Juvenile idiopathic arthritis

Synonyms: Still's disease, juvenile arthritis, juvenile chronic arthritis, juvenile rheumatoid arthritis

What is juvenile idiopathic arthritis?

Juvenile idiopathic arthritis (JIA) is a group of idiopathic inflammatory arthritis affecting children under the age of 16 and lasting for at least 6 weeks.¹ Previously known as juvenile chronic arthritis or juvenile rheumatoid arthritis, juvenile idiopathic arthritis (JIA) has been the preferred name since 1995. It is the most common childhood rheumatological condition, accounting for about 40% of the average paediatric rheumatologist's caseload. ²

The international League of Associations for Rheumatology describes seven subsets of JIA:^{3 1}

• Oligoarticular JIA (50-60% of JIA).

• Polyarticular JIA - RF negative (11-28%).

• Polyarticular JIA - RF positive (2-7%).

• Systemic-onset JIA (10-20%).

• Juvenile psoriatic arthritis (2-15%).

• Enthesitis-related arthritis (1-7%).

• Undifferentiated arthritis (1-10%).

Who gets juvenile idiopathic arthritis? (Epidemiology)¹⁴

The incidence and prevalence varies depending on study design and geographical location. Incidence is between 1.6 and 23 new cases for 100,000 children; prevalence is between 3.8 to 400 cases per 100,000 children. In the USA and Canada, the incidence is thought to be between 4.1 and 6.1 new cases per 100,000 children.

It is generally more common in females, although there are differences depending on the subtype. Specific subtypes are more common in some geographical regions. There is a lower prevalence in Africa and the Middle East.⁵

Juvenile idiopathic arthritis symptoms

JIA is very unpredictable; in some patients it is a self-limiting disease whilst, in others, it is an unremitting disease with a high risk of joint destruction. JIA has the general pattern of inflammatory joint disease (synovitis, joint effusion, soft tissue swelling, osteopenia, bone oedema, and erosions) with some additional elements related to developmental age, such as epiphyseal growth disturbances, premature fusion, and limb length inequality.¹

Symptoms of subtypes of juvenile idiopathic arthritis⁶

Oligoarticular JIA:

• Characterised by inflammation of up to four joints.

• Usually asymmetrical.

• Tends to affect knees and ankles.

• Positive ANA is common.

• There is a high risk of chronic uveitis.

Polyarticular JIA (RF negative):

• Characterised by inflammation of five or more joints.

• Metacarpophalangeal joints and wrists tend to be particularly affected.

• It is usually asymmetrical.

Polyarticular JIA (RF positive):

• Characterised by inflammation of five or more joints.

• Metacarpophalangeal joints and wrists tend to be particularly affected.

• It is usually symmetrical.

Systemic JIA:

• Presents with widespread joint inflammation and also with systemic inflammatory symptoms.

• 10% of children with systemic JIA present with macrophage activation syndrome, a potentially life-threating condition, characterised by pancytopenia, coagulopathy, hepatopathy, neurological disorders and haemophagocytosis. Mortality has been reported to be between 20 and 53%.⁷

• Typical symptoms include spiking fevers, generalized lymphadenopathy, a migratory salmon-pink rash, serositis (pericarditis most common, then pleuritis and peritonitis) and hepatosplenomegaly.

Juvenile psoriatic arthritis:

• Often initially appears like oligoarticular JIA or polyarticular (RhF negative) JIA.

• The small joints are more likely to be affected.

• It is accompanied by dactylitis, psoriasis and/or nail pitting.

• Children under the age of 6 years are more likely to be female, ANA-positive and predisposed to chronic uveitis, with arthritis of wrists and small joints of the hands and feet.

• Children over the age of 6 years are more likely to be male, HLA-B27 positive, with enthesitis and axial disease.

Enthesitis-related JIA:

• Similar to oligoarticular JIA.

• Enthesitis is present - inflammation of the entheses, the insertion sites where tendons and ligaments attach to bone.

• Commonly associated with HLA-B27 status.

• Uveitis is common.

• Some people argue that this is not a true JIA but should be considered a spondyloarthropathy.

Undifferentiated JIA:

• Arthritis that doesn't meet criteria for other JIA categories.

Differential diagnosis

• Septic arthritis:

  • Usually one joint.

  • Fever, systemically unwell, and inability to bear weight are common features.

  • Tuberculosis can cause a chronic infection.

• Osteomyelitis: Fever with severe bony pain - children stop using the affected limb.

• Reactive and post-infectious arthritis:

  • Often gut pathogens or post-viral.

  • Rheumatic fever, Lyme disease.

• Trauma.

• Mechanical pain:

  • Pain usually after activity or late in the day.

• Pain syndromes.

• Inflammatory bowel disease:

  • Arthritis can be first symptom.

  • May be associated with weight loss or family history.

• Malignancy:

  • Night pain, weight loss, easy bruising can all be features.

  • Leukaemia, lymphoma, neuroblastoma, Ewing's sarcoma, bony tumours.

• Connective tissue disease:

  • Systemic lupus erythematosus, juvenile dermatomyositis, sarcoid.

Investigations

There are no specific diagnostic tests for JIA which is a clinical diagnosis.¹

Laboratory

Initial laboratory tests should include:

• FBC.

• ESR (typically raised).

• CRP (typically raised).

• ANA.

• Rheumatoid factor (RF).

• Anti-cyclic citrullinated peptide antibodies (anti-CCP).

• HLA-B27

A positive RF or anti-CCP is of little diagnostic benefit but may indicate a poorer disease course.

Imaging

• X-ray tends to be the initial imaging modality but results are normal in early JIA.

• It is useful to exclude trauma, osteomyelitis or malignancy.

• Ultrasound can show joint fluid, synovial hypertrophy and erosions if present.

• MRI is the most sensitive imaging technique and delineates any bony changes, joint damage and extent of synovitis.

Other

The joint should be aspirated if septic arthritis is suspected. Any suspected septic arthritis should be sent to ED immediately.

Juvenile idiopathic arthritis treatment and management⁶

The management of juvenile idiopathic arthritis requires symptomatic treatment to relieve pain, swelling, and stiffness, together with treatment to control and suppress disease activity. Treatment options include non-steroidal anti-inflammatory drugs (NSAIDs) and disease modifying anti-rheumatic drugs (DMARDs) such as methotrexate or a cytokine modulator.

• Non-drug management includes physiotherapy and occupational therapy to maintain function and prevent deformities.

• Physical therapy emphasizes range of motion with minimal stress on joints. Patients should participate in moderate fitness, flexibility, and strengthening exercises. Swimming can be very beneficial.

• Affected children and adolescents and their families typically need support with long-term medication and the impact on family, social and school life. Expert multidisciplinary teamwork, including physiotherapy, occupational therapy, clinical psychology and play specialist support, is essential.

• Untreated chronic inflammation can lead to growth failure or abnormality, osteoporosis and delayed puberty.

Drugs¹⁶²

• Non-steroidal anti-inflammatory drugs (NSAIDs) offer symptom relief. NSAIDs are less commonly used now that DMARDs have been shown to be of significant benefit.

  • Previously over 50% of children with JIA developed gastric side effects on NSAIDs.

  • However nephrotoxicity is much less common in children than in adults.

• Corticosteroid injection may be the first line treatment if only a single joint is affected. Corticosteroids can be useful in systemic JIA but do not impact on the course of the illness.

• DMARDs. Methotrexate, leflunomide or sulfasalazine are recommended for early use in JIA.

  • Methotrexate is considered to be the first-line treatment for oligoarticular or polyarticular JIA.

  • Leflunomide is also effective in pJIA and is recommended if methotrexate is not tolerated.

  • Sulfasalazine is first line for enthesitis-related JIA.

• TNF inhibitors are commonly used where DMARDs have been unsuccessful. The National Institute for Health and Care Excellence (NICE) guidance is as follows:⁸

  • Abatacept: aged 6 years and older whose disease has responded inadequately to other disease‑modifying anti‑rheumatic drugs (DMARDs) including at least 1 tumour necrosis factor (TNF) inhibitor.

  • Adalimumab: aged 2 years and older whose disease has responded inadequately to 1 or more DMARD

  • Etanercept: aged 2 years and older whose disease has responded inadequately to, or who are intolerant of, methotrexate.

  • Tocilizumab: aged 2 years and older whose disease has responded inadequately to previous therapy with methotrexate.

  • Adalimumab and etanercept are recommended as options for treating enthesitis‑related JIA for people 6 years and older (adalimumab) and 12 years and older (etanercept) whose disease has responded inadequately to, or who are intolerant of, conventional therapy.

  • Etanercept is recommended as an option for treating psoriatic JIA for people aged 12 years and over whose disease has responded inadequately to, or who are intolerant of, methotrexate.

  • Tocilizumab is approved by NICE for treatment of systemic JIA when steroids and methotrexate have failed, and may be used for polyarticular arthritis.⁹

  • NICE recommends tofacitinib as an option for treating active polyarticular juvenile idiopathic arthritis and juvenile psoriatic arthritis in people aged 2 years and older. Tofacitinib can be used with methotrexate, or as monotherapy when methotrexate is not tolerated or if continued treatment with methotrexate is inappropriate. This recommendation only applies if the patient's condition has responded inadequately to previous treatment with disease-modifying antirheumatic drugs (DMARDs) and a TNF-alpha inhibitor is not suitable or does not control the condition well enough. ¹⁰

Surgical

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

Juvenile idiopathic arthritis complications

Complications remain significant but have markedly reduced with the use of DMARDs and TNF inhibitors. Where JIA-associated uveitis was the commonest cause of sight loss in children, this is no longer the case. ⁶

• Joint deformities:

  • Knee flexure contractures.

  • Involved joints mature faster than unaffected joints. This can lead to limb length discrepancy.

  • Accelerated bone age with narrowed joint spaces.

  • Swan-neck and/or boutonnière deformities, and joint subluxation.

  • Cervical spine involvement in RF positive polyarticular JIA.

• A serious complication is uveitis, which can lead to sight loss:

  • Found in 30% of those with oligoarticular JIA and associated with positive ANA,

  • Insidious and asymptomatic. It often affects both eyes.

  • Not linked to arthritis severity.

  • All children require regular screening by an ophthalmologist.

• Complications of systemic JIA include:

  • Macrophage activation syndrome - fever, hepatosplenomegaly, coagulopathy, encephalopathy, pancytopenia, raised liver enzymes with very high ferritin.

  • Secondary amyloidosis.

  • Joint destruction - over 50% of children with chronic systemic JIA require joint surgery.

• Osteoporosis.

• Growth restriction - related to the degree of inflammation.

• Complications from medications.

• Restriction of sports and other leisure activities.

• Psychosocial, behavioural and educational difficulties may occur because of limitations of disability, restriction of interacting with friends and time spent away from school.

Prognosis

The prognosis is now very good for people with JIA who have access to DMARDs and TNF inhibitors. A recent study showed that 48.8% achieved remission off medication, 49.9% achieved remission on medication and only 1.3% did not respond to any drug.¹

Other studies suggest that only 25% of patients are able successfully to come off medication and remain symptom-free.⁶