Background
Melasma is an acquired hyperpigmentation of sun-exposed areas. Melasma presents as symmetrically distributed hyperpigmented macules, which can be confluent, reticulated or punctate. Areas that receive excessive sun exposure, including the cheeks, the upper lip, the chin, and the forehead, are the most common locations; however, melasma can occasionally occur in other sun-exposed locations.
Chloasma is a synonymous term sometimes used to describe the occurrence of melasma during pregnancy. Chloasma is derived from the Greek word chloazein, meaning "to be green." Melas, also Greek, means "black." Because the pigmentation is never green in appearance, melasma is the preferred term.
See Diagnosing Dermatoses in Pregnant Patients: 8 Cases to Test Your Skills, a Critical Images slideshow, for help identifying several types of cutaneous eruptions associated with pregnancy.
Pathophysiology
The pathophysiology of melasma is multifactorial and not entirely characterized. A direct relationship with female hormonal activity appears to be present, because melasma occurs more frequently in females than in males and commonly develops or worsens during pregnancy and with the use of oral contraceptive pills. Indeed, one half of melasma cases present initially during pregnancy. Additionally, the expression of estrogen receptors appears to be up-regulated in melasma lesions. [1] Whether hormone levels play a role in male melasma development is still a topic of debate. Other factors implicated in the pathogenesis of melasma are photosensitizing medications, mild ovarian dysfunction, and certain cosmetics. An exogenous form of melasma known as ochronosis is very frequently caused by specific implicated medications. There is clearly some role for genetic predisposition as well, as family history of melasma is known to be an important risk factor for its development. Somewhere in the range of 55-64% of patients with melasma have a family history of this condition. [2]
The most important factor in the development of melasma is exposure to sunlight. UV light induces production of reactive oxygen species in the skin, which subsequently promotes melanogenesis. [3] Ultraviolet (UV) radiation is also known to induce increased production of alpha-melanocyte–stimulating hormone and corticotropin, as well as interleukin 1 and endothelin 1, all of which contribute to increased melanin production by intraepidermal melanocytes. Fibroblasts located in the dermal layer of the skin may also contribute to the development of melasma; overexpression of the tyrosine kinase receptor c-kit and certain stem cell factors have been identified in melasma lesions, and these are believed to increase melanogenesis. [4] Without the strict avoidance of sunlight, potentially successful treatments for melasma are doomed to fail.
Etiology
A genetic predisposition is a major factor in the development of melasma. Melasma is much more common in women than in men. Persons with light-brown skin types from regions of the world with intense sun exposure are much more prone to the development of melasma. . In a global study of 324 women with melasma, 48% reported a positive family history of the condition. [5] Identical twins have been reported to develop melasma, [6] while other siblings under similar conditions did not.
Another major factor in melasma is exposure to sunlight. Ultraviolet radiation can cause peroxidation of lipids in cellular membranes, leading to generation of free radicals, which could stimulate melanocytes to produce excess melanin. Sunscreens that primarily block UV-B radiation (290-320 nm) are unsatisfactory because longer wavelengths (UV-A and visible radiation, 320-700 nm) also stimulate melanocytes to produce melanin. It has been demonstrated that light in the visible spectrum (415 nm) can cause increased pigmentation that is present in the skin for several months after development. [7]
Hormonal influences play a role in many individuals. The exact mechanism by which pregnancy affects melasma is unknown. Estrogen, progesterone, and melanocyte-stimulating hormone (MSH) levels are normally increased during the third trimester of pregnancy. Nulliparous patients with melasma have no increased levels of estrogen or MSH, but they may show elevated levels of estrogen receptors within lesions. In addition, the occurrence of melasma with estrogen- and progesterone-containing oral contraceptive pills and diethylstilbestrol treatment for prostate cancer has been reported. [8] The observation that postmenopausal woman who are given progesterone develop melasma, while those who are given only estrogen do not, implicates progesterone as playing a critical role in the development of melasma.
A case report of two women who developed melasma after sudden and profound emotional stress implicated the release of MSH by the hypothalamus as a cause. Additionally, one study demonstrated an association between the development of melasma and the presence of melanocytic nevi and lentiginous nevi; patients with melasma showed a significantly higher number of both types of nevi than a control population. This would indicate a relationship between the development of melasma and the overall presence of pigmentation. [9]
Exactly which hormones and what mechanisms are involved in the development of melasma are yet to be determined. Genetic and hormonal influences in combination with ultraviolet radiation are the two most important causes of melasma, yet phototoxic and photoallergic medications and certain cosmetics have been reported to cause melasma in rare instances.
Epidemiology
US frequency
Melasma is very common, affecting over 5 million people in the United States. [10] Prevalence rates range from 8.8% among females of Latino descent living in the southern United States, to 13.4-15.5% seen in a population of Arab-Americans living in the state of Michigan, to up to 40% in some females of southeast Asian populations. [11, 12, 13]
Race
Persons of any race can be affected by melasma. However, melasma is much more common in constitutionally darker skin types than in lighter skin types, and it may be more common in light brown skin types, especially Latinos and Asians, from areas of the world with intense sun exposure.
Sex
Melasma is much more common in women than in men. Although the generally accepted ratio is approximately 9:1 females to males, a 2014 multicenter study of 953 patients from Brazil found a female-to-male ratio closer to 39:1. [14] When men are affected, the clinical and histologic picture is identical.
Age
Melasma is rare before puberty and most commonly occurs in women during their reproductive years. Melasma is present in 15-50% of pregnant patients.
Prognosis
Melasma has no associated mortality or morbidity. There have been no reported cases of malignant transformation, and it has not been associated with an increased risk of melanoma or other malignancies. In fact, it is generally accepted that patients with melasma are considered to be at decreased risk for melanoma. This is likely secondary to lower rates of skin malignancies in patients with a dark complexion.
Dermal pigment may take longer to resolve than epidermal pigment because no effective therapy is capable of removing dermal pigment. However, treatment should not be withheld simply because of a preponderance of dermal pigment. The source of the dermal pigment is the epidermis, and, if epidermal melanogenesis can be inhibited for long periods, the dermal pigment will not replenish and will slowly resolve.
Resistant cases or recurrences of melasma occur often and are certain if strict avoidance of sunlight is not rigidly heeded.
Patient Education
Strict sun avoidance is essential for resolution and to prevent recurrence of melasma. Patients with melasma should apply bleaching creams to areas of darkening only. Resolution with strict sun avoidance and topical bleaching creams can take months; caution patients to expect slow but gradual lightening. Additionally, only bleaching creams that are medically approved should be used, as creams with high concentrations of bleaching agents can lead to paradoxical hyperpigmentation if overused or abused. Additionally, all bleaching agents should be used for no more than 3 months continuously and then discontinued for a window of time to avoid hyperpigmentation. An alternative program of every other day use is sometimes used and may be appropriate. In any case, patients should be cautioned to discontinue the agent and seek follow up if they note hyperpigmentation in the setting of strict sun avoidance.
-
Confluent hyperpigmented macules in a malar distribution.
-
Melasma in a man.
