Topical application of calcipotriol for preventive treatment of hypertrophic scars: a randomized, double-blind, placebo-controlled trial

Background.

The epidermis of hypertrophic scars shows histological abnormalities similar to psoriatic lesions. Calcipotriol is widely used for treatment of psoriasis.

Objectives.
To investigate the efficacy of topical application of calcipotriol in preventing hypertrophic scar formation.

Methods.
In a randomized, double-blind, placebo-controlled trial, 35 women were enrolled. The bilateral reduction mammoplasty wound healing model was used. Starting 10 days postoperative, scar-segments were either treated with calcipotriol or placebo, for the total duration of three months. At 3 weeks, 3 months and 12 months postoperative, the scar aspect was scored, its thickness was measured by ultrasound, and punch biopsies were collected for histological analysis.

Results.
After 3 and 12 months, no significant difference in prevalence of hypertrophic scars was observed between the placebo- and calcipotriol-treated scars. At 3 weeks postoperative, the calcipotriol-treated scars contained significantly more epidermal layers (p=0.017) and proliferating basal keratinocytes (p=0.029). None of the 3-week-old scars without activated keratinocytes became hypertrophic, whereas 48% of the 3-week-old scars that contained activated keratinocytes did (p=0.001). After three months, hypertrophic scars contained more epidermal layers than normotrophic scars (p=0.013).

Conclusions.
Topical application of calcipotriol during the first three months of wound healing did not affect the incidence of hypertrophic scar formation. Contrary to its effects in psoriatic lesions, calcipotriol treatment increased proliferation of keratinocytes and the number of epidermal layers. We observed a strong association between keratinocyte activation and hypertrophic scar formation. These findings contribute to the concept of both dermal and epidermal involvement in the aetiology of hypertrophic scar formation.

The epidermis of hypertrophic scars shows histological abnormalities that are similar to psoriatic lesions. Calcipotriol is widely used for treatment of psoriasis. We investigated the efficacy of topical application of calcipotriol in preventing hypertrophic scar formation.

Evaluations took place under standardized circumstances at 3 weeks, 3 months and 12 months following surgery and were performed by the same observer (IEW).

Ten days following surgery (after reepithelialization had been established), participants received a pair of ointment packages, marked ‘R’ and ‘L’, which were kindly provided by Leo Pharmaceutical Products (Ballerup, Denmark).
These were randomly filled with either calcipotriol 50 ìg/g (Daivonex® in vehicle) or placebo (vehicle only).

Both participant and observer were unaware of the content of the ointment packages. Participants were carefully instructed to apply the content of the package marked ‘R’ with the right hand on the left lateral (LL) and right medial (RM) scars. Accordingly, the content of the package marked ‘L’ had to be applied on the right lateral (RL) and left medial (LM) scars. The application frequency was twice daily, with a total duration of three months.
To verify our data, participants were questioned during the last evaluation about the way the ointment had been applied. This resulted in a minor adaptation of data in one case, as the ointment had been applied oppositely. Not until the final evaluation of the last participant, the key to the exact content of the packages was revealed and inserted into the data file.