Melasma is a common, acquired, symmetrical hypermelanosis. It negatively impacts the patient's quality of life and responds poorly to treatment. Although earlier classified as epidermal and dermal, melasma is now thought to be a complex interaction between epidermal melanocytes, keratinocytes, dermal fibroblasts, mast cells, and vascular endothelial cells. Factors influencing melasma may include inflammation, reactive oxygen species, ultraviolet radiation, genetic factors, and hormones. With a better understanding of the pathogenesis of melasma and the realization that targeting melanin synthesis alone is not very effective, treatments focussing on newly implicated factors have been developed. These include agents targeting hyperactive melanocytes, melanosomal transfer to keratinocytes, defective skin barrier, the mast cells, vasculature, and estrogen receptors as well as drugs with anti-inflammatory and antioxidant activity. Many of these newer agents are botanicals with multimodal mechanisms of action that offer a better safety profile when compared with the conventional drugs. There has also been a focus on oral agents such as tranexamic acid, flutamide, and ascorbic acid. It has been suggested that the "triple therapy of the future" may be a combination of hydroquinone, an antiestrogen and a vascular endothelial growth factor inhibitor, as the "ideal" skin-lightening agent.
