Systemic juvenile idiopathic arthritis (Still's disease)

Overview

•Most severe JIA subtype; accounts for 10-15% of all JIA cases

•Autoinflammatory (innate immune dysregulation via IL-1 and IL-6), not classic autoimmune - RF and ANA typically negative

•Peak onset 1-5 years; equal sex distribution

Presentation

•Classic triad: quotidian fever + salmon-pink evanescent rash + arthritis

•Quotidian fever - daily spike ≥39°C, returns to baseline within 24 hours, often late afternoon/evening; must be documented for ≥2 weeks

•Salmon-pink evanescent rash - non-pruritic, macular/maculopapular on trunk and proximal limbs; appears during fever spikes, fades as temperature normalises; pathognomonic when present with quotidian fever

•Arthritis - ≥1 joint for ≥6 weeks; large joints (knees, wrists, ankles); morning stiffness; may lag behind systemic features by weeks to months

•Lymphadenopathy - generalised, non-tender

•Hepatosplenomegaly - due to systemic inflammation

•Serositis - pericarditis most common; also pleuritis/peritonitis; can cause chest pain

•Uveitis - acute symptomatic (painful red eye, photophobia); contrast with oligoarticular JIA which causes chronic asymptomatic uveitis

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Ask the parent to photograph the rash at home during a fever - it is commonly absent by the time of clinic review.

Investigations

•FBC - normocytic anaemia, neutrophilia, thrombocytosis

•ESR and CRP - markedly elevated; falling ESR in unwell child raises suspicion for MAS

•Serum ferritin - markedly elevated (>500 mcg/L characteristic); very high levels (often >10,000 mcg/L) suggest MAS

•ANA - negative; RF - negative (by definition)

•Blood cultures - exclude sepsis before starting immunosuppression

•LFTs and coagulation - hepatitis and coagulopathy suggest MAS

•Bone marrow aspirate - if haematological malignancy (ALL) cannot be excluded; must be done before starting corticosteroids

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Always exclude leukaemia before starting corticosteroids - steroids will partially treat ALL and mask the diagnosis, delaying potentially curative chemotherapy.

Management

•First-line (mild disease): naproxen or ibuprofen (NSAIDs) - relieve pain, stiffness, and fever; insufficient alone for moderate-severe disease

•First-line (oligoarticular flares): intra-articular corticosteroids (e.g. triamcinolone hexacetonide) - preferred over systemic steroids to avoid systemic side effects

•Second-line (moderate-severe systemic features/MAS): systemic corticosteroids (oral or IV methylprednisolone pulse)

•Second-line (persistent arthritis): methotrexate (DMARD) - steroid-sparing; weekly oral/SC; monitor FBC and LFTs; folate supplementation

•Third-line (biologic - IL-1 pathway): anakinra (IL-1 receptor antagonist) or canakinumab (anti-IL-1β) - preferred biologic for sJIA over TNF inhibitors

•Third-line (biologic - IL-6 pathway): tocilizumab (anti-IL-6 receptor) - effective for both systemic and articular features; licensed in children

Complications

•Macrophage activation syndrome (MAS) - most dangerous complication; occurs in up to 10%; uncontrolled macrophage/T-cell activation → cytokine storm → haemophagocytosis → pancytopenia, coagulopathy, DIC, liver failure; treatment: high-dose corticosteroids + ciclosporin

•AA amyloidosis - rare; chronic SAA production → deposits in kidneys/liver → proteinuria and renal failure; risk reduced by achieving remission

•Growth failure - IL-6 suppresses GH signalling; worsened by prolonged corticosteroids

•Osteoporosis - calcium and vitamin D supplementation for children on long-term steroids

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MAS red flags: persistent fever despite treatment; rapidly falling platelets or WBC; falling ESR despite clinical deterioration (fibrinogen consumption); ferritin rising sharply (often >10,000 mcg/L); new hepatosplenomegaly, coagulopathy, or encephalopathy. This is a medical emergency.

Prognosis

•Monocyclic - single episode then sustained remission (most favourable)

•Polycyclic - recurrent flares with periods of remission

•Persistent - continuous disease into adulthood; greatest risk of MAS and amyloidosis

•MAS remains the leading cause of mortality in sJIA; early biologic therapy (anti-IL-1/IL-6) has significantly improved outcomes

ILAR Diagnostic Criteria

•Arthritis in ≥1 joint with, or preceded by, fever ≥2 weeks (quotidian for ≥3 days) PLUS ≥1 of:

•Evanescent erythematous rash

•Generalised lymphadenopathy

•Hepatomegaly or splenomegaly (or both)

•Serositis

•Exclusions: no psoriasis; no HLA-B27-associated disease; RF negative on two occasions ≥3 months apart