Serum Amyloid A Is a Promising Tool for Screening Periprosthetic Joint Infection

Although the modified Musculoskeletal Infection Society (MSIS) criteria are commonly used, the accurate and timely diagnosis of periprosthetic joint infection (PJI) remains challenging. Serum amyloid A, like C-reactive protein (CRP), is an acute-phase reactant and widely serves as a diagnostic tool for infectious diseases in adults and children. However, the role of serum amyloid A in diagnosing PJI has not been fully explored.

(1) What were the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) of serum amyloid A as a diagnostic test for PJI? (2) How did the diagnostic performance of serum amyloid A compare with that of other commonly used serum biomarkers?

Between October 2020 and October 2023, three surgeons performed 137 revision THA or TKA procedures. All were considered potentially eligible, but we excluded 20% (28 of 137) because of reimplantation, missing blood biomarker data, and periprosthetic fracture, leaving 80% (109) for analysis in this retrospective study. Those were divided into two groups: those believed to have PJI (62) based on the modified 2018 MSIS criteria and those who did not meet 2018 MSIS criteria (non-PJI, n = 47). The PJI group comprised 56% males (median age 66 years) with 23 hips and 39 knees affected, while the non-PJI group included 17% males (median age 66 years) involving 25 hips and 22 knees. All 47 revisions in the non-PJI group were followed for at least 1 year to make sure that they were not false negatives. No patients were lost to follow-up during this period. Diagnostic accuracy was assessed using receiver operating characteristic (ROC) curve analysis. Sensitivity, specificity, PPV, NPV, and AUC were calculated for all four routine tests (serum amyloid A, CRP, erythrocyte sedimentation rate [ESR], and fibrinogen) to determine their diagnostic capacity for PJI.

For the diagnosis of PJI, with a cutoff value of 14 based on the Youden index, serum amyloid A had a sensitivity of 85% (95% confidence interval [CI] 74% to 93%), a specificity of 96% (95% CI 86% to 100%), a PPV of 96% (95% CI 87% to 99%), and an NPV of 83% (95% CI 73% to 90%). Using the optimal cutoffs for the AUC of the ROC as calculated by the Youden index for each test, serum amyloid A was more accurate than the ESR (0.96 versus 0.85; p = 0.005) and plasma fibrinogen (0.96 versus 0.84; p = 0.002) but no different from the CRP (0.96 versus 0.93; p = 0.17).

Our study established serum amyloid A as a promising high-accuracy biomarker for PJI screening, demonstrating superior performance to ESR and fibrinogen while being comparable with the diagnostic performance of CRP. This provides surgeons with a novel tool for screening suspected PJI, particularly when interpreting ambiguous CRP and ESR results or requiring rapid decision-making, as its combination of rapid kinetics, cost-efficiency, short turnaround time, and high specificity reduce diagnostic delays. While our findings demonstrate promise, this study did not stratify PJI subtypes. Future large-scale multicenter studies should validate these findings across diverse patient populations and establish subtype-specific diagnostic thresholds for acute and chronic PJI presentations.

Level III, diagnostic study.