Advances in Synovial Fluid Analysis for the Diagnosis of Crystal Arthropathies

Synovial fluid analysis remains to be a critical aspect of the diagnosis of crystal arthropathies. The gold standard, compensated polarized light microscopy (CPLM), has significant shortcomings due to poor reproducibility and improper training of specialists. Especially in cases of artifacts, low crystal counts, and combinations of crystals, errors are frequently made. There are several new techniques in development to improve the accuracy of crystal identifications. With modified CPLM, microscopes, often aided by machine-learning algorithms, enhance the image contrast, which significantly improves sensitivity. Examples are lens-free polarized light microscopy and polychromatic polarized light microscopy. These techniques have relatively low costs and are easy to use. Another approach is using Raman spectroscopy alone or as a second (verification) step for the objective identification of crystals. This improves objectivity and specificity of diagnosis. Examples include a point-of-care Raman spectroscope and integrated Raman-polarized light microscopy. Although these are more accurate than the microscopy-based platforms, they are often more expensive and require some additional training. Both Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) have also been used for crystal identification in research. FTIR contributes specificity in a manner similar to Raman methods. SEM adds a higher resolution than optical methods and provides a clear view of morphology. In this narrative review, we provide an overview of the available literature comparing innovational techniques in synovial fluid analysis.