What is the next step in managing a 10-year-old with a swollen and painful right knee for 4 weeks, with negative tests for Lyme (Lyme disease) disease, ESR (erythrocyte sedimentation rate) and sed (sedimentation) rate?

Arthrocentesis with Synovial Fluid Analysis is the Next Step

In a 10-year-old with 4 weeks of monoarticular knee swelling and pain, despite negative Lyme serology and normal inflammatory markers, you must perform arthrocentesis to obtain synovial fluid for cell count, Gram stain, culture, and PCR for Borrelia burgdorferi to definitively rule out septic arthritis and seronegative Lyme arthritis. 1, 2

Why Arthrocentesis is Critical

• Seronegative Lyme arthritis exists and can present exactly like this case, with monoarticular knee involvement and negative serologic testing, requiring PCR detection of Borrelia burgdorferi DNA in synovial fluid for diagnosis 1, 2
• A case report documented a 10-year-old with seronegative Lyme arthritis who remained seronegative for 3 years despite confirmed B. burgdorferi DNA in synovial fluid 2
• Septic arthritis remains in the differential even with normal ESR/CRP, as some children with bacterial joint infections can present with relatively modest inflammatory marker elevations 3
• Synovial fluid analysis provides definitive diagnostic information that cannot be obtained any other way, including cell count with differential, culture results, and molecular testing 1

What to Order on Synovial Fluid

Essential Tests

• Cell count with differential: Lyme arthritis typically shows 47,533-64,242 cells/mm³ (median ~55,888 cells/mm³) with neutrophil predominance 4
• Gram stain and bacterial culture: To definitively exclude septic arthritis 1
• PCR for Borrelia burgdorferi DNA: This is the gold standard for diagnosing seronegative Lyme arthritis when serologic testing is negative 1, 2

Interpretation Framework

• Synovial WBC >50,000 cells/mm³ with neutrophil predominance suggests either Lyme arthritis or septic arthritis; culture and PCR differentiate between them 1, 4
• If PCR is positive for B. burgdorferi despite negative serology, diagnose Lyme arthritis and treat accordingly 1, 2
• If both culture and PCR are negative, consider juvenile idiopathic arthritis (JIA) as the primary diagnosis 1

Why Normal ESR/Sed Rate Doesn't Exclude These Diagnoses

• Lyme arthritis can present with relatively modest inflammatory marker elevations, with mean ESR of 41 mm/hr in pediatric hip cases, and some patients having normal values 4
• The 4-week duration makes this chronic rather than acute inflammation, which may explain why acute phase reactants have normalized 1, 5
• Synovial inflammation can be significant even when systemic markers are normal, particularly in oligoarticular presentations 1

Geographic and Exposure Considerations

• Even without recalled tick bite, Lyme arthritis remains possible: Less than half of pediatric Lyme disease patients recall a tick bite 6
• Most patients with Lyme arthritis do not recall having erythema migrans or the characteristic rash, making diagnosis challenging 7
• If you practice in or the patient has traveled to a Lyme-endemic area (Northeast, Mid-Atlantic, Upper Midwest), the index of suspicion should be higher 4, 7

Treatment Implications Based on Arthrocentesis Results

If Lyme Arthritis is Confirmed (Positive PCR)

• Start oral antibiotics immediately: Doxycycline (if ≥8 years old), amoxicillin, or cefuroxime axetil for 28 days 1
• Patients with Lyme arthritis typically have strong serologic reactivity by the time arthritis develops, so negative serology with positive PCR represents an unusual but documented scenario 1, 2
• If arthritis persists after initial treatment, re-treat with another 4-week course of oral antibiotics or consider 2-4 weeks of IV ceftriaxone 1

If Septic Arthritis is Confirmed (Positive Culture)

• Immediate IV antibiotics and possible surgical drainage depending on organism and clinical response 3

If Both Tests are Negative

• Consider juvenile idiopathic arthritis (JIA): This 10-year-old with monoarticular knee involvement for 4 weeks fits the oligoarticular JIA pattern 1
• Start NSAIDs as first-line therapy for oligoarticular JIA without features of poor prognosis 1
• Intra-articular corticosteroid injection is appropriate for persistent monoarticular involvement 1
• Refer to pediatric rheumatology for ongoing management and monitoring 1

Common Pitfalls to Avoid

• Do not assume negative Lyme serology excludes Lyme arthritis: Seronegative cases exist and require PCR for diagnosis 1, 2
• Do not delay arthrocentesis waiting for inflammatory markers to rise: The diagnosis requires synovial fluid analysis regardless of ESR/CRP values 1
• Do not start empiric antibiotics before obtaining synovial fluid: This can render cultures falsely negative and complicate diagnosis 1
• Do not assume 4 weeks of symptoms excludes septic arthritis: While less likely, indolent bacterial infections can present subacutely 3