juvenile%20idiopathic%20arthritis
JUVENILE IDIOPATHIC ARTHRITIS
Juvenile idiopathic arthritis was formerly known as juvenile rheumatoid arthritis or juvenile chronic arthritis.
It presents as chronic joint swelling, pain with functional limitation for at least 6 weeks of unknown cause that starts before 16 year of age.
It is the most common autoimmune-autoinflammatory disease in children.
Around half of the children with juvenile idiopathic arthritis may have active disease until adulthood.

Juvenile%20idiopathic%20arthritis Diagnosis

Diagnosis

  • An early and accurate diagnosis is important to start the correct management to promote normal growth and development, and to lessen disability and deformity
    • Excessive delay in diagnosis causes late treatment that leads to severe damage of joints and other organs, and impairs skeletal maturation

Classification

  • Developed by the International League of Associations for Rheumatology (ILAR) which includes all subtypes of chronic juvenile arthritis
    • Different to the classification criteria of the American College of Rheumatology (ACR) where the disease was divided according to treatment groups
  • Provides important outline for research, helps identify proper management for patients, and predicts the natural history of the disease

    Subtype Peak Age of Onset Diagnostic Features Other Features
    Oligoarthritis - Persistent 2-4 years
    • Affects ≤4 joints throughout course of disease
    • 30% presents with uveitis
    • Lab test: 60% with positive antinuclear antibody (ANA); some with mild elevation in erythrocyte sedimentation rate (ESR)/C-reactive protein (CRP); other test may be normal
    Oligoarthritis - Extended
    •  Affects >4 joints after the first 6 months of disease
    Polyarthritis - Rheumatoid factor (RF)-negative

    2-4 years and 

    10-14 years

    • Affects ≥5 joints in the first 6 months of disease with negative rheumatoid factor (RF)
    • 10% RF-negative patients present with uveitis; 10% RF-positive patients have rheumatoid nodules
    • Lab test: Mild-moderate elevation in ESR; normal-mild increase in CRP; mild anemia; 40% RF-negative patients with positive ANA
    Polyarthritis - Rhuematoid factor (RF)-positive   9-12 years
    • Affects ≥5 joints in the first 6 months of disease with ≥2 positive RF tested at least 3 months apart
    Systemic-onset 1-5 years 
    • Affects ≥1 joints with or preceded by fever of at least 2 weeks duration with quotidian pattern for at least 3 days, plus ≥1 of the following:
      • Transient erythematous rash
      • Generalized enlargement of lymph nodes
      • Hepatomegaly
      • Splenomegaly
      • Pericarditis ± pleuritis ± peritonitis
    • Lab test: Anemia; increase in white blood cells (WBC), platelets, ESR, CRP, ferritin
    Enthesitis-related arthritis 9-12 years
    • Arthritis ± enthesitis plus ≥2 of the following:
      • Presence or history of sacroiliac joint tenderness and/or inflammatory lumbosacral pain
      • Positive human leukocyte (HLA) B27 antigen
      • Onset of arthritis in male >6 years old
      • Acute anterior uveitis
      • History of ankylosing spondylitis, enthesitis-related arthritis, sacroilitis with inflammatory bowel disease, Reiter syndrome, or family history of acute anterior uveitis in a first-degree relative
    • May have acute anterior uveitis, some with associated reactive arthritis or inflammatory bowel disease
    • Lab test: 80% with positive HLA-B27
    Psoriatic arthritis

    2-4 years and

    9-11 years

    • Arthritis ± psoriasis plus ≥2 of the following:
      • Dactylitis
      • Nail pitting and onycholysis
      • First-degree relative with psoriasis
    • 10% presents with uveitis; 50% with psoriasis
    • Lab test: 50% with positive ANA; mild elevation in ESR/CRP; mild anemia
    Undifferentiated arthritis  
    • Arthritis that does not fit into any or in ≥2 of the above categories
     

Modified from: Wu EY, Bryan AR, Rabinovich CE. Juvenile idiopathic arthritis. In: Kliegman RM, Stanton BF, St. Geme JW, et al. Nelson textbook of pediatrics. 20th ed. Philadelphia, PA: Elsevier Saunders; 2016.

Physical Examination

  • Mainly the basis of juvenile idiopathic arthritis (JIA) diagnosis
  • Juvenile idiopathic arthritis is highly considered in patients with:
    • Pain and swelling of ≥1 joints; some children may not complain of pain but is usually elicited by active or passive motion
      • Constant or progressive loss of function
      • At least 10 days duration of fever that has no known cause and is often associated with transient erythematous rash
      • High spiking fever (≥39°C) with a quotidian pattern is the most recognized feature of systemic involvement
      • Lesions are most commonly seen in the trunk and proximal extremities and usually consists of discrete, circumscribed, salmon-pink 2-10 mm sized macules that may be surrounded by a ring of pallor or may develop central clearing and is usually evanescent with fever spikes; may be elicited by rubbing and/or scratching the skin (Koebner response), by hot bath, or by psychological stress
      • Reduced range of motion
      • Warm joints
      • Effusion
    • Patient may have complaints of morning stiffness and gelling after inactivity or swelling of affected joint after trauma
    • Any joint may be involved but large joints are more commonly affected than the smaller joints
      • Arthritis in large joints causes initial linear growth acceleration that leads to longer affected limb; constant inflammation stimulates rapid and premature closure of the growth plate that results in shortened bones
      • Cricoarytenoid arthritis is uncommon but may cause acute airway obstruction
      • Anterior atlantoaxial subluxation and impaction in the upper cervical spine is often observed rendering the affected child at risk of injury due to accident or intubation
    • Patients may also present with scoliosis, small outpouchings of synovium at the extensor hood of the proximal interphalangeal joint around the wrist or ankle, or synovial cyst in the antecubital fossa or anterior to the shoulder
  • Extra-articular manifestations include ocular, cardiac, pulmonary and hematopoietic involvement
    • Uveitis is the most common juvenile idiopathic arthritis extra-articular manifestation which involves the anterior chamber, affecting 9% of all juvenile idiopathic arthritis patients (eg 15-20% of patients with oligoarthritis, 5-10% of those with polyarthritis, and rarely in patients with systemic-onset juvenile idiopathic arthritis)
    • 90% occur within 4 years of juvenile idiopathic arthritis diagnosis and is usually asymptomatic at onset but may eventually cause posterior synechiae, cataract, band keratopathy, glaucoma, or macular edema
    • Growth failure is more commonly seen in patients with systemic arthritis due to its high inflammatory nature and repeated use of long-term oral glucocorticoid agents

Laboratory Tests

  • Helpful in increasing accuracy of the diagnosis, classifying the disease, ruling out other types of arthritis, predicting the progression of patient’s condition to an erosive type, and monitoring progression of the disease
    • Only supportive in diagnosing juvenile idiopathic arthritis (JIA) since results may be normal
  • Advised in patients who present with symptoms of >4 weeks duration

Erythrocyte Sedimentation Rate (ESR) and C-reactive Protein (CRP)

  • Inflammatory markers but have low specificity for juvenile idiopathic arthritis 
    • ESR may be helpful in measuring active disease at onset and during follow up visits, especially in patients with polyarticular or systemic-onset juvenile idiopathic arthritis
    • May be used to monitor disease activity and treatment response

Rheumatoid Factor (RF)

  • Inconclusive test since present in only small percentage of patients with juvenile idiopathic arthritis
  • Recommended in patients with polyarthritis
  • Positive result may indicate possibility of an aggressive disease and poorer prognosis

Complete Blood Count (CBC)

  • May help identify presence of inflammation or anemia
    • Microcytic anemia may be present and attributable to chronic disease
    • Leukocytosis may be seen in children with active disease and platelet count elevated in severe systemic or polyarticular involvement

Antinuclear Antigen (ANA)

  • Should be assessed in all juvenile idiopathic arthritis patients
    • Identifies the risk for the development of asymptomatic uveitis, especially in patients with oligoarticular-onset disease
    • Present in 40-50% of patients with polyarthritis, 70-85% of patients with oligoarthritis, 10% of patients with systemic juvenile idiopathic arthritis and negative in patients with enthesitis-related juvenile idiopathic arthritis
    • Risk for chronic uveitis is increased with ANA seropositivity

Human Leukocyte Antigen (HLA)-B27

  • May be used in diagnosing patients with enthesitis-related arthritis
  • May indicate risk for the development of axial arthritis

Anti-cyclic Citrullinated Peptide (anti-CCP) Antibodies

  • May indicate severe disease but may not be advised in all patients

Others: Double-stranded Deoxyribonucleic Acid (dsDNA), Extractable Nuclear Antigens (ENA), C3, C4 and Immunoglobulin (Ig)

  • May be helpful if the arthritis is part of an underlying connective tissue disease or vasculitis
  • Studies have showed that serum levels Ig correlate with disease activity and acute phase response

Imaging

  • Plain radiographs
    • Less costly, easily available and faster way to evaluate joints but limited and nonspecific for early juvenile idiopathic arthritis (JIA) changes
    • Helps identify erosions which is apparent in a disease of >3 months duration
    • May be used to rule out other diagnosis and to confirm clinical findings
    • Soft tissue swelling, periarticular osteoporosis and periosteal new-bone apposition around affected joints are the early radiographic changes of arthritis
    • Subchondral erosions, loss of cartilage, different degrees of bone destruction and bone fusion may be seen in x-rays of patients with continued active juvenile idiopathic arthritis
    • Serial x-rays may show disease progression and may indicate the need for change in patient’s management 
  • Ultrasound
    • May be used to confirm joint effusions, specifically in the hip and shoulder joints where fluid is often difficult to see clinically
  • Magnetic resonance imaging (MRI)
    • More sensitive to early changes than x-rays
    • Identifies inflammatory changes in the joint and damages in the cartilage, and assesses early changes in the soft-tissue
    • Also accurate in evaluating late manifestations of juvenile idiopathic arthritis (ie erosions, loss of joint space, damage in the cartilage and involvement of ligaments)
  • Technetium-99 bone scan
    • May also help in detecting early stage of inflammatory arthritis

JIA Treatment Group

  • Management of juvenile idiopathic arthritis (JIA) patients were based on their treatment groups since there are few evidence to support the differential treatment of children with juvenile idiopathic arthritis for different category distinctions
    • Based on patient’s disease activity level and presence or absence of poor prognostic features
     Juvenile Idiopathic Arthritis (JIA)  Treatment Group  Juvenile Idiopathic Arthritis (JIA)  Subtype Features of Poor Prognosis (must satisfy at least 1) Disease Activity Levels
    Low 
    (must satisfy all)
    Moderate
    (does not satisfy high or low criteria)
    High 
    (must satisfy at least 3)
    ≤4 joints throughout their disease course
    • Persistent oligoarthritis
    • Psoriatic arthritis
    • Enthesitis-related arthritis
    • Undifferentiated arthritis
    • Hip or cervical spine arthritis
    • Ankle or wrist arthritis and marked or prolonged increase in inflammatory markers
    • Erosions or joint space narrowing seen on X-ray
    • ≤1 active joints
    • Normal erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) level
    • Physician (MD) global assessment1 of overall disease activity <3 of 10
    • Patient/parent global assessment2 of overall well-being <2 of 10
    • ≥1 features more than low disease activity level and <3 features of high disease activity
    • ≥2 active joints
    • ESR or CRP >2x upper limit of normal (ULN)
    • MD global assessment1 of overall disease activity ≥7 of 10
    • Patient/parent global assessment2 of overall well-being ≥4 of 10
    ≥5 joints throughout their disease course
    • Extended oligoarthritis
    • Rheumatoid factor (RF)-negative polyarthritis
    • Rheumatoid factor (RF)-positive polyarthritis
    • Psoriatic arthritis
    • Enthesitis-related arthritis
    • Undifferentiated arthritis
    • Hip or cervical spine arthritis
    • Positive RF or anti-cyclic citrullinated peptides (CCP) antibodies
    • Erosions or joint space narrowing seen on X-ray
    • ≤4 active joints
    • Normal ESR or CRP level
    • MD global assessment1 of overall disease activity <4 of 10
    • Patient/parent global assessment2 of overall well-being <2 of 10
    • ≥1 features more than low disease activity level and <3 features of high disease activity
    • ≥8 active joints
    • ESR or CRP >2x ULN
    • MD global assessment1 of overall disease activity ≥7 of 10
    • Patient/parent global assessment2 of overall well-being ≥5 of 10
    Active sacroiliac arthritis
    • Psoriatic arthritis
    • Enthesitis-related arthritis
    • May be any of the JIA subtype
    • Erosions or joint space narrowing seen on X-ray
    • Normal back flexion
    • Normal ESR or CRP level
    • MD global assessment1 of overall disease activity <4 of 10
    • Patient/parent global assessment2 of overall well-being <2 of 10
    • ≥1 features more than low disease activity level and <2 features of high disease activity
    • ESR or CRP >2x ULN
    • MD global assessment1 of overall disease activity ≥7 of 10
    • Patient/parent global assessment2 of overall well-being ≥4 of 10
    Systemic arthritis with active arthritis and without active systemic features Systemic arthritis with active arthritis
    • Hip arthritis
    • Erosions or joint space narrowing seen on X-ray
    • ≤4 active joints
    • Normal ESR or CRP level
    • MD global assessment1 of overall disease activity <4 of 10
    • Patient/parent global assessment2 of overall well-being <2 of 10
    • ≥1 features more than low disease activity level and <3 features of high disease activity
    • ≥8 active joints
    • ESR or CRP >2x ULN
    • MD global assessment1 of overall disease activity ≥7 of 10
    • Patient/parent global assessment2 of overall well-being ≥5 of 10
    Systemic arthritis with active systemic features and without active arthritis Systemic arthritis with active fever of systemic JIA with or without other systemic features and without active arthritis
    • 6 months duration of significant active systemic disease (eg fever, increased inflammatory markers, systemic corticosteroids required for the treatment)
    • Active fever and MD global assessment1 of overall disease activity <7 of 10
    • Active fever and systemic features of high disease activity that result in MD global assessment1 of overall disease activity ≥7 of 10

    Modified from: Beukelman T, Patkar NM, Saag KG, et al. 2011 American College of Rheumatology recommendations for the treatment of juvenile idiopathic arthritis: initiation and safety monitoring of therapeutic agents for the treatment of arthritis and systemic features. Arthritis Care and Research.2011;63:465-482.

    1Physician’s (MD) global assessment consists of rating the overall level of the child’s disease activity based on a 10 cm visual analogue scale (VAS): 0=no activity; 10=maximum activity
    2Parent’s global assessment consists of their rating on the child’s overall well-being based on a 10 cm VAS: 0=very good; 10=very poor

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