Combined Measurement of Synovial Fluid α-Defensin and C-Reactive Protein Levels: Highly Accurate for Diagnosing Periprosthetic Joint Infection

Background: The diagnosis of periprosthetic joint infection remains a challenge. The purpose of this study was to evaluate the combined measurement of the levels of two synovial fluid biomarkers, alpha-defensin and C-reactive protein (CRP), for the diagnosis of periprosthetic joint infection. Methods: One hundred and forty-nine synovial fluid aspirates, including 112 from patients with an aseptic diagnosis and thirty-seven from patients with periprosthetic joint infection, met the inclusion criteria for this prospective study. Synovial fluid aspirates were tested for alpha-defensin and CRP levels with use of enzyme-linked immunosorbent assay (ELISA). The Musculoskeletal Infection Society (MSIS) definition of periprosthetic joint infection was utilized for the classification of cases as aseptic or infected. Comorbidities, such as inflammatory conditions, that could confound a test for periprosthetic joint infection were documented, but the patients with such comorbidities were included in the study. Results: The combination of synovial fluid alpha-defensin and CRP tests demonstrated a sensitivity of 97% and a specificity of 100% for the diagnosis of periprosthetic joint infection. Synovial fluid alpha-defensin tests alone demonstrated a sensitivity of 97% and a specificity of 96% for the diagnosis of periprosthetic joint infection. Synovial fluid CRP tests, with a low threshold of 3 mg/L, reversed all-false positive alpha-defensin results without affecting the sensitivity of the test. The diagnostic characteristics of these assays were achieved in a population of patients demonstrating a 23% rate of systemic inflammatory diseases (in the series as a whole) and a 27% rate of concurrent antibiotic treatment (in the infection group). The synovial fluid levels of alpha-defensin in the setting of periprosthetic joint infection were unchanged during concurrent antibiotic treatment. Conclusions: The combined measurement of synovial fluid alpha-defensin and CRP levels correctly diagnosed 99% of the cases in this study as aseptic or infected. This was achieved despite the inclusion of patients with systemic inflammatory disease and those receiving treatment with antibiotics.