Diagnostic Approaches for PJI Continue to Evolve

Recently published study details evidence-based and validated criteria

“The 2018 Definition of Periprosthetic Hip and Knee Infection: An Evidence-Based and Validated Criteria,” published in The Journal of Arthroplasty, attempts to address the limitations of previous guidelines and aid clinicians and surgeons in navigating this often-difficult diagnosis. Javad Parvizi, MD, of the Rothman Institute, is the study’s lead author.The definition of periprosthetic joint infection (PJI), a devastating complication that can be challenging to diagnose, with no single test providing absolute accuracy, is evolving. In 2011, the Musculoskeletal Infection Society (MSIS) introduced guidelines to help streamline the definition and diagnosis of PJI, after which the International Consensus Meeting (ICM) developed additional parameters. Unfortunately, the recommendations were based largely on expert opinion. With no true evidence-based criteria in place, along with the emergence of many novel diagnostic markers, new guidelines were necessary.

A new design

With a team of international PJI experts and skilled biostatisticians, Parvizi et al., created the first evidence-based, weight-adjusted, and externally validated scoring system for diagnosing hip and knee PJI. The multicenter group retrospectively evaluated patients undergoing revision hip and knee arthroplasty for suspected PJI. Cases meeting major diagnostic criteria for chronic PJI were included in the development model. Specific diagnostic tests, such as erythrocyte sedimentation rate and C-reactive protein (CRP), were then incorporated and evaluated within the model. Individual tests were evaluated by random forest analysis and converted to single integer point scores reflecting the test’s sensitivity and specificity to accurately diagnose PJI. Consequently, the new weighted scores were established based upon pretest probability. The scores then were organized into a stepwise approach for diagnosing PJI, beginning with serum biomarkers to evaluating intraoperative findings, if needed (Fig. 1).

Once the model was constructed, the new criteria were validated on a separate holdout cohort of patients revised for both PJI and aseptic complications from three major institutions and compared to previous definitions. The results were striking: The new criteria revealed a significantly higher sensitivity than the ICM and MSIS definitions (97.7 percent, 86.9 percent, and 79.3 percent, respectively). Specificity (99.5 percent) remained constant among criteria. A false negative rate of 2.3 percent in the new definition was favorable compared to 20.7 percent with the MSIS criteria.

Practical application

The study results extend beyond establishing evidence-based and externally validated guidelines for PJI. “The new definition has the advantage of guiding the orthopaedic community through a validated and clinically useful algorithm,” said Dr. Parvizi. “The previous diagnostic criteria have been replaced completely by the new diagnostic criteria in my practice,” he added.

The new criteria also account for several novel tests for diagnosing PJI, such as D-dimer, synovial CRP, and alpha-defensin, which were not included in the previous definitions. Interpretation of those markers has traditionally created confusion; however, the new algorithm allows the novel measures to be combined with other common markers to increase pretest probability of PJI. Using the tests in combination through the algorithm increases their utility and orthopaedists’ ability to recognize PJI. Furthermore, serum and synovial biomarkers in combination with intraoperative findings create a relatively simple three-step approach to diagnosis. The score is calculated as an aggregate between steps, with a collective score of six or greater indicating infection. Weighted scores alert physicians to the highest yield testing options for a given patient and may eliminate the need for additional and expensive tests such as bone scans, CT, and MRI.

Fig. 1 Stepwise approach to periprosthetic joint infection diagnosis
Copyright: Parvizi J, Tan TL, Goswami K, et al: The 2018 definition of periprosthetic hip and knee infection: an evidence-based and validated criteria. J Arthroplasty 2018;33:1309-14.e2.

In addition to lacking external validation, weighted scoring, and incorporation of newer tests, previous criteria do not account for PJI chronicity or diagnostic invasiveness. “Based on that data from three institutions, 20 percent to 25 percent of the PJI cases were previously missed [by] MSIS and ICM criteria. The reason being that some PJI cases caused by slow-growing organisms such as Propionibacterium acnes and coagulase-negative Staphylococci did not elicit enough physiological response by the host to cause a rise in the serum and synovial inflammatory markers. The new definition now catches those cases without over-diagnosing PJI,” said Dr. Parvizi.

Although the new definition further simplifies PJI diagnosis, as with any criteria, the scoring system can be tedious to memorize. In a busy practice, this may hinder timely diagnosis. To help, Dr. Parvizi and his team developed a user-friendly mobile app complete with a score calculator. Following a series of questions, the diagnosis is revealed, leading to an evidence-based conclusion. Additionally, the algorithm has the capability of identifying a subset of patients (2 percent to 3 percent) in whom a diagnosis of PJI is unclear—those who do not explicitly meet inclusion or exclusion criteria. For such patients, the guidelines will recommend following the patient or repeating tests.

Future directions

Research that attempts to reveal the unknown and optimize the known with respect to PJI continues to emerge. Although the 2018 definition performs significantly better than previous criteria, a subset of patients will evade correct and timely diagnosis. In their analysis, Parvizi et al., identified several scenarios where the proposed criteria may have limitations. Such cases include adverse local tissue reactions, crystalline deposition arthropathies, inflammatory arthropathy flares, and infections with slow-growing organisms. Further research is needed to differentiate such patients. Next-generation sequencing (NGS) is showing promise when diagnostic results are inconclusive. Although NGS has revealed encouraging results for culture-negative PJI, further studies are needed to elucidate the precise utility of NGS in routine clinical practice.

The 2018 definition and diagnostic criteria for PJI are a validated, evidence-based approach that will likely help orthopaedists reduce the ambiguity of PJI diagnosis. “I believe the new diagnostic criteria will remove the mystery that surrounded the diagnosis of PJI in hip and knee arthroplasty,” said Dr. Parvizi.

For a PJI risk calculator, visit https://bit.ly/2GTXYiW.

Brandon Naylor, DO, is an orthopaedic surgery resident at Mercy Health in Toledo, Ohio, and an AAOS Resident Assembly delegate.

Gabriel Makar, BS, is a third-year medical student at Cooper Medical School of Rowan University in Camden, N.J., and an AAOS Resident Assembly delegate.


  1. Huiskes R: Failed innovation in total hip replacement: diagnosis and proposals for a cure. Acta Orthop Scand 1993;64:699-716.
  2. Hoskin HLD, Furie E, Collins W, et al: Mechanics and complications of reverse shoulder arthroplasty: morse taper failure analysis and prospective rectification. J Phys Conf Ser 2017; 843:012019.
  3. AAOS: Code of Medical Ethics and Professionalism for Orthopaedic Surgeons. Available at: https://www.aaos.org/uploadedFiles/PreProduction/About/Opinion_Statements/ethics/Code%20of%20Ethics%202013%20color%20logo.pdf