A precise pathogenesis of vitiligo is not yet understood, but this article suggests that it is based on oxidative stress and heightened levels of reactive oxygen species.
There are many hypotheses about the pathogenesis of vitiligo, but the most commonly accepted is that of an oxidative stress-induced immune response. This immune response ultimately leads to melanocyte death, which causes vitiligo symptoms. The relationship between the various modes of cell death and oxidative stress can vary, and this study, published in Oxidative Medicine and Cellular Longevity, provides an analysis of that relationship with the goal of inspiring new ideas for exploring potential targets of vitiligo treatment.
Various modes of cell death have been studied in relation to vitiligo, including apoptosis, autophagy, and ferroptosis. Oxidative stress is linked to all of these modes, as it causes heightened levels of reactive oxygen species (ROS). These can induce autophagy by activating the Nrf2 antioxidant pathway in melanocytes. Various mechanisms by which oxidative stress relates to melanocyte condition are described, including iron Fenton reaction and mitochondrial respiration, and the link between the redox homeostasis of melanocytes and the autophagy process, which can be caused by ROS.
The authors conclude by noting that their analysis supports the concept of oxidative stress as the initiating factor of vitiligo through the induction of various changes in keratinocytes, ultimately resulting in the death of melanocytes. Based on a variety of factors, they note that autophagy-deficient melanocytes and vitiligo melanocytes share cellular redox regulation, increased membrane lipid oxidation, and premature senescence. They note their research does not conclusively establish a link between vitiligo onset and ferroptosis, although this link is present in other similar diseases. They suggest that therapeutic interventions that rely on precise manipulation of oxidative stress can restore redox homeostasis and prevent melanocyte death.
Xuan, Y., Yang, Y., Xiang, L., & Zhang, C. (2022). The Role of Oxidative Stress in the Pathogenesis of Vitiligo: A Culprit for Melanocyte Death. Oxid Med Cell Longev, 2022, 8498472. doi:10.1155/2022/8498472