Diagnostic Utility of a Novel Point-of-Care Test of Calprotectin for Periprosthetic Joint Infection After Total Knee Arthroplasty A Prospective Cohort Study

Jared Warren, DO, ATC, CSCS, Hiba K. Anis, MD, Kathleen Bowers, BS, Tejbir Pannu, MD, Jesus Villa, MD, Alison K. Klika, MS, Jessica Colon-Franco, PhD, Nicolas S. Piuzzi, MD, and Carlos A. Higuera, MD

The Journal of Bone and Joint Surgery, Volume 104, Issue 8, April 5, 2021
DOI: 10.2106/JBJS.20.01089

Summary: Ilan Small, BS

As the number of patients who are diagnosed with periprosthetic joint infection (PJI) rises, it is increasingly important to utilize effective diagnostic tools (1). PJI diagnose is complicated by the fact that no individual test is entirely sufficient, yet the various factors to confirm PJI may conflict with each other (2). Although point-of-care (POC) tests to diagnosis PJI are currently being investigated, these tests are not currently commonly used. Prior studies on synovial calprotectin have demonstrated this protein’s ability to act as a biomarker to rule out a PJI diagnosis (3,4). The objective of Warren et al’s study was to determine the feasibility of a calprotectin POC test for diagnosing PJI in patients undergoing revision total knee arthroplasty (rTKA) according to the 2013 Musculo-skeletal Infection Society (MSIS). 

The authors collected synovial fluid from 123 patients undergoing rTKA from two institutions within a single healthcare system from October 2018 to January 2020. Data collected included demographic, clinical, and laboratory data according to MSIS criteria. Aseptic or septic revisions were classified according to 2013 MSIS criteria by two blinded independent reviewers. Calprotectin levels were divided into three diagnostic categories: Low risk: <14 mg/L, moderate risk: 14 – < 50 mg/L, and high risk: ≥ 50 mg/L.  For calprotectin thresholds of 14 mg/L and 50 mg/L, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the receiver operating characteristic curves (AUC) were calculated.

70 rTKAs were aseptic and 53 rTKAs were septic according to MSIS criteria. The sensitivity, specificity, PPV, NPV, and AUC respectively for the ≥ 14 mg/L threshold were found to be 98.1, 87.1, 85.2, 98.4, and 0.926. The sensitivity, specificity, PPV, NPV, and AUC respectively for the ≥ 50 mg/L threshold were found to be 98.1, 95.7, 94.5, 98.5, and 0.969.

As a diagnostic tool, Warren et al. concluded that the calprotectin POC test may be used to diagnose and rule out PJI in rTKA due to its high sensitivity and specificity. These findings are in concordance with two prior pilot studies, which also concluded that calprotectin levels are useful for diagnosing PJI (3,4). Limitations of the study included the relatively small cohort size, lack of clinical follow-up or external validation, and 19 patients did not have histologically evaluated tissues to diagnose PJI via MSIS criteria.

References

  1. Kurtz SM, Lau EC, Son MS, Chang ET, Zimmerli W, Parvizi J. Are we winning or losing the battle with periprosthetic joint infection: trends in periprosthetic joint infection and mortality risk for the Medicare population. J Arthroplasty. 2018 Oct; 33(10):3238-45. Epub 2018 Jun 1.
  2. Tande AJ, Patel R. Prosthetic joint infection. Clin Microbiol Rev. 2014;27(2):302–45.
  3. Wouthuyzen-Bakker M, Ploegmakers JJW, Ottink K, Kampinga GA, Wagen- makers-Huizenga L, Jutte PC, Kobold ACM. Synovial calprotectin: an inexpensive biomarker to exclude a chronic prosthetic joint infection. J Arthroplasty. 2018 Apr; 33(4):1149-53. Epub 2017 Nov 13.
  4. Wouthuyzen-Bakker M, Ploegmakers JJW, Kampinga GA, Wagenmakers-Hui- zenga L, Jutte PC, Muller Kobold AC. Synovial calprotectin: a potential biomarker to exclude a prosthetic joint infection. Bone Joint J. 2017 May;99-B(5):660-5.

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