Topical fluorouracil for actinic keratoses and photoaging: a clinical and molecular analysis.
OBJECTIVE
To examine clinical and molecular changes after topical fluorouracil treatment of photodamaged human facial skin for actinic keratoses.


METHODS
Nonrandomized, open-label 2-week treatment with fluorouracil cream, 5%, followed by clinical and molecular evaluation.


METHODS
Academic referral center.


METHODS
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.


METHODS
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.
Sachs
Dana L
DL
Department 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
Kang
Sewon
S
Hammerberg
Craig
C
Helfrich
Yolanda
Y
Karimipour
Darius
D
Orringer
Jeffrey
J
Johnson
Timothy
T
Hamilton
Ted A
TA
Fisher
Gary
G
Voorhees
John J
JJ
D000287:Administration, Topical; D000368:Aged; D000369:Aged, 80 and over; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D055623:Keratosis, Actinic / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010781:Photography; D011336:Probability; D011446:Prospective Studies; D012333:RNA, Messenger / Q000187:drug effects; D018570:Risk Assessment; D012720:Severity of Illness Index; D015595:Skin Aging / Q000187:drug effects*; D016896:Treatment Outcome
D012333:RNA, Messenger; D005472:Fluorouracil