Chronic Juvenile Arthritis

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

Juvenile Chronic Arthritis 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 per 1000 children. Pauciarticular and polyarticular disease occur more frequently in girls, while both sexes are affected with equal frequency in systemic onset disease.

• 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 characterized by spiking fevers and may be accompanied by a salmon-pink rash, which affects the trunk and extremities.
  • Some children may have a generalized 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 characterized by involvement of hip, sacroiliac joint, heel, foot, Achilles tendon; the spine may also be affected and may progresses 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 cyclosporin 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.
• The tumour necrosis factor inhibitor, etanercept, 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

Surgery such as joint replacement or synovectomy may be required.

• Osteoporosis.
• Growth retardation.
• Systemic-onset JCA: pericarditis, haemolytic anaemia, disseminated intravascular coagulation, endarteritis in the fingers and toes resulting in very poor circulation, myocarditis, amyloidosis.
• 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.
• 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.
• 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.

• 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:⁴
  • 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.