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For years, nothing rivaled hydroquinone for the treatment of melasma or other pigment disorders. While highly effective, hydroquinone is known to confer its fair share of side effects, including a risk for rebound hyperpigmentation.

“Hydroquinone was the standard of care for many years and safe to use for short periods under the care of a dermatologist,” says Jason Miller, MD, a dermatologist at Schweiger Dermatology Group in Freehold, NJ. There is a risk of ochronosis with prolonged use and controversy about the risk of cancer in laboratory animals, he adds.

“Hydroquinone remains the gold standard for pigment reduction but the CARES Act went into effect in September 2020 and has stopped sales of over-the-counter (OTC) hydroquinone, so this is no longer an (OTC) option,” says Hadley King, MD, a New York City-based dermatologist and clinical instructor of dermatology at Weill Medical College of Cornell University.

Recently a slew of hydroquinone alternatives have become available.

Kojic acid. Kojic acid is a non-hydroquinone agent that can help fade dark spots. “Kojic Acid is a chemical produced from some types of fungi,” says Dr. King. “It is used as a skin lightening ingredient for hyperpigmented skin conditions such as melasma and post-inflammatory hyperpigmentation.”

Kojic Acid works by blocking tyrosine from forming, which then prevents melanin production. Patients should avoid Kojic acid if they are allergic to penicillin.

Tranexamic acid. Studies have shown that tranexamic acid slows melanin synthesis by inhibiting the plasminogen/plasmin pathway, Dr. King explains. “Doing so blocks interactions between melanocytes and keratinocytes,” she says. “Consequently, using either oral or topical tranexamic acid can decrease melasma-associated skin pigmentation.”

Some risks are associated with oral use (i.e., blood clots) so close follow-up is important, Dr. Miller adds.

Niacinamide. Niacinamide may help reduce the appearance of age spots and other forms of skin discoloration, Dr. King says. “Niacinamide serves as a precursor to molecules in the body that are responsible for cell proliferation, the repair of cellular damage, and other biochemical necessities,” she explains. “Studies have shown that topical niacinamide can have stabilizing effects on the skin’s barrier function, which can help improve moisture retention and it is also a potent antioxidant that brightens skin by fading hyperpigmentation and reducing redness.”

Moreover, niacinamide increases the skin’s production of ceramides, which help strengthen the skin barrier, preventing loss of moisture. “It’s fine to combine with vitamin C to enhance antioxidant properties and ability to decrease discoloration,” says Dr. King.

Dr. King recommends Olay’s Vitamin C + Peptide 24 Brightening Serum, which contains vitamin C and peptides as well as niacinamide and lactic acid to brighten and hydrate skin. She also likes Mele Skincare’s Even Dark Spot
Control Serum. This serum is formulated for melanin-rich skin and contains pro-retinol to help reduce dark spots, as well as niacinamide, which helps to even skin tone and smooth skin texture. It also contains hexylresorcinol, which helps to brighten skin, as well as vitamin E.

Valerie Harvey, MD, MPH, FAAD, co-director for Hampton University Skin of Color Research Institute in Newport News, VA and President-elect of the Skin of Color Society, recommends SkinCeuticals Discoloration Defense, which contains 3% tranexamic acid, 1% kojic acid, and 5% niacinamide. “I alternate it with Prescription strength hydroquinone when patients are taking a break,” Dr. Harvey says.

Phytic Acid. Phytic acid is a plant-based antioxidant that can help to defend the skin against sun damage while brightening hyperpigmentation, Dr. King says. “It works as an exfoliator and blocks the synthesis of melanin in the epidermis.”

L-cysteamine. Hydroquinone-free Cyspera (L-cysteamine, Scientis) inhibits several steps in the melanogenesis pathway while also working as an antioxidant to protect against damaging free radicals. “It’s a nice alternative to hydroquinone and some studies show that it is just as effective as 4% hydroquinone, “ Dr. Harvey says. Recently launched Cyspera Intensive System is a new three-product system that improves hyperpigmentation.

Additional Considerations

Sunscreen is essential for improving and preventing recurrence/worsening of the dark spots. “Patients with melasma and pigment disorders need to wear sunscreen with an SPF of at least 30 that has protection against visible light as physical light can accentuate pigmentation issues including melasma,” says Dr. Harvey.

Patients should also be reminded that heat, inflammation, and even blue light may all contribute to dyschromias.

Additionally, energy-based devices continue to expand the potential to treat pigmentation, especially in patients with darker skin tones. Devices could be used to jump-start treatment or to address stubborn areas. For example, Aerolase Neo Elite (1064nm) delivers energy in microseconds, meaning that sufficient energy is delivered to destroy a target without delivering too much energy to surrounding tissues. Dermatologists report success with the laser for persistent pigmentation after acne, for brown spots, pigmentation, and solar lentigos.

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