Melasma: How Can I Make It Go Away?

By Daebbang

“Since my mid-30s, brown patches have been spreading over my cheekbones. I was told it is melasma. Will it go away if I get laser treatment? I also heard there is a pill for it.”

It is right to think of melasma not as a blemish that can be removed in one go, but as a chronic pigment disorder that you lighten and then keep from darkening again. In skin with melasma, there is not only more pigment in the epidermis; changes in the dermis are also commonly seen together, such as damage to the boundary membrane between the epidermis and dermis, sun-damaged fibers and increased blood vessels[1, 2]. So in my judgment, melasma should be seen as a state in which the dermal environment has broken down, and restoring the dermal environment should also be a treatment goal alongside treatments that remove pigment.

The foundation of treatment is daily sun protection and topical lightening treatment. The international expert consensus is that other topical medicines such as azelaic acid and kojic acid, as well as oral tranexamic acid, are used as alternatives, that peels and microneedling are used as adjunctive treatments that support topical treatment, and that lasers are chosen carefully when other treatments are not enough[3]. Even after treatment lightens melasma, it commonly darkens again[3, 4].

There are also several pigment disorders that look like melasma but have different causes and treatments[5]. So melasma treatment starts with telling whether your patch is really melasma.

In this article, I will explain, in order, what melasma is and why it develops, how to tell melasma apart from look-alike pigment disorders by their borders and shape, how effective sun protection, topical medicines, oral medicine and peels are, and how far the evidence goes for the lasers many people get these days and for procedures that restore the dermal environment.

What is melasma?

Melasma is a light brown to dark brown patch that appears symmetrically on both sides of the face. It is characterized by irregular borders and a shape that spreads widely like a net. It is most common in the central face, such as the forehead, nose, upper lip and cheeks, and it can also appear only on the cheekbones or along the jawline. It is more common in women and in people with darker skin. How common it is varies widely, from 1% to 50%, depending on the population studied[6].

Under the microscope, melanin pigment is increased in the epidermis, the outer layer of the skin. In a study that compared the skin of 56 Korean patients with melasma with the normal skin right next to it, the melasma areas had more melanin in every layer of the epidermis, and the pigment-producing cells were also more active. Signs of sun damage were also more pronounced[7]. In some cases, there is also pigment in the dermis, the inner layer of the skin, or the small blood vessels are increased[6, 8].

Looking more deeply, melasma also involves changes in the dermis. Between the epidermis and dermis there is a thin boundary membrane called the basement membrane. In a study that examined the skin of 48 patients with melasma, depending on the staining method, this basement membrane was damaged in 83–95.5% of the tissue from melasma areas. Pigmented basal cells of the epidermis were often seen hanging down toward the dermis, and mast cells were increased in the dermis[9]. In a study that looked at the skin of 10 women with melasma under an electron microscope, the basement membrane in melasma areas was also broken or thinned in places. The spots where pigment cells sagged down toward the dermis were where the basement membrane was broken[10].

The dermis itself is also changed. In 83–93% of patients with melasma, solar elastosis, in which sun-damaged elastic fibers are clumped together, was seen[2]. A review that summarized dermal changes in melasma said that basement membrane damage, sagging pigment cells, solar elastosis, cells that have engulfed pigment, mast cells and new blood vessels are commonly seen in melasma, and that these dermal changes may be connected with the pigment changes in the epidermis. It also considered that these changes could become new targets for treatment[1]. There is also a view that melasma should be regarded as a skin disorder caused by sun-induced aging[11].

In my judgment, the fact that melasma spreads widely without clear borders and keeps darkening again even after treatment is closely related to this broken-down dermal environment. This is why treatment that only removes pigment from the epidermis is not enough and the dermal environment must be restored as well.

Why does melasma develop?

Sunlight, female hormones and family history are considered the main causes[6]. One study compared 207 Brazilian women with melasma and 207 women of the same age without melasma. The proportion who said a family member had melasma was 61% in the melasma group and 13% in the group without it. A lifestyle with long sun exposure, a history of pregnancy, the duration of oral contraceptive use and irregular periods were also associated with melasma[13].

Not only ultraviolet light but also visible light, the light we can see, is involved. Visible light can cause pigmentation in people with darker skin[14]. Because small blood vessels are often increased in melasma areas, changes in blood vessels are also being studied as one of the causes[8].

In my judgment, this is what makes melasma most different from other blemishes. As long as there are day-to-day triggers such as sunlight and hormones, melasma can darken again. That is why the word “management” suits it better than “treatment.”

What pigment disorders are confused with melasma?

Brown or gray patches on the face are divided into epidermal, dermal and mixed types according to the depth in the skin at which the pigment is located[5]. Pigment disorders that need to be distinguished from melasma include freckles, lentigines, post-inflammatory hyperpigmentation, acquired bilateral nevus of Ota-like macules and nevus of Ota[6]. When the depth differs, the treatment that works well also differs.

The first thing to look at with the eye is the border. Melasma is a patch with irregular borders that spreads widely like a net[6]. Some melasma can also look sharply bordered[15]. Freckles are small light brown dots of 1–2 mm that appear one by one, separately; they start in childhood and increase in number at puberty. Lentigines are flat brown spots that form on sun-exposed areas, with sharp borders[16]. However, facial pigment disorders often overlap in their appearance and dermoscopic findings, so the diagnosis should not be settled by the border alone; the history, examination and dermoscopy (a magnifying skin examination) should be considered together[17].

In particular, acquired bilateral nevus of Ota-like macules is a dermal pigment disorder common in Asian women, and because it appears on the face, it is easily confused with melasma. Because the pigment sits at the middle depth of the dermis, unlike melasma, a laser that targets pigment is the main treatment[12]. In a study that compared the skin of 50 people with melasma and 46 people with these macules with dermoscopy, melasma was mostly light brown, while these macules were more often gray or blue-brown. Even when the two were present together, dermoscopy helped tell them apart[21]. Before getting laser treatment, it is good to confirm in a clinic visit what kind of pigment it is. I covered the difference between freckles and melasma and the difference between pico toning and spot treatment in Why Are My Freckles and Dark Spots Still There After Pico Toning?, and post-inflammatory hyperpigmentation in detail in Dark Patches After Laser Treatment: Why Does Post-Inflammatory Hyperpigmentation Happen, and How Long Does It Last?.

Why is sun protection the most important?

The international expert consensus named daily use of a broad-spectrum sunscreen as the foundation for every patient with melasma[3]. However, ordinary sunscreens do not block visible light well enough. To block visible light as well, a tinted sunscreen containing pigments such as iron oxide, which leave color on the skin, is helpful[14].

In one randomized study, all 68 patients with melasma applied 4% hydroquinone and were divided into a group using a sunscreen that blocks only ultraviolet light and a group using an iron oxide sunscreen that also blocks visible light. After 8 weeks, the group that also blocked visible light improved 15% more in melasma score[22]. There are also randomized studies in which melasma recurred less in the group that used a sunscreen with added visible-light-blocking ingredients[6].

In my judgment, if you have melasma, it is good to choose a tinted sunscreen and to apply it even indoors if you spend a long time near a window. Use physical protection such as hats and parasols as well.

What topical medicines are there?

Topical medicines are still the center of melasma treatment. An evidence-based review that summarized 113 studies (6,897 people) concluded that hydroquinone alone and triple combination cream (a cream that combines hydroquinone, tretinoin and a steroid) are the most effective and most studied treatments[23]. In a Cochrane review that examined 20 randomized studies (2,125 people), triple combination cream also lightened melasma more than hydroquinone alone. 20% azelaic acid was more effective than 2% hydroquinone, but no clear difference from 4% hydroquinone was found[24].

These medicines should be used under a doctor’s prescription and supervision. The international expert consensus also named triple combination cream as standard treatment while saying that it should be adjusted and used under a doctor’s supervision[3]. Applying hydroquinone for a long time can cause exogenous ochronosis, in which the skin instead turns blue-black, and once it develops, it is very difficult to treat[25]. Long-term use of the steroid in triple combination cream can thin the skin or make small blood vessels visible[6]. When hydroquinone is hard to use, other topical medicines such as azelaic acid or kojic acid are used[3].

Does oral tranexamic acid work?

Tranexamic acid was originally a medicine that reduces bleeding. In melasma, it is being studied as a treatment that suppresses the process by which pigment is made and also acts on the blood vessel changes of melasma[6, 8]. In one randomized study, 44 people with moderate to severe melasma took tranexamic acid or a placebo for 3 months, and all of them used sunscreen. After 3 months, the melasma score decreased by 49% in the tranexamic acid group and by 18% in the placebo group. However, 3 months after stopping the medicine, the difference had narrowed greatly, to 26% and 19%[26]. In an analysis that pooled 24 randomized studies of tranexamic acid used by mouth, on the skin or as intradermal injection, tranexamic acid also increased the effect when added to existing treatment[27].

Because tranexamic acid is a medicine that reduces bleeding, blood clots are the biggest concern. In a summary that pooled randomized studies of oral tranexamic acid, no blood clot events were observed[28]. However, long-term safety needs more research[23]. A consensus of pigment disorder experts also said that a history of blood clots, cardiovascular disease and menstrual history should be checked before starting oral tranexamic acid[29]. Before taking oral tranexamic acid, you must see a doctor and tell them about your own medical history, such as whether you have ever had a blood clot, and the medicines you are taking. Because melasma tends to darken again when the medicine is stopped, topical treatment and sun protection should be continued while you take it.

Do peels help?

A chemical peel is a treatment that uses a mild acid to thinly remove the outer layer of the skin and help pigment come out. In a systematic review that summarized 24 studies (1,075 people) of peels for melasma, peels were safe and effective, and glycolic acid peels were the safest and most effective. However, because the methods differed from study to study, the results could not be combined into one analysis[30]. The international expert consensus recommended peels as an adjunctive treatment that increases the effect of topical treatment[3].

Peels also create inflammation in the skin, so if they are done too strongly, post-inflammatory hyperpigmentation can develop. In my judgment, the safe order is to start with topical treatment first and then add a mild peel on top of it.

What about the lasers and procedures people get these days?

Laser toning is a method in which a 1064 nm Q-switched Nd:YAG laser is applied over the whole face at low fluence in multiple passes. In an analysis that pooled 50 studies (1,772 people), toning alone lightened melasma at first, but its effect decreased over time, and after 24 weeks there was almost no difference from before treatment. Combining it with topical medicines and other treatments was more effective than toning alone. Side effects included hypopigmentation, in which color is lost and the skin turns white, post-inflammatory hyperpigmentation and recurrence, and hypopigmentation was more common with more treatment sessions[31]. A systematic review of 42 studies by Korean researchers also said that, although rare, mottled hypopigmentation can develop and last a long time, and that doing it too strongly can instead cause pigmentation[32].

A picosecond laser is a method that fires the laser in very short bursts. In an analysis that pooled 6 randomized studies, the 1064 nm picosecond laser reduced the melasma score, but the 755 nm picosecond laser did not come out better than topical lightening agents and caused post-inflammatory hyperpigmentation[33]. Even with the same picosecond laser, the results differ with wavelength and intensity.

Results for fractional lasers are mixed. In a randomized study in which one side of the face of 29 people was treated with a non-ablative fractional laser and the other side with triple combination cream, the laser side instead became darker, and 9 people (31%) developed post-inflammatory hyperpigmentation[34]. In an analysis that pooled 22 laser studies (694 people), several lasers reduced the melasma score, but people with darker skin had a risk of post-inflammatory hyperpigmentation and hypopigmentation[35].

Microneedling has evidence when used together with topical medicines. In an analysis that pooled 12 studies (459 people), adding microneedling to topical medicines led to greater improvement at 12–16 weeks than topical medicines alone, and no serious side effects were reported[36]. In an analysis that compared 59 randomized studies together, Q-switched Nd:YAG laser, ablative fractional laser, triple combination cream and oral tranexamic acid ranked ahead, and in 27 of the 31 studies that made the comparison, combined treatment was better than a single treatment[37].

In my judgment, lasers can help lighten melasma, but on their own they are not a treatment that ends melasma. The international expert consensus also said to use lasers when melasma does not respond well to other treatments[3]. If you have had dozens of toning sessions at short intervals and mottled white spots have appeared or the area has instead darkened, stop rather than adding more sessions and see a doctor again. I covered how pico toning differs between melasma and other blemishes in Why Are My Freckles and Dark Spots Still There After Pico Toning?.

Do treatments that restore the dermal environment work?

As we saw above, skin with melasma commonly also has dermal changes. There is a proposal to make these dermal changes a treatment target[1], and besides treatments that break up pigment directly, treatments that aim to restore the dermis and reduce oxidative stress (damage caused by reactive oxygen) and inflammation are being studied as new approaches[38, 39, 40]. Representative ones are low-fluence long-pulsed Nd:YAG laser toning, PDRN, PN and mixed cross-linked and non-cross-linked hyaluronic acid injections (skin boosters).

Low-fluence long-pulsed Nd:YAG laser toning (commonly called “Genesis toning”) is a method that fires the same 1064 nm Nd:YAG laser in microsecond-range pulses, much longer than Q-switched pulses. In one study, the laser was applied until the skin temperature rose to about 40–42°C and the skin turned evenly and slightly red[41]. In a study in which 30 patients whose melasma had instead darkened after other treatments received Q-switched toning combined with long-pulsed toning 10 times, the melasma score decreased from 10.48 to 3.22. The researchers interpreted that the long-pulsed laser may stabilize melasma by remodeling the dermis[42]. In a study of 21 people in which one side of the face received Q-switched toning only and the other side received added microsecond toning, the side with the added treatment had lower melanin values even at 12 months, and redness also decreased more. However, after 6 months, the melasma score showed no clear difference from before treatment[43]. In a randomized study that divided 40 people, the melasma score decreased both in the group that used Q-switched and long-pulsed lasers together and in the picosecond alexandrite laser group, and it decreased more in the combined group. Recurrence at 24 weeks was 0% and 10.5%, with no statistically significant difference[44]. This study did not look separately at the effect of adding the long-pulsed laser; it compared two laser approaches.

PDRN (polydeoxyribonucleotide) is an ingredient made from DNA fragments that has been used to help wound healing and collagen production in sun-aged skin. In cell experiments, PDRN reduced melanin and the enzyme that makes pigment, and there is also an observation that facial hyperpigmentation visibly lightened when 6 women with it received 3 injections into the skin[38]. Another cell experiment also showed an antioxidant effect that removes reactive oxygen and an effect that reduces the enzyme that breaks down collagen[45].

PN (polynucleotide) is a DNA-fragment ingredient with a structure similar to PDRN (for example, Rejuran). In experiments with cells and animal skin exposed to ultraviolet light, PN reduced oxidative stress and inflammatory signals and also reduced melanin buildup[39]. However, in a randomized study in which 30 patients with melasma received radiofrequency microneedling on both sides of the face and then had PN applied to only one side, there was no difference between the two sides up to 6 months[46].

Mixed cross-linked and non-cross-linked hyaluronic acid injection is a skin booster that mixes hyaluronic acid whose molecules are partly linked together (cross-linked) with hyaluronic acid that is not linked (non-cross-linked) (for example, HILOWAVE). In experiments with cells and rats, a hybrid hyaluronic acid in which hyaluronic acids of different molecular sizes were lightly linked increased collagen and elastic fiber production, showed antioxidant and anti-inflammatory effects, suppressed genes that make pigment and reduced melanin built up by ultraviolet light[40]. Human melasma studies are small studies with similar injections. In 6 people whose toning results had stopped improving, melasma lightened further when toning was continued after injection of non-cross-linked hyaluronic acid containing antioxidant ingredients[47]. In a randomized study (36 of 50 people completed it) that added a hyaluronic acid skin booster containing glutathione to Q-switched toning and oral tranexamic acid treatment, the melasma score of the group with the added treatment was 2.50 at 6 months, lower than 3.39 in the group without it, and the difference was still maintained 2 months after treatment[48]. Because this study also included an antioxidant ingredient called glutathione, it is hard to regard the result as the effect of hyaluronic acid alone.

In my judgment, treatments that restore the dermal environment are meaningful in that they target the reason melasma spreads widely and keeps recurring. However, there are still few studies in people, and most are test-tube and animal experiments or small clinical studies. So they are not treatments that replace sun protection and topical medicines; it is right to use them together as adjunctive treatments added to the basic treatment.

How can I keep it from darkening again?

Even after melasma has lightened with treatment, it commonly darkens again. The international expert consensus also named the high recurrence rate as a reason melasma is hard to manage and said that long-term maintenance strategies need more research[3]. A Korean review explains that recurrence is frequent because aging changes such as sun damage and increased blood vessels are also present in skin with melasma[4]. In a randomized study in which people whose melasma had cleared or become mild after 8 weeks of triple combination cream received maintenance treatment for 6 months by applying it less often, 53% stayed free of recurrence[49].

In my judgment, sun protection must continue even after melasma has lightened. Rather than stopping topical medicines right away, it is also good to decide with your doctor whether to continue them less often. Knowing in advance about situations related to melasma, such as a lifestyle with a lot of sun exposure, pregnancy and oral contraceptives, and preparing for them also helps[13].

So what should I do?

Take-home messages

1. Melasma is a brown patch that appears symmetrically on both sides of the face, and sunlight, female hormones and family history are the main causes. Not only pigment in the epidermis but also dermal changes such as basement membrane damage, sun-damaged fibers and increased blood vessels are commonly present.
2. Melasma is a patch with irregular borders that spreads widely, freckles are small dots scattered separately, and lentigines are sharply bordered spots. Pigment disorders that look like melasma differ in depth and treatment, so first confirm the type with an examination before treatment.
3. Daily sun protection is the foundation of treatment. A tinted sunscreen that also blocks visible light helps more.
4. Prescription topical medicines, especially triple combination cream, are the treatment with the most evidence. However, they should be used under a doctor’s supervision.
5. Oral tranexamic acid increases the effect of existing treatment, but melasma tends to darken again when it is stopped. Be sure to see a doctor before taking it.
6. Laser toning can help, but its effect on its own decreases over time, and getting it too often can cause white spots. Results with picosecond lasers differed by wavelength.
7. Treatments that restore the dermal environment, such as long-pulsed Nd:YAG laser toning, PDRN, PN and hyaluronic acid skin boosters, still have few studies, so they are used together as adjunctive treatments added to the basic treatment.
8. Melasma commonly recurs even after it has lightened, so sun protection and maintenance treatment must continue.

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