Celiac disease
- 1. CELIAC DISEASECELIAC DISEASE Iman Galal, MDIman Galal, MD Assistant Professor Pulmonary MedicineAssistant Professor Pulmonary Medicine Ain Shams UniversityAin Shams University E-mail: [email protected]: [email protected]
- 2. Page 2 Objectives:Objectives: Historical aspectHistorical aspect DefinitionDefinition EpidemiologyEpidemiology PathogenesisPathogenesis Pathology & pathological classificationPathology & pathological classification Organ affection & clinical presentationOrgan affection & clinical presentation DiagnosisDiagnosis TreatmentTreatment Follow-upFollow-up PrognosisPrognosis ScreeningScreening
- 3. Page 3 Historical Aspect:Historical Aspect: 2,000 yrs ago, a Greek physician2,000 yrs ago, a Greek physician namednamed Aretaeus the CappadocianAretaeus the Cappadocian provided the 1provided the 1stst known description ofknown description of adult patients with celiac disease. Theadult patients with celiac disease. The namename ‘celiac’‘celiac’ is derived from theis derived from the Greek forGreek for ‘suffering in the bowels’.‘suffering in the bowels’. In October 5, 1887,In October 5, 1887, Dr. Samuel GeeDr. Samuel Gee,, an English Medical Lecturer gave toan English Medical Lecturer gave to medical students a lecture on themedical students a lecture on the ‘celiac affection’ & this constitutes the‘celiac affection’ & this constitutes the modern ‘rediscovery’ of celiac disease.modern ‘rediscovery’ of celiac disease.
- 4. Page 4 Definition:Definition: Celiac diseaseCeliac disease is an inflammatory autoimmuneis an inflammatory autoimmune condition of the small intestine, triggered bycondition of the small intestine, triggered by glutengluten inin genetically susceptiblegenetically susceptible individuals.individuals. It has diverse multi-systemic clinical manifestationsIt has diverse multi-systemic clinical manifestations rather than being a 1ry intestinal disease.rather than being a 1ry intestinal disease. Other terms for celiac disease include:Other terms for celiac disease include: Gluten SensitiveGluten Sensitive EnteropathyEnteropathy,, Non-Tropical SprueNon-Tropical Sprue && Celiac Sprue.Celiac Sprue.
- 5. Page 5 Epidemiology:Epidemiology: Celiac diseaseCeliac disease is more commonly found among whiteis more commonly found among white Europeans or those of European descent.Europeans or those of European descent. It is recognized as a common disorder that can be diagnosedIt is recognized as a common disorder that can be diagnosed at any age but commonly occurs at the age of 1-5 yrs old.at any age but commonly occurs at the age of 1-5 yrs old. Estimates vary from one in 5,000 to as many as one in everyEstimates vary from one in 5,000 to as many as one in every 300 individuals.300 individuals. Celiac disease isCeliac disease is 2020 times more common amongtimes more common among type 1type 1 diabetesdiabetes patients than in the general population, that itpatients than in the general population, that it became recommended to apply screening programs for celiacbecame recommended to apply screening programs for celiac disease among children recently diagnosed with type 1disease among children recently diagnosed with type 1 diabetes.diabetes.
- 6. Page 6 Pathogenesis:Pathogenesis: Genetic predispositionGenetic predisposition HLA-DQ(DQ2 &/or DQ8) genesHLA-DQ(DQ2 &/or DQ8) genes Environmental triggerEnvironmental trigger DietaryDietary Non-dietary??Non-dietary??
- 7. Page 7 Immune Response in Celiac DiseaseImmune Response in Celiac Disease
- 8. Page 8 Pathological Spectrum of Small IntestinePathological Spectrum of Small Intestine The classic pathology changes of celiac disease in the small bowel areThe classic pathology changes of celiac disease in the small bowel are categorized bycategorized by "Marsh Classification""Marsh Classification":: Marsh stage 0:Marsh stage 0: normal mucosanormal mucosa Marsh stage 1:Marsh stage 1: ↑↑ intra-epithelial lymphocytes >20/100 enterocytesintra-epithelial lymphocytes >20/100 enterocytes Marsh stage 2:Marsh stage 2: proliferation of the crypts of Lieberkuhnproliferation of the crypts of Lieberkuhn Marsh stage 3:Marsh stage 3: partial or complete villous atrophypartial or complete villous atrophy Marsh stage 4:Marsh stage 4: hypoplasia of the small bowel architecturehypoplasia of the small bowel architecture
- 9. Page 9 Pathology of Celiac DiseasePathology of Celiac Disease
- 10. Page 10 Clinical Presentation:Clinical Presentation: The most commonly recognized symptoms of celiac disease relate to theThe most commonly recognized symptoms of celiac disease relate to the improper absorption of food in the GIT.improper absorption of food in the GIT. Patient presents withPatient presents with diarrhea (<50%)diarrhea (<50%),, steatorrheasteatorrhea,, flatulenceflatulence,, distended abdomendistended abdomen,, weight lossweight loss, &, & generalized weakness.generalized weakness. Up toUp to 38 %38 % of patients areof patients are asymptomatic.asymptomatic. Unrecognized celiac disease may causeUnrecognized celiac disease may cause malabsorptionmalabsorption,, ironiron deficiency anemiadeficiency anemia,, osteoporosisosteoporosis,, osteomalaciaosteomalacia causingcausing bone fractures, pain & bony deformities.bone fractures, pain & bony deformities. People with celiac disease may also experiencePeople with celiac disease may also experience lactoselactose intoleranceintolerance due todue to lactase enzyme deficiency.lactase enzyme deficiency.
- 11. Page 11 Dermatitis HypertiformisDermatitis Hypertiformis Dermatitis herpetiformis (DH)Dermatitis herpetiformis (DH) is the skinis the skin manifestation of celiac disease.manifestation of celiac disease. It is anIt is an intensely itchy rashintensely itchy rash that occurs in the hands,that occurs in the hands, fingers, forearms, buttocks or scalp or anywhere on the body.fingers, forearms, buttocks or scalp or anywhere on the body. The rash typically consists of intensely itchy, small red dotsThe rash typically consists of intensely itchy, small red dots that may develop into blisters or pimples.that may develop into blisters or pimples. ApproximatelyApproximately 10%10% of patients with celiac disease have DH,of patients with celiac disease have DH, & it is estimated that& it is estimated that > 85%> 85% of patients with DH have celiacof patients with DH have celiac disease .disease .
- 12. Page 12 Dermatitis HypertiformisDermatitis Hypertiformis
- 13. Page 13 Celiac Disease & the Lung:Celiac Disease & the Lung: The association betweenThe association between celiac diseaseceliac disease && diffusediffuse interstitial pulmonary diseaseinterstitial pulmonary disease has been suspectedhas been suspected sincesince 1970.1970. Extrinsic allergic alveolitisExtrinsic allergic alveolitis was found in combinationwas found in combination with celiac disease & it may be considered that both thesewith celiac disease & it may be considered that both these diseases are based on one common immunologic disorder.diseases are based on one common immunologic disorder. The association betweenThe association between pulmonary hemosiderosispulmonary hemosiderosis && celiac disease have been reported 9 times in literature asceliac disease have been reported 9 times in literature as an extremely rare combination.an extremely rare combination.
- 14. Page 14 Other Presentations of Celiac Disease:Other Presentations of Celiac Disease: NeurologicalNeurological symptoms e.g.,symptoms e.g., peripheral neuropathyperipheral neuropathy,, ataxiaataxia oror epilepsy.epilepsy. Apthous ulcersApthous ulcers in the mouth is considered to be anin the mouth is considered to be an autoimmune disorder associated with celiac disease.autoimmune disorder associated with celiac disease. Dental enamel defectsDental enamel defects are frequent.are frequent. Patients with celiac disease may havePatients with celiac disease may have liver diseases.liver diseases. Abnormal liver testsAbnormal liver tests are common at diagnosis & usuallyare common at diagnosis & usually improve with treatment.improve with treatment.
- 15. Page 15 The Celiac IcebergThe Celiac Iceberg SymptomaticSymptomatic Celiac DiseaseCeliac Disease Silent CeliacSilent Celiac DiseaseDisease Latent Celiac DiseaseLatent Celiac Disease GeneticGenetic susceptibility:susceptibility: - DQ2, DQ8- DQ2, DQ8 Positive serologyPositive serology ManifestManifest mucosal lesionmucosal lesion NormalNormal MucosaMucosa
- 16. Page 16 Diagnosis: SerologyDiagnosis: Serology Serum IgA endomysial antibodies (EMA)Serum IgA endomysial antibodies (EMA) && serumserum IgA tissue transglutaminase (tTG) antibodiesIgA tissue transglutaminase (tTG) antibodies havehave bothboth sensitivitysensitivity && specificity > 95%.specificity > 95%. Testing forTesting for gliadin antibodiesgliadin antibodies is no longeris no longer recommended because of itsrecommended because of its low sensitivitylow sensitivity && specificityspecificity for celiac disease.for celiac disease. TheThe tTG antibodytTG antibody is theis the recommended singlerecommended single serologic testserologic test forfor celiac disease screening.celiac disease screening.
- 17. Page 17 Diagnosis: Small Bowel BiopsyDiagnosis: Small Bowel Biopsy Required to confirm the diagnosis of celiac disease.Required to confirm the diagnosis of celiac disease. Should also be considered in patients withShould also be considered in patients with negativenegative serologicserologic test results who are attest results who are at high riskhigh risk or in whom theor in whom the physicianphysician strongly suspectsstrongly suspects celiac disease.celiac disease. Mucosal changes may vary fromMucosal changes may vary from partialpartial toto total villoustotal villous atrophyatrophy, or may be characterized by, or may be characterized by subtle cryptsubtle crypt lengtheninglengthening oror increased epithelial lymphocytes.increased epithelial lymphocytes. To avoid false-negative results on endoscopic biopsy, it isTo avoid false-negative results on endoscopic biopsy, it is recommend to obtain at leastrecommend to obtain at least 4 tissue samples4 tissue samples to increaseto increase the sensitivity of the test.the sensitivity of the test.
- 18. Page 18 Endoscopy & Biopsy in Celiac DiseaseEndoscopy & Biopsy in Celiac Disease Normal small intestine Celiac Disease Normal Villi Villous Atrophy
- 19. Page 19 Diagnosis: HLA Genetic TypingDiagnosis: HLA Genetic Typing Antibody testing & HLA testing haveAntibody testing & HLA testing have similar accuracies.similar accuracies. TestTest SensitivitySensitivity SpecificitySpecificity HLA-DQ2HLA-DQ2 94%94% 73%73% HLA-DQ8HLA-DQ8 12%12% 81%81%
- 20. Page 20 Evaluation of Celiac DiseaseEvaluation of Celiac Disease
- 21. Page 21 Differential Diagnosis of Celiac Disease: Anorexia nervosaAnorexia nervosa Autoimmune enteropathyAutoimmune enteropathy Bacterial overgrowthBacterial overgrowth Collagenous sprueCollagenous sprue Crohn's diseaseCrohn's disease GiardiasisGiardiasis HIV enteropathyHIV enteropathy HypogammaglobulinemiaHypogammaglobulinemia Infective gastroenteritisInfective gastroenteritis Irritable bowel syndromeIrritable bowel syndrome Ischemic enteritisIschemic enteritis Lactose intoleranceLactose intolerance Pancreatic insufficiencyPancreatic insufficiency Soy protein intoleranceSoy protein intolerance Tropical sprueTropical sprue TuberculosisTuberculosis Whipple's diseaseWhipple's disease Zollinger-Ellison syndromeZollinger-Ellison syndrome Intestinal lymphomaIntestinal lymphoma
- 22. Page 22 Treatment Options:Treatment Options: Option #1:Option #1: Remove the genesRemove the genes Option #2:Option #2: Remove the grainsRemove the grains
- 23. Page 23 Dietary Management in Celiac DiseaseDietary Management in Celiac Disease At present, the only effective treatment isAt present, the only effective treatment is aa life-long gluten-free diet (GFD).life-long gluten-free diet (GFD). No medication exists that will preventNo medication exists that will prevent damage or prevent the body fromdamage or prevent the body from attacking the gut when gluten is present.attacking the gut when gluten is present. Strict adherence to the diet allows theStrict adherence to the diet allows the intestines to heal, leading to resolutionintestines to heal, leading to resolution of all symptoms in most cases and,of all symptoms in most cases and, depending on how soon the diet isdepending on how soon the diet is begun, can also eliminate the increasedbegun, can also eliminate the increased risk of complications.risk of complications.
- 24. Page 24 Dietary Management in Celiac DiseaseDietary Management in Celiac Disease
- 25. Page 25 Follow-Up:Follow-Up: Serologic markersSerologic markers (serum IgA tTG)(serum IgA tTG) used to monitorused to monitor compliancecompliance with GFD.with GFD. Antibody levelsAntibody levels return toreturn to normalnormal withinwithin 3-12 months3-12 months ofof starting a GFD but may take up tostarting a GFD but may take up to 30 months30 months if the initialif the initial titers are high.titers are high. Repetition of small bowel biopsyRepetition of small bowel biopsy 3-4 months3-4 months afterafter initiation of a GFD isinitiation of a GFD is not necessarynot necessary if the patient respondsif the patient responds appropriately to therapy.appropriately to therapy. If the patient does not respond as expected revise the→If the patient does not respond as expected revise the→ patient’s adherence to GFD, then the physician shouldpatient’s adherence to GFD, then the physician should consider other differential diagnosis.consider other differential diagnosis.
- 26. Page 26 Prognosis:Prognosis: Treating CD with a strictTreating CD with a strict GFDGFD is alwaysis always completely effective.completely effective. Gastrointestinal complaints & other symptoms resolve in almost allGastrointestinal complaints & other symptoms resolve in almost all patients.patients. Once the diet has been followed for several years, individuals with CD haveOnce the diet has been followed for several years, individuals with CD have similar mortality ratessimilar mortality rates as the general population. However, aboutas the general population. However, about 1010 %% of patients with celiac disease developof patients with celiac disease develop lymphomalymphoma && small bowelsmall bowel adenocarcinoma.adenocarcinoma. A few patients develop aA few patients develop a refractory typerefractory type of CD, in which the GFD noof CD, in which the GFD no longer seems effective.longer seems effective. Experts emphasize the need forExperts emphasize the need for lifelong adherence to the GFDlifelong adherence to the GFD toto avoid the long-term complications of this disorder. They point out thatavoid the long-term complications of this disorder. They point out that although the disease may have symptom-free periods if the diet is notalthough the disease may have symptom-free periods if the diet is not followed, silent damage continues to occur.followed, silent damage continues to occur. According to medical authorities, CDAccording to medical authorities, CD cannot be outgrowncannot be outgrown oror cured.cured.
- 27. Page 27 American Gastroenterological Association InstituteAmerican Gastroenterological Association Institute Recommendations for Celiac Disease ScreeningRecommendations for Celiac Disease Screening Consider testing in symptomatic patients at high riskConsider testing in symptomatic patients at high risk for Celiac Disease with any of the following conditions:for Celiac Disease with any of the following conditions: Autoimmune hepatitisAutoimmune hepatitis Down syndromeDown syndrome Premature onset of osteoporosisPremature onset of osteoporosis Primary biliary cirrhosisPrimary biliary cirrhosis Unexplained elevations in liver transaminase levelsUnexplained elevations in liver transaminase levels Unexplained iron deficiency anemiaUnexplained iron deficiency anemia Type 1 DMType 1 DM
- 28. Page 28 References:References: Presutti J,Cangemi J, Cassidy H, Hill D, Celiac Disease.Presutti J,Cangemi J, Cassidy H, Hill D, Celiac Disease. American Family Physician. December 15, 2007: 1795-American Family Physician. December 15, 2007: 1795- 1802.1802. Hadithi M, von Blomberg BM, Crusius JB, et al. (2007).Hadithi M, von Blomberg BM, Crusius JB, et al. (2007). "Accuracy of serologic tests and HLA-DQ typing for"Accuracy of serologic tests and HLA-DQ typing for diagnosing celiac disease". Ann. Intern. Med. 147: 294–diagnosing celiac disease". Ann. Intern. Med. 147: 294– 302.302. Hood J, Mason AMS. Diffuse pulmonary disease withHood J, Mason AMS. Diffuse pulmonary disease with transfer defect occurring in coeliac disease. Lancettransfer defect occurring in coeliac disease. Lancet 1970;1:445-47.1970;1:445-47.
Editor's Notes
- #8: After absorption in the small intestine these proteins interact with the antigen-presenting cells in the lamina propria causing an inflammatory reaction that targets the mucosa of the small intestine. Gluten is the term for the storage proteins of wheat. The alcohol-soluble fraction, called gliadin
- #10: A histologic section of normal jejunum is seen in the upper left panel. With the dissecting microscope these villi have the appearance of that seen in the lower left panel. A histologic section and a dissecting microscopic view of gluten enteropathy are shown in the upper right and lower right panels respectively.
- #19: Endoscopic and biopsy findings in patients with and without celiac disease. (A) High-definition endoscopic photo of normal small intestine. The villi are clearly visible with no evidence of atrophy or scalloping of the folds. (B) Biopsy specimen of normal small intestine (hematoxylin-eosin; original magnification, × 100). (C) PillCam image of small intestine in a patient with celiac disease, showing scalloping of the mucosal folds (arrows) characteristic of a malabsorption pattern. There is also evidence of villous atrophy compared with normal. (D) Biopsy specimen of small intestine in a patient with celiac disease (hematoxylin-eosin; original magnification, × 100). Note the loss of villous architecture.