{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T03:28:51Z","timestamp":1768879731189,"version":"3.49.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,7,17]],"date-time":"2024-07-17T00:00:00Z","timestamp":1721174400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Topical sirolimus is increasingly utilized off-licence to manage various dermatological conditions while avoiding typical adverse effects associated with systemic sirolimus. However, widespread use is limited by a highly heterogeneous evidence base of mixed quality. Our aim was to evaluate the current evidence base for the indications, efficacy and safety profile of topical sirolimus in dermatology. A literature search was conducted from 2005 to 4 July 2023, of English-language studies, with the following databases consulted: MEDLINE, PubMed, Embase, CENTRAL and EBSCO. Key words included \u2018topical\u2019, \u2018rapamycin\u2019, \u2018sirolimus\u2019 and \u2018dermatology\u2019. Data on drug efficacy, concentration, side-effects, cointerventions and follow-up were extracted. The search identified 202 studies, 71 of which met the inclusion criteria. Efficacy of topical sirolimus was demonstrated in facial angiofibromas (799 patients) compared with placebo across multiple randomized controlled trials, with a predominant concentration of 0.1%. Evidence was mixed for use of sirolimus in port-wine stains (61 patients), with evidence of effectiveness for combined sirolimus and pulsed-dye laser. Multiple case reports demonstrated clinical improvement with topical sirolimus in cutaneous vascular abnormalities (33 patients) at a higher concentration of 1%. Other applications of topical sirolimus were predominantly case reports, demonstrating generally favourable outcomes. Topical sirolimus was generally well tolerated; most reported adverse effects were localized irritation and pruritus. Ointment-based preparations and once-daily dosing appeared to confer a better side-effect profile. Most high-quality data pertain to the efficacy of topical sirolimus in treating facial angiofibromas in tuberous sclerosis. Outcomes are generally promising in other indications, with good tolerability, but data quality is mixed.<\/jats:p>","DOI":"10.1093\/ced\/llae275","type":"journal-article","created":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T21:36:23Z","timestamp":1721165783000},"page":"1-11","source":"Crossref","is-referenced-by-count":2,"title":["Topical sirolimus in dermatology: a systematic review"],"prefix":"10.1093","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8310-5750","authenticated-orcid":false,"given":"Usamah M","family":"Afzal","sequence":"first","affiliation":[{"name":"Harrogate and District Foundation Trust , Harrogate ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1304-8287","authenticated-orcid":false,"given":"Mohammad","family":"Alazemi","sequence":"additional","affiliation":[{"name":"Jaber Al-Ahmed Hospital , Kuwait City ,","place":["Kuwait"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3741-0815","authenticated-orcid":false,"given":"Omar","family":"Ali","sequence":"additional","affiliation":[{"name":"Newcastle upon Tyne NHS Trust , Newcastle upon Tyne ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Faisal R","family":"Ali","sequence":"additional","affiliation":[{"name":"Mid Cheshire NHS Foundation Trust, Crewe ,","place":["UK"]},{"name":"University of Central Lancashire ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John T","family":"Lear","sequence":"additional","affiliation":[{"name":"Mid Cheshire NHS Foundation Trust, Crewe ,","place":["UK"]},{"name":"Manchester Academic Health Science Centre ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,7,17]]},"reference":[{"key":"2024122223532937400_llae275-B1","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1056\/NEJMoa1204166","article-title":"Sirolimus and secondary skin-cancer prevention in kidney transplantation","volume":"367","author":"Euvrard","year":"2012","journal-title":"N Engl J Med"},{"key":"2024122223532937400_llae275-B2","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1111\/ajd.13671","article-title":"Systematic review of sirolimus in dermatological conditions","volume":"62","author":"Swarbrick","year":"2021","journal-title":"Australas J Dermatol"},{"key":"2024122223532937400_llae275-B3","author":"Centre for Evidence-Based Medicine"},{"key":"2024122223532937400_llae275-B4","doi-asserted-by":"crossref","first-page":"1804","DOI":"10.1080\/09546634.2021.1905768","article-title":"Topical rapamycin in the treatment of facial angiofibromas in tuberous sclerosis: a systematic review based on evidence","volume":"33","author":"Cortell Fuster","year":"2022","journal-title":"J Dermatol Treat"},{"key":"2024122223532937400_llae275-B5","doi-asserted-by":"crossref","first-page":"121","DOI":"10.2165\/11634580-000000000-00000","article-title":"Topical rapamycin therapy to alleviate the cutaneous manifestations of tuberous sclerosis complex: a double-blind, randomized, controlled trial to evaluate the safety and efficacy of topically applied rapamycin","volume":"12","author":"Koenig","year":"2012","journal-title":"Drugs R D"},{"key":"2024122223532937400_llae275-B6","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1001\/jamadermatol.2016.3545","article-title":"Efficacy and safety of topical sirolimus therapy for facial angiofibromas in the tuberous sclerosis complex: a randomized clinical trial","volume":"153","author":"Wataya-Kaneda","year":"2017","journal-title":"JAMA 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