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PAEDIATRIC RHEUMATOLOGY – STUDY OF INFLAMMATORY AND NON-

INFLAMMATORY DISORDERS OF CONNECTIVE TISSUE
Dr Monika Esser
Immunology Unit NHLS Tygerberg & Stellenbosch University
18 June 2015

Paediatric Rheumatology

Covers the spectrum of diseases in childhood which manifest frequently with joint disease as:

 Musculoskeletal conditions
 Arthritis
 Auto-inflammatory diseases
 Connective tissue disorder

and their relevant therapies and treatment options

The two lectures will address the following:

 Musculoskeletal conditions
 Arthritis specifically Juvenile Idiopathic Arthritis and differentials
 Auto-inflammatory diseases will only be discussed in detail as relevant to Still’s Disease or
sJIA.
 Other Connective Tissue Disorders will be referred to, but not discussed in detail – please
refer to relevant sections of the other Rheumatology lectures.

Joint Disease in Children

 Musculoskeletal (MSK) complaints are common presenting features in Paediatrics

 Is one of the commoner of the chronic diseases of childhood
 Frequently self-limited, some chronic or even life threatening
 History is useful – but not a good predictor of extent of complaint
 Hence complete and thorough examination is essential

Observing, touching, moving, functioning eg. LIMPING

LIMPING and important causes in children – many are emergencies

1. Septic arthritis
2. Osteomyelitis
3. ALL
4. Bone and joint malignancy - (Minor and often incidental trauma frequently on Hx)
5. Perthes disease
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6. Slipped upper femoral epiphysis

7. Irritable hip
8. Juvenile Idiopathic Arthritis

Septic arthritis

 Acute, hot, swollen joint/ fever of unknown origin

 Systemic features sometimes absent early on
 Severe pain with weight bearing
 ↑ inflammatory markers

Staph aureus commonly causative organism

Other questions – immune compromise, TB, trauma?

Poor response: ?Co-existing osteomyelitis, ? atypical organisms

 Rx – aspirate, culture, rinse, IV antibiotics

Osteomyelitis

 Onset can be more insidious than arthritis and ill-defined with

 Bone erythema and tenderness
 At multiple sites
 In infants remember possible co-existence with septic arthritis
 Bone scan indicated (initial X-rays normal) as periosteal bone elevation only at day 7 – 10
 Rx: antibiotics
 Chronic Multifocal Osteomyelitis ? – if atypical/ recurrent

Leukaemia – ALL

 Peak at 2 – 5 yrs, commonest malignancy of childhood,

 Survival now > 80%
 High risk are male sex, WCC load at diagnosis, cytogenic markers, age
 MSK – swelling, chronic bone pain not limited to joints and occurs also at rest, and systemic
features: fatigue, anaemia, weight loss
 Haematology urgently indicated – starting with FBC and smear

Bone/ soft tissue malignancy

 Osteosarcoma or Ewings may present with swelling around the knee

 Nocturnal bone pain
 ± co-existing with arthritis
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Legg-Calve-Perthes Disease

 Femoral head: Avascular necrosis

 Age 5 – 10 years, males > females
 Presenting with limp – may be painless or in hip or knee
 Up to 20% bilateral
 >6 years or if 50% femoral head involved: poorer outcome.

Slipped Capital Femoral Epiphyses (SCFE, SUFE)

 Adolescent males > females

 ↑ Risk: overweight, Down’s syndrome, hypothyroidism
 Limp, knee or hip pain (referred pain)
 X-ray: frog views
 Bilateral in 20%
 Avascular necrosis risk if not treated

Irritable hip/ transient synovitis

 Diagnosis of exclusion usually

 Commonly preceding viral infection
 Child relatively well
 Painless limp
 Examination – restricted hip rotation only
 US: small effusion possibly
 OPD treatment and follow up if well and afebrile

Age appropriate differential diagnoses

Red flags – for the child with a limp

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 Systemic features
 Bone/ joint pain with fever
 Persistent (night) pain
 Possible neglect/ symptoms not matching

Commonest Rheumatic Disease of Childhood: JIA (Juvenile Idiopathic Arthritis)

 Persistent Arthritis of unknown cause

 Lasting more than 6 weeks
 Onset age younger than 16 years
 Various subtypes with varying characteristics
 Different subtypes usually established within the first 6 months of illness

Juvenile Idiopathic Arthritis (ILAR 1997) (formerly juvenile chronic (EULAR) or rheumatoid (ACR)
arthritis)

Seven Main Groups

 Systemic Onset
 Oligo-arthritis
 Polyarthritis RF(-)
 Polyarthritis RF(+)
 Psoriatic Arthritis
 Enthesitis Arthritis
 Other – does not fit into any of above or fits into more than one group of the above

Pathogenesis
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 Idiopathic
 Complex auto-immune and genetic factors
 Superimposed environmental trigger
 Dysregulated Th1 and Th2 interaction
 Regulatory T-cells, complement, neutrophils, Dentritic cells
 Overproduction of TNF – alpha and TNF – alpha receptors in synovial tissue and fluid
 IL-1 and IL-6 especially in sJIA

Musculoskeletal Examination

 PGALS (Ref)
o Paediatric
o Gait
o Arms
o Legs
o Spine
 Detailed Joint exam

Also observe for:

 Vasculitis
 Uveitis/ Cataract
 Gottron’s papules and other features of Dermatomyositis
 Lupus rash
 Psoriatic rash/ nail changes

Juvenile Idiopathic Arthritis (ILAR 1997)

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Oligo-articular JIA

 Girls peak age at onset 1 – 3 years

 Chronic uveitis 20 – 30%
 High ESR, involvement of more than one joint, upper limb arthritis

 Boys, mostly > 8 years

 Lower limb, hip
 Enthesitis, tendinitis
 Inflammatory back pain
 Extra-articular inflammation (skin, eye, gut)
 Familial occurrence

*Juvenile spondylarthropathy
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 Arthritis with psoriasis or with dactylitis, nail changes, familial psoriasis

 Chronic uveitis

 Girls 5 – 7 years
 Arthritis in minimum 5 joints
 Small and large joints
 Uveitis 5%

Polyarticular JIA

Juvenile Onset of ‘Adult RA’

 Older girls > 8 years

 Arthritis in small and large joints
 Subcutaneous nodules
 Rapidly progressive erosive disease
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Systemic Onset JIA (Stills Disease)

 Male = Female
 Most severe form = Macrophage activation syndrome
 Median age 5 years
 Fluctuating temperature (quotidian) up to 40 degrees once or twice daily accompanied by a
rash usually and fever returns to below baseline
 Macular or urticarial rash salmon colour
 Arthritis (Polyarticular 60%, may start months after onset, severe in 30%)
 Serositis
 Hepatosplenomegaly, lymphadenopathy
 Acute phase response, raised Ferritin
 Systemic features: hence need to rule out other causes of fever

Important Differentials to JIA

?
Benign hypermobility

 Multiple hypermobile joints

 Associated with musculoskeletal pain
 No underlying connective tissue disorder (Marfan’s)
 Extreme variation of normal range of joint motion
 Diagnosis based on set criteria
 Predisposed to injury because of flexibility
 10 – 15% of young children (females > males)

“Growing pains” benign recurrent limb pain

 Up to 20% of children
 4 – 12 years of age
 Equal sex ratio
 Thigh or calf pain, usually evening or night, never morning, bilateral
 Physical exam normal, laboratory exam normal
 X-rays normal
 “Painful families”
 Responds to analgesia and massages
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Differential of JIA

Differential continue

 Reactive Arthritis?
o HLA B27 associated Shigella, Salmonella, Yersinia, Campylobacter, Chlamydia
o Post streptococcal
o Post viral (irritable hip)
 Benign Hypermobility Syndrome

Useful Investigation screen

 FBC and Differential

 ESR, CRP, Ferritin
 RF, Anti CCP, ANF, (HLA B27)
 Mantoux, CXR
 ASOT, Throat swab
 (Joint X-rays)
 Ultrasound, Bone scan
 Biopsy
 Uveitis Screen

Management

Multidisciplinary

 Ophthalmology
 Physiotherapy
 Occupational Therapy
 Social worker
 Orthopaedic Surgeon
 Dentist/ Maxillo Facial
 Support groups and patient organisations eg PRINTO
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Initial Management

 NSAIDS (mild disease and symptomatic relief only)

o Ibuprofen: 10mg/kg/dose (higher than regular)
o Naproxen/ Diclofenac/ Indomethacin
 Corticosteroids ?
o Short term
o Oral or IV initially
o NB: to prevent SIDE EFFECTS – Vit D, Calcium, Diet
 Intra-articular steroid option – especially for single joint
o But can inject multiple joints

Treatment Window of Opportunity

DMARDS

 Methotrexate
o First revolution in JIA
o Massive improvement in outcome
o Low toxicity
o 0.1 – 0.5mg/kg once a week, with Folic Acid
o Nausea and GIT side effects less in children
o Liver injury prevented with Folic Acid
o Monitor FBC and LFT 3 – 6 monthly
o Can start to wean after 6 months of inactive disease
 OTHER AGENTS
o Sulphasalazine, Chloroquine, Azathioprine, Leflunamide, Cyclosporin

Biologics

 Anti-TNF agents
o The second revolution
o Very effective, very expensive
 Etanercept: TNF receptor: FC fusion protein
 Infliximab: chimeric IgG1 monoclonal antibody to TNF-α
 Adalimumab: humanized monoclonal antibody to TNF-α

Other Biologics

 IL-1 antagonists: Anakinra

 IL-6 antagonists: Tocilizumab
 CTLA-4: Abatacept
 More to come …
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JIA Outcome

Mortality 0.29% - 0.86% (0.8% controls 1 – 24 years) > two thirds in systemic subtype

Cardiac, amyloidosis, infection, macrophage activation syndrome

JIA Outcome

Persistent arthritis > 10 years after onset

22 – 41% oligo-articular

45 – 50% poly-articular

27 – 48% systemic

Active disease in adults with a history of or persistent JIA

37 – 43% after mean disease duration 26.4 – 28.3 yr

Zak et al, Rheumatology 2000

Packham et al, Rheumatology 2002

Overall 30 to 60% of JIA patients are in remission when entering adulthood rates of remission reach
peak after 5 – 10 years of ‘end’ of disease, late relapses after prolonged (10 – 15 yrs) remission occur
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Undesirable Outcomes

 Growth failure
 Uneven limb – overgrowth
 Joint destruction
 Bone ankyloses
 Impaired vision/blindness

Message

 JIA is a chronic but manageable disease

 If however not managed effectively, the outcome can be devastating
 Children with joint symptoms should be seen and referred early to maximise chances of good
recovery

Examination Reference

 pGALS – paediatric Gait/Arms/Legs/Spine: rapid, easy MSK assessment

 www.arthritisresearchuk.org
 (credits for additional slides from C. Scott and E. Smith)