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Background: Risk of photocarcinogenesis and the relevance of collagen in wrinkle effacement are two issues related to prolonged use of retinoic acid (RA) that have not been fully addressed., Objective: Our purpose was to investigate the degree of epidermal cellular atypia and the thickness of papillary dermal collagen in photoaging after long-term use of RA., Methods: Thirty-four subjects with photoaged skin were treated daily with 0.05% RA for at least 6 months. Epidermal cellular atypia was graded by means of a semiquantitative scale. Thickness of collagen band was measured by using image-analysis software., Results: Compared with pretreatment findings, melanocytic and keratinocytic atypia was significantly reduced and the collagen band thickness doubled., Limitations: This was an open-label study., Conclusion: Improvement in epidermal cellular atypia is consistent with the ability of RA to act as a chemopreventive agent in epithelial carcinogenesis. Prolonged use also significantly increased collagen matrix deposition in dermal repair zones, which most likely contributes to wrinkle effacement by RA.

Background: Tretinoin is often prescribed before laser resurfacing in an attempt to enhance results., Objective: We sought to assess the clinical and biochemical effects of preoperative tretinoin use before laser resurfacing., Methods: Patients were randomized to apply tretinoin to one forearm and placebo to the other for 3 weeks. Patients' photodamaged forearms were focally treated by carbon-dioxide laser resurfacing. Biopsy specimens were obtained at baseline and various times posttreatment. Real-time polymerase chain reaction technology was used to quantify messenger RNA levels of types I and III procollagen and matrix metalloproteinases-1, 3, and 9. Wounds were assessed for degree of re-epithelialization using a computer graphics-generated template. A colorimeter was used to quantify postoperative erythema., Results: No substantial differences in either biochemical markers or clinical end points were identified between tretinoin and placebo pretreated forearms., Conclusions: We found no evidence of enhanced collagen formation, accelerated re-epithelialization, or quicker resolution of postoperative erythema with tretinoin pretreatment before laser resurfacing.

Objective: To quantitatively examine changes in p53 tumor suppressor gene immunostaining after carbon dioxide (CO(2)) laser resurfacing of photodamaged skin to assess the potential value of this treatment in reducing the risk of progression to cutaneous carcinoma., Design: Serial in vivo immunohistochemical analyses after laser therapy., Setting: Academic referral center, Department of Dermatology, University of Michigan, Ann Arbor., Other Participants: Volunteer sample of 11 adults, 51 to 76 years old, with clinically evident photodamage of the forearms., Intervention: Focal CO(2) laser resurfacing of photodamaged forearms and serial biopsies at baseline, 3 weeks, and 6 months after treatment., Main Outcome Measures: Because keratinocytes with mutations in p53 or altered p53 expression stain via immunohistochemical techniques, image analysis of immunohistochemically stained sections was used to quantify p53 expression., Results: Positive immunostaining for p53 in the interfollicular epidermis was noted in 8 of 11 subjects at baseline, with an average staining density of 250 cells/mm(2). Average staining decreased to 3 cells/mm(2) 3 weeks after treatment. This decrease was sustained at 5 cells/mm(2) 6 months after resurfacing., Conclusions: There was a consistent decrease in p53 immunostaining in the interfollicular epidermis lasting for at least 6 moths after CO(2) laser resurfacing of photodamaged skin. Since p53 mutation or overexpression is observed in a majority of cases of cutaneous carcinoma, the posttreatment repopulation of the epidermis with p53-negative keratinocytes should theoretically decrease the risk of malignant progression. Further study of laser resurfacing as a prophylactic procedure in patients at high risk for skin cancer development appears warranted.

Focuses on a study which revealed that treating photoaged skin with topical tretinoin increase epidermal-dermal anchoring fibrils. Information on anchoring fibrils; Methodology; Results of the study.

A response by Christopher E.M. Griffiths and colleagues to a letter to the editor about their article "Restoration of Collagen Formation in Photodamaged Human Skin by Tretinoin (retinoic acid)," in the August 19, 1993 issue is presented

Although topical applications of retinoids on rodents and humans have been shown to cause epidermal hyperplasia, a detailed study of the influence of retinoids on epidermal differentiation in vivo has not been performed. In order to assess the pharmacologic effects of chronic topical tretinoin application used to improve the appearance of patients with photoaged skin, cutaneous biopsies from 25 patients in a controlled clinical study were examined histologically and immunocytochemically. Chronic application of tretinoin causes epidermal thickening (25 of 25 samples), stratum granulosum thickening (15 of 25), parakeratosis (13 of 25), a marked increase in the number of cell layers expressing epidermal transglutaminase (13 of 25), and focal expression of two keratins, K6 (12 of 25) and K13 (8 of 25), not normally expressed in the epidermis. The morphologic changes correlated with immunohistochemical abnormalities; neither of these correlated with the subjective cosmetic response. Three major epidermal differentiation products, keratins K1, K10, and K14 were not altered, within the limits of the methods used. Thus, chronic topical tretinoin reprograms some, but not all, aspects of human epidermal differentiation in vivo. [ABSTRACT FROM AUTHOR]

Background: and Methods Irregular disfiguring skin hyperpigmentation due to inflammation may develop in black persons. We investigated the treatment of this hyperpigmentation with topical tretinoin (0.1 percent retinoic acid cream). Fifty-four subjects completed a 40-week randomized, double-blind, vehicle-controlled study. Twenty-four subjects applied tretinoin daily to the face, arms, or both areas, and 30 subjects applied vehicle cream. At base line and after 40 weeks of treatment, each subject's postinflammatory hyperpigmented lesions and normal skin were assessed by clinical and colorimetric evaluations and by analysis of biopsy specimens. Results: The facial postinflammatory hyperpigmented lesions of the tretinoin-treated subjects were significantly lighter after the 40 weeks of therapy than those of the vehicle-treated subjects (P<0.001); overall improvement was first noted after 4 weeks of tretinoin treatment. At the end of treatment, colorimetry demonstrated a 40 percent lightening of the lesions toward normal skin color in the tretinoin-treated lesions, as compared with an 18 percent lightening in vehicle-treated lesions (P = 0.05). The epidermal melanin content in the lesions decreased by 23 percent with tretinoin and by 3 percent with vehicle (P = 0.24). Normal skin was minimally lightened by tretinoin as compared with vehicle, according to both clinical evaluation (0.1 vs. -0.1 unit change on an 8-point scale; P = 0.055) and colorimetry (P<0.001). Retinoid dermatitis developed in 12 of the 24 tretinoin-treated subjects who completed the study (50 percent) and in 1 tretinoin-treated subject who withdrew from the study, but diminished as the study progressed. Conclusions: Topical application of tretinoin significantly lightens postinflammatory hyperpigmentation; to a clinically minimal but statistically significant degree, it also lightens normal skin in black persons. (N Engl J Med 1993;328:1438-43.) [ABSTRACT FROM AUTHOR]