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Melasma
Evidence Levels: A Double-blind study B Clinical trial ≥ 20 subjects C Clinical trial < 20 subjects D Series ≥ 5 subjects E Anecdotal case reports
Melasma is an acquired hypermelanosis that most commonly affects females of childbearing age, although males may also be affected. The condition can be classified according to the pattern of facial involvement, which includes centrofacial (forehead, cheeks, chin, and upper lip), malar, and mandibular. Less frequently the neck, arms, and chest may be affected. Melasma is more prevalent in individuals with Fitzpatrick skin types III and above and can have a significant psychosocial impact.
Three histologic subtypes of melasma exist – epidermal, dermal, and mixed – which may be differentiated by the use of a Wood lamp, where epidermal melasma shows enhanced contrast and dermal melasma less contrast. More recently, in vivo reflectance confocal microscopy has been studied as a non-invasive method of evaluating melasma. Histologic features of melasma include increased epidermal and dermal melanin, solar elastosis, damage to the basement membrane, increased vascularity, and increased numbers of dermal mast cells and CD4+ T cells. Epidermal melasma is the most responsive to treatment.
The pathogenesis of melasma is not fully understood; however, a genetic predisposition, hormonal factors, pregnancy, and the use of oral contraceptives are the most common precipitants. Exposure to ultraviolet (UV) radiation both precipitates and exacerbates. Other etiologic factors include phototoxic medications, genetic predisposition, and thyroid disease. Patients should be queried regarding symptoms suggestive of thyroid abnormalities.
Management Strategy
Melasma is often difficult to treat due to the recalcitrant and recurrent nature of the condition and the risk of postinflammatory hyperpigmentation associated with some treatments, particularly in individuals with darker skin. Pregnancy-induced melasma may sometimes resolve spontaneously postpartum, and females taking the oral contraceptive pill may be advised to change to an alternative form of contraception .
Sun exposure increases melanin production and may exacerbate melasma; therefore, all patients should receive sun protection advice and use a high-factor broad-spectrum sunscreen with good protection against ultraviolet A (UVA) . Recent evidence suggests that sunscreens with protection against visible light may provide additional benefit. Patients may also wish to use camouflage makeup, which may also provide significant visible light protection.
Current treatment options include topical lightening agents, chemical peels, laser therapies, tranexamic acid, and oral antioxidants . The response to monotherapy is often limited, and therefore a combination of treatments may optimize outcome. Commonly used treatments include 2%–5% hydroquinone, tretinoin, triple combination creams (containing hydroquinone, tretinoin, and fluocinolone), kojic acid, niacinamide, and azelaic acid. Glycolic acid is the most commonly reported peeling agent and may be used as an adjunct to topical depigmenting agents. Other commonly used peeling agents include salicylic acid, Jessner peel, trichoroacetic acid, and tretinoin. The results of laser therapies are mixed, and treatment carries a significant risk of relapse and postinflammatory hyperpigmentation depending on the type of laser used and skin type of the patient.
Systematic review of randomized controlled trials on interventions for melasma: an abridged Cochrane Review
Jutley GS, Rajaratnam R, Halpern J, et al. J Am Acad Dermatol 2014; 70: 369–73.
This review included 20 studies and concluded that triple combination cream was more effective than hydroquinone or any agent in dual combination. Azelaic acid (20%) was superior to 2% hydroquinone in lightening melasma, and tretinoin led to greater objective improvement in melasma than placebo.
Melasma treatment: an evidence based review
McKesey J, Tovar-Garza A, Pandya AG. Am J Clin Dermatol 2020; 21(2): 173–225.
This review included randomized, controlled trials or controlled clinical trials of melasma. Triple combination cream was the most effective treatment for melasma, as well as hydroquinone alone. Chemical peels and laser light–based therapies had mixed results and a higher rate of complications.
Efficacy and safety of a new triple-combination agent for the treatment of facial melasma
Taylor SC, Torok H, Jones T. Cutis 2003; 72: 67–72.
Two multicenter, randomized studies compared a formulation containing tretinoin 0.05%, hydroquinone 4%, and fluocinolone acetonide 0.01% with the three possible dual combinations of the three agents in 641 patients with melasma (Fitzpatrick skin types I–IV). At week 8, the triple combination formulation was significantly more effective than any of the dual combinations.
Commonly reported adverse effects with triple combination cream include mild erythema, burning, and peeling.
A histologic examination for skin atrophy after 6 months of treatment with fluocinolone acetonide 0.01%, hydroquinone 4%, and tretinoin 0.05% cream
Bhawan J, Grimes P, Pandya AG, et al. Am J Dermatopathol 2009; 31: 794–8.
This study found no evidence of clinical or histologic atrophy in 30 melasma patients after daily use of triple combination cream for 24 weeks.
Topical tretinoin (retinoic acid) improves melasma. A vehicle-controlled, clinical trial
Griffiths CEM, Finkel LJ, Ditre CM, et al. Br J Dermatol 1993; 129: 415–21.
A study of 0.1% tretinoin once daily in 38 Caucasian women for 40 weeks found that 68% of tretinoin-treated patients were improved or much improved, compared with only 5% in the vehicle-treated group. Erythema and desquamation were more common in the tretinoin group.
The efficacy of a broad spectrum sunscreen in the treatment of melasma
Vasquez M, Sanchez JL. Cutis 1983; 92: 95–6.
Broad-spectrum sunscreen compared with vehicle used alongside hydroquinone led to improvement in 96% of subjects compared with 81% of those using vehicle.
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