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San Francisco - Understanding the process by which topical retinoids trip cellular receptors and cause retinoid signaling can explain many effects seen in patients, and may help in improving the atrophic skin in the geriatric population, says Sewon Kang, M.D., professor of dermatology, University of Michigan, Ann Arbor, Mich., who spoke Friday at the 67th Annual Meeting of the American Academy of Dermatology here.
- Understanding the process by which topical retinoids trip cellular receptors and cause retinoid signaling can explain many effects seen in patients, and may help in improving the atrophic skin in the geriatric population, says Sewon Kang, M.D., professor of dermatology, University of Michigan, Ann Arbor, Mich., who spoke Friday at the 67th Annual Meeting of the American Academy of Dermatology here.
Dr. Kang discussed the mechanism of action of topical retinoids, the side effect of retinoid dermatitis and issues in retinol pharmacology.He noted the current definition of a retinoid is "any molecule that, by itself or through metabolic conversion, binds to and activates the retinoic acid receptors, thereby eliciting transcriptional activation of retinoic acid-responsive genes that results in specific biologic responses (Kang & Voorhees. Fitzpatrick's Dermatology in General Medicine [7th Ed.]. 2008)."
The discovery of retinoic acid receptors in the late 1980s and 1990 "allowed people to link structure and function," Dr. Kang said, and led to a broadening of earlier understanding.
Vitamin A enters a cell and can be esterified and stored, or can be sequentially oxidized to all-trans retinoic acid, Dr. Kang explained. "The business end of all-trans retinoic acid really happens in the nucleus," where receptors are located, he said.
Nuclear retinoid receptors mediate the actions of retinoids. In normal human adult skin, 84 percent of the receptors are retinoid-X receptors, of which 90 percent are retinoid-X alpha receptors, while 16 percent are retinoic acid receptors, of which nearly 90 percent are retinoic acid gamma receptors, Dr. Kang said.
"It is the pairing that drives retinoid pharmacology in our skin," he said.
Peeling of the skin after use of topical retinoids appears to be a receptor-mediated event, Dr. Kang said. A comparison of the buttocks skin of patients randomized to use a vehicle cream, .025 percent retinoic acid or 1.6 percent retinol, occluded for three or four days, showed patients treated with retinoic acid showed erythema.
A biopsy would show that the epidermis was at least twofold thicker, compared to the vehicle-treated site, he said.
"Keratinocytes are divided faster in retinoid-treated skin," he said.
Skin samples from patients treated with retinoic acid 0.1 percent for four months showed hyperplasia of the epidermis and compaction of the stratum corneum, he said.
Epidermal peeling associated with topical retinoid use may be linked to epidermal hyperplasia and appears similar to the scale seen in psoriasis, Dr. Kang said.
Topical retinol elicits a retinoic acid-like epidermal histology (hyperplasia and spongiosis), but, unlike retinoic acid, it doesn’t cause significant erythema, he said.
Topical retinol use also can increase collagen synthesis in the naturally aged skin of patients 80 years old or older, Dr. Kang said.
The skin of geriatric patients makes less collagen and breaks down collagen more rapidly than does the skin of younger patients, he noted. A left-right arm comparison study of patients 80 years of age or older showed that 24 weeks of treatment with 1 percent retinol stimulated fibroblasts to make more collagen and also reduced collagen breakdown (Varani, Kang, Chung, Fisher, Voorhees. J Invest Dermatol. 2000;114:480-486). DT