Periprosthetic infections – infections around hip or knee replacements – represent a serious and growing challenge for orthopedic patients, frequently enough leading to implant failure and the need for revision surgery. New research published in The Journal of Arthroplasty suggests a more accurate way to diagnose these infections, particularly in the acute phase, by focusing on the interleukin-6 (IL-6) biomarker. A study conducted at lanzhou University Hospital in China demonstrates IL-6’s potential to improve early detection and treatment strategies for these challenging-to-diagnose infections.
Joint replacement infections, also known as periprosthetic infections (PPIs), are a serious complication and a leading cause of early failure in hip and knee replacements. Diagnosing these infections can be challenging and requires analyzing various tests, including measuring inflammatory markers in the blood such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP).
These markers are commonly used to diagnose chronic periprosthetic infections, but their use is more complex in acute infections. While sensitive, they lack specificity, as the body’s inflammatory response to surgery itself can elevate their levels. Recent research suggests that interleukin-6 (IL-6), a pro-inflammatory cytokine, may be more effective at detecting acute cases.
A recent study published in The Journal of Arthroplasty compared the diagnostic accuracy of five blood-based biomarkers – IL-6, CRP, ESR, fibrinogen (FIB), and platelet count (PLT) – in both acute and chronic periprosthetic infections.
Study Details
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The research was conducted at Lanzhou University Hospital in China and included 218 patients who underwent revision hip or knee surgery between 2016 and 2022.
Patients were divided into three groups:
- Acute periprosthetic infection: 46 participants;
- Chronic periprosthetic infection: 62 participants;
- Non-infectious mechanical failure (control group): 110 participants.
Infection diagnosis followed the 2013 international consensus criteria. Biomarkers were assessed in blood samples collected from patients, and the results were analyzed for sensitivity and specificity using receiver operating characteristic (ROC) curves.
Findings
The results indicated that different biomarkers play a primary role in diagnosing acute versus chronic cases.
- IL-6 showed the best accuracy for diagnosing acute PPI. ROC curve evaluation showed excellent accuracy with a cutoff point of 7.2 pg/mL, resulting in a sensitivity of 93.5% and a specificity of 83.6%. Its negative predictive value was 96.8%, indicating a high probability of ruling out infection with a negative result.
- CRP was the best marker for chronic cases. ROC curve analysis established a cutoff point of 15.1 mg/L for a sensitivity of 77.4% and a specificity of 91.8%.
Why Does IL-6 Stand Out in Acute Infection?
IL-6’s strong performance in evaluating acute cases may be explained by its early action as a cytokine released in the initial stages of an attack, such as an infection. Its role in the inflammatory cascade, as a key inducer of acute-phase proteins including CRP, suggests that in acute PPI cases, where the host response is more vigorous and immediate, IL-6 levels rise more rapidly and prominently, making it a more sensitive marker for early detection.
Even in cases of infection with negative cultures, IL-6 showed a lower rate of false negatives compared to the other biomarkers studied.
How Could This Research Change Practice?
Findings from studies like this could lead to updated protocols and consensus guidelines for screening and diagnosing PPIs, particularly in the setting of acute infections.
Early diagnosis of infection increases the chances of successful treatment that can preserve the implant, avoiding the need for additional surgeries and reducing associated costs and morbidity.
While IL-6 shows promise for evaluating acute cases, CRP remains an important marker for screening for chronic infections.
The study’s results suggest that using IL-6 with a cutoff point of 7.2 pg/mL is a valuable marker for acute periprosthetic infections with excellent accuracy. Incorporating this new marker into future algorithms could optimize the treatment of challenging acute periprosthetic infection cases.
Joint replacement infections are a significant concern for patients, and identifying better diagnostic tools is crucial for improving outcomes.
