{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T19:18:13Z","timestamp":1776885493890,"version":"3.51.2"},"reference-count":24,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,4,16]],"date-time":"2023-04-16T00:00:00Z","timestamp":1681603200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100009592","name":"Beijing Municipal Science and Technology Commission","doi-asserted-by":"publisher","award":["Z221100007422054"],"award-info":[{"award-number":["Z221100007422054"]}],"id":[{"id":"10.13039\/501100009592","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Frequent germline mutations of <jats:italic>HAVCR2<\/jats:italic>, recently identified in subcutaneous panniculitis\u2010like T\u2010cell lymphoma (SPTCL), are associated with an increased risk of hemophagocytic lymphohistiocytosis (HLH). However, SPTCL\u2010HLH represents a challenge because of the difficulties in treatment with poor survival. Its malignant nature, specifically harbouring <jats:italic>HAVCR2<\/jats:italic> mutations, has also been questioned. To better understand its pathology and treatment, we analysed the clinical data of six patients diagnosed at our centre. The median age at onset was 10.5\u2009years (range, 0.8\u201312.4). Five patients presented with skin lesions of subcutaneous nodules\/plaques and\/or ulceration. All patients developed HLH; notably, one infant only had HLH without skin involvement. Histopathologically, only two patients were diagnosed with SPTCL and three were reported as panniculitis with no sufficient evidence of lymphoma. Genetically, germline homozygous mutation of <jats:italic>HAVCR2<\/jats:italic> (p.Y82C) was identified in all patients, with a median diagnosis time of 4.6\u2009months. All patients initially received corticosteroids, immunosuppressants or chemotherapy, achieving unfavourable responses. Strikingly, they responded well to ruxolitinib targeting inflammatory cytokines, allowing rapid disease resolution and\/or long\u2010term maintenance of remission. The excellent efficacy of ruxolitinib highlights this disease as an inflammatory condition instead of neoplastic nature and indicates novel agents targeting key inflammatory pathways as an encouraging approach for this disease entity.<\/jats:p>","DOI":"10.1111\/bjh.18817","type":"journal-article","created":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T05:54:09Z","timestamp":1681710849000},"page":"135-146","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Efficacy of ruxolitinib for <i>HAVCR2<\/i> mutation\u2010associated hemophagocytic lymphohistiocytosis and panniculitis manifestations in children"],"prefix":"10.1111","volume":"202","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0404-5743","authenticated-orcid":false,"given":"Qing","family":"Zhang","sequence":"first","affiliation":[{"name":"Hematologic Disease Laboratory, Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Pediatric Research Institute, Beijing Children's Hospital Capital Medical University, National Center for Children's Health  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun\u2010Ju","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pathology, Beijing Children's Hospital Capital Medical University, National Center for Children's Health  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan\u2010Hong","family":"Li","sequence":"additional","affiliation":[{"name":"Departments of Hematology Hongqi Hospital Affiliated to Mudanjiang Medical University  Heilongjiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7611-1431","authenticated-orcid":false,"given":"Lei","family":"Cui","sequence":"additional","affiliation":[{"name":"Hematologic Disease Laboratory, Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Pediatric Research Institute, Beijing Children's Hospital Capital Medical University, National Center for Children's Health  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei\u2010Jing","family":"Li","sequence":"additional","affiliation":[{"name":"Hematologic Disease Laboratory, Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Pediatric Research Institute, Beijing Children's Hospital Capital Medical University, National Center for Children's Health  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong\u2010Hao","family":"Ma","sequence":"additional","affiliation":[{"name":"Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital Capital Medical University, National Center for Children's Health  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5476-4677","authenticated-orcid":false,"given":"Yun\u2010Ze","family":"Zhao","sequence":"additional","affiliation":[{"name":"Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital Capital Medical University, National Center for Children's Health  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong","family":"Wang","sequence":"additional","affiliation":[{"name":"Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital Capital Medical University, National Center for Children's Health  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5334-9706","authenticated-orcid":false,"given":"Zhi\u2010Gang","family":"Li","sequence":"additional","affiliation":[{"name":"Hematologic Disease Laboratory, Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Pediatric Research Institute, Beijing Children's Hospital Capital Medical University, National Center for Children's Health  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tian\u2010You","family":"Wang","sequence":"additional","affiliation":[{"name":"Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital Capital Medical University, National Center for Children's Health  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Beijing Children's Hospital Capital Medical University, National Center for Children's Health  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2048-6397","authenticated-orcid":false,"given":"Yan\u2010Long","family":"Duan","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Pediatric Oncology Center, Beijing Children\u2019s Hospital Capital Medical University, National Center for Children\u2019s Health  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3727-1192","authenticated-orcid":false,"given":"Rui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital Capital Medical University, National Center for Children's Health  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,4,16]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019000936"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0251-4"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2018028340"},{"issue":"13","key":"e_1_2_11_5_1","first-page":"1058","article-title":"HAVCR2 mutations are associated with severe hemophagocytic syndrome in subcutaneous panniculitis\u2010like T\u2010cell lymphoma","volume":"135","author":"Sonigo G","year":"2020","journal-title":"Blood"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.20502"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-04-087288"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020001497"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.21039"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021014860"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.semdp.2016.11.009"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.13440"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPH.0000000000001434"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPH.0000000000001954"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.14611"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.2340\/00015555-2543"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2018.05.1243"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni988"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1684\/ejd.2016.2914"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-018-02568-9"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2021004562"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1110557"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1409002"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020004823"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.614704"}],"container-title":["British Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bjh.18817","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,10]],"date-time":"2023-11-10T10:32:28Z","timestamp":1699612348000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bjh.18817"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,16]]},"references-count":24,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2023,7]]}},"alternative-id":["10.1111\/bjh.18817"],"URL":"https:\/\/doi.org\/10.1111\/bjh.18817","archive":["Portico"],"relation":{},"ISSN":["0007-1048","1365-2141"],"issn-type":[{"value":"0007-1048","type":"print"},{"value":"1365-2141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,16]]},"assertion":[{"value":"2023-01-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}