Background: Long-term (>1 year) placebo-controlled studies of tretinoin in the treatment of photodamaged skin have not been conducted. Recently, we conducted a 2-year placebo-controlled study of tretinoin emollient cream 0.05%, including histopathologic assessment of safety and analysis of markers of collagen deposition.
Objective: The objective of the study was to determine the long-term safety and efficacy of tretinoin emollient cream 0.05% in the treatment of moderate to severe facial photodamage.
Methods: A total of 204 subjects were treated with tretinoin or placebo (vehicle emollient cream) applied to the entire face once a day for up to 2 years. Clinical and histologic effects were assessed at regularly scheduled clinic visits.
Results: Treatment with tretinoin resulted in significantly greater improvement relative to placebo in clinical signs of photodamage (fine and coarse wrinkling, mottled hyperpigmentation, lentigines, and sallowness), overall photodamage severity, and investigator’s global assessment of clinical response (p < 0.05). Histologic evaluation showed no increase in keratinocytic or melanocytic atypia, dermal elastosis, or untoward effects on stratum corneum following treatment with tretinoin compared with placebo. Immunohistochemistry studies, conducted at three study centers, showed a significant increase relative to placebo in facial procollagen 1C terminal, a marker for procollagen synthesis, at month 12 (p = 0.0074).
Conclusion: Long-term treatment with tretinoin emollient cream 0.05% is safe and effective in subjects with moderate to severe facial photodamage.
Chen VL, Fleischmajer R, Schwartz E, et al. Immunochemistry of elastotic material in sun-damaged skin. J Invest Dermatol. 1986; 87: 334–7PubMedCrossRefGoogle Scholar
Mera SL, Lovell CR, Jones RR, et al. Elastic fibres in normal and sun-damaged skin: an immunohistochemical study. Br J Dermatol. 1987; 117: 21–7PubMedCrossRefGoogle Scholar
Schwartz E, Cruickshank FA, Christensen CC, et al. Collagen alterations in chronically sun-damaged human skin. Photochem Photobiol. 1993; 8: 841–4CrossRefGoogle Scholar
Bernstein EF, Chen YQ, Kopp JB, et al. Long-term sun exposure alters the collagen of the papillary dermis: comparison of sun-protected and photoaged skin by northern analysis, immunohistochemical staining, and confocal laser scanning microscopy. J Am Acad Dermatol. 1996; 34: 209–18PubMedCrossRefGoogle Scholar
Bhawan J, Palko M, Lee J, et al. Reversible histologic effects of tretinoin on photodamaged skin. J Geriatr Dermatol. 1995; 3: 62–7Google Scholar
Bhawan J, Olsen E, Lufrano L, et al. Histologic evaluation of the long term effects of tretinoin on photodamaged skin. J Dermatol Sci. 1996; 11: 177–82PubMedCrossRefGoogle Scholar
Chen S, Kiss I, Tramposch KM. Effects of all-trans retinoic acid on UVB-irradiated and non-irradiated hairless mouse skin. J Invest Dermatol. 1992; 98: 248–54PubMedCrossRefGoogle Scholar
Griffiths CEM, Russman AN, Mjmudar G, et al. Restoration of collagen formation in photodamaged human skin by tretinoin (retinoic acid). N Engl J Med. 1993; 329: 530–5PubMedCrossRefGoogle Scholar
Fisher GJ, Wang ZQ, Datta SC, et al. Pathophysiology of premature skin aging induced by ultraviolet light. N Engl J Med. 1997; 337: 1419–28PubMedCrossRefGoogle Scholar
Talwar HS, Griffiths CE, Fisher GJ, et al. Reduced type I and type III procollagens in photodamaged adult human skin. J Invest Dermatol. 1995; 105: 285–90PubMedCrossRefGoogle Scholar
Varani J, Spearman D, Perone P, et al. Inhibition of type I procollagen synthesis by damaged collagen in photoaged skin and by collagenase-degraded collagen in vitro. Am J Pathol. 2001; 158: 931–42PubMedCrossRefGoogle Scholar
Cho S, Lowe L, Hamilton TA, et al. Long term treatment of photoaged human skin with topical retinoic acid improves epidermal cell atypia and thickens the collagen band in papillary dermis. J Am Acad Dermatol. In pressGoogle Scholar