Calprotectin Lateral Flow Test: Consistent Across Criteria for Ruling Out Periprosthetic Joint Infection

Periprosthetic joint infection remains a major complication following joint replacement surgery. Multiple diagnostic criteria have been proposed to define infection, but their alignment with point-of-care testing remains unclear. Prior research has shown that synovial fluid biomarkers can support diagnosis, but no prior work had resolved how well a single point-of-care test performs across multiple diagnostic frameworks. This gap motivated a study to assess the calprotectin lateral flow test against three widely recognized infection definitions. It was already known that calprotectin is a reliable biomarker in synovial fluid; however, its performance in different diagnostic contexts had not been fully evaluated. The challenge lies in ensuring that a rapid test can consistently support clinical decisions regardless of the diagnostic criteria used. No prior work had resolved how much diagnostic accuracy varies with different criteria sets. This uncertainty drove the need for a prospective evaluation of the calprotectin test across three distinct definitions of periprosthetic joint infection.

The study aimed to evaluate the diagnostic accuracy of the calprotectin lateral flow point-of-care test in patients undergoing revision total knee arthroplasty. The specific problem addressed was the variability in periprosthetic joint infection definitions and how a single biomarker test performs across these definitions. The motivation was to determine whether the calprotectin test can reliably rule out infection regardless of the criteria used. The authors sought to compare the test's sensitivity and specificity using three different reference standards. The goal was to assess whether the test's performance remains consistent or changes depending on the diagnostic framework applied. This approach allows clinicians to use the same test with confidence across different diagnostic systems. The study also aimed to identify which criteria set provides the best alignment with the calprotectin test results. By doing so, the research sought to provide evidence supporting the use of a single point-of-care test across multiple clinical settings.

The study used a prospective design involving synovial fluid samples from revision total knee arthroplasty patients. A calprotectin lateral flow point-of-care assay was applied to each sample. Three established diagnostic criteria sets were used as reference standards: the 2013 Musculoskeletal Infection Society, the 2018 Intentional Consensus Meeting, and the 2019 European Bone and Joint Infection Society criteria. Two independent reviewers adjudicated the final diagnosis, blinded to the calprotectin test results. The study collected 123 intraoperative samples over a 17-month period. Each sample was tested for calprotectin levels using a lateral flow device. The test results were then compared against each of the three diagnostic criteria sets. The diagnostic performance metrics included sensitivity, specificity, positive predictive value, negative predictive value, and area under the curve. This approach allowed for a direct comparison of the test's accuracy across different diagnostic frameworks.

The calprotectin lateral flow test showed high diagnostic accuracy across all three criteria sets. Using the 2013 Musculoskeletal Infection Society criteria, the test had a sensitivity of 98.1%, specificity of 95.7%, and an area under the curve of 0.969. When applying the 2018 Intentional Consensus Meeting criteria, the test demonstrated a sensitivity of 98.2%, specificity of 98.5%, and an area under the curve of 0.984. Under the 2019 European Bone and Joint Infection Society criteria, the test showed a sensitivity of 93.2%, full specificity of 100.0%, and an area under the curve of 0.966. The agreement between the three criteria sets was 91.8%, indicating a high level of consistency in diagnosing infection. The highest performance was observed with the 2018 ICM criteria, which showed the best balance of sensitivity and specificity. The test's negative predictive value was consistently above 98% across all criteria sets. These results suggest that the calprotectin test can reliably detect infection regardless of the diagnostic framework used. The test's performance was not significantly affected by the choice of criteria, supporting its use in clinical practice.

The calprotectin lateral flow point-of-care test demonstrated excellent sensitivity and specificity across the three diagnostic criteria sets evaluated. The test performed best when using the 2018 Intentional Consensus Meeting criteria, with the highest area under the curve. The authors propose that the test can be used confidently to rule out periprosthetic joint infection in revision total knee arthroplasty patients. The high agreement between the three criteria sets suggests that the calprotectin test aligns well with current diagnostic standards. The test's performance was consistent across all three frameworks, supporting its reliability in clinical settings. The authors suggest that the calprotectin test may serve as a valuable tool in the rapid diagnosis of periprosthetic joint infection. The study does not claim that the test is essential for diagnosis but highlights its strong alignment with established criteria. These findings may inform the integration of point-of-care testing into routine diagnostic workflows.