Recent advances in understanding vitiligo

Abstract

Vitiligo, an acquired depigmentation disorder, manifests as white macules on the skin and can cause significant psychological stress and stigmatization. Recent advances have shed light on key components that drive disease onset and progression as well as therapeutic approaches. Vitiligo can be triggered by stress to the melanin pigment-producing cells of the skin, the melanocytes. The triggers, which range from sunburn to mechanical trauma and chemical exposures, ultimately cause an autoimmune response that targets melanocytes, driving progressive skin depigmentation. The most significant progress in our understanding of disease etiology has been made on three fronts: (1) identifying cellular responses to stress, including antioxidant pathways and the unfolded protein response (UPR), as key players in disease onset, (2) characterizing immune responses that target melanocytes and drive disease progression, and (3) identifying major susceptibility genes. The current model for vitiligo pathogenesis postulates that oxidative stress causes cellular disruptions, including interruption of protein maturation in the endoplasmic reticulum (ER), leading to the activation of the UPR and expression of UPR-regulated chemokines such as interleukin 6 (IL-6) and IL-8. These chemokines recruit immune components to the skin, causing melanocytes to be targeted for destruction. Oxidative stress can further increase melanocyte targeting by promoting antigen presentation. Two key components of the autoimmune response that promote disease progression are the interferon (IFN)-γ/CXCL10 axis and IL-17-mediated responses. Several genome-wide association studies support a role for these pathways, with the antioxidant gene NRF2, UPR gene XBP1, and numerous immune-related genes including class I and class II major histocompatibility genes associated with a risk for developing vitiligo. Novel approaches to promote repigmentation in vitiligo are being investigated and may yield effective, long-lasting therapies.

Association of human beta-defensin 1 gene polymorphisms with nonsegmental vitiligo

“…Thus, our findings support the autoimmune hypothesis for vitiligo, considering the chemoattractant properties of HBD‐1 for immature dendritic cells and memory T cells, which in the presence of ‘danger’ signals (e.g. oxidative stress, high levels of IL‐6, IL‐8 and heatshock protein 70) would promote initial autoantigen presentation and depigmentation flares, respectively, a model similar to that previously suggested by Prado‐Montes de Oca et al . for atopic dermatitis …”

“…Although the exact aetiology of vitiligo remains elusive, autoimmunity is believed to play an important role in disease pathogenesis, as vitiligo is often associated with autoimmune diseases . There is also evidence for a direct role for interferon‐γ‐producing CD8+ cytotoxic T lymphocytes (CTLs) in the progression of vitiligo, corresponding to a T helper (Th)1 response . In addition, Th17 response has already been acknowledged to play an important role in vitiligo pathogenesis …”

“…There is also evidence for a direct role for interferon‐γ‐producing CD8+ cytotoxic T lymphocytes (CTLs) in the progression of vitiligo, corresponding to a T helper (Th)1 response . In addition, Th17 response has already been acknowledged to play an important role in vitiligo pathogenesis …”

Herbal Remedies and New Approaches in Vitiligo Treatment

“…12,19 Ayrıca yapılan çalışmalarda, kronik stresin kutan melanogenezi baskılamasıyla, vitiligonun başlamasında çok etkili olduğu bulunmuştur. [20][21][22] VİTİLİGODA CİLTTEKİ HİSTOKİMYASAL BULGULAR Vitiligo hastalığında, ciltte hücresel boyutta bazı farklılıkların olduğu kaydedilmiştir. Bunlar; tirozin eksikliği, etkilenmiş alandaki epidermal bazal hüc-relerin normal cilde oranla daha az RNA içermesi, etkilenmiş alandaki bazal hücrelerin ve sivri hücre-lerin nükleusların normal cilttekilere oranla daha büyük ve daha parçalı olması, DNA'ya karşı daha zayıf reaksiyon gösterirken, hiyalüronik asit tipindeki polisakkaritlere ve alkalen fosfataza karşı daha güçlü reaksiyon vermesi, alfa dendritik hücrelerde melanosit yokluğu ya da etkisizliği olarak sıralana-bilmektedir.…”

Introductory Chapter: Melanin, a Versatile Guardian

“…Disorders of melanin production, whether acquired, such as vitiligo [8], or congenital, such as oculocutaneous albinism [9], are well-recognized human diseases.…”