Makindo Medical Notes

Aspirin should be avoided in individuals under 12 due to the risk of Reye's syndrome. Tumor necrosis factor (TNF) is a pro-inflammatory cytokine that plays a key role in the pathogenesis of juvenile idiopathic arthritis (JIA).

About

• JIA is a systemic form of arthritis that accounts for approximately 10% of all Juvenile Idiopathic Arthritis cases.
• Onset typically occurs in early childhood, usually before the age of 16.
• A similar condition can present in adults, though it is much rarer.

Aetiology

• Most commonly seen in children under the age of 5.
• Onset may occur as early as age 2 or even younger.
• A systemic illness affecting more than just the joints.
• Equal occurrence in males and females, although it is very rarely seen in adults.
• There is a genetic component, with shared HLA alleles being implicated.

Immunology

• Imbalance of Th1 (IFN-gamma secreting T cells) and Th17 (interleukin-17 secreting T cells).
• Persistent activation of innate immunity.
• Tumor necrosis factor (TNF) is a central pro-inflammatory cytokine involved in JIA pathogenesis.

Definitions

• Oligoarthritis: Affects four or fewer joints in the first six months of disease.
• Polyarthritis: Affects five or more joints in the first six months of disease.

Subtypes

• Oligoarthritis: 50-60%
• Rheumatoid Factor (IgM RF) positive polyarthritis: 11-28%
• RF-negative polyarthritis: 2-7%
• Systemic arthritis: Presents with a salmon-colored rash, lymphadenopathy, enlarged spleen and liver, and serositis.
• Psoriatic arthritis
• Enthesitis-related arthritis: 1-6%, associated with HLA-B27
• Undifferentiated arthritis

Clinical Presentation: Fever, Rash, and Joint Pain

• Arthralgias are common, but arthritis may not always be prominent in systemic JIA (sJIA).
• Recurrent fever lasting more than two weeks, often with a rash and painful joints.
• High spiking fevers (>39°C) usually occur in the evening.
• Half of the patients may develop destructive arthritis over time.
• Pink or salmon-colored maculopapular rash.
• Other symptoms: lymphadenopathy, myocarditis, pericarditis, pleurisy, hepatosplenomegaly, dry eyes, and dry mouth.

Investigations

• FBC, U&E, LFT, raised CRP and ESR levels.
• Markedly elevated ferritin, an acute inflammatory marker.
• Usually negative autoantibodies (ANA, RF) and HLA-B27.
• A positive ANA > 1:100 or RF > 1:80 generally excludes the diagnosis.
• Raised neutrophil and platelet counts.
• Imaging: Early radiology may show no changes, but ultrasound can assess synovial thickening, joint effusion, tenosynovitis, and bone erosions.
• MRI: Gold standard for JIA. Capable of detecting bone marrow edema, synovial changes, and bone erosions.

Differential Diagnoses

• Oligoarthritis:
  • Post-streptococcal reactive arthritis
  • Lyme arthritis
  • Acute rheumatic fever
  • Reactive arthritis
  • Toxic synovitis
  • Septic arthritis
  • Pyomyositis
  • Osteomyelitis
  • Steroid-induced osteonecrosis
  • Sickle cell disease
  • Haemophilia
  • Scurvy
  • Chronic nonbacterial osteomyelitis (CNO)
  • Sports injury, non-accidental injury
  • Pigmented villonodular synovitis (PVNS)
  • Bone tumours, neuroblastoma, leukemia, and lymphoma
• Polyarthritis:
  • Post-streptococcal reactive arthritis
  • Lyme arthritis
  • Acute rheumatic fever
  • Reactive arthritis
  • Systemic lupus erythematosus (SLE)
  • Mixed connective tissue disease (MCTD)
  • Sjogren syndrome, scleroderma, sarcoidosis
  • Inflammatory bowel disease (IBD)
  • Chronic recurrent multifocal osteomyelitis (CRMO)
  • Farber disease, benign hypermobility syndrome
• Systemic arthritis:
  • Infections (mycoplasma, cat-scratch disease, bacterial endocarditis, Lyme disease)
  • Acute rheumatic fever, PFAPA syndrome
  • Autoinflammatory syndromes, systemic vasculitis (e.g., polyarteritis nodosa, Kawasaki disease)
  • Inflammatory bowel disease (IBD), malignancy (leukemia, lymphoma, neuroblastoma)
  • Castleman disease, apophysitis (Osgood-Schlatter, Sever disease), amplified musculoskeletal pain syndrome

Complications

• Leg-length discrepancy
• Joint contracture

Management

• Refer all suspected or confirmed JIA cases to a paediatric rheumatologist and prescribe NSAIDs for symptom relief.
• Avoid live vaccines in patients on immunosuppressive drugs; killed (inactivated) vaccines are safe, though immune response may be reduced. Annual influenza vaccination is recommended.
• Some cases may require immunosuppressive therapy.
• Steroids may be required for myocarditis or cardiac tamponade.
• Anti-TNF drugs are used in select cases.
• Methotrexate and other steroid-sparing agents are commonly prescribed for long-term management.

References

• Juvenile Idiopathic Arthritis (JIA)
• Diagnosis and Management of Juvenile Idiopathic Arthritis