Introduction Vitiligo is an acquired depigmenting disorder t

Introduction Vitiligo is an acquired depigmenting disorder that should be differentiated from congenital hypopigmentation such as albinism, piebaldism, dyschromatosis symmetrica hereditaria, and nevus depigmentosus. Idiopathic guttate hypomelanosis, tinea versicolor, and chemically induced leukoderma caused by phenols, catechols, and rhododendrol should also be distinguished from authentic vitiligo. Segmental vitiligo affecting a unilateral dermatome-like cutaneous segment is less frequent than nonsegmental or generalized vitiligo. Occasionally, both nonsegmental and segmental vitiligo appear in one patient (mixed type). Dysregulation of the nervous system is hypothesized to be the cause of segmental vitiligo.
Epidemiology The prevalence of vitiligo is estimated at less than 1%. A precise population-based epidemiological study by Howitz et al revealed that the prevalence of vitiligo was 0.38% (179/47,033) in Denmark, peaking at 60–69 years of age with a male to female ratio of 1:1.13. Although selection bias should be considered in patient-based studies, vitiligo was found in 1134 (1.68%) of 67,448 Japanese dermatological patients, peaking at 66–75 years of age with a male to female ratio of 1:1.37. Women are generally affected by vitiligo more than (or equal to) men. In another study of 912,986 Japanese dermatological patients, congenital and acquired depigmented disorders affected 1748 (0.2%) and 6359 (0.7%) patients, respectively, and 60% of total depigmented disorders consisted of vitiligo. In Korea, the annual prevalence of vitiligo determined by hospital-visiting rate was 0.12% to 0.13%, with a male to female ratio of 1:1.31 over a 3-year period.
Pathogenesis While the pathogenesis of nonsegmental vitiligo remains poorly understood, autoimmune stress and oxidative stress are currently considered to work synergistically in the apoptosis or destruction of melanocytes (Figure 1). Both humoral and cellular immunity are involved in the development of nonsegmental vitiligo. Autoantibodies are variably detected against pigment cell Fostriecin sodium salt cost such as tyrosinase and tyrosinase-related protein 1 and 2. At the center of a vitiligo lesion, complete loss of melanocytes is observed. Infiltration of macrophages, T cells and neutrophils is demonstrated, especially in progressing perilesional skin. The majority of epidermotropic T cells express cutaneous lymphocyte antigen (skin-homing receptor) with an increased CD8/CD4 ratio and interferon γ production. Interferon γ is known to inhibit melanogenesis and to induce apoptosis of melanocytes (Figure 1). Furthermore, interferon α-2a-induced nonsegmental vitiligo occurs in the treatment of Behçet\'s disease. It should be noted that even in normal appearing skin of patients with nonsegmental vitiligo, melanocytes tend to lack expression of E-cadherin; a molecule essential to the adhesion of melanocytes to surrounding basal keratinocytes. This abnormality is associated with the detachment of the melanocytes from the basal to suprabasal layers in the epidermis, leading to apoptosis of melanocytes (Figure 1). Increased oxidative stress (excessive reactive oxygen species) with mitochondrial swelling is detected in the lesional keratinocytes of nonsegmental vitiligo (Figure 1). Low levels of antioxidant enzymes have also been detected in the serum of vitiligo patients. The inflammasome protein, nucleotide-binding domain and leucine-rich repeat containing protein 1 (NLRP1), is a key enzyme to mediate the activation of interleukin (IL)-1β. The NLRP1 and IL-1β immunostaining in the perilesional skin of nonsegmental vitiligo is significantly associated with progressive disease. Oxidative stress causes extensive alterations in conformation and function of tyrosinase, which increases the antigenicity of oxidized tyrosinase. In lesional skin, Langerhans cells are increased in number and activated so that they may facilitate the antigen-presenting process against the oxidized melanocyte antigens. Additionally, oxidative stress or mechanical friction further accelerates the detachment and apoptosis of melanocytes with insufficient expression of E-cadherin (Figure 1). This may explain the frequent occurrence of Koebner\'s phenomenon in vitiligo. Furthermore, decreased levels of copper and zinc may be related to melanogenesis and oxidative stress because these trace elements, which are considered as antioxidants, are integral parts of many metalloenzymes that are essential in the process of melanogenesis.