Vitiligo Pathogenesis and Emerging Treatments

Abstract

The pathogenesis of vitiligo involves interplay between intrinsic and extrinsic melanocyte defects, innate immune inflammation, and T-cell-mediated melanocyte destruction. The goal of treatment is to not only halt disease progression but also promote repigmentation through melanocyte regeneration, proliferation, and migration. Treatment strategies that address all aspects of disease pathogenesis and repigmentation are likely to have greatest efficacy, a strategy that may require combination therapies. Current treatments generally involve nontargeted suppression of autoimmunity, whereas emerging treatments are likely to use a more targeted approach based on in-depth understanding of disease pathogenesis, which may provide higher efficacy with a good safety profile.

Keywords: Autoimmunity; Cellular stress; Chemokines; Melanogenesis; Targeted therapy; Vitiligo.

Copyright © 2016 Elsevier Inc. All rights reserved.

Figures

Fig. 1

Vitiligo pathogenesis begins with altered melanocytes that exhibit an elevated cellular stress response. This triggers autoimmunity, which targets melanocytes for destruction, resulting in focal depigmentation. Repigmentation requires the growth and migration of melanocytes, typically from hair follicles. Thus, there are 3 goals to consider during the treatment of vitiligo: 1) reducing melanocyte stress, 2) suppressing autoimmune targeting of melanocytes, and 3) promoting melanocyte regeneration. Current treatments, including topical immunosuppressants, phototherapy, and surgical approaches, partially address these goals in overall non-targeted ways.

Fig. 2

Autoimmunity in vitiligo is driven by the IFN-γ-CXCL10 cytokine signaling pathway. Activated melanocyte-specific CD8+ T cells secrete IFN-γ, which signals through the IFN-γ receptor (IFN-γR) to activate JAK1/2 and STAT1. This induces the production of CXCL9 and CXCL10, which signal through their receptor CXCR3 to recruit more autoreactive T cells to the epidermis, resulting in widespread melanocyte destruction. Targeting this cytokine pathway represents an emerging treatment strategy for vitiligo.

Fig. 3

Current and emerging treatments address 3 major goals in vitiligo treatment. Current treatments are listed in black, emerging treatments in red.