Juvenile Idiopathic Arthritis (JIA)

Disease course varies greatly; some patients experience mild, self-limiting disease, while others suffer severe, ongoing joint damage.

Introduction

• Definition: Juvenile idiopathic arthritis (JIA) encompasses various forms of arthritis affecting children under 16, persisting for six weeks or more.
• Terminology Evolution: From juvenile chronic arthritis (JCA) and juvenile rheumatoid arthritis (JRA) to JIA in 1995.
• ILAR Classification (2001): JIA is classified into seven subtypes: oligoarthritis, RF-positive polyarthritis, RF-negative polyarthritis, systemic arthritis, psoriatic arthritis, enthesitis-related arthritis, and undifferentiated arthritis.
• Characteristics: Each subtype has unique phenotypes, genetic markers, and prognosis; chronic arthritis is a common requirement.

Etiology

• Unknown Triggers: Chronic arthritis’s cause in JIA is unclear, involving speculative interactions between environmental and genetic factors.
• Environmental Factors: Risks include antibiotic exposure and C-section deliveries, while breastfeeding and siblings may offer protection.
• Microbial Influence: The roles of microorganisms like Parvovirus B19 and Epstein-Barr virus remain inconclusive in JIA development.
• Genetic Influence: Strong familial linkage; specific HLA alleles correlate with JIA subtypes and related conditions like uveitis.

Pathophysiology

• Immune Response: An imbalance in regulatory T cells, Th1, and Th17 cells underlies many JIA subtypes.
• Cytokines: IL-17 and IL-23 are pivotal in promoting inflammation and joint damage in various subtypes, with differing impacts across subtypes.

Histopathology

• Synovial Changes: The synovial membrane in JIA patients shows heavy infiltration by inflammatory cells, villous hypertrophy, and increased vascularization, akin to adult rheumatoid arthritis.

Clinical manifestations

• Disease course varies greatly; some patients experience mild, self-limiting disease, while others suffer severe, ongoing joint damage.
• Diagnostic Criteria: Diagnosis considers children under 16 with persistent arthritis of at least six weeks’ duration, excluding other causes.

1. Arthritis Definition:
   • Presence of joint effusion.
   • Reduced range of motion.
   • Pain on movement.
   • Warmth of the joint.
   • These signs alone are not diagnostic of JIA and can be due to various causes.
2. Variability in Clinical Manifestations:
   • Polyarticular or systemic onset JIA often includes fatigue, anorexia, weight loss, and growth failure.
   • These systemic symptoms are rare in oligoarticular JIA.
3. Pain Characteristics:
   • Pain typically occurs on movement.
   • Aching quality.
   • Mild to moderate severity.
   • Extremely severe pain may suggest a pain amplification syndrome rather than JIA.
4. Impact of Developmental Age on Symptom Communication:
   • Toddlers may show irritability or altered use of affected joints.
   • Non-verbal indications such as refusal to weight-bear on an affected limb.
5. Other Common Symptoms:
   • Morning stiffness.
   • ‘Gelling’ after periods of inactivity.
   • Sluggish movement in the mornings or after naps, improving with activity.
   • Joint swelling often noted post-trauma.
6. Characteristics of Affected Joints:
   • Warmth and swelling.
   • Reduced range of motion.
   • Typically not erythematous.
   • Commonly involves large joints, with smaller joints affected in polyarticular disease.
7. Special Examinations:
   • Includes assessment of the temporomandibular joints and cervical spine.
   • Complications may include bony ankylosis and atlanto-axial subluxation from cervical involvement.
   • Temporomandibular joint issues can lead to significant malocclusion.

Investigations

1. Diagnosis Approach:
   • Primarily a clinical diagnosis.
   • Laboratory investigations support diagnosis and classification.
2. Initial Laboratory Tests:
   • Full Blood Count (FBC).
   • Inflammatory markers like Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP), often elevated in JIA.
   • Recommended if symptoms persist for more than 4 weeks.
3. Findings in Blood Tests:
   • Variable ESR and CRP levels in active JIA.
   • FBC may reveal anemia of chronic disease due to prolonged inflammation.
   • Moderately elevated white cell count at diagnosis; significantly higher in systemic onset JIA.
4. Specific Markers:
   • Rheumatoid Factor (RF) in patients with polyarthritis for prognostic insights.
   • Antinuclear Antibody (ANA) testing in all JIA patients, indicating a risk for asymptomatic uveitis, especially in oligoarticular onset.
5. Additional Tests for Severe Disease Indicators:
   • Anticyclic Citrullinated Peptide (anti-CCP) antibodies, indicative of severe disease, not routinely tested.
6. Genetic Testing:
   • Human Leukocytic Antigen (HLA) B27 testing in cases suggestive of enthesitis-related arthritis, important for assessing risk of axial arthritis.
7. Investigations for Underlying Conditions:
   • If connective tissue disease or vasculitis is suspected, tests like dsDNA, extractable nuclear antigens (ENA), C3, C4, and immunoglobulin levels are beneficial.
8. Imaging Techniques:
   • Plain X-rays to show larger effusions; erosions rare in early stages.
   • Ultrasound for confirming joint effusions.
   • MRI and whole body bone scans typically conducted by pediatric rheumatologists, recommended if symptoms persist beyond 4 weeks.

extra-articular manifestations of Juvenile Idiopathic Arthritis (JIA), focusing on uveitis and growth disturbances:

Uveitis

1. Prevalence and Impact:
   • Most common extra-articular manifestation in JIA.
   • Often asymptomatic initially, affecting the anterior chamber and typically nongranulomatous.
   • Approximately 1/3 of patients may develop severe complications like posterior synechiae, cataract, band keratopathy, glaucoma, or macular edema.
2. Risk and Incidence:
   • Uveitis prevalence is 9% across all JIA categories.
   • 15-20% of children with oligoarthritis and 5-10% with polyarthritis are likely to develop uveitis.
   • Rare in systemic arthritis.
   • 90% of uveitis cases occur within 4 years after JIA diagnosis.
3. Screening and Management:
   • Regular screening by an ophthalmologist is crucial, ideally within 6 weeks of JIA diagnosis.
   • Screening frequency varies based on risk factors per the American Academy of Pediatrics guidelines.
   • Treatment usually involves topical steroids, with methotrexate or biologics for resistant cases.
4. Special Considerations:
   • In HLA-B27 positive patients (10-15% develop uveitis), it is usually symptomatic, altering screening needs.
   • Risk of uveitis development is age-dependent in girls, influencing screening recommendations.

Growth Disturbance

1. General Effects:
   • Generalised growth failure can occur due to prolonged disease activity, particularly marked in systemic arthritis.
   • Prolonged corticosteroid therapy often contributes to growth issues.
2. Treatment and Management:
   • Long-term disease control is crucial to prevent growth restriction.
   • Growth hormone therapy has shown promising results for treating short stature in JIA but requires involvement from a paediatric endocrinologist.
3. Specific Anomalies:
   • Bony overgrowth from prolonged inflammation can cause limb length discrepancy.
   • An exception is the mandibular ramus, where hypoplasia occurs due to the positioning of the growth plate below the articular cartilage.

Goals of Treatment

• Prevent pain and joint damage.
• Maintain normal growth, joint function, and muscle strength.
• Monitor for drug toxicity as part of long-term management.

Common Medications and Patient Monitoring

NSAIDs

• Recommended as first-line therapy along with paracetamol and weak opioids (e.g., codeine).
• Generally well tolerated; main side effects include gastrointestinal symptoms, behavior disturbances, and headaches.
• Long-term cardiovascular risks are not well-defined in children.
• Regular laboratory monitoring specifically for NSAIDs alone is typically unnecessary.

Methotrexate and Biologic Agents

• Methotrexate is well tolerated; side effects primarily include gastrointestinal issues and potential liver enzyme elevation.
• Regular testing for liver enzymes, FBC, and renal function is advised every 1-3 months.
• Biologic agents like TNF-α antagonists (e.g., Etanercept, Abatacept) are used for severe cases when other therapies fail.
• Requires regular monitoring of FBC and liver function, and screening for latent tuberculosis before starting treatment.
• Immunizations with live vaccines are contraindicated during treatment due to increased risk of severe disease from the vaccine strains.

Corticosteroids

• Typically reserved for systemic onset JIA, although their role is diminishing with advances in biologic therapies.

Multidisciplinary Care

• Essential for developing an individualized care plan addressing medical, psychological, and educational needs.
• Key roles for physiotherapists and occupational therapists in maintaining joint function and facilitating school adaptations.
• Supportive Therapies: Physical therapy, including swimming and joint-friendly exercises, is crucial for maintaining mobility.
• Team Care Arrangements beneficial, especially in remote areas.

Long-Term Outcomes

• Significant improvements in mortality and morbidity over the past decades due to advanced therapies.
• Despite improvements, many patients still experience chronic disability and disease activity into adulthood.
• Social impacts significant, with issues like unemployment, body image, and relationship difficulties.

Conclusion

• JIA remains a major childhood rheumatic disease with substantial long-term impact.
• Early detection, initial management, and ongoing monitoring are crucial and can be effectively supported by general practice.
• Multidisciplinary approaches and adherence to guidelines are critical in preventing long-term sequelae.