Is the Enzyme-linked Immunosorbent Assay More Accurate Than the Lateral Flow Alpha Defensin Test for Diagnosing Periprosthetic Joint Infection?

BACKGROUND: Alpha defensin was proposed as a new biomarker in synovial fluid for the diagnostic workup of failed joint prostheses. To our knowledge, no comparative study of the performance of the quantitative enzyme-linked immunosorbent assay (ELISA) and qualitative lateral flow alpha defensin test has been reported. QUESTIONS/PURPOSES: (1) Using the proposed European Bone and Joint Infection Society (EBJIS) criteria for defining periprosthetic joint infection (PJI), is there a difference in the diagnostic accuracy of quantitative ELISA and qualitative lateral flow alpha defensin tests? (2) Is there a difference in the performance of the two alpha defensin tests when using three definition classification systems (Musculoskeletal Infection Society [MSIS], Infectious Diseases Society of America [IDSA], and proposed EBJIS)?
METHODS: In this retrospective study of samples collected earlier as part of a related longitudinal study, we included patients in whom aspiration of the prosthetic hip or knee was performed as routine investigation before every revision arthroplasty. Between October 2016 and April 2017, a total of 73 patients were eligible for inclusion. As a result of an insufficient fluid volume for analysis (< 5 mL), two patients were excluded. Among the 71 patients in the final analysis, 54 had a knee and 17 a hip arthroplasty. Using the proposed EBJIS criteria, PJI was diagnosed in 22 patients (31%) and aseptic failure in 49 (69%). The alpha defensin ELISA and lateral flow tests were performed in synovial fluid. Patients were classified as having PJI or aseptic failure using the MSIS, the IDSA, and the proposed EBJIS criteria. Sensitivity and specificity of ELISA and the lateral flow alpha defensin test were calculated. Based on receiver operating characteristic analysis, area under the curve values were compared.
RESULTS: When measured against the proposed EBJIS criteria, the sensitivity of alpha defensin ELISA and the lateral flow test was low and not different from one another with the numbers available at 50% (95% confidence interval [CI], 31%-69%) and 46% (95% CI, 27%-65%; p = 0.857), respectively, whereas both methods showed high specificity (98% [95% CI, 88%-100%]; p = 1.000). For sensitivity, the highest values were seen when compared against the MSIS criteria (ELISA: 85% [95% CI, 56%-97%], lateral flow: 77% [95% CI]; p = 0.871), intermediate with IDSA criteria (ELISA: 73% [95% CI, 48%-89%], lateral flow: 67% [95% CI]; p = 0.867), and lowest with proposed EBJIS criteria (ELISA: 50% [95% CI, 31%-69%], lateral flow: 46% [95% CI]; p = 0.763). Specificity, however, was high regardless of the criteria used, where ELISA and lateral flow produced results that were not different (MSIS: 98% [95% CI, 90%-100%], IDSA: 98% [95% CI, 90%-100%], EBJIS: 98% [95% CI, 88%-100%]; p = 1.000). The area under the curve of alpha defensin ELISA and the lateral flow test was similar, regardless of the definition criteria used (EBJIS: p = 0.566; IDSA: p = 0.425; MSIS: p = 0.339).
CONCLUSIONS: There is no difference between the quantitative and qualitative alpha defensin test for confirmation of PJI, irrespective of applied definition criteria. Having the advantage of providing results within 10 minutes without the need for a laboratory facility, the qualitative test may be of interest in the intraoperative setting, however, at a cost of higher test expense. LEVEL OF EVIDENCE: Level I, diagnostic study.