Acral lesions of vitiligo: why are they resistant to photochemotherapy?

BACKGROUND: Acral lesions of vitiligo are usually resistant to conventional lines of treatment as well as surgical interventions. OBJECTIVE: To clarify causes underlying resistance of acral lesions to pigmentation in vitiligo by studying some of the factors associated with mechanisms of repigmentation following photochemotherapy. METHODS: The study included twenty patients with active vitiligo. Skin biopsies were taken from lesional and perilesional skin of areas expected to respond (trunk and proximal limb) and skin of acral areas, before and after PUVA therapy. Sections were stained with H and E, Melan-A, MHCII, CD1a, SCF and c-kit protein. RESULTS: Before treatment acral areas showed significantly lower hair follicle density, melanocyte density, Langerhans cell (LC) density, epidermal MHCII expression, lesional SCF expression and perilesional c-kit expression. Following treatment with PUVA in both non-responsive acral and repigmenting non-acral lesions identical immunohistochemical changes in the form of significant decrease in LC density, epidermal MHC-II and SCF expression were observed. CONCLUSION: The surprisingly similar histochemical changes in response to PUVA in acral and non-acral lesions did not manifest with clinical repigmentation except in non-acral ones. Factors such as inherent lower melanocyte density, lower melanocyte stem cell reservoirs and/or lower baseline epidermal stem cell factor may be considered as possible play makers in this respect.

Role of the free radical release process in the pathogenesis of morphea in contrast to systemic sclerosis.

Abstract The objective of this study was to assess the importance of the free radical release process in the pathogenesis of localized scleroderma and compare it with that in systemic sclerosis. The study was conducted on 20 randomly collected cases of morphea (4 single plaque, 7 linear, and 9 disseminated), 16 cases of systemic sclerosis, and 10 age- and sex-matched healthy volunteers. Blood samples and homogenized skin biopsies from lesional and nonlesional skin of patients and controls were examined for superoxide dismutase (SOD) activity using spectrophotometric assay, and for lipid peroxide level using the thiobarbituric acid assay. Morphea and systemic sclerosis cases showed significant elevation of blood, lesional, and nonlesional skin lipid peroxide levels and SOD activity compared with normal controls. When each of the subtypes of morphea were compared with the controls, a significant elevation of SOD was found in lesional skin in all groups, in plasma of linear and disseminated morphea, and in nonlesional skin of cases of disseminated morphea. A comparison of systemic sclerosis and morphea cases revealed no significant differences in blood or tissue SOD activity or lipid peroxide level. In both groups, the degree of skin induration could be correlated with changes in lesional SOD activity and lipid peroxide levels, respectively, but no correlation could be found between SOD or lipid peroxide and antinuclear antibody titer. The free radical release process is as important in the pathogenesis of morphea as it is in systemic sclerosis, where it appears to be involved in the development of skin induration.