Abstract

Background:Synovial fluid analysis (SFA) via compensated polarized light microscopy is still considered the gold standard for the identification and diagnosis of Calcium Pyrophosphate Deposition disease (CPPD)-related arthropathies[1], but very few studies have been published about its diagnostic accuracy.Objectives:The aim of this study was to evaluate the accuracy of SFA in the identification of calcium pyrophosphate dihydrate (CPP) crystals compared to microscopic analysis of joint tissues as the reference standard.Methods:This is an ancillary study of an international, multicentre cross-sectional study performed by the CPPD subgroup of the OMERACT Ultrasound working group[2]. Consecutive patients with knee osteoarthritis (OA) waiting for total knee replacement surgery were enrolled in the study from 2 participating centres, Mexico and Romania. During surgical procedures synovial fluid (SF), menisci and hyaline cartilage were collected and analysed within 48 hours after surgery under transmitted light microscopy and compensated polarised light microscopy for the presence/absence of CPP crystals. All slides were analysed by expert examiners on site, blinded to other findings. A dichotomic score (absence/presence) was used for scoring both SF and tissues. Microscopic analysis of knee tissues was considered the gold standard. Sensitivity, specificity, accuracy, positive and negative predictive values (PPV and NPV) of SFA in the identification of CPP crystals were calculated.Results:15 patients (53% female, mean age 68yo ± 8.4) with OA of grade 3 or 4 according to Kellgren-Lawrence scoring were enrolled. 12 patients (80%) were positive for CPP crystals at SFA and 14 (93%) at tissues microscopic analysis. Among 12 SFA positive patients, all were positive for CPP crystals in either medial or lateral meniscus, and 11 were positive in both; 10 patients were positive at the hyaline cartilage, and all 10 were also positive for at least one meniscus. Regarding the 3 SFA negative patients, only one had no crystals in the examined tissues, while the other 2 patients had CPP crystals in both menisci and hyaline cartilage. The overall diagnostic accuracy of SFA compared to histology analysis for CPPD was 87%, with a sensitivity of 86% and a specificity of 100%, the PPV was 100% and the NPV was 33% (Table 1).Table 1.sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy of synovial fluid analysis compared to the reference standard. CI: Confidential Interval. SF: synovial fluid, in parentheses: numerators and denominators for all percentages provided.SensitivitySpecificityPPVNPVAccuracySF analysis86% (12/14)100% (1/1)100% (12/12)33% (1/3)87% (13/15)(0.65-0.99) CI 95%(0.0-0.25) CI 95%(0.65-0.99) CI 95%(0.0-0.25) CI 95%Conclusion:SFA demonstrated to be an accurate test for the identification of CPP crystals in patients with advanced OA. However, is not always feasible and carries some risks for the patient. Considering the availability of validated imaging techniques for the detection of CPPD, such as US, SFA could be used in those patients where imaging and clinical data are not definitely confirmatory of the disease.

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