Juvenile Idiopathic Arthritis (JIA)

Juvenile idiopathic arthritis is a heterogeneous group of chronic inflammatory arthritides of unknown precise etiology beginning before age 16, lasting ≥6 weeks, and not explained by another condition. Chronic synovitis may lead to joint damage, growth disturbances, pain, disability, and extra‑articular complications (notably uveitis and macrophage activation syndrome in systemic disease).

Classification (ILAR Categories)

• Oligoarthritis: ≤4 joints in first 6 months (persistent or extended >4 joints after 6 months).
• Polyarthritis RF-negative: ≥5 joints, rheumatoid factor (RF) negative.
• Polyarthritis RF-positive: resembles adult seropositive RA (≥2 positive RF tests ≥3 months apart).
• Systemic JIA: arthritis with quotidian fever spikes (≥2 weeks) plus ≥1 of evanescent salmon rash, generalized lymphadenopathy, hepatosplenomegaly, or serositis.
• Enthesitis-related arthritis (ERA): arthritis and enthesitis (or combinations with sacroiliac tenderness/HLA-B27 positivity, onset in a boy >6 years, acute anterior uveitis, family history of HLA-B27–associated disease).
• Psoriatic arthritis: arthritis plus psoriasis, or arthritis plus ≥2 of dactylitis, nail pitting/onycholysis, psoriasis in first-degree relative.
• Undifferentiated: criteria for multiple categories or none.

Pathogenesis (Brief)

Multifactorial: genetic susceptibility (HLA alleles: e.g., HLA-DRB1, HLA-B27; non-HLA loci), dysregulated innate/adaptive immune responses (IL-1, IL-6, TNF pathways; JAK/STAT signaling), and environmental triggers (infections, microbiome shifts). Systemic JIA exhibits autoinflammatory features (IL‑1, IL‑6 driven).

Clinical Features

• Synovitis: joint swelling, warmth, limited motion (often painless early, especially in oligoarthritis). Morning stiffness, activity limitation.
• Growth abnormalities: limb length discrepancy (increased blood flow/overgrowth), micrognathia (TMJ involvement), generalized growth delay (chronic inflammation, steroids).
• Extra-articular: uveitis (chronic anterior; high risk in ANA‑positive oligoarticular and young onset), rash and fevers (systemic JIA), enthesitis (ERA), dactylitis (psoriatic), nail pitting (psoriatic).
• Systemic JIA: quotidian spiking fevers, evanescent macular rash, hepatosplenomegaly, lymphadenopathy, serositis (pleuritis, pericarditis).
• Red flag: persistent high fevers, cytopenias, ferritin surge, coagulopathy → assess for macrophage activation syndrome (MAS).

Macrophage Activation Syndrome (MAS)

Life‑threatening hyperinflammatory complication (overlaps with secondary HLH). Clues: unremitting fever (often when arthritis improving), falling ESR (with high CRP), cytopenias, hyperferritinemia, elevated triglycerides, low fibrinogen, liver dysfunction. Requires urgent immunomodulatory therapy (high‑dose steroids, IL‑1 blockade, sometimes cyclosporine).

Diagnosis

Clinical: chronic arthritis pattern + exclusion of alternative causes (infection, malignancy, other rheumatic diseases). No single diagnostic test.

Baseline Evaluation

• History: fever pattern, rash, morning stiffness, functional limitation, eye symptoms, family history (psoriasis, spondyloarthritis, IBD, uveitis).
• Physical: joint count (active/swollen/tender), enthesitis sites, growth parameters, rash, lymph nodes, organomegaly, nail changes.
• Labs (supportive / exclude other disease): CBC, ESR/CRP, liver panel, ferritin (systemic or MAS suspicion), ANA (uveitis risk stratification), RF (≥2 tests if polyarthritis), anti-CCP (prognostic in RF+ polyarthritis), HLA-B27 (suspected ERA), urinalysis (renal involvement, differential), TB screening before biologics.
• Imaging: baseline ultrasound or MRI (synovitis/effusion, early erosions, sacroiliitis in ERA). Radiographs for chronicity (joint space narrowing, erosions) as disease evolves.
• Ophthalmology: slit-lamp exam at baseline and scheduled intervals (see below).

Differential Diagnosis

Septic arthritis, osteomyelitis, leukemia/lymphoma, Henoch–Schönlein purpura (IgA vasculitis), reactive arthritis, Lyme disease, SLE, sarcoidosis, inflammatory bowel disease–associated arthritis, periodic fever syndromes, hypermobility with pain amplification.

Monitoring & Outcome Measures

• Treat-to-target: aim for clinical inactive disease (CID) or minimal disease activity (MDA) using validated composite scores (JADAS, cJADAS).
• Regular joint counts, functional assessment (CHAQ), growth and pubertal staging, imaging for high-risk joints (wrist, ankle, TMJ, sacroiliac).
• Eye screening: frequency based on risk (e.g., ANA+, oligoarticular onset <7 yrs: every 3–4 months; intermediate risk every 6 months; low risk annually).

Management Overview

Principles: early aggressive control to prevent damage, individualized by category and prognostic factors (polyarticular onset, early erosions, elevated inflammatory markers, RF/anti-CCP positivity, hip involvement, systemic features).

1. Symptomatic/Initial Therapy

• NSAIDs (e.g., naproxen, ibuprofen, indomethacin) for pain/stiffness; monotherapy sometimes adequate in mild persistent oligoarthritis. (Note: tadalafil is not an NSAID and is not used; likely a misreference.)
• Intra-articular corticosteroid injections (triamcinolone hexacetonide preferred) for limited joint involvement (especially knees, ankles, wrists) — may induce prolonged remission in oligoarticular JIA.

2. Conventional DMARDs

• Methotrexate (first-line systemic DMARD in polyarticular/extended oligoarthritis): 10–15 mg/m^2 weekly (up to 25 mg) SC or PO; add folic acid.
• Leflunomide alternative if methotrexate intolerant.
• Sulfasalazine for ERA (especially peripheral arthritis) if methotrexate insufficient.

3. Biologic / Targeted DMARDs

• TNF inhibitors (etanercept, adalimumab, infliximab, golimumab) for methotrexate inadequate response or poor prognostic factors.
• IL‑1 inhibitors (anakinra, canakinumab) and IL‑6 receptor inhibitor (tocilizumab) particularly effective in systemic JIA; also options in refractory polyarticular disease.
• Abatacept (T-cell costimulation modulator) for polyarticular JIA refractory to TNF inhibitors.
• JAK inhibitors (tofacitinib, upadacitinib) emerging options for refractory cases (observe age approvals and safety monitoring).
• Ustekinumab, secukinumab in select psoriatic/ERA categories.

4. Glucocorticoids

• Bridge therapy: short oral taper (e.g., prednisone) to control severe inflammation while awaiting DMARD effect.
• Systemic JIA flare or MAS: high-dose IV methylprednisolone pulses sometimes required.
• Minimize long-term systemic exposure to avoid growth suppression, metabolic complications.

5. Supportive & Multidisciplinary Care

• Physical and occupational therapy: maintain range of motion, muscle strength, function; individualized exercise programs.
• Nutritional support: optimize growth; calcium/vitamin D if steroid use.
• Psychosocial support, school accommodations, transition planning to adult care.
• Pain management: CBT strategies, address pain amplification syndromes.

6. Uveitis Screening & Management

• Silent chronic anterior uveitis risk highest in ANA+ early-onset oligoarticular and psoriatic forms.
• Scheduled slit-lamp exams per risk stratification; treat uveitis (topical steroids, mydriatics; escalate to systemic immunomodulators for refractory disease).

Vaccination Considerations

• Update age-appropriate immunizations before initiating biologics; avoid live vaccines during significant immunosuppression (consult current guidelines for specific agents).
• Annual influenza vaccination; consider pneumococcal vaccination updates.

Prognosis

Variable: many achieve remission, especially in persistent oligoarthritis; poorer outcomes with RF+ polyarthritis, hip/TMJ involvement, early erosions, systemic JIA with MAS episodes. Early treat-to-target DMARD/biologic strategies improve function, reduce deformity risk, and preserve quality of life.

Key Takeaways

• Early recognition + treat-to-target approach prevents irreversible joint damage and growth complications.
• Methotrexate remains cornerstone conventional DMARD; rapid escalation to biologics when targets unmet.
• Systemic JIA and MAS require vigilant monitoring and rapid cytokine-directed therapy.
• Regular ophthalmologic screening critical to prevent vision loss from uveitis.

Educational information only; management decisions should follow up-to-date pediatric rheumatology guidelines and individualized specialist assessment.