Vitiligo: Current Understanding and Future Treatment Directions

Genetic factors play the largest role in the risk for developing vitiligo, but recent research has provided a greater understanding of the pathogenesis of the autoimmune disease as well as its future therapeutic potential, according to a review study published in the Journal of Dermatology.

Proposed pathogenic mechanisms for the pathogenesis of vitiligo involve genetic, oxidative stress, autoimmune responses, melanocyte detachment, and inflammatory components.

There is strong evidence from several studies pointing to a genetic component in vitiligo. Approximately 80% of vitiligo risk may be associated with genetic factors, according to recent research city by the study authors. Polymorphisms in HLA–A are associated with the strongest genetic risk for the skin depigmentation disorder, followed by other genes associated with antigen presentation and processing.

Other research suggests the initial event in the melanocyte destruction is caused by oxidative stress. In patients with vitiligo, melanocytes are more susceptible to the effects of oxidative stress then people without the condition. Studies show vitiligo melanocytes have more dysregulated autophagy and are significantly more sensitive to the effects of oxidative stress caused by impairments in the nuclear factor E2-related factor 2 (Nrf2)-p62 pathway. Patients with vitiligo may also have a disrupted functionality in mitochondria, which plays a key role in the generation of reactive oxygen species.

From a clinical dermatology perspective, successful vitiligo management remains relatively difficult to achieve. Management should primarily focus on halting immune destruction of melanocytes, stopping depigmentation, stabilizing depigmented lesions, inducing repigmentation, and preventing relapse.

Advancements made in the understanding of vitiligo’s pathogenesis and the role of the immune system in the disorder have led to the development of more targeted therapies. Some case reports and open label trials suggest JAK inhibitors may play a role in the treatment of vitiligo.

A proof-of-concept trial showed twice daily topical ruxolitinib 1.5% cream led to significant repigmentation in photo exposed areas after 20 weeks. Another phase 2 randomized control trial demonstrated a similar significant improvement in repigmentation with twice and once daily use of the cream compared with placebo.

In addition, afamelanotide is a long-lasting synthetic analog of alpha-melanocyte-stimulating hormone that may promote repigmentation in concert with narrowband ultraviolet B therapy.

According to the authors of the review study, potential future therapeutic targets for vitiligo, at least based on current research, include “NK cells and CD8+ T cells using anti-NKG2-D type II integral membrane protein antibodies, HSP70 proteins, and TRM cells using anti-interleukin-15 antibodies.”

Reference

Bergqvist C, Ezzedine K. Vitiligo: A focus on pathogenesis and its therapeutic implications. J Dermatol. 2021;48(3):252-270. doi:10.1111/1346-8138.15743