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International Orthopaedics

, Volume 42, Issue 6, pp 1213–1226 | Cite as

Diagnostic accuracy of interleukin-6 and procalcitonin in patients with periprosthetic joint infection: a systematic review and meta-analysis

  • Jung-Ro Yoon
  • Se-Hyun Yang
  • Young-Soo Shin
Original Paper
  • 507 Downloads

Abstract

Purpose

Many studies have found associations between laboratory biomarkers and periprosthetic joint infection (PJI), but it remains unclear whether these biomarkers are clinically useful in ruling out PJI. This meta-analysis compared the performance of interleukin-6 (IL-6) versus procalcitonin (PCT) for the diagnosis of PJI.

Methods

In this meta-analysis, we reviewed studies that evaluated IL-6 or/and PCT as a diagnostic biomarker for PJI and provided sufficient data to permit sensitivity and specificity analyses for each test. The major databases MEDLINE, EMBASE, the Cochrane Library, Web of Science, and SCOPUS were searched for appropriate studies from the earliest available date of indexing through February 28, 2017. No restrictions were placed on language of publication.

Results

We identified 18 studies encompassing a total of 1,835 subjects; 16 studies reported on IL-6 and 6 studies reported on PCT. The area under the curve (AUC) was 0.93 (95% CI, 0.91–0.95) for IL-6 and 0.83 (95% CI, 0.79–0.86) for PCT. The pooled sensitivity was 0.83 (95% CI, 0.74–0.89) for IL-6 and 0.58 (95% CI, 0.31–0.81) for PCT. The pooled specificity was 0.91 (95% CI, 0.84–0.95) for IL-6 and 0.95 (95% CI, 0.63–1.00) for PCT. Both the IL-6 and PCT tests had a high positive likelihood ratio (LR); 9.3 (95% CI, 5.3–16.2) and 12.4 (95% CI, 1.7–89.8), respectively, making them excellent rule-in tests for the diagnosis of PJI. The pooled negative LR for IL-6 was 0.19 (95% CI, 0.12–0.29), making it suitable as a rule-out test, whereas the pooled negative LR for PCT was 0.44 (95% CI, 0.25–0.78), making it unsuitable as a rule-out diagnostic tool.

Conclusions

Based on the results of the present meta-analysis, IL-6 has higher diagnostic value than PCT for the diagnosis of PJI. Moreover, the specificity of the IL-6 test is higher than its sensitivity. Conversely, PCT is not recommended for use as a rule-out diagnostic tool.

Keywords

Interleukin-6 Procalcitonin Diagnosis Meta-analysis 

Notes

Complicance with ethical standards

Conflict of interest

The authors declare that they have to no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

There are no conflicts of interest between any of the contributors to this manuscript.

References

  1. 1.
    Matar WY, Jafari SM, Restrepo C et al (2010) Preventing infection in total joint arthroplasty. J Bone Joint Surg Am 92(Suppl 2):36–46CrossRefPubMedGoogle Scholar
  2. 2.
    Lenski M, Scherer MA (2014) Synovial IL-6 as inflammatory marker in periprosthetic joint infections. J Arthroplast 29(6):1105–1109CrossRefGoogle Scholar
  3. 3.
    Parvizi J, Ghanem E, Menashe S et al (2006) Periprosthetic infection: what are the diagnostic challenges? J Bone Joint Surg Am 88(suppl 4):138–147PubMedGoogle Scholar
  4. 4.
    Zimmerli W, Trampuz A, Ochsner PE (2004) Prosthetic-joint infections. N Engl J Med 351(16):1645–1654CrossRefPubMedGoogle Scholar
  5. 5.
    Austin MS, Ghanem E, Joshi A et al (2008) A simple, cost-effective screening protocol to rule out periprosthetic infection. J Arthroplast 23(1):65–68CrossRefGoogle Scholar
  6. 6.
    Ghanem E, Antoci V, Pulido L et al (2009) The use of receiver operating characteristics analysis in determining erythrocyte sedimentation rate and C-reactive protein levels in diagnosing periprosthetic infection prior to revision total hip arthroplasty. Int J Infect Dis 13(6):e444–e449CrossRefPubMedGoogle Scholar
  7. 7.
    Deirmengian C, Hallab N, Tarabishy A et al (2010) Synovial fluid biomarkers for periprosthetic infection. Clin Orthop Relat Res 468(8):2017–2023CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Parvizi J, Fassihi SC, Enayatollahi MA (2016) Diagnosis of periprosthetic joint infection following hip and knee Arthroplasty. Orthop Clin N Am 47(3):505–515CrossRefGoogle Scholar
  9. 9.
    Parvizi J, Cavanaugh PK, Diaz-Ledezma C (2013) Periprosthetic knee infection: ten strategies that work. Knee Surg Relat Res 25(4):155–164CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Di Cesare PE, Chang E, Preston CF et al (2005) Serum interleukin-6 as a marker of periprosthetic infection following total hip and knee arthroplasty. J Bone Joint Surg Am 87(9):1921–1927CrossRefPubMedGoogle Scholar
  11. 11.
    Maharajan K, Patro DK, Menon J et al (2013) Serum procalcitonin is a sensitive and specific marker in the diagnosis of septic arthritis and acute osteomyelitis. J Orthop Surg Res 8(1):19CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Whiting PF, Rutjes AW, Westwood ME et al (2011) QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med 155(8):529–536CrossRefPubMedGoogle Scholar
  13. 13.
    Deeks JJ (2001) Systematic reviews in health care: systematic reviews of evaluations of diagnostic and screening tests. BMJ 323(7305):157–162CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Glas AS, Lijmer JG, Prins MH et al (2003) The diagnostic odds ratio: a single indicator of test performance. J Clin Epidemiol 56(11):1129–1135CrossRefPubMedGoogle Scholar
  15. 15.
    Deeks JJ, Macaskill P, Irwig L (2005) The performance of tests of publication bias and other sample size effects in systematic reviews of diagnostic test accuracy was assessed. J Clin Epidemiol 58(9):882–893CrossRefPubMedGoogle Scholar
  16. 16.
    Jacovides CL, Parvizi J, Adeli B et al (2011) Molecular markers for diagnosis of periprosthetic joint infection. J Arthroplast 26(Suppl 6):99–103CrossRefGoogle Scholar
  17. 17.
    Abou El-Khier NT, El Ganainy AR, Elgeidy A et al (2013) Assessment of interleukin-6 and other inflammatory markers in the diagnosis of Egyptian patients with periprosthetic joint infection. Egypt J Immunol 20(2):93–99PubMedGoogle Scholar
  18. 18.
    Gollwitzer H, Dombrowski Y, Prodinger PM et al (2013) Antimicrobial peptides and proinflammatory cytokines in periprosthetic joint infection. J Bone Joint Surg Am 95(7):644–651CrossRefPubMedGoogle Scholar
  19. 19.
    Elgeidi A, Elganainy AE, Abou Elkhier N et al (2014) Interleukin-6 and other inflammatory markers in diagnosis of periprosthetic joint infection. Int Orthop 38(12):2591–2595CrossRefPubMedGoogle Scholar
  20. 20.
    Bottner F, Wegner A, Winkelmann W et al (2007) Interleukin-6, procalcitonin and TNF-alpha: markers of peri-prosthetic infection following total joint replacement. J Bone Joint Surg Br 89(1):94–99CrossRefPubMedGoogle Scholar
  21. 21.
    Deirmengian C, Kardos K, Kilmartin P et al (2014) Diagnosing periprosthetic joint infection: has the era of the biomarker arrived? Clin Orthop Relat Res 472(11):3254–3262CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Glehr M, Friesenbichler J, Hofmann G et al (2013) Novel biomarkers to detect infection in revision hip and knee arthroplasties. Clin Orthop Relat Res 471(8):2621–2628CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Worthington T, Dunlop D, Casey A et al (2010) Serum procalcitonin, interleukin-6, soluble intercellular adhesin molecule-1 and IgG to shortchain exocellular lipoteichoic acid as predictors of infection in total joint prosthesis revision. Br J Biomed Sci 67(2):71–76CrossRefPubMedGoogle Scholar
  24. 24.
    Frangiamore SJ, Siqueira MB, Saleh A et al (2016) Synovial cytokines and the MSIS criteria are not useful for determining infection resolution after periprosthetic joint infection explantation. Clin Orthop Relat Res 474(7):1630–1639CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Ettinger M, Calliess T, Kielstein JT et al (2015) Circulating biomarkers for discrimination between aseptic joint failure, low-grade infection and high-grade septic failure. Clin Infect Dis 61:332–341CrossRefPubMedGoogle Scholar
  26. 26.
    Randau TM, Friedrich MJ, Wimmer MD et al (2014) Interleukin-6 in serum and in synovial fluid enhances the differentiation between periprosthetic joint infection and aseptic loosening. PloS One 9(2):e89045CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Tang X, Wang Q, Wang H et al (2016) [Comparison and estimation of different diagnostic methods in detecting the presence of periprosthetic joint infection]. Zhonghua Wai Ke Za Zhi 54(4):251–257PubMedGoogle Scholar
  28. 28.
    Yuan K, Li W-D, Qiang Y et al (2015) Comparison of procalcitonin and C-reactive protein for the diagnosis of periprosthetic joint infection before revision total hip arthroplasty. Surg Infect 16(2):146–150CrossRefGoogle Scholar
  29. 29.
    Saeed K, Dryden M, Sitjar A et al (2013) Measuring synovial fluid procalcitonin levels in distinguishing cases of septic arthritis, including prosthetic joints, from other causes of arthritis and aseptic loosening. Infection 41(4):845–849CrossRefPubMedGoogle Scholar
  30. 30.
    Nilsdotter-Augustinsson A, Briheim G, Herder A et al (2007) 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 78(5):629–639CrossRefPubMedGoogle Scholar
  31. 31.
    Wirtz DC, Heller KD, Miltner O et al (2000) Interleukin-6: a potential inflammatory marker after total joint replacement. Int Orthop 24(4):194–196CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Waddell J, Pritzker KP, Boynton EL (2005) Increased cytokine secretion in patients with failed implants compared with patients with primary implants. Clin Orthop Relat Res 434(434):170–176CrossRefGoogle Scholar
  33. 33.
    Ahmad SS, Shaker A, Saffarini M et al (2016) Accuracy of diagnostic tests for prosthetic joint infection: a systematic review. Knee Surg Sports Traumatol Arthrosc 24(10):3064–3074CrossRefPubMedGoogle Scholar
  34. 34.
    Parvizi J, Zmistowski B, Berbari EF et al (2011) New definition for periprosthetic joint infection: from the workgroup of the musculoskeletal infection society. Clin Orthop Relat Res 469(11):2992–2994CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Fischer JE, Bachmann LM, Jaeschke R (2003) A readers’ guide to the interpretation of diagnostic test properties: clinical example of sepsis. Intensive Care Med 29(7):1043–1051CrossRefPubMedGoogle Scholar

Copyright information

© SICOT aisbl 2018

Authors and Affiliations

  1. 1.Department of Orthopaedic SurgeryVeterans Health Service Medical CenterSeoulRepublic of Korea

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