Clinical Features, Immunopathogenesis, and Therapeutic Strategies in Vitiligo (Jul 10.1007/s12016-021-08868-z, 2021)

Vitiligo is an autoimmune disease of the skin characterized by epidermal melanocyte loss resulting in white patches, with an approximate prevalence of 0.5–2% worldwide. Several precipitating factors by chemical exposure and skin injury present commonly in patients with vitiligo. Although the diagnosis appears to be straightforward for the distinct clinical phenotype and specific histological features, vitiligo provides many challenges including chronicity, treatment resistance, frequent relapse, associated profound psychosocial effect, and negative impact on quality of life. Multiple mechanisms are involved in melanocyte disappearance, including genetics, environmental factors, and immune-mediated inflammation. Compelling evidence supports the melanocyte intrinsic abnormalities with poor adaptation to stressors leading to instability and release of danger signals, which will activate dendritic cells, natural killer cells, and innate lymphoid cells to initiate innate immunity, ultimately resulting in T-cell mediated adaptive immune response and melanocyte destruction. Importantly, the cross- talk between keratinocytes, melanocytes, and immune cells, such as interferon (IFN)-γ signaling pathway, builds inflammatory loops that give rise to the disease deterioration. Improved understanding of the immune pathogenesis of vitiligo has led to the development of new therapeutic options including Janus kinase (JAK) inhibitors targeting IFN-γ signaling pathways, which can effectively reverse depigmentation. Furthermore, definition of treatment goals and integration of comorbid diseases into vitiligo management have revolutionized the way vitiligo is treated. In this review, we highlight recent developments in vitiligo clinical aspects and immune pathogenesis. Our key objective is to raise awareness of the complexity of this disease, the potential of prospective therapy strategies, and the need for early and comprehensive management. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.