{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:13:19Z","timestamp":1791925999187,"version":"4.3.4"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:00:00Z","timestamp":1760054400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Acanthosis nigricans (AN) is a skin disorder marked by darkening and thickening of the skin, often linked to metabolic abnormalities. This systematic review of randomized controlled trials (RCTs) assesses the comparative effectiveness and tolerability of different topical treatment options of AN, aiming to determine the most suitable therapeutic strategies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A comprehensive literature search was conducted across PubMed, Scopus, <jats:uri>ClinicalTrials.gov<\/jats:uri>, Web of Science, and the Cochrane Library, yielding 6,407 studies. After screening and a full-text review, seven randomized controlled trials (<jats:italic>n<\/jats:italic>\u202f=\u202f268) assessed topical urea (10\u201320%), tretinoin (0.025\u20130.05%), salicylic acid (10%), and chemical peels such as glycolic acid (35\u201370%) and trichloroacetic acid (15%) over 8\u202fweeks to 2\u202fmonths, primarily on the neck and axilla. Outcomes included melanin and erythema indices (M\/E), ANASI\/ANSC scores, Investigator\u2019s and Participant\u2019s Global Evaluation (IGE\/PGE), and adverse events.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Urea demonstrated significant efficacy in reducing erythema, particularly at higher concentrations (20%), with mild adverse events such as stinging or irritation. Tretinoin was the most effective for reducing dark pigmentation, especially on the neck, and patients were more satisfied with it than with glycolic acid. Salicylic acid (10%) gave results similar to urea, with only mild side effects like dryness or peeling. Trichloroacetic acid (15%) peel was more effective than glycolic acid (35%) peel, both in skin improvement and patient satisfaction after 8\u202fweeks. Overall, side effects with all treatments were mild and went away on their own.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Both urea and tretinoin are effective treatments for AN, choice of therapy should be individualized tretinoin for predominant hyperpigmentation, urea for erythema or lower irritation tolerance, salicylic acid as a tolerable alternative, and TCA peel when stronger procedural options are suitable glycolic peel showed more modest effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Systematic review registration<\/jats:title><jats:p>Prospero registration number: (CRD42023444441); <jats:uri>https:\/\/www.crd.york.ac.uk\/PROSPERO\/view\/CRD42023444441<\/jats:uri>.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2025.1641322","type":"journal-article","created":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T04:20:04Z","timestamp":1760070004000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The efficacy of topical treatments for acanthosis nigricans: a systematic review of randomized controlled trials"],"prefix":"10.3389","volume":"12","author":[{"given":"Awadh","family":"Alamri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rose A.","family":"Alraddadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhaii","family":"Alzahrani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amal H.","family":"Abualola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadeel A.","family":"Maaddawi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renad F.","family":"Alharthy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alanoud Y.","family":"Alkhashan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Y.","family":"Ashqan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esraa A.","family":"Shaheen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bashaer","family":"Almahdi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hatoon M.","family":"Althobaiti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,10]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1515\/jbcpp.1998.9.2-4.407","article-title":"Acanthosis nigricans","volume":"9","author":"Stuart","year":"1998","journal-title":"J Basic Clin Physiol Pharmacol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"53","DOI":"10.4314\/aipm.v6i1.64043","article-title":"Acanthosis nigricans in the head and neck region","volume":"6","author":"Fasunla","year":"2008","journal-title":"Ann Ib Postgrad Med"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1016\/j.abd.2022.07.006","article-title":"Association of acanthosis nigricans with metabolic syndrome\u2014an analytic cross-sectional study","volume":"98","author":"Choudhary","year":"2023","journal-title":"An Bras Dermatol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"SC05","DOI":"10.7860\/jcdr\/2017\/24902.10203","article-title":"Prevalence of acanthosis nigricans and related factors in Iranian obese children","volume":"11","author":"Sayarifard","year":"2017","journal-title":"J Clin Diagn Res"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1177\/1059840511430952","article-title":"Is acanthosis nigricans a reliable indicator for risk of type 2 diabetes in obese children and adolescents? 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