Melasma

TREATMENT​

Overview (37748556)

Photoprotection

• Daily use of broad-spectrum sunscreen with UV and visible light protection, ideally containing iron oxide, is critical.

• Physical sun barriers (hats, sun avoidance) and consistent reapplication are essential.

• Gentle cleansers and moisturizers help maintain skin barrier function, improving tolerance to treatments.

First-line Therapy

• FDA-approved triple-combination cream (TCC) with 4% hydroquinone, 0.05% tretinoin, and 0.01% fluocinolone acetonide is the gold standard for 2–6 months. (although I personally don't think the lower concentration of 4% HQ tends to be effective, and don't like the prospect of steroid induced acne.)

• Combination therapies are more effective than monotherapy or dual therapy.

• Compounded formulations are used but carry variability in stability and safety, especially at >4% hydroquinone.

Other Topical Agents

• Azelaic acid, retinoids, corticosteroids, and botanical agents (kojic acid, cysteamine, licorice root, niacinamide, vitamin C) can be used in maintenance phases.

• Best used in rotation with TCC to reduce irritation and maintain results.

Oral Therapies

• Tranexamic acid (TA) (oral > intradermal > topical) can be effective, especially in vascular melasma, but requires patient screening for clotting risks.

• Polypodium leucotomos and antioxidants like melatonin or pycnogenol have some supportive data.

Procedures

• Chemical peels, microneedling, certain lasers, and light devices can help but must be used cautiously in darker skin tones to avoid post-inflammatory hyperpigmentation.  Recommended only for practitioners experienced in treating skin of color.

Maintenance & Relapse Prevention

• Cycle patients between active treatment (TCC) and maintenance (non-HQ agents, cosmeceuticals) every 3–6 months.

• Simple regimens (2–3 steps) improve adherence.

• Relapse is common; prompt return to active therapy may be needed.

Hydroquinone                                                                                                                                                                                                ​

Side Effects (thanks to Joseph Bettag for his contributions to this section)

Chronic adverse effects

• Include ​ochronosis, nail discolouration, conjunctival melanosis, and corneal degeneration.  Ochronosis occurs after chronic exposure and is uncommon.  Majority of cases occur at 2% hydroquinone concentrations. It occurs more commonly in Africa, possibly because of more frequent sunscreen use in the USA and the addition of resorcinol in many international preparations. 16898897

Carcinogenicity Concerns (thanks to Joseph Bettag for his contributions to this section)

• Main take home is that although mutagenciity/carcinogenicity has been observed in vitro, and tumorogenicity observed in rodents, it has not been shown to have any of these effects in humans in vivo, especially when used topically.  This is likely due to the small blood levels achieved with topical administration and also rapid metabolism that occurs in vivo into non-toxic byproducts.  38850450

• In 2006, the FDA proposed a ban citing concerns regarding carcinogenicity.  This was based on a study involving oral administration of hydroquinone inducing benign neoplasms in mice and rats (summarized here: 18027166).  Eventually, this resulted in hydroquinone being available only for prescription use.  There have been no reported cases of hydroquinone used topically causing cancer in humans despite being used for decades. (ASDS position)

  • In the rat and mice studies, the animals were fed up to 50mg/kg of hydroquinone 5 days per week for 2 years. 18027166  This would be the equivalent to a 70kg human eating a 30g tube of 12% hydroquinone 5 days per week for 2 years.​

• Despite these findings, there have been no reports of the in vivo induction of cancers.  There are two reports of humans ingesting 300-500mg daily for up to 5 months that failed to induce blood or renal damage.  Hydroquinone or arbutin, a derivative hydrolyzed to hydroquinone in an acidic environment, are found in foods and herbal products such as cranberries, blueberries, coffee, tea, rice, onions, wheat, pears, and bearberry leaf.  1 pear contains 620 micrograms of hydroquinone/arbutin.  At baseline, around 0.038 micrograms per ml may be detectable, essentially equivalent to the 0.04 micrograms per mL found after application of topical hydroquinone.  16898897 ​​​

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