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Arch Dermatol. 2009 Jun;145(6):659-66. doi: 10.1001/archdermatol.2009.97.

Topical fluorouracil for actinic keratoses and photoaging: a clinical and molecular analysis.

Author information

  • 1Department of Dermatology, 1910 Taubman Center, University of Michigan Medical School, 1500 E Medical Center Dr, Ann Arbor, MI 48109-5314, USA. dsachs@med.umich.edu

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.

[PubMed - indexed for MEDLINE]
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