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]Ball Arefiev KL, Hantash BM. Advances in the treatment of melasma: a review of the recent literature. Dermatol Surg. 2012 Jul;38(7 Pt 1):971-84.
http://www.ncbi.nlm.nih.gov/pubmed/22583339?tool=bestpractice.com
[23]Griffiths CE, Finkel LJ, Ditre CM, et al. Topical tretinoin (retinoic acid) improves melasma. A vehicle-controlled, clinical trial. Br J Dermatol. 1993 Oct;129(4):415-21.
http://www.ncbi.nlm.nih.gov/pubmed/8217756?tool=bestpractice.com
[24]Kimbrough-Green CK, Griffiths CE, Finkel LJ, et al. Topical retinoic acid (tretinoin) for melasma in black patients. A vehicle-controlled clinical trial. Arch Dermatol. 1994 Jun;130(6):727-33.
http://www.ncbi.nlm.nih.gov/pubmed/8002642?tool=bestpractice.com
Combination therapy may be better than any of the individual components used alone.[25]Kang HY, Valerio L, Bahadoran P, et al. The role of topical retinoids in the treatment of pigmentary disorders: an evidence-based review. Am J Clin Dermatol. 2009;10(4):251-60.
http://www.ncbi.nlm.nih.gov/pubmed/19489658?tool=bestpractice.com
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]Ball Arefiev KL, Hantash BM. Advances in the treatment of melasma: a review of the recent literature. Dermatol Surg. 2012 Jul;38(7 Pt 1):971-84.
http://www.ncbi.nlm.nih.gov/pubmed/22583339?tool=bestpractice.com
[26]Taylor SC, Torok H, Jones T, et al. Efficacy and safety of a new triple-combination agent for the treatment of facial melasma. Cutis. 2003 Jul;72(1):67-72.
http://www.ncbi.nlm.nih.gov/pubmed/12889718?tool=bestpractice.com
[27]Chan R, Park KC, Lee MH, et al. A randomized controlled trial of the efficacy and safety of a fixed triple combination (fluocinolone acetonide 0.01%, hydroquinone 4%, tretinoin 0.05%) compared with hydroquinone 4% cream in Asian patients with moderate to severe melasma. Br J Dermatol. 2008 Sep;159(3):697-703.
http://www.ncbi.nlm.nih.gov/pubmed/18616780?tool=bestpractice.com
Maintenance therapy with triple combination for 6 months after initial management has been suggested to prevent relapses.[28]Arellano I, Cestari T, Ocampo-Candiani J, et al. Preventing melasma recurrence: prescribing a maintenance regimen with an effective triple combination cream based on long-standing clinical severity. J Eur Acad Dermatol Venereol. 2012 May;26(5):611-8.
http://www.ncbi.nlm.nih.gov/pubmed/21623930?tool=bestpractice.com
[29]Austin E, Nguyen JK, Jagdeo J. Topical treatments for melasma: a systematic review of randomized controlled trials. J Drugs Dermatol. 2019 Nov 1;18(11):S1545961619P1156X.
https://jddonline.com/articles/topical-treatments-for-melasma-a-systematic-review-of-randomized-controlled-trials-S1545961619P1156X
http://www.ncbi.nlm.nih.gov/pubmed/31741361?tool=bestpractice.com
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]Prignano F, Ortonne JP, Buggiani G, et al. Therapeutical approaches in melasma. Dermatol Clin. 2007 Jul;25(3):337-42, viii.
http://www.ncbi.nlm.nih.gov/pubmed/17662899?tool=bestpractice.com
[31]Verallo-Rowell VM, Verallo V, Graupe K, et al. Double-blind comparison of azelaic acid and hydroquinone in the treatment of melasma. Acta Derm Venereol Suppl (Stockh). 1989;143:58-61.
http://www.ncbi.nlm.nih.gov/pubmed/2528260?tool=bestpractice.com
[32]Balina LM, Graupe K. The treatment of melasma. 20% azelaic acid versus 4% hydroquinone cream. Int J Dermatol. 1991 Dec;30(12):893-5.
http://www.ncbi.nlm.nih.gov/pubmed/1816137?tool=bestpractice.com
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]Deo KS, Dash KN, Sharma YK, et al. Kojic acid vis-a-vis its combinations with hydroquinone and betamethasone valerate in melasma: a randomized, single blind, comparative study of efficacy and safety. Indian J Dermatol. 2013 Jul;58(4):281-5.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3726874
http://www.ncbi.nlm.nih.gov/pubmed/23918998?tool=bestpractice.com
However, long-term studies show kojic acid has high irritant potential, and it is mutagenic in the Ames test.[34]Leyden JJ, Shergill B, Micali G, et al. Natural options for the management of hyperpigmentation. J Eur Acad Dermatol Venereol. 2011 Oct;25(10):1140-5.
http://www.ncbi.nlm.nih.gov/pubmed/21623927?tool=bestpractice.com
[35]Burnett CL, Bergfeld WF, Belsito DV, et al. Final report of the safety assessment of Kojic acid as used in cosmetics. Int J Toxicol. 2010 Nov-Dec;29(suppl 6):244S-73.
http://www.ncbi.nlm.nih.gov/pubmed/21164073?tool=bestpractice.com
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]Espinal Perez LE, Moncada B, Castanedo-Cazares JP. A double-blind randomized trial of 5% ascorbic acid vs 4% hydroquinone in melasma. Int J Dermatol. 2004 Aug;43(8):604-7.
http://www.ncbi.nlm.nih.gov/pubmed/15304189?tool=bestpractice.com
When compared with glycolic acid 70% peel, nanosome vitamin C demonstrated improved efficacy with fewer side effects.[37]Sobhi RM, Sobhi AM. A single-blinded comparative study between the use of glycolic acid 70% peel and the use of topical nanosome vitamin C iontophoresis in the treatment of melasma. J Cosmet Dermatol. 2012 Mar;11(1):65-71.
http://www.ncbi.nlm.nih.gov/pubmed/22360337?tool=bestpractice.com
An alternative topical treatment is arbutin.[38]Draelos ZD. Skin lightening preparations and the hydroquinone controversy. Dermatol Ther. 2007 Sep-Oct;20(5):308-13.
http://www.ncbi.nlm.nih.gov/pubmed/18045355?tool=bestpractice.com
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]Gupta AK, Gover MD, Nouri K, et al. The treatment of melasma: a review of clinical trials. J Am Acad Dermatol. 2006 Dec;55(6):1048-65.
http://www.ncbi.nlm.nih.gov/pubmed/17097400?tool=bestpractice.com
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]Chun EY, Lee JB, Lee KH. Focal trichloroacetic acid peel method for benign pigmented lesions in dark-skinned patients. Dermatol Surg. 2004 Apr;30(4 Pt 1):512-6.
http://www.ncbi.nlm.nih.gov/pubmed/15056140?tool=bestpractice.com
[43]Grimes PE. The safety and efficacy of salicylic acid chemical peels in darker racial-ethnic groups. Dermatol Surg. 1999 Jan;25(1):18-22.
https://www.doi.org/10.1046/j.1524-4725.1999.08145.x
http://www.ncbi.nlm.nih.gov/pubmed/9935087?tool=bestpractice.com
[44]Javaheri SM, Handa S, Kaur I, et al. Safety and efficacy of glycolic acid facial peel in Indian women with melasma. Int J Dermatol. 2001 May;40(5):354-7.
http://www.ncbi.nlm.nih.gov/pubmed/11555002?tool=bestpractice.com
[45]Soliman MM, Ramadan SA, Bassiouny DA, et al. Combined trichloroacetic acid peel and topical ascorbic acid versus trichloroacetic acid peel alone in the treatment of melasma: a comparative study. J Cosmet Dermatol. 2007 Jun;6(2):89-94.
http://www.ncbi.nlm.nih.gov/pubmed/17524124?tool=bestpractice.com
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]Prignano F, Ortonne JP, Buggiani G, et al. Therapeutical approaches in melasma. Dermatol Clin. 2007 Jul;25(3):337-42, viii.
http://www.ncbi.nlm.nih.gov/pubmed/17662899?tool=bestpractice.com
The Q-switched alexandrite laser and the CO2 laser as combined therapy may be better than the Q-switched alexandrite laser alone.[46]Nouri K, Bowes L, Chartier T, et al. Combination treatment of melasma with pulsed CO2 laser followed by Q-switched alexandrite laser: a pilot study. Dermatol Surg. 1999 Jun;25(6):494-7.
http://www.ncbi.nlm.nih.gov/pubmed/10469101?tool=bestpractice.com
[47]Angsuwarangsee S, Polnikorn N. Combined ultrapulse CO2 laser and Q-switched alexandrite laser compared with Q-switched alexandrite laser alone for refractory melasma: split-face design. Dermatol Surg. 2003 Jan;29(1):59-64.
http://www.ncbi.nlm.nih.gov/pubmed/12534514?tool=bestpractice.com
Fractional photothermolysis (a form of non-ablative laser therapy), dermabrasion, and cryotherapy are also used.[48]Rokhsar CK, Fitzpatrick RE. The treatment of melasma with fractional photothermolysis: a pilot study. Dermatol Surg. 2005 Dec;31(12):1645-50.
http://www.ncbi.nlm.nih.gov/pubmed/16336881?tool=bestpractice.com
[49]Kunachak S, Leelaudomlipi P, Wongwaisayawan S. Dermabrasion: a curative treatment for melasma. Aesthetic Plast Surg. 2001 Mar-Apr;25(2):114-7.
http://www.ncbi.nlm.nih.gov/pubmed/11349301?tool=bestpractice.com
Fractional photothermolysis lowers the concentration of melanin granules and number of melanocytes.[50]Tierney EP, Hanke CW. Review of the literature: Treatment of dyspigmentation with fractionated resurfacing. Dermatol Surg. 2010 Oct;36(10):1499-508.
http://www.ncbi.nlm.nih.gov/pubmed/20698875?tool=bestpractice.com
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]Wanitphakdeedecha R, Manuskiatti W, Siriphukpong S, et al. Treatment of melasma using variable square pulse Er:YAG laser resurfacing. Dermatol Surg. 2009 Mar;35(3):475-81.
http://www.ncbi.nlm.nih.gov/pubmed/19250309?tool=bestpractice.com
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]Tannous Z. Fractional resurfacing. Clin Dermatol. 2007 Sep-Oct;25(5):480-6.
http://www.ncbi.nlm.nih.gov/pubmed/17870526?tool=bestpractice.com