Background/Purpose: Endothelial cell dysfunction and/or injury are considered critical early events in the pathogenesis of vasculopathy in patients with systemic sclerosis (SSc). Hyperuricemia is known to induce endothelial dysfunction and vascular inflammation; however, the link between uric acid and SSc vasculopathy has not been well established. We investigated whether increased serum uric acid levels (SUA) are associated with the digital ulcers (DUs) in patients with SSc.

Methods: In this cross-sectional study, we consecutively recruited 71 women with SSc and 103 age- and sex-matched healthy subjects at a university-affiliated rheumatology center, and SUA levels were measured in all study subjects. All patients with SSc fulfilled the preliminary classification criteria established by the American College of Rheumatology for SSc. Active DUs were defined as a loss of epithelialization and tissues involving the epidermis, dermis, subcutaneous tissue, and bone. DUs included both, active and healed lesions.

Results:

The mean (±standard deviation) SUA levels in patients with SSc were significantly higher than those in controls (4.5±1 vs. 4.2±0.9 mg/dL, respectively, p=0.027). Patients with SSc showed a significantly lower body mass index (BMI) than healthy subjects (21.8±2.8 vs. 23.3±3.5 kg/m2, respectively, p=0.005) whereas no statistically significant intergroup difference was observed in the estimated glomerular filtration rate (eGFR). Among patients with SSc, 22 (31%) had DUs (active DUs: 8, healed DUs: 14). Patients with SSc presenting with DUs showed significantly higher SUA levels than those without DUs (5±1 vs. 4.3±0.9 mg/dL, respectively, p=0.008). In multivariable logistic regression models adjusting for confounders including BMI and eGFR, increased SUA levels were observed to be independently associated with a higher risk for the presence of DUs as shown in Table 1 (OR 2.3, 95% CI 1.16–4.57, p=0.018). Additionally, the modified Rodnan skin score and the disease duration showed a significant association with DUs (OR 1.14, 95% CI 1.03–1.27, p=0.013; and OR 1.01, 95% CI 1–1.02, p=0.023, respectively).

Table 1. Association between serum uric acid level and digital ulcers ever in patients with systemic sclerosis evaluated by logistic regression models

* Estimated using backward multivariable logistic regression models including SUA levels, MRSS, disease duration, ILD, eGFR and BMI.

Conclusion: Our data revealed that elevated SUA levels are associated with a higher risk for DUs in patients with SSc regardless of confounding factors, thereby suggesting the potential role of hyperuricemia in the pathogenesis of SSc vasculopathy.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/increased-serum-uric-acid-levels-are-associated-with-a-higher-risk-of-digital-ulcers-in-patients-with-systemic-sclerosis/