Differential synovial fluid white blood cell count for the diagnosis of chronic peri-prosthetic joint infection - a systematic review and meta-analysis.

Introduction: Peri-prosthetic joint infection (PJI) is a significant complication of arthroplasty, lacking a single gold standard diagnostic test. Synovial fluid white blood cell (WBC) count and polymorphonuclear neutrophil (PMN) proportion are widely used diagnostic tools, but their optimal cutoffs remain unclear, particularly for chronic PJI. Material and methods: This systematic review and meta-analysis included 74 studies published between 2000 and 2024. Data on diagnostic performance (sensitivity, specificity, and diagnostic odds ratios - DORs) of WBC count and PMN proportions were analysed. Sub-group analyses and heterogeneity assessments were performed, and optimal cutoffs for diagnostic accuracy were identified. Results: The meta-analysis revealed a WBC count summary DOR of 58.38 (95 % CI - confidence interval: 48.48-70.32) with an area under the curve (AUC) of the summarized receiver operating characteristic curve of 0.952. The PMN proportion showed a DOR of 43.17 (95 % CI: 35.31-52.79) and an AUC of 0.941. Optimal diagnostic thresholds for chronic PJI were WBC count $>$ 2600 cells per microlitre and PMN $>$ 70 %. Rule-in thresholds (specificity $>95$ %) were WBC count $\ge$ 3000 cells per microlitre and PMN $\ge$ 75 %, while rule-out thresholds (sensitivity $>$ 95 %) were WBC count $\le$ 1500 cells per microlitre and PMN $\le$ 65 %. Confounding conditions such as fractures, inflammatory arthritis, and metal-related reactions reduced test accuracy. Conclusions: Synovial fluid analysis remains a critical diagnostic tool for chronic PJI. Thresholds of WBC count $<$ 1500 and $>3000$  cells per microlitre and PMN $<$ 65 % and $>75$ % provide reliable negative and positive predictive values. A standardized diagnostic framework is essential for addressing remaining controversies and ensuring consistent interpretation across clinical settings.