Tissue Engineering and Cutaneous Pathophysiology Laboratory, Istituto Dermopatico dell'Immacolata, IDI-IRCCS, Via dei Monti di Creta 104, 00167 Rome, Italy.
Curr Drug Metab. 2010 Jun 1;11(5):451-67. doi: 10.2174/138920010791526105.
Vitiligo is a multifactorial disorder characterized by the appearance of white maculae that may spread over the entire body skin. Depigmentation arises from the loss of functioning melanocytes. Non segmental vitiligo (NSV) is the most common form of the disease: it is usually progressive and may be associated with familiarity and autoimmunity. Segmental vitiligo (SV) frequently stabilizes few years after its onset. Vitiligo etiology involves multiple pathogenetic factors, most of them working in concert. Impaired antioxidative defences lead to accumulation of reactive oxygen species (ROS), which affect melanocytes. Mitochondrial membrane lipid peroxidation may participate to ROS overproduction. A temporal sequence may connect oxidative stress and autoimmunity. Overall, a genetic predisposition renders vitiligo melanocytes more susceptible to precipitating factors than normal healthy melanocytes. The definition of isolated or superimposed manifestations of polygenic skin disorders has been proposed for SV and SV-NSV association. Keratinocytes and melanocytes are both affected and apoptosis, ageing or melanocythorragy are the ultimate effects of the complex deregulation in vitiligo skin. Pathogenetic therapies mainly act by inducing immunosuppression and stimulation of melanocyte proliferation and migration. Here the most popular hypotheses for the pathogenesis of vitiligo are summarized. Fundamental cellular, biochemical and molecular alterations accounting for melanocyte destruction in vitiligo are also described. Last, pathogenetic approaches in the treatment of such a complex disease are discussed, with particular consideration on the cellular and molecular targets of the current therapies.
白癜风是一种多因素疾病，其特征是出现白色斑块，可能会扩散到全身皮肤。色素脱失是由于功能失调的黑素细胞丧失引起的。非节段性白癜风（NSV）是最常见的疾病形式：它通常是进行性的，可能与家族史和自身免疫有关。节段性白癜风（SV）通常在发病后几年内稳定下来。白癜风的病因涉及多种发病因素，其中大多数因素协同作用。抗氧化防御功能受损会导致活性氧（ROS）的积累，从而影响黑素细胞。线粒体膜脂质过氧化可能参与 ROS 的过度产生。氧化应激和自身免疫之间可能存在时间顺序。总的来说，遗传易感性使白癜风黑素细胞比正常健康黑素细胞更容易受到诱发因素的影响。已经提出了将 SV 和 SV-NSV 关联的多基因皮肤疾病的孤立或叠加表现定义为 SV 和 SV-NSV 关联。角质形成细胞和黑素细胞都受到影响，细胞凋亡、衰老或黑素细胞减少是白癜风皮肤复杂失调的最终结果。发病机制治疗主要通过诱导免疫抑制和刺激黑素细胞增殖和迁移来发挥作用。本文总结了白癜风发病机制的最流行假说。还描述了导致白癜风黑素细胞破坏的基本细胞、生化和分子改变。最后，讨论了治疗这种复杂疾病的发病机制方法，特别考虑了当前疗法的细胞和分子靶点。
