Juvenile Idiopathic Arthritis

Juvenile Idiopathic Arthritis (JIA) is chronic inflammatory arthritis in children.

• Definition: Arthritis in children under 16, lasting greater than 6 weeks, with no other cause.
• Incidence: 1-4 per 10,000 children.
• Classification: ILAR classification (7 subtypes).

Pathophysiology of Joint Damage

• Chronic synovitis leads to pannus formation.
• Pannus erodes cartilage and subchondral bone.
• Joint destruction progresses if inflammation uncontrolled.

Growth Disturbance Mechanism

• Early Phase: Chronic inflammation causes hyperemia around physis.
• Hyperemia increases blood flow → physeal overgrowth → limb lengthening.
• Late Phase: Prolonged inflammation damages physeal chondrocytes.
• Physeal damage → premature closure → limb shortening.
• Net Effect: Often initial lengthening followed by shortening.

Common Joint Involvement

• Knee: Most commonly affected. Valgus deformity, flexion contracture.
• Hip: Flexion-adduction contracture, coxa valga.
• Cervical Spine: C1-C2 instability in severe polyarticular JIA.

The topic flags uveitis as the key extra-articular complication (the OAFY risk factors, slit-lamp referral, "regular screening"), but the nature of the disease and the screening logic are worth developing — it is the single most important reason JIA is co-managed with ophthalmology, and a recurrent exam point.

What it is. The classic JIA-associated eye disease is a chronic anterior uveitis (chronic iridocyclitis), often bilateral. Critically, it is typically asymptomatic and "white" — no pain, redness or photophobia — so the eye looks normal while sight-threatening inflammation progresses silently. This is the opposite of the acute, symptomatic anterior uveitis seen in HLA-B27 enthesitis-related arthritis (a painful red photophobic eye). The asymptomatic nature is exactly why screening, not symptoms, drives detection.

Who is at highest risk (the OAFY card). Young, ANA-positive, oligoarticular girls within the first few years of disease carry the greatest risk; risk is highest early and falls with time, but persists for years and is independent of joint disease activity (the eyes can be inflamed while the joints are quiet).

Screening. Asymptomatic high-risk children need regular slit-lamp examination by ophthalmology, with frequency risk-stratified by subtype, ANA status, age at onset and disease duration — as often as roughly every 3 months in the highest-risk early ANA-positive oligoarticular child, spacing out as risk declines, and continued for years after arthritis settles.

Complications if missed. Posterior synechiae, band keratopathy, cataract, glaucoma, macular oedema and permanent vision loss.

Treatment. Topical corticosteroids plus a mydriatic first; for steroid-dependent or refractory disease, systemic methotrexate and then an anti-TNF biologic. A high-yield distinction: the monoclonal antibodies adalimumab and infliximab are effective for uveitis, whereas etanercept is not — so the choice of biologic is driven partly by eye involvement.

• Aggressive Physiotherapy: Essential to maintain gains.
• Splinting: Night splints to prevent recurrence.
• Continue Medical Therapy: Do not stop biologics/DMARDs.
• Rheumatology Co-management: Essential.
• Monitor for Recurrence: Contractures can recur.

• Biologics Era: Dramatically improved outcomes.
• Oligoarticular: Best prognosis.
• RF+ Polyarticular: Worse prognosis, similar to adult RA.
• Systemic: Variable, can be severe.

Global epidemiology

• JIA is the most common chronic inflammatory rheumatic disease of childhood. Population-based studies show wide variation: incidence roughly 1.6-23 per 100,000/year and prevalence 3.8-400 per 100,000.
• Oligoarticular onset predominates in European/North American cohorts; systemic and polyarticular onset are relatively more common in parts of Asia, Africa and Latin America.
• Female predominance overall (especially ANA-positive oligoarticular and uveitis); enthesitis-related arthritis is more common in older boys.

Major guidelines — side by side

Registry & long-term data

• Pharmacovigilance registries (e.g. German BiKeR, UK BSPAR-ETN/BCRD, US CARRA Registry, Pharmachild/PRINTO) track biologic safety — malignancy and serious-infection signals have been reassuring at population scale.
• Joint-replacement registries show end-stage arthroplasty for JIA is now uncommon; when performed, survivorship is good but technically demanding (small implants, deformity, osteopenia).

High- vs limited-resource practice variation

• Well-resourced settings: early methotrexate, prompt biologic access, protocolised slit-lamp uveitis screening, MDT (rheumatology, ophthalmology, physiotherapy, orthopaedics, psychology), structured adolescent transition to adult services.
• Limited-resource settings: delayed diagnosis, reliance on NSAIDs/steroids and methotrexate due to biologic cost/availability, higher burden of established deformity, contractures and growth disturbance at presentation — raising the relative role of orthopaedic soft-tissue and reconstructive surgery.
• Universal priorities: control inflammation early, screen the eyes, preserve growth and function, and assess the cervical spine and TMJ before any anaesthetic in polyarticular disease.

• Classification in flux: A PRINTO consensus is moving toward a biology-based system (e.g. systemic JIA, RF-positive arthritis, enthesitis/spondylitis-related, early-onset ANA-positive arthritis) that may eventually replace the descriptive ILAR categories. Exam answers should acknowledge ILAR as current standard while noting the proposed revision.
• Systemic JIA as an autoinflammatory disease: Increasingly viewed as IL-1/IL-6-driven autoinflammation rather than classic autoimmune arthritis, supporting first-line IL-1/IL-6 blockade and a possible "window of opportunity" for early biologics.
• When to start biologics: Debate between early aggressive biologic use to prevent damage versus a step-up strategy after methotrexate failure, balancing cost, access and long-term safety.
• Treatment de-escalation: Optimal timing and method of tapering biologics after sustained remission remain unresolved; flare risk on withdrawal is significant.
• Surgical timing and choice: Diminishing role of synovectomy and arthroplasty in the biologic era; uncertainty over epiphysiodesis timing for inflammation-driven leg-length discrepancy that may partially self-correct once disease is controlled.
• Macrophage activation syndrome (MAS): A life-threatening complication of systemic JIA; thresholds for diagnosis and the role of anakinra in treatment continue to evolve.

The controversies section names MAS as the life-threatening complication of systemic JIA but does not develop it — and it is a classic "spot-the-emergency" exam scenario, so it is worth setting out.

What it is. MAS is a form of secondary haemophagocytic lymphohistiocytosis (HLH) — an uncontrolled cytokine storm — that complicates systemic JIA (and adult-onset Still's disease, where the general HLH picture is developed in that topic). It may be the presenting feature or be triggered by infection, a disease flare or a medication change.

Clinical picture. Rapid deterioration: unremitting high fever (losing the quotidian pattern), hepatosplenomegaly, lymphadenopathy, encephalopathy / CNS dysfunction, bleeding and disseminated intravascular coagulation, progressing to multi-organ failure.

Laboratory hallmarks — and the paradoxes that catch people out:

• Markedly elevated ferritin — the hallmark; very high values are a major red flag.
• Falling cell counts — platelets, then white cells and haemoglobin (cytopenias from haemophagocytosis).
• A paradoxically falling ESR — fibrinogen is consumed, so the ESR drops while CRP and ferritin climb. A child who looks "less inflamed" by ESR may actually be deteriorating.
• Low fibrinogen, rising triglycerides, and rising transaminases / LDH (hepatic dysfunction and coagulopathy).
• Bone-marrow haemophagocytosis may be seen but is neither always present nor required for diagnosis.

The 2016 EULAR/ACR/PRINTO classification criteria for MAS in systemic JIA combine a febrile patient with a high ferritin plus two or more of: low platelets, high AST, high triglycerides, low fibrinogen.

Treatment. A medical emergency: high-dose corticosteroids (IV methylprednisolone), ciclosporin, and the IL-1 antagonist anakinra, with intensive-care support. Identify and treat any triggering infection.