Topical fluorouracil for actinic keratoses and photoaging: A clinical and molecular analysis

Dana L. Sachs, Sewon Kang, Craig Hammerberg, Yolanda Helfrich, Darius Karimipour, Jeffrey Orringer, Timothy Johnson, Ted A. Hamilton, Gary Fisher, John J. Voorhees

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


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 1β), 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.

Original languageEnglish (US)
Pages (from-to)659-666
Number of pages8
JournalArchives of Dermatology
Issue number6
StatePublished - Jun 2009

ASJC Scopus subject areas

  • Dermatology


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