Background: Various observations suggest monosodium urate (MSU) formation would require a protein template to start crystallization [1], while tophi sections show long, highly-arranged crystals [2], probably formed after other crystals. Hence, a double mechanism of crystallization may exist in the joint tissues. Objectives: To determine whether the length of MSU crystals would vary according to the presence of organized sonographic deposits (likely long crystals deriving from them). Methods: We reported the complete set of patients with crystal-proven gout. Ultrasound of the target joint was performed to detect elementary gout lesions [2021 OMERACT]: double-contour (DC) sign, tophi, and aggregates. Two sonographic models were assessed: Model 1, grade 2-3 of any deposit (DC sign, tophi, or aggregates), and Model 2, limited to grade 2-3 DC sign or tophi. Later, synovial fluid was aspirated. The length of MSU crystals was measured by a blinded observer using a calibrated polarized light microscope. The distribution of MSU crystal length (in µm) and the absolute and relative frequency of long crystals (defined according to percentiles 66, 75, or 90) were tested with each sonographic model using Mann-Whitney U's test. Quantitative data is shown as median (p25-75). Results: The final analysis includes 1076 crystals in 28 joints from 25 patients (three with an oligo-polyarticular flare). The median age was 60 years (54-72), and 32% had subcutaneous tophi. Their median urate levels over the last two years were 7.5 mg/dL (7.1-8.9), with 29% on current urate-lowering treatment. The median length of MSU crystals was 23.3 µm (95%CI 22.3-24.4), where crystals mostly gathered [Figure 1-A]. Applying Model 1 (met by 20 joints, 71.4%), there were no differences in crystal length between those with deposits and those without (22.5 vs 21.7 µm; p=0.42) [Figure 1-B, top] with a similar distribution of long crystals (P66, P75, or P90) [Figure 2, middle and bottom]. In Model 2 (15 joints, 53.6%), crystal length remained nondifferent between groups (22.8 µm versus 21.2 µm; p=0.12) [Figure 2, top], but we found a higher presence of long crystals according to P66 in joints with deposits, both as absolute numbers and percentages, [Figure 1-C and 1-D]. Crystal lengths and the presence of long crystals showed no association with gout characteristics, serum urate levels or local power-Doppler signal. Conclusion: We identified variations in the length of MSU crystals in synovial fluid: a reduced length shared by most crystals, perhaps formed after protein templates, and longer crystals, better identified by the presence of sonographic deposits (DC sign or tophi) as is seen in tophi sections, suggesting a secondary formation using as templates previously formed crystals. REFERENCES: [1] Pascual, et al. Ann Rheum Dis. 1998;57(4):255. [2] Pascual, et al. Nat Rev Rheumatol. 2015;11(12):725-30. Acknowledgements: NIL. Disclosure of Interests: Mariano Andrés Menarini, Grunenthal, M Carmen López González: None declared, Elena Sansano: None declared, Cristina Rodríguez: None declared, Irene Calabuig: None declared, Agustín Martínez-Sanchis: None declared, Eliseo Pascual: None declared.
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