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A Clinical and Molecular Analysis

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

Arch Dermatol. 2009;145(6):659-666.

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.

Author Affiliations: Department of Dermatology (Drs Sachs, Hammerberg, Helfrich, Karimipour, Orringer, Johnson, Fisher, and Voorhees) and Office of Human Research Compliance Review (Mr Hamilton), University of Michigan, Ann Arbor; and Department of Dermatology, The Johns Hopkins University, Baltimore, Maryland (Dr Kang).

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