Study Confirms Photoaging Repair With Topical 5-FU

MONTREAL — Topical 5-fluorouracil used for the treatment of actinic keratosis can also promote dermal remodeling in photoaged skin, according to a small study.

For years, clinicians and patients have noted that, in addition to treating actinic keratosis (AK), topical 5-fluorouracil (5-FU) treatment can result in skin softening and smoothing, Dr. Sewon Kang of Johns Hopkins University, Baltimore, said at the annual meeting of the Society for Investigative Dermatology.

"We knew this anecdotally, but it had never been documented or studied at a molecular level," he said in an interview. "We did this study to confirm people's clinical observation that this happens, and added a few lab measurements to support how it might be happening."

The nonrandomized, non-vehicle-controlled study was funded by Valeant Pharmaceuticals, and Dr. Kang did not disclose any conflicts of interest.

The study included 21 subjects, aged 56–85 years, who received 5% topical 5-FU cream twice daily for 2 weeks for the treatment of facial AK. In addition to AK lesions, all patients had moderate to severe photodamage.

The subjects underwent a baseline clinical skin examination, which was repeated 1 day after the last treatment application and again at 4, 10, and 24 weeks post treatment.

Photographic evaluation was performed, and photoaging parameters were assessed according to a photonumeric scale that included wrinkling, roughness, lentigines, hyperpigmentation, and sallowness. Biopsies were also taken at the same time points.

At the end of the study, the number of AKs was reduced from almost 12 to less than 2 per patient. In addition, photoaging scores dropped from slightly less than 5.5 to about 4.6, he reported.

Biopsies were used to examine the molecular end points of epidermal injury, inflammation, dermal matrix degradation, and collagen, Dr. Kang said.

"Epidermal injury causes an inflammatory reaction in the skin, which triggers collagen repair, and we believe this is the mechanism by which topical 5-FU might improve wrinkles," he explained at the meeting.

Biopsies taken at the end of the study showed a seven-fold increase from baseline in keratin 16, a marker of epidermal injury, and a two-fold increase in inflammatory cytokine expression. Additionally, there was a statistically significant increase in the induction of collagenase (MMP-1) and stromelysin (MMP-3), markers of dermal matrix degradation, he said.

Finally, procollagen protein levels increased significantly from baseline, indicating collagen repair.

"Topical 5-FU induces epidermal wounding by a mechanism similar to microdermabrasion and certain lasers used for the treatment of photoaging. Agents that produce irritation could improve photoaging," Dr. Kang concluded.

MONTREAL — Topical 5-fluorouracil used for the treatment of actinic keratosis can also promote dermal remodeling in photoaged skin, according to a small study.

For years, clinicians and patients have noted that, in addition to treating actinic keratosis (AK), topical 5-fluorouracil (5-FU) treatment can result in skin softening and smoothing, Dr. Sewon Kang of Johns Hopkins University, Baltimore, said at the annual meeting of the Society for Investigative Dermatology.

"We knew this anecdotally, but it had never been documented or studied at a molecular level," he said in an interview. "We did this study to confirm people's clinical observation that this happens, and added a few lab measurements to support how it might be happening."

The nonrandomized, non-vehicle-controlled study was funded by Valeant Pharmaceuticals, and Dr. Kang did not disclose any conflicts of interest.

The study included 21 subjects, aged 56–85 years, who received 5% topical 5-FU cream twice daily for 2 weeks for the treatment of facial AK. In addition to AK lesions, all patients had moderate to severe photodamage.

The subjects underwent a baseline clinical skin examination, which was repeated 1 day after the last treatment application and again at 4, 10, and 24 weeks post treatment.

Photographic evaluation was performed, and photoaging parameters were assessed according to a photonumeric scale that included wrinkling, roughness, lentigines, hyperpigmentation, and sallowness. Biopsies were also taken at the same time points.

At the end of the study, the number of AKs was reduced from almost 12 to less than 2 per patient. In addition, photoaging scores dropped from slightly less than 5.5 to about 4.6, he reported.

Biopsies were used to examine the molecular end points of epidermal injury, inflammation, dermal matrix degradation, and collagen, Dr. Kang said.

"Epidermal injury causes an inflammatory reaction in the skin, which triggers collagen repair, and we believe this is the mechanism by which topical 5-FU might improve wrinkles," he explained at the meeting.

Biopsies taken at the end of the study showed a seven-fold increase from baseline in keratin 16, a marker of epidermal injury, and a two-fold increase in inflammatory cytokine expression. Additionally, there was a statistically significant increase in the induction of collagenase (MMP-1) and stromelysin (MMP-3), markers of dermal matrix degradation, he said.

Finally, procollagen protein levels increased significantly from baseline, indicating collagen repair.

"Topical 5-FU induces epidermal wounding by a mechanism similar to microdermabrasion and certain lasers used for the treatment of photoaging. Agents that produce irritation could improve photoaging," Dr. Kang concluded.

MONTREAL — Topical 5-fluorouracil used for the treatment of actinic keratosis can also promote dermal remodeling in photoaged skin, according to a small study.

For years, clinicians and patients have noted that, in addition to treating actinic keratosis (AK), topical 5-fluorouracil (5-FU) treatment can result in skin softening and smoothing, Dr. Sewon Kang of Johns Hopkins University, Baltimore, said at the annual meeting of the Society for Investigative Dermatology.

"We knew this anecdotally, but it had never been documented or studied at a molecular level," he said in an interview. "We did this study to confirm people's clinical observation that this happens, and added a few lab measurements to support how it might be happening."

The nonrandomized, non-vehicle-controlled study was funded by Valeant Pharmaceuticals, and Dr. Kang did not disclose any conflicts of interest.

The study included 21 subjects, aged 56–85 years, who received 5% topical 5-FU cream twice daily for 2 weeks for the treatment of facial AK. In addition to AK lesions, all patients had moderate to severe photodamage.

The subjects underwent a baseline clinical skin examination, which was repeated 1 day after the last treatment application and again at 4, 10, and 24 weeks post treatment.

Photographic evaluation was performed, and photoaging parameters were assessed according to a photonumeric scale that included wrinkling, roughness, lentigines, hyperpigmentation, and sallowness. Biopsies were also taken at the same time points.

At the end of the study, the number of AKs was reduced from almost 12 to less than 2 per patient. In addition, photoaging scores dropped from slightly less than 5.5 to about 4.6, he reported.

Biopsies were used to examine the molecular end points of epidermal injury, inflammation, dermal matrix degradation, and collagen, Dr. Kang said.

"Epidermal injury causes an inflammatory reaction in the skin, which triggers collagen repair, and we believe this is the mechanism by which topical 5-FU might improve wrinkles," he explained at the meeting.

Biopsies taken at the end of the study showed a seven-fold increase from baseline in keratin 16, a marker of epidermal injury, and a two-fold increase in inflammatory cytokine expression. Additionally, there was a statistically significant increase in the induction of collagenase (MMP-1) and stromelysin (MMP-3), markers of dermal matrix degradation, he said.

Finally, procollagen protein levels increased significantly from baseline, indicating collagen repair.

"Topical 5-FU induces epidermal wounding by a mechanism similar to microdermabrasion and certain lasers used for the treatment of photoaging. Agents that produce irritation could improve photoaging," Dr. Kang concluded.