Inferior performance of established and novel serum inflammatory markers in diagnosing periprosthetic joint infections

Abstract

Purpose Besides other diagnostic test methods, established serum inflammatory markers such as serum C-reactive protein or leukocyte count are widely used preoperatively to aid in diagnosing periprosthetic joint infections (PJI). Although low accuracies were reported, these parameters are easily accessible and routinely available. Novel biomarkers with promising results in diagnosing PJI (platelet count to mean platelet volume ratio) or other infectious conditions (percentage of neutrophils, neutrophils to lymphocytes ratio) were described. The purpose of this study was to investigate the diagnostic value of established and novel serum inflammatory biomarkers for the diagnosis of PJI so as to compare the results to find the serum inflammatory marker with the best performance. Methods In 177 patients with a previous total hip (n = 91) or knee (n = 86) arthroplasty and indicated revision surgery, the diagnostic value of the routinely available serum inflammatory markers C-reactive protein (CRP), white blood cell count (WBC), percentage of neutrophils (%N), neutrophils to lymphocytes ratio (NLR), fibrinogen and platelet count to mean platelet volume ratio (PC/mPV) were examined retrospectively via receiver operating characteristic curve analysis (AUC). The curves were compared using the z-test. Results Sensitivities of serum CRP, WBC, %N, NLR, fibrinogen and PC/mPV were calculated with 68%, 36%, 66%, 63%, 69% and 43%, respectively. Specificities were 87%, 89%, 67%, 73%, 89% and 81%, respectively. Serum CRP (0.78) and fibrinogen (0.79) showed significantly better AUCs compared with serum WBC (0.63), %N (0.67), NLR (0.68) and PC/mPV (0.62) (p < 0.0001). Patients with PJI caused by a low-virulent microorganism (median CRP: 17.6 mg/L) obtained lower CRP levels compared with infections caused by high-virulent microorganisms (median CRP: 49.2 mg/L; p = 0.044). The combination of CRP and fibrinogen showed a better sensitivity (77%) with similar specificity (83%) than one method alone but not at a significant level (CRP (p = 0.200); fibrinogen (p = 0.437)). Conclusion Serum CRP and fibrinogen showed the best accuracies among these widely available serum inflammatory parameters. However, due to the insufficient performance, these biomarkers can only be recommended as suggestive criteria in diagnosing PJI. The preoperative workup should always be complemented by more specific tests such as synovial fluid analysis.

Combined Serum and Synovial C-Reactive Protein Tests: An Economical and Efficient Adjunct to the Diagnosis of Chronic Prosthetic Joint Infection

“…However, the serum CRP showed false-positive cases and, hence, a reduced speci city in our study, resulting in a potential overtreatment with unnecessary surgical revisions and prolonged antimicrobial treatment if used alone. The reasonable explanation is that CRP, a factor secreted by a variety of cells, increases to different degrees when the body is stimulated by in ammation [3,5]. Therefore, we investigated in ammatory markers of local synovial uid in joints with higher speci city [4].…”

“…Patients with chronic PJI, elevated serum in ammatory biomarkers, such as serum C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) may be the primary indications of PJI due to atypical clinical symptoms such as joint effusion, pain, swelling, and redness. However, due to insu cient speci city, these tests are not su cient to diagnose PJI alone [5]. They also need to be supplemented by more speci c tests, such as synovial uid analysis, microbial culture, and histopathology.…”

Soluble Pecam-1 as a Biomarker in Periprosthetic Joint Infection

“…While the existing PJI criteria systems lead to fair results, the diagnostic of persistent low-grade infections are insufficient, calling for the development of highly sensitive tools for early detection. Despite established evaluations of serum inflammatory markers, synovial fluid analysis can be seen as the diagnostic mainstay [8]. Within the current literature, many studies focus on new biomarkers for a reliable detection of PJI [2,9,10].…”

Neutrophil-to-Lymphocyte Ratio (NLR) and Platelet-to-Lymphocyte Ratio (PLR) Are Potentially Valuable Tests for Diagnosing Periprosthetic Joint Infection

“…However, a recent study by Sigmund et al had con icting results, in that NLR (AUC: 0.68) and PVR (AUC: 0.62) had inferior performance in the diagnosis of PJI compared with traditional biomarkers. They therefore suggested these markers should not be used alone for the diagnosis of PJI [16].…”