LAUSR

I read with interest the excellent paper by Vashi et al. on special considerations and treatment of facial hyperpigmentation in patients with skin of color [1]. The authors concisely review several disorders that can cause hyperpigmentation of the face. In particular, they succinctly summarized the salient features regarding the pathogenesis and the treatment of melasma. The etiology of melasma is multifactorial [2]. In addition to genetic predisposition and ultraviolet light, female sex hormones, such as estrogen (following either systemic [3] or topical [4] exposure), and angiogenesis influence the development of melasma. Specifically, estrogens stimulate and estrogen antagonists inhibit melanogenesis of cultured human melanocytes [5]. In addition, melasma lesions show increased estrogen receptor expression [6]. Melasma lesions also have increased vascularity [7]. The expression of vascular endothelial growth factor is increased in melasma lesion keratinocytes as compared with those of nearby non-melasma skin [7]. Additionally, treatment of melasma with anti-fibrinolytic therapy results in decreased hyperpigmentation clinically with not only decreased melanin content, but also diminished vascularization, microscopically [8]. Management intervention for melasma focuses on one or more of the associated mechanisms of pathogenesis [9]. The currently available therapeutic alternatives for melasma include topical agents that are directed at inhibiting melanogenesis (such as hydroquinone, retinoids, and/or corticosteroids with or without sunscreen) and physical agents (such as chemical peels and laser treatments) used alone or in combination [10, 11]. New therapeutic alternatives, directed toward other etiologic factors, might aid in optimizing the treatment of melasma. I recently described a novel topical approach for treating melasma [12]. The therapy involves a topical agent containing not only an anti-estrogen such as a selective estrogen receptor modulator (tamoxifen or raloxifene) or an aromatase inhibitor (anastrozole or tetrozole or exemestane), but also a vascular endothelial growth factor inhibitor (bevacizumab). This treatment would inhibit both the estrogen-related and the angiogenesis-associated etiologic components of melasma. Investigation of this novel topical therapy, alone or in combination with other topical or physical modalities, for treating patients with skin of color with facial hyperpigmentation caused by melasma is warranted.