Introduction

Juvenile idiopathic arthritis develops when dysregulation of the immune system results in persistent inflammation of the synovial membrane. Activated T lymphocytes, B lymphocytes, macrophages, and dendritic cells infiltrate the synovium and release inflammatory cytokines including tumour necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6). These cytokines stimulate synovial proliferation, formation of pannus, angiogenesis, and activation of osteoclasts, leading to progressive destruction of cartilage and subchondral bone. Persistent inflammation may also interfere with normal growth plate development, causing limb-length discrepancies, joint contractures, and growth retardation. In systemic JIA, excessive activation of the innate immune system produces widespread inflammation with fever, rash, and involvement of multiple organs.

Epidemiology

• Most common chronic rheumatic disease in children.

• Onset occurs before 16 years of age.

• Girls are more frequently affected than boys, except in enthesitis-related arthritis.

• Peak onset occurs between 1–3 years and again between 8–12 years depending on the subtype.

• Chronic anterior uveitis is a major extra-articular complication, particularly in ANA-positive oligoarticular disease.

Etiology

The exact cause remains unknown. JIA is believed to result from an abnormal immune response occurring in genetically susceptible children following environmental triggers.

Potential contributing factors include:

• Genetic susceptibility (HLA-associated genes)

• Viral infections

• Bacterial infections

• Environmental factors

• Immune dysregulation

Classification (ILAR classification)

JIA is classified into seven major categories.

Systemic juvenile idiopathic arthritis

Characterized by:

• Arthritis

• Quotidian (daily spiking) fever

• Evanescent salmon-pink rash

• Hepatosplenomegaly

• Generalized lymphadenopathy

• Serositis

Oligoarticular juvenile idiopathic arthritis

• Four or fewer joints involved during the first six months.

• Most commonly affects knees and ankles.

• Highest risk of chronic anterior uveitis.

Polyarticular juvenile idiopathic arthritis

• Five or more joints involved during the first six months.

• May be rheumatoid factor positive or negative.

• Usually presents with symmetrical arthritis involving both small and large joints.

Psoriatic arthritis

Characterized by:

• Arthritis with psoriasis

or

• Arthritis with at least two of the following:

  • Dactylitis

  • Nail pitting

  • Family history of psoriasis

Enthesitis-related arthritis

Characterized by:

• Arthritis

• Enthesitis

• Sacroiliitis

• HLA-B27 association

• Acute anterior uveitis

Undifferentiated arthritis

Patients who do not meet criteria for any category or fulfil criteria for more than one category.

Pathophysiology

Juvenile idiopathic arthritis develops when dysregulation of the immune system results in persistent inflammation of the synovial membrane. Activated T lymphocytes, B lymphocytes, macrophages, and dendritic cells infiltrate the synovium and release inflammatory cytokines including tumour necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6). These cytokines stimulate synovial proliferation, formation of pannus, angiogenesis, and activation of osteoclasts, leading to progressive destruction of cartilage and subchondral bone. Persistent inflammation may also interfere with normal growth plate development, causing limb-length discrepancies, joint contractures, and growth retardation. In systemic JIA, excessive activation of the innate immune system produces widespread inflammation with fever, rash, and involvement of multiple organs.

Risk factors

• Female sex (most subtypes)

• Family history of autoimmune disease

• Positive ANA

• HLA-B27 positivity

• Young age (oligoarticular subtype)

Clinical presentation

General features

• Arthritis lasting at least six weeks (mandatory for diagnosis)

• Morning stiffness or "gelling" after inactivity

• Joint swelling

• Joint pain

• Limping

• Reduced range of motion

• Warm joints

• Fatigue

• Decreased physical activity

• School absenteeism

• Difficulty participating in sports or physical education

Systemic features

Especially in systemic JIA:

• Daily spiking fever

• Evanescent salmon-coloured rash

• Weight loss

• General malaise

• Lymphadenopathy

• Hepatosplenomegaly

• Serositis

Extra-articular manifestations

• Chronic anterior uveitis

• Growth retardation

• Leg-length discrepancy

• Osteoporosis

• Muscle wasting

Diagnostic criteria

Diagnosis is based on the International League of Associations for Rheumatology (ILAR) criteria.

A diagnosis of JIA requires:

• Age less than 16 years at disease onset.

• Arthritis involving one or more joints.

• Arthritis persisting for at least six weeks.

• Exclusion of other causes of chronic arthritis, including:

  • Septic arthritis

  • Osteomyelitis

  • Acute rheumatic fever

  • Systemic lupus erythematosus

  • Malignancy (especially leukemia)

  • Sickle cell disease

  • Reactive arthritis

Investigations

Laboratory investigations

• Erythrocyte sedimentation rate (ESR)

• C-reactive protein (CRP)

• Complete blood count (CBC)

• Liver function tests (LFTs)

• Serum creatinine

• Antinuclear antibody (ANA)

• Rheumatoid factor (RF)

• Anti-cyclic citrullinated peptide antibody (anti-CCP) where available

• Antistreptolysin O titre (ASOT)

• Anti-DNase B

• Urinalysis

Additional investigations

• Blood cultures if infection is suspected

• Bone marrow examination if malignancy is suspected

Synovial fluid analysis

May demonstrate:

• Inflammatory fluid

• Elevated white blood cell count

• Sterile culture (unless septic arthritis coexists)

Imaging

Plain X-ray

May demonstrate:

• Soft tissue swelling

• Periarticular osteopenia

• Joint space narrowing

• Growth abnormalities

• Bone erosions (late disease)

Ultrasound

Useful for detecting:

• Synovitis

• Joint effusion

• Tenosynovitis

MRI

Most sensitive imaging modality.

Demonstrates:

• Early synovitis

• Bone marrow oedema

• Cartilage damage

• Bone erosions

Ophthalmological assessment

Children, particularly those with oligoarticular disease and positive ANA, should undergo regular slit-lamp examination for asymptomatic chronic anterior uveitis.

Differential diagnosis

• Septic arthritis

• Acute rheumatic fever

• Osteomyelitis

• Reactive arthritis

• Systemic lupus erythematosus

• Juvenile dermatomyositis

• Leukemia

• Bone tumours

• Sickle cell disease

• Lyme disease (endemic regions)

Management

Treatment aims to:

• Control inflammation

• Relieve pain

• Prevent joint damage

• Preserve normal growth

• Prevent disability

• Maintain quality of life

Non-pharmacological management

• Psychosocial support

• Physiotherapy once acute pain has subsided

• Occupational therapy

• Regular exercise programme

• Joint protection strategies

• Nutritional assessment

• School participation support

• Family education

Pharmacological treatment

Non-steroidal anti-inflammatory drug

NSAIDs may be used for symptomatic relief, particularly if arthritis has not yet persisted for six weeks.

Ibuprofen

• 10 mg/kg per dose orally every 6–8 hours.

Corticosteroid therapy

Prednisolone

• 0.25–0.5 mg/kg/day orally during the initial stage of treatment.

• In patients with slow response, treatment duration should generally not exceed six months.

Disease-modifying antirheumatic drugs (DMARDs)

Methotrexate

• 0.5 mg/kg orally once weekly.

• Maximum dose: 20 mg/week.

Patients receiving methotrexate should undergo monitoring with:

• Full blood picture (FBP)

• Alanine aminotransferase (ALT)

Monitoring should be performed every 1–3 months to detect leucopenia and hepatotoxicity. Treatment may be tapered and discontinued when sustained remission has been achieved.

OR

Sulfasalazine

• 20–50 mg/kg/day orally in two divided doses.

• Maximum dose: 2,000 mg/day.

Additional treatment considerations

• NSAIDs provide symptomatic relief but do not prevent disease progression.

• Methotrexate is the preferred first-line DMARD for persistent polyarticular disease.

• Systemic corticosteroids should be used at the lowest effective dose for the shortest possible duration because of their effects on growth and bone health.

• Children receiving methotrexate should receive folic acid supplementation according to local protocols.

• Biologic DMARDs (e.g., TNF inhibitors, IL-1 inhibitors, IL-6 inhibitors) may be indicated for refractory disease and should be initiated by a paediatric rheumatologist.

Rehabilitation

• Individualized physiotherapy programme

• Daily range-of-motion exercises

• Muscle strengthening exercises

• Occupational therapy

• Splints when indicated

• Orthotic devices where appropriate

• School reintegration programmes

Monitoring and follow-up

Patients should undergo regular assessment of:

• Disease activity

• Growth and development

• Functional status

• ESR and CRP

• Complete blood count

• Liver function tests

• Renal function

• Drug toxicity

• Eye examination for uveitis

• Radiological progression when indicated

Complications

• Permanent joint deformity

• Joint contractures

• Limb-length discrepancy

• Growth retardation

• Osteoporosis

• Chronic anterior uveitis

• Cataracts

• Glaucoma

• Macrophage activation syndrome (systemic JIA)

• Functional disability

• Psychosocial impairment

Prognosis

The prognosis depends on disease subtype, severity, and response to treatment. Many children with oligoarticular disease achieve long-term remission, whereas polyarticular and systemic disease may follow a more persistent course. Early diagnosis, prompt initiation of DMARD therapy, regular monitoring, and multidisciplinary rehabilitation significantly improve long-term outcomes, reduce joint damage, preserve growth, and enhance quality of life.