Combination Approach to Melasma Treatment Yields Best Results

Doug Brunk

September 11, 2020

When establishing a treatment plan for patients with melasma, counseling them about realistic expectations is key.

"It's important that they understand that this is a chronic condition, so it does require long-term maintenance therapy," Arisa E. Ortiz, MD, said at the virtual annual Masters of Aesthetics Symposium. "We can improve melasma, but it's difficult to cure melasma."

While hydroquinone and other bleaching agents are typical treatment mainstays, chemical peels with glycolic acid, trichloroacetic acid, and salicylic acid can benefit some individuals. "For chemical peels, I really like glycolic acid peels because there is no downtime; it peels at the microscopic level," said Dr. Ortiz, who is director of laser and cosmetic dermatology at the University of California, San Diego. "This is something they may need to repeat monthly, and having a week of peeling may be difficult to go through every month."

Other common melasma treatments include lasers, intense pulsed light (IPL), and oral medications. "I personally am not impressed with microdermabrasion for melasma, so I don't use that very much," she said. "With laser treatment, you want to make sure you're using low-energy lasers so that it doesn't exacerbate or make them relapse or rebound."

While hydroquinone is a mainstay of therapy, "you can't use it chronically because of the risk of ochronosis (permanent darkening), so you do need to take drug holidays," Dr. Ortiz said. "During those drug holidays, you want to make sure patients have a nonhydroquinone bleaching agent so that they don't flare." Options include lignin peroxidase, oligopeptide, Lytera, Melaplex, 4-n-butylresorcinol, Cysteamine cream, tranexamic acid, and oral antioxidants.

In a study sponsored by SkinMedica, investigators conducted a randomized, double-blind, half-face study in females with moderate to severe facial hyperpigmentation to assess the efficacy and tolerability of three new skin brightener formulations containing SMA-432, a prostaglandin E2 inhibitor, compared with topical 4% hydroquinone (J Drugs Dermatol. 2012;11[12]:1478-82). They found that the nonhydroquinone skin formulations were better tolerated and were just as effective as 4% hydroquinone.

In a separate unpublished study of 22 females, investigators assessed the efficacy of the U.SK Advanced Defense Booster, which contains ferulic acid, maslinic acid, peptides, and olive leaf extract. They observed that 98% of patients saw improvement after 28 days of treatment.

When it comes to using lasers for melasma treatment, low-energy devices provide the best outcomes. "I prefer using something like the 1927-nm fractional diode lasers at 3.75% density, really low densities because there's less risk for rebound," Dr. Ortiz said. "They also enhance skin permeability for the use of topicals."

In an observational study of 27 female patients with refractory melasma, Arielle Kauvar, MD, director of New York Laser & Skin Care, combined microdermabrasion with the Q-switched Nd:YAG (Lasers Surg Med. 2012;44:117-24). "The settings she used were very low fluence, so there was no clinical endpoint or no whitening," Dr. Ortiz said. Specifically, she used a laser at 1.6-2 J/cm2 with a 5- or 6-mm spot size immediately following microdermabrasion for 4 weeks. "She got a good improvement using a skin care regimen of sunscreen, hydroquinone, and tretinoin or vitamin C," she said. "Remission lasted at least 6 months."

In a study presented at the 2019 annual meeting of the America Society for Laser Medicine and Surgery, Dr. Ortiz and Tanya Greywal, MD, of the University of California, San Diego, used three passes of the 10764-nm Nd:YAG laser to treat 10 subjects with melasma skin types 2-5. The device has a 650-microsecond pulse duration, a 6-mm spot size, and an energy mode of 11-14 J/cm3. "There was no downtime with these patients, and they saw a mean improvement of 26%-50% as early as 3 weeks," she said. "Patients did require multiple treatments to see adequate resolution, but no anesthesia or numbing cream was required. This is a good option for patients who need chronic maintenance treatment."

Topicals also play a key role following the laser treatment of melasma. Dr. Ortiz characterized clobetasol as "kind of like the magic ointment." She uses one application immediately post procedure "whenever I'm worried about a patient having postinflammatory hyperpigmentation or if I don't want melasma patients to rebound. It can help reduce swelling and inflammation to decrease the risk of postinflammatory hyperpigmentation."

Researchers have discovered that there is a vascular component to melasma. Paul M. Friedman, MD, of the Dermatology and Laser Surgery Center, Houston, and his colleagues used spectrocolorimetry to detect an underlying prominent vascular component in 11 patients with melasma (Lasers Surg Med. 2017;49[1]:20-6). They determined that melasma lesions exhibiting subtle or subclinical telangiectatic erythema may be improved by combined vascular-targeted laser therapy together with fractional low-powered diode laser therapy. "A parallel improvement in telangiectatic erythema suggests a relationship between the underlying vasculature and hyperpigmentation," said Dr. Ortiz, who was not affiliated with the study. "So, patients who have a vascular component to their melasma actually can get improved efficacy."

Another strategy for melasma patients involves oral treatment with Polypodium leucotomos extract (PLE), a fern from the Polypodiaceae family with antioxidant properties that has been shown to be photoprotective against UVA and UVB radiation. "I like to think of it as an internal sunscreen," Dr. Ortiz said. "It does not replace your external sunscreen, but it adds extra protection. It has been shown to significantly reduce the severity of sunburn and decrease the risk of UV radiation–induced skin cancer, as well as prevent skin aging." The purported mechanism of action includes decreasing UV-mediated oxidative damage to DNA, enhancing the activity of endogenous antioxidant systems, increasing the minimal erythema dose, blocking UV radiation–induced cyclooxygenase-2 expression, reducing UV-induced immune suppression, and promoting p53 suppressor gene expression.

In a pilot placebo-controlled study of melasma patients on their normal regimen of hydroquinone and sunscreen, 40 Asian patients with melasma were randomized to receive either oral PLE supplementation or placebo for 12 weeks (J Clin Aesthet Dermatol. 2018;11[3]:14-9). They found that PLE significantly improved and accelerated the outcome reached with hydroquinone and sunscreen from the first month of treatment, compared with placebo.

Dr. Ortiz next discussed the role of oral tranexamic acid, an antifibrinolytic, procoagulant agent that is approved by the Food and Drug Administration for the treatment of menorrhagia and for prevention of hemorrhage in patients with hemophilia undergoing tooth extractions. "It is a synthetic lysine derivative that inhibits plasminogen activation by blocking lysine-binding sites on the plasminogen molecule, and it's a game changer for melasma treatment," she said. "One of the side effects is that it inhibits melanogenesis and neovascularization. It's been effective for melasma, but its use is limited by the risk for thromboembolism. It's a slight increased risk, something patients should be aware of, but not something that should scare us away from prescribing it."

In a study of 561 patients with melasma, 90% improved after a median treatment duration of 4 months, and only 7% had side effects (J Am Acad Dermatol. 2016;75:385-92). The most common side effects were abdominal bloating and pain. One patient developed a DVT during treatment, but that person was found to have a protein S deficiency.

The daily dosing of tranexamic acid for menorrhagia is 3,900 mg daily, while the dose for melasma has ranged from 500 mg-1,500 mg per day, Dr. Ortiz said. It's available as a 650-mg pill in the United States. "I prescribe 325 mg twice a day, but studies have shown that 650 mg once a day is just as effective," she said.

Prior to prescribing tranexamic acid, Dr. Ortiz does not order labs, but she performs an extensive history of present illness. She does not prescribe it in patients with an increased risk of clotting, including people who smoke and those who take oral contraceptives or are on hormone supplementation. Use is also contraindicated in people with a current malignancy, those with a history of stroke or DVT, and those who have any clotting disorder.

She concluded her presentation by noting that she favors a combination approach to treating melasma patients that starts with a broad spectrum sunscreen and PLE. "For bleaching, I like to use 12% hydroquinone with 6% kojic acid in VersaBase," she said. "Once I get them in better control, then I switch them to 4% hydroquinone for maintenance. I use glycolic peels, low-energy lasers, and tranexamic acid if the melasma is severe, and they have no contraindications. A combination approach really achieves the best results, and counseling is key."

Dr. Ortiz disclosed having financial relationships with numerous pharmaceutical and device companies. She is also co-chair of MOA.

Contact Doug Brunk at

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