Background: Due to a lack of reliable detection methods, diagnosing CPP associated arthritis (CPPD) is plagued by flaws. Frequently used diagnostic modalities such as polarized light microscopy, conventional radiology, and ultrasonography suffer from sensitivity issues, poor interrater reliability, and subjectivity. The newly developed 2023 ACR/EULAR CPPD classification criteria provides a well-defined description of the disease for clinicians but is not a diagnostic instrument. There is an urgent need for objective and specific methods to diagnose CPPD. We have integrated a Raman spectroscope with an ordinary polarized light microscope (iRPolM) to increase the specificity and objectivity of synovial fluid analysis. Objectives: In this study, we evaluate the performance of iRPolM analysis of synovial fluids for the diagnosis of CPPD using the criteria set. Methods: We collected 400 unselected synovial fluid samples from patients visiting our outpatient clinic in Venlo, the Netherlands, and analyzed these with Raman spectroscopy for the presence of CPP crystals. The results of Raman spectroscopy were compared to the outcome of the 2023 ACR/EULAR CPPD classification criteria set. This set includes conventional polarized light microscopy (PLM), clinical presentation, and conventional radiology; patients are classified as positive if CPP crystals are identified in synovial fluid using PLM or when over 56 classification criteria points can be awarded. Results: A total of 50 patients were classified as CPPD according to the 2023 ACR/EULAR criteria set. The interrater reliability between iRPolM and the 2023 ACR/EULAR criteria set for CPPD was strong (k = 0.88). The sensitivity was 86.0% (95% CI 73.3 - 94.2), specificity was 99.1% (95% CI 97.5 - 99.8), positive likelihood ratio was 100.3 (95% CI 32.3 - 311.3), negative likelihood ratio was 0.14 (95% CI 0.07 - 0.28), positive predictive value was 93.5% (95% CI 82.2 - 97.8), negative predictive value was 98.0% (95% CI 86.8 - 99.9), and the accuracy was 97.5% (95% CI 95.5 - 98.8). Conclusion: We here demonstrated that Raman spectroscopy can be used to diagnose CPPD with improved performance. Due to a high specificity, we propose that Raman spectroscopic identification of CPP crystals can be applied as the new gold standard in diagnosing CPPD. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: Tom Niessink: None declared, Matthijs Janssen Crystalytics B.V. (Start-up), Cees Otto Hybriscan technologies B.V., Tim Jansen Crystallytics B.V.
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