Synovial Fluid and Serum Neutrophil-to-Lymphocyte Ratio: Novel Biomarkers for the Diagnosis and Prognosis of Native Septic Arthritis in Adults

Abstract

Background: Septic arthritis (SA) is a musculoskeletal emergency for which prompt diagnosis and treatment are critical. However, traditional diagnostic criteria of a synovial fluid (SF) white blood-cell count (WBC) of >50,000 cells/mm 3 or >90% polymorphonuclear leukocytes (%PMN) are not particularly sensitive or specific for the diagnosis of SA. Furthermore, prognostic markers are lacking. The purposes of this study were to assess the discriminative ability of the SF neutrophil-to-lymphocyte ratio (NLR) in the diagnosis of SA and of the serum NLR in the prognosis of SA.

Methods: A multi-institution, retrospective study of 598 patients with native shoulder, hip, or knee SA in 2000 to 2018 was conducted. SF-NLR was calculated from the arthrocentesis cell count with differential. Receiver operating characteristic curves were analyzed, and the optimal threshold of SF-NLR for SA diagnosis was determined using the Youden index. Results were compared with traditional SF diagnostic criteria. Similar analyses assessed the association of serum NLR with 90-day treatment failure and mortality for the subset of patients with confirmed hip or knee SA and with serum complete blood-cell counts with differentials (n = 235). Results were compared with traditional serum prognostic markers (WBC, C-reactive protein [CRP], and erythrocyte sedimentation rate [ESR]).

Results: The SF-NLR (area under the receiver operating characteristic curve [AUC], 0.85 [95% confidence interval (CI), 0.82 to 0.88]) was significantly more accurate for an SA diagnosis than SF-WBC (AUC, 0.80 [95% CI, 0.76 to 0.83]; p = 0.002) and SF-%PMN (AUC, 0.81 [95% CI, 0.77 to 0.84]; p = 0.01). The optimal threshold of SF-NLR was 25 (78% sensitivity and 81% specificity), compared with >50,000 cells/mm 3 for SF-WBC (56% sensitivity and 80% specificity) and >90% for SF-%PMN (65% sensitivity and 78% specificity). Elevated serum NLR was independently associated with 90-day treatment failure (odds ratio [OR], 7.04 [95% CI, 3.78 to 13.14]; p < 0.001) and mortality (OR, 7.33 [95% CI, 2.00 to 26.92]; p = 0.003); elevated serum WBC and CRP were also associated with treatment failure, and WBC, CRP, and ESR were not associated with mortality.

Conclusions: This study provides compelling data on the superior diagnostic and prognostic ability of serum NLR and SF-NLR for SA compared with current clinical standards. Given that this biomarker requires no additional cost or time to return than current laboratory tests already being performed, pending validation, it can readily be used to aid clinicians in the diagnosis and prognostication of SA.

Level of evidence: Diagnostic Level IV . See Instructions for Authors for a complete description of levels of evidence.