Treatment of superficial vascular anomalies with topical sirolimus: A multicenter case series

Abstract

Background Systemic sirolimus (rapamycin) has recently been found effective in treating complex vascular anomalies by reducing the size and associated complications. Many vascular anomalies have a cutaneous component, and thus, we sought to determine whether topical administration of sirolimus may be an effective therapy, as data on the use of topical sirolimus are limited. Objective We reviewed the efficacy and tolerability of topical formulations of sirolimus in the treatment of various simple and combined vascular malformations and tumors. Methods Eighteen patients with any vascular anomaly treated exclusively with topical sirolimus were retrospectively reviewed. Results Eleven patients had combined venous lymphatic malformations, three had tufted angiomas, two had a lymphatic malformation, one had a venous malformation, and one had a verrucous venous malformation. All (100%) patients reported some degree of improvement and 50% of patients reported marked improvement in one or more symptoms, most commonly blebs and lymphatic drainage, and bleeding. Limitations The retrospective nature, small number of patients, and differences in topical preparations limit the broad application of the results. Conclusion Topical sirolimus appears to be a safe and useful non‐invasive therapy that is well‐tolerated in the treatment of the cutaneous portion of a variety of vascular anomalies.

Deep vein thrombosis in the setting of Klippel-Trenaunay syndrome and sirolimus treatment

“… 3 However, recent studies have demonstrated sirolimus as a potential new medication for the management of venous malformations. 8 , 9 , 10 , 11 , 12 The mechanism of action of sirolimus is to inhibit the mTOR protein, which is partially responsible for the pathogenesis of KTS. 6 Sirolimus has been used successfully in >80 case reports of vascular anomalies with lymphatic components.…”

“… 6 Recently, some studies have shown benefits as therapy for vascular malformations. 8 , 9 , 10 , 11 , 12 Furthermore, sirolimus has been emerging as a new medical treatment option for both vascular tumors and vascular malformations as an allosteric inhibitor of mTOR with further downstream inhibition of abnormal signaling through the PI3K/AKT pathway to coordinate proper cell growth and proliferation. Sirolimus seems ideal for “proliferative” vascular tumors through the control of tissue overgrowth disorders caused by inappropriate activation of the PI3K/AKT/mTOR pathway as an antiproliferative agent.…”

Verrucous venous malformation with thrombocytopenia in a neonate

“…3 The use of mTOR inhibitors, like sirolimus, has demonstrated efficacy in the treatment of vascular anomalies. 17,18 Al-Furaih et al reported using sirolimus at a total dose of 1.6 mg/m 2 per day, twice per day for 3 years for a VVM in a 13-year-old boy, which led to decreased risk of secondary infection and ulceration as well as improvement in range of motion.…”

Medical Adjuvants in the Treatment of Surgically Refractory Arteriovenous Malformations of the Head and Face: Case Report and Review of Literature

“…mTOR inhibitors are recently used alternatives to surgical management of large, superficial AVMs in the pediatric population, with rapamycin being the drug of choice in many published reports [3,6]. To date, our study details the 22nd and 23rd known patients to be treated with an mTOR inhibitor for management of a cranial or facial AVM [6,[11][12][13][14][15][16]. There has been substantial variability in dosing and treatment duration across institutions, with treatment duration ranging from 3 to 24.5 months, with a median treatment duration of 12 months across all reported cases [17,18].…”