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 defined as joint inflammation presenting in children under the age of 16 years and persisting for at least six weeks, with other causes excluded¹ . There are several classification systems with the International League of Associations for Rheumatology (ILAR) criteria most widely accepted² . They describe seven subsets of JIA with differing clinical courses:

• Oligoarticular JIA (50% of JIA).

• Polyarticular JIA - RF negative (25%).

• Polyarticular JIA - RF positive (5%).

• Systemic-onset JIA (5-10%).

• Juvenile psoriatic arthritis (2-15%).

• Enthesitis-related arthritis (2-10%).

• Undifferentiated arthritis (1-10%).

Who gets juvenile idiopathic arthritis? (Epidemiology)

The overall prevalence is estimated to be 1-2 per 1,000 children, with an incidence of 1 per 10,000³ . It is more common in females, although there are differences depending on the subset. It is described in all geographical areas but with large variations.

Juvenile idiopathic arthritis symptoms^{1 4 5}

Type of juvenile idiopathic arthritis

Oligoarticular JIA: arthritis affecting 1-4 joints in the first six months. 70% patients are ANA positive:

• Extended oligoarthritis: more than four joints affected after six months.

• Persistent oligoarthritis: no more than four joints affected after six months.

• It usually presents in those under 6 years old and is more common in females.

• It typically presents with one or two swollen joints causing stiffness and reduced movement but often not much pain. The child usually feels well.

• The knee and ankle are most commonly affected.

Polyarticular JIA (RF negative): arthritis affecting five or more joints in the first six months with a negative RF:

• There are two peaks of incidence: toddler to preschool age and pre-adolescent. It is more common in females than in males (ratio 3:1).

• It can be asymmetrical - this carries a higher risk of uveitis.

• It can be symmetrical with large and small joints involved with swelling.

• It can present with stiffness but minimal swelling. This is often a destructive arthritis.

Polyarticular JIA (RF positive): arthritis affecting five or more joints in the first six months with a positive RF seen on two occasions.

• There is symmetrical involvement of small joints - particularly the hands and wrists with swelling and stiffness.

• Rheumatoid nodules may develop.

• Systemic features such as fever, enlarged liver and spleen, lymphadenopathy, serositis and pericardial effusions can be seen.

Systemic JIA: arthritis with at least two weeks of daily fever. The fever must be greater than 39ºC and return to less than 37ºC between peaks on at least three days (called a quotidian fever). There must be one or more of:

1. Rash - evanescent (quickly fading) non-fixed erythematous.

2. Lymph node enlargement.

3. Hepatomegaly and/or splenomegaly.

4. Serositis (pericarditis, pleuritis, peritonitis).
   

Features of systemic JIA include:

• It affects males and females equally, with average age of onset before the age of 5 years.

• A daily high spiking fever, often in the afternoon or evening, with swift return of temperature to normal.

• A rash appears with the fever - classically salmon pink.

• Arthritis is only seen at disease onset in one third of children but commonly develops within a few months. It is usually symmetrical and affects several joints.

Juvenile psoriatic arthritis: arthritis and psoriasis or arthritis plus at least two of:

1. Dactylitis.

2. Nail pitting or onycholysis.

3. Psoriasis in a first-degree relative.

Features of juvenile psoriatic arthritis include:

• It affects females twice as commonly as males, with mean age of onset 6 years.

• Asymmetrical arthritis affecting small and large joints.

• In over 50% arthritis occurs before psoriasis.

Enthesitis-related JIA: arthritis or enthesitis (inflammation at the site of tendon/ligament insertion) plus two of:

1. Sacroiliac or lumbosacral pain.

2. HLA B27-positive.

3. Family history of HLA B27-related disease.

4. Acute anterior uveitis.

5. Onset in a male over the age of 6.

Features of enthesitis-related JIA include:

• It affects males nine times more commonly than females with age of onset usually over 10.

• It often affects a lower limb. It is important to ask about heel pain as a symptom of enthesitis.

• Soft tissue swelling of the knee or foot is a most common examination finding.

• Assess for signs and symptoms of associated psoriasis, uveitis and inflammatory bowel disease.

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 diagnostic tests - JIA is a clinical diagnosis⁶ .

Laboratory

• FBC:
  

  • Normocytic anaemia.

  • Normal or raised WBC with normal differential.

  • Platelets mildly raised.

• ESR or CRP: often elevated.

• ANA, if positive, is associated with an increased risk of uveitis.

• RF and HLA B27 are useful for classification (HLA B27 is positive in 90% of enthesitis-related JIA).

• Viral or bacterial serology if history is suggestive of post-infectious arthritis.

Imaging

• X-ray 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 delineates any bony changes, joint damage and extent of synovitis.

Other

Aspirate the joint if septic arthritis is suspected.

Juvenile idiopathic arthritis treatment and management^{1 4 7 8}

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), a disease modifying anti-rheumatic drug (DMARD) such as methotrexate or a cytokine modulator, and intra-articular, intravenous, or oral corticosteroids⁹ .

• Non-drug management includes physiotherapy and occupational therapy to maintain function and prevent deformities. Hydrotherapy can be very beneficial.

• Patients should be encouraged to participate in as much physical activity as possible, including most sports and dance. Regional paediatric rheumatology services will provide more specific advice.

• 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.

• The use of systemic corticosteroids is now much more limited due to the availability of other treatment options¹⁰ .

Drugs

• Non-steroidal anti-inflammatory drugs (NSAIDs) offer symptom relief.

• Steroids:
  

  • Intra-articular steroid injections for affected joints.

  • Systemic steroids for quick symptom relief and systemic disease. These can cause growth suppression and bone demineralisation if used in the long term.

  • Topical steroids for eye involvement.

• Methotrexate.
  

  • First-line treatment if multiple joints are affected or if the same joint requires injecting more than three times.

  • It is often given as a subcutaneous injection.

  • It requires regular blood test monitoring. As with adult rheumatoid arthritis, there is evidence to support its use early in polyarticular JIA.

• Sulfasalazine and leflunomide may be used for JIA.

NICE guidance¹¹

The National Institute for Health and Care Excellence (NICE) recommends abatacept, adalimumab, etanercept and tocilizumab as options for treating polyarticular juvenile idiopathic arthritis (JIA), including polyarticular‑onset, polyarticular‑course and extended oligoarticular JIA for :

• 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 arthritis¹² .

NICE recommends tofacitinib as an option for treating active polyarticular juvenile idiopathic arthritis and juvenile psoriatic arthritis in people aged 2 years and older¹³ . 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.

Surgical

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

Juvenile idiopathic arthritis complications

• 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 activities¹⁴ .

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

Prognosis¹

This is now very good for people with JIA who have access to a full multidisciplinary team and available medications.

• Oligoarticular JIA:
  

  • 50% will have long-term joint problems - this is more likely if arthritis extends.

  • There is risk of joint contractures and limb length discrepancy without treatment.

• Uveitis:
  

  • 50% of those with eye involvement will have impaired vision.

  • Uveitis can lead to cataracts or glaucoma.

• Polyarticular JIA:
  

  • If RF negative - ten-year remission rate is 25% (remission usually occurs within five years).

  • If RF positive - ten-year remission rate is 6%. It carries a high risk of joint damage and deformities and the need for surgery.

• Systemic JIA:
  

  • 10% have a single disease flare and stay in complete remission.

  • 35% have a relapsing remitting course over several years.

  • 55% have a chronic disease.

• Juvenile psoriatic arthritis:
  

  • At seven-year follow-up 40% had ongoing disease.

• Enthesitis-related JIA:
  

  • Polyarticular presentation predicts chronic disease.

  • Those with hip involvement in childhood are at increased risk of hip replacement in adulthood.

EMIS wishes to acknowledge input from Rosemary Waller, Nick Wilkinson and the team at the Oxford Paediatric and Adolescent Rheumatology Centre in the authoring of this article.