The Limitations of Gram-stain Microscopy of Synovial Fluid in Concomitant Septic and Crystal Arthritis

Curr Rheumatol Rev. 2018;14(3):255-257. doi: 10.2174/1573397113666170329123308.


Background: Rapid diagnosis of septic arthritis from Gram-stain microscopy is limited by an inherent false-negative rate of 25-78%. The presence of concomitant crystal arthritis in 5% of cases represents a particular diagnostic challenge.

Objectives: This study aims to investigate the effects that a concomitant crystal arthropathy has on the ability of Gram-stain microscopy of synovial fluid to diagnose a septic arthritis.

Methods: This is a 22-year retrospective cohort study. Inclusion criteria were a positive synovial fluid culture result with a positive clinical diagnosis of septic arthritis. Results were correlated with the presence or absence of urate and calcium pyrophosphate crystals, and Gram-stain result. During this time our collection and analysis methods remained unchanged. All samples were collected in Lithium Heparin containers. Chi-squared test with a p value < 0.05 was considered significant.

Results: 602 synovial fluid samples were included. 162 cases of concomitant crystal arthritis were identified (27%). Of these, 16 (10%) had an initial negative Gram-stain. Out of the 440 samples with no crystals detected, 18 (4%) had an initial negative Gram-stain microscopy result (p < 0.05).

Conclusion: The incidence of concurrent septic and crystal arthritis may be higher than previously thought. Synovial fluid samples in concomitant septic and crystal arthritis are significantly less likely to have a positive Gram-stain at microscopy than in cases of an isolated septic arthritis. We would advise the clinician to maintain a high index of suspicion for septic arthritis in these patients.

Keywords: Gram-stain; calcium pyrophosphate; crystals; lithium heparin; microscopy; septic arthritis..

MeSH terms

  • Arthritis, Infectious / diagnosis*
  • Arthritis, Infectious / epidemiology
  • Arthritis, Infectious / microbiology
  • Bacteria / isolation & purification*
  • Bacteriological Techniques*
  • Biomarkers / analysis
  • Calcium Pyrophosphate / analysis*
  • Crystal Arthropathies / diagnosis*
  • Crystal Arthropathies / epidemiology
  • Crystal Arthropathies / metabolism
  • Crystallization
  • England / epidemiology
  • Gentian Violet
  • Humans
  • Incidence
  • Microscopy
  • Phenazines
  • Predictive Value of Tests
  • Reproducibility of Results
  • Retrospective Studies
  • Risk Factors
  • Staining and Labeling
  • Synovial Fluid / chemistry*
  • Synovial Fluid / microbiology*
  • Uric Acid / analysis*


  • Biomarkers
  • Gram's stain
  • Phenazines
  • Uric Acid
  • Gentian Violet
  • Calcium Pyrophosphate