What labs should be sent for synovial fluid analysis in a patient with an unexplained knee effusion?

Synovial Fluid Analysis for Unexplained Knee Effusion

For unexplained knee effusion, synovial fluid analysis should include total cell count with differential, Gram stain, aerobic and anaerobic bacterial cultures, crystal analysis, and specialized tests such as leukocyte esterase and alpha-defensin when infection is suspected. 1

Core Synovial Fluid Tests

Essential Tests (Send for All Unexplained Effusions)

• Total cell count and differential leukocyte count 1

  • Helps distinguish inflammatory from non-inflammatory processes
  • Cell count >2,000 cells/mm³ suggests inflammation

  • 90% neutrophils suggests infection or crystal arthropathy

• Crystal analysis 1

  • Polarized light microscopy to identify:
    • Monosodium urate crystals (gout) - needle-shaped, negatively birefringent
    • Calcium pyrophosphate crystals (pseudogout) - rhomboid-shaped, weakly positive birefringent
  • Should be performed even during asymptomatic periods, as crystals may be present in 70% of patients with crystal arthropathy 1

• Aerobic and anaerobic bacterial cultures 1

  • Essential to rule out infection, which can coexist with other conditions
  • Withhold antibiotics for at least 2 weeks prior to aspiration if clinically safe to do so 1

Additional Tests Based on Clinical Suspicion

• When infection is suspected:

  • Gram stain (limited sensitivity but rapid results) 1
  • Leukocyte esterase (rapid bedside test) 1
  • Alpha-defensin (high sensitivity and specificity for prosthetic joint infection) 1
  • C-reactive protein in synovial fluid 1
  • Nucleic acid amplification testing (PCR for bacteria) 1

• When hemarthrosis is suspected:

  • Red blood cell count
  • Examination for sickled erythrocytes in patients with sickle cell disease 2

Clinical Algorithm for Synovial Fluid Analysis

1. Before aspiration:

   • Obtain serum ESR and CRP (abnormal in both suggest infection) 1
   • Obtain plain radiographs 1
   • If on antibiotics, withhold for 2 weeks if medically stable 1
   • Consider blood cultures if fever present 1

2. During aspiration:

   • Note gross appearance (color, clarity, viscosity) 3
   • Collect sufficient fluid for all required tests (minimum 2-3 mL)
   • Use appropriate collection tubes (sterile, no additives for culture)

3. Interpretation of results:

   • Non-inflammatory: <2,000 WBC/mm³, <25% PMNs
   • Inflammatory: 2,000-50,000 WBC/mm³, >50% PMNs
   • Septic: >50,000 WBC/mm³, >90% PMNs
   • Crystal-induced: Variable WBC count, presence of crystals

Important Caveats and Pitfalls

• Coexistent conditions: Septic arthritis can coexist with crystal arthropathy; always culture even when crystals are identified 1
• False negatives: Recent antibiotic use may lead to false-negative cultures 1
• Timing issues: Synovial fluid should be examined promptly (within 1 hour) for accurate crystal analysis 4
• Prosthetic joints: In prosthetic joint infection, multiple samples (3-6) should be collected to increase diagnostic yield 1
• Limited sensitivity: Gross analysis alone has a sensitivity of 94% but specificity of only 58% for determining inflammatory vs. non-inflammatory effusions 3
• Specialized tests: Alpha-defensin testing has shown excellent sensitivity (97%) and specificity (96%) for prosthetic joint infection 1

By following this systematic approach to synovial fluid analysis, clinicians can efficiently diagnose the cause of unexplained knee effusions and provide appropriate treatment to reduce morbidity and improve quality of life.