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Vitiligo: Focus on Clinical Aspects, Immunopathogenesis, and Therapy

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Abstract

Vitiligo is an acquired chronic depigmenting disorder of the skin, with an estimated prevalence of 0.5% of the general population, characterized by the development of white macules resulting from a loss of epidermal melanocytes. The nomenclature has been revised after an extensive international work within the vitiligo global issues consensus conference, and vitiligo (formerly non-segmental vitiligo) is now a consensus umbrella term for all forms of generalized vitiligo. Two other subsets of vitiligo are segmental vitiligo and unclassified/undetermined vitiligo, which corresponds to focal disease and rare variants. A series of hypopigmented disorders may masquerade as vitiligo, and some of them need to be ruled out by specific procedures including a skin biopsy. Multiple mechanisms are involved in melanocyte disappearance, namely genetic predisposition, environmental triggers, metabolic abnormalities, impaired renewal, and altered inflammatory and immune responses. The auto-immune/inflammatory theory is the leading hypothesis because (1) vitiligo is often associated with autoimmune diseases; (2) most vitiligo susceptibility loci identified through genome-wide association studies encode immunomodulatory proteins; and (3) prominent immune cell infiltrates are found in the perilesional margin of actively depigmenting skin. However, other studies support melanocyte intrinsic abnormalities with poor adaptation of melanocytes to stressors leading to melanocyte instability in the basal layer, and release of danger signals important for the activation of the immune system. Recent progress in the understanding of immune pathomechanisms opens interesting perspectives for innovative treatment strategies. The proof of concept in humans of targeting of the IFNγ /Th1 pathway is much awaited. The interplay between oxidative stress and altered immune responses suggests that additional strategies aiming at limiting type I interferon activation pathway as background stabilizing therapies could be an interesting approach in vitiligo. This review covers classification and clinical aspects, pathophysiology with emphasis on immunopathogenesis, and promising therapeutic approaches.

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Abbreviations

CRT:

Calreticulin

CTL:

Cytotoxic T cells

ER:

Endoplasmic reticulum

HSP:

Heat shock protein

IFN:

Interferon

IL:

Interleukin

NK:

Natural killer

pDCs:

Plasmacytoid dendritic cells

PRR:

Pathogen recognition receptors

ROS:

Reactive oxygen species

SV:

Segmental vitiligo

TLR:

Toll-like receptors

TNF:

Tumour necrosis factor

Tregs:

Regulatory T cells

UPR:

Unfolded protein response

VGICC:

Vitiligo Global Issues Consensus Conference

VETF:

Vitiligo European task force

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  1. Katia Boniface and Julien Seneschal equally contributed to this work.

Authors and Affiliations

  1. INSERM U1035, ATIP-AVENIR, Université de Bordeaux, Bordeaux, France

    Katia Boniface, Julien Seneschal & Alain Taïeb

  2. Department of Dermatology and Paediatric Dermatology, National Centre for Rare Skin disorders, Saint-André and Pellegrin Hospital, Bordeaux, France

    Julien Seneschal & Alain Taïeb

  3. San Gallicano Institute, Rome, Italy

    Mauro Picardo

  4. Department of Dermatology and Pediatric Dermatology, St André Hospital, Bordeaux University Hospitals, 1 Rue Jean Burguet, 33075, Bordeaux, France

    Alain Taïeb

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  1. Katia Boniface
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Correspondence to Alain Taïeb.

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Boniface, K., Seneschal, J., Picardo, M. et al. Vitiligo: Focus on Clinical Aspects, Immunopathogenesis, and Therapy. Clinic Rev Allerg Immunol 54, 52–67 (2018). https://doi.org/10.1007/s12016-017-8622-7

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