HIGHLIGHTING SKIN OF COLOR The Stepwise Approach to the Treatment of Melasma Maritza I. Perez, MD Melasma is a symmetric progressive hyperpig- of the pigment within the skin and the reflection of mentation of facial skin that occurs in all races light determine the perception of color. Epidermal but has a predilection for darker skin pheno- pigment is usually light to dark brown; dermal pig- types. Melasma has been associated with hor- ment is gray-blue. On Wood light examination, pig- monal imbalances, sun damage, and genetic ment that resides within the epidermis is predisposition. Clinically, melasma can be accentuated, while dermal pigment is not enhanced. divided into centrofacial, malar, and mandibular Fortunately, epidermal melasma is the most common according to the pigment distribution on the form and also the most treatable.1 Dermal melasma, skin. On Wood light examination, the pigment however, is very difficult to treat because the pig- can be found within the epidermis, where it will ment is entrapped in the dermis in the melanin enhance, or within the dermis, where it will not granules within the melanophages. To date, very few enhance. Melasma can be classified as mild, treatments are effective for dermal melasma. moderate, or severe for evaluation and treatment Clinically, facial melasma is described in accor- purposes. In this article, we will discuss the dance with the anatomic location of the discol- objective evaluation of the patient with melasma, oration.2 The centrofacial area is the most as well as the treatments based on disease commonly affected area, as seen in two thirds of severity. Further recommendations for mainte- patients with melasma; the malar area is the next nance in these patients also will be addressed. most frequently affected area, occurring in 20% of Cutis. 2005;75:217-222. patients; and the mandibular area is implicated in 16% of patients. Most patients with melasma are young and middle-aged women. All races are elasma is a symmetric hyperpigmentation affected. However, certain racial and ethnic that develops and progresses slowly. It is groups, such as Hispanics and Asians, are more sus- M often associated with hormonal changes, ceptible to this condition.2 though exposure to UV light and heat and genetic Higher levels of estrogen and progesterone are factors are its principal causes. Most of this abnormal among the hormonal changes implicated in the pigmentation occurs on facial skin; however, the development of melasma. For example, this pig- exterior surface of the arms also may be involved. mentary disorder can affect 50% to 70% of preg- Facial melasma is characterized by discoloration nant women and is frequently seen with the use of ranging from light brown to dark gray, depending on oral contraceptives.3 Perez et al4 reported that fer- where the pigment resides on the skin. The location tile women who developed melasma without ever having been pregnant or ever having taken oral contraceptives might show a mild ovarian dysfunc- Accepted for publication May 26, 2004. tion consistent with polycystic ovarian disease. From Columbia University, St. Luke’s-Roosevelt Hospital Center, They concluded that estrogen receptor sensitivity and Beth Israel Medical Center, New York, New York. at the melanocyte target site may play a role in the Dr. Perez has been a consultant for Galderma Laboratories, LP, 4 and Medicis. causation of melasma. Reprints: Maritza I. Perez, MD, 57 North St, Suite 421, Despite its association with hormonal changes Danbury, CT 06810 (e-mail: [email protected]). and genetic predisposition, sun exposure remains VOLUME 75, APRIL 2005 217 Highlighting Skin of Color the principal cause of melasma. Melanocyte activ- chronic and adjuvant treatment is necessary for ity is increased in melasma. The melanocytes of successful results. skin affected with melasma have been shown to be Step 1—In any regimen prescribed for the treat- highly dendritic on electron microscopic evalua- ment of melasma, broad-spectrum sun protection tion, exhibit rapid increase of DNA synthesis with against both UVA and UVB light is vital for suc- sun exposure, and multiply rapidly.1 Indeed, cess. If no recurrence of melasma is the goal, the patients with melasma often attest to how rapidly use of sun protection in the patient with melasma the condition recurs after even minimal sun expo- is a lifetime commitment. Because the action spec- sure. It is known that chronic exposure to UVA trum of melanogenesis is considered to be within radiation increases melanin production, resulting the longer wavelength UVA range, UVA protec- in epidermal and dermal cellular damage mani- tion is indispensable. fested as pigment disorders, such as lentigines, Step 2—After the patient accepts the commit- poikiloderma, mottled hyperpigmentation with ment, the next step is to inhibit melanin synthesis hypopigmentation and telangiectasia, and and transportation of melanosomes to keratino- melasma.5 Hence, the multifactorial etiology of cytes. This is accomplished by the use of skin- melasma makes it a difficult dyschromia to treat. lightening agents such as hydroquinone (HQ). HQ Specifics of melasma treatment depend on the is a phenol compound that lightens skin color by severity of the condition. The major factors that decreasing the production of melanocyte pigment determine the severity of the condition as mild, through degradation by auto-oxidation, tyrosinase, moderate, or severe include the extent of surface and phenol oxidases into highly reactive oxygen area affected, intensity of pigmentation, and homo- radicals, semiquinones, and quinones.6 These reac- geneity of the affected area. tive substances prevent melanin production within Surface Area—The greater the percentage of sur- melanosomes and increase degradation of melano- face area affected, the more extensive the condition. some packages after transfer to adjacent kerati- On a scale of 1 to 4, with 4 being maximum involve- nocytes. HQs, therefore, disrupt the function and ment (both cheeksϭ2, chinϭ1, foreheadϭ1), full- proliferation of melanocytes. In this way, topical face melasma is considered severe; a patient with application of HQ produces a gradual reduction of melasma affecting both cheeks and the chin or fore- dyschromia by total melanocyte down-regulation— head will be a 3 (moderate); and a patient with from prevention of production of melanosomes to melasma only on the maxillary area (both cheeks) or their transfer to keratinocytes. only on the chin and forehead will be a 2 (mild). HQ 4% is the standard therapy for melasma and Intensity of Pigmentation Relative to Surrounding has been used for more than 5 decades. Lower con- Skin—On a scale of 1 to 3, with increasing number centrations are generally clinically effective for a illustrating increase in severity, 1 shade difference is milder form of the condition.7 Higher concentra- considered mild, 2 shades’ difference is considered tions of HQ (up to 10%) have been used effectively moderate, and 3 or more shades’ difference is con- in the treatment of severe melasma. However, sidered severe. chronic use of topical HQs, even at lower concen- Homogeneity of Lesions—More homogeneous trations (eg, 2%), can be associated with an lesions are considered more severe than heteroge- increased risk for exogenous ochronosis,8 especially neous ones on a scale of 1 to 3. when used by dark-skinned blacks. Higher concen- Based on these parameters, a score of 3 to 5 out trations of HQs also are likely to induce both more of a possible 10 is classified as mild melasma, 6 to irritation and induction of exogenous ochronosis. 8 is moderate melasma, and 9 to 10 is severe melasma. The effectiveness of HQ 4% is seen after approx- These parameters provide an objective method for imately 20 weeks of use, and efficacy seems to clinical evaluation in patients with melasma. plateau after 6 months’ use as monotherapy. Topical HQ is more effective when applied twice a day to Principles of Stepwise Treatment affected areas. Because excessive lightening of Because melasma is a chronic, recurrent, photo- non–melasma-affected skin has not been docu- induced dyschromia of the skin seen in geneti- mented in patients treated with HQ, application to cally predisposed individuals, the treatment the entire facial area is recommended instead of spot requires consideration of the following 3 princi- treatment.9 More localized applications can lead to a ples: protection from sun exposure is indispens- “bull’s-eye” area of discoloration. Although able and mandatory for success, inhibition of reversible, the effect is disconcerting. melanocyte activity is necessary for successful Exfoliating and moisturizing agents, such as treatment even after removal of the melanin, and ␣-hydroxy acids (eg, glycolic acid),10 have increased 218 CUTIS® Highlighting Skin of Color the penetration and effectiveness of HQ as a skin- of color, sun protection and pretreatment with lightening agent. Moreover, the combination of skin-lightening agents are mandatory before the HQ 4% with tretinoin11 or retinol,12 which in the procedure is performed, and should be resumed skin is transformed to tretinoin,13 has been shown shortly after re-epithelialization of the ablated skin to be effective for chronic photodamage of facial for prevention and treatment of expected postin- skin and the skin of the neck and chest.14 Because flammatory pigmentation.22 tretinoin and retinol have been shown to be effective in prevention and reversal of photodam- An Individualized Approach age at the molecular level, combination products My approach to the treatment of melasma is listed can treat melasma via 2 mechanisms: correcting in the Table. Most importantly, all patients with both the pigmentary abnormality and the photo- melasma should use a sunblock on a daily basis with damage component. a sun protection factor of 30 and with physical and In fact, combination therapy with HQ and hypoallergenic chemical ingredients effective tretinoin is an effective form of treatment for facial against UVA and UVB light.