INSERM U1035, ATIP-AVENIR, Université de Bordeaux, Bordeaux, France.
Department of Dermatology and Paediatric Dermatology, National Centre for Rare Skin disorders, Saint-André and Pellegrin Hospital, Bordeaux, France.
Clin Rev Allergy Immunol. 2018 Feb;54(1):52-67. doi: 10.1007/s12016-017-8622-7.
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.
白癜风是一种获得性慢性皮肤色素脱失病，估计普通人群的患病率为 0.5%，其特征是由于表皮黑素细胞丧失而出现白色斑片。在白癜风全球问题共识会议的广泛国际工作之后，对命名法进行了修订，白癜风（以前称为非节段性白癜风）现在是所有广义白癜风形式的共识伞式术语。白癜风的另外两个子集是节段性白癜风和未分类/未确定的白癜风，它们分别对应于局限性疾病和罕见变异。一系列色素减退性疾病可能会伪装成白癜风，其中一些需要通过特定程序排除，包括皮肤活检。多种机制参与黑素细胞消失，即遗传易感性、环境触发因素、代谢异常、更新受损以及炎症和免疫反应改变。自身免疫/炎症理论是主要假说，因为 (1) 白癜风常与自身免疫性疾病相关；(2) 通过全基因组关联研究确定的大多数白癜风易感性位点编码免疫调节蛋白；和 (3) 在活跃脱色皮肤的病变边缘发现明显的免疫细胞浸润。然而，其他研究支持黑素细胞内在异常，黑素细胞对应激因素适应不良导致基底层黑素细胞不稳定，并释放对免疫系统激活很重要的危险信号。对免疫病理机制的理解的最新进展为创新治疗策略开辟了有趣的视角。靶向 IFNγ/Th1 途径在人类中概念验证的证据备受期待。氧化应激和免疫反应改变之间的相互作用表明，旨在限制 I 型干扰素激活途径作为背景稳定疗法的额外策略可能是白癜风的一种有趣方法。这篇综述涵盖了分类和临床方面、强调免疫发病机制的病理生理学以及有前途的治疗方法。
