Serum and Synovial Biomarkers for Distinguishing Between Chronic Periprosthetic Joint Infections and Rheumatoid Arthritis: A Prospective Cohort Study

Published:September 20, 2021DOI:https://doi.org/10.1016/j.arth.2021.09.009

      Abstract

      Background

      Inflammatory responses in patients with active rheumatoid arthritis (RA) may lead to the current serum and synovial fluid biomarkers that misidentify chronic periprosthetic joint infection (PJI). We sought to investigate the expression of serum and synovial biomarkers in patients with active RA and to calculate thresholds for valuable biomarkers that distinguish between chronic PJI and active RA.

      Methods

      This prospective study was initiated to enroll 70 patients undergoing revision arthroplasty from January 2019 to January 2021, and 30 patients with active RA cumulative knee from August 2020 to March 2021. The Musculoskeletal Infection Society definition of PJI was utilized for the classification of cases as aseptic or infected. Serum d-dimer, erythrocyte sedimentation rate, C-reactive protein, and interleukin-6 (IL-6), as well as synovial IL-6, percentage of polymorphonuclear neutrophils, and CD64 index level were measured preoperatively.

      Results

      An increase in biomarker concentrations were observed in group C (active RA). Synovial fluid CD64 index exhibited good discriminatory power between group B (chronic PJI) and group C with an area under curve of 0.930. For the diagnosis of chronic PJI in the presence of active RA, the optimal threshold value of synovial CD64 index was 0.87, with a sensitivity of 82.86% and a specificity of 93.33%.

      Conclusion

      Current serum biomarkers (erythrocyte sedimentation rate, C-reactive protein, IL-6, and d-dimer) did not apply to the diagnosis of suspected PJI with active RA. Fortunately, satisfactory results can be achieved by adjusting the threshold of synovial fluid biomarkers.

      Keywords

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      References

        • Qin L.
        • Li X.
        • Wang J.
        • Gong X.
        • Hu N.
        • Huang W.
        Improved diagnosis of chronic hip and knee prosthetic joint infection using combined serum and synovial IL-6 tests.
        Bone Joint Res. 2020; 9: 587https://doi.org/10.1302/2046-3758.99.Bjr-2020-0095.R1
        • Ackmann T.
        • Möllenbeck B.
        • Gosheger G.
        • Schwarze J.
        • Schmidt-Braekling T.
        • Schneider K.N.
        • et al.
        Comparing the diagnostic value of serum D-dimer to CRP and IL-6 in the diagnosis of chronic prosthetic joint infection.
        J Clin Med. 2020; 9https://doi.org/10.3390/jcm9092917
        • Tarabichi M.
        • Shohat N.
        • Goswami K.
        • Alvand A.
        • Silibovsky R.
        • Belden K.
        • et al.
        Diagnosis of periprosthetic joint infection: the potential of next-generation sequencing.
        J Bone Joint Surg Am. 2018; 100: 147https://doi.org/10.2106/jbjs.17.00434
        • Parvizi J.
        • Tan T.L.
        • Goswami K.
        • Higuera C.
        • Della Valle C.
        • Chen A.F.
        • et al.
        The 2018 definition of periprosthetic hip and knee infection: an evidence-based and Validated criteria.
        J Arthroplasty. 2018; 33: 1309https://doi.org/10.1016/j.arth.2018.02.078
        • Abdelbary H.
        • Cheng W.
        • Ahmadzai N.
        • Carli A.V.
        • Shea B.J.
        • Hutton B.
        • et al.
        Combination tests in the diagnosis of chronic periprosthetic joint infection: Systematic review and Development of a stepwise clinical decision-making tool.
        J Bone Joint Surg Am. 2020; 102: 114https://doi.org/10.2106/jbjs.20.00097
        • Qin L.
        • Hu N.
        • Li X.
        • Chen Y.
        • Wang J.
        • Huang W.
        Evaluation of synovial fluid neutrophil CD64 index as a screening biomarker of prosthetic joint infection.
        Bone Joint J. 2020; 102-b: 463https://doi.org/10.1302/0301-620x.102b4.bjj-2019-1271.r1
        • Qu P.F.
        • Li R.
        • Xu C.
        • Chai W.
        • Li H.
        • Fu J.
        • et al.
        A clinical Pilot study to evaluate CD64 expression on blood Monocytes as an indicator of periprosthetic joint infection.
        J Bone Joint Surg Am. 2020; 102: e99https://doi.org/10.2106/jbjs.20.00057
        • Zhang Q.
        • Li D.
        • Zhong J.
        • Wu Y.
        • Shi Y.
        • Yang H.
        • et al.
        SPECT imaging and highly efficient therapy of rheumatoid arthritis based on hyperbranched semiconducting polymer nanoparticles.
        Biomater Sci. 2021; 9: 1845https://doi.org/10.1039/d0bm02037k
        • Schrama J.C.
        • Espehaug B.
        • Hallan G.
        • Engesaeter L.B.
        • Furnes O.
        • Havelin L.I.
        • et al.
        Risk of revision for infection in primary total hip and knee arthroplasty in patients with rheumatoid arthritis compared with osteoarthritis: a prospective, population-based study on 108,786 hip and knee joint arthroplasties from the Norwegian Arthroplasty Register.
        Arthritis Care Res. 2010; 62: 473https://doi.org/10.1002/acr.20036
        • Bernatsky S.
        • Hudson M.
        • Suissa S.
        Anti-rheumatic drug use and risk of serious infections in rheumatoid arthritis.
        Rheumatology (Oxford, England). 2007; 46: 1157https://doi.org/10.1093/rheumatology/kem076
        • Daien C.
        • Hua C.
        • Gaujoux-Viala C.
        • Cantagrel A.
        • Dubremetz M.
        • Dougados M.
        • et al.
        Update of French society for rheumatology recommendations for managing rheumatoid arthritis.
        Joint bone Spine. 2019; 86: 135https://doi.org/10.1016/j.jbspin.2018.10.002
        • Kinne R.W.
        • Stuhlmüller B.
        • Burmester G.R.
        Cells of the synovium in rheumatoid arthritis. Macrophages.
        Arthritis Res Ther. 2007; 9: 224https://doi.org/10.1186/ar2333
        • Qin L.
        • Li F.
        • Gong X.
        • Wang J.
        • Huang W.
        • Hu N.
        Combined measurement of D-dimer and C-reactive protein levels: highly accurate for diagnosing chronic periprosthetic joint infection.
        J Arthroplasty. 2020; 35: 229https://doi.org/10.1016/j.arth.2019.08.012
        • Yi P.H.
        • Cross M.B.
        • Moric M.
        • Sporer S.M.
        • Berger R.A.
        • Della Valle C.J.
        The 2013 Frank Stinchfield Award: diagnosis of infection in the early postoperative period after total hip arthroplasty.
        Clin Orthop Relat Res. 2014; 472: 424https://doi.org/10.1007/s11999-013-3089-1
        • Takanashi S.
        • Kaneko Y.
        • Takeuchi T.
        CDAI and DAS28 in the management of rheumatoid arthritis in clinical practice.
        Ann Rheum Dis. 2020; 79: 671https://doi.org/10.1136/annrheumdis-2019-216607
        • Parvizi J.
        • Gehrke T.
        Definition of periprosthetic joint infection.
        J Arthroplasty. 2014; 29: 1331https://doi.org/10.1016/j.arth.2014.03.009
        • Catrina A.I.
        • Joshua V.
        • Klareskog L.
        • Malmström V.
        Mechanisms involved in triggering rheumatoid arthritis.
        Immunol Rev. 2016; 269: 162https://doi.org/10.1111/imr.12379
        • Zaiss M.M.
        • Joyce Wu H.J.
        • Mauro D.
        • Schett G.
        • Ciccia F.
        The gut-joint axis in rheumatoid arthritis.
        Nat Rev Rheumatol. 2021; https://doi.org/10.1038/s41584-021-00585-3
        • Shrivastava A.K.
        • Pandey A.
        Inflammation and rheumatoid arthritis.
        J Physiol Biochem. 2013; 69: 335https://doi.org/10.1007/s13105-012-0216-5
        • Weyand C.M.
        • Goronzy J.J.
        The immunology of rheumatoid arthritis.
        Nat Immunol. 2021; 22: 10https://doi.org/10.1038/s41590-020-00816-x
        • Mikuła T.
        • Sapuła M.
        • Jabłońska J.
        • Kozłowska J.
        • Stańczak W.
        • Krankowska D.
        • et al.
        Significance of Heparin-Binding protein and D-dimers in the early diagnosis of Spontaneous Bacterial Peritonitis.
        Mediators Inflamm. 2018; 2018: 1969108https://doi.org/10.1155/2018/1969108
        • Bloom B.J.
        • Tucker L.B.
        • Miller L.C.
        • Schaller J.G.
        Fibrin D-dimer as a marker of disease activity in systemic onset juvenile rheumatoid arthritis.
        J Rheumatol. 1998; 25: 1620
        • Shahi A.
        • Kheir M.M.
        • Tarabichi M.
        • Hosseinzadeh H.R.S.
        • Tan T.L.
        • Parvizi J.
        Serum D-dimer test is promising for the diagnosis of periprosthetic joint infection and timing of reimplantation.
        J Bone Joint Surg Am. 2017; 99: 1419https://doi.org/10.2106/jbjs.16.01395
        • Cecchi I.
        • Arias de la Rosa I.
        • Menegatti E.
        • Roccatello D.
        • Collantes-Estevez E.
        • Lopez-Pedrera C.
        • et al.
        Neutrophils: Novel key players in Rheumatoid Arthritis. Current and future therapeutic targets.
        Autoimmun Rev. 2018; 17: 1138https://doi.org/10.1016/j.autrev.2018.06.006
        • de Lange-Brokaar B.J.
        • Ioan-Facsinay A.
        • van Osch G.J.
        • Zuurmond A.M.
        • Schoones J.
        • Toes R.E.
        • et al.
        Synovial inflammation, immune cells and their cytokines in osteoarthritis: a review.
        Osteoarthritis Cartilage. 2012; 20: 1484https://doi.org/10.1016/j.joca.2012.08.027
        • Groselj-Grenc M.
        • Ihan A.
        • Derganc M.
        Neutrophil and monocyte CD64 and CD163 expression in critically ill neonates and children with sepsis: comparison of fluorescence intensities and calculated indexes.
        Mediators Inflamm. 2008; 2008: 202646https://doi.org/10.1155/2008/202646
        • Soehnlein O.
        • Lindbom L.
        Phagocyte partnership during the onset and resolution of inflammation.
        Nat Rev Immunol. 2010; 10: 427https://doi.org/10.1038/nri2779
        • Della Valle C.
        • Parvizi J.
        • Bauer T.W.
        • DiCesare P.E.
        • Evans R.P.
        • Segreti J.
        • et al.
        American Academy of Orthopaedic Surgeons clinical practice guideline on: the diagnosis of periprosthetic joint infections of the hip and knee.
        J Bone Joint Surg Am. 2011; 93: 1355https://doi.org/10.2106/JBJS.9314ebo
        • Pérez-Figueroa E.
        • Álvarez-Carrasco P.
        • Ortega E.
        • Maldonado-Bernal C.
        Neutrophils: many ways to die.
        Front Immunol. 2021; 12: 631821https://doi.org/10.3389/fimmu.2021.631821