Synovial fluid calprotectin performs better than synovial fluid polymerase chain reaction and interleukin-6 in the diagnosis of periprosthetic joint infection

Aims The preoperative diagnosis of periprosthetic joint infection (PJI) remains a challenge due to a lack of biomarkers that are both sensitive and specific. We investigated the performance char- acteristics of polymerase chain reaction (PCR), interleukin- 6 (IL6), and calprotectin of synovial fluid in the diagnosis of PJI. Methods We performed systematic search of PubMed, Embase, The Cochrane Library, Web of Science, and Science Direct from the date of inception of each database through to 31 May 2021. Stud- ies which described the diagnostic accuracy of synovial fluid PCR, IL6, and calprotectin using the Musculoskeletal Infection Society criteria as the reference standard were identified. Results Overall, 31 studies were identified: 20 described PCR, six described IL6, and five calprotectin. The sensitivity and specificity were 0.78 (95% confidence interval (CI) 0.67 to 0.86) and 0.97 (95% CI 0.94 to 0.99), respectively, for synovial PCR;, 0.86 (95% CI 0.74 to 0.92), and 0.94 (95% CI 0.90 to 0.96), respectively, for synovial IL6; and 0.94 (95% CI 0.82 to 0.98) and 0.93 (95% CI 0.85 to 0.97), respectively, for synovial calprotectin. Likelihood ratio scattergram analyses rec- ommended clinical utility of synovial fluid PCR and IL6 as a confirmatory test only. Synovial calprotectin had utility in the exclusion and confirmation of PJI. Conclusion Synovial fluid PCR and IL6 had low sensitivity and high specificity in the diagnosis of PJI, and is recommended to be used as confirmatory test. In contrast, synovial fluid calprotectin had both high sensitivity and specificity with utility in both the exclusion and confirmation of PJI. We recommend use of synovial fluid calprotectin studies in the preoperative workup of PJI.