New insights on therapy with vitamin D analogs targeting the intracellular pathways that control repigmentation in human vitiligo.

Vitiligo is a progressive depigmenting disorder affecting 0.5-2% of the population worldwide in which destruction of functional melanocytes from epidermis is a composite of multiple processes influencing melanocyte function and survival. A number of studies have recently reported that the treatment with vitamin D compounds or their combination with ultraviolet light or corticosteroids enhances repigmentation in vitiligo; however, the causal relationship at the cellular and molecular levels has not so far been investigated. This review details the main intracellular pathways through which vitamin D ligands alone or in different combinations may contribute to pigment restoration in vitiligo, outlines the most recent achievements in vitiligo treatment using vitamin D analogs, and compares their efficacy with other treatment regimens in vitiligo. Based on the reviewed literature and data, we foresee the need for designing new vitamin D compounds to achieve maximal therapeutic efficacy. Such compounds should have high selectivity for melanocytes, stimulatory effects on melanogenesis, and minimal suppressive effects on melanocyte growth. An approach combining clinical investigations and focused research on the cellular and molecular mechanisms of vitiligo repigmentation will lead to finding better treatments for this disease.