Vitiligo is a chronic autoimmune disease characterized by the destruction of epidermal melanocyte, resulting in well-demarcated white patches on the skin. Despite the established use of corticosteroids and calcineurin inhibitors and the recent introduction of Janus kinase (JAK) inhibitors, a breakthrough targeted therapy that interrupts the IFN-γ signaling pathway, stable repigmentation remains a major clinical challenge, necessitating deeper investigation into its pathogenesis. Among the factors contributing to vitiligo, including genetic predisposition and autoimmunity, oxidative stress is a central driver of melanocyte damage and the subsequent autoimmune response. Chronic oxidative disequilibrium (high ROS level and impaired mitochondrial activity) and reduced antioxidant capacity (Nrf2/ARE pathway and catalase deficiency) function as triggering factors upstream of most other pathogenic pathways. Consequently, targeting oxidative stress, either as a monotherapy or in synergy with emerging targeted treatments, remains a pivotal area of therapeutic interest even in the current era of targeted therapies. Still, a significant gap remains the lack of standardized oxidative biomarkers to monitor disease activity and therapeutic response. Identifying these indicators is essential for personalized clinical management in vitiligo. This review examines how chronic oxidative disequilibrium and a reduced antioxidant capacity initiate and sustain the autoimmune cascade, leading to disease onset and progression.
Aprile et al. (Tue,) studied this question.