A Practical Approach to Treating Melasma

Melasma is the presence of dark patches on the face that usually develops due to sun exposure or from circulating hormones. It is a frustrating condition for those affected and can often lead to social embarrassment. Treatment can be frustrating as well due to the difficult nature of improving the condition and preventing it in the future. Here are three reasons why melasma forms and practical approaches to combat it from occurring. 

 

Reason #1: The Pigment Producing Cells (Melanocytes) are Overactive

Melanocytes are the pigment-producing cells of the skin and make a form of melanin pigment known as eumelanin; this creates the dark color of the skin. When stimulated by sun exposure, by local injury (such as the use of an irritating skin product), or by hormones, these cells can become overactive.^[1,2] This leads to overactivity of the enzyme known as tyrosinase that is a key player in the synthesis of eumelanin.  

Treatment strategy: Inhibit the tyrosinase enzyme

To reduce the activity of the melanocytes, one strategy is to reduce the actions of the tyrosinase enzyme that is responsible for producing eumelanin. There are several agents that inhibit melanin production via this action: 

• Hydroquinone: Hydroquinone is used for gradually lightening the skin. It does not cause immediate lightening of the skin but rather gradually bleaches the skin by reducing the action of the tyrosinase enzyme. This agent is available over-the-counter in doses up to 2%^[3] and available as a prescription at doses of 4% and higher.^[4,5] 
• Azelaic acid: Azelaic acid reduces the action of the tyrosinase enzyme and has been studied for the treatment of facial pigmentation and melasma.^[6,7] Azelaic acid was found to work as well as 4% hydroquinone when compared against each other.^[6] 
• Kojic acid: Kojic acid is not approved by the FDA but is a chemical produced from the fungus Aspergillus oryzae. Kojic acid and molecules that are similar to it reduce the activity of the tyrosinase enzyme.^[8] It has been studied as part of a regimen to improve melasma,^[9,10] but kojic acid has not been studied by itself.  
• Arbutin: Arbutin has been shown to reduce the effects of tyrosinase in cell culture,^[11] but human studies are needed. 

Treatment strategy: Reduce stimulation of the melanocytes

• Sun protection: Sunlight and ultraviolet light can stimulate melanocytes to produce more pigment. Sun protective clothing and sunscreens are important to reduce light-induced pigmentation of the skin. Sunscreens need to be broad spectrum so that they can block the UVA and UVB component of light.^[2] Sunscreens should be worn even in the shade since sunlight can reflect off surfaces and get to the skin.^[12] Learn more about sunscreens here. 

 

Reason #2: Pigment is Passed from Melanocytes to Surrounding Skin Cells

Melanocytes typically pass their pigment to surrounding skin cells known as keratinocytes to spread pigment evenly. Several strategies have been used to help reduce the pigment in keratinocytes, further reducing the appearance of dark patches on the skin. 

Treatment strategy: Prevent the transfer of pigment from melanocyte to keratinocytes 

• Soy extracts: Enzymes and extracts from soybeans have been shown to prevent melanocytes from transferring their pigment to keratinocytes.^[13,14] Human studies have shown that soy extracts may be helpful in reducing skin pigmentation,^[15,16] but they have not been studied specifically for the treatment of melasma. 

Treatment strategy: Increase how quickly keratinocytes that contain more pigment are replaced

• Retinoids: retinoids are a class of medications that help keratinocyte cells turnover and be replaced.^[17] New keratinocytes have less pigment than longer existing keratinocytes. 

Treatment strategy: Physically remove the pigment containing keratinocytes

• Chemical peels: Chemical peels can improve melasma and work by removing the superficial layers of the skin.^[18] This leads to removal of keratinocytes with extra pigment so that they are replaced by keratinocytes that do not have as much pigment. Chemical peels must be performed by a qualified health practitioner.

 

Reason #3: Pigment can be in a Deeper Layer of the Skin, Making it Harder to Remove

In melasma, the depth of the pigment is important. Superficial (epidermal) pigmentation is relatively easier to treat. However, when the pigment is in the deeper layer of the skin known as the dermis, this type of melasma is harder to treat. Deeper pigmentation is seen in both dermal melasma and in mixed melasma (a mix of epidermal and dermal melasma). Topical treatments do not work as well for this type of melasma. 

Treatment strategy: Directly destroy the pigment

Lasers have been studied for the treatment of dermal melasma.^[19,20] Lasers need to be considered carefully by a qualified medical professional to assess if your skin type can tolerate laser treatments safely. 

Overall Strategy: Combine Multiple Treatment Modalities

A qualified health professional such as a dermatologist can discuss if combining different strategies is right for you. One example of a combination medication that is available by prescription is a mix of hydroquinone with tretinoin (a retinoid) and a steroid.^[21,22] This type of product can work at decreasing pigment via different mechanisms at the same time. 

Melasma is a frustrating skin condition, but there are many treatments that are available. Although treatments are not perfect, understanding the mechanisms and treatment strategies above can help in your discussion with your local dermatologist or qualified healthcare practitioner. Together you can come up with a reasonable treatment plan that fits your type of melasma, your lifestyle, and your pocket.  

 

1.    Cestari T, Arellano I, Hexsel D, et al. Melasma in Latin America: options for therapy and treatment algorithm. J Eur Acad Dermatol Venereol.2009;23(7):760-772; PMID: 19646135.

2.    Handel AC, Miot LD, Miot HA. Melasma: a clinical and epidemiological review. An Bras Dermatol.2014;89(5):771-782; PMID: 25184917.

3.    Hydroquinone Studies Under The National Toxicology Program (NTP).  http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/ucm203112.htm. Accessed August 6, 2016.

4.    Haddad AL, Matos LF, Brunstein F, et al. A clinical, prospective, randomized, double-blind trial comparing skin whitening complex with hydroquinone vs. placebo in the treatment of melasma. Int J Dermatol.2003;42(2):153-156; PMID: 12709008.

5.    Ennes SBP, Paschoalick RC, Alchorne MM. A double-blind, comparative, placebo-controlled study of the efficacy and tolerability of 4% hydroquinone as a depigmenting agent in melasma. Journal of Dermatological Treatment.2000;11(3):173-179

6.    Balina LM, Graupe K. The treatment of melasma. 20% azelaic acid versus 4% hydroquinone cream. Int J Dermatol.1991;30(12):893-895; PMID: 1816137.

7.    Breathnach AS. Melanin hyperpigmentation of skin: melasma, topical treatment with azelaic acid, and other therapies. Cutis.1996;57(1 Suppl):36-45; PMID: 8654129.

8.    Asadzadeh A, Sirous H, Pourfarzam M, et al. In vitro and in silico studies of the inhibitory effects of some novel kojic acid derivatives on tyrosinase enzyme. Iran J Basic Med Sci.2016;19(2):132-144; PMID: 27081457.

9.    Garcia A, Fulton JE, Jr. The combination of glycolic acid and hydroquinone or kojic acid for the treatment of melasma and related conditions. Dermatol Surg.1996;22(5):443-447; PMID: 8634807.

10.    Azzam OA, Leheta TM, Nagui NA, et al. Different therapeutic modalities for treatment of melasma. J Cosmet Dermatol.2009;8(4):275-281; PMID: 19958431.

11.    Maeda K, Fukuda M. Arbutin: mechanism of its depigmenting action in human melanocyte culture. J Pharmacol Exp Ther.1996;276(2):765-769; PMID: 8632348.

12.    David HS. Epidemiological studies of sunlight and cataract: the critical factor of ultraviolet exposure geometry. Ophthalmic Epidemiology.1994;1(2):107-119; PMID.

13.    Seiberg M, Paine C, Sharlow E, et al. The protease-activated receptor 2 regulates pigmentation via keratinocyte-melanocyte interactions. Exp Cell Res.2000;254(1):25-32; PMID: 10623462.

14.    Paine C, Sharlow E, Liebel F, et al. An alternative approach to depigmentation by soybean extracts via inhibition of the PAR-2 pathway. J Invest Dermatol.2001;116(4):587-595; PMID: 11286627.

15.    Hermanns JF, Petit L, Martalo O, et al. Unraveling the patterns of subclinical pheomelanin-enriched facial hyperpigmentation: effect of depigmenting agents. Dermatology.2000;201(2):118-122; PMID: 11053913.

16.    Wallo W, Nebus J, Leyden JJ. Efficacy of a soy moisturizer in photoaging: a double-blind, vehicle-controlled, 12-week study. J Drugs Dermatol.2007;6(9):917-922; PMID: 17941363.

17.    Truchuelo MT, Jimenez N, Jaen P. Assessment of the efficacy and tolerance of a new combination of retinoids and depigmenting agents in the treatment of melasma. J Cosmet Dermatol.2014;13(4):261-268; PMID: 25399618.

18.    Sarkar R, Garg V, Bansal S, et al. Comparative Evaluation of Efficacy and Tolerability of Glycolic Acid, Salicylic Mandelic Acid, and Phytic Acid Combination Peels in Melasma. Dermatol Surg.2016;42(3):384-391; PMID: 26859648.

19.    Tannous ZS, Astner S. Utilizing fractional resurfacing in the treatment of therapy-resistant melasma. J Cosmet Laser Ther.2005;7(1):39-43; PMID: 16020216.

20.    Arora P, Sarkar R, Garg VK, et al. Lasers for treatment of melasma and post-inflammatory hyperpigmentation. J Cutan Aesthet Surg.2012;5(2):93-103; PMID: 23060704.

21.    Torok HM, Jones T, Rich P, et al. Hydroquinone 4%, tretinoin 0.05%, fluocinolone acetonide 0.01%: a safe and efficacious 12-month treatment for melasma. Cutis.2005;75(1):57-62; PMID: 15732437.

22.    Cestari T, Adjadj L, Hux M, et al. Cost-effectiveness of a fixed combination of hydroquinone/tretinoin/fluocinolone cream compared with hydroquinone alone in the treatment of melasma. J Drugs Dermatol.2007;6(2):153-160; PMID: 17373174.