{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:06:41Z","timestamp":1792109201150,"version":"4.4.0"},"reference-count":55,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2021,6,9]],"date-time":"2021-06-09T00:00:00Z","timestamp":1623196800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The somatic <jats:italic>BRAF<\/jats:italic><jats:sup>V600E<\/jats:sup> mutation occurs in 38\u201364% of pediatric cases of Langerhans cell histiocytosis (LCH). Vemurafenib (VMF), a BRAF inhibitor, was approved for refractory <jats:italic>BRAF<\/jats:italic><jats:sup>V600E<\/jats:sup> mutated LCH. In adults, VMF causes frequent cutaneous adverse events (CAE) including skin tumors (squamous cell carcinomas, melanomas), but little is known in children. The objective of this study was to evaluate the frequency, clinical spectrum, and severity of CAEs in children treated with VMF for LCH. In addition, a correlation between CAE occurrence and VMF dose, residual plasma levels (RPLs), and efficacy was searched for.<\/jats:p><\/jats:sec><jats:sec><jats:title>Procedure<\/jats:title><jats:p>Multicentric retrospective observational study including patients &lt;18\u00a0years treated with VMF alone for refractory <jats:italic>BRAF<\/jats:italic><jats:sup>V600E<\/jats:sup> mutated LCH in 13 countries between October 1, 2013 and December 31, 2018.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Fifty\u2010seven patients: 56% female, median age 2.1\u00a0years (0.2\u201314.6), median treatment duration 4.1\u00a0months (1.4\u201329.7). Forty\u2010one patients (72%) had at least one CAE: photosensitivity (40%), keratosis pilaris (32%), rash (26%), xerosis (21%), and neutrophilic panniculitis (16%). No skin tumor was observed. Five percent of CAEs were grade 3. None were grade 4 or led to permanent VMF discontinuation. Dose reduction was necessary for 12% of patients, temporary treatment discontinuation for 16%, none leading to loss of efficacy. VMF dose, median RPL, and efficacy were not correlated with CAE occurrence.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>At doses used for pediatric LCH, CAEs are frequent but rarely severe and have little impact on the continuation of treatment when managed appropriately. Regular dermatological follow\u2010up is essential to manage CAEs and screen for possible induced skin tumors.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.29140","type":"journal-article","created":{"date-parts":[[2021,6,10]],"date-time":"2021-06-10T21:21:02Z","timestamp":1623360062000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Cutaneous adverse events in children treated with vemurafenib for refractory <i>BRAF<\/i><sup>V600E<\/sup> mutated Langerhans cell histiocytosis"],"prefix":"10.1002","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4996-3567","authenticated-orcid":false,"given":"Mathilde","family":"Tardieu","sequence":"first","affiliation":[{"name":"Pediatric Dermatology Department Grenoble Alpes University Hospital  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Am\u00e9lie","family":"N\u00e9ron","sequence":"additional","affiliation":[{"name":"Dermatology Department Grenoble Alpes University Hospital  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Duvert\u2010Lehembre","sequence":"additional","affiliation":[{"name":"Dermatology Department Lille University Hospital  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Islam","family":"Amine Larabi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Paris\u2010Saclay University (Versailles Saint\u2010Quentin\u2010en\u2010Yvelines University), Inserm U\u20101173, Raymond Poincar\u00e9 Hospital  Garches France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Barkaoui","sequence":"additional","affiliation":[{"name":"French Reference Center for Langerhans Cell Histiocytosis Trousseau Hospital  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Francois","family":"Emile","sequence":"additional","affiliation":[{"name":"Pathology Department &amp; EA4340\u2010BECCOH Ambroise Par\u00e9 Hospital, AP\u2010HP &amp; Versailles SQY University  Boulogne France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaud","family":"Seigneurin","sequence":"additional","affiliation":[{"name":"TIMC\u2010IMAG Laboratory Grenoble Alpes University, Grenoble Alpes University Hospital  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franck","family":"Boralevi","sequence":"additional","affiliation":[{"name":"Pediatric Dermatology Unit H\u00f4pital Pellegrin\u2010Enfants  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4485-146X","authenticated-orcid":false,"given":"Jean","family":"Donadieu","sequence":"additional","affiliation":[{"name":"French Reference Center for Langerhans Cell Histiocytosis Trousseau Hospital  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,6,9]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1607548"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20130977"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-04-279083"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0033891"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAT.0b013e328360b61d"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1103782"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2015.0086"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2015.0736"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2016003533"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.25277"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2017.5029"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.00456"},{"key":"e_1_2_9_14_1","unstructured":"European Medicines Agency.Public Summary of Opinion on Orphan Designation. 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