Histologic Improvement in Photodamage After 12 Months of Treatment With Tretinoin Emollient Cream (0.02%)

September 2012 | Volume 11 | Issue 9 | Original Article | 1036 | Copyright © 2012

Abstract

Background and Objective: Topical retinoids, such as tretinoin, have been established as the gold standard for the treatment of photodamaged skin. This was a single-center, open-label, single-group, observational histologic subanalysis of 3 of 19 patients participating in a study of the efficacy and safety of tretinoin emollient cream 0.02% for the treatment of moderate to severe facial photodamage.
Methods: Subjects were female, 18 years of age or older, and instructed to apply tretinoin 0.02% to the treatment areas for 12 months. Histology was undertaken using facial photographs and 2-mm biopsies of the lateral canthus area that were obtained from 3 subjects at baseline and 12 months.
Results: Histopathologic analyses revealed evidence of extensive solar elastosis at baseline for 2 of the 3 subjects who were white, with moderate elastosis observed for the third subject who was African American. Histologic improvements in photodamage following 12 months of treatment with tretinoin 0.02% were observed for each subject. Improvements included smoothing of the epidermis, a slightly thinner keratin layer, and thin, comparatively straight elastic and collagen fibers in the mid- to deep-dermal layer.
Conclusions: The histologic changes in all subjects could be attributed to a remodeling (elastin) or repair (collagen) process that affected the connective tissue fibers in all layers of the dermis. These results suggest that tretinoin 0.02% may be an effective treatment for photodamage, and additional evaluation is warranted in future studies.

J Drugs Dermatol. 2012;11(9):1036-1040.

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INTRODUCTION

Excessive exposure to solar or other sources of ultraviolet (UV) radiation is a primary risk factor for dermatoheliosis (photodamage).1-4 UV exposure and other factors, such as fair skin, tobacco use, increased pack-years of smoking, and estrogen deficiency, cause histologic changes in the dermis including degradation of collagen, elastic fibers, and proteoglycans.5-7 In normal aging, morphologic changes in sun-protected skin include fine wrinkling and laxity, and histology shows general atrophy of the extracellular matrix, including reduced elastin and elastic fiber disintegration.3,8 With photoaging, histopathologic features include atypical epidermal cells, skin thinning and atrophy, degenerative changes in elastic tissue (elastosis), increased skin pigment production and glycosaminoglycans deposition, mild inflammatory infiltrate, loss of cellular polarity, and decreased collagen.1-5,9 The histologic "hallmark" of photodamage is a change in dermal elastosis, which primarily consists of thickened, tangled, and granular amorphous elastic structures.3 These features are attributed to UV-mediated damage to dermal fibroblasts that produce abnormal elastin.1-4,9,10

Topical agents, such as antioxidants and tretinoin, are effective interventions to improve the appearance of photodamaged skin.1 The gold standard among topical treatments for photodamage is topical retinoids, such as tretinoin.11 The US Food and Drug Administration approved tretinoin emollient cream (Renova® 0.02%, Ortho Dermatologics® Ortho-McNeil Pharmaceuticals Inc, Los Angeles, CA) as an adjunctive treatment for mitigation of fine wrinkles, mottled hyperpigmentation, and tactile roughness of facial skin for patients who use comprehensive skin care and sunlight avoidance.12 The efficacy and safety of tretinoin for the treatment of photodamaged skin has been established by a number of randomized, placebo-controlled trials conducted in the past 20 years.1,13-20

Histologic analyses (including granular layer and extracellular collagen-I staining) have shown improvements in UV-related skin damage with the use of topical tretinoin.17,21,22 Studies in patients with mild to moderate facial photodamage have reported increases in epidermal thickness and compaction of the stratum corneum after 24 weeks of treatment with tretinoin cream 0.05%.17,21 Histologic evaluation of biopsies from photodamaged forearm skin compared with those from nondamaged forearm skin in 26 healthy white patients revealed a 56% decrease in collagen-I formation in photodamaged skin.22 Following 10 to 12 months of treatment with tretinoin 0.1% or vehicle cream, an 80% increase in collagen-I formation was evident for these patients treated with tretinoin compared with a 14% decrease among patients treated with vehicle alone (P=.006).22 These favorable efficacy and safety results with topical tretinoin prompted the current investigation, conducted to evaluate histologic changes following 52 weeks of treatment with tretinoin emollient cream 0.02% for moderate to severe facial photodamage.

METHODS

This was a histologic subanalysis using 3 of 19 subjects who consented to skin biopsies, participating in a single-center, open-label, single-group observational study that evaluated the safety and efficacy of tretinoin emollient cream 0.02% for treating facial photodamage.23 The objective of this subanalysis was to determine

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