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Hydroquinone alternatives attack hyperpigmentation


Cosmeceutical researchers are discovering new mechanisms to attack excess pigmentation, according to several physicians who spoke at the 2010 Cosmetic Surgery Forum in Las Vegas in December.

Key Points

Such alternatives assume increasing importance in light of the Food and Drug Administration's proposal to ban hydroquinone from over-the-counter products - a ban that one dermatologist views as inevitable.

Overall, "We have plenty of alternatives for hydroquinone, should the FDA ever make up its mind to ban it in over-the-counter products - and they might," says Vivian W. Bucay, M.D., clinical assistant professor of dermatology, University of Texas Health Science Center, San Antonio. The FDA's 2006 attempt to do this drew significant protests from dermatologists and patients, she says. Although the issue remains stalled, "I believe it's going to happen sooner or later. That's why these alternatives are becoming so important."

Pigment production requires 14 steps, Dr. Bucay says. "And presently, no topical agent affects more than two of those steps. To date, everything that's been available to treat hyperpigmentation has been aimed at either preventing the production of melanin - as hydroquinone does by inhibiting tyrosinase, the enzyme necessary for melanin production - or at accelerating cell renewal, such as peels for removing superficial skin layers."

But a new topical agent already available in Asia called elure (lignin peroxidase, Syneron) could change the game, she says.

"Lignin peroxidase is an enzyme that breaks down lignin in decaying tree bark; lignin gives tree bark its color. Lignin is also similar in composition to melanin. So lignin peroxidase is able to break down existing melanin," she says. "It acts on existing pigment, rather than trying to prevent formation of new pigment." But because lignin does not prevent pigment formation, she says ultimately it won't eliminate the need for hydroquinone or another product that inhibits melanin production.

Nevertheless, in the future, "We will have a more powerful combination," she says. Existing products can prevent production of more pigment, but this process takes several weeks, thereby testing patients' patience. "By having something like lignin peroxidase, we will be able to break down existing pigment. Rather than having to wait six weeks, patients could see results in 10 to 14 days. This advance will unleash a whole new set of compounds that we haven't had before," Dr. Bucay says.

At press time, Syneron was planning to launch the product in the United States in early 2011, says Thomas Albright, president and general manager, topical aesthetics division, Syneron. Dr. Bucay says the product "will not be a prescription product, but for now it will only be available in physicians' offices. That's important - a physician can help assess what a person's exact pigment problem is. This way, people aren't just using products without knowing what they're treating."

The product causes no irritation or allergic reactions, says Dr. Bucay, who has used elure to treat 20 patients of various races who had failed other treatments for hyperpigmentation, including hydroquinone, topical antioxidants, sunblock, tretinoin and azelaic acid. "Elure also works very well on age spots," she says.

Existing options

Along with hydroquinone, other tyrosinase inhibitors include azelaic acid, arbutin, licorice extract, tretinoin, corticosteroids and kojic acid, Dr. Bucay says. However, "Kojic acid can be a contact sensitizer. At higher concentrations that may be needed for efficacy, it can induce contact dermatitis, which could result in increased pigmentation afterwards."

Additional peeling agents include retinoids such as tretinoin, adapalene and tazarotene, plus glycolic acid, salicylic acid and trichloroacetic acid, Dr. Bucay says.

Topical vitamin C also helps to lighten skin because it's an anti-inflammatory agent and an antioxidant, she says.

"Free radicals can also induce pigment production. Therefore, using an antioxidant is an important part of treating hyperpigmentation, whether it's melasma or postinflammatory hyperpigmentation."

Other antioxidants useful for this purpose include green tea and niacinamide. The latter decreases the transfer of melanosomes from the melanocyte to the keratinocyte, Dr. Bucay says.

"Niacinamide is found in over-the-counter products such as the Olay Definity line (Procter & Gamble)," she says. It's also available in EltaMD UV Clear SPF 46 sunscreen (Swiss American Products).

Somewhat similarly, Dr. Bucay says soy inhibits the cell receptors that mediate the transfer of melanosomes from melanocytes to keratinocytes. "N-acetylglucosamine (NAG) inhibits glycosylation of tyrosinase, so NAG also can lighten the skin," she says.

To treat dyschromia, Dr. Bucay says she typically recommends the following regimen:

Disclosures: Dr. Bucay is a consultant or investigator for Medicis, Allergan, Novartis, Johnson & Johnson, Aveeno, Elemé Medical, Ferndale/Biopelle, Galderma, Azure/HydroPeptide, BioForm/Merz Aesthetics and Syneron.

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