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

Abstract

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.

The role of serum vitamin D levels in vitiligo

“…In vitro studies have shown that vitamin D 3 is associated with an increase in tyrosinase activity and melanogenesis [7], which may contribute to repigmentation in vitiligo macules. Vitamin D analogues, including calcipotriol and tacalcitol, are known to enhance repigmentation in vitiligo patients [15–17]. Another study reported that vitamin D exerts immunomodulatory effects by inhibiting the expression of interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, and TNF-γ [18].…”

Therapeutic Comparison between Sun Irradiation vs. Narrowband UVB Phototherapy along with Concomitant Topical Tacalcitol for Vitiligo Vulgaris

“…The results showed sunbathing to be as effective as narrowband UVB regarding the repigmentation rate, and it required to no need to visit the clinic. Vitamin D3 alone is not clinically efficient for vitiligo irrespective of its ability to upregulate stem cell factor and endothelin-1 in vitro [2]. The combination of vitamin D3 with phototherapy yield improved results [3,4], thus the current study compared natural UV irradiation with narrowband UVB.…”

“…Activated vitamin D, 1α24(OH) 2 D 3 , is an alternative treatment for vitiligo that accelerates repigmentation through biological interaction between keratinocytes and/or fibroblast to melanocytes [2]. Narrowband UVB is commonly accepted because it provides more effective repigmentation and is less carcinogenic than broadband UVB and calcipotriol along with phototherapy is also very promising [3,4].…”

Vitiligo, reactive oxygen species and T-cells

“…In particular, UVB induces generation of free radicals, which damage DNA. This can be ameliorated by vitamin D, which up-regulates expression of metallothionein, a free radical scavenger protein with photoprotective properties [120].…”