A synovial fluid test for infected joint replacements

The Accuracy of the Alpha Defensin Lateral Flow Device for Diagnosis of Periprosthetic Joint Infection Comparison with a Gold Standard

These authors examined the accuracy for the detection of periprosthetic hip and knee infections (i.e. those meeting the criteria established by the Musculoskeletal Infection Society) of a rapid lateral flow version of the alpha defensin test in a aspirate of synovial fluid.

The study group included patients with pain after total hips or total knees. There were 119 joints with an aseptic revision and 76 joints with periprosthetic joint infection according to the MSIS criteria (Clin Orthop Relat Res (2011) 469:2992–2994)

The overall sensitivity of the Synovasure Alpha Defensin Test was 92.1%, the specificity was 100%, the positive predictive value was 100%, and the negative predictive value was 95.2%. The overall accuracy of the Synovasure test was 96.9%.

The culture results of the aspirates are shown below.

The authors conclude that the "Synovasure Alpha Defensin Test with a lateral fl ow device demonstrates encouraging results with high accuracy for diagnosing infection following total hip arthroplasty and total knee arthroplasty. However, the test is associated with high costs, which is a limiting factor. Further cost-benefit studies will determine if the high costs of this new tool are justifiable."

Comment: With respect to the use of such a study in the evaluation of patients with pain after a shoulder arthroplasty, we must recall that a high percentage of these patients have positive deep tissue and explant cultures for Propionibacterium but do not meet the MSIS criteria for a periprosthetic infection. It is well recognized that the stealth presentation of a failed shoulder arthroplasty with positive cultures can occur months or years after the joint replacement. It would be of interest to learn the sensitivity of this new test in the evaluation of these patients.

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Shoulder joint replacement arthroplasty - are synovial interleukin-6 (IL-6) and alpha defensin levels a help?

Synovial fluid interleukin-6 as a predictor of periprosthetic shoulder infection.

These authors prospectively enrolled 32 patients evaluated for pain at the site of a shoulder arthroplasty and who subsequently underwent revision surgery.. Cases were categorized into infection (n = 15) and no-infection (n = 20) groups on the basis of objective preoperative and intraoperative findings. Twenty patients treated with arthroscopic rotator cuff repair were also enrolled to serve as a non-infected control group. Synovial fluid was obtained through aspiration intraoperatively for all patients, as well as preoperatively for some. Synovial fluid IL-6 levels were measured with use of a cytokine immunoassay that utilizes electrochemiluminescent detection.

Based on receiver operating characteristic curve analysis, synovial fluid IL-6 measurement had an area under the curve of 0.891 with an ideal cutoff value of 359.3 pg/mL. The sensitivity, specificity, and positive and negative likelihood ratios were 87%, 90%, 8.45, and 0.15, respectively. Seven patients who underwent a single-stage revision had negative results on standard perioperative testing, including the erythrocyte sedimentation rate and C-reactive protein levels, but multiple positive intraoperative tissue cultures. The level of synovial fluid IL-6 was elevated in five of these seven patients, with a median value of 1400 pg/mL. Intraoperative synovial fluid IL-6 values correlated well with preoperative IL-6 synovial fluid values (correlation = 0.61; p = 0.025) and frozen-section histologic findings (p < 0.001). Synovial fluid IL-6 levels were also significantly elevated in patients with Propionibacterium acnes infection (p = 0.01).

The chart below shows the IL-6 levels in pg/mL for the median, 25th and 75th percentiles for different clinical groups.

The graph below shows the same data.

The correlation between preoperative and intraoperative synovial IL-6 levels was only moderate for the nine shoulders having both assays, but 8 of the 9 had preoperative and intraoperative values that were consistent in terms of being above or below the threshold of 359.3 pg/mL.

Comment: Any port in a storm! All of us performing revision shoulder arthroplasty are grateful for preoperative indicators of the presence or absence of Propionibacterium and other 'stealth' organisms.

We look forward to more data on this new approach.

It is of interest to compare the results reported from this study with those from a study of Alpha Defensin by the same authors:

Alpha-Defensin as a predictor of periprosthetic shoulder infection

The authors evaluated 30 patients had 33 revisions for failed arthroplasty. Cases were categorized into infection (n = 11) and no-infection (n = 22) groups on the basis of preoperative and intraoperative findings. Synovial fluid was obtained from preoperative aspirations or intraoperative aspiration before arthrotomy and tested for α-Defensin levels. Synovial fluid was also obtained intraoperatively from a control group undergoing arthroscopic rotator cuff repair (n = 16) for baseline data on normal α-defensin levels in the shoulder.

Synovial α-defensin had an area under the receiver operating curve, sensitivity, specificity, and positive and negative likelihood ratios of 0.78, 63%, 95%, 12.1, and 0.38, respectively. There was a significant difference in α-defensin levels between the infection (median, 3.2 S/CO [signal to cutoff ratio]) and no-infection groups (median, 0.21 S/CO; P = .006). Synovial α-defensin was elevated in the presence of a culture positive for Propionibacterium acnes (median, 1.33 S/CO; P = .03) and showed moderate correlation with the number of positive cultures.

Comparing these two tests, we see that IL-6 is more sensitive and alpha defensin is more specific.

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