Pigmentary Disorders

September 1, 2004

Albert Kligman, M.D., Ph.D., explores pigmentary disorders and develops enduring treatments

Q Please discuss the psychological implications of pigmentary disorders.

Although persons with pigmentary disorders are not physically ill, they suffer anxiety, embarrassment, and low self-esteem because of their cosmetically disfiguring condition. There are good data to show that persons with darker skin types, including Asians and blacks, are more distressed by pigmentary changes than they are by wrinkles, whereas the reverse is true in lighter-skinned populations.

The development of the triple formula consisting of 0.1 percent tretinoin, 5.0 percent hydroquinone, and 0.1 percent dexamethasone arose from systematic clinical research based on a number of unrelated observations. The ability of hydroquinone to produce depigmentation via inhibition of the conversion of tyrosine to dopa was well-described, but responses to monotherapy using hydroquinone in concentrations of 2 to 5 percent were disappointingly slow. Our goal was to see if a combination approach might enhance patient responses. We knew that corticosteroids caused loss of pigment, and the potential for tretinoin to produce skin lightening was also understood from my original research with its use in acne treatment. So, we tested various formula iterations created by modifying the concentrations of the components and omitting one of the three ingredients to find the final formula, which offered the best balance of efficacy and safety.

Q What are the other benefits of combining hydroquinone, a corticosteroid, and tretinoin?

Those three ingredients represent a very good synergistic triad. By thinning out the horny layer, tretinoin may facilitate the penetration of the other ingredients in the formula and thereby enhance their depigmenting efficacy. Tretinoin also causes epidermal hyperplasia and offsets the atrophogenic effect of the steroid, while the anti-inflammatory effect of the corticosteroid is valuable for minimizing retinoid-induced irritation.

Q What is the pathogenesis of post-inflammatory hyperpigmentation, melasma, and solar lentigines?

There are a large number of factors that can cause hyperpigmentary changes in the skin, and for dark-skinned people, inflammation is an important trigger. In my recent research, I have found that the keratinocytes in darker skin types are relatively more fragile than in lighter skin and are more prone to rupture with any inflammatory insult. In addition, their basal membrane extends down into the dermis, and so the ruptured keratinocytes dump their melanin granules into the dermis. Melanin sits in the dermis for a long time because it is not recognized as a foreign material, and the resulting persistent hyperpigmentation is very distressing to dark-skinned people. Melasma is usually an epidermal process. It develops with UV exposure, but it also appears to have a genetic basis and has been associated with other factors, including hormones and exposure to heat.

As its name denotes, a solar lentigo is a "photo" dermatitis. Solar lentigines are epidermal lesions that develop predominantly in persons with lighter skin as a result of excessive sun exposure.

Q What is your current regimen for treating a patient with epidermal melasma, and how long would you expect it to take to achieve clearing?

Effective treatment of melasma requires use of a prescription agent containing 4 percent hydroquinone. The best responses are achieved using a combination approach, with either one of a variety of commercially available agents incorporating hydroquinone with other ingredients to enhance its efficacy and/or adjunctive therapies.