Background/Purpose: The diagnosis of gout or pseudogout hinges upon identification of monosodium urate (MSU) crystals and calcium pyrophosphate (CPPD) crystals in synovial fluid (SF) aspirates from affected joints. Prompt recognition of SF crystals using polarizing light microscopy (PLM) depends upon a skilled observer identifying negatively and/or positively birefringent crystals. However, appropriate personnel to perform and interpret PLM are not always available. Failure to promptly diagnose crystalline arthritis results in delay in treatment and even hospital admission due to uncertainty about diagnosis.

Methods: We have built a desktop instrument to perform Raman spectroscopy (RS) on synovial fluids that is sensitive and specific for identifying monosodium urate and CPPD crystals can be commercialized and developed for point of service (POS) use. Discarded SF from clinically indicated joint aspirates were analysed using PLM either by a rheumatologist and/or pathologist. Remaining SF was aliquoted and frozen at -80°C. SF was digested with hyaluronidase, Proteinase K, and sodium dodecyl sulfate (SDS) and concentrated for use in RS.

Results: Eighty samples were analyzed.  MSU crystals were detected by PLM in 19/80 and CPPD crystals in 10/80 samples. Initial measurement using RS detected crystals in 26/29 samples with a sensitivity of 89.65% and a specificity of 100%. In 80 samples, 2 MSU and 1 CPPD sample were identified by PLM but missed by RS and 3 CPPD containing samples were identified by RS but missed by PLM. 

Conclusion: Based on our observations, development of a benchtop point of service clinical grade RS instrument would be useful in speeding the time to, and accuracy of, clinical diagnosis of gout and pseudogout. While the presence of MSU crystals is suspicious for gout even when they are extracellular, the same is not true for CPPD. CPPD found in SF but not in WBC may not be the primary cause of joint inflammation, and therefore diagnosis of pseudogout requires both positive identification of CCPD crystals and demonstration that the CPPD crystals are intracellular. CCPD crystals are typically more difficult to identify than MSU crystals by PLM, but not by RS. Further, pseudogout may accompany infection that can be detected only by microbiological testing. Thus the value in benchtop RS lies in the ability to quickly and accurately detect the presence of SF MSU and CPPD crystals. Identification of SF MSU as evidence of gout flare faciliates prompt treatment with outpatient follow up. Whether hospital admission(s) can be reduced by POS RS diagnosis of gout or potential pseudogout is an open question. While RS facilitates detection of both MSU and CPPD crystals, limitations of the study include the inability of Raman spectroscopy to distinguish intra and extracellular crystals. Nonetheless, RS used at POS for SF crystal detection could reduce the need for inpatient admission in patients with joint effusion and whose diagnosis might otherwise be uncertain, potentially improving use of inpatient resources and improving the quality of patient care. Prospective testing of this RS instrument at POS is a future priority.

These studies were funded by NIAMS award AR# 057812 to OXA

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/raman-spectroscopy-point-of-service-diagnosis-is-sensitive-and-specific-a-tool-for-improving-accuracy-and-reducing-future-hospital-admission/