Accuracy of synovial fluid analysis compared to histology for the identification of calcium pyrophosphate crystals: an ancillary study of the OMERACT US Working Group - CPPD subgroup
The aim of this study was to evaluate the accuracy of synovial fluid analysis in the identification of calcium pyrophosphate dihydrate crystals compared to microscopic analysis of joint tissues as the reference standard. This is an ancillary study of an international, multicentre cross-sectional study performed by the calcium pyrophosphate deposition disease (CPPD) subgroup of the OMERACT Ultrasound working group. Consecutive patients with knee osteoarthritis (OA) waiting for total knee replacement surgery were enrolled in the study from 2 participating centres in Mexico and Romania. During the surgical procedures, synovial fluid, menisci and hyaline cartilage were collected and analysed within 48 hours from surgery under transmitted light microscopy and compensated polarised light microscopy for the presence/absence of calcium pyrophosphate crystals. All slides were analysed by expert examiners on site, blinded to other findings. A dichotomic score (absence/ presence) was used for scoring both synovial fluid and tissues. Microscopic analysis of knee tissues was considered the gold standard. Sensitivity, specificity, accuracy, positive and negative predictive values of synovial fluid analysis in the identification of calcium pyrophosphate crystals were calculated. 15 patients (53% female, mean age 68 yo ± 8.4) with OA of grade 3 or 4 according to Kellgren-Lawrence scoring were enrolled. 12 patients (80%) were positive for calcium pyrophosphate crystals at the synovial fluid analysis and 14 (93%) at the tissue microscopic analysis. The overall diagnostic accuracy of synovial fluid analysis compared with histology for CPPD was 87%, with a sensitivity of 86% and a specificity of 100%, the positive predictive value was 100% and the negative predictive value was 33%. In conclusion synovial fluid analysis proved to be an accurate test for the identification of calcium pyrophosphate dihydrate crystals in patients with advanced OA.
Zhang W, Doherty M, Bardin T, et al. European League Against Rheumatism recommendations for calcium pyrophosphate deposition. Part I: terminology and diagnosis. Ann Rheum Dis. 2011; 70: 563–570. DOI: https://doi.org/10.1136/ard.2010.139105
Salaffi F, De Angelis R, Grassi W, et al. Prevalence of musculoskeletal conditions in an Italian population sample: results of a regional community-based study. I. The MAPPING study. Clin Exp Rheumatol. 2005; 23: 819–828.
De la Garza-Montaño P, Pineda C, Lozada-Pérez CA, et al. Prevalence of chondrocalcinosis in a Mexican tertiary care institution of musculoskeletal disorders. Clin Rheumatol. 2019; 38: 2595–2602. DOI: https://doi.org/10.1007/s10067-019-04614-1
Neame RL, Carr AJ, Muir K, Doherty M. UK community prevalence of knee chondrocalcinosis: evidence that correlation with osteoarthritis is through a shared association with osteophyte. Ann Rheum Dis. 2003; 62: 513–518. DOI: https://doi.org/10.1136/ard.62.6.513
Maravic M, Ea H-K. Hospital burden of gout, pseudogout and other crystal arthropathies in France. Joint Bone Spine. 2015; 82: 326–329. DOI: https://doi.org/10.1016/j.jbspin.2015.01.011
Ciancio G, Bortoluzzi A, Govoni M. Epidemiology of gout and chondrocalcinosis. Reumatismo. 2012; 63: 207–220. DOI: https://doi.org/10.4081/reumatismo.2011.207
Mccarty DJ, Kohn NN, Faires JS. The significance of calcium phosphate crystals in the synovial fluid of arthritic patients: the “pseudogout syndrome.” Ann Intern Med. 1962; 56: 711–737. DOI: https://doi.org/10.7326/0003-4819-56-5-711
Mccarty DJ, Hollander JL. Identification of urate crystals in gouty synovial fluid. Ann Intern Med. 1961; 54: 452–460. DOI: https://doi.org/10.7326/0003-4819-54-3-452
McCarty DJ. Calcium pyrophosphate dihydrate crystal deposition disease: nomenclature and diagnostic criteria. Ann Intern Med. 1977; 87: 241–242. DOI: https://doi.org/10.7326/0003-4819-87-2-240
Filippou G, Adinolfi A, Cimmino MA, et al. Diagnostic accuracy of ultrasound, conventional radiography and synovial fluid analysis in the diagnosis of calcium pyrophosphate dihydrate crystal deposition disease. Clin Exp Rheumatol. 2016; 34: 254–260.
Gordon C, Swan A, Dieppe P. Detection of crystals in synovial fluids by light microscopy: sensitivity and reliability. Ann Rheum Dis. 1989; 48: 737–742. DOI: https://doi.org/10.1136/ard.48.9.737
Swan A, Amer H, Dieppe P. The value of synovial fluid assays in the diagnosis of joint disease: a literature survey. Ann Rheum Dis. 2002; 61: 493–498. DOI: https://doi.org/10.1136/ard.61.6.493
Filippou G, Scanu A, Adinolfi A, et al. Criterion validity of ultrasound in the identification of calcium pyrophosphate crystal deposits at the knee: an OMERACT ultrasound study. Ann Rheum Dis. 2020: annrheumdis-2020-217998.
Tausche A-K, Gehrisch S, Panzner I, et al. A 3-day delay in synovial fluid crystal identification did not hinder the reliable detection of monosodium urate and calcium pyrophosphate crystals. J Clin Rheumatol. 2013; 19: 241–245. DOI: https://doi.org/10.1097/RHU.0b013e31829cde53
Bossuyt PM, Reitsma JB, Bruns DE, et al. STARD 2015: an updated list of essential items for reporting diagnostic accuracy studies. BMJ 2015; 351: h5527. DOI: https://doi.org/10.1136/bmj.h5527
Kellgren JH, Lawrence JS. Radiological assessment of osteo-arthrosis. Ann Rheum Dis. 1957; 16: 494–502. DOI: https://doi.org/10.1136/ard.16.4.494
Filippou G, Filippucci E, Mandl P, Abhishek A. A critical review of the available evidence on the diagnosis and clinical features of CPPD: do we really need imaging? Clin Rheumatol. 2020: 1–12. DOI: https://doi.org/10.1007/s10067-020-05516-3
Filippou G, Adinolfi A, Iagnocco A, et al. Ultrasound in the diagnosis of calcium pyrophosphate dihydrate deposition disease. A systematic literature review and a meta-analysis. Osteoart Cartil. 2016; 24: 973–981. DOI: https://doi.org/10.1016/j.joca.2016.01.136
Cipolletta E, Filippou G, Scirè CA, et al. The diagnostic value of conventional radiography and musculoskeletal ultrasonography in calcium pyrophosphate deposition disease: a systematic literature review and meta-analysis. Osteoart Cartil. 2021: S1063458421000352. DOI: https://doi.org/10.1016/j.joca.2021.01.007
Filippou G, Pascart T, Iagnocco A. Utility of ultrasound and dual energy ct in crystal disease diagnosis and management. Curr Rheumatol Rep. 2020; 22: 15. DOI: https://doi.org/10.1007/s11926-020-0890-1
Budzik J-F, Marzin C, Legrand J, et al. Can dual-energy computed tomography be used to identify early calcium crystal deposition in the knees of patients with calcium pyrophosphate deposition? Arthrit Rheum. 2021; 73: 687–692. DOI: https://doi.org/10.1002/art.41569
Li B, Singer NG, Yeni YN, et al. A point-of-care raman spectroscopy-based device for the diagnosis of gout and pseudogout: comparison with the clinical standard microscopy. Arthritis Rheumatol. 2016; 68: 1751–1757. DOI: https://doi.org/10.1002/art.39638
Zhang Y. Wide-field imaging of birefringent synovial fluid crystals using lens-free polarized microscopy for gout diagnosis. Sci Rep. 14.
Lumbreras B, Pascual E, Frasquet J, et al. Analysis for crystals in synovial fluid: training of the analysts results in high consistency. Ann Rheum Dis. 2005; 64: 612–615. DOI: https://doi.org/10.1136/ard.2004.027268
Trevethan R. Sensitivity, Specificity, and predictive values: foundations, liabilities, and pitfalls in research and practice. Front Public Health. 2017; 5: 307. DOI: https://doi.org/10.3389/fpubh.2017.00307
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