Topical rapamycin treatment for sebaceous hyperplasia: A retrospective case series from a tertiary referral center

Dear Editor, Sebaceous hyperplasia (SH) is a common condition characterized by the overgrowth of sebaceous lobules, with its prevalence increasing with ultraviolet exposure and aging. Despite its benign nature, the yellowish papular appearance may be disfiguring and lead to significant psychological distress and cosmetic concerns, prompting some patients to seek removal. Complete eradication of SH requires full destruction of the affected sebaceous glands with the risk of scarring, making its management challenging.[1] Rapamycin is an inhibitor of the mechanistic target of rapamycin (mTOR) signaling pathway, and topical rapamycin is the only drug approved for the treatment of angiofibromas in patients with tuberous sclerosis.[2] Herein, we present our clinical experience with the off-label use of topical rapamycin (Rapats Gel 0.2%, Shiner Pharm Corp, Taiwan) for the treatment of SH. We retrospectively reviewed all six patients who were treated with topical rapamycin for SH [Supplementary Table 1]. The median age was 65 years (range: 46–80), and the diagnoses of SH in all patients were established clinically. Five patients were treatment naïve, while one (Case 1) had a prior history of laser therapy with rapid lesion relapse.Supplementary Table 1: Demographic characteristics and clinical outcomes of patients with sebaceous hyperplasia treated with topical rapamycinAfter 2 months of once- to twice-daily application of topical rapamycin gel, four patients (Cases 1 to 4) exhibited significant lesion flattening, with two of them consenting to the publication of their photographs (Case 2 and 3) [Figure 1]. Notably, one patient (Case 2) achieved near-complete resolution of the right cheek lesion [Figure 1]. In contrast, two patients (Cases 5 and 6) demonstrated minimal-to-no response to the treatment. No notable differences in lesion characteristics or demographics were observed between responsive and unresponsive cases.Figure 1: Clinical improvement of sebaceous hyperplasia in two patients following topical rapamycin therapy. (a) A characteristic skin-colored papule (arrow) on the right cheek of Case 2 before the application of topical rapamycin. (b) Near-complete resolution of the right cheek papule after 2 months of once-daily application of rapamycin gel. (c) Pretreatment image showing multiple papules (arrows) on the left cheek of Case 3. (d) Significant flattening of the left cheek papules 2 months after twice-daily application of topical rapamycin.Two patients (Cases 1 and 3) experienced mild but tolerable burning sensations, while one (Case 4) reported mild pruritus. No patients discontinued the treatment due to adverse events. Lesion recurrence was observed in Cases 1 and 4, typically within 1–2 weeks after treatment discontinuation, presenting as gradual lesion enlargement. Recurrence tended to be more prominent following sun exposure, during summer months, or in larger lesions. Case 3 showed no recurrence 2 months after treatment discontinuation, while recurrence was unassessable in Case 2 due to ongoing treatment. All recurrent lesions responded favorably to retreatment. In addition, once-weekly or more frequent applications of topical rapamycin may help sustain treatment response and prevent recurrence. The mTOR signaling pathway plays a pivotal role in regulating various biological processes, such as cellular metabolism, immune responses, autophagy, proliferation, and differentiation.[2,3] Consequently, topical rapamycin at concentrations ranging from 0.1% to 1% has been used in the treatment of various inflammatory and neoplastic skin conditions, including nevus sebaceus.[2,4] Although the pathogenesis of SH remains incompletely understood, in vitro studies have indicated that cell growth and lipogenesis in human sebocytes are regulated through the mTOR-p70 S6K (T389) and mTOR-SREBP-1/PPARγ signaling pathways, respectively.[5] Inhibition of the mTOR signaling cascade may, therefore, promote sebaceous gland atrophy and reduce sebum production, potentially providing therapeutic benefits for various sebaceous gland-associated disorders. Alternatively, a vascular nature has been found in SH,[6] and topical rapamycin is best known for its antiangiogenic effect,[2] further supporting its theoretical rationale as a treatment of SH. Various destructive treatment modalities have been explored for SH, including cryotherapy, electrodessication, curettage, shave excision, topical trichloroacetic acid, topical photodynamic therapy, and laser-based interventions. However, most of these approaches carry the potential risks of scarring or dyspigmentation. The only commonly used medical treatment for SH is oral isotretinoin, but its use is limited by its systemic toxicities and high recurrence rates after discontinuation.[1] Topical application of rapamycin has demonstrated a favorable safety profile. A meta-analysis reported an incidence of adverse events with topical rapamycin at 23.6%, all of which were localized and primarily consisted of local irritation. In addition, although 10.0% of patients using topical rapamycin exhibited detectable blood concentrations, none of the levels exceeded the threshold for immunosuppression.[2] In our study, four of the six patients experienced significant clinical improvement with topical rapamycin, and none reported systemic side effects. Although no well-established evidence currently demonstrates the improvement of SH with systemic mTOR inhibitors, some case reports have noted clinical improvement in sebaceous neoplasms following a switch from tacrolimus to systemic mTOR inhibitors in kidney transplant recipients.[7,8] These findings suggest a potential benefit of mTOR inhibition in sebaceous proliferations and align with the therapeutic effect of topical rapamycin observed in our study. In conclusion, this case series suggested that topical rapamycin might represent a potential medical therapy for SH. However, further studies are required to understand the underlying mechanism and predictors for its efficacy. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patients has given their consent for their images and other clinical information to be reported in the journal. The patients understand that names and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed. Data availability statement The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. Financial support and sponsorship Nil. Conflicts of interest Prof. Tsen-Fang Tsai, an editorial board member at Dermatologica Sinica, had no role in the peer review process of or decision to publish this article. All authors declared no conflicts of interest in writing this paper.