Utilizing combination therapy to optimize melasma outcomes

Journal of Drugs in Dermatology, Sept-Oct, 2004 by Marta I. Rendon

Abstract

Melasma is a chronic and recurrent disorder. It has been underdiagnosed and undertreated due to lack of effective therapies and the perception that it is merely a cosmetic nuisance. Hydroquinone, corticosteroids, licorice extracts and kojic acid have been used as monotherapy to treat melasma. However, the present standard of care in melasma therapy is combination therapy. To date, the most effective treatment is a triple-combination agent that contains hydroquinone 4%, tretinoin 0.05% and fluocinolone acetonide 0.01%. In clinical trials, its use led to complete or near-complete clearing of melasma in 8 weeks. A long-term study demonstrated its continuing efficacy and safety for as long as 360 days. In an examination of quality of life parameters, patients using the triple-combination cream showed significant improvements in self-perception by all 1290 patients. Various combinations of melasma therapy, such as chemical peels, particularly as adjuvants to the triple-combination cream, are discussed.

**********

Introduction

Melasma is a common acquired hypermelanosis predominantly of the face and neck and, occasionally, the forearms, According to the American Academy of Dermatology, 5-6 million American women have melasma. Melasma is primarily a disease of women of child-bearing age although 10% of cases occur in men (1). It occurs in all skin types but is most common in Fitzpatrick skin types IV-VI, with dark-haired women more susceptible. Its racial distribution is centered among Hispanic, Asian, Indian, African and African-American peoples (2).

[ILLUSTRATION OMITTED]

Melasma has largely been underdiagnosed and therefore undertreated in the United States. This is partly attributable to the fact that many physicians consider melasma a "nuisance" rather than a medical problem or one with significant psychosocial impacts. While dermatologists are the specialists most likely to treat melasma, obstetricians and gynecologists (OB/GYNs), family practitioners or internal medicine doctors also see patients with melasma (3). As it frequently develops during pregnancy, many women first present with melasma during visits for prenatal care. Many physicians outside the dermatologic community have not been aware of available treatments and therefore, have typically not addressed the problem unless asked, or have reassured their patients that the hyperpigmentation would fade after delivery. Likewise, many women with melasma do not ask their physicians about their symptoms and do not visit a dermatologist specifically to address the problem. Due to cultural and ethnic misperceptions about skin diseases in general, particularly disorders of pigmentation, affected individuals may not ever seek help for what is a treatable, though chronic, condition.

Melasma has a significant cosmetic impact for many women. However, it also carries a psychosocial burden. It is particularly distressing to women from cultures which favor flawless, evenly pigmented skin. In some Asian cultures, facial pigmentary abnormalities are associated with bad luck. Melasma and other dyspigmentation is also extremely distressing to women in Latin cultures where such stigmata are frequently associated with ill health or poor nutrition. Pigmentary abnormalities are considered disfiguring in Latin cultures where women tend to be especially beauty-conscious. Latina women have the highest prevalence of melasma (2,3).

Melasma Etiology

While the precise etiology of melasma is unknown, multiple factors have been implicated. They include genetic influences, exposure to ultraviolet (UV) and visible light radiation, female hormones in the settings of pregnancy, oral contraception (OC) and post-menopausal hormone replacement therapy (HRT), thyroid autoimmunity, cosmetic ingredients and phototoxic drugs (3). UV radiation and genetic influences have been suggested to be the most important pathogenic factors (4). UV radiation increases melanocyte size, tyrosinase activity and the transfer of melanosomes to keratinocytes. These changes may occur as a consequence of DNA repair.

Melasma is estimated to occur in 50%-70% of pregnancies among US women, usually during the 2nd or 3rd trimester (5). No specific genetic studies have been conducted, but there is a higher incidence in patients with a significant family history (mothers and daughters) as well as in women with skin of color and pigmented races living in areas of high insolation (6).

Among Mexican women, the incidence is estimated to be about 80%, with more than one-third of these patients having the disease for life (7). However, melasma subsequent to OC use typically does not clear and may last up to 5 years following termination of therapy (6). Other evidence regarding hormonal influences includes the finding of significantly increased levels of luteinizing hormone and reduced serum estradiol suggestive of mild ovarian dysfunction (8). Lufti et al found an incidence of thyroid disorders 4 times higher in patients with melasma than in controls. Moreover, there was also a significant association between the development of melasma during pregnancy or subsequent to OC use and thyroid autoimmunity (9).