Less frequent skin ulcers among patients with Werner syndrome treated with pioglitazone: findings from the Japanese Werner Syndrome Registry

Werner syndrome (WS) is an autosomal recessive, adult-onset, progeroid syndrome caused by mutations. As refractory skin ulcers significantly affect the quality of life of patients with WS, this study identified ulcer risk factors and assessed prevention methods. We analyzed the data of 51 patients with WS enrolled in the Japanese Werner Syndrome Registry between 2016 and 2022. A cross-sectional analysis was performed to determine the association with skin ulcers at baseline. Statistical analyses were conducted, including Welch's and Pearson's chi-square tests. Age was adjusted using a logistic regression model. The mean patient age was 48.8±7.6 years, and 66.7% of patients presented with skin ulcers. Univariate analysis showed that patients with skin ulcers were older than those without ulcers. Systolic blood pressure (SBP) was higher in patients with skin ulcers. Patients without skin ulcers received metformin and pioglitazone treatment significantly more often than those with ulcers. Logistic regression analysis adjusted for age showed that higher SBP remained a significant risk factor for skin ulcers. Patients administered pioglitazone had lower ulcer morbidity. Age and SBP are risk factors for skin ulcers in patients with WS. Moreover, pioglitazone treatment may prevent skin ulcers.