151. Topical fluorouracil for actinic keratoses and photoaging: a clinical and molecular analysis.
- Author
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Sachs DL, Kang S, Hammerberg C, Helfrich Y, Karimipour D, Orringer J, Johnson T, Hamilton TA, Fisher G, and Voorhees JJ
- Subjects
- Administration, Topical, Aged, Aged, 80 and over, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Fluorouracil adverse effects, Follow-Up Studies, Humans, Keratosis, Actinic diagnosis, Male, Middle Aged, Photography, Probability, Prospective Studies, RNA, Messenger drug effects, Risk Assessment, Severity of Illness Index, Treatment Outcome, Fluorouracil therapeutic use, Keratosis, Actinic drug therapy, Skin Aging drug effects
- Abstract
Objective: To examine clinical and molecular changes after topical fluorouracil treatment of photodamaged human facial skin for actinic keratoses., Design: Nonrandomized, open-label 2-week treatment with fluorouracil cream, 5%, followed by clinical and molecular evaluation., Setting: Academic referral center., Patients: Twenty-one healthy volunteers, 56 to 85 years old, with actinic keratoses and photodamage. Interventions Twice-daily application of fluorouracil cream for 2 weeks and biopsies and clinical evaluation at baseline and periodically after treatment., Main Outcome Measures: Gene and protein expression of molecular effectors of epidermal injury, inflammation, and extracellular matrix remodeling 24 hours after fluorouracil treatment; clinical improvement measured by evaluators, photography, and patient questionnaires., Results: One day after the final fluorouracil treatment, gene expression of the effectors of epidermal injury (keratin 16), inflammation (interleukin 1beta), and extracellular matrix degradation (matrix metalloproteinases 1 and 3) was significantly increased. Types I and III procollagen messenger RNA were induced at week 4 (7-fold and 3-fold, respectively). Type I procollagen protein levels were increased 2-fold at week 24. Actinic keratoses and photoaging were statistically significantly improved. Most patients rated photoaging as improved and were willing to undergo the therapy again., Conclusions: Topical fluorouracil causes epidermal injury, which stimulates wound healing and dermal remodeling resulting in improved appearance. The mechanism of topical fluorouracil in photoaged skin follows a predictable wound healing pattern of events reminiscent of that seen with laser treatment of photoaging.
- Published
- 2009
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