Systemic inflammation in asymptomatic hyperuricaemia with sonographic crystal deposits, including a comparison with normouricaemia and gout.

OBJECTIVE: To describe the inflammatory profile of asymptomatic hyperuricaemia (AH) with ultrasound evidence of monosodium urate (MSU) crystals (AH-MSUpos), vs AH without deposits (AH-MSUneg), intercritical gout and normouricaemia. METHODS: Based on serum urate levels, musculoskeletal ultrasound and history of flares, we divided 122 participants into four groups: normouricaemia, AH-MSUneg, AH-MSUpos and intercritical gout. We tested four ultrasound definitions for MSU deposition in AH: grade 2-3 (G2-3) double contour and/or tophi, G1-3 double contour and/or tophi, G1-3 Stewart scheme (double contour sign in knee cartilage and/or first metatarsophalangeal joint and/or tophi in first metatarsophalangeal joint) and G2-3 Stewart scheme. Serum acute phase reactants, cytokines, pyroptosis derivates and neutrophil-related proteins were measured and compared between groups. A linear regression model was fitted to correlate crystal and inflammatory burden (measured by ultrasound) with inflammatory markers in hyperuricaemics. RESULTS: Rates of MSU deposition in AH ranged from 26.0% to 68.8%, depending on the definition used. Levels of CRP, leukocytes, IL-1RA, IL-6, sIL-6R, IL-18, TNF-α, TGF-β and galectin-3 were higher in hyperuricaemics vs normouricaemics. Sex, obesity and comorbidity scores influenced some comparisons. We saw no differences comparing AH-MSUposvs AH-MSUneg groups, except for higher calprotectin using G1-3 sonographic definitions and higher CRP and TGF-β when restricted to women and obese participants. CONCLUSIONS: Hyperuricaemia is associated with substantial inflammation and some degree of active pyroptosis. Four different ultrasound definitions for AH with MSU deposits yielded similar findings, although we noted some differences in calprotectin, CRP, and TGF-β. Sex, obesity, and comorbidities influenced some inflammatory responses.