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Something old, something new: Combine current, emerging therapies to treat pigmentary disorders


For treating difficult pigmentary disorders, an expert recommends combining the best of standard treatments with promising newer agents and modalities.

Los Angeles - Treating tough pigmentary disorders requires combining current therapies while keeping abreast of emerging therapies, including new sunscreens, resurfacing procedures and promising monotherapeutic bleaching agents and oral treatments, an expert says.

In treating difficult pigmentary disorders such as melasma and postinflammatory hyperpigmentation (PIH), "The wave of the future will involve combination therapies. We have multiple agents that impact different pathways," says Pearl E. Grimes, M.D., director, Vitiligo and Pigmentation Institute of Southern California, and clinical professor of dermatology, University of California, Los Angeles, David Geffen School of Medicine.

Therapeutic goals include stabilization, decreasing the contrast between hyperpigmented and normal skin and improving quality of life, she says.

In the latter area, Dr. Grimes says dermatologists must consider pigmentary disorders in light of the emotional and psychological devastation they can cause for patients.


Options that could help prevent pigmentary disorders include broad-spectrum sunscreen ingredients such as Mexoryl (ecamsule, L'Oreal), Tinosorb (CIBA) and Helioplex (Neutrogena), Dr. Grimes explains.

In one clinical test involving 185 pregnant women who used a broad-spectrum sunscreen containing Mexoryl, titanium dioxide, octocrylene and avobenzone, only five new melasma cases occurred, which study authors say was significantly lower than the expected frequency of more than 50 percent in the study population (Lakhdar H et al. J Euro Acad Dermatol Venereol. 2007 Jul;21(6):738-742.)

Combination bleaching agents include Tri-Luma (hydroquinone, tretinoin and fluocinolone, Galderma) and EpiQuin Micro (microentrapped hydroquinone and retinol, SkinMedica). Both products have shown efficacy in clinical trials, Dr. Grimes says.


As for the concern that long-term Tri-Luma use can cause epidermal atrophy, Dr. Grimes says a study she co-authored has shown no evidence of atrophy and only mild increases in the incidence of telangiectasia.

In the study, patients with melasma applied Tri-Luma Cream once daily for up to 24 weeks, with facial skin biopsies performed at baseline and weeks 12 and 24.

As for hydroquinone, Dr. Grimes says that it's backed by more than 50 years' clinical use and experience and, when properly used, remains the gold standard of treatment for pigmentary problems. "Its major side effect is limited to irritation," she says.

However, in 2006 the Food and Drug Administration (FDA) proposed banning over-the-counter (2 percent) hydroquinone and requiring prescription (4 percent) formulations to pass the new drug application process.

The agency's concerns include a possible risk of ochronosis, which Dr. Grimes says occurs more commonly with 2 percent formulations than with prescription formulations, and possible carcinogenicity. However, she says the FDA has put this proposal on the back burner.

Furthermore, she says, "No epidemiological studies to date have documented an increase in malignancies from topical use of hydroquinone."

Novel agents

Additional bleaching agents that have become part of the standard of care for pigmentary disorders include retinol, retinoic acid, kojic acid, ascorbic acid, licorice and azelaic acid, she says.

New and emerging monotherapeutic agents for treating pigmentary problems include tyrosinase inhibitors, such as rucinol; melanosome transfer inhibitors, such as niacinamide and resveratrol, which inhibits tyrosinase; and COX-2 and scavenges reactive oxygen species, Dr. Grimes says.

Resurfacing procedures

Among resurfacing procedures, newer options include nonablative lasers and intense pulsed-light (IPL) sources, as well as fractional laser resurfacing (Fraxel, Reliant Technologies), Dr. Grimes says.

"Resurfacing procedures are key in my practice,&334 she says. "We use them synergistically in combination with topical bleaching modalities."

However, she advises caution when using resurfacing modalities in darker-skinned patients.

Oral agents

Going forward, Dr. Grimes says, "We will be hearing more about oral agents for hyperpigmentation." These include pycnogenol and grape seed extract, which act as antioxidants and scavengers of reactive oxygen species.

Somewhat similarly, she says, tranexamic acid, a plasmin inhibitor that reduces tyrosinase activity, has grown popular in Asia, although it is associated with side effects including thrombosis.

Additionally, she says that Polypodium leucotomos, a photoprotective agent that provides immunomodulation, shows promise as a treatment for melasma and PIH. DT

Disclosures: Dr. Grimes has performed clinical research for Allergan, Altana, Astellas, Biogen, Galderma, Inamed, Mary Kate, SkinMedica and Stiefel. She also is a consultant for Combe and GammaCan.

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