Approach

The goal of treatment is to fade existing hyperpigmentation and prevent further hyperpigmentation. Initial advice includes using broad-spectrum ultraviolet (UV) protection and ceasing oral contraceptive pills and facial cosmetics that may contain photosensitising components.

Lightening agents, such as hydroquinone and tretinoin, are used as first-line therapy alone or as part of the Kligman formulation (which also contains a topical corticosteroid).[1][23][24] Combination therapy may be better than any of the individual components used alone.[25] For example, the combination of fluocinolone 0.01%, hydroquinone 4%, and tretinoin 0.05% (modified Kligman formula) has shown significantly greater efficacy compared with hydroquinone 4% alone.[1][26][27] Maintenance therapy with triple combination for 6 months after initial management has been suggested to prevent relapses.[28][29] However, hydroquinone, particularly long-term use of preparations containing concentrations >3% without sun protection by patients with Fitzpatrick skin type V or VI, can cause a condition called exogenous ochronosis (deposition of polymerised homogentisic acid in the skin, causing permanent hyperpigmentation). Azelaic acid is also used as a lightening agent in concentrations of 15% to 20%.[30][31][32]

Kojic acid, which is produced by Penicillium and Aspergillus species of moulds, chelates copper and causes inactivation of tyrosinase. It can be used alone or in combination with other compounds; when used in combination with hydroquinone 5%, there is a synergistic effect and subsequent improvement in the Melasma Area and Severity Index (MASI) score.[33] However, long-term studies show kojic acid has high irritant potential, and it is mutagenic in the Ames test.[34][35]Topical vitamin C (ascorbic acid) serums are often used in the treatment of melasma. Ascorbic acid decreases melanogenesis, prevents the production of free radicals, and offers some photoprotection. One trial showed 5% ascorbic acid to be equivalent to 4% hydroquinone in treating melasma; ascorbic acid was also associated with fewer adverse effects than hydroquinone.[36] When compared with glycolic acid 70% peel, nanosome vitamin C demonstrated improved efficacy with fewer side effects.[37] An alternative topical treatment is arbutin.[38]

Because most topical agents can cause some skin irritation, adherence can be an issue. Topical corticosteroids can be used as part of combination regimens, primarily to reduce this irritation, although they do cause some skin lightening as well. Long-term use of corticosteroids on the face (generally >12 weeks) can cause skin atrophy, telangiectasias, and/or an acneiform eruption.[39]

Pregnancy

For women who are pregnant, therapy may consist of topical azelaic acid together with use of broad-spectrum UV protection and cessation of facial cosmetics that may contain photosensitising components. Azelaic acid is considered safe during pregnancy.[40] However, it is usually recommended that treatment be deferred until the pregnancy is complete, because the hormonal influence will then be reduced.[41]

Chemical peels, laser and light therapies

Chemical peels may be used alone or in combination with topical therapy, if tolerated, as a second-line therapy in non-pregnant people with melasma for whom topical therapies are ineffective. The most commonly used peeling agent is glycolic acid in concentrations of 50% to 70%.[42][43][44][45] Trichloroacetic acid and salicylic acid peels are also reported to be effective in treating melasma. Adverse effects of chemical peels can include irritation and post-inflammatory hyperpigmentation. Topical therapy may be continued in conjunction with chemical peels.

Laser and light therapies are used if topicals (with or without peels) do not achieve adequate results or cannot be tolerated. The most commonly used, and most effective, modalities include the Q-switched neodymium:YAG/alexandrite laser, the CO2 laser, and intense pulsed light.[30] The Q-switched alexandrite laser and the CO2 laser as combined therapy may be better than the Q-switched alexandrite laser alone.[46][47] Fractional photothermolysis (a form of non-ablative laser therapy), dermabrasion, and cryotherapy are also used.[48][49] Fractional photothermolysis lowers the concentration of melanin granules and number of melanocytes.[50] The variable square pulse (VSP) Er:YAG laser has been used as a treatment option in affected patients, resulting in significant improvement in the MASI score with less downtime, no crust formation, and less chance of adverse effects.[51]

Post-inflammatory hyperpigmentation is common following laser therapy, but it is usually transient and can be managed with pre- and post-treatment hydroquinone therapy.[52]

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