Melasma is an acquired disorder of melanogenesis leading to hyperpigmentation and manifested by almost always symmetrical brown to gray-black macules and patches with serrated irregular edges. It occurs especially in sun-exposed areas and typically affects young to middle-aged women [1]. It is most commonly seen on the face and, less commonly, on extrafacial locations such as the neck, arms, and chest [2]. In spite of being asymptomatic, melasma lesions cause aesthetic impairment and significantly affect the quality of life.

The word melasma comes from the Greek “melas” which means black and refers to its brownish clinical presentation [3]. Disease descriptions are recognized since the reports of Hippocrates (470–360 BC), when its worsening was referred to occur after sun exposure, fire heat, cold, and skin inflammations [3].

Three clinical patterns are usually described: centrofacial, with patches on the frontal region, nasal dorsum, cheekbones, and chin areas (65 % of the cases); malar, which occurs in 20 % of the cases; and mandibular, seen in about 15 % of the patients [4, 5].

Pigmentation disorders, including melasma, are the third most frequent complaint in dermatological appointments and predominate in the age between 30 and 40 years [5].

Although occurring in all ethnic groups, the incidence of melasma varies according to the studied population. It is known that there is a predominance among Asian, Hispanic, and African descendants [2, 6], as well as among those who live in intertropical areas where the exposure to ultraviolet radiation (UVR) is inevitable [2, 7]. Its prevalence is also higher in intermediate phototypes (III, IV, V) [3, 6]. In lighter skin phototypes (Fitzpatrick skin type II and III), it is usually influenced by the presence of family history, in contrast to a negative family history in Fitzpatrick’s phototypes IV and V [8, 9].

In India, the demographic and clinical findings show regional variability, ranging from 4 to 10 % in urban areas and up to 41 % in rural settings. Taking into consideration the different regions and their ethnic compositions, the incidence of melasma is estimated to occur in 15–35 % of adult Brazilian women [10]. In Iran, melasma was identified in 39.5 % of women, 9.5 % of which were pregnant women [3]. In the United States, melasma affects five to six million people [6, 11].

Melasma is more prevalent in women, in an estimated 9:1 ratio compared to men [3, 7], although this ratio can vary depending on the populations. In Southeast Asia, for example, the prevalence reaches 40 % in adult women and 20 % in adult men [12]. In Puerto Rico, on the other hand, men formed only 10 % of the total melasma patients [13]. In India, 20–25 % of patients with melasma are men. This difference is probably related to the country’s climate, a large number of outdoor workers, and a greater cosmetic awareness among male patients [14].

Most cases develop between 20 and 40 years of age [3], with a decreasing prevalence after menopause [8] suggesting a hormonal relationship in its pathogenesis. The extrafacial forms of melasma, on the other hand, are most common in postmenopausal women.

Although the exact cause of melasma is unknown, several factors are associated with its development and worsening. The most commonly reported precipitating factors are pregnancy, oral contraceptives, and sun exposure [7].

The family history of melasma occurs in about 50 % of patients, particularly in those with darker skin types [15]. These rates suggest a hereditary etiological component which is being considered the most important risk factor for melasma development [4]. With a family history of melasma, patients tend to have the disorder earlier [16] and to present longer duration of symptoms [8]. A recent discovery found the role of the H19 gene in melasma. This gene transcribes a noncoding ribonucleic acid and is downregulated in melasma lesions, inducing melanogenesis and the transference of melanin from melanocytes to keratinocytes [1, 17]. In addition, several other genes associated with melanogenesis were analyzed, and studies showed that they are upregulated in melasma skin, when compared to unaffected areas [18].

The association between ultraviolet radiation (UVR) and melasma is well established, and it is seen as the main triggering factor for the disorder [3, 7, 19]. The UVR increases melanogenic activity, causing darker epidermal pigmentation in regions with melasma than in the adjacent skin [3]. Intense and long-term exposure to UVR activates an inflammatory cascade mainly through oxidative stress and the formation of reactive oxygen species. Inflammatory signals stimulated by UVR, which include cytokines and alpha-melanocyte-stimulating hormone, can also cause melanogenesis [16]. In most patients melasma onset happens predominantly in the summer [4], and reports of worsening and higher recurrence rates with sun exposure are common. There is also a high prevalence of the disease in places of greater solar irradiation. Moreover, centrofacial melasma is more prevalent in the regions corresponding to the areas where the UVR focuses more directly. Other radiation wavelengths such as visible light and infrared also have a melanogenic potential, although to a lesser degree [3].

Melasma is also sensitive to hormonal influence. The use of oral contraceptives (OCP), hormone replacement therapy (HRT), ovarian tumors, and endocrine disorders have been linked to the pigmentation onset or worsening [19, 20]. The relationship with hormonal activity is supported by the fact that women are more frequently affected, and the beginning of melasma usually occurs after adolescence, during pregnancy, or while using OCP. Moreover, its prevalence decreases after menopause and rarely manifests before puberty [20]. Estrogen and progesterone increase the activity of tyrosinase. It has been demonstrated by immunohistochemical analysis that the skin affected by melasma has increased expression of estrogen receptor beta as well as progesterone receptors around small vessels when compared to the adjacent normal skin [16, 21]. Thus, it is believed that the pigmentation is related to the effects of estrogen and progesterone in melanocytes.

In male patients, luteinizing hormone (LH) circulating levels are higher, while testosterone concentration is lower in melasmic men when compared to controls, suggesting a role of subtle testicular resistance in the pathogenesis of melasma [1, 14, 22].

The association of melasma occurrence and the use of OCP are well known and reported by around 25 % of patients [15]. This is seen especially in cases with a positive family history for the disorder. Its discontinuation or change for a lower estrogenic dose, however, did not seem to improve the pigmentation [7]. Thus, a systematic change in hormonal contraception in melasma patients seems unwarranted. Melasma occurs in up to 75 % of pregnancies [23], and 26–29 % of women have reported to have their onset during pregnancy [8, 15]. The stimulus for melanogenesis occurs especially in the third trimester and can be explained by the increase of placental, ovarian, and pituitary hormones [3].

There are some studies correlating the appearance of melasma to endocrine diseases, especially thyroid abnormalities. In a recent study, the frequency of thyroid disorders in patients with melasma was around 20 %, almost five times greater than in control subjects [24]. It was also observed that the association between thyroid autoimmunity and melasma was mainly seen in women whose melasma developed during pregnancy or after the ingestion of OCP [25].

The use of light and laser technologies may trigger or exacerbate preexisting clinical or subclinical melasma. In addition, they may predispose to a rebound effect after using intense pulsed light by the association to post-inflammatory hyperpigmentation [26]. Other cosmetic procedures, such as chemical peelings, which may cause skin inflammation, can also lead to exacerbation of melasma. These changes are seen most frequently in people of higher phototypes [27].

In addition to OCPs, other drugs also can cause melasma. Photosensitizing drugs may activate melasma or dark preexisting lesions, and the mechanism is probably similar to that of exacerbation after cosmetic procedures. Pigmentation resembling melasma develops in 10 % of patients receiving phenytoin. The drug exerts direct action on melanocytes causing dispersion of melanin granules and also induces increased pigmentation in the basal epidermis [1]. Finasteride’s inhibition of 5α-reductase may lead to increased levels of progesterone in the skin, inducing hyperpigmentation, relating to the appearance of melasma [28]. Diethylstilbestrol for treatment of prostate cancer was also related to melasma onset [1].