TOPICAL TREATMENT OF MELASMA

Abstract

Melasma is a common hypermelanotic disorder affecting the face that is associated with considerable psychological impacts. The management of melasma is challenging and requires a long-term treatment plan. In addition to avoidance of aggravating factors like oral pills and ultraviolet exposure, topical therapy has remained the mainstay of treatment. Multiple options for topical treatment are available, of which hydroquinone (HQ) is the most commonly prescribed agent. Besides HQ, other topical agents for which varying degrees of evidence for clinical efficacy exist include azelaic acid, kojic acid, retinoids, topical steroids, glycolic acid, mequinol, and arbutin. 

Topical medications modify various stages of melanogenesis, the most common mode of action being inhibition of the enzyme, tyrosinase. Combination therapy is the preferred mode of treatment for the synergism and reduction of untoward effects. The most popular combination consists of HQ, a topical steroid, and retinoic acid. Prolonged HQ usage may lead to untoward effects like depigmentation and exogenous ochronosis. The search for safer alternatives has given rise to the development of many newer agents, several of them from natural sources. Well-designed controlled clinical trials are needed to clarify their role in the routine management of melasma.

Introduction

Melasma (from the Greek word, ‘melas’ meaning black) is a common, acquired, circumscribed hypermelanosis of sun-exposed skin. It presents as symmetric, hyperpigmented macules having irregular, serrated, and geographic borders. The most common locations are the cheeks, upper lips, the chin, and the forehead, but other sun-exposed areas may also occasionally be involved. The term, “chloasma” (from the Greek word, ‘chloazein’ meaning ‘to be green’) is often used to describe melasma developing during pregnancy; however, as the pigmentation never appears to be green, the term, “melasma” should be preferred.

Although melasma may affect any race, it is much more common in constitutionally darker skin types (skin types IV to VI) than in lighter skin types, and it may be more common in light brown skins, especially in people of East Asian, Southeast Asian, and Hispanic origin who live in areas of the world with intense solar ultraviolet exposure. Melasma is the most common pigmentary disorder among Indians.[1]. It is much more common in women during their reproductive years but about 10% of the cases do occur in men. The clinical and histological features of melasma in men are the same as those of melasma in women.[2]

Pathophysiology of Melasma

The pathophysiology of melasma remains elusive, but multiple factors have been implicated. The role of female hormonal activity has been suggested by the increased frequency of occurrence of melasma in pregnancy and in those on oral contraceptive pills, estrogen replacement therapy, and estrogen treatment for prostatic cancer. The mechanism of induction of melasma by estrogen may be related to the presence of estrogen receptors on the melanocytes that stimulate the cells to produce more melanin. Genetic factors are indicated by familial occurrence of melasma and its increased incidence in people of Asian and Hispanic origins. Other factors implicated in the etiopathogenesis of melasma are photosensitizing and anticonvulsant medications, mild ovarian or thyroid dysfunction, and certain cosmetics. One of the most important factors in the development of melasma is ultraviolet exposure from sunlight or other sources. Exacerbation of melasma is universally seen after prolonged sunexposure but the pigmentation fades after periods of avoidance of sunexposure. Whatever the mechanisms, melasma results in an increased deposition of melanin in the epidermis, in the dermis within melanophages, or both. The number of melanocytes in the lesions has been variably reported to be normal[3] or increased.[4] The melanosomes within the melanocytes and keratinocytes have been reported to be increased in size.[3,4]

Types of Melasma

The lesions range in color from light brown to dark brownish-black and affect the regions of the face in different patterns. Three clinical patterns of distribution of the pigmentation may be recognized: Centrofacial, malar, and mandibular.[5]

The centrofacial pattern is the most common and involves the cheeks, nose, forehead, upper lip, and chin. The malar pattern involves the cheeks and nose. The ramus of the mandible is involved in the mandibular pattern. Melasma does not involve the mucous membrane.

With the help of Wood's lamp examination, melasma may be classified into four histological types according to the depth of pigment deposition[6]. The epidermal type is the most common in which the pigmentation appears more intense under Wood's lamp examination. Melanin is distributed throughout the epidermis; topical treatment may work best in this type of melasma. In the dermal type, the pigmentation is not intensified with Wood's light. The pigmentation is due to plenty of melanophages in the dermis. In the mixed type, Wood's light intensifies pigmentation in some areas while other areas remain unchanged. The pigmentation is due to increased epidermal melanin as well as dermal melanophages. Wood's lamp examination is of no benefit in very dark individuals, and this type is classified as indeterminate. This classification may partly work in lighter skin types but not in brown or black skin types.[7] Moreover, there may not be good correlation between the findings of Wood's lamp examination and histological depth of pigmentation.[7]

Depending on the natural history of the lesions, melasma may also be classified into transient and persistent types.[7] The transient type disappears within one year of cessation of hormonal stimuli like pregnancy or oral contraceptive pills. The persistent type continues to be present more than one year after the hormonal stimulus is removed and is caused by the action of UV rays and other factors, highlighting the role of sun-avoidance in the management of melasma.

Topical Treatment

By causing cosmetic disfigurement of the face, melasma is frequently associated with a significant emotional effect. There is no universally effective specific therapy for the disease—existing agents have varying degrees of effectiveness, and the condition, more often than not, relapses.[8] Most cases are treated with topical agents, used alone, or in combinations. Other modalities of treatment utilized in the management of this hypermelanotic disorder are chemical peels and physical therapies in the form of various lasers or intense pulse light sources. All patients with melasma should be counseled about the natural course of the disease and the necessity for adherence to a long-term treatment plan. Careful history about the possible precipitating or aggravating factors must be taken with special attention to the intake of oral contraceptives or other hormonal preparations, phototoxic and anti-seizure medications, and the usage of cosmetics. 

Discontinuation of oral pills and avoidance of scented cosmetics is advised. Recurrence of melasma occurs on exposure to sunlight and other sources of ultraviolet rays. Photoprotective measures like the avoidance of direct sun-exposure and the regular use of a broad-spectrum sunscreen are always advised, although clinical studies on their role are lacking. Treatment with demelanizing agents must be continued for several months before significant clinical benefits become noticeable. Topical agents are much more effective in the epidermal type of melasma.