Laboratory Workup for Suspected Infectious Arthritis
When infectious arthritis is suspected, immediately obtain ESR and CRP (both should be drawn together for optimal sensitivity), complete blood count with differential, synovial fluid analysis via arthrocentesis (including cell count with differential, Gram stain, and aerobic/anaerobic cultures), and blood cultures if fever or acute symptoms are present. 1, 2, 3, 4
Essential Initial Laboratory Tests
Inflammatory Markers (Draw First)
- ESR and CRP should be obtained in all patients with suspected infectious arthritis - the combination provides the best sensitivity and specificity for diagnosis 1, 2
- Use low thresholds for interpretation: ESR ≥10-15 mm/h has 94-98% sensitivity, and CRP ≥20 mg/L has 92% sensitivity for septic arthritis 5
- CRP is the most sensitive marker with 73-91% sensitivity and 81-86% specificity for prosthetic joint infection 2
- These markers are critical even though they are nonspecific, as normal values help exclude infection 4, 5
Complete Blood Count
- CBC with differential should be obtained to evaluate for systemic infection and leukocytosis 1, 6
- Note that peripheral WBC count is often NOT elevated in prosthetic joint infections, so a normal count does not exclude infection 2
Synovial Fluid Analysis (Most Critical Test)
Arthrocentesis should be performed in all patients with suspected acute infectious arthritis unless the diagnosis is clinically evident and surgery is already planned 1, 6
The synovial fluid analysis must include:
- Total cell count and differential leukocyte count - expect WBC >50,000/mm³ in native joint septic arthritis (but as low as >1,100/mm³ with >64% neutrophils in prosthetic joints) 1, 3, 4
- Gram stain - guides initial antibiotic selection 3, 4
- Aerobic and anaerobic cultures - definitive for pathogen identification 1, 3
- Crystal analysis - to exclude crystal arthropathy (gout/pseudogout), which can coexist with infection 6, 3
Critical timing consideration: If the patient is medically stable, withhold antimicrobial therapy for at least 2 weeks prior to collecting synovial fluid to increase organism recovery 1, 2
Blood Cultures
- Obtain blood cultures for aerobic and anaerobic organisms if: fever is present, acute onset of symptoms, or conditions suggesting bloodstream infection (e.g., suspected Staphylococcus aureus) 1, 6
Additional Laboratory Tests Based on Clinical Context
Baseline Metabolic Assessment
- Urinalysis - to exclude other systemic diseases 1
- Transaminases (liver function tests) - baseline before potential antibiotic therapy 1
- Renal function - baseline assessment 1
Autoimmune Screening (If Diagnosis Uncertain)
- Antinuclear antibodies (ANA) - to exclude connective tissue diseases that may mimic infection 1
- Rheumatoid factor and anti-CCP antibodies - if rheumatoid arthritis is in the differential 1, 6
Advanced Biomarkers (When Available)
For Prosthetic Joint Infections
- Interleukin-6 (IL-6) - provides higher predictive value than traditional markers when combined with CRP 2
- Synovial fluid alpha-defensin - highly accurate with 97% sensitivity and 96% specificity; when combined with synovial CRP, specificity increases to 100% 2
Common Pitfalls to Avoid
- Do NOT delay arthrocentesis - synovial fluid analysis is required to confirm diagnosis and cannot be replaced by serum markers alone 1, 6, 4
- Do NOT rely on fever or constitutional symptoms - these are poorly sensitive for septic arthritis 3, 4
- Do NOT use higher cutoffs for inflammatory markers - ESR ≥10 mm/h and CRP ≥20 mg/L are the appropriate thresholds for ruling out infection 5
- Do NOT start antibiotics before obtaining cultures when clinically feasible - this significantly reduces organism recovery 1, 2
- Do NOT assume normal peripheral WBC excludes infection - especially in prosthetic joint infections where leukocytosis is often absent 2
- Do NOT forget that crystal arthropathy and infection can coexist - always perform crystal analysis even when infection is suspected 6, 3