Chronic Juvenile Arthritis

Synonyms: juvenile rheumatoid arthritis; juvenile idiopathic arthritis; Still's disease; juvenile arthritis

Juvenile chronic arthritis (JCA) is a group of systemic inflammatory disorders of unknown aetiology, which cause chronic joint inflammation and affect children under the age of 16 years.¹ The subset for each patient is classified according to the presentation within the first six months from the initial onset. The three major subsets are:

• Pauciarticular onset - with 4 or less joints involved. Is the commonest type (about 50% of cases).
• Polyarticular onset - with more than 4 joints involved. Accounts for 20% of cases in the UK.
• Systemic onset - with fever, rash and arthritis.

• Prevalence is estimated to be 1-2 per 1000 children.¹
• Pauciarticular and polyarticular disease occur more frequently in girls, while both sexes are affected with equal frequency in systemic onset disease.

Risk factors

• The Spondyloarthropathies are strongly associated with HLA B27.
• Sero-positive polyarticular JCA is associated with HLA DR1 and DR4.
• Early onset pauciarticular JCA with chronic uveitis is associated with HLA DR5 and DR 8.
• Early onset pauciarticular JCA is associated with DQW1 and DPW2.
• Systemic onset JCA is associated with HLA DR4.

• Based on the presence of arthritis that persists for at least 6 weeks, with all other causes excluded. The onset can be gradual or abrupt, with morning stiffness and joint pain.
• Joint pain is variable but may be severe and there may be a marked limp.
• Fatigue and weight loss may occur and uveitis may cause photophobia.
• Systemic onset JCA:
  • Is characterised by spiking fevers and may be accompanied by a salmon-pink rash, which affects the trunk and extremities.
  • Some children may have a generalised myalgia. Hepatosplenomegaly is often present and there may also be lymphadenopathy.
  • Arthralgia is often present but joint swelling is unusual and a definite diagnosis of systemic onset JCA cannot be made until the development of arthritis, which may not occur for months following the onset.
  • Pleuritis, pericarditis, peritonitis and myocarditis may occur.
• Pauciarticular disease:
  • Characteristically affects larger joints (e.g. knees, ankles, wrists). May be associated with uveitis (especially if antinuclear antibody positive) or sacroiliitis.
• Pauciarticular JCA usually has an asymmetrical presentation.
• Pauciarticular JCA with sacroiliitis is characterised by involvement of hip, sacroiliac joint, heel, foot, Achilles tendon; the spine may also be affected and may progress to ankylosing spondylitis.
• Polyarticular disease:
  • Affects both large and small joints and is usually symmetrical. Joint involvement includes the elbows, knees, ankles, hands, and feet.
  • Onset is usually insidious but may be abrupt.
  • Rheumatoid factor positive subtype: rheumatoid nodules are often present.
  • Cervical spine involvement, with risk of atlantoaxial subluxation.
  • More rarely the temporomandibular joint, spine, hips and shoulder joints are involved.

• Infection: viral, bacterial, tuberculosis or lyme disease.
• Post-infectious, e.g. post streptococcal.
• Non-inflammatory causes such as trauma, slipped epiphysis, osteochondrosis.
• Haematological, e.g. leukaemia or haemophilia with recurrent intra-articular bleeds.
• Connective tissue disorders, e.g. systemic lupus erythematosus, scleroderma.
• Malignancy including bone tumours, neuroblastoma.
• Other possibilities include ankylosing spondylitis, psoriasis, sarcoidosis.

• ESR is always elevated in children with systemic onset, usually elevated in polyarticular disease, but is often normal in those with pauciarticular disease.
• Full blood count may show anaemia (often microcytic), lymphopenia and thrombocytopenia.
• Positive antinuclear antibody is seen in up to 25%, especially in those with pauciarticular disease:
  • Pauciarticular with chronic iridocyclitis (type I): high frequency of ANA antibodies.
  • Pauciarticular with sacroiliitis (type II): ANA antibodies are absent.
• Rheumatoid factor is rare in children with systemic JCA and is considered as a marker for persistence of polyarticular JCA into adulthood.
• X-rays, CT scan, MRI and bone scans are often important in establishing the diagnosis and ruling out other possible diagnoses.
• Echocardiography is performed if the child has possible systemic JCA or has fevers or orthopnoea (to rule out pericarditis).
• Dual-energy x-ray absorptiometry scanning may be important in order to assess osteopenia in a child with polyarticular JCA.
• Septic arthritis may need to be excluded by arthrocentesis.

• Non-drug management includes physiotherapy and occupational therapy to maintain function and prevent deformities.
• It is important to maintain activity as much as possible but also to rest swollen joints.
• Hydrotherapy is very beneficial.
• Affected children and their families may need a great deal of emotional support and also physical aids for both home and school.

Drugs

• Non-steroidal anti-inflammatory drugs, e.g. ibuprofen, naproxen.
• Analgesics including paracetamol can be used for control of pain and fever.
• As with adult rheumatoid arthritis, disease modifying drugs (DMARDs) are now used early in the disease process:
  • All have significant potential toxicity and require careful monitoring.
  • Methotrexate is now considered by many experts to be the most effective agent.
  • Other agents used include hydroxychloroquine, gold, penicillamine, sulphasalazine and immunosuppressants such as ciclosporin A, azathioprine, cyclophosphamide and chlorambucil.
• Intravenous Gamma globulin has been used in systemic JCA with vasculitis.
• Corticosteroids:
  • Are indicated for those children with life threatening complications and also topically for eye involvement.
  • They are extremely effective, but systemic use is a major cause of growth retardation and bone demineralisation.
  • Low dose may be beneficial for children with severe polyarthritis who are unresponsive to other therapies.
  • Intra-articular steroid injections may also be useful for a joint which is particularly badly affected.
• Etanercept (a cytokine modulator):
  • Has been shown to be effective and well-tolerated.²
  • Etanercept is recommended for children aged 4 to 17 years who have active JCA in at least five joints and whose condition has not responded adequately to methotrexate or who have been unable to tolerate treatment with methotrexate.³

Surgical

Surgical intervention such as joint replacement or synovectomy may be required.

• Osteoporosis.
• Growth retardation.
• Uveitis
  • The prevalence of uveitis in JCA is approximately 8-30%, but in the young pauciarticular onset group the prevalence may be as high as 45-57%.⁴
  • The uveitis in JCA is asymptomatic and therefore screening by slit-lamp is essential for diagnosis.⁴
• Macrophage activation syndrome: rare and often fatal complication, which may closely resemble a flare of arthritis but causes a coagulopathy with thrombocytopenia and other abnormalities of coagulation.
• Complications from medications: both NSAIDs and DMARDs have a relatively high risk of side effects.
• Psychosocial, behavioural and educational difficulties may occur because of limitations of disability, restriction of interacting with friends and time spent away from school.
• Complications associated with each type of JCA:
  • Systemic-onset JCA: pericarditis, haemolytic anaemia, disseminated intravascular coagulation, endarteritis in the fingers and toes resulting in very poor circulation, myocarditis, amyloidosis.
  • Pauciarticular JCA: knee flexion contractures, reduced leg length.
  • Polyarticular JCA: skeletal abnormalities - accelerated bone age, narrowed joint spaces, swan-neck and/or boutonniere deformities, and joint subluxation; cervical spine involvement.

• Rarely fatal and resolves in up to 80% of affected children, who regain normal function.
• The course is unpredictable in each individual child.
• Prognosis is overall favourable but depends on the sub-type:
  • Pauciarticular:
    • 80% have resolved after 15 years.
    • 15% go on to develop Polyarticular arthritis and severe joint involvement.
    • Eye involvement is a major problem and 50% will have reduced visual acuity at ten years after presentation and 25% will have developed cataracts or glaucoma.
    • Of the group with spondyloarthropathy, 10% are still affected after 15 years.
  • Polyarticular rheumatoid factor sero-negative: only 10 - 15% have severe limitation at 15 years and often go into remission with little erosive disease.
  • Polyarticular sero-positive: more severe course with only 33% independent after 15 years.
  • Systemic onset: 50% remit without recurrence, but the rest have polyarticular arthritis and 33% have severe destruction.
• Prognosis is worst in those with disease onset before the age of 5 years.
• About 4% die from infection and amyloidosis.