Agreement Among Multiple Observers on Crystal Identification by Synovial Fluid Microscopy

Abstract

Objective. Despite the fact that polarized microscopy remains the gold standard for diagnosing crystal arthritis, some uncertainties hamper full implementation in clinical practice. We undertook this study to analyze the agreement among multiple observers in crystal identification using compensated polarized microscopy, as well as to assess potential outcome modifiers.Methods. This was a cross-sectional, observational study with consecutive synovial fluid sampling. Samples were immediately analyzed when possible or kept refrigerated at 4 C. Five observers analyzed them separately, blinded to clinical data, using a compensated polarized optical microscope (400×), through 3 stages (ordinary, simple polarized, and compensated polarized light) to detect and identify crystals. They recorded the presence and type of crystal (no crystals, monosodium urate [MSU], and calcium pyrophosphate dihydrate [CPP]). Interrater agreement was measured by Cohen's kappa. Subanalyses were performed on visualization delay and cumulative expertise. Discrepancies between each stage of the microscopy and the final decision were also examined.Results. A total of 250 observations from 50 samples completed full assessment. Overall, κ = 0.74 (95% confidence interval [95% CI] 0.64-0.84), indicating good agreement. Agreement for crystal detection was κ = 0.71 (95% CI 0.59-0.82), for MSU was κ = 0.88 (95% CI 0.75-1.0), and for CPP was κ = 0.69 (95% CI 0.56-0.82). Most of the crystal identifications were already made by ordinary light. No differences between observations made before or after 24 hours (P = 0.859) or in expertise on crystal analysis (P = 0.989) were found. Observations performed under ordinary light matched the final diagnosis in 96.8% of cases (242 of 250).Conclusion. Compensated polarized microscopy remained consistent in detecting and identifying crystals in synovial fluid, even when examined among multiple observers, confirming its high utility for clinical practice.

The 2023 ACR/EULAR Classification Criteria for Calcium Pyrophosphate Deposition Disease

“…Color figure can be viewed in the online issue, which is available at http://onlinelibrary.wiley.com/doi/10.1002/art.42619/abstract. significant interobserver variability (11)(12)(13)(14). Challenges of CPP crystal identification include small crystal size and absent or weak positive birefringence (11).…”

“…A practical gold standard for CPPD disease does not exist in clinical settings, as SF CPP crystal positivity on polarized light microscopy is specific but has a high false‐negative rate and significant interobserver variability (11–14). Challenges of CPP crystal identification include small crystal size and absent or weak positive birefringence (11).…”

“…For definite diagnosis, they required evidence of crystals based on the presence of both typical calcification on radiography and findings consistent with CPP crystals on SF polarized light microscopy, or alternatively by research laboratory techniques that are not widely available (7). These diagnostic criteria have since been recognized to be problematic, because conventional radiography (CR) has low sensitivity for CPPD (8)(9)(10), advanced imaging modalities such as ultrasonography and dual-energy computed tomography were not available in the 1960s, and SF analysis for CPP crystals has a high false-negative rate and high interobserver variability (11)(12)(13)(14).…”

How can ultrasonography help in the management of CPPD? From diagnosis to clinical subset identification

“…Diagnosis of CPPD traditionally relies on the detection of CPP crystals in synovial fluid through polarized light microscopy [1]. However, even if it is a specific technique, some limitations should be kept in mind, starting from its highly variable interobserver reliability (operator dependence) that affects the correct identification of patients [12][13][14]. Additionally, synovial fluid analysis (SFA) is a surrogate for the presence of CPP crystals in joints and this affects also the sensitivity of the exam when compared to histopathologic evidence of CPPD.…”

Improved polarized light microscopic detection of gouty crystals via dissolution with formalin and ethylenediamine tetraacetic acid

“…Differential birefringence by polarized light microscope is the standard method for synovial fluid analysis in the search for MSUM and CPPD crystals. Although MSUM crystals are strongly birefringent, CPPD crystals are poorly birefringent 5 , 6 . There are some reports mentioned that a relatively higher birefringence was found due to co-aggregation or contamination of other crystals 7 , 8 .…”