Endothelial Cells Promote Pigmentation through Endothelin Receptor B Activation.

Findings of increased vascularization in melasma lesions and hyperpigmentation in acquired bilateral telangiectatic macules suggested a link between pigmentation and vascularization. Using high-magnification digital epiluminescence dermatoscopy, laser confocal microscopy, and histological examination, we showed that benign vascular lesions of the skin have restricted but significant hyperpigmentation compared with the surrounding skin. We then studied the role of microvascular endothelial cells in regulating skin pigmentation using an in vitro co-culture model using endothelial cells and melanocytes. These experiments showed that endothelin 1 released by microvascular endothelial cells induces increased melanogenesis signaling, characterized by microphthalmia-associated transcription factor phosphorylation, and increased tyrosinase and dopachrome tautomerase levels. Immunostaining for endothelin 1 in vascular lesions confirmed the increased expression on the basal layer of the epidermis above small vessels compared with perilesional skin. Endothelin acts through the activation of endothelin receptor B and the mitogen-activated protein kinase, extracellular signal-regulated kinase (ERK)1/2, and p38, to induce melanogenesis. Finally, culturing of reconstructed skin with microvascular endothelial cells led to increased skin pigmentation that could be prevented by inhibiting EDNRB. Taken together these results demonstrated the role of underlying microvascularization in skin pigmentation, a finding that could open new fields of research for regulating physiological pigmentation and for treating pigmentation disorders such as melasma.

A case of linear atrophoderma of Moulin successfully treated with methotrexate.

Linear atrophoderma of Moulin is an acquired rare and self-limited skin condition. It is characterized by atrophic bandlike skin lesions that often show hyperpigmentation and always follow the lines of Blaschko. Usually it begins in childhood or adolescence and there is no evidence of any long term progression. We describe a case of a 21-year-old woman with clinical and histological features of linear atrophoderma of Moulin. The patient was successfully treated with methotrexate 20 mg/week during 6 months with an improvement of skin pigmentation and atrophy. Approximately, 30 cases of linear atrophoderma of Moulin were described in the literature. There is not a proven effective treatment of this dermatosis. High dose penicillin, topical corticosteroids, heparin, and oral potassium aminobenzoate have been used but found to be uneffective. To our knowledge, this is the first case of extensive linear atrophoderma of Moulin treated with methotrexate.