The role of serum inflammatory biomarkers in the timely and accurate diagnosis of periprosthetic joint infections

Abstract

Periprosthetic joint infection (PJI) is a major complication in arthroplasty, where rapid and accurate diagnosis is critical to preserving prosthetic function and reducing morbidity. PJI triggers innate immune activation, cytokine release, and acute-phase protein production, leading to measurable serum biomarker changes. Acute PJIs typically show marked elevations in C-reactive protein (CRP) and interleukin-6 (IL-6), whereas chronic biofilm associated infections present with attenuated responses. Conventional biomarkers—CRP, erythrocyte sedimentation rate (ESR), and WBC count—remain first-line tests, each with distinct kinetics, thresholds, and limitations. Novel biomarkers such as IL-6, procalcitonin (PCT), D-dimer, and presepsin, as well as cytokines like TNF-α and IL-1β, may offer superior diagnostic performance, particularly when traditional results are inconclusive. Comparative studies and meta analyses show high sensitivity for CRP and IL 6 in acute settings, while D dimer and presepsin add value in selected cases. Combining biomarkers—especially CRP with IL-6—can achieve sensitivities and specificities above 90–95%. Importantly, low grade infections from organisms such as Cutibacterium acnes may yield near normal systemic markers, highlighting the role of adjunctive synovial fluid analysis. Overall, both traditional and emerging serum biomarkers are indispensable when incorporated into a multimodal diagnostic strategy, enhancing timely and accurate PJI detection.

Keywords: Periprosthetic joint infection, Serum biomarkers, Inflammatory markers, Diagnosis, C-reactive protein