Synovial C-Reactive Protein is a Useful Adjunct for Diagnosis of Periprosthetic Joint Infection



      The diagnostic utility of synovial C-reactive protein (CRP) has been debated for a while. Existing studies are limited by small sample sizes and using outdated criteria for periprosthetic joint infection (PJI). Furthermore, the relationship between synovial and serum CRP has rarely been investigated in the setting of PJI. This study aimed to evaluate the diagnostic utility of synovial CRP and to assess its relationship with serum CRP and other common biomarkers.


      We reviewed 621 patients who underwent evaluation for PJI prior to revision arthroplasty from 2014 to 2021. Biomarkers, including serum CRP and erythrocyte sedimentation rate, synovial CRP, polymorphonuclear leukocyte percentage, white blood cell count, and alpha-defensin, were evaluated using the 2018 International Consensus Meeting criteria.


      In total, 194 patients had a PJI; 394 were considered aseptic failures and 33 were inconclusive. Synovial CRP showed an area under the curve (AUC) of 0.951 (95% CI, 0.932-0.970) with 74.2% sensitivity and 98.0% specificity, whereas, serum CRP had an AUC of 0.926 (95% CI, 0.903-0.949) with 83.5% sensitivity and 88.3% specificity. There was a good correlation between synovial and serum CRP (R = 0.703; 95% CI, 0.604-0.785). The combination of serum and synovial CRP yielded a significantly higher AUC than that obtained when using serum CRP alone (AUC 0.964 versus 0.926, P = .016).


      Synovial CRP demonstrated excellent accuracy when used to determine the presence of PJI. There was a good correlation between serum and synovial CRP levels in revision arthroplasty patients and the combined use of serum and synovial CRP proved to be more accurate than the serum test alone. These findings support the use of synovial CRP as an adjunct in the workup of PJI.


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        • Wildeman P.
        • Rolfson O.
        • Söderquist B.
        • Wretenberg P.
        • Lindgren V.
        What are the long-term outcomes of mortality, quality of life, and hip function after prosthetic joint infection of the hip? A 10-year follow-up from Sweden.
        Clin Orthop Relat Res. 2021; 479: 2203-2213
        • Kurtz S.M.
        • Lau E.
        • Watson H.
        • Schmier J.K.
        • Parvizi J.
        Economic burden of periprosthetic joint infection in the United States.
        J Arthroplasty. 2012; 27: 61-65.e1
        • Kurtz S.M.
        • Higgs G.B.
        • Lau E.
        • Iorio R.R.
        • Courtney P.M.
        • Parvizi J.
        Hospital costs for unsuccessful two-stage revisions for periprosthetic joint infection.
        J Arthroplasty. 2022; 37: 205-212
        • Goh G.S.
        • Parvizi J.
        Diagnosis and treatment of culture-negative periprosthetic joint infection.
        J Arthroplasty. 2022; ([Epub ahead of print])
        • Goh G.S.
        • Parvizi J.
        Laboratory diagnosis of periprosthetic joint infections.
        in: Longo U.G. Budhiparama N.C. Lustig S. Becker R. Espregueira-Mendes J. Infection in knee replacement. Springer International Publishing, Cham2022: 61-84
        • American Academy of Orthopaedic Surgeons
        American academy of orthopaedic surgeons clinical practice guideline on the diagnosis and prevention of periprosthetic joint infections. AAOS quality & practice resources.
        ([accessed 11.30.20])
        • 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: 1309-1314.e2
        • Parvizi J.
        • Gehrke T.
        • Chen A.F.
        Proceedings of the international consensus on periprosthetic joint infection.
        Bone Joint J. 2013; 95-B: 1450-1452
        • Deirmengian C.
        • Kardos K.
        • Kilmartin P.
        • Cameron A.
        • Schiller K.
        • Parvizi J.
        Diagnosing periprosthetic joint infection: has the era of the biomarker arrived?.
        Clin Orthop Relat Res. 2014; 472: 3254-3262
        • Sproston N.R.
        • Ashworth J.J.
        Role of C-reactive protein at sites of inflammation and infection.
        Front Immunol. 2018; 9: 754
        • Parvizi J.
        • Jacovides C.
        • Adeli B.
        • Jung K.A.
        • Hozack W.J.
        • Mark B.
        Coventry award: synovial C-reactive protein: a prospective evaluation of a molecular marker for periprosthetic knee joint infection.
        Clin Orthop Relat Res. 2012; 470: 54-60
        • Ahmad S.S.
        • Hirschmann M.T.
        • Becker R.
        • Shaker A.
        • Ateschrang A.
        • Keel M.J.B.
        • et al.
        A meta-analysis of synovial biomarkers in periprosthetic joint infection: SynovasureTM is less effective than the ELISA-based alpha-defensin test.
        Knee Surg Sports Traumatol Arthrosc. 2018; 26: 3039-3047
        • Lee Y.S.
        • Koo K.-H.
        • Kim H.J.
        • Tian S.
        • Kim T.-Y.
        • Maltenfort M.G.
        • et al.
        Synovial fluid biomarkers for the diagnosis of periprosthetic joint infection: a systematic review and meta-analysis.
        J Bone Joint Surg. 2017; 99: 2077-2084
        • Parvizi J.
        • McKenzie J.C.
        • Cashman J.P.
        Diagnosis of periprosthetic joint infection using synovial C-reactive protein.
        J Arthroplasty. 2012; 27: 12-16
        • Omar M.
        • Ettinger M.
        • Reichling M.
        • Petri M.
        • Guenther D.
        • Gehrke T.
        • et al.
        Synovial C-reactive protein as a marker for chronic periprosthetic infection in total hip arthroplasty.
        Bone Joint J. 2015; 97-B: 173-176
        • Tetreault M.W.
        • Wetters N.G.
        • Moric M.
        • Gross C.E.
        • Della Valle C.J.
        Is synovial C-reactive protein a useful marker for periprosthetic joint infection?.
        Clin Orthop Relat Res. 2014; 472: 3997-4003
        • Sousa R.
        • Serrano P.
        • Gomes Dias J.
        • Oliveira J.C.
        • Oliveira A.
        Improving the accuracy of synovial fluid analysis in the diagnosis of prosthetic joint infection with simple and inexpensive biomarkers: C-reactive protein and adenosine deaminase.
        Bone Joint J. 2017; 99-B: 351-357
        • Stone W.Z.
        • Gray C.F.
        • Parvataneni H.K.
        • Al-Rashid M.
        • Vlasak R.G.
        • Horodyski M.
        • et al.
        Clinical evaluation of synovial alpha defensin and synovial C-reactive protein in the diagnosis of periprosthetic joint infection.
        J Bone Joint Surg. 2018; 100: 1184-1190
        • Plate A.
        • Anagnostopoulos A.
        • Glanzmann J.
        • Stadler L.
        • Weigelt L.
        • Sutter R.
        • et al.
        Synovial C-reactive protein features high negative predictive value but is not useful as a single diagnostic parameter in suspected periprosthetic joint infection (PJI).
        J Infect. 2019; 78: 439-444
        • Praz C.
        • Gubbiotti L.
        • Buia G.
        • Chapus V.
        • Dunet J.
        • Grandhomme F.
        • et al.
        Value of the synovial C-reactive protein test in the diagnosis of total hip and knee periprosthetic joint infections: a case-control study.
        Orthop Traumatol Surg Res. 2021; 107: 102903
        • Wang H.
        • Qin L.
        • Wang J.
        • Hu N.
        • Huang W.
        Combined serum and synovial C-reactive protein tests: a valuable adjunct to the diagnosis of chronic prosthetic joint infection.
        BMC Musculoskelet Disord. 2021; 22: 670
        • Yu B.-Z.
        • Li R.
        • Li X.
        • Chai W.
        • Zhou Y.-G.
        • Chen J.-Y.
        The relationship of C-reactive protein/interleukin-6 concentrations between serum and synovial fluid in the diagnosis of periprosthetic joint infection.
        J Orthop Surg Res. 2021; 16: 733
        • Wasterlain A.S.
        • Goswami K.
        • Ghasemi S.A.
        • Parvizi J.
        Diagnosis of periprosthetic infection: recent developments.
        J Bone Joint Surg Am. 2020; 102: 1366-1375
        • Charlson M.E.
        • Pompei P.
        • Ales K.L.
        • MacKenzie C.R.
        A new method of classifying prognostic comorbidity in longitudinal studies: development and validation.
        J Chronic Dis. 1987; 40: 373-383
        • ASA House of Delegates/Executive Committee
        ASA Physical Status Classification System.
        American Society of Anaesthesiologists, Schaumburg, IL2014
        • Wang C.
        • Wang Q.
        • Li R.
        • Duan J.-Y.
        • Wang C.-B.
        Synovial fluid C-reactive protein as a diagnostic marker for periprosthetic joint infection: a systematic review and meta-analysis.
        Chin Med J (Engl). 2016; 129: 1987-1993
        • Li R.
        • Lu Q.
        • Chai W.
        • Hao L.-B.
        • Lu S.-B.
        • Chen J.-Y.
        Saline solution lavage and reaspiration for culture with a blood culture system is a feasible method for diagnosing periprosthetic joint infection in patients with insufficient synovial fluid.
        J Bone Joint Surg. 2019; 101: 1004-1009
        • Catterall J.B.
        • Stabler T.V.
        • Flannery C.R.
        • Kraus V.B.
        Changes in serum and synovial fluid biomarkers after acute injury (NCT00332254).
        Arthritis Res Ther. 2010; 12: R229
        • Pannu T.S.
        • Villa J.M.
        • Higuera C.A.
        Diagnosis and management of infected arthroplasty.
        SICOT J. 2021; 7: 54
        • Davis J.S.
        • Metcalf S.
        • Clark B.
        • Robinson J.O.
        • Huggan P.
        • Luey C.
        • et al.
        Predictors of treatment success after periprosthetic joint infection: 24-month follow up from a multicenter prospective observational cohort study of 653 patients.
        Open Forum Infect Dis. 2022; 9: ofac048
        • Barrack R.
        • Bhimani S.
        • Blevins J.L.
        • Blevins K.
        • Demetres M.
        • Figgie M.
        • et al.
        General assembly, diagnosis, laboratory test: Proceedings of international consensus on orthopedic infections.
        J Arthroplasty. 2019; 34: S187-S195