{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T16:36:51Z","timestamp":1788367011520,"version":"build-2803163510"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T00:00:00Z","timestamp":1677628800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"},{"start":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T00:00:00Z","timestamp":1677628800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Dermatol Ther (Heidelb)"],"published-print":{"date-parts":[[2023,4]]},"DOI":"10.1007\/s13555-023-00902-6","type":"journal-article","created":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T15:03:48Z","timestamp":1677683028000},"page":"1013-1027","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Severity of Local Skin Reactions with 4% 5-Fluorouracil Plus Emollient versus 4% 5-Fluorouracil Alone in Patients with Actinic Keratosis: A Single-Blind Randomised Trial"],"prefix":"10.1007","volume":"13","author":[{"given":"Eggert","family":"Stockfleth","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9080-3661","authenticated-orcid":false,"given":"Thomas","family":"Jouary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7088-9077","authenticated-orcid":false,"given":"Francesca","family":"Farnetani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4056-5260","authenticated-orcid":false,"given":"Antonio Macaya","family":"Pascual","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"De Almeida Agudo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Jacques","family":"Voisard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"B\u00e9geault","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Delarue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,3,1]]},"reference":[{"key":"902_CR1","doi-asserted-by":"publisher","first-page":"e209","DOI":"10.1016\/j.jaad.2021.02.082","volume":"85","author":"DB Eisen","year":"2021","unstructured":"Eisen DB, Asgari MM, Bennett DD, et\u00a0al. Guidelines of care for the management of actinic keratosis. J Am Acad Dermatol. 2021;85:e209\u201333.","journal-title":"J Am Acad Dermatol"},{"key":"902_CR2","first-page":"275","volume":"18","author":"MV Heppt","year":"2020","unstructured":"Heppt MV, Leiter U, Steeb T, et\u00a0al. S3 Guideline for actinic keratosis and cutaneous squamous cell carcinoma - short version, part 1: diagnosis, interventions for actinic keratoses, care structures and quality-of-care indicators. J Dtsch Dermatol Ges. 2020;18:275\u201394.","journal-title":"J Dtsch Dermatol Ges"},{"key":"902_CR3","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1111\/jdv.14375","volume":"31","author":"P Arenberger","year":"2017","unstructured":"Arenberger P, Arenbergerova M. New and current preventive treatment options in actinic keratosis. J Eur Acad Dermatol Venereol. 2017;31:13\u20137.","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"902_CR4","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1016\/j.abd.2019.10.004","volume":"94","author":"CPH Reinehr","year":"2019","unstructured":"Reinehr CPH, Bakos RM. Actinic keratoses: review of clinical, dermoscopic, and therapeutic aspects. An Bras Dermatol. 2019;94:637\u201357.","journal-title":"An Bras Dermatol"},{"key":"902_CR5","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1080\/09546634.2019.1682504","volume":"32","author":"C Navarrete-Dechent","year":"2021","unstructured":"Navarrete-Dechent C, Marghoob AA, Marchetti MA. Contemporary management of actinic keratosis. J Dermatolog Treat. 2021;32:572\u20134.","journal-title":"J Dermatolog Treat"},{"key":"902_CR6","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1111\/ijd.14147","volume":"58","author":"ECV de Oliveira","year":"2019","unstructured":"de Oliveira ECV, da Motta VRV, Pantoja PC, et\u00a0al. Actinic keratosis\u2014review for clinical practice. Int J Dermatol. 2019;58:400\u20137.","journal-title":"Int J Dermatol"},{"key":"902_CR7","doi-asserted-by":"publisher","first-page":"1971","DOI":"10.1038\/jid.2013.134","volume":"133","author":"SC Flohil","year":"2013","unstructured":"Flohil SC, van der Leest RJ, Dowlatshahi EA, Hofman A, de Vries E, Nijsten T. Prevalence of actinic keratosis and its risk factors in the general population: the Rotterdam Study. J Invest Dermatol. 2013;133:1971\u20138.","journal-title":"J Invest Dermatol"},{"key":"902_CR8","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.1016\/S0190-9622(88)70270-4","volume":"19","author":"A Green","year":"1988","unstructured":"Green A, Beardmore G, Hart V, Leslie D, Marks R, Staines D. Skin cancer in a Queensland population. J Am Acad Dermatol. 1988;19:1045\u201352.","journal-title":"J Am Acad Dermatol"},{"key":"902_CR9","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1111\/j.1365-2133.1986.tb06644.x","volume":"115","author":"R Marks","year":"1986","unstructured":"Marks R, Foley P, Goodman G, Hage BH, Selwood TS. Spontaneous remission of solar keratoses: the case for conservative management. Br J Dermatol. 1986;115:649\u201355.","journal-title":"Br J Dermatol"},{"key":"902_CR10","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1159\/000112925","volume":"216","author":"P Bernard","year":"2008","unstructured":"Bernard P, Dupuy A, Sasco A, et\u00a0al. Basal cell carcinomas and actinic keratoses seen in dermatological practice in France: a cross-sectional survey. Dermatology. 2008;216:194\u20139.","journal-title":"Dermatology"},{"key":"902_CR11","doi-asserted-by":"crossref","unstructured":"Harvey I, Frankel S, Marks R, Shalom D, Nolan-Farrell M. Non-melanoma skin cancer and solar keratoses. Methods and descriptive results of the South Wales Skin Cancer Study. Br J Cancer. 1996;74:1302\u20137.","DOI":"10.1038\/bjc.1996.534"},{"key":"902_CR12","doi-asserted-by":"publisher","first-page":"1154","DOI":"10.1046\/j.1365-2133.2000.03541.x","volume":"142","author":"AA Memon","year":"2000","unstructured":"Memon AA, Tomenson JA, Bothwell J, Friedmann PS. Prevalence of solar damage and actinic keratosis in a Merseyside population. Br J Dermatol. 2000;142:1154\u20139.","journal-title":"Br J Dermatol"},{"key":"902_CR13","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1684\/ejd.2017.3126","volume":"27","author":"MC Fargnoli","year":"2017","unstructured":"Fargnoli MC, Altomare G, Benati E, et\u00a0al. Prevalence and risk factors of actinic keratosis in patients attending Italian dermatology clinics. Eur J Dermatol. 2017;27:599\u2013608.","journal-title":"Eur J Dermatol"},{"key":"902_CR14","doi-asserted-by":"crossref","unstructured":"Ferr\u00e1ndiz C, Plazas MJ, Sabat\u00e9 M, Palomino R, EPIQA Study Group. Prevalence of actinic keratosis among dermatology outpatients in Spain. Actas Dermosifiliogr. 2016;107:674\u201380.","DOI":"10.1016\/j.ad.2016.05.016"},{"key":"902_CR15","doi-asserted-by":"publisher","first-page":"1415","DOI":"10.1111\/bjd.13132","volume":"171","author":"J Eder","year":"2014","unstructured":"Eder J, Prillinger K, Korn A, Geroldinger A, Trautinger F. Prevalence of actinic keratosis among dermatology outpatients in Austria. Br J Dermatol. 2014;171:1415\u201321.","journal-title":"Br J Dermatol"},{"key":"902_CR16","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1056\/NEJMoa1811850","volume":"380","author":"MHE Jansen","year":"2019","unstructured":"Jansen MHE, Kessels J, Nelemans PJ, et\u00a0al. Randomized trial of four treatment approaches for actinic keratosis. N Engl J Med. 2019;380:935\u201346.","journal-title":"N Engl J Med"},{"key":"902_CR17","doi-asserted-by":"crossref","unstructured":"Ezzedine K, Painchault C, Brignone M. Systematic literature review and network meta-analysis of the efficacy and acceptability of interventions in actinic keratoses. Acta Derm Venereol. 2021;101:adv00358.","DOI":"10.2340\/00015555-3690"},{"key":"902_CR18","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1111\/bjd.12343","volume":"169","author":"AK Gupta","year":"2013","unstructured":"Gupta AK, Paquet M. Network meta-analysis of the outcome \u201cparticipant complete clearance\u201d in nonimmunosuppressed participants of eight interventions for actinic keratosis: a follow-up on a Cochrane review. Br J Dermatol. 2013;169:250\u20139.","journal-title":"Br J Dermatol"},{"key":"902_CR19","doi-asserted-by":"publisher","DOI":"10.1111\/dth.12822","volume":"32","author":"Y Wu","year":"2019","unstructured":"Wu Y, Tang N, Cai L, Li Q. Relative efficacy of 5-fluorouracil compared with other treatments among patients with actinic keratosis: a network meta-analysis. Dermatol Ther. 2019;32: e12822.","journal-title":"Dermatol Ther"},{"key":"902_CR20","unstructured":"European Medicines Agency. Tolak (4% 5-fluorouracil): summary of product characteristics. 2020. https:\/\/docetp.mpa.se\/LMF\/Tolak%20cream%20ENG%20SmPC_09001bee809dbaa1.pdf. Accessed 06 July 2022."},{"key":"902_CR21","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1007\/s13555-021-00668-9","volume":"12","author":"E Stockfleth","year":"2022","unstructured":"Stockfleth E, B\u00e9geault N, Delarue A. Intensity of local skin reactions during 5-fluorouracil treatment related to the number of actinic keratosis lesions: a post hoc, exploratory analysis. Dermatol Ther. 2022;12:467\u201379.","journal-title":"Dermatol Ther"},{"key":"902_CR22","unstructured":"US Food and Drug Administration. Tolak (fluorouracil) cream, 4%, for topical use. Prescribing information. 2015. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2015\/022259s000lbl.pdf. Accessed 13 May 2022."},{"key":"902_CR23","first-page":"1218","volume":"15","author":"MA Dohil","year":"2016","unstructured":"Dohil MA. Efficacy, safety, and tolerability of 4% 5-fluorouracil cream in a novel patented aqueous cream containing peanut oil once daily compared with 5% 5-fluorouracil cream twice daily: meeting the challenge in the treatment of actinic keratosis. J Drugs Dermatol. 2016;15:1218\u201324.","journal-title":"J Drugs Dermatol"},{"key":"902_CR24","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1007\/s13555-014-0059-9","volume":"4","author":"R Rosen","year":"2014","unstructured":"Rosen R, Marmur E, Anderson L, Welburn P, Katsamas J. A new, objective, quantitative scale for measuring local skin responses following topical actinic keratosis therapy with ingenol mebutate. Dermatol Ther (Heidelb). 2014;4:207\u201319.","journal-title":"Dermatol Ther (Heidelb)."},{"key":"902_CR25","first-page":"227","volume":"37","author":"KR Cohen","year":"2012","unstructured":"Cohen KR, Frank J, Salbu RL, Israel I. Pruritus in the elderly: clinical approaches to the improvement of quality of life. P T. 2012;37:227\u201339.","journal-title":"P T"}],"container-title":["Dermatology and Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13555-023-00902-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s13555-023-00902-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13555-023-00902-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,29]],"date-time":"2023-03-29T16:43:39Z","timestamp":1680108219000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s13555-023-00902-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,1]]},"references-count":25,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,4]]}},"alternative-id":["902"],"URL":"https:\/\/doi.org\/10.1007\/s13555-023-00902-6","relation":{},"ISSN":["2193-8210","2190-9172"],"issn-type":[{"value":"2193-8210","type":"print"},{"value":"2190-9172","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,1]]},"assertion":[{"value":"6 January 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 February 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 March 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}]}}