Diagnostic Accuracy of Neutrophil Counts in Histopathological Tissue Analysis in Periprosthetic Joint Infection Using the ICM, IDSA, and EBJIS Criteria

Overview

Journal Bone Joint Res

Date 2021 Aug 19

PMID 34409845

Citations 11

Authors

Irene K Sigmund

Martin A McNally

Markus Luger

Christoph Bohler

Reinhard Windhager

Irene Sulzbacher

Affiliations

Soon will be listed here.

Abstract

Aims: Histology is an established tool in diagnosing periprosthetic joint infections (PJIs). Different thresholds, using various infection definitions and histopathological criteria, have been described. This study determined the performance of different thresholds of polymorphonuclear neutrophils (≥ 5 PMN/HPF, ≥ 10 PMN/HPF, ≥ 23 PMN/10 HPF) , when using the European Bone and Joint Infection Society (EBJIS), Infectious Diseases Society of America (IDSA), and the International Consensus Meeting (ICM) 2018 criteria for PJI.

Methods: A total of 119 patients undergoing revision total hip (rTHA) or knee arthroplasty (rTKA) were included. Permanent histology sections of periprosthetic tissue were evaluated under high power (400× magnification) and neutrophils were counted per HPF. The mean neutrophil count in ten HPFs was calculated (PMN/HPF). Based on receiver operating characteristic (ROC) curve analysis and the z-test, thresholds were compared.

Results: Using the EBJIS criteria, a cut-off of ≥ five PMN/HPF showed a sensitivity of 93% (95% confidence interval (CI) 81 to 98) and specificity of 84% (95% CI 74 to 91). The optimal threshold when applying the IDSA and ICM criteria was ≥ ten PMN/HPF with sensitivities of 94% (95% CI 79 to 99) and 90% (95% CI 76 to 97), and specificities of 86% (95% CI 77 to 92) and 92% (95% CI 84 to 97), respectively. In rTKA, a better performance of histopathological analysis was observed in comparison with rTHA when using the IDSA criteria (p < 0.001).

Conclusion: With high accuracy, histopathological analysis can be supported as a confirmatory criterion in diagnosing periprosthetic joint infections. A threshold of ≥ five PMN/HPF can be recommended to distinguish between septic and aseptic loosening, with an increased possibility of detecting more infections caused by low-virulence organisms. However, neutrophil counts between one and five should be considered suggestive of infection and interpreted carefully in conjunction with other diagnostic test methods. Cite this article: 2021;10(8):536-547.

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References

Parvizi J . New definition for periprosthetic joint infection. Am J Orthop (Belle Mead NJ). 2012; 40(12):614-5. View

Morawietz L, Tiddens O, Mueller M, Tohtz S, Gansukh T, Schroeder J . Twenty-three neutrophil granulocytes in 10 high-power fields is the best histopathological threshold to differentiate between aseptic and septic endoprosthesis loosening. Histopathology. 2009; 54(7):847-53. DOI: 10.1111/j.1365-2559.2009.03313.x. View

McNally M, Sousa R, Wouthuyzen-Bakker M, Chen A, Soriano A, Vogely H . The EBJIS definition of periprosthetic joint infection. Bone Joint J. 2020; 103-B(1):18-25. PMC: 7954183. DOI: 10.1302/0301-620X.103B1.BJJ-2020-1381.R1. View

Parvizi J, Tan T, Goswami K, Higuera C, Della Valle C, Chen A . The 2018 Definition of Periprosthetic Hip and Knee Infection: An Evidence-Based and Validated Criteria. J Arthroplasty. 2018; 33(5):1309-1314.e2. DOI: 10.1016/j.arth.2018.02.078. View

Kwiecien G, George J, Klika A, Zhang Y, Bauer T, Higuera Rueda C . Intraoperative Frozen Section Histology: Matched for Musculoskeletal Infection Society Criteria. J Arthroplasty. 2016; 32(1):223-227. DOI: 10.1016/j.arth.2016.06.019. View

Banit D, Kaufer H, Hartford J . Intraoperative frozen section analysis in revision total joint arthroplasty. Clin Orthop Relat Res. 2002; (401):230-8. DOI: 10.1097/00003086-200208000-00026. View

Nilsdotter-Augustinsson A, Briheim G, Herder A, Ljunghusen O, Wahlstrom O, Ohman L . Inflammatory response in 85 patients with loosened hip prostheses: a prospective study comparing inflammatory markers in patients with aseptic and septic prosthetic loosening. Acta Orthop. 2007; 78(5):629-39. DOI: 10.1080/17453670710014329. View

. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013; 310(20):2191-4. DOI: 10.1001/jama.2013.281053. View

Tohtz S, Muller M, Morawietz L, Winkler T, Perka C . Validity of frozen sections for analysis of periprosthetic loosening membranes. Clin Orthop Relat Res. 2009; 468(3):762-8. PMC: 2816749. DOI: 10.1007/s11999-009-1102-5. View

10.

Buttaro M, Martorell G, Quinteros M, Comba F, Zanotti G, Piccaluga F . Intraoperative synovial C-reactive protein is as useful as frozen section to detect periprosthetic hip infection. Clin Orthop Relat Res. 2015; 473(12):3876-81. PMC: 4626517. DOI: 10.1007/s11999-015-4340-8. View

11.

Renz N, Yermak K, Perka C, Trampuz A . Alpha Defensin Lateral Flow Test for Diagnosis of Periprosthetic Joint Infection: Not a Screening but a Confirmatory Test. J Bone Joint Surg Am. 2018; 100(9):742-750. DOI: 10.2106/JBJS.17.01005. View

12.

Athanasou N, Pandey R, de Steiger R, McLardy Smith P . The role of intraoperative frozen sections in revision total joint arthroplasty. J Bone Joint Surg Am. 1997; 79(9):1433-4. View

13.

Parvizi J, Zmistowski B, Berbari E, Bauer T, Springer B, Della Valle C . New definition for periprosthetic joint infection: from the Workgroup of the Musculoskeletal Infection Society. Clin Orthop Relat Res. 2011; 469(11):2992-4. PMC: 3183178. DOI: 10.1007/s11999-011-2102-9. View

14.

Feldman D, Lonner J, Desai P, Zuckerman J . The role of intraoperative frozen sections in revision total joint arthroplasty. J Bone Joint Surg Am. 1995; 77(12):1807-13. DOI: 10.2106/00004623-199512000-00003. View

15.

Zhao X, Guo C, Zhao G, Lin T, Shi Z, Yan S . Ten versus five polymorphonuclear leukocytes as threshold in frozen section tests for periprosthetic infection: a meta-analysis. J Arthroplasty. 2013; 28(6):913-7. DOI: 10.1016/j.arth.2012.10.015. View

16.

Della Valle C, Sporer S, Jacobs J, Berger R, Rosenberg A, Paprosky W . Preoperative testing for sepsis before revision total knee arthroplasty. J Arthroplasty. 2007; 22(6 Suppl 2):90-3. DOI: 10.1016/j.arth.2007.04.013. View

17.

Sigmund I, Holinka J, Lang S, Stenicka S, Staats K, Hobusch G . A comparative study of intraoperative frozen section and alpha defensin lateral flow test in the diagnosis of periprosthetic joint infection. Acta Orthop. 2019; 90(2):105-110. PMC: 6461083. DOI: 10.1080/17453674.2019.1567153. View

18.

Pons M, Angles F, Sanchez C, Matamala A, Cuchi E, Salavert M . Infected total hip arthroplasty--the value of intraoperative histology. Int Orthop. 1999; 23(1):34-6. PMC: 3619779. DOI: 10.1007/s002640050299. View

19.

Tsaras G, Maduka-Ezeh A, Inwards C, Mabry T, Erwin P, Murad M . Utility of intraoperative frozen section histopathology in the diagnosis of periprosthetic joint infection: a systematic review and meta-analysis. J Bone Joint Surg Am. 2012; 94(18):1700-11. DOI: 10.2106/JBJS.J.00756. View

20.

Fink B, Makowiak C, Fuerst M, Berger I, Schafer P, Frommelt L . The value of synovial biopsy, joint aspiration and C-reactive protein in the diagnosis of late peri-prosthetic infection of total knee replacements. J Bone Joint Surg Br. 2008; 90(7):874-8. DOI: 10.1302/0301-620X.90B7.20417. View