Test characteristics of Raman spectroscopy integrated with polarized light microscopy for the diagnosis of acute gouty arthritis

Objectives: We studied the performance of Raman spectroscopy integrated with polarized light microscopy (iRPolM) as a next-generation technique for synovial fluid analysis in gout. Methods: This is a prospective study, including consecutive synovial fluid samples drawn from any peripheral swollen joint. Diagnostic accuracy was compared to the 2015 ACR/EULAR Gout classification criteria as a reference test and to polarized light microscopy (PLM) analysis by a rheumatologist. Synovial fluid was analysed with iRPolM after unblinding the PLM results. Results: Two hundred unselected consecutive patient samples were included in this study. Validation against clinical criteria: 67 patients were classified as gout according to 2015 ACR/EULAR classification criteria. Compared to the 2015 ACR/EULAR gout classification criteria, iRPolM had a sensitivity of 77.6% (95% CI: 65.8–86.9), specificity of 97.7% (95% CI: 93.5–99.5), positive predictive value (PPV) of 94.5% (95% CI: 84.9–98.2), negative predictive value (NPV) of 89.7% (95% CI: 84.7–93.1), an accuracy of 91.0% (95% CI: 86.2–94.6), a positive likelihood ratio of 34.4 (95% CI: 11.16–106.10) and a negative likelihood ratio of 0.23 (95% CI: 0.15–0.36). Validation against PLM: 55 samples were positive for MSU according to PLM. The interrater agreement between PLM and iRPolM was near perfect (к = 0.90). The sensitivity of iRPolM to identify MSU in PLM-positive samples was 91.2% (95% CI: 80.7–97.1), the specificity was 97.6% (95% CI: 93.0–99.5), the PPV was 94.6% (95% CI: 85.0–98.2), NPV was 96.0% (95% CI: 91.2–98.2) and the accuracy was 95.6% (95% CI: 91.4–98.2). The positive likelihood ratio was 37.4 (95% CI: 12.20–114.71), and the negative likelihood ratio was 0.09 (95% CI: 0.04–0.21). Conclusion: iRPolM is a promising next-generation diagnostic tool for rheumatology by diagnosing gout with high specificity, increased objectivity, and a sensitivity comparable to PLM.