Histopathological Features of Vitiligo and Melanocyte Degeneration
The affected skin in vitiligo demonstrates melanin loss and absence of or reduced numbers of melanocytes in the epidermis [16]. This decrease varies according to the disease stage [13]. Melanocytes as revealed by using an appropriate monoclonal antibody technique or the Fontana Masson (FM) stain, remain present, however, they disappear from affected skin of vitiligo as the disease progress [17]. Immunohistochemical studies of vitiligo lesions show the absence of melanocytes from the basal layer, but they may exist in decreased numbers and can demonstrate degenerative changes [18].
Even though it is clear that depigmentation in vitiligo results from melanocyte loss from the skin, it remains unclear whether this occurs through a degenerative or autoimmune process. Defective in vitrogrowth of melanocytes derived from individuals with vitiligo [19, 20] and increased susceptibility of vitiligo melanocytes to exogenous stimuli suggests that degeneration may elucidate melanocyte loss [21].
Melanocytes from vitiligo subjects were shown to poorly proliferate compared to healthy normal melanocytes [19] and also they show inadequate antioxidant activity with high levels of superoxide dismutase and low levels of catalase [22]. Under normal circumstances, superoxide dismutase catalyses the first step of dismutation by converting the superoxide anion into oxygen and hydrogen peroxide and then catalase enzyme transforms hydrogen peroxide into water and oxygen, protecting cells from reactive oxygen species (ROS). In fact, melanocytes synthesise high ROS levels as by-product of melanogenesis. Therefore, compensatory media supplements such as growth factors or catalase are required to culture melanocytes derived from vitiligo patients [20, 23]. Also, increased expression of hydrogen peroxide and elevated oxidative by-products within vitiligo patient skin has been reported [22, 24, 25]. In addition, melanocytes from vitiligo patients were more sensitive to in vitro oxidative therapies such as cumene hydroperoxide and UVB light [26, 27]. However, exogenous treatment of catalase (pseudocatalase), which was proposed to cure vitiligo by regulating ROS, was ineffective in treating vitiligo lesions [28]. Thus, dysregulated redox balance in vitiligo might be a consequence, but not a cause, of vitiligo. Melanocytes from vitiligo patients show morphological and physiological abnormalities. Those in peri-lesional borders are seen to be enlarged with longer dendritic ends than normal melanocytes [29]. However, rapid regimentation of the skin following engrafting of human vitiligo lesional skin on nude mouse was achieved, indicating that intrinsic melanocyte defect was not the only cause of melanocyte destruction in vitiligo [30]. Histochemical and immunohistochemical examination shows infiltration of a large number of T lymphocytes at the edge of vitiligo lesions with a complete microscopic loss of melanin in lesional skin [31]. Therefore, it is certain that vitiligo melanocytes are abnormal compared to healthy melanocytes, but this abnormality does not seem to be sufficient for the disorder.