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Does Systemic Isotretinoin Inhibit Wound Healing in a Porcine Model?
Purpose: Controversy exists regarding the effect of systemic isotretinoin (Accutane®) on wound healing. Traditional practice is to wait a minimum of 6-12 months after completion of systemic isotretinoin therapy before an invasive procedure. Review of the literature on this subject shows only anecdotal patient reports and conflicting research using inappropriate animal models (dog, rat, guinea pig, and rabbit). To date, there is no conclusive evidence demonstrating a correlation between systemic isotretinoin and inhibition of wound healing. Therefore, we investigated the healing of both partial and full thickness wounds in a porcine model after treatment with systemic isotretinoin.
Methods: Following IRB approval, two mature sibling Hanford Miniature pigs were obtained. One pig received 60 days of therapy with isotretinoin at a dose of 2 mg/kg/day; the other received only pig feed and no drug. Four days after completion of therapy, each animal was anesthetized and a grid of twenty-four 2 cm x 2 cm squares was marked on the right and left flank. On the left side of each pig, a 1.7 cm diameter, 5 mm deep punch biopsy was performed in each square. On the right side of each pig, partial thickness wounds of 1.7 cm x 1.7 cm were created in each square using a 1.6% croton oil-phenol peel. A total of 24 full thickness wounds and 24 partial thickness wounds were created on each pig. The wounds were examined, photographed, and biopsied on postoperative days 14 and 28. Wound sizes were evaluated by loading a standardized photo of each wound into MetaVue® software. The area of each wound was measured by the number of pixels/square cm. Histological analysis of the wounds was also performed.
Results: Objectively, there appeared to be no difference in wound size in the same area of the respective flanks of each pig at 14 days; similar healing was also observed at 28 days. The average full-thickness wound size in the control at 14 days was 0.435 cm² and 0.069 cm² at 28 days. The average full-thickness wound size in the isotretinoin group at 14 days was 0.469 cm² and 0.036 cm² at 28 days.
The croton oil-phenol peel results did not lend themselves to statistical analysis, but were documented by photo. Subjectively, the peel wounds of both pigs healed equally at 14 and 28 days. There was no evidence of unusual scarring or pigmentation in either animal.
Conclusions: There appears to be no statistical or observational difference between the wound healing rate of a pig treated with isotretinoin and that of a control pig. The clinical application of this data would suggest that invasive surgery might be safely performed in the presence of recent isotretinoin therapy. This finding challenges the current practice of waiting greater than six months after completing therapy to perform surgery.

No difference in mean wound size for control and isoretinoin pigs treated at 2 weeks and 4 weeks.

	2 weeks			4 weeks
	Mean (sq cm)	StdDev	p value*	Mean (sq cm)	StdDev	p value*
Control (n=24)	0.4346	0.0816	0.21	0.06989	0.0866	0.12
Isotretinoin (n=24)	0.4685	0.10133	0.21	0.0363	0.0493	o.12
*two sample T test