Innovative Approaches to Melasma Treatment in Skin of Color

As dermatologists, we recognize that melasma is a persistent and often challenging condition that can deeply affect our patients’ self-esteem, particularly in those with skin of color, who may face additional diagnostic and therapeutic complexities. Effectively managing this condition requires a nuanced approach, and we are fortunate to have experts like Dr. Seemal Desai, president of the AAD, founder and medical director of Innovative Dermatology (Plano, Texas), and assistant professor at the University of Texas Southwestern Medical Center, who is dedicated to improving treatments for pigmentary disorders. In his insightful lecture at the Skin of Color Update 2024, Dr. Desai shared a wealth of knowledge, providing valuable guidance on navigating the complexities of melasma management. He emphasized that melasma is a chronic, relapsing condition that requires long-term management and a polytherapy approach. Patients should be informed from the beginning that melasma is not curable, but it can be controlled and improved over time with consistent treatment. Setting realistic expectations early is key to successful management, as melasma treatment is often a prolonged journey, not a quick fix.

Key Treatment Modalities: Topical and Oral Therapies

Dr. Desai reviewed a wide array of treatment options, stressing that no single therapy is universally effective. Instead, a combination approach is essential. Below is a breakdown of the key therapies discussed:

Topical Treatments

• • Topical Retinoids & Combination Therapy: These are often used as a foundational part of treatment for melasma, particularly in combination with other agents to improve efficacy and reduce the likelihood of recurrence.
  • Azelaic Acid¹:
    • A dicarboxylic acid that selectively targets melanocytes by inhibiting tyrosinase and mitochondrial respiratory enzymes.
    • Azelaic acid is particularly useful in skin of color due to its safety profile, with only minimal side effects such as erythema, pruritus, and mild burning.
    • It can serve as an effective maintenance therapy after initial lightening treatments, supporting long-term control of the disease.
    • In a study involving 132 patients with facial melasma, 73% saw improvement after six months of therapy using 20% azelaic acid twice daily.¹
  • Hydroquinone (HQ):
    • HQ remains the gold standard for treating melasma, particularly during the induction phase of therapy.
    • While other non-HQ therapies are becoming more prominent, HQ will likely remain a key part of the therapeutic ladder for the foreseeable future.
    • Desai predicted a gradual decline in dependence on HQ as newer therapies gain traction, but he emphasized that HQ will still play an important role in combination treatments.
  • Chemical Peels, Cosmeceuticals, and Lasers:
    • These therapies are often used as adjunctive treatments to topical agents, particularly in patients who are resistant to first-line therapies.
    • Chemical peels and lasers can be used to induce skin lightening in a controlled and monitored manner, but these treatments should be handled with care in skin of color to avoid complications like post-inflammatory hyperpigmentation (PIH).
  • Reassurance and Time: Dr. Desai stressed the importance of counseling patients that melasma treatment takes time and that they should be patient and persistent with their regimen. The journey toward improvement can be long, but gradual results are often achievable with consistent care.

Oral Therapies: Several oral treatments have emerged as promising options for melasma, particularly for patients with skin of color who may require additional support beyond topical agents.

• • Oral Antioxidants:
    • Antioxidants such as green tea extracts, procyanidins, and oral zinc supplements can provide supportive treatment by reducing oxidative stress, which plays a role in melasma pathogenesis.
    • Polypodium leucotomos, in particular, has gained attention for its ability to protect against UV-induced pigmentation.² Desai recommended a dose of 240mg TID for 12 weeks, cautioning that many over-the-counter formulations (especially from Brazil) may not contain pure forms of the ingredient, leading to additional side effects. He advised patients to take Polypodium leucotomos one hour prior to sun exposure for optimal results.
  • Tranexamic Acid (TXA):
    • Although tranexamic acid is primarily used off-label in melasma, Dr. Desai highlighted its role in controlling pigmentation through its anti-inflammatory effects, which help inhibit the release of prostaglandins and other mediators involved in melanogenesis.³
    • TXA is particularly effective in patients who have failed other therapies, with oral dosing at 325mg BID for approximately 3 months. Dr. Desai stressed that if no improvement is seen within this period, continued use is not recommended in his opinion.
    • It is important to screen patients for hypercoagulability and other risk factors, such as smoking, deep vein thrombosis (DVT), and pregnancy, as these could increase the risks associated with TXA. In addition, patient counseling on the off-label use must be discussed along with other potential side effects, and thorough chart documentation is recommended.

Emerging Therapies

Dr. Desai introduced several new treatments that show promise for treating melasma, especially in skin of color:

• • Occidentalis: A potent anti-tyrosinase botanical extract, R. occidentalis has shown comparable efficacy to 4% hydroquinone in studies using a 3% cream.⁴ This makes it a potential alternative for patients seeking non-HQ therapies.
  • Methimazole: Originally a thyroid medication, methimazole has shown potential as a topical treatment for melasma due to its inhibition of peroxidase, which leads to changes in melanocyte morphology.⁵ A 5% methimazole solution applied BID can be effective without the need for monitoring thyroid function.
  • Malassezin: This is a naturally occurring indole produced by the skin microbiome’s Malassezia furfur. Early studies suggest that malassezin could have therapeutic effects in skin lightening and the treatment of melasma, as well as in conditions like post-inflammatory hyperpigmentation (PIH) in acne.⁶
  • Cysteamine: Cysteamine offers a physiologically based method of delivering antioxidant activity to the skin, targeting multiple melanogenesis pathways without causing permanent inhibition of tyrosinase. This makes it a safer option for long-term use.
  • Thiamidol: A novel human tyrosinase inhibitor, thiamidol is the first of its kind to be developed and has shown impressive results in reducing melasma pigmentation.7 It requires very low concentrations to be effective, and visible improvements can be seen within 12 weeks of use. Although it is not yet available in the U.S., its potential could revolutionize the treatment landscape for melasma.

The Role of Photoprotection and Prevention

Throughout his talk, Dr. Desai emphasized that photoprotection is the single most important part of managing melasma. Without adequate protection from ultraviolet (UV) light, no treatment regimen will be fully effective. He advised patients to use broad-spectrum sunscreen consistently and to combine sun protection measures with other treatments to optimize outcomes.

Extrafacial Melasma and Toxic Product Warnings

Dr. Desai reminded attendees that melasma is not just limited to the face. The bilateral dorsal forearms are the most common extra-facial site affected, and similar treatment protocols can be applied to these areas.

He also issued a strong caution about products available in other countries, particularly those sold online, which may contain toxic or even fatal ingredients. These products often lack regulatory oversight and should be avoided.

In summary, Dr. Desai’s presentation reinforced the need for a multimodal and individualized approach to melasma treatment, particularly in patients with skin of color. With the introduction of newer topical and oral agents, along with a focus on photoprotection and patient education, the treatment of melasma is evolving, offering more options and better outcomes. However, practitioners must remain vigilant about product safety and continually assess the best combinations of therapies for each patient. 

References

1. 1. Verallo-Rowell VM, Verallo V, Graupe K, Lopez-Villafuerte L, Garcia-Lopez M. Double-blind comparison of azelaic acid and hydroquinone in the treatment of melasma. Acta Derm Venereol Suppl (Stockh). 1989;143:58-61. doi:10.2340/000155551435861
   2. Ahmed AM, Lopez I, Perese F, et al. A randomized, double-blinded, placebo-controlled trial of oral Polypodium leucotomos extract as an adjunct to sunscreen in the treatment of melasma. JAMA Dermatol. 2013;149(8):981-983. doi:10.1001/jamadermatol.2013.4294
   3. Tse TW, Hui E. Tranexamic acid: an important adjuvant in the treatment of melasma. J Cosmet Dermatol. 2013;12(1):57-66. doi:10.1111/jocd.12026
   4. Mendoza CG, Singzon IA, Handog EB. A randomized, double-blind, placebo-controlled clinical trial on the efficacy and safety of 3% Rumex occidentalis cream versus 4% hydroquinone cream in the treatment of melasma among Filipinos. Int J Dermatol. 2014;53(11):1412-1416. doi:10.1111/ijd.12690
   5. Malek J, Chedraoui A, Nikolic D, Barouti N, Ghosn S, Abbas O. Successful treatment of hydroquinone-resistant melasma using topical methimazole. Dermatol Ther. 2013;26(1):69-72. doi:10.1111/j.1529-8019.2012.01540.x
   6. Grimes PE, Bhawan J, Howell MD, et al. A novel proof-of-concept study assessing the lightening effects and safety of malassezin for treatment of facial hyperpigmentation. J Am Acad Dermatol. 2022;87(2):456-458. doi:10.1016/j.jaad.2021.10.008
   7. Cordes P, Sun W, Wolber R, Kolbe L, Klebe G, Röhm KH. Expression in non-melanogenic systems and purification of soluble variants of human tyrosinase. Biol Chem. 2013;394(5):685-693. doi:10.1515/hsz-2012-0300

This information was presented by Dr. Seemal Desai during the 2024 Skin of Color Update conference. The above session highlights were written and compiled by Dr. Nidhi Shah.

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