Should Isotretinoin be Stopped Prior to Surgery?

Oral isotretinoin, otherwise known as Accutane, is frequently prescribed for the management of acne vulgaris and has been shown to be an effective option for patients. However, it has been suggested that isotretinoin may result in atypical wound healing, with increased keloid formation and hypertrophic scars.1 This has been theorized due to isotretinoin's effects on skin thinning and inhibition of sebaceous glands, resulting in skin dryness and deeper injury to the dermis, as epidermal cell sprouting from sebaceous glands contributes to split-thickness skin healing.1 Therefore, several prior studies have recommended discontinuing isotretinoin up to 6 to 24 months prior to surgical intervention.1, 2 However, this practice remains controversial as several studies have reported no increased risk of side effects of the skin in patients using isotretinoin, and recent literature has suggested no increased incidence of facial scarring after surgery. The purpose of this summary is to review the existing evidence on whether isotretinoin should be stopped prior to surgical management (Table I). A 2016 review by Ungarelli et al. identified 47 studies focusing both on the skin changes associated with isotretinoin use, as well as its effects on muscle, bone, and cartilage.1 This study ultimately concluded that there was insufficient evidence to determine whether or not isotretinoin has an impact on wound healing. The 10 experimental studies included used animal models and appeared to show no increased incidence of atypical wound healing except at higher doses of isotretinoin use (10 mg/kg/day), with the caveat that animal studies may not adequately model hypertrophic scarring and keloid formation. In comparison, a standard clinical isotretinoin dosing regimen is 0.5 to 1 mg/kg/day.1 Furthermore, the 27 studies involving human subjects primarily comprised case reports and case series, limiting the level of evidence. The included studies also did not show any adverse changes to cartilage or bone healing, but did find that isotretinoin may cause myalgias, creatinine phosphokinase elevations, and, rarely, rhabdomyolysis. A more recent systemic review by Spring et al. included 32 publications of the effect of retinoids on outcomes of cutaneous procedures including dermabrasion, chemical peels, cutaneous surgery, and laser surgery.3 Of the 10 studies that investigated isotretinoin's effects on cutaneous surgery, one case report identified skin thinning and a nasal tip deformity following rhinoplasty. In contrast, the other studies reported normal healing and no evidence of any significant differences in the incidence of scarring or development of granulation tissue. The authors subsequently concluded that there was insufficient evidence to withhold or delay cutaneous surgery due to isotretinoin use, and that the current practice of withholding isotretinoin prior to procedures could unnecessarily delay the treatment of acne vulgaris. One of the studies included in this review was a prospective trial by Hernandez-Perez et al. in which 60 patients were randomized to 10 to 20 mg oral isotretinoin therapy thrice weekly for a 2-month period prior to completion of surgical procedures including blepharoplasty in 12 patients, liposuction in 9 patients, fat transfer in 9 patients, and facelift in 9 patients.4 Outcomes of skin appearance, which were evaluated by medical observers and the patient, were compared to control subjects who did not receive isotretinoin prior to comparable surgical procedures. Patients taking isotretinoin were found to have significantly more elasticity in skin appearance as well as a higher degree of patient satisfaction compared to controls. Furthermore, there were no reported wound healing complications, though skin dryness was appreciated in less than 10% of cases. This study suggests that oral isotretinoin can be safely continued during surgery and may actually improve cosmetic results of age-related facial procedures. In addition, based on personal communications, several physicians have been considering use of isotretinoin as an adjunct medication in rhinoplasty for thick-skinned individuals due to its skin-thinning effects. A review by McDonald et al. compared 11 studies supporting the discontinuation of isotretinoin prior to procedures (representing a total of 25 patients) to 11 studies concluding that there was insufficient evidence to support this practice (representing a total of 327 patients).2 The vast majority of included patients (n = 327, 93%) were found to have normal wound healing despite the use of isotretinoin, and only three patients among the studies opposing common practice demonstrated post-procedure scarring. Furthermore, while the authors suggested that the overall level of evidence on this topic was low, studies supporting pre-procedure withholding of isotretinoin were typically of lower level of evidence such as case reports or case series. Authors additionally noted that many studies did not investigate a personal or family history of atypical wound healing, and that different procedures and provider expertise could lead to varying levels of dermal injury and scarring. Based on the existing evidence, the authors concluded that while the current literature suggests that preoperative discontinuation of isotretinoin is not indicated, further cohort and prospective trial studies were warranted to better inform practice guidelines. Finally, in a 2020 randomized controlled trial, Yahyavi et al. studied 303 patients undergoing rhinoplasty in which patients in the experimental group were given low-dose (0.3 mg/kg/day) isotretinoin therapy 2 weeks prior to surgery until 2 months following surgery.5 Patients taking isotretinoin were found to have a significantly lower severity of acne and significantly higher level of satisfaction of nose appearance, as measured by the Likert scale. Additionally, no patients experienced keloid formation, scarring, or cartilage deformities. This study did have limitations in that a minimal number of skin incisions were made in patients undergoing rhinoplasty and the long-term effects of isotretinoin use could not be assessed as patients were given a short preoperative course. However, there was no appreciable difference in wound healing among those taking isotretinoin. Furthermore, rhinoplasty represents a common and important cosmetic procedure among patients in the age group expected to be taking isotretinoin. Although earlier case reports and animal studies have suggested compromise to wound healing related to the use of isotretinoin, recent prospective clinical studies have not found an increased incidence of facial scarring in patients using isotretinoin in the perioperative period. Isotretinoin carries well-known side effects such as neutropenia and transaminitis,5 which warrants careful consideration prior to prescription of this drug. In addition, isotretinoin-induced skin thinning could result in poor epithelialization which may result in subsequent scarring for long-term isotretinoin use.1 Nonetheless, the practice of holding isotretinoin prior to surgical intervention may not be indicated and may result in a delay of surgical treatment and may also lead to the persistence or recurrence of acne. These recommendations are based on three systematic reviews, which include randomized controlled trials, retrospective cohort studies, and case reports (level 5 evidence) and two randomized controlled trials (level 2 evidence).