Current Concepts of Vitiligo Immunopathogenesis

Abstract

Vitiligo is an acquired immune-mediated disorder of pigmentation clinically characterized by well-defined depigmented or chalk-white macules and patches on the skin. The prevalence of vitiligo varies by geographical area, affecting 0.5% to 2% of the population. The disease imposes a significant psychological burden due to its major impact on patients’ social and emotional aspects of life. Given its autoimmune background, vitiligo is frequently associated with other autoimmune diseases or immune-mediated diseases. Vitiligo is a multifaceted disorder that involves both genetic predisposition and environmental triggers. In recent years, major predisposing genetic loci for the development of vitiligo have been discovered. The current findings emphasize the critical role of immune cells and their mediators in the immunopathogenesis of vitiligo. Oxidative-stress-mediated activation of innate immunity cells such as dendritic cells, natural killer, and ILC-1 cells is thought to be a key event in the early onset of vitiligo. Innate immunity cells serve as a bridge to adaptive immunity cells including T helper 1 cells, cytotoxic T cells and resident memory T cells. IFN-γ is the primary cytokine mediator that activates the JAK/STAT pathway, causing keratinocytes to produce the key chemokines CXCL9 and CXCL10. Complex interactions between immune and non-immune cells finally result in apoptosis of melanocytes. This paper summarizes current knowledge on the etiological and genetic factors that contribute to vitiligo, with a focus on immunopathogenesis and the key cellular and cytokine players in the disease’s inflammatory pathways.

Presentation of vitiligo in a case of COVID‐19 infection concomitant with receiving remdesivir

“…showed that RDV suppresses mitochondrial respiration, induces mitochondrial fragmentation, and decreases the redox potential resulting in cardiotoxicity 17 . As mentioned before, mitochondrial dysfunction decreases the resistance of melanocytes to oxidative stress and predisposes patients to vitiligo 5 . Therefore, RDV administration might have played a role in vitiligo manifestation in our patient.…”

COVID‐19 vaccine–associated vitiligo: A cross‐sectional study in a tertiary referral center and systematic review

“…Numerous pathomechanisms have been proposed to elucidate melanocyte destruction in vitiligo, including oxidative stress, innate and adaptive immune responses, inflammasome activation, genetic susceptibility, and melanocyte detachment mechanisms 17–19 . While a precise cause is still subject to debate, most evidence supports a central role of the interferon gamma (IFN‐γ)–CXCR3‐CXCL9/10 axis in inducing cytotoxic CD8+ T cell–targeted destruction of melanocytes.…”

Is the targeted approach for vitiligo satisfactory?

“…IFN-γ, which activates JAK/STAT pathway and causes keratinocytes to produce the chemokines CXCL9 and CXCL10. 6 Fig. 4: Mediators in vitiligo Tumor necrosis factor-alpha (TNF-α) is one of the major cytokines implicated in the pathogenesis of vitiligo.…”