{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:01:09Z","timestamp":1787241669705,"version":"build-2736575974"},"reference-count":20,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,10,19]],"date-time":"2017-10-19T00:00:00Z","timestamp":1508371200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Acad Dermatol Venereol"],"published-print":{"date-parts":[[2018,3]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n \n Actinic keratosis (\n AK<\/jats:styled-content>\n ) is a common skin disorder that can progress to invasive squamous\u2010cell carcinoma.\n AK<\/jats:styled-content>\n can present as clinical (visible) or subclinical (invisible) lesions within areas of chronic sun damage. The importance of treating subclinical\n AK<\/jats:styled-content>\n is gaining support. We present a subanalysis of a previously published Phase\n III<\/jats:styled-content>\n , double\u2010blind, vehicle\u2010controlled study (\n NCT<\/jats:styled-content>\n 02289768), to assess 5\u2010fluorouracil (5\u2010\n FU<\/jats:styled-content>\n ) 0.5%\/salicylic acid 10% treatment of subclinical\n AK<\/jats:styled-content>\n lesions, based on reflectance confocal microscopy (\n RCM<\/jats:styled-content>\n ).\n <\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n \n To determine the efficacy of 5\u2010\n FU<\/jats:styled-content>\n 0.5%\/salicylic acid 10% as field\u2010directed treatment for subclinical\n AK<\/jats:styled-content>\n lesions using\n RCM<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n For inclusion in this subanalysis, patients had to have at least three subclinical\n AK<\/jats:styled-content>\n lesions within a 25 cm\n 2<\/jats:sup>\n area of skin. Subclinical\n AK<\/jats:styled-content>\n lesions were diagnosed according to the presence of three key\n RCM<\/jats:styled-content>\n criteria: architectural disarray; keratinocyte atypia and pleomorphism at the basal, spinous and granular layer. Subclinical\n AK<\/jats:styled-content>\n lesions were evaluated by\n RCM<\/jats:styled-content>\n at baseline, after 4, 6 and 12 weeks of 5\u2010\n FU<\/jats:styled-content>\n 0.5%\/salicylic acid 10% treatment or vehicle, and 8 weeks following the end of treatment.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Twenty\u2010seven patients were included: 17 [mean age = 72.2 years, standard deviation (\n SD<\/jats:styled-content>\n ) = 6.3] received 5\u2010\n FU<\/jats:styled-content>\n 0.5%\/salicylic acid 10% treatment and 10 (mean age = 76.4 years,\n SD<\/jats:styled-content>\n = 3.9) received vehicle. Eight weeks following the end of treatment, the mean number of subclinical lesions declined (from 3.0 at baseline) to 0.3 (95% confidence interval [\n CI<\/jats:styled-content>\n ] 0.06\u20130.57) for the 5\u2010\n FU<\/jats:styled-content>\n 0.5%\/salicylic acid 10% group and 1.6 (95%\n CI<\/jats:styled-content>\n 0.52\u20132.68) in the vehicle group (reductions of 90% [95%\n CI<\/jats:styled-content>\n 72.1\u2013107.1] vs. 47% [95%\n CI<\/jats:styled-content>\n 24.8\u201369.5], respectively;\n P<\/jats:italic>\n = 0.005). The proportion of patients receiving 5\u2010\n FU<\/jats:styled-content>\n 0.5%\/salicylic acid 10% showing complete clearance of three preselected subclinical\n AK<\/jats:styled-content>\n lesions was numerically greater than in the vehicle group (69% vs. 40%, respectively;\n P =<\/jats:italic>\n 0.183).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n To the best of our knowledge, this is the first randomized, vehicle\u2010controlled study investigating 5\u2010\n FU<\/jats:styled-content>\n 0.5%\/salicylic acid 10% treatment for subclinical\n AK<\/jats:styled-content>\n lesions. The present data suggest some treatment efficacy for subclinical\n AK<\/jats:styled-content>\n lesions detected using\n RCM<\/jats:styled-content>\n . However, this subanalysis was not sufficiently powered and should be reproduced in a larger, subsequent cohort.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/jdv.14611","type":"journal-article","created":{"date-parts":[[2017,9,28]],"date-time":"2017-09-28T12:32:49Z","timestamp":1506601969000},"page":"390-396","source":"Crossref","is-referenced-by-count":10,"title":["Use of reflectance confocal microscopy to evaluate 5\u2010fluorouracil 0.5%\/salicylic acid 10% in the field\u2010directed treatment of subclinical lesions of actinic keratosis: subanalysis of a Phase\n III<\/scp>\n , randomized, double\u2010blind, vehicle\u2010controlled trial"],"prefix":"10.1111","volume":"32","author":[{"given":"M.","family":"Ulrich","sequence":"first","affiliation":[{"name":"CMB Collegium Medicum Berlin GmbH Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"U.","family":"Reinhold","sequence":"additional","affiliation":[{"name":"Dermatological Center Bonn Friedensplatz Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Falqu\u00e9s","sequence":"additional","affiliation":[{"name":"Almirall S.A. Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Rodriguez Azeredo","sequence":"additional","affiliation":[{"name":"Almirall S.A. Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Stockfleth","sequence":"additional","affiliation":[{"name":"Department of Dermatology Ruhr\u2010University Bochum Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,10,19]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2012.09.052"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.14852"},{"key":"e_1_2_6_4_1","first-page":"241","article-title":"What is the role of field\u2010directed therapy in the treatment of actinic keratosis? 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URLhttp:\/\/www.medicines.org.uk\/emc\/medicine\/24614(last accessed: 16 October 2017)."},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2011.10387.x"},{"key":"e_1_2_6_19_1","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1684\/ejd.2012.1707","article-title":"Recurrence rates and patient assessed outcomes of 0.5% 5\u2010fluorouracil in combination with salicylic acid treating actinic keratoses","volume":"22","author":"Stockfleth E","year":"2012","journal-title":"Eur J Dermatol"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.2340\/00015555-2167"},{"key":"e_1_2_6_21_1","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1111\/ddg.12685","article-title":"Efficacy of low\u2010dose 5\u2010fluorouracil\/salicylic acid in actinic keratoses in relation to treatment duration","volume":"13","author":"Szeimies RM","year":"2015","journal-title":"J Dtsch Dermatol Ges"}],"container-title":["Journal of the European Academy of Dermatology and Venereology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjdv.14611","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jdv.14611","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T06:04:02Z","timestamp":1695535442000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jdv.14611"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,10,19]]},"references-count":20,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2018,3]]}},"alternative-id":["10.1111\/jdv.14611"],"URL":"https:\/\/doi.org\/10.1111\/jdv.14611","archive":["Portico"],"relation":{},"ISSN":["0926-9959","1468-3083"],"issn-type":[{"value":"0926-9959","type":"print"},{"value":"1468-3083","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,10,19]]}}}