Pathogenesis of melasma

Abstract

To adequately guide future therapies, it is important to elucidate the pathogenesis of melasma. Chronic ultraviolet (UV) radiation exposure, hormonal stimulation, and genetic predisposition play a role in melasma. A widely accepted theory for the pathogenesis of melasma is the increase of melanin through UV, which leads to the upregulation of melanin stimulating receptors (MSR) such as melanocortin-1 receptors (MC1R), resulting in increased hormone binding and melanin production. Furthermore, there are similarities between the histopathologic presentation of melasma and solar elastosis, a hallmark of photo-aged skin. These overlaps include altered basement membrane, increased vascularization, and increased mast cell count. There is significant data showing greater degree of solar elastosis in the melasma skin compared to the perilesional skin. Additionally, an etiologic factor in the pathogenesis of melasma is hormonal exposure to estrogen. Melasma has increased prevalence among menstruating women, women on oral contraceptives, and pregnant women. In melasma lesions, studies have shown an increased number of estrogen receptors and progesterone receptors in the dermis and epidermis, respectively. Previously, increased melanogenesis was thought to be the sole contributing factor to the pathogenesis of melasma but more recently, aberrant vasodilation and angiogenesis have been found to play a role. Nitric oxide, a potent vasodilator, was found to be overexpressed at the dermal-epidermal junction and was hypothesized to contribute to melasma through stimulation of tyrosinase and increasing vascularity. In conclusion, the various mechanisms implicated in melasma include melanocyte dysfunction, solar elastosis, mast cell dysfunction, hormonal influence, vascular transformation, and basement membrane damage.