Vitiligo: From mechanisms of disease to treatable pathways

Abstract

Vitiligo is a chronic autoimmune-mediated disease characterised by the loss of pigmentary melanocytes in the epidermis. Vitiligo is associated with loss of functional epithelium and significant reductions in quality of life with limited long-term treatment options, highlighting a continued unmet clinical need. A comprehensive understanding of the pathophysiology and newly investigated treatment pathways may guide multimodal treatment strategies and identify future drug targets. The pathology of vitiligo is multifactorial; however, environmental insults in genetically susceptible populations may lead to disease development. Autoreactive CD8+ T-cells that target melanocytes and release inflammatory mediators, including interferon-γ and interleukins 2, 6, 15, 17 and 33 among others, have been identified in vitiligo pathogenesis. Treatment modalities for vitiligo revolve around six broad disease concepts, including procedural modalities (tissue and cellular grafting), phototherapy, stem cells, anti-inflammatories, genetic polymorphisms and antioxidants/vitamins/herbals. Genetic polymorphisms, such as catalase gene variations and toll-like receptor polymorphisms, along with stem cell targets such as melanocytes derived from stem cells, have been implicated in vitiligo onset and possible treatment. Novel JAK-STAT inhibitors have been recently investigated for vitiligo, whereas topical corticosteroids and calcineurin inhibitors continue to be used. Vitamin D, vitamin E, zinc, copper, piperine, pseudo catalase and other vitamins/herbals may improve vitiligo outcomes primarily through antioxidant supplementation pathways. Future studies should investigate alternative drug pathways and targets implicated in vitiligo in large patient cohorts, as well as treatments that target suspected causative immune cells, including memory T-cells, which may provide long-lasting disease-free remission.

FIGURE 1

Summary of vitiligo pathophysiology and drug targets of common treatment modalities.

FIGURE 2

Summary of vitiligo treatment pathways and drug targets.