{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T14:31:01Z","timestamp":1774881061664,"version":"3.50.1"},"reference-count":108,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,9,24]],"date-time":"2014-09-24T00:00:00Z","timestamp":1411516800000},"content-version":"vor","delay-in-days":54,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003478","name":"Ministry of Health, Labour and Welfare","doi-asserted-by":"publisher","award":["H24 076"],"award-info":[{"award-number":["H24 076"]}],"id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatrics International"],"published-print":{"date-parts":[[2014,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The purpose of this review is to provide an updated overview of the pathogenesis and treatment of Langerhans cell histiocytosis (<jats:styled-content style=\"fixed-case\">LCH<\/jats:styled-content>). The pathogenesis of <jats:styled-content style=\"fixed-case\">LCH<\/jats:styled-content> remains obscure and the optimal treatment for <jats:styled-content style=\"fixed-case\">LCH<\/jats:styled-content> has not been established, although incremental progress has been made. Proinflammatory cytokines and chemokines are known to play a role in <jats:styled-content style=\"fixed-case\">LCH<\/jats:styled-content>, which suggests that <jats:styled-content style=\"fixed-case\">LCH<\/jats:styled-content> is an immune disorder. However, the oncogenic <jats:italic><jats:styled-content style=\"fixed-case\">BRAF<\/jats:styled-content><\/jats:italic> mutation is also detected in more than half of <jats:styled-content style=\"fixed-case\">LCH<\/jats:styled-content> patients, which suggests that <jats:styled-content style=\"fixed-case\">LCH<\/jats:styled-content> is a neoplastic disorder. Remaining major issues in the treatment of <jats:styled-content style=\"fixed-case\">LCH<\/jats:styled-content> are how to rescue patients who have risk\u2010organ involvement but do not respond to first\u2010line therapy, the optimal treatment for the orphan disease of multifocal adult <jats:styled-content style=\"fixed-case\">LCH<\/jats:styled-content>, and how to reduce and treat central nervous system\u2010related consequences, such as central diabetes insipidus and neurodegeneration. More research is needed to better understand the pathogenesis of this disease and to resolve the treatment issues.<\/jats:p>","DOI":"10.1111\/ped.12380","type":"journal-article","created":{"date-parts":[[2014,5,19]],"date-time":"2014-05-19T11:19:38Z","timestamp":1400498378000},"page":"451-461","source":"Crossref","is-referenced-by-count":90,"title":["Recent advances in Langerhans cell histiocytosis"],"prefix":"10.1111","volume":"56","author":[{"given":"Akira","family":"Morimoto","sequence":"first","affiliation":[{"name":"Department of Pediatrics Jichi Medical University of Medicine  Shimotsuke Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukiko","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Jichi Medical University of Medicine  Shimotsuke Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoko","family":"Shioda","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology National Center for Child Health and Development  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuko","family":"Kudo","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology Shizuoka Children's Hospital  Shizuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshihiko","family":"Imamura","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Kyoto Prefectural University of Medicine  Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,9,24]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.2008.144527"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.21498"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-013-1364-2"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0609.2006.00648.x"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-8049(03)00672-5"},{"key":"e_1_2_10_7_1","first-page":"1009","article-title":"Langerhans\u2019 cell histiocytosis: is there a role for genetics?","volume":"86","author":"Aric\u00f2 M","year":"2001","journal-title":"Haematologica"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0889-8588(05)70516-5"},{"key":"e_1_2_10_9_1","first-page":"358","volume-title":"WHO Classification of Tumours, Tumours of Haematopoietic and Lymphoid Tissues","author":"Jaffe R","year":"2008"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e31815b212b"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1017\/CBO9780511545252.016"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.20362"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2013.05.028"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199407213310303"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(94)91842-2"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1053\/hupa.2002.124035"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-04-279083"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0033891"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20130977"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V97.5.1241"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0902336"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-02-410241"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-05-025601"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.21044"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20030137"},{"key":"e_1_2_10_26_1","unstructured":"QuispelW Stegehuis\u2010KampJ Santos\u2010BoeijS van denBosC vanHalterenA EgelerRM.CXCR4 expression by Langerhans cell histiocytosis cells is associated with disease outcome.29th Annual Meeting of The Histiocyte Society.2013 [abstract]."},{"key":"e_1_2_10_27_1","first-page":"4195","article-title":"Differential in situ cytokine profiles of Langerhans\u2010like cells and T cells in Langerhans cell histiocytosis: abundant expression of cytokines relevant to disease and treatment","volume":"94","author":"Egeler RM","year":"1999","journal-title":"Blood"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-8049(00)00296-3"},{"key":"e_1_2_10_29_1","first-page":"696","article-title":"Comprehensive analysis of serum cytokine\/ chemokine and growth factors in pediatric patients with Langerhans cell histiocytosis","volume":"56","author":"Morimoto A","year":"2011","journal-title":"Pediatr. Blood Cancer"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2009.080689"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1827.2011.02649.x"},{"key":"e_1_2_10_32_1","doi-asserted-by":"crossref","unstructured":"OhY MorimotoA ShiodaY ImamuraT KudoK ImashukuS.High serum osteopontin levels in pediatric patients with high risk Langerhans cell histiocytosis. Cytokine.2014Jul 30. doi:10.1016\/j.cyto.2014.07.002. [Epub ahead of print].","DOI":"10.1016\/j.cyto.2014.07.002"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0040253"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20041785"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.20595"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1694"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-012-1360-6"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.24695"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.22224"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1017\/CBO9780511545252.007"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1017\/CBO9780511545252.009"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-009-0420-4"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.21782"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00247-006-0246-7"},{"key":"e_1_2_10_45_1","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1017\/CBO9780511545252.008","volume-title":"Histiocytic Disorders of Children and Adults","author":"Krafchik B","year":"2005"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1001\/archdermatol.2009.360"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.20479"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-7-16"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.mph.0000137365.34865.96"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2011.12.035"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPH.0b013e3181d7acc5"},{"key":"e_1_2_10_52_1","unstructured":"Histiocyte Society.Langerhans cell histiocytosis: evaluation and treatment guidelines 2009. [Cited 15 April 2009.] Available from URL:http:\/\/www.histiocytesociety.org\/document.doc?id=290."},{"key":"e_1_2_10_53_1","first-page":"E222","article-title":"Langerhans cell histiocytosis: literature review and descriptive analysis of oral manifestations","volume":"14","author":"Madrigal\u2010Mart\u00ednez\u2010Pereda C","year":"2009","journal-title":"Med. Oral Patol. Oral Cir. Bucal"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.22663"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2009-1742"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2007.03.015"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.24603"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.21030"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.20746"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2010.03.001"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-011-0965-x"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.20425"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2003.12.030"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.20003"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-011-0955-z"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1097\/00043426-200411000-00009"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2007.12.042"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A0509"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh403"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.22478"},{"key":"e_1_2_10_71_1","unstructured":"ShiodaY MorimotoA ImamuraT KudoK ImashukuS.Analysis of permanent consequences in pediatric patients with Langerhans cell histiocytosis: data of the JLSG\u201096 and JLSG\u201002 studies in Japan.29th Annual Meeting of The Histiocyte Society.2013 [abstract]."},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.11827"},{"key":"e_1_2_10_73_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.21259"},{"key":"e_1_2_10_74_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.22326"},{"key":"e_1_2_10_75_1","doi-asserted-by":"publisher","DOI":"10.1067\/mpd.2001.111331"},{"key":"e_1_2_10_76_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2401089"},{"key":"e_1_2_10_77_1","doi-asserted-by":"publisher","DOI":"10.1017\/CBO9780511545252.015"},{"key":"e_1_2_10_78_1","doi-asserted-by":"publisher","DOI":"10.1097\/01241398-199211000-00021"},{"key":"e_1_2_10_79_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-08-106211"},{"key":"e_1_2_10_80_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-09-455774"},{"key":"e_1_2_10_81_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.21985"},{"key":"e_1_2_10_82_1","first-page":"E80","article-title":"Intensified and prolonged therapy improved the outcome in multi\u2010system Langerhans cell histiocytosis","volume":"60","author":"Morimoto A","year":"2013","journal-title":"Pediatr. Blood Cancer"},{"key":"e_1_2_10_83_1","doi-asserted-by":"publisher","DOI":"10.1002\/mpo.10166"},{"key":"e_1_2_10_84_1","first-page":"695","article-title":"Outcome of poor responders at 6 weeks of induction therapy: JLSG\u201002 protocol study for multisystem Langerhans cell histiocytosis in Japan","volume":"56","author":"Kudo K","year":"2011","journal-title":"Pediatr. Blood Cancer"},{"key":"e_1_2_10_85_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa012087"},{"key":"e_1_2_10_86_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-8-72"},{"key":"e_1_2_10_87_1","doi-asserted-by":"publisher","DOI":"10.3960\/jslrt.52.121"},{"key":"e_1_2_10_88_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V93.12.4125"},{"key":"e_1_2_10_89_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdp455"},{"key":"e_1_2_10_90_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0043257"},{"key":"e_1_2_10_91_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-012-1245-0"},{"key":"e_1_2_10_92_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2005.02.007"},{"key":"e_1_2_10_93_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPH.0b013e31817e4a32"},{"key":"e_1_2_10_94_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.24772"},{"key":"e_1_2_10_95_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-07-446286"},{"key":"e_1_2_10_96_1","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2009.245"},{"key":"e_1_2_10_97_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bmt.1705015"},{"key":"e_1_2_10_98_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.22703"},{"key":"e_1_2_10_99_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.22229"},{"key":"e_1_2_10_100_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-010-0558-0"},{"key":"e_1_2_10_101_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.23087"},{"key":"e_1_2_10_102_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-013-1343-7"},{"key":"e_1_2_10_103_1","doi-asserted-by":"publisher","DOI":"10.1002\/mpo.1306"},{"key":"e_1_2_10_104_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.tp.0000200304.64613.af"},{"key":"e_1_2_10_105_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2008.05.002"},{"key":"e_1_2_10_106_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.21315"},{"key":"e_1_2_10_107_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.20021"},{"key":"e_1_2_10_108_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-012-1220-9"},{"key":"e_1_2_10_109_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002326"}],"container-title":["Pediatrics International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fped.12380","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ped.12380","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T11:23:42Z","timestamp":1695986622000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ped.12380"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,8]]},"references-count":108,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2014,8]]}},"alternative-id":["10.1111\/ped.12380"],"URL":"https:\/\/doi.org\/10.1111\/ped.12380","archive":["Portico"],"relation":{},"ISSN":["1328-8067","1442-200X"],"issn-type":[{"value":"1328-8067","type":"print"},{"value":"1442-200X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,8]]}}}