Serum versus synovial fluid interleukin-6 for periprosthetic joint infection diagnosis: a systematic review and meta-analysis of 30 diagnostic test accuracy studies

Abstract

Background Early and accurate detection of periprosthetic joint infection (PJI) after hip and/or knee arthroplasty remains challenging. This systematic review and meta-analysis of diagnostic test accuracy studies aimed to evaluate the diagnostic accuracy of serum and synovial fluid interleukin (IL)-6 in detecting PJI. Methods We searched 3 databases for studies through December 31, 2021, using medical sub-headings terms and keywords. Studies reported sensitivity and specificity of serum and synovial fluid IL-6 in detecting PJI were considered. We calculated the pooled sensitivity, specificity, positive and negative likelihood ratio, diagnostic odds ratio (DOR), and the area under the summary receiver operating characteristic curve (AUC) to evaluate the diagnostic accuracy of serum and synovial fluid IL-6. Results Thirty studies were included. The pooled sensitivity, specificity, positive and negative likelihood ratio, DOR, and AUC of serum IL-6 in detecting PJI were 0.76 (0.69–0.81), 0.88 (0.82–0.92), 6.2 (4.3–9.0), 0.28 (0.22–0.35), 22 (14–36), and 0.88 (0.85–0.91), respectively. However, synovial fluid IL-6 achieved a pooled sensitivity of 0.87 (0.75–0.93), specificity of 0.90 (0.85–0.93), positive and negative likelihood ratio of 8.5 (5.3–13.6) and 0.15 (0.08–0.29), DOR of 57 (21–156), and AUC of 0.94 (0.92–0.96), which were higher than serum IL-6. Conclusions Synovial fluid IL-6 test may be a promising test for PJI after hip and/or knee arthroplasty. However, considering the limited volume of synovial fluid and invasive acquisition of synovial fluid IL-6, serum IL-6 test may be also considered.

Diagnostic accuracy of interleukin-6 in multiple diseases: An umbrella review of meta-analyses

“…The sensitivity, specificity, and AUC of synovial IL-6 as a diagnostic biomarker for periprosthetic joint infection (PJI) in patients who underwent arthroplasty were found to be 0.76 (95% CI: 0.65, 0.84), 0.91 (95% CI: 0.88, 0.94), and 0.93, respectively [ 57 ]. In patients undergoing hip and/or knee replacement, the sensitivity, specificity, DOR, AUC, PLR, and NLR of serum IL-6 for PJI were 0.76 (95% CI: 0.69, 0.81), 0.88 (95% CI: 0.82, 0.92), 22.00 (95% CI: 14.00, 36.00), 0.88 (95% CI: 0.85, 0.91), 6.20 (95% CI: 4.30, 9.00), and 0.28 (95% CI: 0.22, 0.35), respectively [ 58 ]. The data for the corresponding synovial IL-6 for PJI were 0.87 (95% CI: 0.75, 0.93), 0.90(95% CI: 0.85, 0.93), 57.00 (95% CI: 21.00, 156.00), 0.94 (95% CI: 0.92, 0.96), 8.50 (95% CI: 5.30, 13.60), and 0.15 (95% CI: 0.08, 0.29), respectively [ 58 ].…”

“…In patients undergoing hip and/or knee replacement, the sensitivity, specificity, DOR, AUC, PLR, and NLR of serum IL-6 for PJI were 0.76 (95% CI: 0.69, 0.81), 0.88 (95% CI: 0.82, 0.92), 22.00 (95% CI: 14.00, 36.00), 0.88 (95% CI: 0.85, 0.91), 6.20 (95% CI: 4.30, 9.00), and 0.28 (95% CI: 0.22, 0.35), respectively [ 58 ]. The data for the corresponding synovial IL-6 for PJI were 0.87 (95% CI: 0.75, 0.93), 0.90(95% CI: 0.85, 0.93), 57.00 (95% CI: 21.00, 156.00), 0.94 (95% CI: 0.92, 0.96), 8.50 (95% CI: 5.30, 13.60), and 0.15 (95% CI: 0.08, 0.29), respectively [ 58 ]. In adults and children (<18 years) who underwent major abdominal gastrointestinal (GI) and hepatobiliary (HPB) surgeries, the sensitivity, specificity, and DOR of IL-6 for PJI were 0.84 (95% CI: 0.72, 0.92), 0.76 (95% CI: 0.68, 0.84), and 17.36 (95% CI: 7.10, 42.43), respectively [ 59 ].…”

Diagnosis of Periprosthetic Joint Infection: The Utility of Biomarkers in 2023

“…In a recent systematic review and meta-analysis by Li et al [ 64 ], which encompassed thirty studies, the pooled sensitivity and specificity of serum IL-6 in detecting PJI ranged from 0.76 to 0.88. Interestingly, the literature reports varying sensitivity and specificity values at different cutoff values when investigating the utility of IL-6 in detecting PJI.…”