Association of Vitiligo With Metabolic and Cardiovascular Comorbidities: A Multicenter Propensity‐Matched Cohort Analysis

Vitiligo is a chronic autoimmune skin disorder characterized by melanocyte loss, depigmented macules, and involves complex pathogenesis [1, 2]. Vitiligo is viewed as having systemic implications beyond skin pigmentation; non-segmental vitiligo in particular shows higher rates of autoimmune and metabolic comorbidities [1]. Further validation across large electronic health records (EHR) is needed to assess the robustness and generalizability of cardiometabolic associations in vitiligo. Therefore, we conducted a retrospective cohort study using TriNetX EHR to perform a propensity score-matched cohort study of adults with vitiligo versus non-vitiligo controls [1]. The vitiligo cohort was defined as patients with at least one diagnosis of vitiligo (International Classification of Diseases, Tenth Revision, Clinical Modification [ICD-10-CM] L80) and an encounter coded as follow-up after completed treatment for malignant neoplasm (Z08) or for other conditions (Z09). The control cohort consisted of patients with a Z08/Z09 encounter but no vitiligo diagnosis. We performed 1:1 propensity score matching between vitiligo and control patients to balance baseline characteristics. Matching variables included age, sex, race, and ethnicity. While demographic characteristics were well balanced, residual confounding from unmeasured factors such as metabolic syndrome is likely under-coded in the EHR data. Outcomes were assessed from 1 day after index date through the end of follow-up. We included patients even if they had the outcome diagnosis before the index date to capture prevalent cases as well. The primary outcomes of interest were type 2 diabetes mellitus (ICD-10 E11), essential (primary) hypertension (I10), disorders of lipoprotein metabolism/dyslipidemia (E78), ischemic heart disease (I20–I25), metabolic syndrome (E88.81), and a composite obesity outcome. For obesity, we defined cases by any of ICD-10 codes E66 (overweight/obesity) or body mass index (BMI) Z-codes (Z68.3 indicating a BMI of 30–39 [Obesity Classes I and II] and Z68.4 representing a BMI of 40 or greater [Class III/Morbid Obesity]) in adults. We compared outcome frequencies between cohorts and calculated risk ratios (RRs) with 95% confidence intervals (95% CI) using Wald's method. The matched cohorts included 13,917 vitiligo patients and 13,917 controls (Table 1). The frequency of cardiometabolic conditions was consistently higher in the vitiligo group (Table 2). Type 2 diabetes was present in 3719 vitiligo patients (26.72%) versus 3319 controls (23.85%), corresponding to a relative risk (RR) of 1.121 (95% CI 1.076–1.167), p < 0.0001. Hypertension occurred in 7240 vitiligo patients (52.02%) versus 6619 controls (47.56%) (RR = 1.094, 95% CI 1.068–1.120, p < 0.0001). Dyslipidemia was diagnosed in 7265 (52.20%) of the vitiligo group compared with 6099 (43.82%) of controls (RR = 1.191, 95% CI 1.162–1.221, p < 0.0001). Ischemic heart disease affected 2975 vitiligo patients (21.38%) versus 2753 controls (19.78%) (RR = 1.081, 95% CI 1.032–1.132, p = 0.001). Metabolic syndrome was recorded in 225 vitiligo patients (1.62%) compared with 140 controls (1.01%) (RR = 1.607, 95% CI 1.303–1.982, p < 0.0001). Obesity was more common in the vitiligo cohort (4478; 32.18%) than in controls (3888; 27.94%) (RR = 1.152, 95% CI 1.111–1.194, p < 0.0001). Vitiligo patients had approximately a 9%–19% higher relative risk of metabolic and vascular conditions than controls, with the largest relative increase observed for metabolic syndrome (RR = 1.61). Our finding of higher diabetes prevalence (RR = 1.12) also resonates with prior observations of insulin resistance in vitiligo [1]. The increased ischemic heart disease (21.4% vs. 19.8%) also supports a systemic link. Together, these studies consistently suggest that vitiligo entails systemic inflammation or immune dysregulation that promotes atherosclerosis and metabolic disturbance [3-5]. Our results confirm that adults with vitiligo had significantly higher prevalence of type 2 diabetes, hypertension, dyslipidemia, ischemic heart disease, metabolic syndrome, and obesity compared to matched controls [1, 2]. Clinicians should be aware of these risks and consider cardiovascular risk factor screening in patients with vitiligo. The authors have nothing to report. The authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.