Melasma: What is It and How is It Treated?

My wife anticipated she would develop melasma after we found out she was pregnant with our first child. She is of Iranian descent, after all. Her mother also experienced severe cases after her pregnancy with my wife and her brother. Melasma is an unfortunately common consequence of pregnancy for many women, especially those of Latin America, Africa, Middle Eastern, and Asia descent (1). It is something many women are aware of primarily in the context of pregnancy but otherwise know little about. This blog post is my effort at:

• Explaining what melasma is
• Reviewing the potential causes of melasma
• Summarizing the available treatment options for melasma

My intention with this blog post is not to provide direct medical advice nor to serve as an alternative to direct medical advice. Instead, the purpose of this blog post is to give readers a better sense of the conversation to expect when they sit down with a qualified medical provider for a consultation.

Melasma Is Caused by Excessive Melanin Deposition in the Skin

Melanocytes are the factory that produces melanin, the molecule that gives our skin pigmentation, thereby darkening it (hyperpigmentation). Melanocytes exist in the top layer of skin, called the epidermis, and the bottom layer of skin, called the dermis. The machinery in the melanin factory is called the melanosome. In summary, melasma is caused by the excessive production of melanin by melanosomes in melanocytes which is quite a tongue-twister (2).

Melasma Has Multiple Potential Causes, Differing Distributions, and Variable Depth

There are multiple potential causes of melasma (1, 3, 4) including, but not limited to:

• Light exposure
• Genetics
• Pregnancy
• Use of oral contraceptives
• Hormone replacement therapy
• Sensitivity to a variety of topical medications

Furthermore, there are multiple distribution patterns on the face such as the more common centralized and diffuse hyperpigmentation (3).

The depth of melasma differs between individuals as well, including deeper versions that are more difficult to treat (3).

Not only does melasma result in hyperpigmented areas but those areas also exhibit signs of advanced aging as well as redness due to increased blood vessel formation, called neovascularization (2).

Melasma Has a High Recurrence Rate and Often Requires Long-Term Treatment

Melasma is a chronic condition that is very difficult to cure and has a high chance of returning regardless of the cause, distribution, depth, and primary treatment. Moreover, there are potential risks and side effects from available treatments that prevent them from being viable long-term i.e. longer than a few months. It is for those reasons that many physicians have a treatment protocol that includes a primary treatment followed by maintenance therapy with potentially less effective but better-tolerated medications.

Primary Treatment Is Focused on Stopping Melanocytes From Producing Melanosomes

It is helpful to begin the discussion of treatments for melasma with topical therapies, which happen to be the first method used to treat melasma in most instances. It is important to emphasize that, regardless of the treatment, the use of a tinted sunscreen that protects against both visible light and ultraviolet (UV) light, is an essential component not only for the prevention of melasma but also of the initial and maintenance treatment, regardless of other medications used (2, 4).

There is one medication that is approved by the Food and Drug Administration (FDA) for the treatment of melasma (Tri-Luma® cream). It is a cream applied to the skin consisting of:

1. Hydroquinone
2. A retinoid
3. A corticosteroid

Hydroquinone is a skin lightening agent and probably the most studied and frequently used individual medication to treat hyperpigmentation of the skin, including melasma (3, 4). In fact, many physicians start by treating melasma with hydroquinone only. It works by stopping the creation of melanin in melanosomes by blocking a specific enzyme in the melanosome.

Tretinoin is itself an FDA-approved treatment for photoaging, which is the premature aging of the skin secondary to exposure to ultraviolet (UV) rays from the sun. As a result, it is frequently used to treat and prevent the development of fine lines, wrinkles, and other features of photoaging. I was treated with tretinoin as a teenager for fine "bumps" on my cheeks like those many people develop on the backs of their arms, called keratosis pilaris. Tretinoin works synergistically with hydroquinone, preventing its breakdown and allowing it to work deeper in the skin (1). It also reduces the production of the enzyme that creates melanin and accelerates the turnover of surface pigment in the epidermis (4).

A mild-potency corticosteroid i.e. steroid is added to reduce the amount of redness, peeling, and itching that are side effects of both hydroquinone and tretinoin (1). It is not used as a treatment for melasma alone.

The problem with the above "triple therapy" is that it is generally not used for prolonged periods of time due to the risk of long-term complications from the three medications, especially the hydroquinone and corticosteroid.

Again, it is important to emphasize that there are many ways to treat melasma with topical medications other than with "triple therapy." For example, I have dermatology colleagues who alternate hydroquinone and tretinoin as individual therapies to reduce the potential for the development of side effects from these medications. Though "triple therapy" has been shown in studies to be more effective that any single medication or combination of the two medications above, there may be good reasons to avoid it. For example, patient intolerance of one or more medications or a desire to minimize the risk of complications from the use of these medications may prevent its use (1). An example of a rare complication from the long-term use of hydroquinone is called exogenous ochronosis, which is the paradoxical formation of blue grey "bumps" on the skin in the area(s) treated (4).

Though not FDA-approved for the purposes of treating melasma, there has been a great deal of research on the use of tranexamic acid (TXA) for its treatment, especially melasma located in the dermis, or deeper layer of skin (1, 5). While it is generally not the first treatment used for melasma, many consider it a secondary option for appropriately selected patients when the first-line therapies do not adequately treat the condition (4, 5). TXA is FDA-approved to reduce blood loss during surgery when administered intravenously (IV) and menstruation when administered by mouth (orally). The mechanism whereby it treats melasma is not clear (1). TXA has been administered:

• Orally
• Topically
• Injection directly into the hyperpigmented skin

The most used form of TXA is oral (1, 5). Potential side effects of the oral use of TXA include nausea, vomiting, diarrhea, an increased risk of blood clot, an allergic reaction, damage to color vision, and kidney damage. That is why this treatment is typically only considered if the initial treatment failed and only for those patients who undergo a detailed screening to make sure, for example, they do not have a baseline blood clotting disorder and/or color blindness (5).

There are many other treatments under investigation. Substances studied include:

• Thiamidol
• Pycnogenol

and others (4).

Chemical peels, especially glycolic acid, have been used as an adjunct to topical medications with some limited benefit simply by removing the pigmented skin itself (4). The multitude of lasers studied for the treatment of melasma often result in rapid recurrence of melasma, especially after sun exposure (4). These treatments will not be discussed at length here for sake of simplicity as their evidence base is shallow. They would likely be considered only as an adjunct to other topical medications or as an alternative if all other treatments fail.

Maintenance Therapy Is Often Considered After the Initial Treatment Course Is Complete

As stated previously, a tinted sunscreen to protect from not only from visible light but also from UV light – both UVA and UVB – is a mainstay of maintenance therapy after the initial treatment is complete. Other than sunscreen, the concept behind maintenance therapy is that the treatments can be administered long-term with a decreased potential for side effects or complications from the medications. Importantly, maintenance therapy tends to be less effective than the initial therapy. Possible options include the continued use of tretinoin only as well as cosmeceuticals such as Vitamin C (ascorbic acid) and/or E. But while there is a known mechanism whereby Vitamin C and/or Vitamin E could reduce the activity of the enzyme that makes melanin, their effect on the treatment of melasma does not have strong evidence. They may more rightly be considered as simply an enhanced photoprotective regimen (1).

The Treatment of Melasma Is Complex and Usually Frustrating and Requires Close Observation by a Qualified Medical Professional

In summary, the treatment of melasma is often complex and frustrating. The Cochrane Library, a world-renowned Danish organization that produces studies referencing only the highest quality studies available, labeled the treatment of melasma as "unsatisfactory" because available therapies are often incomplete, complicated by side effects, and melasma has a high likelihood of recurring (3). That is why it is essential to be evaluated and treated by a qualified medical provider, usually a dermatologist. These professionals can follow patients long-term, responding to their specific skin type, their specific type of melasma. They can have a long discussion about the potential benefits, risks, and alternatives to any treatment option.

References

1. Mahajan VK, Patil A, Blicharz L, Kassir M, Konnikov N, Gold MH, Goldman MP, Galadari H, Goldust M. Medical therapies for melasma. J Cosmet Dermatol. 2022 Sep;21(9):3707-3728.
2. Artzi O, Horovitz T, Bar-Ilan E, Shehadeh W, Koren A, Zusmanovitch L, Mehrabi JN, Salameh F, Isman Nelkenbaum G, Zur E, Sprecher E, Mashiah J. The pathogenesis of melasma and implications for treatment. J Cosmet Dermatol. 2021 Nov;20(11):3432-3445.
3. Rajaratnam R, Halpern J, Salim A, Emmett C. Interventions for melasma. Cochrane Database Syst Rev. 2010 Jul 7;(7):CD003583.
4. Gan C, Rodrigues M. An Update on New and Existing Treatments for the Management of Melasma. Am J Clin Dermatol. 2024 Sep;25(5):717-733. doi: 10.1007/s40257-024-00863-2. Epub 2024 Jun 19.
5. Konisky H, Balazic E, Jaller JA, Khanna U, Kobets K. Tranexamic acid in melasma: A focused review on drug administration routes. J Cosmet Dermatol. 2023 Apr;22(4):1197-1206.