Differential Diagnoses for Juvenile Arthritis in Lyme-Endemic Areas
In a Lyme-endemic region, the primary differential diagnoses for a juvenile patient with arthritis include systemic juvenile idiopathic arthritis (sJIA), oligoarticular JIA, polyarticular JIA, Lyme arthritis, reactive arthritis, and septic arthritis—with careful attention to excluding infectious etiologies before diagnosing JIA. 1, 2
Critical Initial Distinction: Infectious vs. Inflammatory Arthritis
Lyme Arthritis (High Priority in Endemic Areas)
- Lyme disease typically presents with oligoarticular arthritis (most commonly affecting the knee) developing weeks to months after initial infection 1
- Look for history of tick exposure, erythema migrans rash (though may be absent), and constitutional symptoms 1
- Serologic testing (Lyme IgG/IgM with Western blot confirmation) is essential in endemic areas 1
- Lyme arthritis responds to antibiotic therapy, whereas JIA does not—making this distinction critical 1
Septic Arthritis
- Acute onset (hours to days), monoarticular involvement, severe pain with refusal to bear weight 1
- Fever, elevated inflammatory markers, and joint aspiration showing purulent fluid with positive cultures 1
- Requires immediate arthrocentesis and empiric antibiotics—delay can cause irreversible joint damage 1
Systemic Juvenile Idiopathic Arthritis (sJIA)
Pathognomonic Clinical Triad
- Quotidian fever (daily spiking fevers to ≥39°C), evanescent salmon-pink maculopapular rash, and polyarthritis 3, 4
- The rash is typically non-pruritic, appears with fever spikes, and disappears between episodes 3, 4
- Fever must persist for ≥2 weeks with arthritis in ≥1 joint 2, 4
Additional Systemic Features
- Lymphadenopathy, hepatosplenomegaly, and serositis (pericarditis, pleuritis) 5, 4
- Markedly elevated ferritin (>1000 ng/mL) with decreased glycosylated ferritin (<20%) strongly supports sJIA 1, 3
- Leukocytosis with neutrophilia, elevated ESR/CRP, negative ANA, and negative RF 3, 4
Life-Threatening Complication
- Macrophage activation syndrome (MAS) occurs in 24-36% of sJIA patients and requires immediate recognition 6, 4
- MAS presents with persistent fever, cytopenias, elevated ferritin (often >10,000 ng/mL), elevated triglycerides, decreased fibrinogen, and hepatosplenomegaly 6, 4
Oligoarticular JIA
Clinical Presentation
- Arthritis affecting ≤4 joints during the first 6 months, with large joints (knees, ankles) more commonly involved than small joints 2, 7
- Typically affects young girls (peak age 2-4 years), often with positive ANA 2, 7
- Absence of systemic features (no fever, rash, or organomegaly) distinguishes this from sJIA 2, 7
Critical Complication
- Chronic anterior uveitis occurs in up to 30% of ANA-positive oligoarticular JIA patients and is asymptomatic 5, 2
- Requires slit-lamp examination every 3 months for high-risk patients (ANA+, age <6 years, disease duration <4 years) 5
- Uveitis can cause blindness if untreated—direct ophthalmoscopy is inadequate for detection 5
Polyarticular JIA
Defining Features
- Arthritis in ≥5 joints cumulatively, including both RF-positive and RF-negative subtypes 2, 7
- RF-positive polyarticular JIA resembles adult rheumatoid arthritis with symmetrical small joint involvement and erosive disease 1, 7
- RF-negative polyarticular JIA has variable joint involvement patterns 2, 7
Laboratory Findings
- Anti-citrullinated protein antibody (ACPA) has 90% specificity and 60% sensitivity, correlating with erosive disease 1
- Elevated CRP is the most clinically useful biomarker for disease activity 1
Enthesitis-Related Arthritis (ERA)
Clinical Criteria
- Arthritis and enthesitis, OR arthritis/enthesitis with ≥2 of: sacroiliac tenderness/inflammatory back pain, HLA-B27 positivity, family history of HLA-B27-associated disease, anterior uveitis, or male onset >6 years 1
- Lower extremity large joint arthritis (knees, ankles, hips) with enthesitis at Achilles insertion, plantar fascia, or patellar tendon 1
- Acute anterior uveitis (painful, red eye) differs from the chronic asymptomatic uveitis of oligoarticular JIA 1
Reactive Arthritis
Distinguishing Features
- Develops 1-6 weeks after gastrointestinal (Salmonella, Shigella, Campylobacter, Yersinia) or genitourinary (Chlamydia) infection 1
- Asymmetric oligoarthritis affecting lower extremities, often with enthesitis 1
- Self-limited course (typically resolves within 6 months) distinguishes reactive arthritis from JIA, which persists ≥6 weeks 1, 7
Essential Diagnostic Workup
Mandatory Laboratory Testing
- CBC with differential, ESR, CRP, ANA with titer, RF, ferritin, liver function tests, and albumin 1
- Lyme serology (IgG/IgM with Western blot) is mandatory in endemic areas 1
- Blood cultures if septic arthritis suspected 1
Imaging Studies
- Ultrasound and MRI are superior to clinical examination for detecting joint inflammation—ultrasound detects synovitis 1.19-fold more than clinical examination at the knee 1
- MRI detects synovitis 2.46-fold more than clinical examination in the temporomandibular joint 1
- Conventional radiography may be normal in early disease 1
Joint Aspiration
- Perform arthrocentesis for monoarticular arthritis to exclude septic arthritis—synovial fluid analysis with cell count, Gram stain, culture, and crystal analysis 1
Critical Pitfalls to Avoid
Premature JIA Diagnosis
- JIA is a diagnosis of exclusion—infectious arthritis, malignancy (leukemia, neuroblastoma), and other rheumatic diseases (SLE, vasculitis) must be excluded first 1, 7
- In Lyme-endemic areas, failure to test for Lyme disease before diagnosing JIA can result in inappropriate immunosuppression and progression of untreated infection 1
Delayed Ophthalmologic Screening
- Chronic uveitis in oligoarticular JIA is asymptomatic—waiting for visual symptoms results in irreversible vision loss 5
- Slit-lamp examination must begin at diagnosis and continue at risk-stratified intervals 5
Missing MAS in sJIA
- Persistent fever despite treatment, sudden clinical deterioration, or new cytopenias in sJIA should trigger immediate MAS evaluation 6, 4
- MAS has 8-20% mortality if untreated 4