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Basics ⬇

[Section Outline]

Author:

Kathleen A.Kerrigan

SulynnWalker

Description!!navigator!!

Etiology!!navigator!!

Believed to be an autoimmune and autoinflammatory disease triggered by an unknown environmental trigger in a genetically susceptible host

Diagnosis ⬆ ⬇

[Section Outline]

Subtypes!!navigator!!

ALERT
  • Systemic onset JIA patients are at risk for macrophage activation syndrome (MAS)
  • MAS is a proliferation of macrophages with cytokine release causing a DIC-like picture with resultant fever, mucosal bleeding, neurologic changes, and multiorgan failure which may be fatal mortality 8-22%
  • Immediate treatment needed
  • ESR may be normal in active MAS
  • Oligoarticular:
    • 30-60% of JIA
    • 3:1 girls, peak incidence 2-4 yr olds
    • Insidious onset and child appears healthy
    • ≤4 joints involved at 6 mo:
      • Involves larger joints asymmetrically, (89% knee) hip rarely affected
      • Joints swollen, mildly tender, no erythema, with decreased range of motion (ROM), possible leg-length discrepancy
      • Boys >6 yr old no HLA-B27
      • No enthesitis
    • Uveitis in about 20%; increased if ANAs present; no other systemic signs
    • Subsets: Based on joints affected after 6 mo persistent (1-4); extended (>4) worse prognosis
  • Polyarticular:
    • 20-30% of cases, girls > boys, bimodal peaks: 2-5 and 10-14 yr
    • Subgroups based on RF- and RF+, RF- > RF+
    • >4 joints involved at 6 mo:
      • Arthritis often symmetrical, small or large joints - commonly knees, wrists, and ankles
      • Decreased ROM of cervical and lumbar spine and temporomand ibular joint (TMJ)
    • Systemic involvement rare in RF - except for fatigue and anemia
    • Older girls with RF+ often go on to develop typical adult rheumatoid arthritis (RA) and are placed in a separate subtype
  • Psoriatic:
    • Arthritis; asymmetric large joints of lower extremities and back
    • Classified by arthritis and psoriatic rash or arthritis and 2 of the following: Dactylitis, nail pitting, onycholysis (separation of nail from nail bed, or psoriatic rash in first-degree relative
    • Enthesitis(inflammation at the insertion of a muscle or tendon) related
    • Bimodal peak of onset
    • May only affect 1 joint; 80% <5 joints
    • Sacroiliac (SI) joint pain
    • Limited flexion of lumbar spine
    • Uveitis in 10-15%
    • Often FH
  • Enthesitis-related arthritis (ERA):
    • Classified by arthritis or enthesitis and at least 2 of the following: SI tenderness, HLA-B27, anterior uveitis (symptomatic) or + FH of anterior uveitis, spondyloarthropathy, or IBD
    • Large or small joint involvement, multiple joints
    • Symmetrical axial involvement
    • May be previously diagnosed with spondyloarthritis
    • Male >6 yr
  • Other:
    • Arthritis that does not fully fulfil any above category or fits into multiple categories

History

  • Findings based on specific subtype
  • Classic presentation is insidious arthritis, worse in AM and with periods of immobility, improved with ROM
  • New-onset systemic subtype most likely to use ED because they appear acutely ill, whereas other subtypes have a more insidious onset
ALERT
  • Child with severe pain and red-hot joint probably does not have new-onset JIA
  • Initial presentation may be very similar to infection or malignancy; always consider
  • Rapid onset of polyarticular joint involvement is atypical for JIA; infectious or reactive cause of arthritis should be ruled out
  • Beware of occult infection in patients on immunosuppressants

Physical Exam

  • Determine if child is systemically ill: Search for fever, rash, or other nonarthritic involvement
  • Do careful joint evaluation, documenting the number of joints involved and noting whether they are red, warm, and swollen or have limited ROM

Essential Workup!!navigator!!

Diagnostic Tests & Interpretation!!navigator!!

Lab

  • CBC, ESR; if ill appearance, add blood cultures
  • Other labs if suspicious of specific subtype: Rheumatoid factor (RF)X2 >3 mo apart, antinuclear antibodies (ANA), HLA-B27, LFTs:
    • Systemic - ESR often elevated, leukocytosis, thrombocytosis, anemia, minor AST/ALT elevations, positive RF or ANA rarely seen, MAS may be associated with elevated LFTs, hypertriglyceridemia, hypofibrinogenemia, cytopenia, and elevated ferritin but will often have normal ESR
    • Oligoarticular - common to have positive ANA in young girls; other labs usually normal; if anemic or elevated ESR, are probably misclassified or extended subtype
    • Polyarticular - may be anemic; if positive RF more likely to go on to adult RA, ESR may be elevated
    • Enthesitis - more likely positive HLA; presence of positive RF or positive ANA specifically excludes enthesitis subtype
    • Psoriatic arthritis - usually seronegative RF
  • Unfortunately, RF and ESR may also be elevated in acute infection unrelated to JIA
ALERT
Consider adding Lyme titer if new joint swelling in endemic area

Imaging

  • Joint radiograph:
    • Early presentation: Soft tissue swelling, joint effusion
    • Late presentation: Osteoporosis, joint destruction, early growth plate closure
  • US:
    • Can detect subclinical synovitis
    • Improves classification for subtypes
    • Captures early articular damage
    • Intra-articular steroid (IAS) injection guidance
    • Useful for guiding arthrocentesis

Diagnostic Procedures/Surgery

Arthrocentesis if concern for septic arthritis: 5,000-8,000 WBC/mm3 with negative Gram stain and culture typical for JIA

Differential Diagnosis!!navigator!!

Treatment ⬆ ⬇

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Initial Stabilization/Therapy!!navigator!!

Toxic-appearing children: IV access, O2

ED Treatment/Procedures!!navigator!!

Medication!!navigator!!

ALERT
As early aggressive therapy may prevent some of the long-term complications of JIA, start DMARDs and biologic agents early. These medications have serious potential side effects, including:
  • Immunosuppression
  • Decreased vaccine response (live vaccinations are contraindicated)
  • TB activation - children should initially be tested for latent TB and if risk, change to moderate or high
  • Increased potential for malignancy
  • NSAIDs:
    • First line for oligoarticular and polyarticular +/- IAS
    • NSAIDs rarely lead to disease activity reduction
    • Ibuprofen: 30-40 mg/kg divided t.i.d-q.i.d
    • Naproxen: 10-20 mg/kg divided b.i.d; max daily dose 1,000 mg
    • Indomethacin: 1-2 mg/kg/d in 2-4 doses
    • Side effects: Gastritis, hepatitis, renal, headache, dermatitis
  • IAS:
    • Triamcinolone hexacetonide: 1 mL/mg of 20 mg/mL solution
    • Often provide long-term (6-18 mo) relief; if <4 mo consider escalation of therapy
  • Systemic corticosteroids:
    • Corticosteroids - uncommon; may be used as short-course bridge in patients with severe polyarticular disease or in systemic JIA with MAS, myocarditis, or serositis
    • Prednisone: 0.5-2 mg/kg PO
    • Methylprednisolone: 30 mg/kg daily IV up to 1 g for 1-5 d for high-dose pulse steroids
    • Side effects: Gastritis, adrenal suppression, osteopenia, Cushing syndrome, infection
  • DMARDs:
    • MTX: 5-15 mg/m2 PO/SC/IM per week - inhibits dihydrofolate reductase (SC better bioavailability)
      • First-line DMARD
      • Improvement usually in 6-8 wk
      • Side effects: GI, nausea, liver toxicity, teratogenic
    • Leflunomide: 100 mg for 1, 2, or 3 d then 10 or 20 mg based on weight. To be used in patients with mild disease who are intolerant to MTX (not FDA approved)
    • Biologic agents - engineered to target specific key cytokines, very expensive
    • Tissue necrosis factor binders
  • Biologics:
    • Target-specific cytokines - used on patients who fail or are intolerant to DMARDS
    • TNF-α inhibitors; use when MTX >3 mo with moderate to high disease activity
    • Etanercept: 0.4 mg/kg SC twice a week or 0.8 mg/kg SC once a week
    • Adalimumab: <30 kg: 20 mg, >30 kg: 40 mg given SC administered every other week
      • Side effects: Infection, injection-site reactions, inhibit T-cell activation
    • Abatacept: 10 mg/kg infusion q4wk
      • Selective T-cell costimulatory blocker
      • Side effects: Infusion reaction, HA, cough, nausea, infection
    • Tocilizumab: 8-12 mg/kg infusion q4wk (or 8 mg/kg IV q2wk for systemic JIA)
      • IL6 receptor antagonist
      • Side effects: Infection, metabolic, hepatic
    • Anakinra: 2 mg/kg SC daily
      • IL1 receptor antagonist
      • For patients with recalcitrant systemic features
      • Side effects: Infection, antibody development, headache, vomiting
      • Not FDA approved
    • Canakinumab: 4 mg/kg q4wk; use in SJIA
      • IL1 receptor antagonist
      • Side effects: Infection, Injection site reaction, weight gain, diarrhea
  • Stem cell transplants are used rarely for severe cases unresponsive to medical treatment:
    • Treatment for MAS is nonstand ardized but may include high-dose steroids, cyclosporine, or intravenous immunoglobulin

Follow-Up ⬆ ⬇

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Disposition!!navigator!!

Admission Criteria

Unclear diagnosis in ill-appearing child or if concern of secondary joint infection

Discharge Criteria

  • No evidence of septic joint, systemic infection, or organ failure from drug therapy
  • Patient appears comfortable
  • Appropriate follow-up has been arranged

Issues for Referral

  • Orthopedics if septic joint suspected
  • Rheumatologist if meds need adjustment

Follow-up Recommendations!!navigator!!

Pearls and Pitfalls ⬆ ⬇

  • Rule out acute joint infection (always consider Lyme disease in the appropriate geographic context) and malignancy
  • Consider SJIA in child with prolonged diurnal febrile illness that is unresponsive to antibiotics
  • Consider MAS in SJIA patients who appear septic and treat immediately
  • Review patient's medications to identify potential side effects or immunosuppression

Additional Reading ⬆ ⬇

See Also (Topic, Algorithm, Electronic Media Element)

Codes ⬆

ICD9

ICD10

SNOMED