL OR MESODERMAL
preoperative traction for 2–3 weeks relaxes soft tissues
about the hip. Following traction in which the femur is
TISSUES
brought down opposite the acetabulum, reduction can 1. Arthrogryposis Multiplex Congenita
be easily achieved without force under general anesthe- (Amyoplasia Congenita)
sia. After reduction a hip spica is used for 6 months. If
the reduction is not stable within a reasonable range of Arthrogryposis multiplex congenita consists of incom-
motion after closed reduction, open reduction is indi- plete fibrous ankylosis (usually bilateral) of many or all
cated. If reduction is done at an older age, operations to joints of the body. Upper extremity contractures usu-
correct the deformities of the acetabulum and femur ally consist of adduction of the shoulders; extension of
may be necessary as well as open reduction. the elbows; flexion of the wrists; and stiff, straight fin-
gers with poor muscle control of the thumbs. In the
Committee on Quality Improvement, Subcommittee on Develop-
lower extremities, common deformities are dislocation
mental Dysplasia of the Hip. American Academy of Pedi- of the hips, extension contractures of the knees, and se-
atrics: Clinical practice guideline: Early detection of develop- vere club feet. The joints are fusiform and the joint cap-
mental dysplasia of the hip. Pediatrics 2000;105(4 Pt sules decreased in volume due to lack of movement
1):896 [PMID: 10742345]. during fetal development. Various investigations have
attributed the basic defect to an abnormality of muscle
4. Torticollis or the lower motor neurons. Muscle development is
poor, and muscles may be represented only by fibrous
Wryneck deformities in infancy may be due either to bands. Passive mobilization of joints is the early treat-
injury to the sternocleidomastoid muscle during deliv- ment. Prolonged casting for correction of deformities is
ery or to disease affecting the cervical spine. When con- contraindicated in these children because further stiff-
tracture of the sternocleidomastoid muscle causes torti- ness results. Use of removable splints combined with
collis, the chin is rotated to the side opposite to the vigorous therapy is the most effective conservative treat-
affected muscle, and the head is tilted toward the side ment. Surgical release of the affected joints is often nec-
of the contracture. A mass felt in the midportion of the essary. The clubfoot associated with arthrogryposis is
sternocleidomastoid muscle is not a true tumor but very stiff and nearly always requires an operation.
rather fibrous transformation within the muscle. Surgery about the knees, including capsulotomy, os-
In most cases, passive stretching is effective. If the teotomy, and tendon lengthening, is used to correct de-
deformity has not been corrected by passive stretching formity. In the young child, a dislocated hip may be re-
within the first year of life, surgical release of the muscle duced operatively by the medial approach. Multiple
origin and insertion will correct it. Excising the operative procedures about the hip are contraindicated
“tumor” of the sternocleidomastoid muscle creates an because further stiffness may be produced with conse-
unsightly scar and is unnecessary. If the deformity is left quent impairment of motion. Affected children are
untreated, a striking facial asymmetry will persist. often able to walk if the dislocations and contractures
Torticollis is occasionally associated with congenital are reduced surgically. The long-term prognosis for
deformities of the cervical spine, and radiographs of the physical and vocational independence is guarded. These
 ORTHOPEDICS / 813

patients have normal intelligence, but they have such and torticollis may be present. The deformity occurs
severe physical restrictions that gainful employment is alone or in association with Klippel–Feil syndrome. If
hard to find. the deformity is functionally limiting, the scapula may
be surgically relocated lower in the thorax. Excision of
Bernstein RM: Arthrogryposis and amyoplasia. J Am Acad Orthop the upper portion of the scapula improves cosmetic ap-
Surg 2002;10(6):417 [PMID: 12470044]. pearance but has little effect on function.

2. Marfan Syndrome Williams MS: Developmental anomalies of the scapula—the “omo”st

forgotten bone. Am J Med Genet 2003;120A(4):583 [PMID:
Marfan syndrome is a connective tissue disorder charac- 12884444].
terized by unusually long fingers and toes (arachno-
dactyly); hypermobility of the joints; subluxation of the
ocular lenses; other eye abnormalities including 5. Osteogenesis Imperfecta
cataract, coloboma, megalocornea, strabismus, and nys- Osteogenesis imperfecta is a rare genetic connective tis-
tagmus; a high-arched palate; a strong tendency to scol- sue disease characterized by multiple and recurrent frac-
iosis; pectus carinatum; and thoracic aortic aneurysms tures. The severe fetal type (osteogenesis imperfecta
due to weakness of the media of the vessels (see Chapter congenita) is characterized by multiple intrauterine or
33). Serum mucoproteins may be decreased, and uri- perinatal fractures. Moderately affected children have
nary excretion of hydroxyproline increased. The condi- numerous fractures and are dwarfed as a result of bony
tion is easily confused with homocystinuria, because the deformities and growth retardation. Intelligence is not
phenotypic presentation is identical. The two diseases affected. The shafts of the long bones are reduced in
are differentiated by detecting homocystine in the urine cortical thickness, and wormian bones are present in
of patients with homocystinuria. the skull. Other features include blue scleras, thin skin,
Treatment is usually supportive for associated prob- hyperextensibility of ligaments, otosclerosis with signif-
lems such as flatfoot. Scoliosis may involve more vigor- icant hearing loss, and hypoplastic and deformed teeth.
ous treatment by bracing or spine fusion. The long- In the tarda type, fractures begin to occur at variable
term prognosis has improved for patients because better times after the perinatal period, resulting in relatively
treatment for their aortic aneurysms has been devised. fewer fractures and deformities. Affected patients are
sometimes suspected of having suffered induced frac-
Aburawi EH et al: Marfan’s syndrome: A review. Hosp Med tures, and the condition should be ruled out in any case
2001;62:153 [PMID: 11291465]. of nonaccidental trauma.
Molecular genetic studies have identified more than
3. Klippel–Feil Syndrome 150 mutations of the COL1A1 and COL1A2 genes,
which encode for type I procollagen. Parents without
Klippel–Feil syndrome is characterized by failure of seg- this mutation can be counseled that the likelihood of a
mentation of some or all of the cervical vertebrae. Mul- second affected child is negligible.
tiple congenital spinal anomalies may be present, with Bisphosphonates show promise for decreasing the
hemivertebrae and scoliosis. The neck is short and stiff, incidence of fractures. Surgical treatment involves cor-
the hairline is low, and the ears are low-set. Common rection of deformity of the long bones. Multiple in-
associated defects include congenital scoliosis, cervical tramedullary rods have been used to prevent deformity
rib, spina bifida, torticollis, web neck, high scapula, from poor healing of fractures. Patients are often con-
renal anomalies, and deafness. If there is evidence of ab- fined to wheelchairs during adulthood.
normal renal function, renal ultrasound is indicated as
well as a hearing test. Scoliotic deformities, if progres- Chevrel G, Meunier PJ: Osteogenesis imperfecta: Lifelong manage-
sive, are an indication for spinal arthrodesis. ment is imperative and feasible. Joint Bone Spine 2001;68:
125 [PMID: 11324928].
Guilde JT et al: The natural history of Klippel–Feil syndrome:
Clinical roentgenographic and magnetic resonance imaging
findings at adulthood. J Pediatr Orthop 1995;15:617 6. Osteopetrosis (Osteitis Condensans
[PMID: 7593574]. Generalisata, Marble Bone Disease,
Albers–Schönberg Disease)
4. Sprengel Deformity Osteopetrosis is a rare disorder of osteoclastic resorp-
Sprengel deformity is a congenital condition in which tion of bone, resulting in abnormally dense bones. The
one or both scapulas are elevated and small. The child marrow spaces are reduced, resulting in anemia. There
cannot raise the arm completely on the affected side, are two types: a milder autosomal dominant type and a
814 / CHAPTER 24

more malignant autosomal recessive type. The findings hypoplastic odontoid with atlantoaxial instability. The
may appear at any age. On radiologic examination, the child generally appears normal at birth and begins to
bones show increased density, transverse bands in the develop deformities between ages 1 and 4 years as a re-
shafts, clubbing of ends, and vertical striations of long sult of abnormal deposition of mucopolysaccharides.
bones. Thickening about the cranial foramina is pre- Radiographs demonstrate wedge-shaped flattened
sent, and heterotopic calcification of soft tissues is pos- vertebrae and irregular, malformed epiphyses. The ribs
sible. are broad and have been likened to canoe paddles. The
The autosomal recessive form of osteopetrosis can lower extremities are more severely involved than the
be treated successfully by allogeneic bone marrow trans- upper ones.
plantation. The major treatment issue revolves around the pre-
vention of cervical myelopathy. Bone marrow trans-
Armstrong DG et al: Orthopaedic management of osteopetrosis: plantation has been successful in alleviating some of the
Results of a survey and review of the literature. J Pediatr Or- symptoms.
thop 1999;19:122 [PMID: 9890301].

Peters C, Steward CG: Hematopoietic cell transplantation for in-

7. Achondroplasia herited metabolic diseases: An overview of outcomes and
(Classic Chondrodystrophy) practice guidelines. Bone Marrow Transplant 2003;31(4):
229 [PMID: 12621457].
Skeletal dysplasia is suspected based on abnormal
stature, disproportion, dysmorphism, or deformity.
Measurement of height is an excellent clinical screening
tool. Achondroplasia is the most common form of
short-limbed dwarfism. The upper arms and thighs are GROWTH DISTURBANCES
proportionately shorter than the forearms and legs. OF THE MUSCULOSKELETAL
Findings frequently include bowing of the extremities,
a waddling gait, limitation of motion of major joints, SYSTEM
relaxation of the ligaments, short stubby fingers of al-
most equal length, frontal bossing, moderate hydro- SCOLIOSIS
cephalus, depressed nasal bridge, and lumbar lordosis.
Intelligence and sexual function are normal. The disor- Scoliosis is characterized by lateral curvature of the
der is transmitted as an autosomal dominant trait, but spine associated with rotation of the involved vertebrae.
80% of cases result from a random mutation. Radi- Scoliosis is classified by its anatomic location, in either
ographs demonstrate short, thick tubular bones and ir- the thoracic or lumbar spine, with rare involvement of
regular epiphysial plates. The ends of the bones are the cervical spine. The convexity of the curve is desig-
thick, with broadening and cupping. Epiphysial ossifi- nated right or left. Thus a right thoracic scoliosis would
cation may be delayed. Because the spinal canal is nar- denote a thoracic curve in which the convexity is to the
rowed, a herniated disk in adulthood may lead to acute right; which is the most common type of idiopathic
paraplegia. Growth hormone is given to some children curve. Posterior curvature of the spine (kyphosis) is
with bone dysplasia. Limb lengthening is controversial, normal in the thoracic area, although excessive curva-
but possible. ture is pathologic. Anterior curvature of the spine, or
lordosis, is normal in the lumbar and cervical spines.
Aldegheri R, Dall’Oca C: Limb lengthening in short stature pa- Idiopathic scoliosis generally begins at age 8 or 10 years
tients. J Pediatr Orthop B 2001;10:238 [PMID: 11497369]. and usually progresses during growth. In rare instances,
Kanaka-Gantenbein C: Present status of the use of growth hor- infantile scoliosis may be seen in children age 2 years or
mone in short children with bone diseases (diseases of the younger.
skeleton). J Pediatr Endocrinol Metab 2001;14:17 [PMID: Idiopathic scoliosis is about four or five times more
11220700]. common in girls. The disorder is usually asymptomatic
in the adolescent years, but severe curvature can cause
8. Osteochondrodystrophy pain or loss of pulmonary function in later years. The
screening examination for scoliosis is performed by hav-
(Morquio Disease) ing the patient bend forward 90 degrees with the hands
Morquio disease is an autosomal recessive disorder of joined in the midline. An abnormal finding consists of
mucopolysaccharide storage. Skeletal abnormalities in- asymmetry of the height of the ribs or paravertebral
clude shortening of the spine, kyphosis, scoliosis, short- muscles on one side, indicating rotation of the trunk as-
ened extremities, pectus carinatum, genu valgum, and a sociated with lateral curvature.
 ORTHOPEDICS / 815

Diseases that may be associated with scoliosis in- the lateral curvature increases in severity. Deformity of
clude neurofibromatosis, Marfan syndrome, cerebral the rib cage causes long-term problems when lung vol-
palsy, muscular dystrophy, poliomyelitis, and myelo- umes are reduced.
dysplasia.
Between 5% and 7% of cases of scoliosis are due to Treatment
congenital vertebral anomalies such as a hemivertebra
or unilateral vertebral bridge. These curves are more Treatment of scoliosis depends on curve magnitude,
rigid than the more common idiopathic curve (see later skeletal maturity, and risk of progression. Curvatures of
discussion) and will often increase with growth, espe- less than 20 degrees usually do not require treatment
cially during adolescence. Eighty percent of cases of unless they show progression. Bracing is indicated for
scoliosis are idiopathic. Because 30% of family mem- curvature of 20–40 degrees in a skeletally immature
bers are also affected, siblings of an affected child child. Treatment is indicated for any curvature that
should be examined. demonstrates progression on serial radiologic examina-
Idiopathic infantile scoliosis, occurring in children tion. Curvatures greater than 40 degrees are resistant to
age 2–4 years, is uncommon in the United States but treatment by bracing. Thoracic curvatures greater than
more common in Great Britain. If the rib–vertebral 60 degrees have been correlated with poor pulmonary
angle of Mehta is less than 20 degrees, the curve will re- function in adult life. Curvatures of such severity are an
solve spontaneously. If the angle is greater, the curve indication for surgical correction and posterior spinal
will progress. Sciatic scoliosis may result from pressure fusion to maintain the correction. Curvatures of
on the spinal cord or roots by infectious processes or 40–60 degrees may also require spinal fusion if they are
herniation of the nucleus pulposus; the underlying progressive, are causing decompensation of the spine,
cause must be sought. Secondary curvature will resolve or cause unacceptable deformity.
as the primary problem is treated. Surgical fusion involves decortication of the bone
over the laminas and spinous processes, with the addi-
tion of bone graft. Rods, hooks, or pedicle screws main-
Clinical Findings tain postoperative correction, with activity restriction
A. SYMPTOMS AND SIGNS for several months until the bone fusion is solid. Treat-
Scoliosis in adolescents does not cause significant pain. ment requires a team approach and is best done in cen-
If a patient has significant pain, seek the underlying ters with full support facilities.
cause because the scoliosis is usually secondary to some
other disorder such as a bone or spinal cord tumor. De- Prognosis
formity of the rib cage and asymmetry of the waistline Compensated small curves that do not progress may be
are evident with curvatures of 30 degrees or more. A well tolerated throughout life, with minor deformity.
lesser curvature may be detected by the forward bend- Counsel the patients regarding the genetic transmission
ing test described in the preceding section, which is de- of scoliosis and caution that their children’s backs
signed to detect early abnormalities of rotation that should be examined as part of routine physicals. Large
may not be apparent when the patient is standing erect. thoracic curvatures greater than 60 degrees are associ-
B. IMAGING ated with shortened life span and may progress during
adult life. Large lumbar curvatures may lead to sub-
The most valuable radiographs are those taken of the luxation of the vertebrae and premature arthritic
entire spine in the standing position in both the degeneration of the spine, producing disabling pain in
anteroposterior and lateral planes. Usually one primary adulthood. Early detection allows for simple brace
curvature is evident with a compensatory curvature that treatment.
develops to balance the body. At times two primary
curvatures may be seen, usually in the right thoracic Danielsson A, L Nachemson A: Back pain and function 22 years
and left lumbar regions. Any left thoracic curvature after brace treatment for adolescent idiopathic scoliosis: A
should be suspected of being secondary to neurologic case-control study—part I. Spine 2003;28(18):2078.
disease, prompting a more meticulous neurologic exam-
ination. If the curvatures of the spine are balanced
(compensated), the head is centered over the center of
SLIPPED CAPITAL FEMORAL EPIPHYSIS
the pelvis and the patient is “in balance.” If the spinal Slipped capital femoral epiphysis is a condition caused
alignment is uncompensated, the head will be displaced by displacement of the proximal femoral epiphysis due
to one side, which produces an unsightly deformity. to disruption of the growth plate. The head of the
Rotation of the spine may be measured by scoliometer. femur is usually displaced medially and posteriorly rela-
This rotation is associated with a marked rib hump as tive to the femoral neck. The condition occurs in ado-
816 / CHAPTER 24

lescence and is most common in obese males. The time adult alignment is attained. Criteria for referral to
cause is unclear, although some authorities have shown an orthopedist include persistent bowing beyond age
experimentally that the strength of the perichondrial 2 years, bowing that is increasing rather than decreas-
ring stabilizing the epiphysial area is sufficiently weak- ing, bowing of one leg only, and knock-knee associated
ened by hormonal changes during adolescence such with short stature.
that the overload of excessive body weight can produce Bracing may be appropriate. Rarely an osteotomy is
a pathologic fracture through the growth plate. Hor- necessary for a severe problem such as Blount disease
monal studies in these children are usually normal, al- (proximal tibial epiphysial dysplasia).
though slipped capital femoral epiphysis is associated
with hypothyroidism. Zayer M: Long-term results after physiological genu varum. J Pedi-
The condition occasionally occurs acutely following atr Orthop B 2000;9:271.
a fall or direct trauma to the hip. More commonly,
vague symptoms occur over a protracted period in an TIBIAL TORSION
otherwise healthy child who presents with pain and
limp. The pain can be referred into the thigh or the “Toeing in” in small children is a common parental
medial side of the knee. Examine the hip joint in any concern. Tibial torsion is rotation of the leg between
obese child complaining of knee pain! The consistent the knee and the ankle. Internal rotation amounts to
finding on physical examination is limitation of inter- about 20 degrees at birth but decreases to neutral rota-
nal rotation of the hip. The diagnosis may be clearly ap- tion by age 16 months. The deformity is sometimes ac-
parent only in the lateral radiographic view. centuated by laxity of the knee ligaments, allowing ex-
Treatment is based on the same principles that gov- cessive internal rotation of the leg in small children. In
ern treatment of any fracture of the femoral neck in children who have a persistent internal rotation of the
that the head of the femur is internally fixed to the neck tibia beyond age 16–18 months, the condition is often
of the femur and the fracture line allowed to heal. Un- due to sleeping with feet turned in and can be reversed
fortunately, the severe complication of avascular necro- with an external rotation splint worn only at night.
sis occurs in 30% of these patients. There is a positive
correlation between forceful reduction of the slip and Arazi M et al: Normal development of the tibiofemoral angle in
children: A clinical study of 590 normal subjects from 3 to
avascular necrosis. In cases of acute slip, as evidenced by 17 years of age. J Pediatr Orthop 2001;21:264.
the absence of any callus formation about the growth
plate, it may be possible to reduce the hip by gentle
traction. In more chronic cases, a more expeditious pro- FEMORAL ANTEVERSION
cedure is to pin the slip as it lies. Remodeling of the Toeing in beyond age 2 or 3 years is usually secondary
fracture site often improves the position of the hip to femoral anteversion, which is characterized by more
without further surgery. internal rotation of the hip compared with external ro-
The long-term prognosis is guarded because most of tation. This femoral alignment follows a natural history
these patients continue to be overweight and overstress of progressive decrease toward neutral during growth.
their hip joints. Follow-up studies have shown a high Studies comparing the results of treatment with shoes
incidence of premature degenerative arthritis in this dis- or braces to the natural history have shown that little is
ease, even in those who do not develop avascular necro- gained by active treatment. Active external rotation ex-
sis. The development of avascular necrosis almost guar- ercises, such as skating or bicycle riding, can be encour-
antees a poor prognosis, because new bone does not aged. Osteotomy for rotational correction is rarely re-
readily replace the dead bone at this late stage of skele- quired. Children who have no external rotation of hip
tal development. About 30% of patients have bilateral in extension are candidates for orthopedic consultation.
involvement, which may occur as late as 1 or 2 years
after the primary episode. Lincoln TL, Suen PW: Common rotational variations in children.
J Am Acad Orthop Surg 2003;11(5):312.
Dobbs MB, Weinstein SL: Natural history and long-term out-
comes of slipped capital femoral epiphysis. Instr Course Lect
2001;50:571.
COMMON FOOT PROBLEMS
When a child begins to stand and walk, the long arch of
GENU VARUM & GENU VALGUM the foot is flat with a medial bulge over the inner bor-
der of the foot. The forefeet are mildly pronated or ro-
Genu varum (bowleg) is normal from infancy through tated inward, with a slight valgus alignment of the
age 2 years. The alignment then changes to genu val- knees. As the child grows and joint laxity decreases, the
gum (knock-knee) until about age 8 years, at which long arch is better supported and more normal relation-
 ORTHOPEDICS / 817

ships occur in the lower extremities. (See also sections Conservative therapy is ineffective. In symptomatic
on Metatarsus Varus and Talipes Equinovarus.) cases, surgery may be necessary to lengthen the con-
tracted extensor and flexor tendons and to release the
plantar fascia and other tight plantar structures. The as-
1. Flatfoot sociated varus heel deformity causes more problems
Flatfoot is a normal condition in infants. If the heel than the high arch.
cord is of normal length, full dorsiflexion is possible
with the heel in the neutral position. As long as the heel Mosca VS: The cavus foot. J Pediatr Orthop 2001;21:423.
cord is of normal length and a longitudinal arch is
noted when the child is sitting in a non-weight-bearing 4. Bunions (Hallux Valgus)
position, the parents can be assured that a normal arch
will probably develop. There is usually a familial inci- Adolescents may present with lateral deviation of the
dence of relaxed flatfeet in children who have no appar- great toe associated with a prominence over the head of
ent arch. In any child with a shortened heel cord or the first metatarsal. This deformity is painful only with
stiffness of the foot, other causes of flatfoot such as shoe wear and almost always can be relieved by fitting
tarsal coalition or vertical talus should be ruled out by a shoes that are wide enough in the toe. Surgery should
complete orthopedic examination and radiograph. be avoided in the adolescent, because further growth
In the child with an ordinary relaxed flatfoot, no ac- tends to cause recurrence of the deformity.
tive treatment is indicated unless calf or leg pain is pre-
sent. In children who have leg pains attributable to flat- Talab YA: Hallux valgus in children: A 5–14-year follow-up study
foot, a supportive shoe with scaphoid pad, such as a of 30 feet treated with a modified Mitchell osteotomy. Acta
Orthop Scand 2002;73(2):195.
good-quality sports shoe, is useful. An orthotic that
holds the heel in neutral and supports the arch may re-
lieve discomfort if more support is needed. An arch in-
sert should not be prescribed unless passive correction DEGENERATIVE PROBLEMS
of the arch is easily accomplished; otherwise, the skin
over the medial side of the foot will be irritated. (ARTHRITIS, BURSITIS, &
TENOSYNOVITIS)
Song KM: Flexible flatfeet in pre-school children. J Pediatr Orthop
2002;22(1):134.
Degenerative arthritis may follow childhood skeletal
problems, such as infection, slipped capital femoral epi-
2. Talipes Calcaneovalgus physis, avascular necrosis, or trauma, or it may occur in
association with hemophilia. Early effective treatment
Talipes calcaneovalgus is characterized by excessive dor- of these disorders can prevent arthritis. Degenerative
siflexion at the ankle and eversion of the foot. It is often changes in the soft tissues around joints may occur as a
present at birth and is due to intrauterine position. result of overuse syndrome in adolescent athletes.
Treatment consists of passive exercises, stretching the Young boys throwing excessive numbers of pitches, es-
foot into plantar flexion. In rare instances, it may be pecially curve balls, may develop “little leaguer” elbow,
necessary to use plaster casts to help with manipulation consisting of degenerative changes around the humeral
and positioning. Complete correction is the rule. condyles associated with pain, swelling, and limitation
of motion (see Chapter 25). In order to enforce the rest
necessary for healing, a plaster cast may be necessary. A
3. Cavus Foot more reasonable preventive measure is to limit the
This deformity consists of an unusually high longitudi- number of pitches thrown by children.
nal arch of the foot. It may be hereditary or associated Acute bursitis is uncommon in childhood, and other
with neurologic conditions such as poliomyelitis, Char- causes should be ruled out before this diagnosis is ac-
cot–Marie–Tooth disease, Friedreich ataxia, and di- cepted.
astematomyelia. There is usually an associated contrac- Tenosynovitis is most common in the region of the
ture of the toe extensor, producing a claw toe deformity knees and feet. Children taking dancing lessons, partic-
in which the metatarsal phalangeal joints are hyperex- ularly toe dancing, may have pain around the flexor
tended and the interphalangeal joints acutely flexed. tendon sheaths in the toes or ankles. Rest is effective
Any child presenting with cavus feet should receive a treatment. At the knee level, the patellar ligament may
careful neurologic examination and radiographs of the be irritated, with associated swelling in the infrapatellar
spine. fat pad. Synovitis in this area is usually due to overuse
818 / CHAPTER 24

and is treated by rest and nonsteroidal anti-inflammato- ciently to allow complete healing, which may take
ry drugs (NSAIDs). Corticosteroid injections are con- 3–6 weeks. Rehabilitation to include strengthening and
traindicated. restitution of kinesthetic sensation can prevent long-
term disability.

McGuine TA et al: Balance as a predictor of ankle injuries in high

TRAUMA school basketball players. Clin J Sport Med 2000;10:239.
Tabrizi P et al: Limited dorsiflexion predisposes to injuries of the
ankle in children. J Bone Joint Surg Br 2000;82:1103.
SOFT TISSUE TRAUMA
(Sprains, Strains, & Contusions)
2. Knee Sprains
A sprain is the stretching of a ligament, and a strain is a
stretch of a muscle or tendon. Contusions are generally Sprains of the collateral and cruciate ligaments are un-
due to tissue compression, with damage to blood vessels common in children. These ligaments are so strong that
within the tissue and the formation of hematoma. it is more common to injure the epiphysial growth
A severe sprain is one in which the ligament is com- plates, which are the weakest structures in the region of
pletely disrupted, resulting in instability of the joint. A the knees of children. In adolescence, however, the
mild or moderate sprain is one in which incomplete physes have started to close, and the knee joint is more
tearing of the ligament occurs but in which local pain like that of an adult, so that rupture of the anterior cru-
and swelling results. ciate ligament can result from a hyperextension injury.
Mild or moderate sprains are treated by rest of the If the injury produces avulsion of the tibial spine, open
affected joint, with ice and elevation to prevent pro- anatomic reduction is often required.
longed symptoms. By definition, mild or moderate Effusion of the knee after trauma deserves referral to
sprain is not associated with instability of the joint. an orthopedic specialist. The differential diagnosis in-
If more severe trauma occurs, resulting in tearing of cludes torn ligament, torn meniscus, and osteochondral
a ligament, instability of the joint may be demonstrated fracture. Nontraumatic effusion should be evaluated for
by gross examination or by stress testing with radio- inflammatory conditions (eg, juvenile rheumatoid
graphic documentation. Such deformity of the joint arthritis) or patellar malalignment.
may cause persistent instability resulting from inaccu-
rate apposition of the ligament ends during healing. If Gabriel SE et al: Change in diagnosis among orthopedists com-
instability is evident, surgical repair of the torn liga- pared to non-orthopedists in the management of acute knee
ment may be indicated. If a muscle is torn at its tendi- injuries. J Rheumatol 2000;27:2412.
nous insertion, it should be repaired.
The initial treatment of any sprain consists of ice, 3. Internal Derangements of the Knee
compression, and elevation. Splinting of the affected
joint protects against further injury and relieves Meniscal injuries are uncommon in children younger
swelling and pain. Ibuprofen and other NSAIDs are than age 12 years. Clicking or locking of the knee may
useful for pain. occur in young children as a result of a discoid lateral
meniscus, which is a rare congenital anomaly. As the
child approaches adolescence, internal damage to the
1. Ankle Sprains knee from a torsion weight-bearing injury may result in
The history will indicate that the injury was by either locking of the knee if tearing and displacement of a
forceful inversion or eversion. The more common in- meniscus occurs. Osteochondral fractures secondary to
version injury results in tearing or injury to the lateral osteochondritis dissecans may also present as internal
ligaments, whereas an eversion injury will injure the derangements of the knee in adolescence. Posttraumatic
medial ligaments of the ankle. The injured ligaments synovitis may mimic a meniscal lesion. In any severe in-
may be identified by means of careful palpation for jury to the knee, epiphysial injury should be suspected;
point tenderness around the ankle. The joint should be stress films will sometimes demonstrate separation of
supported or immobilized at a right angle, which is the the distal femoral epiphysis in such cases. Epiphysial in-
functional position. Adhesive taping may be effective jury should be suspected whenever tenderness is present
but should be changed frequently to prevent blisters. on both sides of the metaphysis of the femur after in-
Use of a posterior plaster splint or air splint produces jury.
joint rest, and the extremity can be protected by using
crutches. Prolonged use of a plaster cast is usually not Smith AD: The skeletally immature knee: What’s new in overuse
necessary, but the sprained ankle should be rested suffi- injuries. Instr Course Lect 2003;52:691.
 ORTHOPEDICS / 819

4. Back Sprains can usually be reduced by gentle sustained traction. It

often happens that no anesthetic is necessary for several
Sprains of the ligaments and muscles of the back are hours after the injury, because of the protective anes-
unusual in children but may occur as a result of violent thesia produced by the injury. Following reduction, the
trauma from automobile accidents or athletic injuries. joint should be splinted for transportation of the pa-
Back pain in a child may be the only symptom of sig- tient.
nificant disease and warrants clinical investigation. In- The dislocated joint should be treated by immobi-
flammation, infection, renal disease, or tumors can lization for at least 3 weeks, followed by graduated ac-
cause back pain in children, and sprain should not be tive exercises through a full range of motion. Vigorous
accepted as a routine diagnosis. passive manipulation of the joint by a therapist may be
harmful.
Balague F et al: Low-back pain in children. Lancet 2003;361
(9367):1403.
Wall EJ et al: Backpacks and back pain: Where’s the epidemic? 1. Subluxation of the Radial Head
J Pediatr Orthop 2003;23(4):437.
(Nursemaid Elbow)
Infants may sustain subluxation of the radial head as a
5. Contusions result of being lifted or pulled by the hand. The child
Contusion of muscle with hematoma formation pro- appears with the elbow fully pronated and painful. The
duces the familiar “charley horse” injury. Treatment of usual complaint is that the child’s elbow will not bend.
such injuries is by application of ice, compression, and Radiographic findings are normal, but there is point
rest. Exercise should be avoided for 5–7 days. Local tenderness over the radial head. When the elbow is
heat may hasten healing once the acute phase of tender- placed in full supination and slowly moved from full
ness and swelling is past. flexion to full extension, a click may be palpated at the
level of the radial head. The relief of pain is remarkable,
as the child usually stops crying immediately. The
6. Myositis Ossificans elbow may be immobilized in a sling for comfort for a
Ossification within muscle occurs when there is suffi- day. Occasionally, symptoms last for several days, re-
cient trauma to cause a hematoma that later heals in the quiring more prolonged immobilization.
manner of a fracture. The injury is usually a contusion Pulled elbow may be a clue to battering. This should
and occurs most commonly in the quadriceps of the be considered during examination, especially if the
thigh or the triceps of the arm. When a severe injury problem is recurrent.
with hematoma is recognized, it is important to splint
the extremity and avoid activity. If further trauma
causes recurrent injury, ossification may reach spectacu- 2. Recurrent Dislocation of the Patella
lar proportions and resemble an osteosarcoma. Recurrent dislocation of the patella is more common in
Disability is great, with local swelling and heat and loose-jointed individuals, especially adolescent girls. If
extreme pain on the slightest motion of the adjacent the patella completely dislocates, it nearly always goes
joint. The limb should be rested, with the knee in ex- laterally. Pain is severe, and the patient is brought to
tension or the elbow in 90 degrees of flexion, until the the doctor with the knee slightly flexed and an obvious
local reaction has subsided. After local heat and tender- bony mass lateral to the knee joint associated with a flat
ness have decreased, gentle active exercises may be initi- area over the anterior knee. Radiologic examination
ated. Passive stretching exercises are not indicated, be- confirms the diagnosis. The patella may be reduced by
cause they may stimulate the ossification reaction. If extending the knee and placing slight pressure on the
surgery is necessary, it should not be attempted before patella while gentle traction is exerted on the leg. In
9 months to 1 year after injury, because it may restart subluxation of the patella, the symptoms may be more
the process and lead to an even more severe reaction. subtle, and the patient will complain that the knee
“gives out” or “jumps out of place.”
TRAUMATIC SUBLUXATIONS In the case of complete dislocation, the knee should
be immobilized for 3–4 weeks, followed by a physical
& DISLOCATIONS therapy program for strengthening the quadriceps mus-
Dislocation of a joint is always associated with severe cle. Operation may be necessary to tighten the knee
damage to the ligaments and joint capsule. In contrast joint capsule if dislocation or subluxation is recurrent.
to fracture reduction, which may be safely postponed, In such instances, if the patella is not stabilized, re-
dislocations must be reduced immediately. Dislocations peated dislocation produces damage to the articular car-
820 / CHAPTER 24

tilage of the patellofemoral joint and premature degen- the time required for remodeling. The fracture can be
erative arthritis. considered healed when no tenderness or local heat is
present and when adequate bony callus is seen on radi-
Eilert RE: Congenital dislocation of the patella. Clin Orthop ograph.
2001;:22.

FRACTURES 4. Fracture of the Clavicle

Clavicular fractures are very common injuries in infants
1. Epiphysial Separations and children. The patient can be immobilized in a sling
In children, epiphysial separations and fractures are for comfort. The healing callus will be apparent when
more common than ligamentous injuries. This finding the fracture has consolidated, but this unsightly lump
is based on the fact that the ligaments of the joints are will generally resolve over a period of months to a year.
generally stronger than the associated growth plates. In
instances in which dislocation is suspected, a radi- 5. Supracondylar Fractures
ograph should be taken in order to rule out epiphysial
fracture. Radiographs of the opposite extremity, espe- of the Humerus
cially for injuries around the elbow, may be valuable for Supracondylar fractures tend to occur in children age
comparison. Reduction of a fractured epiphysis should 3–6 years and are potentially dangerous because of the
be done under anesthesia to align the growth plate with proximity to the brachial artery in the distal arm. They
the least amount of force. Fractures across the growth are usually associated with a significant amount of
plate may produce bony bridges that will cause prema- trauma, so that swelling may be severe. Most often,
ture cessation of growth or angular deformities of the these fractures are treated by closed reduction and per-
extremity. Epiphysial fractures around the shoulder, cutaneous pinning. Complications associated with
wrist, and fingers can usually be treated by closed re- supracondylar fractures include Volkmann ischemic
duction, but fractures of the epiphyses around the contracture of the forearm due to vascular compromise
elbow often require open reduction. In the lower ex- and cubitus varus (decreased carrying angle) secondary
tremity, accurate reduction of the epiphysial plate is to poor reduction. The so-called gunstock deformity of
necessary to prevent joint deformity if a joint surface is the elbow may be somewhat unsightly but does not
involved. If angular deformities result, corrective os- usually interfere with joint function.
teotomy may be necessary.
Gosens T, Bongers KJ: Neurovascular complications and func-
Peterson HA: Physeal fractures: Part 3. Classification. J Pediatr Or-
tional outcome in displaced supracondylar fractures of the
thop 1994;14:439 [PMID: 8077424].
humerus in children. Injury 2003;34(4):267 [PMID:
12667778].
2. Torus Fractures
Torus fractures consist of “buckling” of the cortex due 6. General Comments on Other
to compression of the bone. They usually occur in the Fractures in Children
distal radius or ulna. Alignment is usually satisfactory,
and simple immobilization for 3 weeks is sufficient. Reduction of fractures in children is usually accom-
plished by simple traction and manipulation; open re-
duction is indicated if a satisfactory alignment is not
3. Greenstick Fractures obtained. Remodeling of the fracture callus usually pro-
Greenstick fractures involve frank disruption of the cor- duces an almost normal appearance of the bone over a
tex on one side of the bone but no discernible cleavage matter of months. The younger the child, the more re-
plane on the opposite side. These fractures are angu- modeling is possible. Angular deformities remodel reli-
lated but not displaced, because the bone ends are not ably. Rotatory malalignment does not remodel.
separated. Reduction is achieved by straightening the The physician should be suspicious of child abuse
arm into normal alignment, and reduction is main- whenever the age of a fracture does not match the his-
tained by a snugly fitting plaster cast. It is necessary to tory given or when the severity of the injury is more
get a radiograph of greenstick fractures again in a week than the alleged accident would have produced. In sus-
to 10 days to make certain that the reduction has been pected cases of battering where no fracture is present on
maintained in the cast. A slight angular deformity can the initial radiograph, a repeat radiograph 10 days later
be corrected by remodeling of the bone. The farther the is in order. Bleeding beneath the periosteum will be cal-
fracture is from the growing end of the bone, the longer cified by 7–10 days, and the radiographic appearance is
 ORTHOPEDICS / 821

almost diagnostic of severe closed trauma characteristic Puncture wounds are especially liable to lead to os-
of a battered child. teomyelitis and should be carefully debrided.
Initially, broad-spectrum antibiotics should be ad-
ministered, but the final choice of antibiotics is directed
by culture results. A tetanus toxoid booster may be in-
dicated. Gas gangrene is best prevented by adequate de-
INFECTIONS OF THE BONES bridement.
& JOINTS After exogenous osteomyelitis has become estab-
lished, treatment becomes more complicated, requiring
extensive surgical debridement and intravenous antibi-
OSTEOMYELITIS otics.
Osteomyelitis is an infectious process that usually starts
in the spongy or medullary bone and then extends to 2. Hematogenous Osteomyelitis
involve compact or cortical bone. The lower extremities
are most often affected, and there is commonly a his- Hematogenous osteomyelitis is usually caused by pyo-
tory of trauma. Osteomyelitis may occur as a result of genic bacteria; 85% of cases are due to staphylococci.
direct invasion from the outside through a penetrating Streptococci are a less common cause of osteomyelitis.
wound (nail) or open fracture, but hematogenous Pseudomonas organisms are common in cases of nail
spread of infection (eg, pyoderma or upper respiratory puncture wounds. Children with sickle cell anemia are
tract infection) from other infected areas is much more especially prone to osteomyelitis caused by salmonellae.
common. The most common infecting organism is
Staphylococcus aureus, which has a tendency to infect Clinical Findings
the metaphyses of growing bones. Anatomically, circu-
lation in the long bones is such that the arterial supply
A. SYMPTOMS AND SIGNS
to the metaphysis just below the growth plate is close to In infants, the manifestations of osteomyelitis may be
end arteries, which turn sharply to end in venous sinu- subtle, presenting as irritability, diarrhea, or failure to
soids, causing a relative stasis. In the infant younger feed properly; the temperature may be normal or
than age 1 year, there is direct vascular communication slightly low; and the white blood count may be normal
with the epiphysis across the growth plate, so that di- or only slightly elevated. There may be pseudoparalysis
rect spread may occur from the metaphysis to the epi- of the involved limb. In older children, the manifesta-
physis and subsequently into the joint. In the older tions are more striking, with severe local tenderness and
child, the growth plate provides an effective barrier, the pain, often high fever, rapid pulse, and elevated white
epiphysis is usually not involved, and the infection blood count and erythrocyte sedimentation rate (ESR).
spreads retrograde from the metaphysis into the diaph- Osteomyelitis of a lower extremity often occurs around
ysis and, by rupture through the cortical bone, down the knee joint in children age 7–10 years. Tenderness is
along the diaphysis beneath the periosteum. most marked over the metaphysis of the bone where the
process has its origin. For a child who refuses to bear
weight, ostomyelitis is high in the differential diagnosis.
1. Exogenous Osteomyelitis B. LABORATORY FINDINGS
To avoid osteomyelitis by direct extension, all wounds Blood cultures are often positive early. The most signif-
must be carefully examined and cleansed. Osteomyelitis icant test in infancy is the aspiration of pus. It is useful
is a common occurrence from pressure sores in anes- to needle the bone in the area of suspected infection
thetic areas, such as in patients with spina bifida. Cul- and aspirate any fluid present. This fluid should be
tures of the wound made at the time of exploration and stained for organisms and cultured. Even edema fluid
debridement may be useful if signs of infection develop may be useful for determining the causative organism.
subsequently. Copious irrigation is necessary, and all Elevation of the ESR above 50 mm/h is typical for os-
nonviable skin, subcutaneous tissue, fascia, and muscle teomyelitis. C reactive protein is elevated earlier than
must be excised. In extensive or contaminated wounds, the ESR.
antibiotic coverage is indicated. Contaminated lacera-
tions should be left open and secondary closure per- C. IMAGING
formed 3–5 days later. If at the time of delayed closure Nonspecific local swelling is the first radiographic find-
further necrotic tissue is present, it should be excised. ing. This is followed by elevation of the periosteum,
Leaving the wound open allows the infection to stay at with formation of new bone from the cambium layer of
the surface rather than extend inward to the bone. the periosteum occurring after 3–6 days. As the infec-
822 / CHAPTER 24

tion becomes chronic, areas of cortical bone are isolated Prognosis

by pus spreading down the medullary canal, causing
rarefaction and demineralization of the bone. Such iso- When osteomyelitis is diagnosed in the early clinical
lated pieces of cortex become ischemic and form se- stages and prompt antibiotic therapy is begun, the
questra (dead bone fragments). These radiographic prognosis is excellent. If the process has been unat-
findings are late but specific. Osteomyelitis should be tended for a week to 10 days, there is almost always
diagnosed clinically before significant radiographic some permanent loss of bone structure, as well as the
findings are present. Bone scan is sensitive but nonspe- possibility of growth abnormality.
cific and should be interpreted in the clinical context
before radiographic findings become positive. Magnetic
resonance imaging can demonstrate edema early or soft Song KM, Sloboda JF: Acute hematogenous osteomyelitis in chil-
tissue thickening later. dren. J Am Acad Orthop Surg 2001;9:166 [PMID:
11421574].

Treatment
A. SPECIFIC MEASURES PYOGENIC ARTHRITIS
Antibiotics should be started intravenously as soon as
the diagnosis of osteomyelitis is made. Oral antibiotics The source of pyogenic arthritis varies according to the
are begun when tenderness, fever, the white cell count, child’s age. In the infant, pyogenic arthritis often develops
and the ESR are all decreasing and the culture is posi- by spread from adjacent osteomyelitis. In the older child,
tive. Agents that cover S aureus and Streptococcus pyo- it presents as an isolated infection, usually without bony
genes (eg, oxacillin, nafcillin, cefazolin, clindamycin) are involvement. In teenagers with pyogenic arthritis, an un-
appropriate for most cases. For specific recommenda- derlying systemic disease or an organism (eg, the gono-
tions and for possible Pseudomonas infection, see Chap- coccus) that has an affinity for joints is usually the cause.
ter 38. The infecting organism varies with age: group B
Chronic infections are treated for months. Follow- streptococcus and S aureus in those younger than age
ing surgical debridement, Pseudomonas foot infections 4 months; Haemophilus influenzae and S aureus in those
usually respond to 1–2 weeks of antibiotic treatment. age 4 months to 4 years; and S aureus and S pyogenes in
older children and adolescents. H influenzae is now un-
B. GENERAL MEASURES common because of effective immunization. Kingella
Splinting of the limb minimizes pain and decreases kingae is a gram-negative bacterium that occasionally
spread of the infection by lymphatic channels through causes pyarthrosis.
the soft tissue. The splint should be removed periodi- The initial effusion of the joint rapidly becomes pu-
cally to allow active use of adjacent joints and prevent rulent. An effusion of the joint may accompany os-
stiffening and muscle atrophy. In chronic osteomyelitis, teomyelitis in the adjacent bone. A white cell count ex-
splinting may be necessary to guard against fracture of ceeding 100,000/µL in the joint fluid indicates a
the weakened bone. definite purulent infection. Generally, spread of infec-
tion is from the bone into the joint, but unattended
C. SURGICAL MEASURES pyogenic arthritis may also affect adjacent bone. The
Aspiration of the metaphysis for culture and Gram ESR is often above 50 mm/h.
stain is the most useful diagnostic measure in any case
of suspected osteomyelitis. In the first 24–72 hours, it
may be possible to treat osteomyelitis with antibiotics Clinical Findings
alone. If frank pus is aspirated from the bone, however,
surgical drainage is indicated. If the infection has not A. SYMPTOMS AND SIGNS
shown a dramatic response within 24 hours, surgical In older children, the signs may be striking, with fever,
drainage is also indicated. It is important that all devi- malaise, vomiting, and restriction of motion. In infants,
talized soft tissue be removed and adequate exposure of paralysis of the limb due to inflammatory neuritis may
the bone obtained to permit free drainage. Excessive be evident. Infection of the hip joint in infants should
amounts of bone should not be removed when draining be suspected if decreased abduction of the hip is present
acute osteomyelitis, because it will not be completely in an infant who is irritable or feeding poorly. A history
replaced by the normal healing process. Bone damage is of umbilical catheter treatment in the newborn nursery
limited by surgical drainage, whereas failure to evacuate should alert the physician to the possibility of pyogenic
pus in acute cases may lead to widespread damage. arthritis of the hip.
 ORTHOPEDICS / 823

B. IMAGING out by negative skin testing. The joints most commonly

Early distention of the joint capsule is nonspecific and affected in children are the intervertebral disks, result-
difficult to measure by radiograph. In the infant with ing in gibbus or dorsal angular deformity at the site of
unrecognized pyogenic arthritis, dislocation of the joint involvement.
may follow within a few days as a result of distention of Treatment is by local drainage of the abscess, fol-
the capsule by pus. Later changes include destruction of lowed by antituberculous therapy. Prolonged immobi-
the joint space, resorption of epiphysial cartilage, and lization in a plaster cast or prolonged bed rest is neces-
erosion of the adjacent bone of the metaphysis. The sary to promote healing. Spinal fusion may be required
bone scan shows increased flow and increased uptake to preserve stability of the vertebral column.
about the joint.
Rasool MN: Osseous manifestations of tuberculosis in children.
J Pediatr Orthop 2001;21:749 [PMID: 11675548].
Treatment
Aspiration of the joint is the key to diagnosis. In the hip DISKITIS
joint, pyogenic arthritis is most easily treated by surgical
drainage because the joint is deep and difficult to aspirate Results of a study of 47 patients support the view that
and is also inaccessible to thorough cleaning through so-called diskitis is pyogenic infectious spondylitis in
needle aspiration. Arthroscopic irrigation and debride- children and that supportive treatment and intravenous
ment have been successful in treating pyogenic arthritis antibiotics are likely to lead to rapid relief of symptoms
of the knee. If fever and clinical symptoms do not sub- and signs without recurrence.
side within 24 hours after treatment is begun, open sur-
gical drainage is indicated. Antibiotics can be selected Brown R et al: Discitis in young children. J Bone Joint Surg Br
based on the child’s age, results of the Gram stain, and 2001;83:106 [PMID: 11245515].
culture of the aspirated pus. Reasonable empiric therapy
in infants is nafcillin or oxacillin plus a third-generation TRANSIENT SYNOVITIS OF THE HIP
cephalosporin. An antistaphylococcal agent alone is usu-
ally adequate for children older than age 5 years. For The most common cause of limping and pain in the
staphylococcal infections, 3 weeks of therapy is recom- hip in children in the United States is transitory synovi-
mended; for other organisms, 2 weeks is usually suffi- tis, an acute inflammatory reaction that often follows
cient. Oral therapy may be begun when clinical signs an upper respiratory infection and is generally self-lim-
have improved markedly. It is not necessary to give intra- ited. In questionable cases, aspiration of the hip yields
articular antibiotics, because good levels are achieved in only yellowish fluid, ruling out pyogenic arthritis. Gen-
the synovial fluid with parenteral administration. erally, however, toxic synovitis of the hip is not associ-
ated with elevation of the ESR, white blood count, or
Prognosis temperature above 38.3°C. It classically affects children
age 3–10 years and is more common in boys than girls.
The prognosis for the patient with pyogenic arthritis is There is limitation of motion of the hip joint, particu-
excellent if the joint is drained early, before damage to larly internal rotation, and radiographic changes are
the articular cartilage has occurred. If infection is pre- nonspecific, with some swelling apparent in the soft tis-
sent for more than 24 hours, dissolution of the proteo- sues around the joint.
glycans in the articular cartilage takes place, with subse- Treatment consists of bed rest and the use of trac-
quent arthrosis and fibrosis of the joint. Damage to the tion with slight flexion of the hip. NSAIDs shorten the
growth plate may also occur, especially within the hip course of the disease, although even with no treatment,
joint, where the epiphysial plate is intracapsular. the disease usually runs its course in days. It is impor-
tant to maintain radiographic follow-up because toxic
Kothari NA et al: Imaging of musculoskeletal infections. Radiol synovitis may be the precursor of avascular necrosis of
Clin North Am 2001;39:653 [PMID: 11549164]. the femoral head (described in the next section) in a
small percentage of patients. Radiographs can be ob-
TUBERCULOUS ARTHRITIS tained at 6 weeks, or earlier if either a persistent limp or
pain is present.
Tuberculous arthritis is now a rare disease in the
United States. Children in poor social circumstances, Vila-Verde VM, da Silva KC: Bone age delay in Perthes disease and
however, such as homeless families, are prone to tuber- transient synovitis of the hip. Clin Orthop 2001;4:118
culous arthritis. Generally the infection may be ruled [PMID: 11302301].
824 / CHAPTER 24

Table 24–1. The osteochondroses.

VASCULAR LESIONS &
Typical
AVASCULAR NECROSIS Ossification Age
(Osteochondroses) Center Eponym (years)
Capital femoral Legg–Calvé–Perthes disease 4–8
Osteochondrosis due to vascular lesions may affect vari- Tarsal navicular Köhler bone disease 6
ous growth centers. Table 24–1 indicates the common
sites and the typical ages at presentation. Second metatarsal Freiberg disease 12–14
head
In contrast to other body tissues that undergo in-
farction, bone removes necrotic tissue and replaces it Vertebral ring Scheuermann disease 13–16
with living bone in a process called creeping substitu- Capitellum Panner disease 9–11
tion. This replacement of necrotic bone may be so
complete and so perfect that a completely normal bone Tibial tubercle Osgood–Schlatter disease 11–13
results. Adequacy of replacement depends on the pa- Calcaneus Sever disease 8–9
tient’s age, the presence or absence of associated infec-
tion, the congruity of the involved joint, and other
physiologic and mechanical factors.
Because of their rapid growth in relation to their
blood supply, the secondary ossification centers in the is effusion of the joint associated with slight widening
epiphyses are subject to avascular necrosis. Despite the of the joint space and periarticular swelling. Decreased
number of different names referring to avascular necro- bone density in and around the joint is apparent after a
sis of the epiphyses, the process is identical, necrosis of few weeks. The necrotic ossification center appears
bone followed by replacement (see Table 24–1). more dense than the surrounding viable structures, and
Even though the pathologic and radiographic fea- the femoral head is collapsed or narrowed.
tures of avascular necrosis of the epiphyses are well As replacement of the necrotic ossification center
known, the cause is not generally agreed on. Necrosis occurs, rarefaction of the bone occurs in a patchwork
may follow known causes such as trauma or infection, fashion, producing alternating areas of rarefaction and
but idiopathic lesions usually develop during periods of relative density, referred to as “fragmentation” of the
rapid growth of the epiphyses. epiphysis.
In the hip, widening of the femoral head may occur
associated with flattening, or coxa plana. If infarction
AVASCULAR NECROSIS has extended across the growth plate, a radiolucent le-
OF THE PROXIMAL FEMUR sion will be evident within the metaphysis. If the
(Legg–Calvé–Perthes Disease) growth center of the femoral head has been damaged so
that normal growth is arrested, shortening of the
The vascular supply of the proximal femur is precari- femoral neck results.
ous, and when it is interrupted, necrosis results. Eventually, complete replacement of the epiphysis
develops as living bone replaces necrotic bone by creep-
Clinical Findings ing substitution. The final shape of the head depends
on the extent of the necrosis and collapse of weakened
A. SYMPTOMS AND SIGNS
bone.
The highest incidence of Legg–Calvé–Perthes disease is
between ages 4 and 8 years. Persistent pain is the most
common symptom, and the patient may present with
Differential Diagnosis
limp or limitation of motion. Differential diagnosis must include inflammation and
infection and dysplasia. Transient synovitis of the hip
B. LABORATORY FINDINGS may be distinguished from Legg–Calvé–Perthes disease
Laboratory findings, including studies of joint aspirates, by serial radiographs.
are normal.
C. IMAGING Treatment
Radiographic findings correlate with the progression of The principle of treatment is protection of the joint. If
the process and the extent of necrosis. The early finding the joint is deeply seated within the acetabulum and
 ORTHOPEDICS / 825

normal joint motion is maintained, a reasonably good

hip can result. Little benefit has been shown from brac- NEUROLOGIC DISORDERS
ing.
INVOLVING THE
Prognosis MUSCULOSKELETAL SYSTEM
The prognosis for complete replacement of the necrotic
femoral head in a child is excellent, but the functional ORTHOPEDIC ASPECTS
result depends on the amount of deformity that devel- OF CEREBRAL PALSY
ops during the time the softened structure exists. In
Legg–Calvé–Perthes disease, the prognosis depends on Early physical therapy to encourage completion of the
the completeness of involvement of the epiphysial cen- normal developmental patterns may benefit patients
ter. In general, patients with metaphysial defects, those with cerebral palsy. The greatest gains from this therapy
in whom the disease develops late in childhood, and are obtained during the first few years of life, and ther-
those who have more complete involvement of the apy should not be continued when no improvement is
femoral head have a poorer prognosis. apparent.
Bracing and splinting are of questionable benefit, al-
though night splints may be useful in preventing equi-
Joseph B et al: Natural evolution of Perthes disease: A study of
610 children under 12 years of age at disease onset. J Pediatr
nus deformity of the feet or adduction contractures of
Orthop 2003;23(5):590 [PMID: 12960621]. the hips. Orthopedic surgery is useful for treating joint
Hesse B, Kohler G: Does it always have to be Perthes’ disease? contractures that interfere with function. In general,
What is epiphyseal dysplasia? Clin Orthop 2003(414):219 muscle transfers are unpredictable in cerebral palsy, and
[PMID: 12966296]. most orthopedic procedures are directed at tendon
lengthening or bony stabilization by osteotomy or
arthrodesis.
OSTEOCHONDRITIS DISSECANS Flexion and adduction of the hip due to hyperactiv-
In osteochondritis dissecans, a wedge-shaped necrotic ity of the adductors and flexors may produce a progres-
area of bone and cartilage develops adjacent to the ar- sive paralytic dislocation of the hip, which can lead to
ticular surface. The fragment of bone may be broken pain and dysfunction. Treatment of this dislocation is
off from the host bone and displaced into the joint as a difficult and unsatisfactory. The principal preventive
loose body. If it remains attached, the necrotic frag- measure is abduction bracing, but this must often be
ment may be completely replaced by creeping substitu- supplemented by release of the adductors and hip flex-
tion. ors in order to prevent dislocation. In severe cases, os-
The pathologic process is the same as that described teotomy of the femur may also be necessary to correct
previously for avascular necrosing lesions of ossification the bony deformities of femoral anteversion and coxa
centers. Because these lesions are adjacent to articular valga that are invariably present. Patients with a pre-
cartilage, however, joint damage may occur. dominantly athetotic pattern are poor candidates for
The most common sites of these lesions are the knee any surgical procedure or bracing.
(medial femoral condyle), the elbow joint (capitellum), Because it is difficult to predict the outcome of sur-
and the talus (superior lateral dome). Joint pain is the gical procedures in cerebral palsy, the surgeon must ex-
usual presenting complaint. However, local swelling or amine patients on several occasions before any operative
locking may be present, particularly if a fragment is free procedure is undertaken. Follow-up care by a physical
in the joint. Laboratory studies are normal. therapist to maximize the anticipated long-term gains
Treatment consists of protection of the involved should be arranged before the operation.
area from mechanical damage. If a fragment is free
within the joint as a loose body, it must be removed. Koman LA: Cerebral palsy: Past, present, and future. J South Or-
For some marginal lesions, it may be worthwhile to thop Assoc 2002;11(2):93 [PMID: 12741589].
drill the necrotic fragment to encourage more rapid vas-
cular ingrowth and replacement. If large areas of a ORTHOPEDIC ASPECTS
weight-bearing joint are involved, secondary degenera-
tive arthritis may result. OF MYELODYSPLASIA
Patients born with spina bifida cystica (aperta) should
Wall E, Von Stein D: Juvenile osteochondritis dissecans. Orthop be examined early by an orthopedic surgeon. The level
Clin North Am 2003;34(3):341 [PMID: 12974484]. of neurologic involvement determines the muscle im-
826 / CHAPTER 24

balance that will be present and apt to produce defor- causes of knee pain are traumatic, infectious, or devel-
mity with growth. The involvement is often asymmetri- opmental in origin.
cal and tends to change during the first 12–18 months
of life. Early closure of the sac is the rule, although Miller SL, Hoffer FA: Malignant and benign bone tumors. Radiol
there has been some hesitancy to provide treatment to Clin North Am 2001;39:673 [PMID: 11549165].
all of these patients because of the extremely poor prog-
nosis associated with congenital hydrocephalus, high Osteochondroma
levels of paralysis, and associated congenital anomalies.
A high percentage of these children have hydro- Osteochondroma is the most common bone tumor in
cephalus, which may be evident at birth or shortly children. It usually presents as a pain-free mass. When
thereafter, requiring shunting. Associated muscu- present, pain is caused by adventitious bursitis or ten-
loskeletal problems may include clubfoot, congenital dinitis due to irritation by the tumor. The lesion may
dislocation of the hip, arthrogryposis-type changes of be single or multiple. Pathologically, the lesion is a
the lower extremities, and congenital scoliosis. The bone mass capped with cartilage. These masses tend to
most common lesions are at the level of L3–4 and tend grow during childhood and adolescence in proportion
to affect the hip joint, with progressive dislocation oc- to the child’s growth.
curring during growth. Foot deformities may be in any On radiograph the tumors tend to be in the meta-
direction and are complicated by the fact that sensation physial region of long bones and may be pedunculated
is generally absent. Spinal deformities develop in a high or sessile. The cortex of the underlying bone “flows”
percentage of these children, with scoliosis present in into the base of the tumor.
approximately 40%. Ambulation may require long leg An osteochondroma should be excised if it interferes
braces. Careful urologic follow-up must be obtained to with function, is frequently traumatized, or is large
prevent complications from bladder dysfunction. enough to be deforming. The prognosis is excellent.
In children who have a reasonable likelihood of Malignant transformation is very rare.
walking, operative treatment consists of reduction of
the hip and alignment of the feet in the weight-bearing Bottner F et al: Surgical treatment of symptomatic osteochon-
droma: A three- to eight-year follow-up study. J Bone Joint
position as well as stabilization of the scoliosis. In chil- Surg Br 2003;85(8):1161 [PMID: 14653600].
dren who lack active quadriceps function and extensor
power of the knee, the likelihood of ambulation is
greatly decreased. In such patients, aggressive surgery in Osteoid Osteoma
the hip region may result in stiffening of the joints, Osteoid osteoma classically produces night pain that
thus preventing sitting. Multiple foot operations are can be relieved by aspirin. On physical examination
also contraindicated in these children. there usually is tenderness over the lesion. An osteoid
The overall treatment of the child with spina bifida osteoma in the upper femur may cause pain referred to
should be coordinated in a multidisciplinary clinic the knee.
where various medial specialists work with therapists, On radiograph the lesion is a radiolucent nidus sur-
social workers, and teachers to provide the best possible rounded by dense osteosclerosis that may obscure the
care. nidus. Bone scan shows intense uptake in the lesion.
Surgical incision of the nidus is curative and may be
Bartonek A, Saraste H: Factors influencing ambulation in
done using computed tomography imaging and mini-
myelomeningocele: A cross-sectional study. Dev Med Child mally invasive technique. The prognosis is excellent,
Neurol 2001;43:253 [PMID: 11305403]. with no known cases of malignant transformation, al-
though the lesion has a tendency to recur.

NEOPLASIA OF THE Enchondroma

MUSCULOSKELETAL SYSTEM Enchondroma is usually a silent lesion unless it pro-
Neoplastic diseases of the musculoskeletal system are a duces a pathologic fracture. On radiograph it is radiolu-
serious problem because of the poor prognosis of malig- cent, usually in a long bone. A speckled calcification
nant tumors arising in bone or other tissues derived may be present. The classic lesion looks as though
from mesoderm. Fortunately, few of the benign lesions someone dragged his or her fingernails through clay,
undergo malignant transformation. Accurate diagnosis making streaks in the bones. Enchondroma is treated
depends on correlation of the clinical, radiograph, and by surgical curettage and bone grafting. The prognosis
microscopic findings. Complaints about the knee is excellent. Malignant transformation may occur but is
should be investigated for tumor, although the usual very rare in childhood.
 ORTHOPEDICS / 827

Chondroblastoma tial diagnosis. The lesion may be multicentric. Ewing

sarcoma is radiolucent and destroys the cortex, fre-
In chondroblastoma, the presenting complaint is pain quently in the diaphysial region. Reactive bone forma-
around a joint. This neoplasm may produce a patho- tion may occur about the lesion, seen as successive lay-
logic fracture. On radiograph the lesion is radiolucent ers of so-called onion skin layering.
and can perforate the epiphysial cartilage. Calcification Treatment is with multiagent chemotherapy, radia-
is unusual, with little or no reactive bone. The lesion is tion, and surgical resection. The prognosis is poor with
treated by surgical curettage and bone grafting. The large tumor size, pelvic lesions, and poor response to
prognosis is excellent if complete curettage is per- chemotherapy.
formed. There is no known malignant transformation.

Masui F et al: Chondroblastoma: A study of 11 cases. Eur J Surg

Oncol 2002;28(8):869 [PMID: 12477480]. MISCELLANEOUS DISEASES
OF BONE
Nonossifying Fibroma
Nonossifying fibroma is also called benign cortical de- FIBROUS DYSPLASIA
fect and is nearly always an incidental finding on radi-
ograph. The most frequent sites are the distal femur Dysplastic fibrous tissue replacement of the medullary
and proximal tibia. Nonossifying fibroma is a radiolu- canal is accompanied by the formation of metaplastic
cent lesion eccentrically located in the bone. Usually a bone in fibrous dysplasia. Three forms of the disease are
thin sclerotic border is evident. Multiple lesions may be recognized: monostotic, polyostotic, and polyostotic
present. No treatment is needed because these lesions with endocrine disturbances (precocious puberty in fe-
heal as they ossify with maturation of the bone and males, hyperthyroidism, and hyperadrenalism [Albright
growth. syndrome]).

Osteosarcoma Clinical Findings

In osteosarcoma, the presenting complaint is usually A. SYMPTOMS AND SIGNS
pain in a long bone, although functional loss, the mass The lesion or lesions may be asymptomatic. Pain, if
of the tumor, or limp may be the complaint. Pathologic present, is probably due to pathologic fractures. In fe-
fracture is common. The malignant osseous tumor pro- males, endocrine disturbances may be present in the
duces a destructive expanding and invasive lesion. A tri- polyostotic variety and associated with café au lait
angle may be adjacent to the tumor produced by ele- spots.
vated periosteum and subsequent tumor ossification.
The lesion may contain calcification and violates the B. LABORATORY FINDINGS
cortex of the bone. Femur, tibia, humerus, and other Laboratory findings are normal unless endocrine distur-
long bones are the sites usually affected. bances are present, in which case secretion of go-
Surgical excision (limb salvage) or amputation is in- nadotropic, thyroid, or adrenal hormones may be in-
dicated based on the extent of the tumor. The lesion is creased.
radioresistant and does not respond to chemotherapy.
Adjuvant chemotherapy is routinely used prior to surgi- C. IMAGING
cal excision. The prognosis is improving, with 30% The lesion begins centrally within the medullary canal,
5-year survival rates being reported in modern series. usually of a long bone, and expands slowly. Pathologic
Death usually occurs as a result of lung metastasis. fracture may occur. If metaplastic bone predominates,
the contents of the lesion will be of the density of bone.
Smeland S et al; Scandinavian Sarcoma Group Osteosarcoma Study The disease is often asymmetrical, and limb length dis-
SSG VIII: Prognostic factors for outcome and the role of re- turbances may occur as a result of stimulation of epi-
placement salvage chemotherapy for poor histological respon- physial cartilage growth. Marked deformity of the bone
ders. Eur J Cancer 2003;39(4):488 [PMID: 12751380]. may result, and a shepherd’s crook deformity of the
upper femur is a classic feature of the disease.
Ewing Sarcoma
In Ewing sarcoma, the presenting complaint is usually
Differential Diagnosis
pain and tenderness. Fever and leukocytosis may also be The differential diagnosis includes other fibrous lesions
present, which makes osteomyelitis the main differen- of bone as well as destructive lesions such as unicameral
828 / CHAPTER 24

bone cyst, eosinophilic granuloma, aneurysmal bone ate it from osteosarcoma or hemangioma. Treatment is
cyst, nonossifying fibroma, enchondroma, and chon- by curettage and bone grafting. The prognosis is good.
dromyxoid fibroma.
Papagelopoulos PJ et al: Treatment of aneurysmal bone cysts of the
pelvis and sacrum. J Bone Joint Surg Am 2001;83:1674
Treatment [PMID: 11701790].
If the lesion is small and asymptomatic, no treatment is Wyatt-Ashmead J et al: Primary aneurysmal bone cysts: 16q22 and/
needed. If the lesion is large and produces or threatens or 17p13 chromosome abnormalities. Pediatr Dev Pathol
2001;4:418 [PMID: 11441369].
pathologic fracture, curettage and bone grafting are in-
dicated.
INFANTILE CORTICAL HYPEROSTOSIS
Prognosis (Caffey Syndrome)
Unless the lesions impair epiphysial growth, the prog- Infantile cortical hyperostosis is a benign disease of un-
nosis for patients with fibrous dysplasia is good. Lesions known cause that has its onset before age 6 months and
tend to enlarge during the growth period but are stable is characterized by irritability; fever; and nonsuppurat-
during adult life. Malignant transformation is rare. ing, tender, painful swellings. Swellings may involve al-
most any bone of the body and are frequently wide-
spread. Classically, swellings of the mandible and
UNICAMERAL BONE CYST clavicle occur in 50% of patients; swellings of the ulna,
Unicameral bone cyst occurs in the metaphysis of a humerus, and ribs also occur. The disease is limited to
long bone, usually in the femur or humerus. It begins the shafts of bones and does not involve subcutaneous
within the medullary canal adjacent to the epiphysial tissues or joints. It is self-limited but may persist for
cartilage. It probably results from some fault in enchon- weeks or months. Anemia, leukocytosis, an increased
dral ossification. The cyst is considered active as long as ESR, and elevation of the serum alkaline phosphatase
it abuts onto the metaphysial side of the epiphysial car- concentration are usually present. Cortical hyperostosis
tilage, and there is a risk of growth arrest with or with- is demonstrable by a typical radiographic appearance
out treatment. and may be diagnosed on physical examination by an
When a border of normal bone exists between the experienced pediatrician.
cyst and the epiphysial cartilage, the cyst is inactive. Fortunately the disease appears to be decreasing in
The lesion is usually identified when a pathologic frac- frequency. Indomethacin may be useful for treatment.
ture occurs, producing pain. Laboratory findings are The prognosis is good, and the disease usually termi-
normal. On radiograph, the cyst is identified centrally nates without deformity.
within the medullary canal, producing expansion of the
cortex and thinning over the widest portion of the cyst. GANGLION
Treatment consists of curettage and bone grafting.
The cyst may heal after a fracture. A ganglion is a smooth, small cystic mass connected by
a pedicle to the joint capsule, usually on the dorsum of
the wrist. It may also occur in the tendon sheath over
Wilkins RM: Unicameral bone cysts. J Am Acad Orthop Surg the flexor surfaces of the fingers. These ganglia can be
2000;8(4):217 [PMID: 10951110].
excised if they interfere with function or cause persis-
tent pain.
ANEURYSMAL BONE CYST
Aneurysmal bone cyst is similar to unicameral bone BAKER CYST
cyst, but it contains blood rather than clear fluid. It A Baker cyst is a herniation of the synovium in the knee
usually occurs in a slightly eccentric position in the joint into the popliteal region. In children, the diagno-
long bone, expanding the cortex of the bone but not sis may be made by aspiration of mucinous fluid, but
breaking the cortex. Involvement of the flat bones of the cyst nearly always disappears with time. Whereas
the pelvis is less common. On radiographs, the lesion Baker cysts may be indicative of intra-articular disease
appears somewhat larger than the width of the epi- in the adult, they occur without internal derangement
physial cartilage. This feature distinguishes it from uni- in children and rarely require excision.
cameral bone cyst.
Chromosomal abnormalities have been associated Van Rhijn LW et al: Long-term follow-up of conservatively treated
with anuerysmal bone cyst. The lesion may appear ag- popliteal cysts in children. J Pediatr Orthop B 2000;9(1):62
gressive histologically, and it is important to differenti- [PMID: 10647115].
 Rehabilitation & Sports Medicine 25
Pamela E. Wilson, MD, & Dennis J. Matthews, MD

The development of sports medicine as a unique disci- Types of Muscle Contraction

pline has grown since the 1980s in response to the ex-
panding body of knowledge in the areas of exercise Dynamic contractions are those movements that result
physiology, biomechanics, and musculoskeletal medi- in motion of a limb or rotation around a joint axis.
cine. The boom in physical fitness and physical activity These contractions can be further divided into isotonic
has generated a need for specialty training in these and isokinetic contractions. In an isotonic contraction,
areas. With the current popularity of starting younger constant tension is generated during muscle contrac-
children in more structured athletics, it is essential that tion; in an isokinetic contraction, constant velocity is
the pediatric general practitioner have an understand- maintained during the contraction. Isotonic exercises
ing of sports medicine. can be further classified as detailed in the following sec-
tions:

A. CONCENTRIC
BASIC PRINCIPLES In concentric exercises the force of a muscle contraction
overcomes an external resistance, which results in short-
The basic unit of the musculoskeletal system is the ening of the muscle. These muscles accelerate a distal
muscle fiber, which can be classified as slow twitch, fast segment in the kinetic chain and are therefore referred
twitch, or of intermediate type. Slow twitch, or type I, to as open-chain movements. An example of such an
fibers are smaller, are recruited in muscle contractions exercise is a biceps curl, during which the biceps is ac-
first, and are innervated by smaller motor neurons. Fast tively contracting or shortening to lift the weight.
twitch, or type II, fibers make up white muscle and
have a tendency to be larger. They are recruited when B. ECCENTRIC
the body needs to produce rapid muscle tension. In
general they produce more lactic acid than type I fibers. In eccentric exercises, contractions increase muscle ten-
An intermediate type IIa fiber, called fast oxidative gly- sion associated with lengthening of the muscle and are
colytic or FOG, also exists. Untrained individuals have used to decelerate a distal segment in the kinetic chain.
a 50:50 proportion of type I to type II fibers. Elite This type of exercise is exemplified by the squatting
long-distance runners can have up to 90% type I fibers. motion, in which the quadriceps are lengthening under
This apparent adaptation raises the interesting question tension to control downward motion. If the terminal
as to whether an athlete is genetically programmed or segment in the chain is fixed, this type of movement is
can develop adaptations to be successful in sports. called closed kinetic chain movement.
Exercise generates specific effects on the cardiorespi-
ratory system that include increased VO2 max (maxi- C. ISOMETRIC
mum amount of oxygen that can be consumed), in- In contrast to dynamic contractions, isometric contrac-
creased cardiac output, reduced resting heart rate, and tions increase muscle tension without a change in
improved blood pressure responses. length. An example of this type of exercise would be
Biomechanics, the study of movement and how the pushing against a wall. Tension is generated in the
forces generated by the neuromuscular system translate muscle, but no movement occurs.
into these movements, integrates principles of biology
and physics. Through biomechanics we can understand
the intricacies of movement and how these movements Young JL, Press JM: The physiologic basis of sports rehabilitation.
affect athletic performance and result in injuries. Phys Med Rehabil Clin North Am 1994;5:9.
829
Copyright © 2005, 2001, by The McGraw-Hill Companies, Inc. Click here for terms of use.
830 / CHAPTER 25

Strength Training cluding the example in Figure 25–1. The history must
include the following areas:
Strength is defined as the peak force that can be gener-
ated during a maximal single contraction. Strength A. CARDIOVASCULAR HISTORY
training is therefore the use of progressive resistance to The physician should note any history of cardiac mur-
improve an athlete’s ability to resist or exert force. This murs, chest pain at rest or with exertion, sycopal
can be achieved by a variety of techniques, including episodes or sudden fatigue, shortness of breath, or re-
body weight, free weight, and machine resistance. The cent illnesses with chest pain. The family history should
benefits of weight training programs are improved per- specifically ask about underlying cardiac diseases, in-
formance, endurance, and muscular strength. These cluding hypertrophic cardiomyopathy, prolonged QT
programs can be started in prepubescent athletes and, if syndrome, Marfan syndrome, arrhythmias, and sudden
designed appropriately, can be done safely with mini- death in family members. These questions are necessary
mal risk for injury. Tanner staging (see Chapter 30) to identify potentially life-threatening cardiac lesions.
helps to define readiness for progression into more The most common cause of sudden death in young
strenuous programs. Power lifting and weight lifting athletes on the playing field is hypertrophic cardiomy-
should be restricted to those athletes who have reached opathy and congenital heart lesions.
or passed Tanner stage V. Individuals at Tanner stage
IV or less can safely participate in a strength training B. HISTORY OF HYPERTENSION
program that is specifically and carefully designed for Any history of hypertension requires further investiga-
younger athletes. These programs incorporate submaxi- tion. The current guidelines for the diagnosis of hyper-
mal resistance with multiple repetitions. They can be tension are blood pressure over 130/75 mm Hg in a
generalized or sport-specific. Care should be taken to child younger than age 10 years or blood pressure over
prevent injuries while using weight training equipment 140/85 mm Hg in a child age 10 years and older.
at home.
C. HISTORY OF CHRONIC DISEASES
American Academy of Pediatrics: Strength training, weight and Diseases such as asthma or exercise-induced asthma, di-
power lifting, and body building by children and adolescents. abetes, renal disease, neurologic disorders, and hemato-
Pediatrics 1990;86:801 [PMID: 2235239]. logic diseases should be noted.
Faigenbaum AD: Strength training for children and adolescents.
Clin Sports Med 2000:19;4:593 [PMID: 11019731]. D. MUSCULOSKELETAL LIMITATIONS
Jones CS, Christensen C, Young M: Weight training injury: A AND PRIOR INJURIES
20 year survey. Phys Sportsmed 2000;28:7:61. The physician should explore abnormal range of mo-
tion or prior injuries that may affect future perfor-
mance.
PREPARTICIPATION HISTORY
& PHYSICAL EXAMINATION E. MENSTRUAL HISTORY IN FEMALES
The preparticipation medical examination is designed The physician should pay particular attention to the so-
to evaluate children and screen for potential medical called female athletic triad: amenorrhea, eating disor-
problems that could occur during athletic participation. ders, and osteoporosis.
The objectives of this evaluation are to establish base- F. NUTRITIONAL ISSUES
line medical information, detect any medical condition
The physician should record methods the athlete uses
that may limit athletic participation, evaluate the ath-
to maintain, gain, or lose weight.
lete for preventable injuries, meet the legal or insurance
requirements of most states, assess the athlete’s matu- G. MEDICATION HISTORY
rity, and make recommendations for necessary protec- This information will provide data on current medica-
tive equipment. The ideal timing of this examination is tions along with the opportunity to discuss the possible
in preseason, at least 4–6 weeks before training starts. use of performance-enhancing supplements such as an-
This allows time for any needed interventions by the abolic steroids, creatine, stimulants, and narcotics.
physician.
Physical Examination
Preparticipation History The physical examination should be focused on the
The history is the most important part of the en- needs of the athlete. It may be the only time that an
counter. Many key elements need to be explored with athlete has contact with medical personnel and can be
the athlete. Several standardized forms are available, in- used to promote wellness along with screening for
 REHABILITATION & SPORTS MEDICINE / 831

PREPARTICIPATION HISTORY
Name_____________________________________________DOB____________Age________Sex (M or F)
Primary Physician___________________________Sports ________________________________________
Allergies (medications, latex, foods, bees, etc) __________________________________________________________
Medications (include prescription, nonprescription, supplements and vitamins) ________________________________________________
________________________________________________________________________________________
Answer questions by checking Yes (Y)/no (N)/don't know (? )
Y N ?
General Health
1. Have you had any injuries or illnesses?
2. Have you ever been hospitalized?
3. Do you think you are too thin or overweight?
4. Have you ever used anything to gain or loss weight?
5. Any problems exercising in the heat: heat cramps, heat exhaustion or heat stroke?
6. Ever had frostbite?
7. Any vision problems?
8. Do you wear glasses, contact lens, or eye protection?
9. Any dental appliances?
10. Have you had any surgeries?
11. Any organs missing?
12. Immunizations (tetanus/ hepatitis B) are they current?
13. Any concerns about participating in sports?
Cardiac/Respiratory History
1. Has any family member died suddenly, have heart disease before age 50 or other heart problems?
2. Do you have any dizziness, chest pain, a racing heart, or shortness of breath with exercise?
3. Have you ever passed out?
4. Do you have a heart murmur, high blood pressure, or any heart condition?
5. Can you exercise as much as your friends?
6. Any history of asthma, problems breathing, coughing with exercise?
Neurologic History
1. Any history of a head injury/concussion: being knocked out, dazed, or having memory loss?
2. Have you ever had a seizure or convulsion?
3. Any nerve problems: stingers, burners, pinched nerves or numbness?
4. Any problems with headaches?
Musculoskeletal History
1. Do you have a history of sprains, strains or fractures?
2. Any hip, knee or ankle injuries?
3. Any shoulder, elbow, wrist, hand or finger injuries?
4. Any back or neck problems?
5. Ever have to be in a splint, cast or use crutches?
6. Do you use any special equipment when competing (braces, orthotics, pads etc)
Females Only
1. Any problems with menstruation: cramps, irregularity, etc.
2. When was your last period? _______________________________________________________

COMMENT ON YES ANSWERS

Figure 25–1. Preparticipation history.

832 / CHAPTER 25

physical activity. Figure 25–2 is an example of a stan- REHABILITATION OF SPORTS INJURIES

dardized physical examination form. The examination
should include routine vital signs including blood pres- Participation in sports can have tremendous benefits for
sure measurements obtained in the upper extremity. the individual. It provides physical activity, acquisition
The cardiovascular examination should include palpa- of motor skills, and social opportunities. All sports par-
tion of pulses, auscultation for murmurs with the pa- ticipation, however, carries an inherent risk of injuries.
tient both sitting and standing, and evaluation of the These injuries are classified as either acute or chronic.
effects of exercise on the individual. The musculoskele- Chronic injuries occur over time and are related to
tal examination is used to determine strength, range of repetitive stress. These injuries develop in response to
motion, flexibility, and previous injuries. Table 25–1 is overuse, repeated microtrauma, and inadequate repair
a quick guide that can be used to screen for abnormali- of injured tissue. Acute injuries, or macrotrauma, are
ties in this area. The remainder of the examination one-time events that can cause alterations in biome-
should emphasize the following areas: chanics and physiology. In response to an acute injury
the body responds in a predictable fashion. The first
A. SKIN week is characterized by an acute inflammatory re-
Are there any contagious lesions such as herpes or im- sponse. During this time initial vasoconstriction is fol-
petigo? lowed by vasodilatation. Chemical mediators of inflam-
mation are released and result in the classical physical
B. VISUAL findings of local swelling, warmth, pain, and loss of
Are there any visual problems? Is there any evidence of function. This phase is essential for injury healing. The
retinal problems? Are both eyes intact? next phase occurs over 2–4 weeks and involves repair
and clean-up. Fibroblasts infiltrate and lay down new
C. ABDOMINAL collagen. This allows for repair of the injured area.
Is there any evidence of hepatosplenomegaly? The management of acute sports injuries is geared
toward optimizing healing and restoring function. The
D. GENITOURINARY goals of immediate care are to minimize the effects of
Is there any history of testicular abnormalities or hernia the injury by reducing pain and swelling, to educate the
symptoms? athlete about the nature of the injury and how to take
E. NEUROLOGIC care of it, and to maintain the health of the rest of the
body. The treatment for an acute injury is captured in
Are there any problems with coordination, gait, or the acronym PRICE:
mental processing?
F. SEXUAL MATURITY • Protect the injury from further damage (taping,
splints, braces)
What Tanner stage is this individual?
• Rest the area
Recommendations for Participation • Ice
• Compression of the injury
After completing the medical examination (history and • Elevation immediately
physical) the physician can make recommendations to
the athlete on sports clearance. The options are unre- The use of nonsteroidal anti-inflammatory agents
stricted participation, limited participation, or no par- reduces the inflammatory response and reduces discom-
ticipation. The American Academy of Pediatrics (AAP) fort. These medications may be used immediately after
has a list of guidelines, which can be found on their the injury. Glucocorticoids should be administered ju-
Website. Table 25–2 shows considerations and recom- diciously. If administered inappropriately they may
mendations for sports activities based on body systems. prolong the acute phase of recovery. Therapeutic use of
physical modalities, including early cold and later heat,
American Academy of Pediatrics Committee on Sports Medicine hydrotherapy, massage, electrical stimulation, ion-
and Fitness: Adolescents and anabolic steroids: A subject re- tophoresis, and ultrasound, can enhance recovery in the
view. Pediatrics 1997;99:904 [PMID: 9190555].
acute phase.
Lively MW: Preparticipation physical examination: A collegiate ex-
perience. Clin J Sport Med 1999;9:3 [PMID: 10336045].
The recovery phase can be lengthy and requires ath-
Myers A, Sickles T: Preparticipation sports examination. Prim Care
lete participation. Initial treatment is focused on joint
1998;25:225 [PMID: 9469925]. range of motion and flexibility. Range-of-motion exer-
West RV: The female athlete. The triad of disordered eating, amen- cises should follow a logical progression of starting with
orrhea and osteoporosis. Sports Med 1998;26:63 [PMID: passive motion, then moving to active assistive, and fi-
9777680]. nally to active movement. Active range of motion is ini-
 REHABILITATION & SPORTS MEDICINE / 833

PREPARTICIPATION PHYSICAL EXAM

Name_________________________________________________________
Date of birth/age_______________________________________________
Height_____________Weight_______________BP___________________
Pulse R wrist_____________L wrist________________other___________
Vision R 20/___________L 20/__________ (was it corrected Y or N)
GENERAL EXAM (circle normal or abnormal and record results on the form)
APPEARANCE normal
abnormal______________________________________________________________
HEENT normal
abnormal______________________________________________________________
LUNGS normal
abnormal______________________________________________________________
HEART normal
& PULSES abnormal ________________________________________________
ABDOMEN normal
abnormal______________________________________________________________
GU normal
abnormal______________________________________________________________
SKIN & normal
LYMPH NODES abnormal______________________________________________________________
NEURO normal
abnormal______________________________________________________________
MUSCULOSKELETAL EXAM (record ROM or instabilities if abnormal)
NECK normal
abnormal______________________________________________________________
BACK normal
abnormal______________________________________________________________
SHOULDERS normal
abnormal______________________________________________________________
ELBOW & normal
WRIST abnormal______________________________________________________________
HANDS & normal
FINGERS abnormal______________________________________________________________
HIP normal
abnormal______________________________________________________________
KNEE normal
abnormal______________________________________________________________
ANKLE & normal
FOOT abnormal______________________________________________________________
Cleared for sports: YES or NO If not cleared for sport WHY?_________________
______________________________________________________________________
Further evaluation/rehab or/secondary clearance:__________________________
______________________________________________________________________
Signature examinee:______________________________Date_________________
Figure 25–2. Preparticipation physical evaluation.
834 / CHAPTER 25

Table 25–1. The screening sports exam.a tiated once normal joint range has been reestablished.
Flexibility is sport-specific and aimed at reducing tight
General Have person stand in front of the examiner
musculature. Strength training can begin early in this
evaluation and evaluate both front and back along
phase of rehabilitation. Initially only isometric exercises
with posture
are encouraged. As recovery progresses and flexibility
Look at general body habitus
increases, isotonic and isokinetic exercises can be added
Look for asymmetry in muscle bulk, scars or
to the program. These should be done at least three
unusual postures
times per week. As the athlete approaches near-normal
Watch how the patient moves when in-
strength and is pain-free, the final maintenance phase
structed
can be introduced. During this phase the athlete will
continue to build strength and work on endurance.
Neck Evaluate ROM by having person bend head The biomechanics of sport-specific activity needs to be
evaluation forward (chin to chest), rotate from side to analyzed and retraining incorporated into the exercise
side, and laterally bend (ear to shoulder) program. Generalized cardiovascular conditioning
Observe for asymmetry, lack of motion or should continue during the entire rehabilitation treat-
pain with movement ment.
Shoulder Observe clavicles, shoulder position, scapular
and upper position, elbow position, and fingers
extremity ROM screening
evaluation Fully abduct arms with palms in jumping COMMON SPORTS MEDICINE
jack position ISSUES AND INJURIES
Internally and externally rotate shoulder
Flex and extend wrist, pronate and supi-
nate wrist, flex and extend fingers INFECTIOUS DISEASES
Do the following manual muscle testing: Infectious diseases are common in both recreational
Have person shrug shoulders (testing and competitive athletes. These illnesses have an effect
trapezius) on basic physiologic function and athletic performance.
Abduct to 90 degrees (testing deltoid) Given this knowledge, physicians, parents, and coaches
Flex elbow (testing biceps) can adopt the common-sense guidelines listed in Table
Extend elbow over head (testing triceps) 25–3.
Test wrist flexion and extension
Have person grasp fingers
American Academy of Pediatrics Committee on Sports Medicine
Back General inspection to look for scoliosis or and Fitness: Human immunodeficiency virus (acquired im-
evaluation kyphosis munodeficiency syndrome—AIDS virus) in the athletic set-
ROM screening ting. Pediatrics 1991;88:640 [PMID: 1881749].
Bend forward touching toes with knees
straight (spine flexion and hamstring
range) HEAD & NECK INJURIES
Rotation, side bending, and spine extension Head and neck injuries occur most commonly in con-
Gait and lower General observation while walking tact and individual sports. The sports with the highest
extremity Walk short distance normally (look at sym- incidence of brain injury are football, bicycling, base-
evaluation metry, heel-toe gait pattern, look at all ball, horseback riding, and golf. The treatment of these
joints involved in gait and leg lengths, any is controversial, with multiple guidelines being devel-
evidence of joint effusions or pain) oped. Because young children have developing central
Have person toe-walk and heel-walk for short nervous systems, injuries in these children should be
distance and check tandem walking (bal- treated conservatively.
ance beam walking) Concussion is a temporary and immediate impair-
ment of neurologic function and is classified by length
a
If any abnormalities are found, then a more focused evaluation is of unconsciousness, posttraumatic amnesia (PTA), and
required. confusion. Concussions are categorized as grade
1 (mild), grade 2 (moderate), or grade 3 (severe). Re-
turn-to-competition guidelines have been developed by
several resources. Table 25–4 reviews guidelines for re-
turn to play.
 REHABILITATION & SPORTS MEDICINE / 835

Table 25–2. Recommendations and considerations for paticipation in sports

Disorders Considerations and Recommendations References

Cardiac
Anticoagulation treatment Need to avoid all contact sports
Aortic stenosis Individualize treatment based on disease and systolic gradient
Mild: < 20 mm Hg, all sports if asymptomatic.
Moderate: limited sports.
Severe: no competitive sports.
Arrhythmias Consult with cardiologist as WPW and long QT syndrome can have serious
consequences.
Congestive heart failure Screen patient with LVEF < 30 % for ischemia. Braith, 2002
(CHF) Use AHA risk stratification criteria to define exercise capacity.
Heart implants No jumping, swimming, or contact sports.
Hypertrophic Single most common cause of cardiac death in young athletes. Maron, 2002a,b
cardiomyopathy Athletes should not participate in sports except possibly low intensity forms
(eg, golf, bowling).
Consult with cardiologist.
Marfan syndrome Aortic root dilation is associated with mitral valve prolapse and regurgitation. Salim et al, 2001
Participate in sports with minimal physical demands.
Mitral valve prolapse Fairly common condition.
No restrictions unless there is a history of syncope, positive family history of
sudden death, arrhythmias with exercise, or moderate regurgitation.
Syncope Unexplained syncopal episodes during exercise must be evaluated by ECG, Firoozi, 2002
echocardiograph, Holter, and tilt test prior to resumption of any activities.
Endocrine
Diabetes type I No restrictions to activity, however: Birrer et al, 2003
Short-term exercise = no insulin changes. Draznin, 2000
Vigorous exercise = 25% reduction in insulin with 15–30 g of carbohydrates
before and every 30 min during exercise.
Strenuous exercise = may require up to an 80% reduction in insulin with
extra carbohydrates.
Generally monitor blood glucose closely.
Eye
Detached retina Do not participate in strenuous sports regardless of contact risk. Moeller, 1996
One eye Consider avoiding contact sports although if patient does participate use of Vinger, 2000
eye protection is a must.
Gentiourinary
One testicle Need to wear protective cups in collision/contact sports.
Solitary kidney Advise not to participate in collision/contact sports. Terrell, 1997
Hematologic
Hemophilia Avoid contact/collision sports.
Sickle cell trait No restrictions if disorder well under control.
Athletes should avoid dehydration and acclimate to altitude.
There is however a known association between exercise and sudden death.
(continued)
836 / CHAPTER 25

Table 25–2. Recommendations and considerations for paticipation in sports (continued)

Disorders Considerations and Recommendations References

Infectious Disease
General considerations Fevers; should not participate in activities with moderate fevers; exercise affects Howe, 2003
fluid balance, immune system function, and temperature regulation. Primos, 1996
Intense exercise may worsen or prolong some viral illnesses.
Enterovirus, coxsackie virus Causes respiratory and GI symptoms but more importantly can cause myocarditis. Primos, 1996
Anyone with systemic symptoms such as fever or myalgias should avoid
strenuous exercise.
Herpes simplex, impetigo, Close contact is required for transmission; use commone sense guidelines. Moeller, 1996
tinea corpora For contact sports participation should not be allowed until lesions are crusted
over or healed.
Infectious mononucleosis Splenic rupture is most important consideration. MacKnight, 2002
Risk of spleen rupture highest during second and third weeks of illness.
No athletic participation for a minimum of 21 days!
Splenic ultrasounds should be considered in decision making.
Too early a return to sports could cause EBV reactivation and relapse.
First week of return to activity should be noncontact.
Graded increases in intensity if fatigue tolerance is improved.
Return to full activity if: no abdominal pain, normal spleen and normal labs.
Sinusitis Similar considerations as cold (see below) except diving should be restricted
until symptoms resolve.
Streptococcus A Restrict from activity until afebrile and on antibiotics for > 24 h O’Kane, 2002
Upper respiratory infections “Neck check,” with symptoms (fevers, myalgias, arthralgias, etc) above the neck Primos 1996
(including common cold) participation can be allowed; however, if they migrate below that level activity
should be limited.
Neurologic
Epiliepsy Majority of sports are safe with good seizure control; contact sports are allowed Howard, 2004
with proper protection.
Definitely wear a helmet.
Fitness may reduce number of seizures.
Swimming and water sports should be supervised.
Sports such as free climbing, hang gliding, scuba not recommended.
Herniated disk (with cord Avoid contact and collision sports.
compression)
Muscle disease or myopathy Exercise within physical limits. Tarnopolsky, 2002
Low to moderate intensity activity is appropriate for patients with slow Ansved, 2003
progressive disorders.
Patients with disorder that are rapidly progressing should avoid high resistance
and eccentric muscle activity.
Modification of exercise with intercurrent illness.
Spinal stenosis Avoid contact and colision sports.
Orthopedic
Scoliosis No restrictions unless severe.
Spondylolisthesis Grade 2 and above should avoid high-risk sports.
Spondylolysis Pars intrarticularis stress fracture.
No restrictions if pain-free.
(continued)
 REHABILITATION & SPORTS MEDICINE / 837

Table 25–2. Recommendations and considerations for paticipation in sports (continued)

Disorders Considerations and Recommendations References

Respiratory
Asthma No activity restrictions. Disabella et al.
Use common sense about when to use medications. 1998
Pneumothorax Can occur in sports, expecially in males.
Increased risk for reoccurrence; should consider not participating in strenuous
and contact sports.
TB Not allowed to participate because of exposure to other athletes.
Other
Cerebral palsy Full participation with modifications.
Developmental disabilities Athletes with developmental disabilities often have associated medical Platt, 2001
problems including diabetes, obesity, and hypokinesia.
Downs syndrome 10–20% have atlantoaxial instability. Platt, 2001
All athletes need to be cleared with a lateral view radiograph including flexion Winell, 2003
and extension.
If abnormal no contact sports should be allowed.
Evaluation of underlying congenital heart disorders should be considered in
this population.
Spinal cord injury/ Full participation.
spina bifida Consider modification of equipment to accommodate activity and/or
modification of activity to accommodate disability.
Consider how modification affects performance.
Beaware of thermoregulatory dysfunction, medications, and pressure areas.

Second impact syndrome is a rare but potentially American Academy of Pediatrics Committee on Sports Medicine
deadly complication of head injuries. It occurs in ath- and Fitness: Atlantoaxial instability in Down syndrome: Sub-
ject review. Pediatrics 1995;96:151 [PMID: 7596705].
letes who have a second brain injury before recovering
from a prior brain injury. It results in loss of vascular Cantu RC: Guidelines for return to contact sports after a cerebral
concussion. Phys Sportsmed 1986;14:75.
autoregulation and subsequent malignant cerebral
Cole AJ et al: Cervical spine athletic injuries: A pain in the neck.
edema. Phys Med Rehabil Clin North Am 1994;5:37.
Cervical spine injuries are fairly common but po- Colorado Medical Society: Report of the Sports Medicine Committee:
tentially serious. They can cause ligamentous injuries Guidelines for the Management of Concussion in Sports (re-
along with spinal cord injuries The most frequent neck vised). Colorado Medical Society, 1991.
injury is a cervical strain. Return to play is allowed
when neck range of motion is full and pain-free, and Burners and stingers are common injuries in con-
strength is normal. tact sports, especially football. These types of cervical
Atlantoaxial instability is common in children radiculopathies or brachial plexopathies occur when the
with Down syndrome because of underlying ligamen- head is laterally bent and the shoulder depressed.
tous laxity. Cervical neck films including the neck in Symptoms include immediate burning pain and pares-
flexion and extension evaluate the atlantodens interval. thesias down one arm, generally lasting only minutes.
Normal is less than 2.5 mm, but up to 4.5 mm is ac- Weakness in the muscles of the upper trunk
ceptable in this population. Children with an interval (supraspinatous, deltoid, and bicep) can persist for
greater than 4.5 mm should be restricted in activities. weeks. Work-up includes a thorough neurologic assess-
ment. If symptoms persist, then a diagnostic evaluation
American Academy of Neurology: Practice parameter: The man-
should include cervical spine radiographs, magnetic res-
agement of concussion in sports (Summary statement). Re- onance imaging (MRI) scans, and electromyography.
port of the Quality standards subcommittee. Neurology The athlete can return to play once symptoms have re-
1997;48:581 [PMID: 9065530]. solved, neck and shoulder range of motion is pain-free,
838 / CHAPTER 25

Table 25–3. Sports participation guidelines: graphic, and MRI scans. Treatment generally is conser-
infectious diseases. vative because most back injuries improve sponta-
neously. The athlete can rest the back for a short period
Athletes with temperatures higher than 100°F should not and then begin on a structured exercise program of ex-
participate in sporting activities. tension and isometrics followed by flexion exercises. If
Athletes who have had recent infectious mononucleosis can symptoms persist, then a short course of steroids may
return to noncontact training at 3 wk as long as there is be indicated. Surgery is recommended only if neuro-
no splenic enlargement. They may return to contact sports logic compromise persists.
after 4 wk and a normal abdominal examination. Spondylolysis is an injury to the pars interarticu-
Athletes with a streptococcal pharyngitis can resume activity laris. Pars defects are present in 4–6 % of the popula-
once treatment has been initiated and they are afebrile. tion. Repetitive stress to this area results in fractures.
If a localized herpes gladiatorum or impetigo lesion is pre- The injury is common in gymnasts, dancers, and foot-
sent, no contact sports are allowed until the lesions have ball players. Spondylolysis occurs at L5 in 85% of cases.
resolved. Athletes with herpes zoster have the same restric- Pain usually develops during an adolescent growth
tions. There are no restrictions for athletes with common spurt. Back pain may radiate into the buttocks or thigh
warts. Athletes with molluscum contagiosum can compete area. Extension of the spine increases pain. Evaluation
if the affected areas are covered. Athletes with furuncles includes an oblique radiographic view of the spine to
cannot be involved in contact sports or swimming until the look for the “Scottie dog sign.” Treatment includes rest
lesions are healed.
Athletes with HIV infection may compete in all types of sports.
Universal precautions should be used with all athletes who
have sustained injuries. Table 25–4. Return-to-competition guidelines
following concussion.

Grade 1 or mild concussion

reflexes and strength are normal, and the Spurling’s test No loss of consciousness (LOC)
is negative. Preventative strategies include always PTA or confusion lasting less than 15 min
wearing protective gear, proper blocking and tackling First Injury
techniques, and maintaining good neck and shoulder • Remove from game
strength. • Return to play in 15 minutes if exam is normal
Second injury
Feinberg JH: Burners and stingers. Phys Med Rehabil Clin North • Return to play if asymptomatic after one week
Am 2000;11:4:771 [PMID: 11092018]. Grade 2 or moderate concussion
No LOC
PTA or confusion lasting longer than 15 minutes
SPINE INJURIES First Injury
• Remove from game
Injuries to the spine are fairly common even in the pe- • Hospital evaluation if symptoms persist for more
diatric population. As children have become more com- than one hour
petitive in sports, the number of reported injuries has • Return to play if asymptomatic after one week
increased. Sports with a fairly high incidence of back • CT or MRI if symptoms persist for more than 1 wk
injuries are golf, gymnastics, football, dance, wrestling, Second Injury
and weight lifting. Pain lasting more than 2 weeks indi- • Return to play if asymptomatic after two weeks
cates a possible structural problem and needs to be in- Third Injury
vestigated. • Out for season
Herniated discs account for a small percentage of Grade 3 or severe concussion
back injuries in children. These injuries are almost un- Any LOC
heard of in preadolescence. Most injuries occur at the First Injury
L4–5 and L5–S1 vertebrae. Symptoms include back • Transport to hospital for evaluation
and leg pain. Pain may be increased with activities such • With a brief LOC (seconds), return to play if asympto-
as bending, sitting, and coughing. Pain often radiates matic after one week
down the lower extremity in a radicular pattern. Evalu- • With a longer LOC (minutes), return to play if asymp-
ation comprises a physical and neurologic exam, in- tomatic after 2 wk
cluding straight-leg testing, sensory testing, and check- Second Injury
ing reflexes. If symptoms persist, then the evaluation • No play for at least one month following absence of
symptoms; consider ending season
should include electromyographic, computed tomo-
 REHABILITATION & SPORTS MEDICINE / 839

from sporting activities, stretching of the hamstrings, Medial Elbow Pain

stabilization exercises, lumbosacral bracing, and occa-
sionally surgery. Medial elbow pain can have multiple causes, but one of
If a bilateral pars injury occurs, then slippage of one the most common is medial epicondylitis, an overuse
vertebra over another (spondylolisthesis) can occur. injury caused by valgus stress at the elbow. Little
These injuries are graded on a scale of 1 to 4 based on league elbow consists of a group of abnormalities that
the percentage of slippage: grade 1, 0–25%; grade 2, develop in young baseball pitchers. These abnormalities
25–49%%; grade 3, 50–74%; and grade 4, 75–100%. are secondary to the biomechanical forces generated
Diagnosis is based on lateral radiographs, and treatment around the elbow during throwing. These forces can re-
is symptomatic. Asymptomatic athletes with less than sult in shearing, inflammation, traction, and abnormal
30% slippage have no restrictions and are followed up bone development. Pitching can be divided into four
on a routine basis. Slippage of 50% requires interven- phases: wind-up, cocking, acceleration, and follow-
tions of stretching hip flexors and hamstrings, along through. The acceleration phase is where most forces
with bracing or surgery. are generated.. The symptoms are primarily swelling,
pain, performance difficulties, and weakness. The pain
localizes to the medial epicondyle, which may be tender
Drezner JA, Herring SA: Managing low back pain: Steps to opti- to palpation. Wrist flexion and pronation increase
mize and hasten return to activity. Phys Sportsmed 1999; symptoms. The different phases of throwing should be
272:37.
analyzed to isolate when the pain appears. If pain is pre-
Letts M, McDonald P: Sports injuries to the pediatric spine. Spine: sent in all phases this may indicate a severe injury.
State of the Art Review 1990;4:49.
Work-up includes a series of elbow radiographs, includ-
ing stress films and comparison films, to look for
SHOULDER INJURIES widening of the epiphysial lines, and MRI studies.
Treatment of the acute injury includes rest. It is not un-
In evaluating shoulder injuries it is necessary to look at common for a player to be benched for up to 6 weeks.
both macro- and microtrauma. Fractures and disloca- Competition can be resumed once the player is asymp-
tions account for most macrotrauma. The balance of tomatic.
other injuries are related to repetitive overuse and tissue The key to treating this injury is prevention. Chil-
failure. Rotator cuff injuries are common in athletics dren should be properly conditioned and coached in
that require repetitive overhead motions (eg, gymnas- correct throwing biomechanics. Guidelines are available
tics, and pitching in baseball). Muscle imbalances and for pitching limits in youth baseball. Little League lim-
injury cause the position of the humeral head to be ab- its 10- to 12-year-old children to six innings/week and
normal which may cause impingement of the 13- to 15-year-old children to nine innings/week. Lim-
supraspinatous tendon under the acromial arch. Pain is iting pitches per game has been outlined as shown in
usually reported in the anterior and lateral shoulder and Table 25–5.
is increased with overhead activities. Diagnostic work- Other causes of medial elbow pain include ulnar
up includes plain radiographs and an outlet view to collateral ligament injury, ulnar neuritis, apophysitis,
look for anatomic variability. The rehabilitation of this and fractures.
injury is geared toward reduction of inflammation, im-
proved flexibility, and strengthening of the scapular sta-
bilizers and rotator cuff muscles. This is achieved by a
progression of isometric followed by isotonic or isoki-
netic exercises. A biomechanics evaluation can assist in
the recovery process by building sport-specific skills and Table 25–5. Guidelines for pitching limits in
eliminating substitution patterns. youth baseball.

Tytherleigh-Strong G et al: Rotator cuff disease. Curr Opin Age (years) Pitches/gamea
Rheumatol 2001:13;2:135 [PMID: 11224738]. 8–10 52 ± 15
11–12 68 ± 18
ELBOW & FOREARM INJURIES 13–14 76 ± 16
Injuries in the forearm are quite common, with both 15–16 91 ± 16
chronic and acute causes (eg, the chronic overuse “little
league elbow” and the frequent childhood fracture 16–17 106 ± 16
when falling on an outstretched arm). a
Based on 2 games/week.
840 / CHAPTER 25

Lateral Elbow Pain 1. Hand Injuries

Lateral elbow pain can be the result of a few unique Distal Phalanx Injuries
problems in growing athletes. Panner disease is also
caused by valgus stress at the elbow. It is a focal process Tuft injury requires splinting for 6 weeks or until the
in the capitellum and occurs in players age 5–12 years. patient is pain-free. If displacement is significant, then
The child presents with dull aching in the lateral elbow a K-wire can be used for reduction. Nail bed injury
that generally worsens when the child throws some- often requires splinting and drainage of subungual
thing. Swelling and reduced elbow extension are usually hematomas.
present. Radiographs show an abnormal capitellum
with fragmentation and areas of sclerosis. Treatment is Distal Interphalangeal Injuries
conservative, using rest, ice, and splinting. The child
can return to play after the radiographs normalize. Mallet finger or extensor tendon avulsion occurs in
The same type of pain in a 13- to 15-year-old ath- ball-handling sports. The mechanism of injury is a
lete is usually osteochondritis dissecans. This injury is force applied to an extended finger. Treatment is splint-
basically avascular necrosis of the capitellum, which can ing in extension for 6 weeks for fractures and 8 weeks
result in the formation of loose bodies. Radiographs are for tendon rupture.
needed in the diagnosis and help to classify the injury
into one of three categories. Treatment is based on the Thumb Injuries
classification and can be either conservative or surgical
in nature. The child should be seen by an orthopedic Gamekeeper’s thumb is an injury to the ulnar collat-
specialist. eral ligament from forced abduction of the metacarpal
Lateral epicondylitis is common in racquet sports, phalangeal joint. It is a common skiing injury. If a radi-
particularly tennis. It is an overuse of the extensor mus- ograph shows an avulsed fragment is displaced less than
cle in the forearm and causes pain in the lateral elbow. 2 mm, a thumb spica cast can be used. If no fragment is
Pain is increased by wrist extension. Initial treatment is apparent and less than 35 degrees of lateral joint space
aimed at inflammation control. Stretching and opening occurs, a spica cast is indicated for 6 weeks.
strengthening of forearm muscles are the primary inter- Surgery is required for more serious injuries.
ventions during the subsequent phases. Stroke mechan-
ics may need to be altered and a forearm brace used to Fractures
decrease the forces in the extensor muscles.
Boxer’s fracture is a neck fracture of the fifth digit.
These fractures can be treated by closed reduction and
Posterior Elbow Pain casting for 3 weeks. A displaced fracture requires open
Posterior elbow pain is not very common. Causes in- reduction and internal fixation.
clude dislocations, fractures, triceps avulsions, and ole-
cranon bursitis. 2. Wrist Injuries
Most swollen wrists without evidence of instability can
Abrams JS: Special shoulder problems in the throwing athlete:
Pathology, diagnosis and nonoperative management. Clin be splinted for several weeks. Radial and ulnar fractures
Sports Med 1991;10:839 [PMID: 1934100]. must be ruled out because these are fairly common in
Axe M: Recommendation for protecting youth baseball pitches. children.
Sports Med Arthoscopy Rev 2001;9. Scaphoid fractures are caused by a force applied to
Chumbley EM et al: Evaluation of overuse elbow injuries. Am Fam a hyperextended wrist. If evidence of snuff box tender-
Physician 2000;1:61:69 [PMID: 10695582]. ness and swelling is present, the wrist must be immobi-
Hall TJ: Osteochondritis dissecans of the elbow: Diagnosis, treat- lized for 10 days and then reassessed, even if radi-
ment and prevention. Phys Sportsmed 1999;272:75. ographs are normal. A nondisplaced fracture requires at
Johnson EW: Tennis elbow misconceptions and widespread least 6 weeks of immobilization in a thumb spica cast.
mythology. Am J Phys Med Rehabil 2000;79:2:113 [PMID:
10744183].
Geissler WB: Carpal fractures in athletes. Clin Sports Med
2001;1563:1961 [PMID: 11227704].
HAND & WRIST INJURIES Krasin et al: Review of the current methods in the diagnosis and
treatment of scaphoid fractures. Postgrad Med J 2001;77:
All hand and wrist injuries have the potential for long- 906:235 [PMID: 11264484].
term, often serious disability and deserve a thorough Wang QC, Johnson BA: Fingertip injuries. Am Fam Physician
evaluation. 2000;1:61:69 [PMID: 11388710].
 REHABILITATION & SPORTS MEDICINE / 841

HIP INJURIES Hip dislocations in skeletally mature athletes are al-

most always associated with acetabular and femoral
Because the pelvis and hip articulate with both the lower neck fracture. The preadolescent, skeletally immature
extremities and the spine, this is an area rich in ligaments, competitor may have an isolated injury. This is a true
muscle attachments, and nerves. Injuries in young chil- on-field emergency, and the athlete should be trans-
dren are rare, but sprains and strains are common. ported to the nearest facility that has an orthopedic sur-
Groin pull, or adductor strain, is generally caused geon available. Severe bleeding, avascular necrosis, and
by forced abduction as in running, falling, twisting, or nerve damage can result. Once reduction has been es-
tackling. The associated pain is in the adductor muscle. tablished in a noncomplicated case, protected weight
Pain may arise with adduction or hip flexion, and ten- bearing on crutches for 6 weeks is recommended, fol-
derness may be present over the adductor tubercle. lowed by another 6 weeks of range-of-motion and
Treatment includes rest, ice, protection, and strength- strengthening exercises. An athlete may return gradu-
ening of the muscle when it heals. ally to competition after 3 months when strength and
Quadriceps contusion is caused by a direct motion are normal.
macroinjury to the muscle, resulting in bruising, Femoral neck fractures (stress fractures) are gener-
swelling, and pain. The anterior and lateral thigh re- ally the result of repetitive microtrauma. They com-
gions are most commonly injured. If the muscle re- monly occur in track athletes who have increased their
mains firm on examination after 2 weeks, then radi- mileage. Athletes with this type of injury present with
ographs of the thigh should be done to rule out persistent pain in the groin and pain with internal and
myositis ossificans. (Myositis ossificans is an abnormal external rotation. Range of motion may be limited in
deposition of calcium in the muscle that may be in- hip flexion and internal rotation. If plain radiographs
duced by aggressive stretching of the muscle too early are negative, then a bone scan is indicated. Treatment is
in the clinical course.) Treatment is rest, ice, and pro- based on the type of fracture. A transverse fracture
tection for the first 24 hours. The knee should be kept generally requires internal fixation to prevent femoral
in a fully flexed position. Two to three days after the in- displacement from occurring and potentially causing
jury, range-of-motion exercises may begin in both flex- avascular necrosis. A compression fracture is less likely
ion and extension. Once 120 degrees of motion has to be displaced; treatment is conservative and involves
been established and movement does not cause pain, resting the hip until it heals. Cardiovascular condition-
the athlete may return to competitive activity. ing can be maintained easily through nonimpact exer-
Hamstring strain is very common in many sports. cises and activity.
The mechanism of injury is forced extension of the
knee. Examination reveals pain on palpation of the Maffulli N: Lower limb injuries in children in sports. Clin Sports
muscle. Pain also occurs with knee flexion against resis- Med 2000;19:637 [PMID: 11019733].
tance. Treatment is rest, ice, and compression. The ath-
lete can walk as soon as he or she can tolerate the activ-
ity. It is particularly important to stretch the hamstring
KNEE INJURIES
because, as a two-joint muscle, it is more susceptible to Knee injuries are one of the most common problems
injury than other types of muscle. evaluated by any practitioner. The function of the knee
The bursa is a structure that allows for improved is for mobility and stability. Knee movements include
motion by reducing friction. When a bursa becomes in- flexion, extension, rotation, rolling, and gliding. The
flamed, movement is painful and may be limited. Areas knee is stabilized through a variety of ligaments, ten-
susceptible to bursal inflammation are the shoulder, dons, and the meniscus.
elbow, patella, and hip. Trochanteric bursitis, causing
pain when the hip is flexed, often results from reduced Anterior Knee Pain
flexibility of the iliotibial band and gluteus medius ten-
dons. It is best evaluated in a side-lying position, and The most common knee compliant is anterior knee
pain is reproduced when the hip is actively flexed from pain. This complaint can have multiple causes but
a fully extended hip. Initial treatment is to alter the of- should always include hip pathology as a possibility.
fending activity and then start a stretching program Patellofemoral syndrome is a common cause of anterior
geared at the iliotibial band and hip abductors. Corti- knee pain. The differential diagnosis is quite extensive
costeroid injections may be used after conservative and requires a thorough examination.
treatment has failed. Patellofemoral overuse syndrome occurs in runners
Most hip dislocations are in the posterior direction. and in athletes participating in sports with repetitive stress
Athletes with this injury classically present with hip in the lower extremity. Classically, pain is located over the
flexion, adduction, and internal rotation. medial surface and under surface of the patella. It is asso-
842 / CHAPTER 25

ciated with swelling and crepitus of the knee joint. The bursitis. Pain over the lateral femoral condyle is present
Q-angle often is increased. The Q-angle is measured by along with a positive Ober test. The Ober test is done
drawing a line from the anterior superior iliac spine down with the athlete in a side-lying position. The knee and
to the center of the patella and then through the tibial tu- hip are flexed to 90 degrees, then the hip is maximally
bercle. The intersecting angle is the Q-angle. Normal is abducted and extended. From this position the leg is al-
14 degrees for males and 17 degrees for females. Q-angles lowed to drop by gravity while the knee is still con-
greater than 20 degrees tend to track the patella laterally, trolled. It will not relax if the iliotibial band is tight.
changing the knee biomechanics. Treatment involves rest and stretching. Athletics should
Plicae alares are normal synovial folds in the knee not be resumed until the patient is pain-free. This may
joint. If they become thickened or fibrosed they can be- take up to 6 weeks. Other sources of lateral knee pain
come entrapped. This happens with direct macrotrauma are popliteus tendonitis and biceps tendonitis.
or repetitive microtrauma. The athlete complains of
snapping or popping in the knee. The knee pain is worse Posterior Knee Pain
with knee flexion, and activity intensifies symptoms. On
examination the hamstrings may be tight. Physical find- Posterior knee pain usually results from an injury to the
ings include localized tenderness and occasionally pop- gastrocnemius–soleus complex caused by overuse. It
ping palpable at 30–60 degrees of knee flexion. can also include a Baker cyst, tibial stress fracture, or
Tendonitis of the patellar tendon is caused by tendonitis of the hamstring. Treatment is rest, ice, and
overuse. The mechanism is repetitive loading of the strengthening exercises after symptoms have improved.
quadriceps during running or jumping. Osgood–Schlat-
ter disease occurs in the preteen and adolescent years. It Meniscal Injuries
is most common in boys age 12–15 years and in girls age
11–13 years. Pain usually is present at the tibial tubercle, The meniscus of the knee cushions forces in the knee
and activities using eccentric quadriceps muscle move- joint, increases nutrient supply to the cartilage, and sta-
ment aggravate the pain. The pain can become so exten- bilizes the knee. Most injuries are related to directional
sive that routine activity must be curtailed. Radiographs changes on a weight-bearing extremity. Medial menis-
may or may not show abnormalities. Type 1 disease has cus injuries have a history of tibial rotation in a
no findings, whereas type 2 shows evidence of fragmen- weight-bearing position. This happens frequently in
tation of the tibial tubercle. Many other conditions can ball-handling sports. Lateral meniscus injuries occur
cause anterior knee pain and need to be ruled out, in- with tibial rotation with a flexed knee. These injuries
cluding arthritis, complex regional pain syndrome, infec- are uncommon in children younger than age 10 years.
tions, and neoplasm. Finally, chondromalacia patellae The athlete with such an injury has a history of knee
is an arthroscopic diagnosis and should not be used as a pain, swelling, snapping, or locking, or may report a
clinical diagnosis. feeling of the knee giving way. Physical examination re-
veals joint line tenderness and a positive McMurray hy-
perflexion/rotation test. The diagnostic test of choice is
Treatment of Anterior Knee Pain MRI of the knee, although standard knee radiographs
As with any acute injury, control of inflammation is es- should be included. Arthrograms are still used by some
sential. This begins with rest and ice. Alignment problems practitioners. Treatment may be symptomatic for iso-
should be corrected with stretching and strengthening. lated injuries of the meniscus with no ligamentous in-
Orthotics may need to be used for correction of foot de- volvement or mechanical blocks. . If surgery is needed,
formities. Quadriceps strengthening begins with isometric the athlete should not bear weight on the knee for
exercises that progress to a concentric program. These in- 3 weeks. During this time, range-of-motion and
clude short-arc (the last 10 degrees of knee extension) strengthening exercises can be done.
contractions of the vastus medialis. In the last part of the
therapy program, eccentric loading of the quadriceps can Medial & Lateral Collateral
be incorporated. During this time the athlete should be
working on endurance and cardiovascular conditioning.
Ligament Injuries
Knee bracing is controversial, and the major benefits are The medial and lateral collateral ligaments are posi-
proprioceptive feedback and patellar tracking. tioned along either side of the knee and act to stabilize
it. They help to control varus and valgus stress applied
to the knee joint. Excessive varus or valgus stress causes
Lateral Knee Pain stretching of the ligament, producing tears. Medial in-
Lateral knee pain is most commonly associated with a juries occur with a blow to the lateral aspect of the
tight iliotibial band, which can lead to tendonitis and knee, as seen in a football tackle. The athlete may feel a
 REHABILITATION & SPORTS MEDICINE / 843

pop or lose sensation along the medial aspect of the perflexion of the knee. The examination begins with
knee. The examination reveals an effusion and tender- the noninjured knee and proceeds to the injured side.
ness medially. A valgus stress test done in full extension Confirmatory testing includes the posterior drawer test
and 20–30 degrees of flexion will reproduce pain. Diag- done with the patient supine with the knee flexed to
nosis is made by routine and stress radiographs of the 90 degrees and the foot stabilized. Grading is based on
knee. the amount of translation. Grade 1 (mild) is translation
Treatment is almost always conservative. Initial in- up to 5 mm, grade 2 (moderate) is 5–10 mm, and
juries should be iced and elevated. A protective brace grade 3 (severe) is greater than 10 mm. Diagnostic
needs to be worn, and full knee motion in the brace can imaging includes plain radiographs and MRI scan.
be done after 7 days. Weight bearing is allowed, and a Treatment can be determined as soon as the exact
strengthening program can be started. The athlete injury has been isolated. The use of surgical versus non-
should use the brace until he or she is pain-free and has surgical management is controversial. The use of braces
full range of motion. The use of a functional brace is and a progressive rehabilitation program have been
often required when a player returns to competition. used successfully in athletes with grade 1 and 2 injuries.
This is only temporary until the ligaments heal prop- Grade 3 injuries generally require surgery.
erly.
Andrish JT: Anterior cruciate ligament injuries in the skeletally im-
Anterior Cruciate Ligament Injuries mature patient. Am J Orthop 2001;30:2:103 [PMID:
11234936].
The anterior cruciate ligament (ACL) has three bands Beynnon BD et al: The effect of anterior cruciate ligament trauma
and prevents anterior subluxation of the tibia. The and bracing on knee proprioception. Am J Sports Med
ACL is injured by deceleration, twisting, and cutting 1999;27:150 [PMID: 10102093].
motions. The mechanism of the injury involves force Evans NA et al: The natural history and tailored treatment of ACL
applied to the knee during hyperextension, with exces- injury. Phys Sportsmed 2001;29:19.
sive valgus stress and forced external rotation of the
femur on a fixed tibia. Evaluation of the knee begins
with examining the noninjured knee. The Lachman
FOOT & ANKLE INJURIES
test will provide information on knee stability in rela- Injuries in the lower leg, ankle, and foot are quite com-
tion to the ACL. All other structures of the knee need mon in pediatric athletes. The types of injuries sus-
to be examined to rule out concomitant injuries. Imag- tained tend to depend on the age group. Young chil-
ing of the knee includes plain radiographs along with dren tend to have diaphysial injuries, in contrast to
MRI scan. older children in rapid growth, who tend to have epi-
Treatment options include both conservative and physial and apophysial injuries. Perhaps the most com-
surgical procedures. Conservative treatment includes mon injury evaluated is the ankle sprain. When a liga-
bracing, strengthening, and restricting physical activity. ment is overloaded, tearing occurs. These injuries are
The braces used today enhance proprioception and graded on a scale of 1 to 3. A grade 1 injury is a stretch
control terminal extension. Surgical repair is quite pop- without instability, grade 2 is a partial tear with some
ular, and a patellar tendon graft is used frequently. Re- instability, and grade 3 is a total disruption of the liga-
habilitation of the knee starts immediately after surgery. ment with instability of the joint. The ankle has three
A continuous passive range-of-motion machine is used lateral ligaments (anterior talofibular, calcaneofibular,
postoperatively. Partial weight bearing is allowed in a and posterior talofibular) and a medial deltoid liga-
brace that is set in full extension as the quadriceps ment. Inversion of the foot generally damages the an-
strengthen. After 2 weeks, partial weight bearing and terior talofibular ligament, whereas eversion injures the
walking are started. The goals of the subsequent pro- deltoid ligament. Physical examination often reveals
gram are continued strength, muscle reeducation, en- swelling, bruising, and pain. The anterior drawer test is
durance, agility, and coordination. an easy to perform and reliable test of the anterior
talofibular ligament. Other maneuvers include the talar
tilt and valgus stress test. Diagnostic testing should be
Posterior Cruciate Ligament Injuries done when a bony injury is suspected. The adult Ot-
The posterior cruciate ligament (PCL) runs from the tawa criteria do not pertain to patients younger than
medial femoral condyle to the posterior tibial plateau 18 year old. Tenderness over the malleoli, tenderness
and has two parts. Its main function is to prevent pos- beyond ligament attachments, and excessive swelling
terior tibial subluxation. This is an extremely rare in- are reasons to obtain radiographs.
jury and occurs when the individual falls on a flexed Treatment of ankle injuries is imperative to ensure
knee with the ankle in plantarflexion or with forced hy- full recovery and should begin immediately after the in-
844 / CHAPTER 25

jury. Phase 1 care involves immediate compressive physicians in order to ensure the safety of children par-
wrapping and icing to control swelling and inflamma- ticipating in sports. These include inspecting playing
tion. Protected weight bearing is allowed in the early fields for potential hazards, adapting rules to the devel-
phase of rehabilitation. The second phase begins when opmental level of the participants, and matching oppo-
the athlete can ambulate without pain. During this nents equally.
time ankle range of motion is emphasized, along with The use of the preparticipation history and physical
isometric contractions of the ankle dorsiflexors. Once examination can identify potential problems and allow
90% of strength has returned, active eccentric and con- for prevention and early intervention. Proper training
centric exercises can be added. Phase 3 is designed to techniques reduce injuries by encouraging flexibility,
increase strength, improve proprioception, and add bal- promoting endurance, and teaching correct biomechan-
listic activity. The “foot alphabet” and “tilt board” are ics. Sports education reinforces the concepts of fitness
excellent methods for improving ankle proprioception. and a healthy lifestyle along with sport-specific training.
This program may take up to 6 weeks before an athlete Early identification of an injury allows the athlete to
can return to full activity. The athlete should wear a modify techniques and avoid micro- and macrotrauma.
protective brace for 3 to 4 months and continue to ice Once an injury has occurred, it needs to be identified
after exercising. properly and appropriate measures used to minimize
Plantar fasciitis is common problem that manifests inflammation. Rehabilitation of the injury starts as
itself as heel pain. It happens in runners who log more soon as it has been identified. Early and appropriate
than 30 miles per week and in athletes who have tight care offers the athlete an optimal chance for full recov-
Achilles tendons or poorly fitting shoes. It is common ery and return to full participation.
in people with cavus feet and in individuals who are
overweight. The pain is worse on first standing up in
the morning and taking a few steps. A bone spur is REFERENCES
often found on examination. Treatment involves local Ansved T: Muscular dystrophies: Influence of physical condition-
massage, stretching of the gastrocsoleus, nonsteroidal ing on the disease evolution. Curr Opin Clin Nutr Metab
anti-inflammatory drugs, arch supports, and local Care 2003;6(4):435 [PMID: 12806218].
steroid injections. Runners may need to cut back on Birrer RB, Sedaghat V: Exercise and diabetes mellitus: Optimizing
their weekly mileage until these measures eliminate performance who have type 1 diabetes. Phys Sportsmed
pain. 2003;31(5).
Braith RW: Exercise for those with chronic heart failure. Phys
Sportsmed 2002;30(9).
Anderson SJ: Soccer: A case-based approach to ankle and knee in- Disabella V, Sherman C: Your guide to exercising with asthma.
juries. Pediatr Ann 2000;29:3:178 [PMID: 10734652]. Phys Sportsmed 1998;26(6).
Aronen JG, Garrick JG: Sports-induced inflammation in the lower Draznin MB: Type 1 diabetes and sports participation: Strategies
extremities. Hosp Pract (Off Ed) 1999;34:51 [PMID: for training and competing safely. Phys Sportsmed
10047760]. 2000;28(12).
Hockenbury RT, Sammarco J: Evaluation and treatment of ankle Firoozi S et al: Risk of competitive sport in young athletes with
sprains: Clinical recommendations for a positive outcome. heart disease. Heart 2003;89(7):710 [PMID: 12807837].
Phys Sportsmed 2001;29:2:57.
Howard GM et al: Epilepsy and sports participation. Curr Sports
Med Rep 2004;3(1):15.
PREVENTION Howe WB: Preventing infectious disease in sports. Phys Sportsmed
2003;31(2).
As in all activities most sports-related injuries can be MacKnight JM: Infectious mononucleosis: Ensuring a safe return
prevented by the use of protective equipment, common to sport. Phys Sportsmed 2002;30(1).
sense, and proper training. Protective equipment Maron BJ: Hypertrophic Cardiomyopathy: Practical Steps for Pre-
should be properly fitted and maintained by an individ- venting Sudden Death. Phys Sportsmed 2002;30 (1).
ual with training and instruction. Helmets should be Maron BJ: The young competitive athlete with cardiovascular ab-
used in football, baseball, hockey, bicycling, skiing, in- normalities: Causes of sudden death, detection by prepartici-
line skating, skateboarding, or any sport with risk for pation screening, and standards for disqualification. Card
Electrophysiol Rev 2002;6(1-2):100 [PMID: 11984027].
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Moeller JL: Contraindications to Athletic Participation: Spinal,
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Primos WA: Sports and exercise during acute illness: Recommend- Terrell T et al: Blunt trauma reveals a single kidney: A disqualifica-
ing the right course for patients. Phys Sportsmed 1996;24(1). tion dilemma. Phys Sportsmed 1997;25 (11).
Salim MA, Alpert BS: Sports and Marfan syndrome. Phys Vinger PF: A practical guide for sports eye protection. Phys
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Tarnopolsky MA: Metabolic myopathies and physical activity: Winell J, Burke SW: Sports participation of children with Down
When fatigue is more than simple exertion. Phys Sportsmed syndrome. Orthop Clin North Am 2003;34(3):439 [PMID:
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 Rheumatic Diseases 26
J. Roger Hollister, MD

JUVENILE RHEUMATOID ARTHRITIS can be expected within 1 year. They do not develop iri-
(JUVENILE CHRONIC ARTHRITIS) docyclitis.
The polyarticular pattern resembles the adult dis-
ease, with chronic pain and swelling of many joints in a
ESSENTIALS OF DIAGNOSIS symmetrical fashion. Both large and small joints are
& TYPICAL FEATURES usually involved. Systemic features are less prominent,
although low-grade fever, fatigue, rheumatoid nodules,
and anemia may be present. Patients with this form
• Nonmigratory monarticular or polyarticular tend to have long-standing arthritis, although the dis-
arthropathy, with a tendency to involve large ease may wax and wane. Iridocyclitis occurs occasion-
joints or proximal interphalangeal joints and last- ally in this group. Older children may have a positive
ing more than 3 months. rheumatoid factor test.
• Systemic manifestations with fever, erythema- The third pattern is characterized by pauciarticular
tous rashes, nodules, leukocytosis, and, occasion- disease, a chronic arthritis of a few joints—often the
ally, iridocyclitis, pleuritis, pericarditis, anemia, fa- large weight-bearing joints—in an asymmetrical distri-
tigue, and growth failure. bution. The synovitis is usually mild and may be pain-
less. Systemic features are uncommon, but extra-articu-
lar involvement is severe, with inflammation in the eye.
Up to 30% of children with pauciarticular JRA develop
insidious, asymptomatic iridocyclitis, which may cause
General Considerations blindness if untreated. The activity of the eye disease
does not correlate with that of the arthritis. Therefore,
Patients with juvenile rheumatoid arthritis (JRA) have routine ophthalmologic screening with slitlamp exami-
immunogenetic traits different from those of adults nation must be performed at 3-month intervals if the
with rheumatoid arthritis. In JRA, human leukocyte ANA test is positive and at 6-month intervals if the
antigen (HLA)-DR5 is associated with iritis and the ANA test is negative for 4 years after the onset of arthri-
production of antinuclear antibodies (ANA), whereas tis.
HLA-DR4 is found in seropositive, polyarticular dis-
ease. These traits may be important in the formation of B. LABORATORY FINDINGS
antisuppressor cell antibodies, immune complex gener-
ation, and consequent chronic inflammatory disease. No completely reliable diagnostic test is available for
Genomics by microarray analysis show great promise in JRA. Rheumatoid factor is positive in about 15% of pa-
understanding the genetic predisposition to JRA. tients, usually in patients with polyarticular disease
Tumor necrosis factor (TNF) may be the final common whose onset occurs after age 8 years. ANA are most
cytokine that perpetuates inflammation. often present in pauciarticular disease with iridocyclitis
and may be an indicator of this complication; they are
also fairly common in the late-onset rheumatoid factor-
Clinical Findings positive group. A normal erythrocyte sedimentation
rate (ESR) does not exclude the diagnosis.
A. SYMPTOMS AND SIGNS Table 26–1 lists the general characteristics of joint
Three major clinical presentations in JRA provide clues fluid in various conditions. A positive Gram stain or
to the prognosis and possible sequelae of the disease. In culture is the only definitive test for infection. A leuko-
the acute febrile form, an evanescent salmon-pink mac- cyte count over 2000/µL suggests inflammation due to
ular rash, arthritis, hepatosplenomegaly, leukocytosis, infection, any of the collagen–vascular diseases,
and polyserositis characterize the constellation de- leukemia, or reactive arthritis. A very low glucose con-
scribed by George Still. Patients with this form have centration (< 40 mg/dL) or very high polymorphonu-
episodic illness, and remission of the systemic features clear leukocyte count (> 60,000/µL) is highly sugges-
846
Copyright © 2005, 2001, by The McGraw-Hill Companies, Inc. Click here for terms of use.
 RHEUMATIC DISEASES / 847

Table 26–1. Joint fluid analysis. in a single joint demand synovial fluid examination and
culture to identify the pathogen.
Disorder Cells/␮L Glucosea The arthritis of rheumatic fever is migratory, tran-
sient, and often more painful than that of JRA.
Trauma More red cells than Normal Rheumatic fever is rare in children younger than age
white cells; usually 5 years. Evidence of rheumatic carditis should be
< 2000 white cells sought. Evidence of recent streptococcal infection is es-
Reactive arthritis 3000–10,000 white Normal sential to the diagnosis. The fever pattern in rheumatic
cells, mostly mono- fever is low grade and persistent compared with the
nuclears spiking fever in the systemic form of JRA. Lyme arthri-
Juvenile rheumatoid 5000–60,000 white Usually normal
arthritis and other cells, mostly or slightly low
inflammatory neutrophils
arthritides Table 26–2. Differential diagnosis of limb pain
Septic arthritis > 60,000 white cells, Low to normal
in children.
> 90% neutrophils
a Orthopedic
Normal value is 75% or more of serum glucose value.
Stress fracture
Overuse syndrome
Chondromalacia patellae
Osgood–Schlatter disease
tive of bacterial arthritis in a child. Chemical analysis of Slipped capital femoral epiphysis
synovial fluid is otherwise of little diagnostic benefit. Legg–Calvé–Perthes disease
Hypermobility syndrome
C. IMAGING Reactive arthritis
In the early stages of the disease, only soft tissue Schönlein–Henoch purpura
swelling and regional osteoporosis are seen. Magnetic Reactive arthritis following diarrhea
resonance imaging (MRI) of involved joints may show Toxic synovitis of the hip
joint damage earlier in the course of the disease than Transient synovitis following viral infection
other imaging modalities. Rheumatic fever
Infections
Bacterial
Differential Diagnosis Lyme arthritis
Table 26–2 lists the most common causes of limb pain Osteomyelitis
in childhood. A few points of information may indicate Septic arthritis
the most likely diagnosis. For instance, orthopedic Discitis
Viral
causes are due to increased physical activity, not major
Parvovirus (in adolescents)
trauma. Reactive arthritides are suggested by a preced- Rubella
ing viral infection, strep throat, or purpuric rash, and Hepatitis B arthritis
their course waxes and wanes over several days. Collagen–vascular
Monarticular arthritis is the most important disor- Juvenile rheumatoid arthritis
der in the differential diagnosis to establish. Pain in the Spondyloarthropathy
hip or lower extremity is a frequent symptom of child- Systemic lupus erythematosus
hood cancer, especially leukemia, neuroblastoma, and Dermatomyositis
rhabdomyosarcoma. Infiltration of bone by tumor and Neoplastic
actual joint effusion may be seen. Radiographs of the Leukemia
affected site and a careful examination of the blood Lymphoma
smear for unusual cells and thrombocytopenia are nec- Neuroblastoma
essary. A normal lactate dehydrogenase value is helpful Reticuloendotheliosis
in the exclusion of neoplastic disease. In doubtful cases, Osteoid osteoma
bone marrow examination is indicated. Bone tumors (benign or malignant)
Bacterial arthritis is usually acute and monarticular Syndromes of psycho-organic origin
except for arthritis associated with gonorrhea, which Growing pains
may be associated with a migratory pattern. Fever, Fibromyalgia
leukocytosis, and increased ESR with an acute process Reflex neurovascular dystrophy
848 / CHAPTER 26

tis resembles pauciarticular JRA, but the former occurs Prognosis

as discrete, recurrent episodes of arthritis lasting
2–6 weeks. A negative test for antibodies to Borrelia In the primarily articular forms of JRA, disease activity
burgdorferi argues strongly against this diagnosis. diminishes progressively with age and ceases by puberty
in about 85% of patients. In a few instances, the disor-
der will persist into adult life. Problems after puberty
Treatment relate primarily to residual joint damage. Presentation
The objectives of therapy are to restore function, relieve in the teen years usually presages adult disease. The
pain, and maintain joint motion. In recent years, other children most liable to be handicapped permanently are
nonsteroidal anti-inflammatory drugs (NSAIDs) have those with unremitting synovitis, hip involvement, or
replaced salicylates in the medical treatment of JRA. Al- positive rheumatoid factor tests.
though their anti-inflammatory potency is not different
from that of aspirin, their liquid form, decreased fre- Anthony KK, Schanberg LE: Pain in children with arthritis: A re-
view of the current literature. Arthritis Rheum 2003;49:272.
quency of dosing, and diminished side effects appear to
Bowyer SL et al: Health status of patients with juvenile rheumatoid
enhance compliance, cause fewer side effects, and jus- arthritis at 1 and 5 years after diagnosis. J Rheumatol
tify their increased cost. Naproxen, 7.5 mg/kg twice 2003;30:394.
daily; ibuprofen, 10 mg/kg four times daily; or di- Flato B et al: Prognostic factors in juvenile rheumatoid arthritis: A
clofenac, 1 mg/kg given twice daily, may be used. If case–control study revealing early predictors and outcomes
benefit occurs in the first 2 days, improvement will after 14.9 years. J Rheumatol 2003;30:386.
continue, with the maximum effect occurring at Franco CA et al: Factors related to severe uveitis at diagnosis in
6 weeks. Celecoxib and rofecoxib, two NSAIDs that are children with juvenile idiopathic arthritis in a screening pro-
selective cyclo-oxygenase-2 (COX) inhibitors, show gram. Am J Ophthalmol 2003;135:757.
promise in relieving the gastrointestinal irritation seen Ilowite NT: Current treatment of juvenile rheumatoid arthritis. Pe-
with older NSAIDs which have both COX 1 and 2 ac- diatrics 2002;109:109.
tivity. Dosages for children are under investigation. Jarvis JN: Juvenile rheumatoid arthritis: A guide for pediatricians.
Pediatr Ann 2002;31:437.
Range-of-motion and muscle-strengthening exercises
should be taught and supervised by a therapist, and a Lovell DJ et al: Long-term efficacy and safety of etanercept in chil-
dren with polyarticular-course juvenile rheumatoid arthritis:
home program should be instituted. Bed rest is to be Interim results from an ongoing multicenter, open-label, ex-
avoided except in the most acute stages. Joint casting is tended-treatment trial Arthritis Rheum 2003;48(1):218.
almost never indicated. Patel H, Goldstein D: Pediatric uveitis. Pediatr Clin North Am
Patients with JRA unresponsive to aspirin or other 2003;50:125.
NSAIDS have a number of alternatives. Methotrexate is
the second-line medication of choice. Symptomatic re- SPONDYLOARTHROPATHY
sponse usually occurs within 3–4 weeks. The low
dosages used (5–10 mg/m2/wk as a single dose) have Lower extremity arthritis, particularly in males older
been associated with few side effects. Stomatitis usually than age 10 years, suggests a form of spondyloarthropa-
resolves with continued administration. Nausea may be thy. Inflammation of tendinous insertions (enthesopa-
prevented by splitting the dose. Hepatotoxicity, includ- thy) such as the tibial tubercle or the heel occurs in
ing fibrosis, has been reported. A complete blood count these diseases and not in JRA. Low back pain and
and liver function tests should be obtained at 2-month sacroiliitis are quite specific for this form of arthritis.
intervals. Liver biopsy may be performed if there are Carriage of HLA-B27 antigen occurs in 80% of pa-
recurrent elevations of aminotransferases. Two new sec- tients with this disorder. No autoantibodies are found,
ond-line agents are available for patients with progres- but inflammatory indicators such as an elevated ESR or
sive disease. Leflunomide is an antipyrimidine medica- C-reactive protein are usually present. The episodes are
tion that is as effective as methotrexate. Side effects may usually intermittent, in contrast to the more chronic
include diarrhea and alopecia. Etanercept is a TNFα symptoms of JRA. Acute, not chronic, uveitis may
receptor construct that must be administered sub- occur.
cutaneously twice a week (0.4 mg/kg/dose). Infliximab, The NSAIDs, particularly indomethacin (2–4
an anti-TNFα antibody, administered in combina- mg/kg/d) and naproxen (15 mg/kg/d), are more effective
tion with methotrexate, is another second-line treat- than salicylates in treating the spondyloarthropathies.
ment. Iridocyclitis should be treated by an ophthalmol- Refractory cases may respond to methotrexate, etaner-
ogist, and methotrexate may be used in difficult cases. cept, or infliximab. Local corticosteroid injections are
Local corticosteroid injections into joints, synovec- contraindicated in Achilles tendinitis.
tomy, or joint replacement may be indicated in selected The disorder does not frequently progress to joint
patients. destruction or ankylosis in children as it does in adults.
 RHEUMATIC DISEASES / 849

Burgos-Vargas R: Juvenile onset spondyloarthropathies: Therapeu- to be due not to tissue-specific autoantibodies but
tic aspects. Ann Rheum Dis 2002;61 (Suppl) 3:iii33. rather to tissue damage by lymphocytes, neutrophils,
and complement evoked by the deposition of
ENTEROPATHIC ARTHRITIS antigen–antibody complexes. Many antigen–antibody
systems are present in this disorder, but disease activity
Enteropathic arthritis comprises several syndromes, in- correlates best with DNA/anti-DNA complexes. Labo-
cluding Reiter syndrome, reactive arthritis, and the ratory tests of these antibodies and complement com-
arthritis of inflammatory bowel disease and celiac dis- ponents give an objective assessment of disease patho-
ease. The unifying feature of these arthritides is the as- genesis and response to therapy. Autoreactive T
sociation of lower extremity arthritis with antecedent or lymphocytes that have escaped clonal deletion and un-
concurrent gastrointestinal symptoms. Reactive arthritis regulated B-lymphocyte production of autoantibodies
after diarrhea caused by Salmonella, Shigella, Yersinia, may initiate the disease. A genetic predisposition to
or Chlamydia infection occurs in individuals who are lupus appears critical to causation of the disease.
HLA-B27-positive. The human gene product shares a
six-amino acid homology with the cell wall of the
provocative organism. Transvection experiments in Clinical Findings
which human HLA-B27 genes are inserted into rats A. SYMPTOMS AND SIGNS
and mice have supported the central role of the genetic
predisposition in this form of arthritis. However, ani- SLE is more common in girls than boys (8:1). Disease
mals raised in a germ-free environment have less dis- onset most often occurs between ages 9 and 15 years.
ease, emphasizing the role of enteric organisms in these The symptoms depend on the organ involved with im-
spondyloarthropathies. In an analogous manner, the mune complex deposition.
arthritis associated with Crohn disease and ulcerative 1. Joint symptoms—Joint symptoms are the most
colitis usually begins after or concurrent with active common presenting feature. Nondeforming arthritis
bowel disease. Other extraintestinal manifestations such may involve any joint, often in a symmetrical manner.
as uveitis, stomatitis, hepatitis, and erythema nodosum Myositis may also occur and is more painful than the
may occur in these individuals. inflammation in dermatomyositis.
Treatment for the musculoskeletal manifestations of
inflammatory bowel disease includes controlling bowel 2. Systemic manifestations—These include weak-
disease and the use of NSAIDs, as in ankylosing ness, anorexia, fever, fatigue, and weight loss.
spondylitis.
3. Skin lesions—Lesions include butterfly erythema
and induration, small ulcerations in skin and mucous
Baeten D et al: Immune linkages between inflammatory bowel dis- membranes, purpura, alopecia, and Raynaud phenome-
ease and spondyloarthopathies. Curr Opin Rheumatol
2002;14:342.
non. The sun sensitivity of the dermal lesions may be
striking.
SYSTEMIC LUPUS ERYTHEMATOSUS 4. Polyserositis—Polyserositis may include pleurisy
with effusions, peritonitis, and pericarditis. Libman–
Sacks endocarditis may occur in patients with antiphos-
ESSENTIALS OF DIAGNOSIS pholipid antibodies.
& TYPICAL FEATURES 5. Gastrointestinal findings—Hepatosplenomegaly
and lymphadenopathy may occur. Gastrointestinal pre-
• Multisystem inflammatory disease of joints, sentations of SLE are unusual, with the exception of
serous linings, skin, kidneys, and the CNS. acute pancreatitis.
• ANA must be present in active, untreated disease. 6. Renal manifestations—Renal SLE produces few
symptoms at onset but is often progressive and is the
leading cause of death among patients with SLE. Renal
biopsy is indicated in patients who do not respond to
corticosteroids or who cannot have corticosteroids ta-
General Considerations pered to a less-toxic, alternate-day regimen. The histo-
Systemic lupus erythematosus (SLE) is the prototype of logic pattern of diffuse proliferative nephritis requires
immune complex diseases; its pathogenesis is related to the most aggressive treatment. Late complications are
the deposition in the tissue of circulating soluble im- nephrosis and uremia. Control of hypertension is criti-
mune complexes. The spectrum of symptoms appears cal to maintaining renal function.
850 / CHAPTER 26

7. Central nervous system (CNS)—CNS involve- Treatment

ment produces a variety of symptoms such as seizures;
coma; hemiplegia; focal neuropathies; chorea; and be- The treatment of SLE should be tailored to the organ
havior disturbances, including psychosis. system involved so that toxicities are minimized. Pred-
nisone, 0.5–1 mg/kg/d orally, has significantly lowered
the mortality rate in SLE and should be used in all pa-
B. LABORATORY FINDINGS tients with renal, cardiac, or CNS involvement. The
Leukopenia and anemia are frequently found with a dosage should be varied using clinical and laboratory
low incidence of Coombs positivity. Thrombocytope- parameters of disease activity, and the minimum
nia and purpura may be early manifestations even in amount necessary to control the disease should be used.
the absence of other organ involvement. The ESR is el- Alternate-day regimens of corticosteroid are frequently
evated, and hypergammaglobulinemia is often present. possible. Skin manifestations, arthritis, and fatigue may
Renal involvement is indicated by the presence of red be treated with antimalarials such as hydroxychloro-
cells, white cells, red cell casts, and protein in the urine. quine, 5–7 mg/kg/d orally. Pleuritic pain or arthritis
The ANA test is invariably positive in patients with ac- can usually be managed with NSAIDs.
tive untreated SLE, and a negative ANA test excludes If disease control is inadequate with prednisone or if
the diagnosis. For patients with a positive ANA test, a the dose required produces intolerable side effects, an
profile identifying individual disease-specific antibodies immunosuppressant should be added. Either azathio-
should be ordered. Anticardiolipin antibody and the prine, 2–3 mg/kg/d orally, or cyclophosphamide,
lupus anticoagulant are two autoantibodies that iden- 0.5–1 g/m2, administered intravenously once a month,
tify lupus patients at risk for thrombotic events. has been most widely used. Recent studies indicate that
In managing the disease, elevated titers of anti-DNA mycophenolate mofetil may used in place of intra-
antibody and depressed levels of serum complement venous cyclophosphamide to induce remission or sus-
(C3) accurately reflect active disease, especially renal, tain remission after intravenous cyclophosphamide
CNS, and skin disease. A computed tomography or therapy. These drugs are ineffective during acute crises
MRI scan may identify pathologic conditions of the such as seizures. Thrombotic events due to clotting an-
brain in lupus cerebritis, such as infarction, vasculitis, tibodies require long-term anticoagulation.
or atrophy. The toxicities of the regimens must be carefully con-
sidered. Growth failure, osteoporosis, Cushing syndrome,
adrenal suppression, and aseptic necrosis are serious side
Differential Diagnosis effects of chronic use of prednisone. When high doses of
SLE may simulate many inflammatory diseases such as corticosteroids are used (> 2 mg/kg/d), the risk of sepsis is
rheumatic fever, rheumatoid arthritis, and viral infec- real. Cyclophosphamide causes bladder epithelial dyspla-
tions. It is essential to review all organ systems carefully sia, hemorrhagic cystitis, and sterility. Azathioprine has
to establish a clinical pattern. Renal and CNS involve- been associated with liver damage, pancreatitis, and bone
ment is unique to SLE. A negative ANA test excludes marrow suppression. Immunosuppressant treatment
the diagnosis of SLE. Tests yielding false-positive re- should be withheld if the total white count falls below
sults are usually of low titer (1:320). 3000/µL or the neutrophil count below 1000/µL. Retinal
An overlap syndrome known as mixed connective damage from chloroquine derivatives has not been ob-
tissue disease, with features of several collagen–vascular served with recommended dosages. Intravenous pulse
diseases, occurs in adults and children. The symptom steroid therapy and plasmapheresis are treatments that
complex is diverse and does not readily fit previous clas- may be useful in selected cases.
sifications. Arthritis, fever, skin tightening, Raynaud Amenorrhea may be a result of uncontrolled SLE
phenomenon, muscle weakness, and rashes are com- but may also be a consequence of treatment with pred-
monly present. Important factors in recognition of this nisone, cyclophosphamide, or azathioprine.
disease entity are the relative infrequency of renal dis-
ease, which implies a better prognosis than SLE, and Course & Prognosis
the corticosteroid responsiveness of symptoms, which
distinguishes mixed connective tissue disease from scle- The prognosis in SLE relates to the severity of renal in-
roderma. The definition of the disease includes the volvement or infectious complications of treatment.
presence of serum antibody to a ribonuclear protein. With improved diagnosis, milder cases are now identi-
The initial ANA test is positive in very high titers. The fied. Nonetheless, the survival rate has improved from
ANA profile demonstrates the antibody to ribonuclear 51% at 5 years in 1954 to 90% today. The disease has a
protein. Pulmonary disease in childhood produces natural waxing and waning cycle, and periods of com-
major morbidity. plete remission are not unusual.
 RHEUMATIC DISEASES / 851

Arbuckle MR et al: Development of autoantibodies before the clin- stiffness, and swelling may be found but are not strik-
ical onset of systemic lupus erythematosus. N Engl J Med ing. Neurologic findings, such as absence of tendon re-
2003;349:1526.
flexes, are not seen until late in the disease. Pharyngeal
Bijl et al: Mycophenolate mofetil prevents a clinical relapse in pa- and respiratory involvement can be life-threatening.
tients with systemic lupus erythematosus at risk. Ann
Rheumatol Dis 2003;62:534. Flexion contractures and muscle atrophy produce sig-
Boon SJ, McCurdy D: Childhood systemic lupus erythematosus.
nificant residual deformities. Calcinosis may follow the
Pediatr Ann 2002;31:407. inflammation in muscle and skin.
Egner W: The use of laboratory tests in the diagnosis of SLE. J Clin The rash of dermatomyositis is very helpful in the
Pathol 2000;53:424. diagnosis. Characteristically, the rash involves the upper
Greenberg SB: Infections in the immunocompromised rheumato- eyelids and extensor surfaces of the knuckles, elbows,
logic patient. Crit Care Clin 2002;18:931. and knees with a distinctive heliotrope color that pro-
Klein-Gitelman et at: Systemic lupus erythematosus in childhood. gresses to a scaling and atrophic appearance. Periorbital
Rheum Dis Clin North Am 2002;28:561. edema is not uncommon. Nail-fold capillary abnormal-
ities are associated with poorer prognosis. None of the
DERMATOMYOSITIS (POLYMYOSITIS) rashes associated with other childhood rheumatic dis-
eases have these features of distribution. The severity of
the rash frequently does not parallel that of the muscle
ESSENTIALS OF DIAGNOSIS disease.
& TYPICAL FEATURES B. LABORATORY FINDINGS
• Pathognomonic skin rash.
Determination of muscle enzyme levels in blood is the
most helpful tool in diagnosis and treatment. All en-
• Weakness of proximal muscles and occasionally zymes, including serum aldolase, should be screened to
of pharyngeal and laryngeal groups. detect an abnormality that reflects activity of the disease.
• Pathogenesis related to vasculitis. In later years of the illness, MRI of weak muscles may
show disease activity even when enzymes are normal.
The ANA test may be positive. Electromyography is use-
ful for distinguishing myopathic from neuropathic causes
General Considerations of muscle weakness. Muscle biopsy is indicated in doubt-
Dermatomyositis, a rare inflammatory disease of muscle ful cases of myositis without the pathognomonic rash.
and skin in childhood, is uniquely responsive to cortico-
steroid treatment. The vasculitis in childhood dermato- Treatment
myositis differs pathologically from the adult disease. Prednisone in high dosages (1–2 mg/kg/d orally) has
Small arteries and veins are involved, with an exudate of been shown to speed recovery. The dosage should be
neutrophils, lymphocytes, plasma cells, and histiocytes. maintained or increased until muscle enzymes have re-
The lesion progresses to intimal proliferation and turned to normal. Functional recovery will lag some-
thrombus formation. These vascular changes are found what behind laboratory improvement. With improve-
in the skin, muscle, kidney, retina, and gastrointestinal ment, the dosage may be cut to a level that maintains
tract. Postinflammatory calcinosis is frequent. disease control and normal muscle enzymes. Treatment
The autoimmune pathogenesis of dermatomyositis must be continued for an average of 2 years.
has been difficult to unravel. Recent studies have shown Methotrexate, 1 mg/kg/wk, is an effective, steroid-spar-
that both cellular and humoral mechanisms may be in- ing treatment. Intravenous immune globulin or cy-
volved. Lymphocytes from patients undergo blastogene- closporine therapy is used in refractory cases. Physical
sis in the presence of muscle tissue and release lympho- therapy is critical to prevent or allay contractures.
toxin, which destroys cultured fetal muscle cells. Biopsies
studied with immunofluorescence techniques demon-
strate immunoglobulin and complement in perivascular
Course & Prognosis
distribution. The putative antigen has not been identi- Most children recover and discontinue medications in
fied, and results of viral studies have been negative. 1–3 years. Relapses may occur. Functional ability is
very good in most patients. Myositis in childhood is
Clinical Findings not associated with an increased risk of cancer.
A. SYMPTOMS AND SIGNS
Mukamel M et al: New insight into calcinosis of juvenile dermato-
The predominant symptom is proximal muscular weak- myositis: A study of composition and treatment. J Pediatr
ness affecting pelvic and shoulder girdles. Tenderness, 2001;138:763.
852 / CHAPTER 26

Pachman LM: Juvenile dermatomyositis: Immunogenetics, patho- subcutaneous tissue becomes atrophied and contrac-
physiology, and disease expression. Rheum Dis Clin North tures develop in affected joints. Physical therapy and
Am 2002;28:579.
treatment with methotrexate or vitamin D analogues
Ramanan AV, Feldman BM: Clinical features and outcomes of ju- may limit extension of the lesions but do not reverse
venile dermatomyositis and other childhood onset myositis
syndromes. Rheum Dis Clin North Am 2002;28:833. previous damage. It is rare for the limited forms to
Rennebohm R: Juvenile dermatomyositis. Pediatr Ann
progress to systemic sclerosis.
2002;31:426. In systemic sclerosis, the dermal process is general-
Trapani S, et al: Pulmonary involvement in juvenile dermatomyosi- ized. Raynaud phenomenon is almost invariably pre-
tis: A two-year longitudinal study. Rheumatology 2001; sent. Arthralgias, esophageal dysfunction, and renal dis-
40:216. ease are present. Involvement of the lungs and kidneys
may lead to rapid demise. The pathogenesis of systemic
scleroderma is unknown and there are no effective ther-
POLYARTERITIS NODOSA apies.
Polyarteritis nodosa is a rare disease, but a significant
number of cases have been reported in childhood and Murray KJ, Laxer RM: Scleroderma in children and adolescents.
infancy. No single cause has been found, but evidence Rheum Dis Clin North Am 2002;28:603.
of a streptococcal trigger and poorly controlled par-
vovirus infection have been found in some series. RAYNAUD PHENOMENON
Pathologically, the disease is a vasculitis of medium-
sized arteries with fibrinoid degeneration in the media Raynaud phenomenon is an intermittent vasospastic
extending to the intima and adventitia. Neutrophils disorder of fingers and sometimes the toes. As much as
and eosinophils comprise the inflammatory reaction. 10% of the adult population may have this disorder,
Aneurysms may be palpated or seen radiographically. and onset in childhood is not uncommon. The classic
Thrombosis of diseased arteries may cause infarction in triphasic presentation is cold-induced pallor, then
many organs. Fibrosis of vessels and surrounding tissues cyanosis, followed by hyperemia, but incomplete forms
accompanies healing. are common. In adults older than age 35 years who are
Symptoms arise from many organ systems, making ANA-positive, Raynaud phenomenon may be a harbin-
diagnosis difficult. Unexplained fever, conjunctivitis, ger of rheumatic disease. This progression is rarely seen
CNS involvement, and cardiac disease are more promi- in childhood. Evaluation should include a detailed his-
nent in children than in adults. Many cases appear as tory with review of systems relevant to rheumatic dis-
acute myocarditis, and the peripheral neuropathy so ease and examination for nail-fold capillary abnormali-
common in adults with the disease is unusual in chil- ties. In the absence of positive findings, Raynaud
dren. Diagnosis depends on biopsy-proved vasculitis or phenomenon is likely to be idiopathic.
characteristic aneurysms on angiography. Treatment involves education about hand warming
The mortality rate is high, especially with cardiac in- (eg, using mittens not gloves); the role of stress, which
volvement. Treatment usually consists of prednisone may be a precipitant; and in very symptomatic patients,
(1–1.5 mg/kg/d orally), immunosuppressants, and in- treatment with calcium channel blockers such as
travenous immune globulin, but controlled studies on nifedipine during winter months.
the efficacy of these therapies are not available.
Nigrovic PA et al: Raynaud’s phenomenon in children: A retro-
spective review. Pediatrics 2003;111:715.
Besbas N et al: Renal involvement in polyarteritis nodosa: Evalua-
tion of 26 Turkish children. Pediatr Nephrol 2000;14:325.
Frankel SK et al: Vasculitis: Wegener granulomatosis, Churg–
Strauss, microscopic polyangiitis, polyarteritis, Takayasu ar- NONRHEUMATIC PAIN
teritis. Crit Care Clin 2002;18:855.
SYNDROMES
SCLERODERMA
Fortunately, the most common forms of scleroderma in
1. Reflex Sympathetic Dystrophy
childhood are linear scleroderma and morphea, not sys- Reflex sympathetic dystrophy is a painful condition
temic sclerosis. The skin disease begins with the appear- that is frequently confused with arthritis. The preva-
ance of indurated and depigmented patches (morphea) lence and recognition of the condition appear to be in-
or streaks of skin on an extremity (linear scleroderma). creasing. Severe extremity pain leading to nearly com-
As the linear form progresses over a 2- or 3-year period, plete loss of function is the hallmark of the condition.
 RHEUMATIC DISEASES / 853

Evidence of autonomic dysfunction is demonstrated by Schikler KN: Is it juvenile rheumatoid arthritis or fibromyalgia?
color changes, temperature differences, and dyshidrosis Med Clin North Am 2000;84:967.
in the affected extremity. Foot involvement is more Worrel LM et al: Treating fibromyalgia with a brief interdiscipli-
common than hand involvement. A puffy swelling of nary program: Initial outcomes and predictors of response.
Mayo Clin Proc 2001;76:384.
the entire hand or foot is common. On examination,
cutaneous hyperesthesia is evident to even the slightest
touch. Results of laboratory tests are negative. Radi- 3. Chronic Fatigue Syndrome
ographic findings are normal except for the late devel- Since 1985, chronic fatigue syndrome has become an
opment of osteoporosis. Bone scans are helpful and increasingly common diagnosis. The distinction be-
demonstrate either increased or decreased blood supply tween this apparent organic fatigue and fatigue associ-
to the painful extremity. ated with emotional causes is not easily made. Criteria
The cause of this condition is unknown. Unlike have been developed by the National Institutes of
adults, children only occasionally have a history of signif- Health to assist in classification. The fatigue should
icant physical trauma at disease onset. How autonomic have a defined date of onset, and there is a long list of
dysfunction causes severe somatic pain is unknown, but excludable diagnoses. Other clinical manifestations in-
the feedback cycle does provide the basis for treatment. clude low-grade fevers, sore throat, painful lymph
In mild cases, a program of rehabilitative physical ther- nodes, and neuropsychiatric problems. Epstein–Barr
apy in combination with desensitization techniques will virus infection does not account for all the patients de-
restore function and relieve pain. Patients with reflex scribed. Treatment is symptomatic and somewhat un-
sympathetic dystrophy who are unresponsive to therapy satisfactory.
need family counseling and may respond to steroids or
ganglionic blocks by local anesthesia. Long-term progno- Bell DS et al: Thirteen-year follow-up of children and adolescents
sis is good if recovery is rapid; recurrent episodes imply a with chronic fatigue syndrome. Pediatrics 2001;107:994.
less favorable prognosis. Krilov LR, Fisher M: Chronic fatigue syndrome in youth: Maybe
not so chronic after all. Contemp Ped 2002;19:61.

Sherry D: An overview of amplified musculoskeletal pain syn- HYPERMOBILITY SYNDROME

dromes. J Rheumatol 2000;27:44.
Ligamentous laxity, which previously was thought to
occur only in Ehlers–Danlos syndrome or Down syn-
drome, is now recognized as a common cause of joint
2. Fibromyalgia pain.
Fibromyalgia is a diffuse pain syndrome in which pa- Children are now participating in a wide range of
tients experience pain all over their bodies without ob- physically demanding sports and activities. Patients
jective physical findings. Weather changes and fatigue with hypermobility present with episodic joint pain and
exacerbate symptoms. A sleep disturbance, such as occasionally with swelling that lasts a few days after in-
insomnia or prolonged periods of awakening at night, creased physical activity. Depending on the activity, al-
is an almost universal symptom. Patients should most any joint may be affected.
be carefully questioned about these symptoms. On ex- Physical examination may reveal joint swelling and
amination, patients are normal except for pain tenderness, but the key to diagnosis is the demonstra-
during palpation of characteristic trigger points at the tion of ligamentous laxity. Five criteria have been estab-
insertion of muscles, especially along the neck, spine, lished: (1) passive opposition of the thumb to the flexor
and pelvis. surface of the forearm; (2) passive hyperextension of the
Treatment consists of physical therapy and attention fingers so that they are parallel to the extensor surface of
to relieving the sleep disorder. Low-dose antidepressant the forearm; (3) hyperextension of the elbow; (4) hy-
medication (amitriptyline, 25 mg) taken before sleep perextension of the knee (genu recurvatum); and
may produce a remarkable degree of pain relief. Physi- (5) palms on floor with knees extended. Results of labo-
cal therapy should emphasize a graded rehabilitative ap- ratory tests are normal. The pain associated with the
proach to stretching and exercise. Analgesics are often syndrome is produced by improper joint alignment
ineffective and should be avoided if possible to avoid caused by laxity that is promoted by the stresses of vig-
habituation to narcotic medications. orous exercise.
The prognosis for young patients is unclear, and Treatment consists of a graded conditioning pro-
long-term strategies may be necessary to enable them to gram designed to provide muscular support of the
cope with the condition. joints involved to compensate for the loose ligaments.
854 / CHAPTER 26

The prognosis is good, provided conditioning before REFERENCES

activities is adequate.
Cassidy JT, Petty RE: Textbook of Pediatric Rheumatology, 4th ed.
WB Saunders, 2001.
Grahame R et al: The revised (Brighton 1998) criteria for the diag- Jacobs JC: Pediatric Rheumatology for the Practitioner, 2nd ed.
nosis of benign joint hypermobility syndrome (BJHS). Springer, 1993.
J Rheumatol 2000;27:1777.
 Hematologic Disorders 27
Daniel R. Ambruso, MD, Taru Hays, MD, Peter A. Lane, MD, & Rachelle Nuss, MD

NORMAL HEMATOLOGIC VALUES cytopenias who lack evidence of peripheral red cell,
white cell, or platelet destruction. Macrocytosis often
The normal ranges for peripheral blood counts vary sig- accompanies bone marrow failure. Many of the consti-
nificantly with age. Normal neonates show a relative tutional bone marrow disorders are associated with a
polycythemia with a hematocrit of 45–65%. The retic- variety of congenital anomalies.
ulocyte count at birth is relatively high at 2–8%.
Within the first few days of life, erythrocyte production Young NS, Maciejewski J: The pathophysiology of acquired aplas-
decreases, and the levels of hemoglobin and hematocrit tic anemia. N Engl J Med 1997;336:1365 [PMID:
fall to a nadir at about 6–8 weeks. During this period, 9134878].
known as physiologic anemia of infancy, normal infants
have hemoglobins as low as 10 g/dL and hematocrits as CONSTITUTIONAL APLASTIC ANEMIA
low as 30%. Thereafter, the normal values for hemoglo-
bin and hematocrit gradually increase until adult values (Fanconi Anemia)
are reached after puberty. Premature infants can reach a
nadir hemoglobin level of 7–8 g/dL at 8–10 weeks. ESSENTIALS OF DIAGNOSIS
Newborns have larger red cells than children and
adults, with a mean corpuscular volume (MCV) at & TYPICAL FEATURES
birth of more than 94 fL. The MCV subsequently falls
to a nadir of 70–84 fL at about age 6 months. There- • Progressive pancytopenia.
after, the normal MCV increases gradually until it • Macrocytosis.
reaches adult values after puberty. • Multiple congenital anomalies.
The normal number of white blood cells is higher in
infancy and early childhood than later in life. Neu- • Increased chromosome breakage in peripheral
trophils predominate in the differential white count at blood lymphocytes.
birth and in the older child. Lymphocytes predominate
(up to 80%) between about ages 1 month and 6 years.
Normal values for the platelet count are 150,000–
400,000/µL and vary little with age. General Considerations
Fanconi anemia is a syndrome characterized by defec-
tive DNA repair that is caused by a variety of genetic
BONE MARROW FAILURE mutations. Inheritance is autosomal recessive, and the
disease occurs in all ethnic groups. Hematologic mani-
festations usually begin with thrombocytopenia or neu-
Failure of the marrow to produce adequate numbers of tropenia and subsequently progress over the course of
circulating blood cells may be congenital or acquired months or years to pancytopenia. Typically the diagno-
and may cause pancytopenia (aplastic anemia) or in- sis is made between ages 2 and 10 years.
volve only one cell line (single cytopenia). Constitu-
tional and acquired aplastic anemias are discussed in Clinical Findings
this section and the more common single cytopenias in
later sections. Bone marrow failure caused by malig- A. SYMPTOMS AND SIGNS
nancy or other infiltrative disease is discussed in Chap- Symptoms are determined principally by the degree of
ter 28. It is important to remember that many drugs hematologic abnormality. Thrombocytopenia may
and toxins may affect the marrow and cause single or cause purpura, petechiae, and bleeding; neutropenia
multiple cytopenias. may cause severe or recurrent infections; and anemia
Suspicion of bone marrow failure is warranted in may cause weakness, fatigue, and pallor. Congenital
children with pancytopenia and in children with single anomalies are present in at least 50% of patients. The
855
Copyright © 2005, 2001, by The McGraw-Hill Companies, Inc. Click here for terms of use.
856 / CHAPTER 27

most common include abnormal pigmentation of the growth hormone deficiency, hypothyroidism, or im-
skin (generalized hyperpigmentation, café au lait or hy- paired glucose metabolism. In addition, persons with
popigmented spots), short stature with delicate features, Fanconi anemia have a significantly increased risk of
and skeletal malformations (hypoplasia, anomalies, or developing malignancies, especially acute nonlympho-
absence of the thumb and radius). More subtle anom- cytic leukemia, solid tumors, and myelodysplastic syn-
alies include hypoplasia of the thenar eminence or a dromes. Death is usually the result of thrombocy-
weak or absent radial pulse. Associated renal anomalies topenic hemorrhage, overwhelming infection, or
include aplasia, “horseshoe” kidney, and duplication of malignancy.
the collecting system. Other anomalies are micro-
cephaly, microphthalmia, strabismus, ear anomalies, Treatment
and hypogenitalism.
Attentive supportive care is a critical feature of manage-
B. LABORATORY FINDINGS ment. Patients with neutropenia who develop fever re-
Thrombocytopenia or leukopenia typically occurs first, quire prompt evaluation and parenteral broad-spectrum
followed over the course of months to years by anemia antibiotics. Transfusions are important but should be
and progression to severe aplastic anemia. Macrocytosis used judiciously, especially in the management of
is virtually always present, is usually associated with thrombocytopenia, which frequently becomes refrac-
anisocytosis and an elevation in fetal hemoglobin levels, tory to platelet transfusions as a consequence of alloim-
and is an important diagnostic clue. The bone marrow munization. Transfusions from family members should
reveals hypoplasia or aplasia. The diagnosis is con- be discouraged because of the negative effect on the
firmed by the demonstration of an increased number of outcome of bone marrow transplantation. At least 50%
chromosome breaks and rearrangements in peripheral of patients with Fanconi anemia respond, albeit incom-
blood lymphocytes. The use of diepoxybutane to stim- pletely, to oxymetholone, and many recommend insti-
ulate these breaks and rearrangements provides for a tution of androgen therapy before transfusions are
sensitive assay that is virtually always positive in chil- needed. However, oxymetholone is associated with he-
dren with Fanconi anemia, even before the onset of patotoxicity, hepatic adenomas, and masculinization,
hematologic abnormalities. which is particularly troublesome for female patients.
Specific molecular markers/genes called Fanc-A, B, Successful bone marrow transplantation cures the
C, and so on are found in different ethnic populations. aplastic anemia and is an important treatment option
These markers are identified in research laboratories for children with Fanconi anemia who have a human
and are not available as routine clinical tests. leukocyte antigen (HLA)-identical sibling donor. Be-
fore transplantation the prospective donor must be
screened for Fanconi anemia by testing his or her lym-
Differential Diagnosis phocytes for chromosome breakage.
Because patients with Fanconi anemia frequently pre-
sent with thrombocytopenia, the disorder must be dif- Prognosis
ferentiated from idiopathic thrombocytopenic purpura
(ITP) and other more common causes of decreased Many patients succumb to bleeding, infection, or ma-
platelets. In contrast to patients with ITP, those with lignancy in adolescence or early adulthood. The long-
Fanconi anemia usually exhibit a gradual fall in the term outlook for those undergoing successful bone
platelet count, and counts less than 20,000/µL are marrow transplantation is uncertain, particularly with
often accompanied by neutropenia or anemia, along regard to the risk of subsequently developing malignan-
with phenotypical features. Fanconi anemia may also be cies.
manifested initially by pancytopenia, and must be dif-
ferentiated from acquired aplastic anemia and other dis- Alter BP: Fanconi’s anemia and malignancies. Am J Hematol
orders such as acute leukemia. Examination of the bone 1996;3:99 [PMID: 8892734].
marrow and chromosome studies of peripheral blood Butturini A et al: Hematologic abnormalities in Fanconi anemia:
lymphocytes will usually distinguish between these dis- An international Fanconi anemia registry study. Blood
orders. 1994;84:1650 [PMID: 8068955].
Dufour C et al: Stem cell transplantation from HLA-matched re-
lated donor for Fanconi’s anaemia: A retrospective review of
Complications the multicentric Italian experience on behalf of AIEOP-
GITMO. Br J Haematol 2001;112:796 [PMID: 11260086].
The most important complications of Fanconi anemia Joenje H, Patel KJ: The emerging genetic and molecular basis of
are those related to thrombocytopenia and neutropenia. Fanconi anemia. Nat Rev Genet 2001;2:446 [PMID:
Endogenous endocrine dysfunction may include 11389461].
 HEMATOLOGIC DISORDERS / 857

ACQUIRED APLASTIC ANEMIA Preleukemic conditions also may present with pancy-
topenia and hypocellular bone marrows. Cytogenetic
analysis of the marrow is helpful, because a clonal ab-
ESSENTIALS OF DIAGNOSIS normality may predict the subsequent development of
& TYPICAL FEATURES leukemia. Because some children with Fanconi anemia
may not have apparent congenital anomalies, patients
• Weakness and pallor. with newly diagnosed aplastic anemia should be studied
for chromosome breaks and rearrangements in periph-
• Petechiae, purpura, and bleeding. eral blood lymphocytes.
• Frequent or severe infections.
• Pancytopenia with hypocellular bone marrow.
Complications
Acquired aplastic anemia is characteristically compli-
cated by infection and hemorrhage; these two compli-
General Considerations cations are the leading causes of death. Other complica-
tions are those associated with therapy.
Acquired aplastic anemia is characterized by peripheral
pancytopenia with a hypocellular bone marrow. Ap-
proximately 50% of the cases in childhood are idio- Treatment
pathic. Other cases are secondary to idiosyncratic reac- Comprehensive supportive care is most important in
tions to drugs such as phenylbutazone, sulfonamides, the management of acute acquired aplastic anemia.
nonsteroidal anti-inflammatories, and anticonvulsants. Febrile illnesses require prompt evaluation and usually
Toxic causes include exposure to benzene, insecticides, parenteral antibiotics. Red blood cell transfusions alle-
and heavy metals. Infectious causes include viral hepati- viate symptoms of anemia. Platelet transfusions may be
tis (usually non-A, non-B, non-C), infectious mononu- lifesaving, but they should be used sparingly because
cleosis, and human immunodeficiency virus (HIV). In many patients eventually develop platelet alloantibodies
immunocompromised children, aplastic anemia has and become refractory to platelet transfusions.
been associated with human parvovirus B19. Immune Bone marrow transplantation is generally considered
mechanisms of marrow suppression are suspected in the treatment of choice for severe aplastic anemia when
most cases. an HLA-compatible sibling donor is available. Because
the likelihood of success with transplantation is influ-
Clinical Findings enced adversely by multiple transfusions, HLA typing
A. SYMPTOMS AND SIGNS of family members should be undertaken as soon as the
diagnosis of aplastic anemia is made. An increasing
Weakness, fatigue, and pallor result from anemia; pe- number of patients who lack HLA-matched siblings are
techiae, purpura, and bleeding occur because of throm- able to find matched donors through the National
bocytopenia; and fevers due to generalized or localized Bone Marrow Registry.
infections occur with neutropenia. Hepatosplenomegaly The best alternative to bone marrow transplantation
and significant lymphadenopathy are unusual. from an HLA-matched sibling donor is immunosup-
B. LABORATORY FINDINGS pression, usually with antithymocyte globulin (ATG)
and cyclosporine. Responses are good. Most patients
Anemia is usually normocytic, with a low reticulocyte show hematologic improvement and become transfu-
count. The white blood cell count is low, with a sion-independent.
marked neutropenia. The platelet count is typically
below 50,000/µL and frequently below 20,000/µL.
Bone marrow aspiration and biopsy show hypocellular- Prognosis
ity, often marked.
Children receiving early bone marrow transplantation
from an HLA-identical sibling have a long-term sur-
Differential Diagnosis vival rate of greater than 80%. Sustained, complete re-
Examination of the bone marrow usually excludes pan- missions may be seen in 65–80% of patients receiving
cytopenia caused by peripheral destruction of blood immunosuppressive therapy. However, both therapies
cells or by infiltrative processes such as acute leukemia, are associated with an increased risk of myelodysplastic
storage diseases, and myelofibrosis. Many of these other syndromes, acute leukemia, and other malignancies in
conditions are associated with hepatosplenomegaly. long-term survivors.
858 / CHAPTER 27

Fouladi M et al: Improved survival in severe acquired aplastic ane- hypersplenism), or evidence of chronic or recurrent in-
mia of childhood. Bone Marrow Transplant 2000;26:1149 fections.
[PMID: 11149724].
The initial laboratory evaluation of the anemic child
Ohara A et al: Myelodysplastic syndrome and acute myelogenous consists of a complete blood count (CBC) with differ-
leukemia as a late clonal complication in children with aplas-
tic anemia. Blood 1997;90:1009 [PMID: 9242530]. ential and platelet count, review of the peripheral blood
Rosenfeld S et al: Antithymocyte globulin and cyclosporine for se-
smear, and a reticulocyte count. The algorithm in Fig-
vere aplastic anemia: Association between hematologic re- ure 27–1 uses limited laboratory information, together
sponse and long-term outcome. JAMA 2003;289:1130 with the history and physical examination, to reach a
[PMID: 12622583]. specific diagnosis or to focus additional laboratory in-
Rosenfeld SJ et al: Intensive immunosuppression with antithymo- vestigations on a limited diagnostic category (eg, micro-
cyte globulin and cyclosporine as treatment for severe aplastic cytic anemia, bone marrow failure, pure red cell aplasia,
anemia. Blood 1995;85:3058 [PMID: 7756640]. or hemolytic disease). This diagnostic scheme depends
principally on the MCV to determine whether the ane-
mia is microcytic, normocytic, or macrocytic, according
to the percentile curves of Dallman and Siimes (Figure
27–2).
ANEMIAS The incidence of iron deficiency in the United
States has decreased significantly with improvements in
APPROACH TO THE CHILD infant nutrition. Still, iron deficiency is an important
cause of microcytic anemia, especially at ages
WITH ANEMIA 6–24 months. A trial of therapeutic iron is appropriate
Anemia is a relatively common finding, and identifying in such children, provided the dietary history is com-
the cause is important. Even though anemia in child- patible with iron deficiency and the physical examina-
hood has many causes, the correct diagnosis can usually tion or CBC count does not suggest an alternative
be established with relatively little laboratory cost. cause for the anemia. If this is not the case or if a trial of
Frequently the cause is suggested by a careful his- therapeutic iron fails to correct the anemia and micro-
tory. The possibility of nutritional causes should be ad- cytosis, further laboratory evaluation is warranted.
dressed by inquiry about dietary intake; growth and de- Another key element of Figure 27–1 is the use of
velopment; and symptoms of chronic disease, both the reticulocyte count and the peripheral blood
malabsorption, or blood loss. Hemolytic disease may be smear to determine whether a normocytic or macro-
suggested by a history of jaundice (including neonatal cytic anemia is due to hemolysis. Typically hemolytic
jaundice) or by a family history of anemia, jaundice, disease is associated with an elevated reticulocyte count,
gallbladder disease, splenomegaly, or splenectomy. The but some children with chronic hemolysis initially pre-
child’s ethnic background may suggest the possibility of sent during a period of virus-induced aplasia when the
certain hemoglobinopathies or of deficiencies of red cell reticulocyte count is not elevated. Thus review of the
enzymes such as glucose-6-phosphate dehydrogenase peripheral blood smear for evidence of hemolysis (eg,
(G6PD). The review of systems may reveal clues to a spherocytes, red cell fragmentation, sickle forms) is im-
previously unsuspected systemic disease with which portant in the evaluation of children with normocytic
anemia may be associated. The patient’s age is impor- anemias and low reticulocyte counts. When hemolysis
tant because some causes of anemia are age-related. For is suggested, the correct diagnosis may be suspected by
example, patients with iron deficiency anemia and β- specific abnormalities of red cell morphology or by
globin disorders present more commonly at ages clues from the history or physical examination. Au-
6–36 months than at other times in life. toimmune hemolysis is usually excluded by Coombs
The physical examination may also reveal clues to testing. Review of blood counts and the peripheral
the cause of anemia. Poor growth may suggest chronic blood smears of the mother and father may suggest ge-
disease or hypothyroidism. Congenital anomalies may netic disorders such as hereditary spherocytosis. Chil-
be associated with constitutional aplastic anemia (Fan- dren with normocytic or macrocytic anemias, with rela-
coni anemia) or with congenital hypoplastic anemia tively low reticulocyte counts and no evidence of
(Diamond–Blackfan anemia). Other disorders may be hemolysis on the blood smear, usually have anemias
suggested by the findings of petechiae or purpura caused by inadequate erythropoiesis in the bone mar-
(leukemia, aplastic anemia, hemolytic–uremic syn- row. The presence of neutropenia or thrombocytopenia
drome), jaundice (hemolysis or liver disease), general- in such children suggests the possibility of aplastic ane-
ized lymphadenopathy (leukemia, juvenile rheumatoid mia, malignancy, or severe folate/vitamin B12 defi-
arthritis, HIV infection), splenomegaly (leukemia, ciency, and usually dictates examination of the bone
sickle cell disease, hereditary spherocytosis, liver disease, marrow.
 HEMATOLOGIC DISORDERS / 859

Anemia

MCV

LOW NORMAL
OR HIGH

History, physical examination and CBC Reticulocyte

compatible with iron deficiency count

YES NO LOW HIGH

Response to Peripheral Peripheral

trial of iron smear smear

NO (APLASTIC CRISIS) NO
YES NO HEMOLYSIS HEMOLYSIS
HEMOLYSIS

Iron Laboratory evaluation Neutrophils, Specific tests Investigate

deficiency of microcytic anemia platelets dictated by history, blood loss
physical, and red cell
morphology

LOW NORMAL
OR HIGH

Bone marrow Pure red cell aplasia or

failure megaloblastic anemia

Figure 27–1. Investigation of anemia.

Pure red cell aplasia may be congenital (Dia- be diagnosed until the anemia is exacerbated by an
mond–Blackfan anemia), acquired and transient (tran- episode of red cell aplasia that results in a rapidly falling
sient erythroblastopenia of childhood), a manifestation hemoglobin level. In such cases, cardiovascular com-
of a systemic disease such as renal disease or hypothy- promise and congestive heart failure may develop
roidism, or due to malnutrition or mild deficiencies of quickly.
folate or vitamin B12.

Hermiston ML, Mentzer WC: A practical approach to the evalua- 1. Congenital Hypoplastic Anemia
tion of the anemic child. Pediatr Clin North Am
2002;49:877 [PMID: 12430617]. (Diamond–Blackfan Anemia)

PURE RED CELL APLASIA ESSENTIALS OF DIAGNOSIS

Infants and children with normocytic or macrocytic & TYPICAL FEATURES
anemia, a low reticulocyte count, and normal or ele-
vated numbers of neutrophils and platelets should be • Age: birth to 1 year.
suspected of having pure red cell aplasia. Examination • Macrocytic anemia with reticulocytopenia.
of the peripheral blood smear in such cases is important
because signs of hemolytic disease suggest chronic he- • Bone marrow with erythroid hypoplasia.
molysis complicated by an aplastic crisis due to par- • Short stature or congenital anomalies in one third
vovirus infection. Appreciation of this phenomenon is of patients.
important because chronic hemolytic disease may not
860 / CHAPTER 27

GIRLS BOYS
16 97 17
HEMOGLOBIN, PERCENTILES 97 HEMOGLOBIN, PERCENTILES 90
90 15 16
50
14 50 14 15

13 13 14 10 14
g/dL

g/dL
10
3 12 3 13
12 13

11 12

11
97
MCV, PERCENTILES MCV, PERCENTILES 97
90
90 90 90
50
85 85 85 50 85
10 80
80 80 10 80
3
3
fL

fL
75 75 75 75

70 70

2 4 6 8 10 12 14 16 2 4 6 8 10 12 14 16
Age (years) Age (years)

Figure 27–2. Hemoglobin and red cell volume in infancy and childhood. (Reproduced, with permission, from Dall-
man PR, Siimes MA: Percentile curves for hemoglobin and red cell volume in infancy and childhood. J Pediatr 1979;94:26.)

General Considerations B. LABORATORY FINDINGS

Diamond–Blackfan anemia is a relatively rare cause of Diamond–Blackfan anemia is characterized by severe
anemia that usually presents in infancy or early child- anemia and marked reticulocytopenia. The neutrophil
hood. Early diagnosis is important because treatment count is usually normal or slightly decreased, and the
with corticosteroids results in increased erythropoiesis platelet count is normal or elevated. The bone marrow
in about two thirds of patients, thus avoiding the diffi- usually shows a marked decrease in erythroid precursors
culties and complications of long-term chronic transfu- but is otherwise normal. In older children, fetal hemo-
sion therapy. The cause is unclear, and both autosomal globin levels are usually increased and there is evidence
dominant and autosomal recessive modes of inheritance of persistent fetal erythropoiesis, such as the presence of
have been reported. the i antigen on erythrocytes. In addition, the level of
adenosine deaminase in erythrocytes is elevated.
Clinical Findings
A. SYMPTOMS AND SIGNS Differential Diagnosis
Signs and symptoms are generally those of chronic ane- The principal differential diagnosis is transient ery-
mia, such as pallor; congestive heart failure sometimes throblastopenia of childhood. Children with Dia-
follows. Jaundice, splenomegaly, or other evidence of mond–Blackfan anemia generally present at an earlier
hemolysis is usually absent. Short stature or other con- age, often have macrocytosis, and have evidence of fetal
genital anomalies are present in one third of patients. A erythropoiesis and an elevated level of red cell adeno-
wide variety of anomalies have been described; those af- sine deaminase. In addition, short stature and congeni-
fecting the head, face, and thumbs are the most com- tal anomalies, which occur in one third of patients with
mon. Diamond–Blackfan anemia, are not associated with
 HEMATOLOGIC DISORDERS / 861

transient erythroblastopenia. Lastly, transient erythro- • Absence of hepatosplenomegaly or lymphade-

blastopenia of childhood usually resolves within nopathy.
6–8 weeks of diagnosis, whereas Diamond–Blackfan • Erythroid precursors initially absent from bone
anemia is generally a lifelong affliction. Other disorders marrow.
associated with decreased red cell production such as
renal failure, hypothyroidism, and the anemia of
chronic disease need to be considered.

Treatment General Considerations

Oral corticosteroids should be initiated as soon as the di- Transient erythroblastopenia of childhood is a relatively
agnosis of Diamond–Blackfan anemia is made. Two common cause of acquired anemia in early childhood.
thirds of patients will respond to prednisone, 2 mg/kg/d, The disorder is suspected when a normocytic anemia is
and many of those who respond subsequently tolerate discovered during evaluation of pallor or when a CBC
significant tapering of the dose. Patients who are unre- is obtained for another reason. Because the anemia is
sponsive to prednisone require chronic red cell transfu- due to decreased red cell production, and thus develops
sion therapy, which inevitably causes transfusion-in- slowly, the cardiovascular system has time to compen-
duced hemosiderosis and the need for chelation with sate. Therefore, children with hemoglobin levels as low
parenteral deferoxamine. Bone marrow transplantation is as 4 or 5 g/dL may look remarkably well. The disorder
an alternative therapy that should be considered for is thought to be autoimmune in most cases, because
transfusion-dependent patients who have HLA-matched IgG from some patients has been shown to suppress
siblings. Hematopoietic growth factors have been used in erythropoiesis in vitro.
some cases with limited success. Unpredictable, sponta-
neous remissions occur in up to 20% of patients. Clinical Findings
Pallor is the most common sign, and hepatospleno-
Prognosis megaly and lymphadenopathy are absent. The anemia
The prognosis for patients responsive to corticosteroids is normocytic, and the peripheral blood smear shows no
is generally good, particularly if remission is maintained evidence of hemolysis. The platelet count is normal or
with low doses of alternate-day prednisone. Patients de- elevated, and the neutrophil count is normal or, in
pendent on transfusion are at risk for the complications some cases, decreased. Early in the course, no reticulo-
of hemosiderosis, including death from congestive heart cytes are identified. The Coombs test is negative, and
failure, cardiac arrhythmias, or hepatic failure. This re- there is no evidence of chronic renal disease, hypothy-
mains a significant threat, particularly during adoles- roidism, or other systemic disorder. Bone marrow ex-
cence, when compliance with nightly subcutaneous in- amination shows severe erythroid hypoplasia initially;
fusions of deferoxamine is often difficult to ensure. subsequently, erythroid hyperplasia develops along with
reticulocytosis, and the anemia resolves.
Vlachos A et al: The Diamond–Blackfan Anemia Registry: Tool for
investigating the epidemiology and biology of Diamond– Differential Diagnosis
Blackfan anemia. J Pediatr Hematol Oncol 2001;23:377
[PMID: 11563775]. Transient erythroblastopenia of childhood must be dif-
Vlachos A et al: Hematopoietic stem cell transplantation for Dia-
ferentiated from Diamond–Blackfan anemia, particu-
mond–Blackfan anemia: A report from the Diamond–Black- larly in infants younger than age 1 year. In contrast to
fan Anemia Registry. Bone Marrow Transplant 2001;27: Diamond–Blackfan anemia, transient erythroblastope-
381 [PMID: 11313667]. nia is not associated with macrocytosis, short stature, or
congenital anomalies, or with evidence of fetal erythro-
2. Transient Erythroblastopenia poiesis prior to the phase of recovery. Also in contrast
to Diamond–Blackfan anemia, transient erythro-
of Childhood blastopenia is associated with normal levels of red cell
adenosine deaminase. Transient erythroblastopenia of
ESSENTIALS OF DIAGNOSIS childhood must also be differentiated from chronic dis-
orders associated with decreased red cell production,
& TYPICAL FEATURES such as renal failure, hypothyroidism, and other
chronic states of infection or inflammation. As with
• Age: 6 months to 4 years. other single cytopenias, the possibility of malignancy
• Normocytic anemia with reticulocytopenia. (ie, leukemia) should always be considered, particularly
862 / CHAPTER 27

if fever, bone pain, hepatosplenomegaly, or lymphade- childhood must take into consideration a relatively
nopathy is present. In such cases, examination of the greater likelihood of other causes.
bone marrow is generally diagnostic. Confusion may Normal-term infants are born with sufficient iron
sometimes arise when the anemia of transient erythro- stores to prevent iron deficiency for the first 4–5
blastopenia is first identified during the early phase of months of life. Thereafter, enough iron needs to be ab-
recovery when the reticulocyte count is high. In such sorbed to keep pace with the needs of rapid growth. For
cases, the disorder may be confused with the anemia of this reason, nutritional iron deficiency is most common
acute blood loss or with hemolytic disease. In contrast between 6 and 24 months of life. A deficiency earlier
to hemolytic disorders, transient erythroblastopenia of than age 6 months may occur if iron stores at birth are
childhood is not associated with jaundice or peripheral reduced by prematurity, small birth weight, neonatal
destruction of red cells. anemia, or perinatal blood loss or if there is subsequent
iron loss due to hemorrhage. Iron-deficient children
older than age 24 months should be evaluated for blood
Treatment & Prognosis loss.
By definition, this is a transient disorder. Some children A significant body of evidence indicates that iron
require red cell transfusions if cardiovascular compro- deficiency, in addition to causing anemia, has adverse
mise is present. Resolution of the anemia is heralded by effects on multiple organ systems. Thus, the impor-
an increase in the reticulocyte count, which generally tance of identifying and treating iron deficiency extends
occurs within 4–8 weeks of diagnosis. In contrast to past the resolution of any symptoms directly attribut-
other autoimmune disorders of childhood (eg, ITP, au- able to a decreased hemoglobin concentration.
toimmune hemolytic anemia), transient erythro-
blastopenia of childhood is not treated with corticoster- Clinical Findings
oids.
A. SYMPTOMS AND SIGNS
Cherrick I et al: Transient erythroblastopenia of childhood:
Symptoms and signs vary with the severity of the defi-
Prospective study of fifty patients. Am J Pediatr Hematol ciency. Mild iron deficiency is usually asymptomatic.
Oncol 1994;16:320 [PMID: 7978049]. In infants with more severe iron deficiency, pallor, fa-
Miller R, Berman B: Transient erythroblastopenia of childhood in tigue, irritability, and delayed motor development are
infants < 6 months of age. Am J Pediatr Hematol Oncol common. Children whose iron deficiency is due in part
1994;16:246 [PMID: 8037344]. to ingestion of unfortified cow’s milk may be fat and
flabby, with poor muscle tone. A history of pica is com-
mon.
NUTRITIONAL ANEMIAS
B. LABORATORY FINDINGS
1. Iron Deficiency Anemia
The severity of anemia depends on the degree of iron
deficiency, and the hemoglobin level may be as low as
ESSENTIALS OF DIAGNOSIS 3–4 g/dL in severe cases. Red cells are microcytic and
& TYPICAL FEATURES hypochromic, with a low MCV and low mean corpus-
cular hemoglobin (MCH). The red blood cell distribu-
tion width (RDW) is typically elevated, even with mild
• Pallor and fatigue. iron deficiency. The reticulocyte count is usually nor-
• Poor dietary intake of iron (ages 6–24 months). mal or slightly elevated, but the reticulocyte index or
• Chronic blood loss (age > 2 years). absolute reticulocyte count is decreased. Iron studies
• Microcytic hypochromic anemia. show a decreased serum ferritin and a low serum iron,
elevated total iron-binding capacity, and decreased
transferrin saturation. These laboratory abnormalities
are usually present with moderate to severe iron defi-
ciency, but mild cases may be associated with variable
laboratory results. The peripheral blood smear shows
General Considerations microcytic, hypochromic red blood cells with anisocy-
Long considered the most common cause of anemia in tosis, and occasional target, teardrop, and fragmented
pediatrics, the incidence of iron deficiency has de- red cells. Leukocytes are normal, and very often platelet
creased substantially due to improved nutrition and the count is increased with normal morphology.
increased availability of iron-fortified infant formulas The bone marrow examination is not helpful in the
and cereals. Thus the current approach to anemia in diagnosis of iron deficiency in infants and small chil-
 HEMATOLOGIC DISORDERS / 863

dren because little or no iron is stored as marrow hemo- documents compliance and response to therapy. When
siderin at these ages. iron deficiency is the only cause of anemia, adequate
treatment usually results in a resolution of the anemia
within 4–6 weeks. Treatment is generally continued for
Differential Diagnosis a few additional months to replenish iron stores.
The differential diagnosis is that of microcytic,
hypochromic anemia. The possibility of thalassemia (α- Buchanan GR: The tragedy of iron deficiency during infancy and
thalassemia, β-thalassemia, hemoglobin E disorders) early childhood. J Pediatr 1999;135:413 [PMID: 10518073].
should be considered, especially in infants of African, Hermiston ML, Mentzer WC: A practical approach to the evalua-
Mediterranean, or Asian ethnic background. In con- tion of the anemic child. Pediatr Clin North Am 2002;
trast to infants with iron deficiency, those with tha- 49:877 [PMID: 12430617].
lassemia generally have an elevated number of erythro- Kwiatkowski JL et al: Severe iron deficiency anemia in young chil-
cytes (the index of the MCV divided by the red cell dren. J Pediatr 1999;135:514 [PMID: 10518088].
number is usually less than 13) and are less likely, in
mild cases, to have an elevated RDW. Thalassemias are 2. Megaloblastic Anemias
associated with normal or increased levels of serum iron
and ferritin and with normal iron-binding capacity.
The hemoglobin electrophoresis in β-thalassemia ESSENTIALS OF DIAGNOSIS
minor typically shows an elevation of hemoglobin A2 & TYPICAL FEATURES
levels, but coexistent iron deficiency may lower the per-
centage of hemoglobin A2 into the normal range. He-
moglobin electrophoresis will also identify children • Pallor and fatigue.
with hemoglobin E, a cause of microcytosis common in • Nutritional deficiency or intestinal malabsorp-
Southeast Asians. In contrast, the hemoglobin elec- tion.
trophoresis in α-thalassemia trait is normal. Lead poi- • Macrocytic anemia.
soning has also been associated with microcytic anemia,
• Megaloblastic bone marrow changes.
but anemia with lead levels less than 40 mg/dL is often
due to coexistent iron deficiency.
The anemia of chronic inflammation or infection is
normocytic but in late stages may be microcytic. This
anemia is usually suspected because of the presence of a
chronic systemic disorder. The level of serum iron is
General Considerations
low, but the iron-binding capacity is normal, and the Megaloblastic anemia is a macrocytic anemia caused by
serum ferritin level is elevated. Relatively mild infec- deficiency of cobalamin (vitamin B12), folic acid, or
tions, particularly during infancy, may cause transient both. Cobalamin deficiency due to dietary insufficiency
anemia. As a result, caution should be exercised when may occur in infants who are breast-fed by mothers
the diagnosis of mild iron deficiency is entertained in who are strict vegetarians or who have pernicious ane-
infants and young children who have had recent viral or mia. Intestinal malabsorption is the usual cause of
bacterial infections. Ideally, screening tests for anemia cobalamin deficiency in pediatrics and occurs with
should not be obtained within 3–4 weeks of such infec- Crohn disease, chronic pancreatitis, bacterial over-
tions. growth of the small bowel, infection with the fish tape-
worm (Diphyllobothrium latum), or after surgical resec-
tion of the terminal ileum. Deficiencies due to inborn
Treatment errors of metabolism (transcobalamin II deficiency,
The recommended oral dose of elemental iron is methylmalonic aciduria) have also been described. Mal-
4–6 mg/kg/d in three divided daily doses. Mild cases absorption of cobalamin due to deficiency of intrinsic
may be treated with 3 mg/kg/d given once daily before factor (pernicious anemia) is rare in childhood.
breakfast. Parenteral administration of iron is rarely Folic acid deficiency may be caused by inadequate
necessary. Iron therapy results in an increased reticulo- dietary intake, malabsorption, increased folate require-
cyte count within 3–5 days, which is maximal between ments, or some combination of the three. Folate defi-
5 and 7 days. The hemoglobin level begins to increase ciency due to dietary deficiency alone is rare but occurs
thereafter. The rate of hemoglobin rise is inversely re- in severely malnourished infants and has been reported
lated to the hemoglobin level at diagnosis. In moderate in infants fed goat’s milk not fortified with folic acid.
to severe cases, an elevated reticulocyte count 1 week Folic acid is absorbed in the proximal small bowel, and
after initiation of therapy confirms the diagnosis and deficiencies are encountered in malabsorptive syn-
864 / CHAPTER 27

dromes such as celiac disease. Anticonvulsant medica- an elevated reticulocyte count (hemolytic anemias),
tions (eg, phenytoin and phenobarbital) and cytotoxic bone marrow failure syndromes (Fanconi anemia, Dia-
drugs (eg, methotrexate) have also been associated with mond–Blackfan anemia), liver disease, and hypothy-
folate deficiency, caused by interference with folate ab- roidism.
sorption or metabolism. Finally, folic acid deficiency is
more likely to develop in infants and children with in- Treatment
creased requirements. This occurs during infancy be-
cause of rapid growth and also in children with chronic Treatment of cobalamin deficiency due to inadequate
hemolytic anemia. Premature infants are particularly dietary intake is readily accomplished with oral supple-
susceptible to the development of the deficiency be- mentation. Most cases, however, are due to intestinal
cause of low body stores of folate. malabsorption and require parenteral treatment. In se-
vere cases, parenteral therapy may induce life-threaten-
ing hypokalemia and require supplemental potassium.
Clinical Findings Folic acid deficiency is treated effectively with oral folic
A. SYMPTOMS AND SIGNS acid in most cases. Children at risk for the development
Infants with megaloblastic anemia may show pallor and of folic acid deficiencies, such as premature infants and
mild jaundice as a result of ineffective erythropoiesis. those with chronic hemolysis, are often given folic acid
Classically, the tongue is smooth and beefy red. Infants prophylactically.
with cobalamin deficiency may be irritable and may be
poor feeders. Older children with cobalamin deficiency Graham SM et al: Long-term neurologic consequences of nutri-
tional vitamin B12 deficiency in infants. J Pediatr 1992;121:
may complain of paresthesias, weakness, or an unsteady 710 [PMID: 1432418].
gait and may show decreased vibratory sensation and
Pappo AS et al: Etiology of red blood cell macrocytosis during
proprioception on neurologic examination. childhood: Impact of new diseases and therapies. Pediatrics
1992;89:1063 [PMID: 1534402].
B. LABORATORY FINDINGS
Rosenblatt DS, Whitehead VM: Cobalamin and folate deficiency:
The laboratory findings of megaloblastic anemia in- Acquired and hereditary disorders in children. Semin Hema-
clude an elevated MCV and MCH. The peripheral tol 1999;36:19 [PMID: 9930566].
blood smear shows numerous macro-ovalocytes with
anisocytosis and poikilocytosis. Neutrophils are large ANEMIA OF CHRONIC DISORDERS
and have hypersegmented nuclei. The white cell and
platelet counts are normal with mild deficiencies, but Anemia is a common manifestation of many chronic
may be decreased in more severe cases. Examination of illnesses in children. In some instances, causes may be
the bone marrow typically shows erythroid hyperplasia mixed. For example, children with chronic disorders in-
with large erythroid and myeloid precursors. Nuclear volving intestinal malabsorption or blood loss may have
maturation is delayed compared with cytoplasmic mat- anemia of chronic inflammation in combination with
uration, and erythropoiesis is ineffective. The serum in- nutritional deficiencies of iron, folate, or cobalamin. In
direct bilirubin concentration may be slightly elevated. other settings, the anemia is due to dysfunction of a
Children with cobalamin deficiency have a low single organ (eg, renal failure, hypothyroidism), and
serum vitamin B12 level, but decreased levels of serum correction of the underlying abnormality resolves the
vitamin B12 may also be found in about 30% of pa- anemia.
tients with folic acid deficiency. The level of red cell fo-
late is a better reflection of folate stores than is the 1. Anemia of Chronic Inflammation
serum folic acid level. Serum levels of metabolic inter-
mediates, methylmalonic acid, and homocysteine may Anemia is frequently associated with chronic infections
help establish the correct diagnosis. Elevated methyl- or inflammatory diseases. The anemia is usually mild to
malonic acid levels are consistent with cobalamin defi- moderate in severity, with a hemoglobin level of
ciency, whereas elevated levels of homocysteine occur 8–12 g/dL. In general, the severity of the anemia corre-
with both cobalamin and folate deficiency. sponds to the severity of the underlying disorder, and
there may be microcytosis but not hypochromia. The
reticulocyte count is low. The anemia is thought to be
Differential Diagnosis due to inflammatory cytokines that inhibit erythro-
Most macrocytic anemias in pediatrics are not mega- poiesis and impair iron release by reticuloendothelial
loblastic. Other causes of an increased MCV include cells. Levels of erythropoetin are relatively low for the
drug therapy (eg, anticonvulsants, anti-HIV nucleoside severity of the anemia. The serum iron concentration is
analogues), congenital heart disease, Down syndrome, low, but in contrast to iron deficiency, anemia of
 HEMATOLOGIC DISORDERS / 865

chronic inflammation is not associated with elevated CONGENITAL HEMOLYTIC ANEMIAS:

iron-binding capacity and is associated with an elevated RED CELL MEMBRANE DEFECTS
serum ferritin level. Treatment consists of correction of
the underlying disorder, which, if controlled, generally The congenital hemolytic anemias are usually divided
results in improvement in hemoglobin level. into three categories: defects of the red cell membrane,
hemoglobinopathies, and disorders of red cell metabo-
Ambruso DR: The anemias of chronic disease. In Gross S, Roath S lism. Hereditary spherocytosis and elliptocytosis are the
(eds): Hematology: A Problem Oriented Approach. Williams & most common red cell membrane disorders and are de-
Wilkins, 1996, p 179. scribed here. The diagnosis is suggested by the periph-
Hagar W et al: Diseases of iron metabolism. Pediatr Clin North eral blood smear, which shows characteristic red cell
Am 2002;49:893 [PMID: 12430618]. morphology (eg, spherocytes, elliptocytes). These disor-
ders usually have an autosomal dominant inheritance,
2. Anemia of Chronic Renal Failure and the diagnosis may be suggested by a family history.
The hemolysis is due to the deleterious effect of the
Severe normocytic anemia occurs in most forms of membrane abnormality on red cell deformability. De-
renal disease that have progressed to renal insufficiency. creased cell deformability leads to entrapment of the
Although white cell and platelet production remain abnormally shaped red cells in the spleen. Many pa-
normal, the bone marrow shows significant hypoplasia tients have splenomegaly, and splenectomy usually alle-
of the erythroid series and the reticulocyte count is low. viates the hemolysis.
The principal mechanism is deficiency of erythropoi-
etin, a hormone produced in the kidney, but other fac-
tors may contribute to the anemia. In the presence of 1. Hereditary Spherocytosis
significant uremia, a component of hemolysis may also
be present. In the past, treatment of the anemia of
chronic renal failure depended on transfusions of ESSENTIALS OF DIAGNOSIS
packed red blood cells. However, recombinant human & TYPICAL FEATURES
erythropoietin (epoetin alfa) corrects the anemia, and
its use has largely eliminated the need for transfusions. • Anemia and jaundice.
• Splenomegaly.
Brandt JR et al: Safety and efficacy of erythropoietin in children
with chronic renal failure. Pediatr Nephrol 1999;13: • Positive family history of anemia, jaundice, or
143 [PMID: 10229004]. gallstones.
Seeherunvong W et al: Identification of poor responders to erythro- • Spherocytosis with increased reticulocytes.
poietin among children undergoing hemodialysis. J Pediatr
• Increased osmotic fragility.
2001;138:710 [PMID: 11343048].
Yorgin PD et al: The clinical efficacy of higher hematocrit levels in • Negative direct antiglobulin test (DAT).
children with chronic renal insufficiency and those undergo-
ing dialysis. Semin Nephrol 2001;21:451 [PMID:
11559886].

3. Anemia of Hypothyroidism General Considerations

Some patients with hypothyroidism develop significant Hereditary spherocytosis is a relatively common inher-
anemia. Occasionally, anemia is detected before the di- ited hemolytic anemia that occurs in all ethnic groups
agnosis of the underlying disorder. A decreased growth but is most common in persons of Northern European
velocity in an anemic child suggests hypothyroidism. ancestry, in whom the incidence is about 1:5000. The
The anemia is usually normocytic or macrocytic, but it disorder is a heterogeneous one, marked by variable de-
is not megaloblastic and hence not due to deficiencies grees of anemia, jaundice, and splenomegaly. In some
of cobalamin or folate. Replacement therapy with thy- persons, the disorder is mild and there is no anemia be-
roid hormone is usually effective in correcting the ane- cause erythroid hyperplasia fully compensates for he-
mia. molysis. Severe cases are transfusion-dependent prior to
splenectomy. The hallmark of hereditary spherocytosis
Cheu J-Y et al: Anemia in children and adolescents with hypothy-
is the presence of microspherocytes in the peripheral
roidism. Clin Pediatr 1981;20:696 [PMID: 7297010]. blood. The disease is inherited in an autosomal domi-
Franzese A et al: Anemia in infants with congenital hypothyroidism nant fashion in about 75% of cases; the remainder is
diagnosed by neonatal screening. J Endocrinol Invest thought to be autosomal recessive or to be caused by
1996;19:613 [PMID: 8957746]. new mutations.
866 / CHAPTER 27

Hereditary spherocytosis is usually the result of a disease caused by ABO or other blood type incompati-
partial deficiency of spectrin, an important structural bilities. Older patients with autoimmune hemolytic
protein of the red cell membrane skeleton. Spectrin de- anemia frequently present with jaundice and
ficiency weakens the attachment of the cell membrane splenomegaly and with spherocytes on the peripheral
to the underlying membrane skeleton and causes the blood smear. The DAT is positive in most cases of im-
red cell to lose membrane surface area. This process cre- mune hemolysis and negative in hereditary spherocyto-
ates spherocytes that are poorly deformable and have a sis. Occasionally, the diagnosis is confused in patients
shortened life span because they are trapped in the mi- with splenomegaly from other causes, especially when
crocirculation of the spleen and engulfed by splenic hypersplenism increases red cell destruction and when
macrophages. The extreme heterogeneity of hereditary some spherocytes are noted on the blood smear. In such
spherocytosis is related directly to variable degrees of cases, the true cause of the splenomegaly may be sug-
spectrin deficiency. In general, children who inherit gested by signs or symptoms of portal hypertension or
spherocytosis in an autosomal dominant fashion have by laboratory evidence of chronic liver disease. In con-
lesser degrees of spectrin deficiency and mild or moder- trast to children with hereditary spherocytosis, those
ate hemolysis. In contrast, those with nondominant with hypersplenism typically have some degree of
forms of spherocytosis tend to have greater deficiencies thrombocytopenia or neutropenia.
of spectrin and a more severe anemia.
Complications
Clinical Findings
Severe jaundice may occur in the neonatal period and,
A. SYMPTOMS AND SIGNS if not controlled by phototherapy, may occasionally re-
Hemolysis causes significant neonatal hyperbilirubine- quire exchange transfusion. Splenectomy is associated
mia in 50% of affected children. Splenomegaly subse- with an increased risk of overwhelming bacterial infec-
quently develops in the majority and is often present by tions, particularly with pneumococci. Gallstones occur
age 5 years. Jaundice is variably present and in many in 60–70% of adults who have not undergone splenec-
patients may be noted only during infection. Patients tomy and may form as early as age 5–10 years.
with significant chronic anemia may complain of pal-
lor, fatigue, or malaise. Intermittent exacerbations of Treatment
the anemia are caused by increased hemolysis or by
aplastic crises and may be associated with severe weak- Supportive measures include the administration of folic
ness, fatigue, fever, abdominal pain, or even congestive acid to prevent the development of red cell hypoplasia
heart failure. due to folate deficiency. Acute exacerbations of anemia,
due to increased rates of hemolysis or to aplastic
B. LABORATORY FINDINGS crises due to infection with human parvovirus, may be
Most patients have mild chronic hemolysis with hemo- severe enough to require red cell transfusions. Splenec-
globin levels of 9–12 g/dL. In some cases, the hemolysis tomy is performed in many cases and always results in
is fully compensated and the hemoglobin level is in the significant improvement. The procedure increases the
normal range. Rare cases of severe disease require fre- survival of the spherocytic red cells and leads to com-
quent transfusions. The anemia is usually normocytic plete correction of the anemia in most cases. Patients
and hyperchromic, and many patients have an elevated with more severe disease may show some degree of he-
MCH concentration. The peripheral blood smear molysis after splenectomy. Except in unusually severe
shows numerous microspherocytes and polychromasia. cases, the procedure should be postponed until the
The reticulocyte count is elevated, often higher than child is at least age 5 years because of the greater risk of
might be expected for the degree of anemia. White postsplenectomy sepsis prior to this age. Alternatively,
blood cell and platelet counts are usually normal. The partial splenectomy may be considered for young chil-
osmotic fragility is increased, particularly after incuba- dren with severe hemolysis. All patients scheduled for
tion at 37°C for 24 hours. Serum bilirubin usually splenectomy should be immunized with pneumococcal
shows an elevation in the unconjugated fraction. DAT vaccine prior to the procedure, and some clinicians rec-
is negative. ommend penicillin prophylaxis afterward. The need for
splenectomy in mild cases is somewhat controversial.
Splenectomy in the middle childhood years prevents
Differential Diagnosis the subsequent development of cholelithiasis and elimi-
Spherocytes are frequently present in persons with im- nates the need for the activity restrictions recom-
mune hemolysis. Thus, in the newborn, hereditary mended for children with splenomegaly. However,
spherocytosis must be distinguished from hemolytic these benefits must be weighed against the risks of the
 HEMATOLOGIC DISORDERS / 867

surgical procedure and the subsequent lifelong risk of ilocytosis/elliptocytosis syndrome. J Clin Invest 1987;79:
postsplenectomy sepsis. 943 [PMID: 3818955].
Palek J, Sahr KE: Mutations of the red cell membrane proteins:
From clinical evaluation to detection of the underlying ge-
Prognosis netic defect. Blood 1992;8:308 [PMID: 1627793].

Splenectomy eliminates signs and symptoms in all but

the most severe cases and reduces the risk of cholelithia- CONGENITAL HEMOLYTIC ANEMIAS:
sis. The abnormal red cell morphology and increased HEMOGLOBINOPATHIES
osmotic fragility persist without clinical consequence.
The hemoglobinopathies are an extremely heteroge-
neous group of congenital disorders that occur in many
Delhommeau F et al: Natural history of hereditary spherocytosis different ethnic groups. The relatively high frequency
during the first year of life. Blood 2000;95:393 [PMID:
10627440].
of these genetic variants is related to the malaria protec-
tion afforded to heterozygous individuals. The hemo-
Hassoun H et al: Characterization of the underlying molecular de-
fect in hereditary spherocytosis associated with spectrin defi- globinopathies are generally classified into two major
ciency. Blood 1997;90:398 [PMID: 9207476]. groups. The first, the thalassemias, are caused by quan-
Michaels LA et al: Screening for hereditary spherocytosis by use of titative deficiencies in the production of globin chains.
automated erythrocyte indexes. J Pediatr 1997;130:957 These quantitative defects in globin synthesis cause mi-
[PMID: 9202619]. crocytic and hypochromic anemias. The second group
Tchernia G et al: Initial assessment of the beneficial effect of partial of hemoglobinopathies are those caused by structural
splenectomy in hereditary spherocytosis. Blood 1993;81: abnormalities of globin chains. The most important of
2014 [PMID: 8471763]. these, hemoglobins S, C, and E, are all the result of
point mutations and single amino acid substitutions in
2. Hereditary Elliptocytosis β-globin. Many, but not all, infants with hemoglo-
binopathies are identified by routine neonatal screen-
Hereditary elliptocytosis is a heterogeneous disorder ing.
that ranges in severity from an asymptomatic carrier Figure 27–3 shows the normal developmental
state with normal red cell morphology to severe he- changes that occur in globin-chain production during
molytic anemia. Most affected persons have numerous gestation and the first year of life. At birth, the predom-
elliptocytes on the peripheral blood smear but mild or inant hemoglobin is fetal hemoglobin (hemoglobin F),
no hemolysis. Those with hemolysis have an elevated which is composed of two α-globin chains and two γ-
reticulocyte count and may have jaundice and globin chains. Subsequently, the production of γ-globin
splenomegaly. These disorders are caused by mutations decreases and the production of β-globin increases so
of red cell membrane skeletal proteins, and most have that adult hemoglobin (two α chains and two β chains)
an autosomal dominant inheritance. Because most pa- predominates after 2–4 months. Because α-globin
tients are asymptomatic, no treatment is indicated. Pa- chains are present in both fetal and adult hemoglobin,
tients with significant degrees of hemolytic anemia may disorders of α-globin synthesis (α-thalassemia) are clin-
benefit from folate supplementation or from splenec- ically manifest in the newborn as well as later in life. In
tomy. contrast, patients with β-globin disorders such as β-tha-
Some infants with hereditary elliptocytosis present lassemia and sickle cell disease are generally asympto-
in the neonatal period with moderate to marked hemol- matic during the first 3–4 months of age and present
ysis and significant hyperbilirubinemia. This disorder clinically after γ-chain production—and therefore fetal
has been termed “transient infantile poikilocytosis” be- hemoglobin levels—have decreased substantially.
cause such infants exhibit bizarre erythrocyte morphol-
ogy with elliptocytes, budding red cells, and small mis-
shapen cells that defy description. The MCV is low, 1. α-Thalassemia
and the anemia may be severe enough to require red
cell transfusions. Typically, one parent has hereditary
elliptocytosis, usually mild or asymptomatic. The in- ESSENTIALS OF DIAGNOSIS
fant’s hemolysis gradually abates during the first year of & TYPICAL FEATURES
life, and the erythrocyte morphology subsequently be-
comes more typical of hereditary elliptocytosis. • African, Mediterranean, Middle Eastern, Chinese,
or Southeast Asian ancestry.
Mentzer WC et al: Modulation of erythrocyte membrane mechani- • Microcytic, hypochromic anemia of variable
cal stability by 2,3-diphosphoglycerate in the neonatal poik- severity.
868 / CHAPTER 27

α α
100
γ
Polypeptide chains (percent)

β
80

60

40
Figure 27–3. Changes in hemoglo-
bin polypeptide chains during
20 ζ
β γ human development. (Reproduced,
ε
0 δ with permission, from Miller DR,
Months 0 2 4 6 8 2 4 6 8 10 12 Baehner RL: Blood Diseases of Infancy
Embryo Fetus Birth Infant and Childhood, 6th ed. Mosby, 1989.)

• Hemoglobin Bart’s detected by neonatal screen- lassemia trait. In Asians, deletions of one or of both α-
ing. globin genes on the same chromosome are common.
Thus heterozygous individuals are either silent carriers
or have α-thalassemia trait, and homozygous individu-
als or compound heterozygous individuals have α-tha-
lassemia trait, hemoglobin H disease, or hydrops fetalis.
General Considerations Thus the presence of α-thalassemia in a child of Asian
Most of the α-thalassemia syndromes are the result of ancestry may have important implications for genetic
deletions of one or more of the α-globin genes on chro- counseling, whereas this is not usually the case in fami-
mosome 16. Normal diploid cells have four α-globin lies of African ancestry.
genes; thus the variable severity of the α-thalassemia
syndromes is related to the number of gene deletions
(Table 27–1). The severity of the α-thalassemia syn-
Clinical Findings
dromes varies among affected ethnic groups, depending The clinical findings depend on the number of α-glo-
on the genetic abnormalities prevalent in the popula- bin genes deleted. Table 27–1 summarizes the α-tha-
tion. In persons of African ancestry, α-thalassemia is lassemia syndromes.
usually caused by the deletion of only one of the two α- Persons with three α-globin genes (one-gene dele-
globin genes on each chromosome. Thus, in the tion) are asymptomatic and have no hematologic ab-
African population, heterozygous individuals are silent normalities. Hemoglobin levels and MCV are normal.
carriers and homozygous individuals have α-tha- Hemoglobin electrophoresis in the neonatal period

Table 27–1. The α-thalassemias

Usual ␣ Gene Clinical Hemoblobin Electrophoresisb

Genotypesa Number Features Birth > 6 mos
αα/αα 4 Normal N N
−α/αα 3 Silent carrier 0–3% Hb Bart’s N
--/αα or -α/-α 2 α-thal trait 2–10% Hb Bart’s N
--/-α 1 Hb H disease 15–30% Hb Bart’s Hb
H present
--/-- 0 Fetal hydrops > 75% Hb Bart’s -
a
α indicates presence of α-globin gene, − indicates deletion of α-globin gene
b
N = normal results, Hb = hemoglobin, Hb Bart’s = γ4, Hb H = β4.
 HEMATOLOGIC DISORDERS / 869

shows 0–3% Bart’s hemoglobin, a variant hemoglobin hypochromia on the blood smear. With the exception
composed of four γ-globin chains. Hemoglobin elec- of β-thalassemia, most other significant hemolytic dis-
trophoresis after the first few months of life is normal. orders have a normal or elevated MCV and are not
Thus this condition is usually suspected only in the hypochromic. Infants with hydrops fetalis due to severe
context of family studies or when a small amount of α-thalassemia must be distinguished from those with
Bart’s hemoglobin is detected by neonatal screening for hydrops due to other causes of anemia such as isoim-
hemoglobinopathies. munization.
Persons with two α-globin genes (two-gene dele-
tion) are typically asymptomatic. The MCV is usually Complications
less than 100 fL at birth. Hematologic studies in older
infants and children show a normal or slightly de- The principal complication of α-thalassemia trait is the
creased hemoglobin level with a low MCV and a needless administration of iron, given in the belief that
slightly hypochromic blood smear with some target a mild microcytic anemia is due to iron deficiency. Per-
cells. The hemoglobin electrophoresis typically shows sons with hemoglobin H disease may have intermittent
2–10% Bart’s hemoglobin in the neonatal period but is exacerbations of their anemia, which occasionally re-
normal in older children and adults. quire blood transfusions. Splenomegaly may exacerbate
Persons with one α-globin gene (three-gene dele- the anemia and may require splenectomy. Women
tion) have a mild to moderately severe microcytic he- pregnant with hydropic α-thalassemia fetuses are sub-
molytic anemia (hemoglobin level of 7–10 g/dL), ject to increased complications of pregnancy, particu-
which may be accompanied by hepatosplenomegaly larly toxemia and postpartum hemorrhage.
and some bony abnormalities caused by the expanded
medullary space. The reticulocyte count is elevated, and Treatment
the red cells show marked hypochromia and microcyto-
sis with significant poikilocytosis and some basophilic Persons with α-thalassemia trait require no treatment.
stippling. Hemoglobin electrophoresis in the neonatal Those with hemoglobin H disease should receive sup-
period typically shows 15–30% Bart’s hemoglobin. plemental folic acid and avoid the same oxidant drugs
Later in life, hemoglobin H (composed of four β-glo- that cause hemolysis in persons with G6PD deficiency,
bin chains) is present. Incubation of red cells with bril- because exposure to these drugs may exacerbate their
liant cresyl blue (hemoglobin H preparation) shows in- anemia. The anemia may also be exacerbated during
clusion bodies formed by denatured hemoglobin H. periods of infection, and transfusions may be required.
The deletion of all four α-globin genes causes severe Hypersplenism may develop later in childhood and re-
intrauterine anemia and asphyxia and results in hydrops quire surgical splenectomy. Genetic counseling and
fetalis and fetal demise or neonatal death shortly after prenatal diagnosis should be offered to families at risk
delivery. Extreme pallor and massive hepatospleno- for hydropic fetuses.
megaly are present. Hemoglobin electrophoresis reveals
a predominance of Bart’s hemoglobin with a complete Chui DH, Waye JS: Hydrops fetalis caused by α-thalassemia: An
absence of normal fetal or adult hemoglobin. emerging health care problem. Blood 1998;91:2213 [PMID:
9516118].
Lau Y-L et al: Prevalence and genotypes of α- and β-thalassemia
Differential Diagnosis carriers in Hong Kong—Implication for population screen-
ing. N Engl J Med 1997;336:1298 [PMID: 9113933].
α-Thalassemia trait (two-gene deletion) must be differ- Miller ST et al: A fast hemoglobin variant on newborn screening is
entiated from other mild microcytic anemias, including associated with α-thalassemia trait. Clin Pediatr 1997;36:75
iron deficiency and β-thalassemia minor. In contrast to [PMID: 9118593].
children with iron deficiency, those with α-thalassemia
trait show normal or increased levels of ferritin and
serum iron. In contrast to children with β-thalassemia
2. β-Thalassemia
minor, those with α-thalassemia trait have a normal he-
moglobin electrophoresis after age 4–6 months. Finally, ESSENTIALS OF DIAGNOSIS
the history of a low MCV (96 fL) at birth or the pres-
ence of Bart’s hemoglobin on the neonatal hemoglo-
& TYPICAL FEATURES
binopathy screening test suggests α-thalassemia.
Children with hemoglobin H disease may have β-Thalassemia minor:
jaundice and splenomegaly, and the disorder must be • Normal neonatal screening test.
differentiated from other hemolytic anemias. The key • African, Mediterranean, Middle Eastern, or Asian
to the diagnosis is the decreased MCV and the marked ancestry.
870 / CHAPTER 27

• Mild microcytic, hypochromic anemia. creased MCV with or without mild anemia. The pe-
• No response to iron therapy. ripheral blood smear typically shows hypochromia, tar-
• Elevated level of hemoglobin A2. get cells, and sometimes basophilic stippling. Hemoglo-
bin electrophoresis performed after 6–12 months of age
β-Thalassemia major: is usually diagnostic when levels of hemoglobin A2, he-
• Neonatal screening shows hemoglobin F only. moglobin F, or both are elevated. β-Thalassemia major
• Mediterranean, Middle Eastern, or Asian ancestry. is often initially suspected when Hb A is absent on
• Severe microcytic, hypochromic anemia with neonatal screening. Such infants are hematologically
marked hepatosplenomegaly. normal at birth but develop severe anemia after the first
few months of life. The peripheral blood smear typi-
cally shows a severe hypochromic, microcytic anemia
with marked anisocytosis and poikilocytosis. Target
cells are prominent, and nucleated red blood cells often
General Considerations exceed the number of circulating white blood cells. The
hemoglobin level usually falls to 5–6 g/dL or less, and
In contrast to the four α-globin genes, only two β-glo- the reticulocyte count is elevated but the reticulocyte
bin genes are present in diploid cells, one on each chro- index is normal to decreased. Platelet and white blood
mosome 11. Some β-thalassemia genes produce no β- cell counts may be increased, and the serum bilirubin
globin chains and are termed β0-thalassemia. Other level is elevated. The bone marrow shows marked ery-
β-globin genes produce some β-globin but in dimin- throid hyperplasia but is rarely needed for diagnosis.
ished quantities and are termed β+-thalassemia. Persons Hemoglobin electrophoresis shows only fetal hemoglo-
affected by β-thalassemia may be heterozygous or ho- bin and hemoglobin A2 in children with homozygous
mozygous. Individuals heterozygous for most β-tha- β0-thalassemia. Those with β+-thalassemia genes make
lassemia genes have β-thalassemia minor. Homozygous some hemoglobin A but have a marked increase in fetal
individuals have β-thalassemia major (Cooley anemia), hemoglobin and hemoglobin A2 levels. The diagnosis
a severe transfusion-dependent anemia, or a condition of homozygous β-thalassemia may also be suggested by
known as thalassemia intermedia, which is more severe the finding of β-thalassemia minor in both parents.
than thalassemia minor but is not generally transfusion
dependent. β-Thalassemia major is the most common
worldwide cause of transfusion-dependent anemia in Differential Diagnosis
childhood. In addition, β-thalassemia genes interact β-Thalassemia minor must be differentiated from other
with genes for structural β-globin variants such as he- causes of mild microcytic, hypochromic anemias, prin-
moglobin S and hemoglobin E to cause serious disease cipally iron deficiency and α-thalassemia. In contrast to
in compound heterozygous individuals. These disorders patients with iron-deficiency anemia, those with β-tha-
are discussed further in the sections dealing with sickle lassemia minor typically have an elevated number of
cell disease and with hemoglobin E disorders. red blood cells, and the index of the MCV divided by
the red cell count is under 13. Generally, the finding of
Clinical Findings an elevated hemoglobin A2 level is diagnostic; however,
the A2 level is lowered by coexistent iron deficiency,
A. SYMPTOMS AND SIGNS which may lead to some confusion. Thus, in children
Persons with β-thalassemia minor are usually asympto- thought to be iron-deficient, hemoglobin electrophore-
matic with a normal physical examination. Those with sis with quantitation of hemoglobin A2 is sometimes
β-thalassemia major are normal at birth but develop deferred until after a course of iron therapy.
significant anemia during the first year of life. If the dis- β-Thalassemia major is rarely confused with other
order is not identified and treated with blood transfu- disorders. Hemoglobin electrophoresis and family stud-
sions, such children grow poorly and develop massive ies readily distinguish it from hemoglobin E–β-tha-
hepatosplenomegaly and enlargement of the medullary lassemia, which is the other important cause of transfu-
space with thinning of the bony cortex. The skeletal sion-dependent thalassemia.
changes cause characteristic facial deformities (promi-
nent forehead and maxilla) and predispose the child to
pathologic fractures.
Complications
The principal complication of β-thalassemia minor is
B. LABORATORY FINDINGS the unnecessary use of iron therapy in a futile attempt
Children with β-thalassemia minor have normal neona- to correct the microcytic anemia. Children with β-tha-
tal screening results but subsequently develop a de- lassemia major who are inadequately transfused experi-
 HEMATOLOGIC DISORDERS / 871

ence poor growth and recurrent infections and may 3. Sickle Cell Disease
have hepatosplenomegaly, thinning of the cortical
bone, and pathologic fractures. Without treatment,
most children die within the first decade of life. The ESSENTIALS OF DIAGNOSIS
principal complications of β-thalassemia major in & TYPICAL FEATURES
transfused children are hemosiderosis, splenomegaly,
and hypersplenism. Transfusional hemosiderosis re- • Neonatal screening test with hemoglobin FS, FSC,
quires chelation therapy with deferoxamine to prevent or FSA.
cardiac, hepatic, and endocrine dysfunction. Noncom-
pliance with chelation in adolescents and young adults • African, Mediterranean, Middle Eastern, Indian, or
may lead to death from congestive heart failure, cardiac Caribbean ancestry.
arrhythmias, or hepatic failure. Even with adequate • Anemia, elevated reticulocyte count, jaundice.
transfusions, many patients develop splenomegaly and • Recurrent episodes of musculoskeletal or abdomi-
some degree of hypersplenism. This may require surgi- nal pain.
cal splenectomy because of the increasing transfusion
• Hemoglobin electrophoresis with hemoglobins S
requirements, but the procedure increases the risk of
and F; hemoglobins S and C; or hemoglobins S, A,
thrombosis and overwhelming septicemia.
and F with S > A.
Treatment • Splenomegaly in early childhood with later disap-
pearance.
β-Thalassemia minor requires no specific therapy but • High risk of bacterial sepsis.
may have important genetic implications for the family.
For patients with β-thalassemia major, two approaches
to treatment are now available: chronic transfusion with
iron chelation and stem cell transplantation. Programs
of blood transfusion are generally targeted to maintain
a nadir hemoglobin level of 9–10 g/dL. This approach
gives increased vigor and well-being, improved growth, General Considerations
and fewer overall complications. However, mainte- A high prevalence of sickle hemoglobin is found in per-
nance of good health currently requires iron chelation sons of central African origin. It also occurs in other
with nightly subcutaneous infusion of deferoxamine. ethnic groups in Sicily, Italy, Greece, Turkey, Saudi
Small doses of supplemental ascorbic acid may enhance Arabia, and India. Sickle cell anemia is caused by ho-
the efficacy of iron chelation. Newly developed oral mozygosity for the sickle gene and is the most common
iron chelators are under study. Patients who undergo form of sickle cell disease. Other clinically important
splenectomy to reduce transfusion requirements, and sickling disorders are compound heterozygous condi-
hence iron loading, should receive pneumococcal vac- tions in which the sickle gene interacts with genes for
cine prior to the procedure and prophylactic penicillin hemoglobin C, DPunjab, OArab, CHarlem, or β-thalassemia.
and urgent treatment of all febrile illness afterward. Overall, sickle cell disease occurs in about one of
Bone marrow or umbilical cord blood transplanta- every 400 African American infants. Eight percent of
tion is an important therapeutic option for children African Americans are heterozygous carriers of the
with β-thalassemia major who have an HLA-identical sickle gene and are said to have sickle cell trait.
sibling donor. The probability of hematologic cure is The protean clinical manifestations of sickle hemo-
greater than 90% when transplantation is performed globinopathies can be linked directly or indirectly to
prior to the development of hepatomegaly or portal fi- the propensity of deoxygenated hemoglobin S to poly-
brosis. merize. Polymerization of sickle hemoglobin distorts
erythrocyte morphology, decreases red cell deformabil-
Lucarelli G et al: Marrow transplantation in patients with tha- ity, causes a marked reduction in red cell life span, in-
lassemia responsive to iron chelation therapy. N Engl J Med creases blood viscosity, and predisposes to episodes of
1993;329:840 [PMID: 8355742].
vaso-occlusion.
Olivieri NF: Medical progress: The β-thalassemias. N Engl J Med
1999;34:99 [PMID: 10395635].
Neonatal screening for sickle hemoglobinopathies is
Olivieri NF, Brittenham GM: Iron-chelating therapy and the treat-
now routine in most of the United States. The identifi-
ment of thalassemia. Blood 1997;89:739 [PMID: 9028304]. cation of affected infants at birth, when combined with
Olivieri NF et al: Survival in medically treated patients with ho- follow-up programs of parental education, comprehen-
mozygous β-thalassemia. N Engl J Med 1994;331:574 sive medical care, and prophylactic penicillin, markedly
[PMID: 8047081]. reduces morbidity and mortality in early childhood.
872 / CHAPTER 27

Clinical Findings Table 27–2. Common clinical manifestations

of sickle cell disease.
A. SYMPTOMS AND SIGNS
These are related to the hemolytic anemia and to tissue
Acute Chronic
ischemia and organ dysfunction caused by vaso-occlu-
sion. Children are normal at birth, and onset of symp- Children Bacterial sepsis or Functional asplenia
toms is unusual before age 3–4 months because high meningitisa Delayed growth and
levels of fetal hemoglobin inhibit sickling. A moderately Splenic sequestrationa development
severe hemolytic anemia may be present by age 1 year; Aplastic crisis Avasular necrosis of the
causes pallor, fatigue, and jaundice; and predisposes to Vaso-occlusive events hip
the development of gallstones during childhood and Dactylitis Hyposthenuria
adolescence. Intense congestion of the spleen with sick- Bone infarction Cholelithiasis
led cells may cause splenomegaly in early childhood and Acute chest
syndromea
results in functional asplenia as early as age 3 months.
Strokea
This places children at great risk for overwhelming in- Priapism
fection with encapsulated bacteria, particularly pneu-
mococci. Up to 30% of patients experience one or Adults Bacterial sepsisa Leg ulcers
more episodes of acute splenic sequestration, character- Aplastic crisis Proliferative retinopathy
ized by sudden enlargement of the spleen with pooling Vaso-occlusive events Avascular necrosis of the
of red cells, acute exacerbation of anemia, and, in severe Bone infarction hip
cases, shock and death. Acute exacerbation of anemia Acute chest syn- Cholecystitis
also occurs with aplastic crises, usually caused by infec- dromea Chronic organ failurea
tion with human parvovirus, and other viruses. Strokea Liver
Priapism Lung
Recurrent episodes of vaso-occlusion and tissue is-
Acute multiorgan Kidney
chemia cause myriad acute and chronic problems. failure syndromea Decreased fertility
Dactylitis, or hand-and-foot syndrome, is the most
a
common initial symptom of the disease and occurs in Associated with significant mortality rate.
up to 50% of children before age 3 years. Recurrent
episodes of ischemic pain, particularly abdominal and
musculoskeletal pain, may occur throughout life.
Strokes occur in about 8% of children and tend to be globin level may be normal or only slightly decreased
recurrent. The acute chest syndrome, characterized by because the rate of hemolysis is much less than in sickle
fever, pleuritic chest pain, and acute pulmonary infil- cell anemia.
trates with hypoxemia, is caused by pulmonary in- Most infants with sickle hemoglobinopathies born
fection, infarction, or fat embolism from ischemic in the United States are now identified by neonatal
bone marrow. All tissues are susceptible to damage screening. Results indicative of possible sickle cell dis-
from vaso-occlusion, and multiple organ dysfunction is ease require prompt confirmation with hemoglobin
common by adulthood. Table 27–2 lists the common electrophoresis. Children with sickle cell anemia and
manifestations of sickle cell disease in children and with sickle β0-thalassemia have only hemoglobins S and
adults. F. Persons with sickle β+-thalassemia have a preponder-
B. LABORATORY FINDINGS ance of hemoglobin S with a lesser amount of hemoglo-
bin A. Persons with sickle hemoglobin C disease have
Children with sickle cell anemia (homozygous sickle equal amounts of hemoglobin S and hemoglobin C.
cell disease) generally show a baseline hemoglobin level The use of solubility tests to screen for the presence of
of 7–10 g/dL. This value may fall to life-threatening sickle hemoglobin should be avoided because a negative
levels at the time of a sequestration or aplastic crisis. result is frequently encountered in infants with sickle
The baseline reticulocyte count is elevated markedly. cell disease, and because a positive result in an older
The anemia is usually normocytic or macrocytic, and child does not differentiate sickle cell trait from sickle
the peripheral blood smear typically shows the charac- cell disease. Thus hemoglobin electrophoresis is always
teristic sickle cells as well as numerous target cells. Pa- necessary to accurately identify a sickle disorder.
tients with sickle β-thalassemia generally have a low
MCV and hypochromia as well. Those with sickle β+- Differential Diagnosis
thalassemia tend to have lesser degrees of hemolysis and
anemia. Persons with sickle hemoglobin C disease have Hemoglobin electrophoresis and sometimes hemato-
fewer sickle forms and more target cells, and the hemo- logic studies of the parents are usually sufficient to con-
 HEMATOLOGIC DISORDERS / 873

firm the correct diagnosis of a sickle cell disorder. In- episodes of vaso-occlusive pain. Simple or partial ex-
fants whose neonatal screening test shows only hemo- change transfusion to reduce the percentage of circulat-
globins F and S occasionally have disorders other than ing sickle cells is indicated for some severe acute vaso-
sickle cell anemia or sickle β0-thalassemia. The most im- occlusive events and may be lifesaving. These events
portant of these disorders is a compound heterozygous include stroke, moderate to severe acute chest syn-
condition of sickle hemoglobin and pancellular heredi- drome, and acute life-threatening failure of other or-
tary persistence of fetal hemoglobin. Such children, gans. Transfusions may also be used prior to high-risk
when older, typically have 30% fetal hemoglobin and procedures such as surgery with general anesthesia and
70% hemoglobin S, but they do not have significant arteriograms with ionic contrast materials. Some pa-
anemia nor are they subject to vaso-occlusive episodes. tients who develop severe vaso-occlusive complications
may benefit from chronic transfusion therapy. The
most common indication for this type of transfusion is
Complications stroke. Without transfusions, children with stroke have
Repeated tissue ischemia and infarction causes damage a 70–80% chance of recurrent stroke within a 2-year
to virtually every organ system. Table 27–2 lists the period. This risk of recurrent neurologic events is re-
most important complications. Patients who require duced markedly by the transfusion therapy.
multiple transfusions are at risk for transfusional hemo- Successful stem cell transplantation cures sickle cell
siderosis and the development of red cell alloantibodies. disease, but to date its use has been limited because of
the risks associated with the procedure, the inability to
predict in young children the severity of future compli-
Treatment cations, and the paucity of HLA-identical sibling
The cornerstone of treatment is enrollment in a pro- donors. Daily administration of oral hydroxyurea in-
gram involving patient and family education, compre- creases levels of fetal hemoglobin, decreases hemolysis,
hensive outpatient care, and appropriate treatment of and reduces by 50% episodes of pain in severely af-
acute complications. Important to the success of such a fected adults with sickle cell anemia. The hematologic
program are psychosocial services, blood bank services, effects and short-term toxicity of hydroxyurea in chil-
and the ready availability of baseline patient informa- dren are similar to those in adults. Thus hydroxyurea is
tion in the setting in which acute illnesses are evaluated being used increasingly for selected children and adoles-
and treated. Management of sickle cell anemia and cents who have frequent, severe complications.
sickle β0-thalassemia includes prophylactic penicillin,
which should be initiated by age 2 months and contin-
ued at least until age 5 years. The routine use of peni-
Prognosis
cillin prophylaxis in sickle hemoglobin C disease and Early identification by neonatal screening of infants
sickle β+-thalassemia is controversial. Pneumococcal with sickle cell disease, combined with comprehensive
conjugate and polysaccharide vaccine should be admin- care that includes prophylactic penicillin, has markedly
istered to all children who have sickle cell disease. reduced mortality in childhood. Most patients are now
Other routine immunizations, including yearly vaccina- expected to live well into adulthood, but they eventu-
tion against influenza, should be provided. All illnesses ally succumb to complications.
associated with fever greater than 38.5°C should be
evaluated promptly, bacterial cultures preformed, par- Academy of Pediatrics, Section on Hematology/Oncology and
enteral broad-spectrum antibiotics administered, and Committee on Genetics: Health supervision for children with
careful inpatient or outpatient observation conducted. sickle cell disease. Pediatrics 2002;109:526 [PMID:
Treatment of painful vaso-occlusive episodes in- 11875155].
cludes the maintenance of adequate hydration (with Kinney TR et al: Safety of hydroxyurea in children with sickle cell
avoidance of overhydration), correction of acidosis if anemia: Results of the HUG-KIDS study, a phase I/II trial.
present, administration of adequate analgesia, mainte- Blood 1999;94:1550 [PMID: 10477679].
nance of normal oxygen saturation, and the treatment Lane PA: Sickle cell disease. Pediatr Clin North Am 1996;43:
of any associated infections. 639 [PMID: 8649903].
Red cell transfusions play an important role in man- Ohene-Frempong K et al: Cerebrovascular accidents in sickle cell
disease: Rates and risk factors. Blood 1998;91:288 [PMID:
agement. Transfusions are indicated to improve oxy- 9414296].
gen-carrying capacity during acute exacerbations of Steinberg MH: Drug therapy: Management of sickle cell disease.
anemia, as occurs during episodes of splenic sequestra- N Engl J Med 1999;340:1021 [PMID: 10099145].
tion or aplastic crisis. Red cell transfusions are not indi- Vichinsky EP et al: Causes and outcomes of the acute chest syn-
cated for the treatment of chronic steady-state anemia, drome in sickle cell disease. N Engl J Med 2000;342:
which is usually well tolerated, or for uncomplicated 1855 [PMID: 10861320].
874 / CHAPTER 27

Walters MC et al: Bone marrow transplantation for sickle cell dis- Kark JA et al: Sickle cell trait as a risk factor for sudden death in
ease. N Engl J Med 1996;335:369 [PMID: 8663884]. physical training. N Engl J Med 1987;317:781 [PMID:
3627196].
4. Sickle Cell Trait Nuss R et al: Cardiopulmonary function in men with sickle cell dis-
ease who reside at moderately high altitude. J Lab Clin Med
Individuals who are heterozygous for the sickle gene are 1993;122:382 [PMID: 8228552].
said to have sickle cell trait. This genetic carrier state Pearson HA: Sickle cell trait and competitive athletics: Is there a
occurs in 8% of African Americans and is more com- risk? Pediatrics 1989;83:613 [PMID: 2928004].
mon in some areas of Africa and the Middle East. In-
fants with sickle cell trait are identified by neonatal
screening results that show hemoglobins FAS. Accurate
5. Hemoglobin C Disorders
identification of older persons with sickle cell trait de- Hemoglobin C is detected by neonatal screening. Two
pends on hemoglobin electrophoresis, which typically percent of African Americans are heterozygous for he-
shows about 60% hemoglobin A and about 40% he- moglobin C and are said to have hemoglobin C trait.
moglobin S. No anemia or hemolysis is present, and Such individuals have no symptoms, anemia, or hemol-
the physical examination is normal. Persons with sickle ysis, but the peripheral blood smear may show some
cell trait are generally healthy, and most experience no target cells. Identification of persons with hemoglobin
illness attributable to the presence of sickle hemoglobin C trait is important for genetic counseling, particularly
in their red cells. Life expectancy is normal. with regard to the possibility of sickle hemoglobin C
Sickle trait erythrocytes are capable of sickling, par- disease in offspring.
ticularly under conditions of significant hypoxemia, and Persons with homozygous hemoglobin C have a
a number of clinical abnormalities have been linked to mild microcytic hemolytic anemia and may develop
this genetic carrier state. Exposure to environmental hy- splenomegaly. The peripheral blood smear shows
poxia (altitude > 3100 m [10,000 ft] above sea level) prominent target cells. As with other hemolytic ane-
may precipitate splenic infarction. However, most per- mias, complications of homozygous hemoglobin C in-
sons with sickle cell trait who choose to visit such alti- clude gallstones and aplastic crises.
tudes for skiing, hiking, or climbing do so without diffi-
culty. Many develop some degree of hyposthenuria, and Olson JF et al: Hemoglobin C disease in infancy and childhood.
about 4% experience painless hematuria, usually micro- J Pediatr 1994;125:745 [PMID: 7965426].
scopic but occasionally macroscopic. For the most part,
these renal abnormalities are subclinical, and they do
not progress to significant renal dysfunction. The inci- 6. Hemoglobin E Disorders
dence of bacteriuria and pyelonephritis may be increased
during pregnancy, but overall rates of maternal and in- Hemoglobin E is the second most common hemoglo-
fant morbidity and mortality are not affected by the bin variant worldwide, with a gene frequency greater
presence of sickle cell trait in the pregnant woman. than 10% in some areas of Thailand and Cambodia. In
An epidemiologic study of army recruits in military Southeast Asia, an estimated 30 million people have he-
basic training found a higher risk of sudden unex- moglobin E trait. Persons heterozygous for hemoglobin
plained death following strenuous exertion in recruits E show hemoglobins FAE by neonatal screening and
with sickle cell trait than in those with normal hemo- are asymptomatic and usually not anemic, but they
globin. This study has raised concerns about exercise may develop mild microcytosis. Persons homozygous
and exertion for persons with the trait. However, con- for hemoglobin E are also asymptomatic but may have
siderable evidence suggests that exercise is generally safe mild anemia; the peripheral blood smear shows micro-
and that athletic performance is not adversely affected cytosis and some target cells.
by sickle cell trait. Exercise tolerance is normal, and the Hemoglobin E is most important because of its in-
incidence of sickle cell trait in black professional foot- teraction with β-thalassemia. Compound heterozygotes
ball players is similar to that of the general African for hemoglobin E and β0-thalassemia are normal at
American population, suggesting no barrier to achieve- birth and, like infants with homozygous E, show hemo-
ment in such a physically demanding profession. Thus globins FE on neonatal screening. Unlike homozygotes,
restrictions on athletic competition for children with they subsequently develop mild to severe microcytic
sickle cell trait are not warranted. Sickle cell trait is hypochromic anemia. Such children may exhibit jaun-
most significant for its genetic implications. dice, hepatosplenomegaly, and poor growth if the dis-
order is not recognized and treated appropriately. In
American Academy of Pediatrics Committee on Sports Medicine:
some cases, the anemia becomes severe enough to re-
Recommendations for participation in competitive sports. quire lifelong transfusion therapy. In certain areas of
Pediatrics 1988;81:737 [PMID: 3357741]. the United States, hemoglobin E–β0-thalassemia has
 HEMATOLOGIC DISORDERS / 875

become a more common cause of transfusion-depen- nant disorder. The diagnosis is confirmed by finding a
dent anemia than homozygous β-thalassemia. low level of the deficient enzyme.
The two most common disorders of erythrocyte me-
Glader BE, Look KA: Hematologic disorders in children from tabolism are G6PD deficiency and pyruvate kinase defi-
Southeast Asia. Pediatr Clin North Am 1996;43:665 [PMID: ciency.
8649904].
Krishnamurti L et al: Coinheritance of α-thalassemia-1 and hemo-
globin E/β0-thalassemia: Practical implications for neonatal 1. Glucose-6-Phosphate Dehydrogenase
screening and genetic counseling. J Pediatr 1998;132:863 (G6PD) Deficiency
[PMID: 9602201].
Weatherall DJ: Hemoglobin E–β0-thalassemia: An increasingly
common disease with some diagnostic pitfalls. J Pediatr ESSENTIALS OF DIAGNOSIS
1998;132:765 [PMID: 9602183].
& TYPICAL FEATURES
7. Other Hemoglobinopathies • African, Mediterranean, or Asian ancestry.
Hundreds of other human globin-chain variants have • Neonatal hyperbilirubinemia.
been identified and described. Some, such as hemoglo- • Sporadic hemolysis associated with infection or
bins D and G, are relatively common. Heterozygous in- with ingestion of oxidant drugs or fava beans.
dividuals, who are frequently identified during the
course of neonatal screening programs for hemoglo- • X-linked inheritance.
binopathies, are generally asymptomatic and usually
have no anemia or hemolysis. The principal signifi-
cance of most hemoglobin variants is the potential for
disease in compound heterozygous individuals who also General Considerations
inherit a gene for β-thalassemia or sickle hemoglobin.
For example, children who are compound heterozygous Deficiency of G6PD is the most common red cell en-
for hemoglobins S and DPunjab (DLos Angeles) have sickle zyme defect that causes hemolytic anemia. The disorder
cell disease. has X-linked recessive inheritance and occurs with high
frequency among persons of African, Mediterranean,
CONGENITAL HEMOLYTIC ANEMIAS: and Asian ancestry. Hundreds of different G6PD vari-
ants have been characterized. In most instances, the de-
DISORDERS OF RED CELL METABOLISM ficiency is due to enzyme instability; thus, older red
Erythrocytes depend on the anaerobic metabolism of cells are more deficient than younger ones. The conse-
glucose for the maintenance of adenosine triphosphate quence is the inability of erythrocytes to generate suffi-
(ATP) levels sufficient for homeostasis. Glycolysis also cient amounts of NADPH to maintain the levels of re-
produces the 2,3-diphosphoglycerate (2,3-DPG) levels duced glutathione necessary to protect the red cells
needed to modulate the oxygen affinity of hemoglobin. against oxidant stress. Thus most persons with G6PD
Glucose metabolism via the hexosemonophosphate deficiency do not have a chronic hemolytic anemia but
shunt is necessary to generate sufficient reduced nicoti- have episodic hemolysis at times of exposure to the oxi-
namide adenine dinucleotide phosphate (NADPH) and dant stress of infection or of certain drugs or food sub-
reduced glutathione to protect red cells against oxidant stances. The severity of the disorder varies among eth-
damage. Congenital deficiencies of many glycolytic nic groups; G6PD deficiency in persons of African
pathway enzymes have been associated with hemolytic ancestry usually is less severe than in other ethnic
anemias. In general, the morphologic abnormalities groups.
present on the peripheral blood smear are nonspecific,
and the inheritance of these disorders is autosomal re- Clinical Findings
cessive or X-linked. Thus the possibility of a red cell en-
zyme defect should be considered during the evaluation A. SYMPTOMS AND SIGNS
of a patient with a congenital hemolytic anemia when Infants with G6PD deficiency may have significant hy-
the peripheral blood smear does not show red cell mor- perbilirubinemia and may require phototherapy or
phology typical of membrane or hemoglobin defects exchange transfusion to prevent kernicterus. The defi-
(eg, spherocytes, sickle forms, target cells), when hemo- ciency is an important cause of neonatal hyperbiliru-
globin disorders are excluded by hemoglobin elec- binemia in infants of Mediterranean or Asian ancestry
trophoresis and by isopropanol precipitation tests, and but less so in infants of African ancestry. Older children
when family studies do not suggest an autosomal domi- with G6PD deficiency are asymptomatic and appear
876 / CHAPTER 27

Table 27–3. Some common drugs and chemicals treated promptly and antibiotics given when appropri-
that can induce hemolytic anemia in persons with ate. Most episodes of hemolysis are self-limiting, but
G6PD deficiency. red cell transfusions may be lifesaving when signs and
symptoms indicate cardiovascular compromise.
Acetanilide Niridazole
Beutler E: G6PD deficiency. Blood 1994;84:3613 [PMID:
Doxorubicin Nitrofurantoin
7949118].
Furazolidone Phenazopyridine
Kaplan M et al: Conjugated bilirubin in neonates with glucose-
Methylene blue Primaquine
6-phosphate dehydrogenase deficiency. J Pediatr 1996;
Nalidixic acid Sulfamethoxazole 128:695 [PMID: 8627445].
From Beutler E: Glucose-6-phosphate dehydrogenase deficiency. Seidman DS et al: Role of hemolysis in neonatal jaundice associ-
N Engl J Med 1991;324:171. ated with glucose-6-phosphate dehydrogenase deficiency.
J Pediatr 1995;127:804 [PMID: 7472840].

normal between episodes of hemolysis. Hemolytic

2. Pyruvate Kinase Deficiency
episodes are often triggered by infection or by the in- Pyruvate kinase deficiency is an autosomal recessive dis-
gestion of oxidant drugs such as antimalarial com- order observed in all ethnic groups but is most com-
pounds and sulfonamide antibiotics (Table 27–3). In- mon in northern Europeans. The deficiency is associ-
gestion of fava beans may trigger hemolysis in children ated with a chronic hemolytic anemia of varying
of Mediterranean or Asian ancestry but usually not in severity. Approximately one third of those affected pre-
children of African ancestry. Episodes of hemolysis are sent in the neonatal period with jaundice and hemolysis
associated with pallor, jaundice, hemoglobinuria, and that require phototherapy or exchange transfusion. Oc-
sometimes cardiovascular compromise. casionally, the disorder causes hydrops fetalis and
neonatal death. In older children, the hemolysis may
B. LABORATORY FINDINGS require red cell transfusions or be mild enough to go
The hemoglobin, reticulocyte count, and peripheral unnoticed for many years. Jaundice and splenomegaly
blood smear are usually normal in the absence of oxi- frequently occur in the more severe cases. The diagnosis
dant stress. Episodes of hemolysis are associated with a of pyruvate kinase deficiency is occasionally suggested
variable fall in hemoglobin. “Bite” cells or blister cells by the presence of echinocytes on the peripheral blood
may be seen, along with a few spherocytes. Hemoglo- smear, but these findings may be absent prior to
binuria is common, and the reticulocyte count increases splenectomy. The diagnosis depends on the demonstra-
within a few days. Heinz bodies may be demonstrated tion of low levels of pyruvate kinase activity in red cells.
with appropriate stains. The diagnosis is confirmed by Treatment of pyruvate kinase depends on the sever-
the finding of reduced levels of G6PD in erythrocytes. ity of the hemolysis. Blood transfusions may be required
Because this enzyme is present in increased quantities for significant anemia, and splenectomy may be benefi-
in reticulocytes, the test is best performed at a time cial. The procedure does not cure the disorder but ame-
when the reticulocyte count is normal or near normal. liorates the anemia and its symptoms. Characteristically,
the reticulocyte count increases and echinocytes become
Complications more prevalent after splenectomy, despite the decreased
hemolysis and increased hemoglobin level.
Kernicterus is a risk for infants with significant neonatal
hyperbilirubinemia. Episodes of acute hemolysis in Gilsanz F et al: Fetal anaemia due to pyruvate kinase deficiency.
older children may be life-threatening. Rare G6PD Arch Dis Child 1993;69:523 [PMID: 8285758].
variants are associated with chronic hemolytic anemia;
the clinical course of patients with such variants may be
complicated by splenomegaly and by the formation of ACQUIRED HEMOLYTIC ANEMIA
gallstones. 1. Autoimmune Hemolytic Anemia
Treatment
ESSENTIALS OF DIAGNOSIS
The most important treatment issue is avoidance of
drugs known to be associated with hemolysis (see Table & TYPICAL FEATURES
27–3). For some patients of Mediterranean, Middle
Eastern, or Asian ancestry, the consumption of fava • Pallor, fatigue, jaundice, and dark urine.
beans must also be avoided. Infections should be • Splenomegaly common.
 HEMATOLOGIC DISORDERS / 877

• Positive DAT. B. LABORATORY FINDINGS

• Reticulocytosis and spherocytosis. The anemia is normochromic and normocytic and may
vary from mild to severe (hemoglobin concentration <
5 g/dL). The reticulocyte count is usually increased but
occasionally may be normal or low. Spherocytes and
nucleated red cells may be seen on the peripheral blood
General Considerations smear. Although leukocytosis and elevated platelet
counts are a common finding, thrombocytopenia occa-
Acquired autoimmune hemolytic anemia is rare during
sionally occurs. Other laboratory data consistent with
the first 4 months of life but is one of the more com-
hemolysis are present such as increased indirect and
mon causes of acute anemia after the first year. It may
total bilirubin, lactic dehydrogenase, aspartate amino-
arise as an isolated problem or may complicate an infec-
transferase, and urinary urobilinogen. Intravascular he-
tion (hepatitis, upper respiratory tract infections,
molysis is indicated by hemoglobinemia or hemoglo-
mononucleosis, cytomegalovirus [CMV] infection);
binuria. Examination of bone marrow shows marked
systemic lupus erythematosus and other autoimmune
erythroid hyperplasia and hemophagocytosis, but is sel-
syndromes; immunodeficiency states; or malignancies.
dom required.
Serologic studies are helpful in defining pathophysi-
Clinical Findings ology, planning therapeutic strategies, and assessing
prognosis (Table 27–4). In almost all cases, the direct
A. SYMPTOMS AND SIGNS and indirect antiglobulin (DAT and IAT) tests are posi-
The disease usually has an acute onset, manifested by tive. Further evaluation allows distinction into one of
weakness, pallor, dark urine, and fatigue. Jaundice is a three syndromes. The presence of IgG on the patient’s
prominent finding, and splenomegaly is often present. red blood cells, maximal in vitro antibody activity at
Some cases are chronic and insidious in onset. Clinical 37°C, and either no antigen specificity or an Rh-like
evidence of an underlying disease may be present. specificity constitute warm autoimmune hemolytic ane-

Table 27–4. Classification of autoimmune hemolytic anemia (AIHA) in children.

Syndrome Warm AIHA Cold AIHA Paroxysmal Cold Hemoglobinuria

Specific antiglobulin test
IgG Strongly positive Negative Negative
Complement Negative or mildly positive Strongly positive Strongly positive
Temperature at maximal 37°C 4 °C 4 °C
reactivity (in vitro)
Antigen specificity May be panagglutinin or may have I or i P
an Rh-like specificity
Other ... ... Positive biphasic hemolysin test
Pathophysiology Extravascular hemolysis, destruction Intravascular hemolysis Intravascular hemolysis
by the RES (eg, spleen) (may have extra- (may have extravascular
vascular component) component)
Prognosis May be more chronic (> 3 months) Generally acute (< 3 Acute, self-limited. Associated
with significant morbidity and mor- months). Good prog- with infection.
tality. May be associated with a pri- nosis: Often associated
mary disorder (lupus, immunodefi- with infection.
ciency, etc)
Therapy Respond to RES blockade, including May not respond to Usually self-limited. Symptom-
steroids (prednisone, 2 mg/kg/d), RES blockade. Severe atic management.
IVIG (1 g/kg/d for 2 days), or cases may benefit from
splenectomy plasmapheresis.
RES = reticuloendothelial system; IVIG = intravenous immune globulin.
878 / CHAPTER 27

mia with extravascular destruction by the reticuloen- tory cases, recent studies have documented responses to
dothelial system. In contrast, the detection of comple- rituximab or bone marrow transplantation.
ment alone on red blood cells, optimal reactivity in Patients with cold autoimmune hemolytic anemia
vitro at 4°C, and I or i antigen specificity are diagnostic and paroxysmal cold hemoglobinuria are less likely to
of cold autoimmune hemolytic anemia with intravascu- respond to corticosteroids or IVIG. Because these syn-
lar hemolysis. Although these are relatively common dromes are most apt to be associated with infections
(~10%) in normal individuals, clinically significant and have an acute, self-limited course, supportive care
cold antibodies exhibit in vitro reactivity at 30°C or may be all that is required. Plasma exchange is effective
above. in severe cold autoimmune (IgM) hemolytic anemia
Paroxysmal cold hemoglobinuria usually has a dif- and may be helpful in severe cases because the offend-
ferent cause. The laboratory evaluation is identical to ing antibody has only an intravascular distribution.
cold autoimmune hemolytic anemia except for antigen Supportive therapy is crucial. Patients with cold-re-
specificity (P) and the exhibition of in vitro hemolysis. acting antibodies, particularly paroxysmal cold hemo-
Almost always paroxysmal cold hemoglobinuria is asso- globinuria, should be kept in a warm environment.
ciated with significant infections, such as Mycoplasma, Transfusion may be necessary because of the complica-
Epstein–Barr virus (EBV), and CMV. Warm IgM anti- tions of severe anemia but should be used only when
bodies are very rare. there is no alternative. In most patients, cross-
match–compatible blood will not be found, and the
least incompatible unit should be identified. Transfu-
Differential Diagnosis sion must be conducted carefully, beginning with a test
Autoimmune hemolytic anemia must be differentiated dose (see Transfusion Medicine section). Identification
from other forms of congenital or acquired hemolytic of the patient’s phenotype for minor red cell alloanti-
anemias. The DAT discriminates antibody-mediated gens may be helpful in avoiding alloimmunization or in
hemolysis from other causes, such as hereditary sphero- providing appropriate transfusions if alloantibodies
cytosis. arise after initial transfusions. Patients with severe in-
travascular hemolysis may have associated disseminated
intravascular coagulation (DIC), and heparin therapy
Complications should be considered in such cases.
The anemia may be very severe and result in cardiovas-
cular collapse, requiring emergency management. The
complications of the underlying disease such as dissemi- Prognosis
nated lupus erythematosus or an immunodeficiency The outlook for autoimmune hemolytic anemia in
state may be present. childhood is usually good unless associated diseases are
present (eg, congenital immunodeficiency, acquired
immunodeficiency syndrome [AIDS], lupus erythe-
Treatment matosus), in which case the hemolysis is likely to run a
Medical management of the underlying disease is im- chronic course. In general, children with warm autoim-
portant in symptomatic cases. Defining the clinical syn- mune hemolytic anemia are at greater risk for more se-
drome provides a useful guide to treatment. Most pa- vere and chronic disease with higher morbidity and
tients with warm autoimmune hemolytic anemia (in mortality rates. Hemolysis and positive antiglobulin
which hemolysis is extravascular) respond to pred- tests may continue for months or years. Patients with
nisone. After the initial treatment, the dose of cortico- cold autoimmune hemolytic anemia or paroxysmal cold
steroids may be decreased slowly. Patients may respond hemoglobinuria are more likely to have acute, self-lim-
to 1 g of intravenous immune globulin (IVIG) per kilo- ited disease (< 3 months). Paroxysmal cold hemoglo-
gram per day for 2 days, but fewer patients respond to binuria is almost always associated with infection (eg,
IVIG than to prednisone. Although the rate of remis- with Mycoplasma infection, CMV, EBV).
sion with splenectomy may be as high as 50%, particu-
larly in warm autoimmune hemolytic anemia, this
should be carefully considered in younger patients and Petz LD, Garratty G: Unusual problems regarding autoimmune
hemolytic anemias. In Acquired Immune Hemolytic Anemias.
withheld until other treatments have been tried. In se- Churchill Livingstone, 1980.
vere cases unresponsive to more conventional therapy,
Shirey RS et al: Prophylactic antigen-matched donor blood for pa-
immunosuppressive agents such as cyclophosphamide, tients with warm autoantibodies: An algorithm for transfu-
azathioprine, busulfan, and cyclosporine may be tried sion management. Transfusion 2002;42:1435 [PMID:
alone or in combination with corticosteroids. In refrac- 12421216].
 HEMATOLOGIC DISORDERS / 879

Zecca M et al: Rituximab for the treatment of refractory autoim- Juvonen E et al: Autosomal dominant erythrocytosis caused by in-
mune hemolytic anemia in children. Blood 2003;101: creased sensitivity to erythropoietin. Blood 1991;78:
3857 [PMID: 12531800]. 3066 [PMID: 1954391].
Sokol L et al: Primary familial polycythemia: A frameshift mutation
in the erythropoietin receptor gene and increased sensitivity
2. Nonimmune Acquired of erythroid progenitors to erythropoietin. Blood
Hemolytic Anemia 1995;86:15 [PMID: 7795221].

Hepatic disease may alter the lipid composition of the

red cell membrane. This usually results in the formation SECONDARY POLYCYTHEMIA
of target cells and is not associated with significant he- Secondary polycythemia occurs in response to hypox-
molysis. Occasionally, hepatocellular damage is associ- emia. The most common cause of secondary poly-
ated with the formation of spur cells and brisk he- cythemia in children is cyanotic congenital heart dis-
molytic anemia. Renal disease may also be associated ease. It also occurs in chronic pulmonary disease such as
with significant hemolysis; hemolytic–uremic syndrome cystic fibrosis. Persons living at extremely high alti-
is one example. In this disorder, hemolysis is associated tudes, as well as some with methemoglobinemia,
with the presence, on the peripheral blood smear, of develop polycythemia. It has on rare occasions been de-
echinocytes, fragmented red cells, and spherocytes. scribed without hypoxemia in association with renal
A microangiopathic hemolytic anemia with frag- tumors, brain tumors, Cushing disease, or hydro-
mented red cells and some spherocytes may be observed nephrosis.
in a number of conditions associated with intravascular Polycythemia may occur in the neonatal period; it is
coagulation and fibrin deposition within vessels. This particularly exaggerated in infants who are preterm or
occurs with DIC such as may complicate severe infec- small for gestational age. In these infants, polycythemia
tion, but it may also occur when the intravascular coag- is sometimes associated with other symptoms. It may
ulation is localized, as with giant cavernous hemangio- occur in infants of diabetic mothers, in Down syn-
mas (Kasabach–Merritt syndrome). Fragmented red drome, and as a complication of congenital adrenal hy-
cells may also be seen with mechanical damage (eg, as- perplasia.
sociated with artificial heart valves). Iron deficiency may complicate polycythemia and
aggravate the associated hyperviscosity. This complica-
tion should always be suspected when the MCV falls
below the normal range. Coagulation and bleeding ab-
POLYCYTHEMIA & normalities, including thrombocytopenia, mild con-
METHEMOGLOBINEMIA sumption coagulopathy, and elevated fibrinolytic activ-
ity, have also been described in severely polycythemic
cardiac patients. Bleeding at surgery may be severe.
CONGENITAL ERYTHROCYTOSIS The ideal treatment of secondary polycythemia is
(FAMILIAL POLYCYTHEMIA) correction of the underlying disorder. When this can-
not be done, phlebotomy may be necessary to control
In pediatrics, polycythemia is usually secondary to symptoms. Iron sufficiency should be maintained. Ade-
chronic hypoxemia. However, a number of families quate hydration of the patient and phlebotomy with
with congenital erythrocytosis have been described. plasma replacement may be indicated prior to major
The disorder differs from polycythemia vera in that surgical procedures; these measures prevent the compli-
only red blood cells are affected; the white blood cell cations of thrombosis and hemorrhage. Isovolumetric
and platelet counts are normal. It occurs as an autoso- exchange transfusion is the treatment of choice in se-
mal dominant or recessive disorder. There are usually vere cases.
no physical findings except for plethora and
splenomegaly. The hemoglobin level may be as high as Balcerzak SP, Bromberg PA: Secondary polycythemia. Semin
27 g/dL. Patients usually have no symptoms other than Hematol 1975;12:353 [PMID: 1105791].
headache and lethargy. Studies in a number of families
have revealed (1) an abnormal hemoglobin with in-
creased oxygen affinity, (2) reduced red cell diphospho-
METHEMOGLOBINEMIA
glycerate, (3) autonomous increase in erythropoietin Methemoglobin is continuously formed at a slow rate
production, or (4) hypersensitivity of erythroid precur- by the oxidation of heme iron to the ferric state. Nor-
sors to erythropoietin. mally, it is enzymatically reduced back to hemoglobin.
Treatment is not indicated unless symptoms are Methemoglobin is unable to transport oxygen and
marked. Phlebotomy is the treatment of choice. causes a shift in the dissociation curve of the residual
880 / CHAPTER 27

oxyhemoglobin. Cyanosis is produced with methemo- ing hemoglobin, probably because their NADH methe-
globin levels of approximately 15% or greater. Levels of moglobin reductase is transiently deficient. Infants with
methemoglobin increase by several mechanisms. metabolic acidosis from diarrhea and dehydration or
other causes may also develop methemoglobinemia.
1. Hemoglobin M Patients with the acquired form of methemoglobine-
mia respond dramatically to methylene blue in a dose of
The designation M is given to several abnormal hemo- 1–2 mg/kg intravenously. For infants and young chil-
globins associated with methemoglobinemia. Affected dren, a smaller dose (1–1.5 mg/kg) is recommended.
individuals are heterozygous for the gene, which is Ascorbic acid administered orally or intravenously also
transmitted as an autosomal dominant disorder. The reduces methemoglobin, but it acts more slowly.
different types of hemoglobin M result from different
amino acid substitutions in α-globin or β-globin. He- Mansouri A, Lurie AA: Concise review: Methemoglobinemia. Am
moglobin electrophoresis at the usual pH will not al- J Hematol 1993;42:7 [PMID: 8416301].
ways demonstrate the abnormal hemoglobin, and iso- Osterhoudt KC et al: Rebound severe methemoglobinemia from
electric focusing may be needed. The patient has ingestion of a nitroethane artificial-fingernail remover. J Pedi-
cyanosis but is otherwise usually asymptomatic. Exer- atr 1995;126:819 [PMID: 7752015].
cise tolerance may be normal, and life expectancy is not Sager S et al: Methemoglobinemia associated with acidosis of prob-
able renal origin. J Pediatr 1995;126:59 [PMID: 7815226].
affected. This type of methemoglobinemia does not re-
spond to any form of therapy.

Vichinsky EP, Lubin BH: Unstable hemoglobins, hemoglobins DISORDERS OF LEUKOCYTES

with altered oxygen affinity, and M-hemoglobins. Pediatr
Clin North Am 1980;27:421 [PMID: 7383714].
NEUTROPENIA
2. Congenital Methemoglobinemia
Due to Enzyme Deficiencies ESSENTIALS OF DIAGNOSIS
Congenital methemoglobinemia is caused most fre- & TYPICAL FEATURES
quently by congenital deficiency of the reducing en-
zyme diaphorase I (coenzyme factor I). It is transmitted • Increased frequency of infections.
as an autosomal recessive trait. Affected patients may
• Ulceration of oral mucosa and gingivitis.
have as high as 40% methemoglobin but usually have
no symptoms, although a mild compensatory poly- • Normal numbers of red cells and platelets.
cythemia may be present. Patients with methemoglo-
binemia associated with a deficiency of diaphorase I re-
spond readily to treatment with ascorbic acid and
methylene blue (see following section), but treatment is General Considerations
not usually indicated.
Neutropenia is an absolute neutrophil (granulocyte)
count of less than 1500/µL in childhood, or below
3. Acquired Methemoglobinemia 1000/µL between ages 1 week and 2 years. During the
A number of compounds activate the oxidation of he- first few days of life, an absolute neutrophil count of
moglobin from the ferrous to the ferric state, forming less than 3500 cells/µL may be considered neutropenia.
methemoglobin. These include the nitrites and nitrates Neutropenia results from absent or defective gran-
(contaminated water), chlorates, and quinones. Drugs ulocyte stem cells, ineffective or suppressed myeloid
in this group are the aniline dyes, sulfonamides, ac- maturation, decreased production of hematopoietic cy-
etanilid, phenacetin, bismuth subnitrate, and potassium tokines (eg, granulocyte colony-stimulating factor
chlorate. Poisoning with a drug or chemical containing [G-CSF], granulocyte-macrophage colony-stimulating
one of these substances should be suspected in any in- factor [GM-CSF]), decreased marrow release, increased
fant or child who presents with sudden cyanosis. neutrophil destruction or consumption, or, in pseu-
Methemoglobin levels in such cases may be extremely doneutropenia, from an increased neutrophil marginat-
high and can produce anoxia, dyspnea, unconscious- ing pool (Table 27–5).
ness, circulatory failure, and death. Young infants and The most severe types of congenital neutropenia in-
newborns are more susceptible to acquired methemo- clude reticular dysgenesis (congenital aleukocytosis),
globinemia because their red cells have difficulty reduc- Kostmann syndrome (severe neutropenia with matura-
 HEMATOLOGIC DISORDERS / 881

Table 27–5. Classification of neutropenia of childhood.

Congenital neutropenia with stem cell abnormalities

Reticular dysgenesis
Cyclic neutropenia
Congenital neutropenia with abnormalities of committed myeloid progenitor cells
Neutropenia with immunodeficiency disorders (T cells and B cells)
Severe congenital neutropenia (Kostmann syndrome)
Chronic idiopathic neutropenia of childhood
Myelocathexis with dysmyelopoiesis
Chédiak–Higashi syndrome
Shwachman syndrome
Cartilage-hair hypoplasia
Dyskeratosis congenita
Fanconi anemia
Organic acidemias (eg, propionic, methylmalonic)
Glycogenosis Ib
Osteopetrosis
Acquired neutropenias affecting stem cells
Malignancies (leukemia, lymphoma) and preleukemic disorders
Drugs or toxic substances
Ionizing radiation
Aplastic anemia
Acquired neutropenias affecting committed myeloid progenitors and/or survival of mature neutrophils
Ineffective granulopoiesis (vitamin B12, folate, and copper deficiency)
Infection
Immune (neonatal alloimmune or autoimmune; autoimmune or chronic benign neutropenia of childhood)
Hypersplenism

tion defect in the marrow progenitor cells), Shwachman risk is increased when the absolute neutrophil count is
syndrome (neutropenia with pancreatic insufficiency), less than 500/µL, the actual susceptibility is variable
neutropenia with immune deficiency states, cyclic neu- and depends on the cause of neutropenia, marrow re-
tropenia, and myelocathexis or dysgranulopoiesis. Ge- serves, and other factors. The most common types of
netic mutations for Chédiak–Higashi syndrome and infection include septicemia, cellulitis, skin abscesses,
Shwachman syndrome have recently been identified. pneumonia, and perirectal abscesses. Sinusitis, aph-
Neutropenia may also be associated with storage and thous ulcers, gingivitis, and periodontal disease also
metabolic diseases and immunodeficiency states. The cause significant problems for these patients. In addi-
most common causes of neutropenia are viral infection tion to local signs and symptoms, patients may have
or drugs resulting in decreased production in the mar- chills, fever, and malaise. In most cases, the spleen and
row or increased destruction or both. Severe bacterial liver are not enlarged. Staphylococcus aureus and gram-
infections may be associated with neutropenia. Al- negative bacteria are the most common pathogens.
though rare, neonatal alloimmune neutropenia can be
severe and associated with increased risk for infection. B. LABORATORY FINDINGS
Autoimmune neutropenia in the mother can result in Neutrophils are absent or markedly reduced in the pe-
passive transfer of antibody to and neutropenia in the ripheral blood smear. In most forms of neutropenia or
neonate. Malignancies, osteopetrosis, marrow failure agranulocytosis, the monocytes and lymphocytes are
syndromes, and hypersplenism are not usually associ- normal and the red cells and platelets are not affected.
ated with isolated neutropenia. The bone marrow usually shows a normal erythroid se-
ries, with adequate megakaryocytes but a marked re-
Clinical Findings duction in the myeloid cells or a significant delay in
maturation of this series. Total cellularity may be de-
A. SYMPTOMS AND SIGNS creased.
Acute severe bacterial or fungal infection is the most In the evaluation of neutropenia (eg, persistent, in-
significant complication of neutropenia. Although the termittent, cyclic), careful attention should be paid to
882 / CHAPTER 27

the duration and pattern of neutropenia, the types of Patients with Kostmann syndrome also have a potential
infections and their frequency, and phenotypic abnor- for leukemia. Recombinant hematopoietic hormones
malities on physical examination. A careful family his- (ie, G-CSF) increase peripheral counts and decrease in-
tory and blood counts from the parents are useful. If an fectious complications.
acquired cause, such as viral infection or drug, is not
obvious and no other primary disease is present, white
Ambruso DR et al: Infectious and bleeding complications in pa-
blood cell counts, white cell differential, and platelet tients with glycogenesis Ib. Am J Dis Child 1985;139:
and reticulocyte counts should be completed once or 691 [PMID: 3860000].
twice weekly for 4–6 weeks to determine the possibility Ancliff PJ et al: Long-term follow-up of granulocyte colony-stimu-
of cyclic neutropenia. Bone marrow aspiration and lating factor receptor mutations in patients with severe con-
biopsy are most important to characterize the morpho- genital neutropenia: Implications for leukaemogenesis and
logic features of myelopoiesis. Measuring the neu- therapy. Br J Haematol 2003;120:685 [PMID: 12588357].
trophil counts in response to steroid infusion will docu- Ancliff PJ et al: Mutations in ELA2 gene encoding neutrophil elas-
ment the marrow reserves. Tests for specific causes of tase are present in most patients with sporadic severe congeni-
neutropenia include measurement of neutrophil anti- tal neutropenia but only in some patients with the familial
form. Blood 2001;98:2645 [PMID: 11675333].
bodies, immunoglobulin levels, antinuclear antibodies,
Dale DC et al: A randomized controlled phase III trial of recombi-
and lymphocyte phenotyping to detect immunodefi- nant human granulocyte colony-stimulating factor (filgras-
ciency states. Cultures of bone marrow are important tim) for treatment of severe chronic neutropenia. Blood
for defining the numbers of stem cells and progenitors 1993;81:2496 [PMID: 8490166].
committed to the myeloid series or the presence of cy- Dale DC et al: Mutations in the gene encoding neutrophil elastase
totoxic lymphocytes or humoral inhibitory factors. Cy- in congenital and cyclic neutropenia. Blood 2000;
tokine levels in plasma or mononuclear cells can be 96:2317 [PMID: 11001877].
measured directly. Some neutropenia disorders have ab- Kyono W, Coates TD: A practical approach to neutrophil disor-
normal neutrophil function. Recent studies have docu- ders. Pediatr Clin North Am 2002;49:929 [PMID:
mented abnormalities in the elastase gene in severe con- 12430620].
genital and cyclic neutropenias. Increased apoptosis in
marrow precursors or circulating neutrophils has been
described in several congenital disorders.
NEUTROPHILIA
Neutrophilia is an increase in the absolute neutrophil
Treatment count in the peripheral blood to greater than
7500–8500 cells/µL for infants, children, and adults.
Identifiable toxic agents should be eliminated, or asso- To support the increased peripheral count, neutrophils
ciated diseases (eg, infections) treated. Prophylactic an- may be mobilized from bone marrow storage or periph-
timicrobial therapy is not indicated for afebrile, asymp- eral marginating pools. Neutrophilia occurs acutely in
tomatic patients. Recombinant G-CSF and GM-CSF association with bacterial or viral infections, inflamma-
will increase neutrophil counts in most patients. Pa- tory diseases (eg, juvenile rheumatoid arthritis, inflam-
tients may be started on 3–5 µg/kg/d of G-CSF (filgras- matory bowel disease, Kawasaki disease), surgical or
tim) given subcutaneously or intravenously once a day. functional asplenia, liver failure, diabetic ketoacidosis,
Depending on the counts, the dose may be increased or azotemia, congenital disorders of neutrophil function
decreased. For patients with congenital neutropenia, (eg, chronic granulomatous disease and leukocyte ad-
the dose should be regulated to keep the absolute herence deficiency), and hemolysis. Drugs such as corti-
neutrophil count less than 10,000/µL. Some pa- costeroids, lithium, and epinephrine increase the blood
tients maintain adequate counts with G-CSF given neutrophil count. Corticosteroids cause release of neu-
2–3 times/week. trophils from the marrow pool and inhibit egress from
capillary beds and postpone apoptotic cell death. Epi-
nephrine causes release of the marginating pool. Acute
Prognosis neutrophilia has been reported after stress such as from
The prognosis varies greatly with the cause and severity electric shock, trauma, burns, surgery, and emotional
of the neutropenia. In severe cases with persistent upset. Tumors involving the bone marrow, such as
agranulocytosis, the prognosis is poor in spite of antibi- lymphomas, neuroblastomas, and rhabdomyosarcoma,
otic therapy; in mild or cyclic forms of neutropenia, may be associated with leukocytosis and the presence of
symptoms may be minimal and the prognosis for nor- immature myeloid cells in the peripheral blood. Infants
mal life expectancy excellent. Up to 50% of patients with Down syndrome have defective regulation of pro-
with Shwachman syndrome may develop aplastic ane- liferation and maturation of the myeloid series and may
mia, myelodysplasia, or leukemia during their lifetime. develop neutrophilia. At times this process may affect
 HEMATOLOGIC DISORDERS / 883

other cell lines and mimic myeloproliferative disorders Clinical Findings

or acute leukemia.
The neutrophilias must be distinguished from Recurrent bacterial or fungal infections are the hall-
myeloproliferative disorders such as chronic myeloge- mark of neutrophil dysfunction. Although many pa-
nous leukemia and juvenile chronic myelogenous tients will have infection-free periods, episodes of pneu-
leukemia. In general, abnormalities involving other cell monia, sinusitis, cellulitis, cutaneous and mucosal
lines, the appearance of immature cells on the blood infections (including perianal or peritonsillar abscesses),
smear, and the presence of hepatosplenomegaly are im- and lymphadenitis are frequent. As with neutropenia,
portant differentiating characteristics. aphthous ulcers of mucous membranes, severe gingivi-
tis, and periodontal disease are also major complica-
tions. In general, S aureus, along with gram-negative or-
DISORDERS OF NEUTROPHIL ganisms, is commonly isolated from infected sites;
FUNCTION other organisms may be specifically associated with a
defined neutrophil function defect. In some disorders,
Neutrophils play a key role in host defenses. Circulat- fungi account for an increasing number of infections.
ing in capillary beds, they adhere to the vascular en- Deep or generalized infections such as osteomyelitis,
dothelium adjacent to sites of infection and inflamma- liver abscesses, sepsis, meningitis, and necrotic or even
tion. Moving between endothelial cells, the neutrophil gangrenous soft tissue lesions occur in specific syn-
migrates toward the offending agent. Contact with a dromes (eg, leukocyte adherence deficiency or chronic
microbe that is properly opsonized with complement or granulomatous disease). Patients with severe neutrophil
antibodies triggers ingestion, a process in which cyto- dysfunction may die in childhood from severe infec-
plasmic streaming results in the formation of tions or associated complications. Table 27–6 summa-
pseudopods that fuse around the invader, encasing it in rizes pertinent laboratory findings.
a phagosome. During the ingestion phase, the oxidase
enzyme system assembles and is activated, taking oxy-
gen from the surrounding medium and reducing it to Treatment
form toxic oxygen metabolites critical to microbicidal
activity. Concurrently, granules from the two main The mainstays of management of these disorders re-
classes (azurophil and specific) fuse and release their main the anticipation of infections and aggressive at-
contents into the phagolysosome. The concentration of tempts to identify the foci and the causative agents.
toxic oxygen metabolites (eg, hydrogen peroxide, Surgical procedures to achieve these goals may be both
hypochlorous acid, hydroxyl radical) and other com- diagnostic and therapeutic. Broad-spectrum antibiotics
pounds (eg, proteases, cationic proteins, cathepsins, de- covering the range of possible organisms should be ini-
fensins) increases dramatically, resulting in the death tiated without delay, switching to specific antimicrobial
and dissolution of the microbe. Complex physiologic agents when the microbiologic diagnosis is made.
and biochemical processes subserve and control these When infections are unresponsive or they recur, granu-
functions. Defects in any of these processes may lead to locyte transfusions may be helpful.
inadequate cell function and an increased risk of infec- Chronic management includes prophylactic antibi-
tion. otics. Trimethoprim–sulfamethoxazole and other an-
tibiotic compounds enhance the bactericidal activity of
neutrophils from patients with chronic granulomatous
Classification disease. Some patients with Chédiak–Higashi syn-
Table 27–6 summarizes congenital neutrophil function drome improve clinically when given ascorbic acid. Re-
defects. Recently described is a syndrome of severe neu- combinant γ-interferon has been shown to decrease the
trophil dysfunction and severe infections associated number and severity of infections in patients with
with a mutation in a GTPase signaling molecule, Rac2. chronic granulomatous disease. Demonstration of this
Other congenital or acquired causes of mild to moder- activity with one patient group raises the possibility
ate neutrophil dysfunction include metabolic defects that cytokines, growth factors, and other biologic re-
(eg, glycogen storage disease, diabetes mellitus, renal sponse modifiers may be helpful in other conditions in
disease, hypophosphatemia), viral infections, and cer- preventing recurrent infections. Bone marrow trans-
tain drugs. Neutrophils from newborn infants have ab- plantation has been attempted in most major congeni-
normal adherence, chemotaxis, and bactericidal activ- tal neutrophil dysfunction syndromes, and reconstitu-
ity. Cells from patients with thermal injury, trauma, tion with normal cells and cell function has been
and overwhelming infection have defects in cell motil- documented. Combining genetic engineering with au-
ity and bactericidal activity similar to those seen in tologous bone marrow transplantation may provide a
neonates. future strategy for curing these disorders.
884 / CHAPTER 27

Table 27–6. Classification of congenital neutrophil function deficits.

Disorder Clinical Manifestations Functional Defect Biochemical Defect Inheritance

Chédiak–Higashi Oculocutaneous albinism, Neutropenia. Neutrophils, Unknown. Alterations in Autosomal-reces-
syndrome photophobia, nystagmus, monocytes, lymphocytes, membrane fusion with for- sive
ataxia. Recurrent infections platelets, and all granule- mation of giant granules.
of skin, respiratory tract, containing cells have giant Other biochemical abnor-
and mucous membranes granules. Most significant malities in cAMP and
with gram-positive defect is in chemotaxis. cGMP, microtubule assem-
and gram-negative organ- Also milder defects in micro- bly.
isms. Many die during bicidal activity and degranu-
lymphoproliferative phase lation.
with hepatomegaly, fever.
This may be a viral-associ-
ated hemophagocytic syn-
drome secondary to
Epstein–Barr virus infection.
Older patients may develop
degenerative CNS disease.
Leukocyte Recurrent soft tissue infec- Neutrophilia. Diminished ad- Absence or partial defi- Autosomal-reces-
adherence tions, including gingivitis, herence to surfaces, lead- ciency of CD11/CD18 cell sive
deficiency I otitis, mucositis, periodon- ing to decreased surface adhesive glycopro-
titis, skin infections. De- chemotaxis. teins.
layed separation of the cord
in newborn and problems
with wound healing.
Leukocyte Recurrent infections, men- Neutrophilia. Deficient “roll- Deficient fucosyl transfer- Autosomal-reces-
adherence tal retardation, craniofacial ing” interaction with endo- ase results in deficient sialyl sive
deficiency II abnormalities, short stature. thelial cells. Red cells have Lewis X antigen, which in-
Bombay phenotype. teracts with P selectin on
endothelial cell to establish
neutrophil rolling, a pre-
requisite for adherence and
diapedesis.
Chronic Recurrent purulent infec- Neutrophilia. Neutrophils A number of molecular de-
granuloma- tions with catalase-positive demonstrate deficient bac- fects in oxidase compo-
tous disease bacteria and fungi. May in- tericidal activity but normal nents. Absent cytochrome
volve skin, mucous mem- chemotaxis and ingestion. b558 with decreased expres-
branes. Also develop deep Defect in the oxidase enzyme sion of either (1) or (2):
infections (lymph nodes, system, resulting in absence (1) gp91-phox (1) X-linked (60–
lung, liver, bones) and or diminished production of 65% of cases).
sepsis oxygen metabolites (2) p22-phox (2) Autosomal re-
toxic to microbes. cessive (< 5%
of cases).
Absent p47-phox or p67- Autosomal-reces-
phox (cytosolic compo- sive (30% of
nents). cases).
Myeloperoxidase Generally healthy. Fungal Diminished capacity to en- Diminished or absent Autosomal-reces-
deficiency infections when deficiency hance hydrogen peroxide– myeloperoxidase; sive
associated with systemic mediated microbicidal posttranslational defect in
diseases (eg, diabetes) activity. processing protein.
Specific granule Recurrent skin and deep Decreased chemotaxis and Failure to produce specific Autosomal-reces-
deficiency tissue infections. bactericidal activity. granules or their contents sive
during myelopoiesis.
 HEMATOLOGIC DISORDERS / 885

Prognosis phil production is stimulated by the cytokine inter-

leukin-5. Allergies, particularly eczema, are the most
For mild to moderate defects, anticipation and conserv- common primary causes of eosinophilia in children.
ative medical management ensure a reasonable outlook. Eosinophilia also occurs in drug reactions, with tumors
For severe defects, excessive morbidity and significant (Hodgkin and non-Hodgkin lymphomas and brain tu-
mortality still exist. In some diseases, the development mors), and with immunodeficiency and histiocytosis
of noninfectious complications, such as the lymphopro- syndromes. Increased eosinophil counts are a promi-
liferative phase of Chédiak–Higashi syndrome or in- nent feature of many invasive parasitic infections. Gas-
flammatory syndromes in chronic granulomatous dis- trointestinal disorders such as chronic hepatitis, ulcera-
ease, may influence prognosis. tive colitis, Crohn disease, and milk precipitin disease
may be associated with eosinophilia. Increased blood
Ambruso DR et al: Human neutrophil immunodeficiency syn- eosinophil counts have been identified in several fami-
drome is associated with an inhibitory Rac2 mutation. Proc
Natl Acad Sci U S A 2000;97:4654 [PMID: 10758162].
lies without association with any specific illness. Rare
causes of eosinophilia include the hypereosinophilic
Etzioni A et al: Brief report: Recurrent severe infections caused by a
novel leukocyte adhesion deficiency. N Engl J Med syndrome, characterized by counts greater than
1992;327:1789 [PMID: 1279426]. 1500/µL and organ involvement and damage (he-
Kyono W, Coates TD: A practical approach to neutrophil disor- patosplenomegaly, cardiomyopathy, pulmonary fibro-
ders. Pediatr Clin North Am 2002;49:929 [PMID: sis, and central nervous system injury). This is a disor-
12430620]. der of middle-aged adults and is rare in children.
Eosinophilic leukemia has been described, but its exis-
LYMPHOCYTOSIS tence as a distinct entity is controversial.
Eosinophils are sometimes the last type of mature
From the first week up to the fifth year of life, lympho- myeloid cell to disappear after marrow ablative
cytes are the most numerous leukocytes in human chemotherapy. Increased eosinophil counts are associ-
blood. The ratio then reverses gradually to reach the ated with graft versus host disease after bone marrow
adult pattern of neutrophil predominance. An absolute transplantation, and elevations are sometimes docu-
lymphocytosis in childhood is associated with acute or mented during rejection episodes in patients who have
chronic viral infections, pertussis, syphilis, tuberculosis, solid organ grafts.
and hyperthyroidism. Other noninfectious conditions,
drugs, and hypersensitivity and serum sickness-like re-
actions cause lymphocytosis.
Fever, upper respiratory symptoms, gastrointestinal
complaints, and rashes are clues in distinguishing infec- BLEEDING DISORDERS
tious from noninfectious causes. The presence of en-
larged liver, spleen, or lymph nodes is crucial to the dif-
ferential diagnosis, which includes acute leukemia and Bleeding disorders may occur as a result of (1) quanti-
lymphoma. Most cases of infectious mononucleosis are tative or qualitative abnormalities of platelets, (2) quan-
associated with hepatosplenomegaly or adenopathy. titative or qualitative abnormalities in plasma coagu-
The absence of anemia and thrombocytopenia helps to lation factors, (3) vascular abnormalities, or (4)
differentiate these disorders. Evaluation of the mor- accelerated fibrinolysis. The coagulation cascade and
phology of lymphocytes on peripheral blood smear is fibrinolytic system are shown in Figures 27–4 and
crucial. Infectious causes, particularly infectious 27–5.
mononucleosis, are associated with atypical features in For the bleeding patient, obtaining a detailed per-
the lymphocytes such as basophilic cytoplasm, vacuoles, sonal and family history is the most critical aspect of
finer and less dense chromatin, and an indented nu- evaluation. The personal history should include bleed-
cleus. These features are distinct from the characteristic ing complications associated with dental interventions,
morphology associated with lymphoblastic leukemia. surgeries, suture placement and removal, and fractures.
Lymphocytosis in childhood is most commonly associ- A history of mucosal bleeding is suggestive of a platelet
ated with infections and resolves with recovery from the disorder, von Willebrand disease, dysfibrinogenemia, or
primary disease. vasculitis. Bleeding into muscles and joints suggests a
coagulation protein abnormality. A thorough physical
EOSINOPHILIA examination should be performed with special atten-
tion to the skin, oral and nasal mucosa, liver, spleen,
Eosinophilia in infants and children is an absolute and joints. Excessive bleeding may be due to a congeni-
eosinophil count greater than 300/µL. Marrow eosino- tal or acquired abnormality.
886 / CHAPTER 27

Vascular injury Screening tests to investigate patients for possible

Endothelial bleeding disorders should initially include the follow-
cell ing:
HK • PK Kallikrein TF
•
XII VIIa
1. Prothrombin time (PT) to screen for clotting ac-
XIIa tivity of factors VII, X, II, V, and fibrinogen.

Ca++
2. Activated partial thromboplastin time (aPTT) to
HK • XI XIa
Ca++
IX
screen for clotting activity of the following fac-

Ca++
tors: high-molecular-weight kininogen (HMWK),
VIII prekallikrein (PK), XII, XI, IX, VIII, X, V, II, and
fibrinogen.
VIIIa • IXa 3. Platelet count and size.
PL Ca++ X V 4. Functional assessment of vascular, platelet, von
Willebrand factor interaction by platelet function
analyzer-100 (PFA-100) or bleeding time, to
Xa • Va • II
Thrombin screen for small vessel integrity, platelet function,
PL Ca++
and von Willebrand disease.
XIII XIIIa
Fibrinogen fibrin cross-linked The following may be useful:
fibrin
1. Thrombin time (TT) to measure the generation
Figure 27–4. The procoagulant system and formation of fibrin following conversion of prothrombin to
of a fibrin clot. Vascular injury initiates the coagulation thrombin as well as the antithrombin effect of fib-
process by exposure of tissue factor (TF); the dashed rin-split products or heparin.
lines indicate thrombin actions in addition to clotting 2. Fibrinogen level. Additional tests to be performed
of fibrinogen. The finely dotted lines indicate the feed- in hospitalized patients include measurement of
back activation of the VII-TF complex by Xa and Ixa. Ab- fibrin degradation products (FDP) and euglobu-
breviations: HK = high-molecular-weight kininogen; PK lin lysis time (ELT), a measure of fibrinolysis.
= prekallikrein; Ca2+ = calcium; PL = phospholipid. (Re-
produced, with permission, from Goodnight SH, Hath-
away WE [eds]: Disorders of Hemostatis & Thrombosis: A Journeycake JM, Buchanan GR: Coagulation disorders. Pediatr
Rev 2003;24:83 [PMID: 12612185].
Clinical Guide, 2nd ed. McGraw-Hill, 2001.)

tPA uPA • uPAR

Figure 27–5. The fibrinolytic system. Solid ar-
PAI rows indicate activation; dotted line arrows indi-
Kallikrein cate inhibition. tPA = tissue plasminogen activa-
Plasminogen tor; uPA = urokinase; uPAR = cellular urokinase
receptor; PAI = plasminogen activator inhibitor;
TAFI FDP = fibrinogen–fibrin degradation products;
MMP = matrix metalloproteinases; ECM = extra-
Fibrinogen-fibrin Plasmin MMP cellular matrix; TAFI = thrombin activatable fibri-
nolysis inhibitor. (Reproduced, with permission,
from Goodnight SH, Hathaway WE [eds]: Disorders of
α2-Antiplasmin
Hemostatis & Thrombosis: A Clinical Guide, 2nd ed.
FDP ECM degradation
McGraw-Hill, 2001.
 HEMATOLOGIC DISORDERS / 887

ABNORMALITIES OF PLATELET sent. Rarely, concurrent infection with EBV or CMV

NUMBER OR FUNCTION may cause hepatosplenomegaly or lymphadenopathy,
simulating acute leukemia.
1. Idiopathic Thrombocytopenic B. LABORATORY FINDINGS
Purpura
1. Blood—The platelet count is markedly reduced
(usually < 50,000/µL and often < 10,000/µL), and
platelets frequently are of larger size on peripheral
ESSENTIALS OF DIAGNOSIS blood smear, suggesting bone marrow response and in-
& TYPICAL FEATURES creased production. The white blood count and differ-
ential count are normal. Anemia is not present unless
• Otherwise healthy child. hemorrhage has occurred.
• Decreased platelet count. 2. Bone marrow—The number of megakaryocytes
• Petechiae, ecchymoses. (which may be larger than normal) is increased. Ery-
throid and myeloid cellularity is normal.
3. Other laboratory tests—Because the PFA-100 and
bleeding time are generally prolonged if the platelet
count is less than 40,000/µL, these tests are not indi-
General Considerations cated. PTT and PT are normal and also not indicated.
Acute idiopathic thrombocytopenic purpura (ITP) is Platelet-associated IgG or IgM or both may be demon-
the most common bleeding disorder of childhood. It strated on the platelets or in the serum.
occurs most frequently in children age 2–5 years and
often follows infection with viruses such as rubella, Differential Diagnosis
varicella, measles, parvovirus, influenza, or EBV. Most Table 27–7 lists common causes of thrombocytopenia.
patients recover spontaneously within a few months. ITP is a diagnosis of exclusion. Bone marrow examina-
Chronic ITP (> 6 months’ duration) occurs in just tion should be performed if the history is atypical, if ab-
10–20% of patients with ITP. The thrombocytopenia normalities other than purpura and petechiae are pre-
results from immune clearance of platelets, which gen- sent on physical examination, if other cell lines are
erally have IgM or IgG on their surface. The spleen affected on the CBC, or possibly if corticosteroid ther-
plays a major role by forming antibodies and by seques- apy is to be administered. Family history or the finding
tering damaged platelets. of predominantly giant platelets on the peripheral
blood smear should be helpful in determining whether
Clinical Findings thrombocytopenia is hereditary.
A. SYMPTOMS AND SIGNS
Complications
Onset of ITP is usually acute, with the appearance of
multiple ecchymoses. Petechiae are often present, espe- Severe hemorrhage and bleeding into vital organs are
cially on the lips and buccal mucosa, and epistaxis is the feared complications of ITP. Intracranial hemor-
common. No other physical findings are usually pre- rhage is the most serious but rarely seen complication.

Table 27–7. Common causes of thrombocytopenia.

Destruction Decreased Production

Antibody-Mediated Coagulopathy Other Congenital Acquired
Idiopathic thrombocytic Disseminated intravascular Hemolytic—uremic Fanconi anemia Aplastic anemia
purpura coagulopathy syndrome Wiskott–Aldrich Leukemia and other
Infection Sepsis Thrombotic thrombocyto- syndrome malignancies
Immunologic diseases Necrotizing enterocolitis penic purpura Thrombocytopenia Vitamin B12 and
Thrombosis Hypersplenism with absent radii folate
Cavernous hemangioma Respiratory distress Metabolic disorders deficiencies
syndrome Osteopetrosis
Wiskott–Aldrich syndrome
888 / CHAPTER 27

The most important risk factors for hemorrhage are a tive only in Rh-positive patients with a functional
platelet count less than 10,000/µL and mean platelet spleen. The time required for platelet increase is slightly
volume less than 8 fL. longer than with steroids or IVIG. However, approxi-
mately 80% of children with acute or chronic ITP re-
Treatment spond well. Coombs-positive hemolysis may occur
transiently with an average hemoglobin concentration
A. GENERAL MEASURES decrease of 0.8 g/dL. Severe hemolysis occurs in 5% of
Most children require no therapy. Treatment should be treated children. Rho(D) immune globulin is substan-
given for bleeding, not just because the platelet count is tially less expensive than IVIG and is administered over
low. Aspirin and aspirin-containing drugs should not just a few minutes.
be administered. Trauma should be avoided. Platelet
transfusion should be avoided unless life-threatening E. SPLENECTOMY
bleeding is present and emergent splenectomy is to be Most children with chronic ITP have platelet counts
pursued, when other therapies are ineffective, or when a greater than 30,000/µL. Up to 70% of them recover to a
procedure such as a craniotomy is necessary. platelet count greater than 100,000/µL without therapy
within 1 year. For those who do not do so, corticoster-
B. CORTICOSTEROIDS oids, IVIG, and Rho(D) immune globulin are treatment
Patients with significant bleeding (ie, hematuria, hema- options that are usually successful. Splenectomy pro-
tochezia, epistaxis) or those with a platelet count of less duces permanent remission in 70–90% but should be
than 10,000/µL may benefit from prednisone at considered only after persistence of significant thrombo-
4 mg/kg orally per day for 3–5 days, decreasing to cytopenia for at least 1 year. Preoperative treatment with
2 mg/kg/d for a total of 14 days. The dosage is then ta- IVIG or Rho(D) immune globulin is indicated if the
pered and stopped. No further prednisone is given re- platelet count is decreased significantly. If the patient has
gardless of the platelet count unless significant bleeding been receiving corticosteroid therapy, the dose should be
recurs, at which time prednisone is administered in the appropriately increased during and after surgery. Antico-
smallest dose that will give symptomatic relief (usually agulant therapy is not indicated postoperatively, even
2.5–5 mg twice daily). The patient is then followed up though the platelet count may rise to 1 million/µL. The
until spontaneous remission occurs or until the patient risk of overwhelming infection is increased after splenec-
is a candidate for further therapy. tomy, particularly in the young child. Therefore, the pro-
cedure should be postponed, if possible, until the child is
C. INTRAVENOUS IMMUNE GLOBULIN at least age 5 years. Administration of pneumococcal and
As an alternative or adjunct to corticosteroid treatment, Haemophilus influenzae b vaccines at least 2 weeks prior
IVIG may be given to raise the platelet count in both to splenectomy is recommended. Meningococcal vaccine
acute and chronic ITP of childhood. The platelet re- is controversial. Penicillin prophylaxis should be started
sponse to IVIG is comparable to the response to postoperatively and continued for 1–3 years.
methylprednisolone (30 mg/kg/d for 7 days in acute
ITP). IVIG may be effective even when the patient is Prognosis
resistant to corticosteroids; responses are prompt and
may last for several weeks. Most patients receive Ninety percent of children with ITP will have a sponta-
1 g/kg/d for 1–3 days. IVIG is the treatment of choice neous remission. Features associated with the develop-
for severe, life-threatening bleeding. Platelets may be ment of chronic ITP include female sex, age older than
given simultaneously but are rapidly destroyed. IVIG- 10 years at presentation, a more insidious onset of
associated transient neurologic complications, includ- bruising, and the presence of other autoantibodies.
ing headache, nausea, and aseptic meningitis, occur in Teens with immune-mediated thrombocytopenia are at
one third of patients. These symptoms mimic those of higher risk for chronic autoantibody diseases.
intracranial hemorrhage and can necessitate radiologic
evaluation of the brain. A transient decrease in neu- Bolton-Maggs PHB et al: The nontreatment of childhood ITP (or
trophil number may also be seen. [The art of medicine consists of amusing the patient until na-
ture cures the disease]). Semin Thromb Hemost 2001;
D. RHO(D) IMMUNE GLOBULIN 27:269 [PMID: 11446660].
Buchanan G, Adix L: Outcome measures and treatment endpoints
The intravenous preparation of anti-D immunoglobu- other than platelet count in childhood idiopathic thrombocy-
lin is a polyclonal immunoglobulin that binds to the D topenic purpura. Semin Thromb Hemost 2001;27:
antigen on red blood cells, and the coated cells are 277 [PMID: 11446661].
cleared by the spleen as a result. The antibody-coated DiPaola JA, Buchanan GR: Immune thrombocytopenic purpura.
platelets are then not phagocytized. The drug is effec- Pediatr Clin North Am 2002:49:911 [PMID: 12430619].
 HEMATOLOGIC DISORDERS / 889

2. Thrombocytopenia in the Newborn dothelial system, have also been successful in raising the
platelet count. If alloimmunization is less severe, obser-
Thrombocytopenia is one of the most common causes vation alone may be all that is required.
of purpura in the newborn and should be considered Intracranial hemorrhage in a previous child sec-
and investigated in any newborn with petechiae or a ondary to alloimmune thrombocytopenia is the worst
significant bleeding tendency. A platelet count less than risk factor for severe fetal thrombocytopenia in a subse-
150,000/µL establishes a diagnosis of thrombocytope- quent pregnancy. Amniocentesis or chorionic villus
nia. This occurs in approximately 0.9% of unselected sampling to obtain fetal DNA for platelet antigen typ-
neonates. A platelet count less than or equal to ing is sometimes performed if the father is heterozygous
50,000/µL occurs in 0.1–0.2% of otherwise well for HPA-1a. If alloimmunization has occurred with a
neonates. A number of specific entities may be respon- previous pregnancy, ultrasound examination of the fetal
sible (see Table 27–7); however, one-half of such brain to detect hemorrhage should be obtained at
neonates have alloimmune thrombocytopenia. Infec- 20 weeks’ gestation and repeated regularly. Cordocen-
tion and intravascular coagulation syndromes are the tesis should be performed about 20 weeks’ gestation
most common causes of thrombocytopenia in sick full- with concentrated, irradiated, filtered, maternal
term newborns and in preterm newborns. In the well- platelets transfused to protect against fetal hemorrhage.
appearing newborn, antibody-mediated thrombocy- If the fetal platelet count is less than 100,000/µL, IVIG
topenia (alloimmune or maternal autoimmune), viral should be administered to the mother weekly. Delivery
syndrome, hyperviscosity, and major vessel thrombosis by elective cesarean section is recommended if the fetal
are frequent causes of thrombocytopenia. Management platelet count is less than 50,000/µL.
is directed toward alleviation of the specific cause.
Thrombocytopenia Associated
Thrombocytopenia Associated with Idiopathic Thrombocytopenic
with Platelet Alloimmunization Purpura in the Mother
Platelet alloimmunization occurs in one out of approxi- Infants born to mothers with ITP or antiphospholipid
mately 350 pregnancies. Unlike Rh incompatibility, antibodies may develop thrombocytopenia as a result of
30–40% of affected neonates are first-born. Thrombo- transfer of IgG antibody from the mother to the infant.
cytopenia is progressive over the duration of the gesta- Unfortunately, maternal platelet count, maternal an-
tion and worse in subsequent pregnancies. Alloimmu- tiplatelet antibody levels, and fetal scalp platelet counts
nization occurs when a platelet antigen of the infant are unreliable predictors of bleeding risk. Antenatal ad-
differs from that of the mother and when the mother is ministration of prednisone is generally begun once ma-
sensitized by platelets that cross from the fetal to the ternal platelet count falls less than 50,000/µL. IVIG
maternal circulation. In Caucasians, alloimmune has been administered but is not well-studied.
thrombocytopenia is most often due to HPA-1a incom- Most neonates with thrombocytopenia secondary to
patibility. Sensitization of a mother homozygous for passive transfer of maternal antibody do not bleed, and
human platelet antigen 1b against paternally acquired thus no specific treatment is indicated. The risk for in-
fetal HPA-1a antigen results in severe fetal thrombocy- tracranial hemorrhage is 0.2–2%. If petechiae or punc-
topenia in 1 in 1200 fetuses. Only 1 in 20 HPA-1a- ture wound bleeding ensues, a 1- to 2-week course of
positive fetuses of HPA-1a-negative mothers develop al- oral prednisone, 2 mg/kg/d, may be administered. If
loimmunization. The presence of antenatal platelet the platelet count remains consistently less than
antibodies on more than one occasion persisting in the 20,000/µL or if severe hemorrhage is present, IVIG
third trimester is predictive of severe neonatal thrombo- should be given. Platelet transfusions may not be help-
cytopenia. A weak or undetectable antibody does not ful without prior removal of antibody by exchange
exclude thrombocytopenia. Severe intracranial hemor- transfusion. The platelet nadir is usually on the fourth
rhage occurs in 10–30% of affected neonates as early as to sixth day of life. Because the antiplatelet IgG may be
20 weeks’ gestation. Petechiae or other bleeding mani- passed through breast milk, the platelet count should
festations are usually present shortly after birth. The be monitored. For infants with severe thrombocytope-
disease is self-limited, and the platelet count normalizes nia, full recovery may take 2–4 months.
within 4 weeks.
If severe alloimmunization occurs, platelet concen- Neonatal Thrombocytopenia
trate from the mother will be more effective than ran-
dom donor platelets in raising the platelet count. Type-
Associated with Infections
matched platelets from a donor are also effective. IVIG Thrombocytopenia is commonly associated with severe
infusions and steroids, which block the reticuloen- generalized infections during the newborn period. Be-
890 / CHAPTER 27

tween 50% and 75% of neonates with bacterial sepsis disease, and may replace the bleeding time for this pur-
are thrombocytopenic. Intrauterine infections such as pose. Platelet morphology is assessed with the light mi-
rubella, syphilis, toxoplasmosis, CMV, herpes simplex, croscope and electron microscope.
enteroviruses, and parvovirus are often associated with Platelet dysfunction may be inherited or acquired,
thrombocytopenia. but acquired platelet dysfunction is more common.
In addition to specific treatment for the underlying Persons with platelet function defects have skin and
disease, platelet transfusions may be indicated in severe mucosal bleeding similar to that occurring in persons
cases. Platelet concentrates in doses of 10 mL/kg will with thrombocytopenia. Platelet aggregation and de-
raise the platelet count by about 75,000/µL. granulation studies are not uniformly predictive of the
severity of clinical symptoms.
Thrombocytopenia Associated Persons with hereditary platelet dysfunction gener-
ally have a prolonged bleeding time with normal
with Giant Hemangiomas platelet number and morphology. The inherited disor-
(Kasabach–Merritt Syndrome) ders are due to defects in platelet–vessel interaction,
A rare but important cause of thrombocytopenic pur- platelet–platelet interaction, platelet granule defects,
pura in the newborn is giant hemangioma. These le- signal transduction, thromboxane and arachidonic acid
sions have a different histologic pattern from classic in- pathway dysfunction, and platelet coagulant–protein
fantile hemangiomas. They are more appropriately interaction.
termed “kaposiform hemangioendotheliomas,” or An example of a platelet–vessel wall dysfunction is
“tufted angiomas.” Platelet sequestration in the lesion Bernard–Soulier syndrome. In this condition the platelets
results in peripheral depletion of platelets. The bone are large and the platelet count slightly decreased. Because
marrow usually shows megakaryocytic hyperplasia. The the platelets lack or have defective glycoprotein 1b on
thrombocytopenia may be associated with hemolytic their surface they cannot adhere to the vessel wall von
anemia and DIC and result in fatal hemorrhage. Treat- Willebrand factor (vWF). Glycoproteins V and IX may
ment is indicated if a serious coagulopathy is present or also be deficient. An example of platelet–platelet dysfunc-
if the lesion exerts pressure on a vital structure or is cos- tion is Glanzmann thromboasthenia. In this condition
metically unacceptable. glycoprotein IIb–IIIa is deficient or defective so platelets
Surgery is usually contraindicated because of the risk cannot bind to fibrinogen to aggregate. Both conditions
of hemorrhage. Prednisone therapy has been associated are rare and transmitted in an autosomal recessive pattern.
with marked regression. Antiplatelet drugs and pentoxi- Bleeding is treated with platelet concentrates.
fylline may be helpful. If DIC is present, heparin or Two examples of platelet granule defects are storage
aminocaproic acid may be useful. Vascular emboliza- pool disease and Quebec platelet disorder. Persons with
tion may be an option. Interferon-α has also been storage pool disease are missing adenosine dinucleotide
shown to be efficacious, but its use is controversial. phosphate and adenosine trinucleotide phosphate from
When patients have been unresponsive to other treat- the dense granules and are usually deficient in dense
ment, chemotherapy has been given with some efficacy. granules. The dense granules are also deficient in Her-
mansky–Pudlak, Chédiak–Higashi, and Wiskott–
Bussel JB: Alloimmune thrombocytopenia in the fetus and neonate.
Aldrich syndromes. Deficient α-granules result in the
Semin Thromb Hemost 2001;27:245 [PMID: 11446658]. gray platelet syndrome. Quebec platelet disorder is as-
Hall GW: Kasabach–Merritt syndrome: Pathogenesis and manage- sociated with abnormal proteolysis of α-granule pro-
ment. Br J Haematol 2001;112:851 [PMID: 11298580]. teins, deficiency of platelet α-granule multimerin, and
Modlin JF et al: Case 25-2003: A newborn boy with petechiae and marked impaired aggregation with epinephrine.
thrombocytopenia. N Engl J Med 2003;349:691 [PMID: Signal transduction defects translate to primary de-
12917307]. granulation defects. Platelet dysfunction may also result
from abnormalities in the thromboxane and arachi-
donic acid pathways. Scott syndrome involves a defect
3. Disorders of Platelet Function in factor Va–Xa interaction on platelets. Platelet dys-
Platelet function has traditionally been screened by function may occur in persons with Down syndrome.
measurement of the bleeding time. If the bleeding time Acquired disorders of platelet function may occur
is prolonged, aggregation of platelets with agonists such secondary to uremia, cirrhosis, sepsis, myeloprolifera-
as adenosine diphosphate, collagen, arachidonic acid, tive disorders, acyanotic congenital heart disease, and
and ristocetin has been studied. Results are compared viral infections. Many pharmacologic agents decrease
with those of a normal control subject. A relatively new platelet function. The most common agents are aspirin,
instrument, the PFA-100, has become available for nonsteroidal anti-inflammatory agents, and synthetic
screening for platelet dysfunction and von Willebrand penicillins.
 HEMATOLOGIC DISORDERS / 891

Treatment muscles, and viscera. In contrast, patients with mild factor

VIII deficiency (5–40% factor VIII activity) bleed only at
Many individuals with hereditary and acquired platelet times of trauma or surgery. Those with moderate factor
function defects will respond to therapy with desmo- VIII deficiency (1– < 5% factor VIII activity) have inter-
pressin acetate. If this therapy is ineffective, treatment is mediate bleeding manifestations. The most crippling as-
with random donor platelets as discussed in the transfu- pect of factor VIII deficiency is the tendency to develop
sion medicine section. Recombinant VIIa has variable recurrent hemarthroses that incite joint destruction.
efficacy.
B. LABORATORY FINDINGS
Almeida AM et al: The use of recombinant factor VIIa in children
with inherited platelet function disorders. Br J Haematol
Persons with factor VIII deficiency have a prolonged
2003;121:477 [PMID: 12716372]. PTT. The bleeding time and PT are usually normal.
Hayward CP: Inherited platelet disorders. Curr Opin Hematol The diagnosis is confirmed by finding decreased factor
2003;10:362 [PMID: 12913791]. VIII activity with normal vWF activity. Cord blood can
be assayed accurately to determine factor VIII activity.
In two thirds of families of hemophilic patients, the
INHERITED BLEEDING DISORDERS females are carriers and some are mildly symptomatic.
Table 27–8 lists normal values for coagulation factors. Carriers of hemophilia can be detected by determina-
The more common factor deficiencies are discussed in tion of the ratio of factor VIII activity to vWF antigen
this section. All persons with bleeding disorders should and by molecular genetic techniques.
avoid exposure to medications that inhibit platelet
function. Participation in contact sports such as foot- Complications
ball and ice hockey should be considered in the context
of the severity of the bleeding disorder. Intracranial hemorrhage is the leading disease-related
cause of death among those with hemophilia. Up to
80% of intracranial hemorrhages are not trauma-associ-
1. Factor VIII Deficiency ated. Hemarthroses begin early in childhood and, if re-
(Hemophilia A, Classic Hemophilia) current, result in joint destruction. Large intramuscular
hematomas can lead to a compartment syndrome with
resultant muscle and nerve death. Each of these compli-
ESSENTIALS OF DIAGNOSIS cations is more common in persons with severe hemo-
& TYPICAL FEATURES philia but may be experienced by persons with moderate
or mild disease. A serious complication of hemophilia is
• Bruising, bleeding, and hemarthroses. the development of an acquired circulating antibody to
• Prolonged PTT. factor VIII after treatment with factor VIII concentrate.
Inhibitors or antibodies to factor VIII develop in
• Reduced factor VIII activity.
15–25% of severe factor VIII-deficient persons. The in-
hibitor is an antibody that may be amenable to desensi-
tization and immunosuppressive therapy. Factor IX
concentrate or activated prothrombin complex concen-
General Considerations trates may be of help in stopping hemorrhage. Recombi-
nant factor VIIa concentrate is an alternative.
Factor VIII activity is reported in units per milliliter, Therapy-related complications have included infec-
with 1 unit/mL equal to 100% of the factor activity tion with HIV and hepatitis B (until about 1985 in the
found in 1 mL of normal plasma. The normal range for United States) and hepatitis C (removed from most US
factor VIII activity is 50–150%. The disease occurs pre- preparations by 1990). By selecting donors seronegative
dominantly in males as an X-linked disorder. One third for these infections and by heat- or chemically treating
of cases are due to a new mutation. The incidence of the factor concentrates to inactivate viruses, the risks of
factor VIII deficiency is 1:5000 male births. these infections have been eliminated. Safe concentrates
are expensive and unobtainable in many parts of the
Clinical Findings world. Transmission of parvovirus and hepatitis A re-
mains a problem, even with concentrates that have had
A. SYMPTOMS AND SIGNS viral inactivation. Immunization with hepatitis A and
Patients with severe factor VIII deficiency (< 1% circulat- hepatitis B vaccines is recommended. Recombinant fac-
ing factor VIII activity) have frequent spontaneous bleed- tor VIII concentrates are available but some contain
ing episodes involving skin, mucous membranes, joints, pooled plasma-derived human albumin.
892 / CHAPTER 27

Table 27–8. Physiologic alterations in measurements of the hemostatic system.

Normal Fetus Preterm Term Infant Pregnancy Exercise Aging

Measurement Adults (20 wk) (25–32 wk) Infant (6 mo) (term) (acute) (70–80 y)
Platelets
Count µL/103 250 107–297 293 332 — 260 ↑18–40% 225
Size (fL) 9.0 8.9 8.5 9.1 — 9.6 ↑ —
Aggregation ADP N + ↓ ↓ — ↑ ↓15% —
Collagen N ↓ ↓ ↓ — N ↓60% N
Ristocetin N — ↑ ↑ — — ↓10% —
BT (min) 2–9 — 3.6±2 3.4±1.8 — 9.0±1.4 — 5.6
Procoagulant System
PTT* 1 4.0 3 1.3 1.1 1.1 ↓15% ↓
PT* 1.00 2.3 1.3 1.1 1 0.95 N —
TCT* 1 2.4 1.3 1.1 1 0.92 N —
Fibrinogen 278 (0.61) 96 (50) 250 (100) 240 (150) 251 (160) 450 (100) ↓25% ↑15%
mg/dL
II, U/mL 1 (0.7) 0.16 (0.10) 0.32 (0.18) 0.52 (0.25) 0.88 (0.6) 1.15 (0.68–1.9) — N
V, U/mL 1.0 (0.6) 0.32 (0.21) 0.80 (0.43) 1.00 (0.54) 0.91 ( 0.55) 0.85 (0.40–1.9) — N
VII, U/mL 1.0 (0.6) 0.27 (0.17) 0.37 (0.24) 0.57 (0.35) 0.87 (0.50) 1.17 (0.87–3.3) ↑200% ↑25%
VIIIc, U/mL 1.0 (0.6) 0.50 (0.23) 0.75 (0.40) 1.50 (0.55) 0.90 (0.50) 2.12 (0.8–6.0) ↑250% 1.50
vWF, U/mL 1.0 (0.6) 0.65 (0.40) 1.50 (0.90) 1.60 (0.84) 1.07 (0.60) 1.7 ↑75–200% ↑
IX, U/mL 1.0 (0.5) 0.10 (0.05) 0.22 (0.17) 0.35 (0.15) 0.86 (0.36) 0.81–2.15 ↑25% 1.0–1.40
X, U/mL 1.0 (0.6) 0.19 (0.15) 0.38 (0.20) 0.45 (0.3) 0.78 (0.38) 1.30 — N
XI, U/mL 1 (0.6) 0.13 (0.08) 0.2 (0.12) 0.42 (0.20) 0.86 (0.38) 0.7 — N
XII, U/mL 1.0 (0.6) 0.15 (0.08) 0.22 (0.09) 0.44 (0.16) 0.77 (0.39) 1.3 (0.82) — ↑16%
XIII, U/mL 1.04 0.30 0.4 0.61 (0.36) 1.04 (0.50) 0.96 — —
(0.55)
PreK, U/mL 1.12 0.13 (0.08) 0.26 (0.14) 0.35 (0.16) 0.86 (0.56) 1.18 — ↑27%
(0.06)
HK, U/mL 0.92 0.15 (0.10) 0.28 (0.20) 0.64 (0.50) 0.82 (0.36) 1.6 — ↑32%
(0.48)
Anticoagulant System
AT-U/mL 1.0 0.23 0.35 0.56 1.04 1.02 ↑14% N
α2MG, U/mL 1.05 0.18 (0.10) — 1.39 (0.95) 1.91 (1.49) 1.53 (0.85) — —
(0.79)
C1IN, U/mL 1.01 — — 0.72 1.41 — — —
PC, U/mL 1.0 0.10 0.29 0.50 0.59 0.99 N N
Total PS, U/mL 1.0 (0.6) 0.15 (0.11) 0.17 (0.14) 0.24 (0.1) 0.87 (0.55) 0.89 — N
Free, PS, U/mL 1.0 (0.5) 0.22 (0.13) 0.28 (0.19) 0.49 (0.33) — 0.25 — —
Heparin 1.01 0.10 (0.06) 0.25 (0.10) 0.49 ( 0.33) 0.97 (0.59) — — ↓15%
Cofactor II, U/mL (0.73)
TFPI, ng/mL 73 21 20.6 38 — — — —
Fibrinolytic System
Plasminogen U/mL 1.0 0.20 0.35 (0.20) 0.37 (0.18) 0.90 1.39 ↓10% N
t-PA, ng/mL 4.9 — 8.48 9.6 2.8 4.9 ↑300% N
α2-AP, U/mL 1.0 1.0 0.74 (0.5) 0.83 (0.65) 1.11 (0.83) 0.95 N N
PAI-1, U/mL 1.0 — 1.5 1.0 1.07 4.0 ↓5% N
Overall fibrinolysis N ↑ ↑ ↑ — ↓ ↑ ↓
Except as otherwise indicated values are mean ±2 SD or values in () are lower limits (–2SD or lower range); +, positive or present;
↓, decreased; ↑, increased; N, normal or no change; *, values as ratio or subject/mean of reference range; BT, bleeding time; TCT,
thrombin clotting time: PreK, prekallikrein; HK, high molecular weight kininogen; PC, protein C; PS, protein S; t-PA, tissue plasmino-
gen activator; PAI, plasminogen activator inhibitor; vWF, von Willebrand factor; AT, antithrombin; ADP, adenosine diphosphate; α2-
AP, α2-antiplasmin; α2-MG, α2-macroglobulin; C1IN, C1 esterase inhibitor; TFPI, tissue factor pathway inhibitor. Overall fibrinolysis is
measured by euglobulin lysis time.
Adapted with permission from Goodnight SH, Hathaway WE (eds): Disorders of Hemostasis & Thrombosis: A Clinical Guide. McGraw-
Hill, 2001.
 HEMATOLOGIC DISORDERS / 893

Treatment but PT and thrombin time are normal. Diagnosis is

made by assaying factor IX activity, and severity is de-
The aim of treatment is to correct the factor VIII activ- termined similarly to factor VIII deficiency.
ity to normal to prevent or stop bleeding. Some pa- Factor IX concentrate is the treatment product. Un-
tients with mild factor VIII deficiency may respond to like factor VIII, about 50% of the administered dose of
desmopressin; however, most patients require adminis- human-derived factor IX diffuses into the extravascular
tration of factor VIII concentrates to achieve hemosta- space. One unit of human-derived factor IX per kilo-
sis. Factor VIII is available as concentrates from human gram is expected to increase the factor IX level by 1%.
plasma or as a recombinant protein. The in vivo half- Recovery after recombinant factor IX concentrate is
life of factor VIII is generally 8–12 hours. Factor VIII more variable. Factor IX has a half-life of 20–22 hours
must be prescribed in units rather than vials. Non-life- in vivo. Cryoprecipitates and factor VIII concentrates
threatening hemorrhages are treated with about do not contain factor IX and should not be given.
20–30 units of factor VIII concentrate per kilogram of Virus-inactivating techniques for factor IX concentrates
body weight. This dosage will increase factor VIII activ- appear effective in eradicating HIV and hepatitis C. If
ity to 40–60%, respectively. Life-threatening hemor- recombinant factor IX concentrate is administered,
rhage is treated initially with approximately 50 units of strong consideration should be given to measuring a
factor VIII concentrate per kilogram of body weight, factor IX activity level to assess response because the in-
which will increase factor VIII activity by 100%. Subse- dividual response is highly variable. Only 1–3% of per-
quent doses are determined according to the situation. sons with factor IX deficiency form an inhibitor, but
The dose given is determined by vial size. Excess factor those who do may develop anaphylaxis when receiving
VIII concentrate should always be infused rather than factor IX concentrate. The prognosis for persons with
discarded. Monitoring the factor VIII activity may be factor IX deficiency is comparable to those with factor
warranted, depending on the situation. The majority of VIII deficiency. Gene therapy trials are ongoing.
moderately to severely affected persons with hemophilia
administer factor concentrate intravenously at home to
Bolton Maggs PH, Pasi KJ: Haemophilias A and B. Lancet
treat routine bleeding episodes. 2003;361:1801 [PMID: