Systematic evidence grading evaluates multisystemic associations and risks of vitiligo.

Vitiligo, a chronic autoimmune skin disorder characterized by refractory depigmentation, has inconsistent associations with various biomarkers and diseases due to confounding factors. Here, we conduct a comprehensive umbrella review and comparative analysis to evaluate the validity and strength of evidence from observational studies on vitiligo. 103 meta-analyses and 150 Mendelian randomization (MR) analyses are included, spanning categories including cardiometabolism, cancer, autoimmune, dermatosis, psychiatry/neurology/senses, and biomarkers/lifestyle. Evidence grading reveals seven convincing meta-analysis findings: five factors (fasting blood glucose, Graves' disease, thyroid antibodies, cataracts, and glaucoma) are associated with an increased risk of vitiligo, while vitiligo is related to two conditions (a decreased risk of overall cancer and an increased risk of inflammatory bowel disease). Future similar research is unlikely to alter these findings according to fail-safe number. Among them, the protective effect of vitiligo on overall cancer risk is also supported by causal associations from MR evidence, indicating a reassuring cancer risk in vitiligo. This study establishes an evidence hierarchy for vitiligo, which may inform multidisciplinary management strategies.