{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T12:45:31Z","timestamp":1785242731117,"version":"3.55.0"},"reference-count":46,"publisher":"Elsevier BV","issue":"5","license":[{"start":{"date-parts":[[2011,11,1]],"date-time":"2011-11-01T00:00:00Z","timestamp":1320105600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Pediatrics"],"published-print":{"date-parts":[[2011,11]]},"DOI":"10.1016\/j.jpeds.2011.04.045","type":"journal-article","created":{"date-parts":[[2011,10,16]],"date-time":"2011-10-16T20:52:36Z","timestamp":1318798356000},"page":"808-812","source":"Crossref","is-referenced-by-count":70,"title":["Association of Crohn\u2019s Disease, Thiopurines, and Primary Epstein-Barr Virus Infection with Hemophagocytic Lymphohistiocytosis"],"prefix":"10.1016","volume":"159","author":[{"given":"Vincent F.","family":"Biank","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehul K.","family":"Sheth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Talano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Margolis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pippa","family":"Simpson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subra","family":"Kugathasan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Stephens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jpeds.2011.04.045_bib1","doi-asserted-by":"crossref","first-page":"601","DOI":"10.3201\/eid0606.000608","article-title":"Hemophagocytic syndromes and infection","volume":"6","author":"Fisman","year":"2000","journal-title":"Emerg Infect Dis"},{"key":"10.1016\/j.jpeds.2011.04.045_bib2","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1002\/(SICI)1096-911X(199705)28:5<342::AID-MPO3>3.0.CO;2-H","article-title":"HLH-94: a treatment protocol for hemophagocytic lymphohistiocytosis. HLH Study Group of the Histiocyte Society","volume":"28","author":"Henter","year":"1997","journal-title":"Med Pediatr Oncol"},{"key":"10.1016\/j.jpeds.2011.04.045_bib3","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/S0889-8588(05)70520-7","article-title":"Familial hemophagocytic lymphohistiocytosis: primary hemophagocytic lymphohistiocytosis","volume":"12","author":"Henter","year":"1998","journal-title":"Hematol Oncol Clin North Am"},{"key":"10.1016\/j.jpeds.2011.04.045_bib4","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1002\/pbc.21039","article-title":"HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis","volume":"48","author":"Henter","year":"2007","journal-title":"Pediatr Blood Cancer"},{"key":"10.1016\/j.jpeds.2011.04.045_bib5","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/S0022-3476(97)70195-1","article-title":"Hemophagocytic lymphohistiocytosis in infancy and childhood","volume":"130","author":"Imashuku","year":"1997","journal-title":"J Pediatr"},{"key":"10.1016\/j.jpeds.2011.04.045_bib6","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1182\/asheducation-2005.1.82","article-title":"Familial and acquired hemophagocytic lymphohistiocytosis","author":"Janka","year":"2005","journal-title":"Hematology Am Soc Hematol Educ Program"},{"key":"10.1016\/j.jpeds.2011.04.045_bib7","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1111\/j.1651-2227.1991.tb11878.x","article-title":"Incidence in Sweden and clinical features of familial hemophagocytic lymphohistiocytosis","volume":"80","author":"Henter","year":"1991","journal-title":"Acta Paediatr Scand"},{"key":"10.1016\/j.jpeds.2011.04.045_bib8","series-title":"Nelson textbook of pediatrics","author":"Kliegman","year":"2007"},{"key":"10.1016\/j.jpeds.2011.04.045_bib9","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1097\/00005176-200410000-00020","article-title":"Cytomegalovirus-associated hemophagocytic syndrome in a child with Crohn disease receiving azathioprine","volume":"39","author":"Babu","year":"2004","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"10.1016\/j.jpeds.2011.04.045_bib10","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1002\/art.11368","article-title":"Reactive hemophagocytic syndrome in adult systemic disease: report of twenty-six cases and literature review","volume":"49","author":"Dhote","year":"2003","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.jpeds.2011.04.045_bib11","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1097\/MPG.0b013e31816a30b9","article-title":"Hemophagocytic syndrome in an adolescent with Crohn disease receiving azathioprine and infliximab","volume":"47","author":"Francolla","year":"2008","journal-title":"J\u00a0Pediatr Gastroenterol Nutr"},{"key":"10.1016\/j.jpeds.2011.04.045_bib12","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1097\/01.MIB.0000225333.83861.16","article-title":"Reactive hemophagocytic syndrome complicating the treatment of inflammatory bowel disease","volume":"12","author":"James","year":"2006","journal-title":"Inflamm Bowel Dis"},{"key":"10.1016\/j.jpeds.2011.04.045_bib13","doi-asserted-by":"crossref","first-page":"216","DOI":"10.2500\/aap.2008.29.3103","article-title":"A boy with fever, lymphadenopathy, hepatosplenomegaly, and lymphocytosis","volume":"29","author":"Kaza","year":"2008","journal-title":"Allergy Asthma Proc"},{"key":"10.1016\/j.jpeds.2011.04.045_bib14","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1097\/00005792-198811000-00002","article-title":"Hematophagic histiocytosis: a report of 23 new patients and a review of the literature","volume":"67","author":"Reiner","year":"1988","journal-title":"Medicine (Baltimore)"},{"key":"10.1016\/j.jpeds.2011.04.045_bib15","first-page":"197","article-title":"Hemophagocytic lymphohistiocytosis: report of 122 children from the International Registry. FHL Study Group of the Histiocyte Society","volume":"10","author":"Arico","year":"1996","journal-title":"Leukemia"},{"key":"10.1016\/j.jpeds.2011.04.045_bib16","first-page":"29","article-title":"Diagnostic guidelines for hemophagocytic lymphohistiocytosis. The FHL Study Group of the Histiocyte Society","volume":"18","author":"Henter","year":"1991","journal-title":"Semin Oncol"},{"key":"10.1016\/j.jpeds.2011.04.045_bib17","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1002\/mpo.10314","article-title":"Treatment of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) in young adults: a report from the HLH study center","volume":"41","author":"Imashuku","year":"2003","journal-title":"Med Pediatr Oncol"},{"key":"10.1016\/j.jpeds.2011.04.045_bib18","unstructured":"Adamiak Tw-J, Fish D, Brown C, Tung J, Khan K, Faulion W, et\u00a0al. Burden of childhood onset inflammatory bowel disease (IBD) in the United States (US): a large populaiton-based tudy Determines the Incidence, Prevalence and Cumulative Medication Exposure In The NASPGHAN-CDHNF Partnership: A Clinical & Scientific Conference. San Diego, CA; 2008."},{"key":"10.1016\/j.jpeds.2011.04.045_bib19","unstructured":"US Census Bureau. [about 2 screens]. http:\/\/factfinder.census.gov\/servlet\/STTable?_bm = y&-geo_id = 04000US55&-qr_name = ACS_2008_3YR_G00_S0101&-ds_name = ACS_2008_3YR_G00_. Accessed June 20, 2011."},{"key":"10.1016\/j.jpeds.2011.04.045_bib20","series-title":"Rudolph\u2019s Pediatrics","author":"Rudolph","year":"2003"},{"key":"10.1016\/j.jpeds.2011.04.045_bib21","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1542\/peds.75.6.1011","article-title":"Epstein-Barr virus infectious mononucleosis in children. II. Heterophil antibody and viral-specific responses","volume":"75","author":"Sumaya","year":"1985","journal-title":"Pediatrics"},{"key":"10.1016\/j.jpeds.2011.04.045_bib22","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1080\/07853890500465189","article-title":"Hemophagocytic lymphohistiocytosis: diagnosis, pathophysiology, treatment, and future perspectives","volume":"38","author":"Verbsky","year":"2006","journal-title":"Ann Med"},{"key":"10.1016\/j.jpeds.2011.04.045_bib23","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/S0889-8588(05)70521-9","article-title":"Infection- and malignancy-associated hemophagocytic syndromes: secondary hemophagocytic lymphohistiocytosis","volume":"12","author":"Janka","year":"1998","journal-title":"Hematol Oncol Clin North Am"},{"key":"10.1016\/j.jpeds.2011.04.045_bib24","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1086\/500262","article-title":"Cytomegalovirus ileitis and hemophagocytic syndrome associated with use of anti-tumor necrosis factor-alpha antibody","volume":"42","author":"Kohara","year":"2006","journal-title":"Clin Infect Dis"},{"key":"10.1016\/j.jpeds.2011.04.045_bib25","first-page":"147","article-title":"Epstein-Barr virus-associated hemophagocytic syndrome masquerading as lymphoma: a case report","volume":"34","author":"Jaing","year":"2001","journal-title":"J Microbiol Immunol Infect"},{"key":"10.1016\/j.jpeds.2011.04.045_bib26","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/S0755-4982(05)83984-3","article-title":"[Macrophage activation syndrome after treatment with infliximab for fistulated Crohn disease]","volume":"34","author":"Chauveau","year":"2005","journal-title":"Presse Med"},{"key":"10.1016\/j.jpeds.2011.04.045_bib27","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1111\/j.1572-0241.1998.00554.x","article-title":"Hemophagocytic syndrome associated with fulminant ulcerative colitis and presumed acute pancreatitis","volume":"93","author":"Kanaji","year":"1998","journal-title":"Am J Gastroenterol"},{"key":"10.1016\/j.jpeds.2011.04.045_bib28","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1007\/s10350-004-0543-x","article-title":"Hemophagocytic syndrome caused by fulminant ulcerative colitis and cytomegalovirus infection: report of a case","volume":"47","author":"Koketsu","year":"2004","journal-title":"Dis Colon Rectum"},{"key":"10.1016\/j.jpeds.2011.04.045_bib29","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1136\/gut.36.2.311","article-title":"Fatal infectious mononucleosis: a severe complication in the treatment of Crohn\u2019s disease with azathioprine","volume":"36","author":"Posthuma","year":"1995","journal-title":"Gut"},{"key":"10.1016\/j.jpeds.2011.04.045_bib30","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1007\/s002770050174","article-title":"Fever and progressive pancytopenia in a 20-year-old woman with Crohn\u2019s disease","volume":"72","author":"Sijpkens","year":"1996","journal-title":"Ann Hematol"},{"key":"10.1016\/j.jpeds.2011.04.045_bib31","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1002\/ibd.20823","article-title":"Epstein-Barr virus-associated lymphoproliferation awareness in hemophagocytic syndrome complicating thiopurine treatment for Crohn\u2019s disease","volume":"15","author":"Serrate","year":"2009","journal-title":"Inflamm Bowel Dis"},{"key":"10.1016\/j.jpeds.2011.04.045_bib32","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1016\/0016-5085(90)91160-8","article-title":"Long-term 6-mercaptopurine treatment in adolescents with Crohn\u2019s disease","volume":"99","author":"Markowitz","year":"1990","journal-title":"Gastroenterology"},{"key":"10.1016\/j.jpeds.2011.04.045_bib33","first-page":"44","article-title":"Immunosuppressive therapy in pediatric inflammatory bowel disease: results of a survey of the North American Society for Pediatric Gastroenterology and Nutrition, Subcommittee on Immunosuppressive Use of the Pediatric IBD Collaborative Research Forum","volume":"88","author":"Markowitz","year":"1993","journal-title":"Am J Gastroenterol"},{"key":"10.1016\/j.jpeds.2011.04.045_bib34","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1053\/gast.2000.18144","article-title":"A multicenter trial of 6-mercaptopurine and prednisone in children with newly diagnosed Crohn\u2019s disease","volume":"119","author":"Markowitz","year":"2000","journal-title":"Gastroenterology"},{"key":"10.1016\/j.jpeds.2011.04.045_bib35","first-page":"928","article-title":"Immunomodulatory therapy for pediatric inflammatory bowel disease: changing patterns of use, 1990-2000","volume":"97","author":"Markowitz","year":"2002","journal-title":"Am J Gastroenterol"},{"key":"10.1016\/j.jpeds.2011.04.045_bib36","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1097\/00005176-200211000-00021","article-title":"Severe pancytopenia from thiopurine methyltransferase deficiency: a preventable complication of 6-mercaptopurine therapy in children with Crohn disease","volume":"35","author":"Rosen","year":"2002","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"10.1016\/j.jpeds.2011.04.045_bib37","doi-asserted-by":"crossref","first-page":"429","DOI":"10.3109\/08923977909040545","article-title":"The effects of azathioprine and 6 MP on immunity","volume":"1","author":"Winkelstein","year":"1979","journal-title":"J Immunopharmacol"},{"key":"10.1016\/j.jpeds.2011.04.045_bib38","first-page":"249","article-title":"Immunosuppression in the treatment of inflammatory bowel disease. II. The effects of azathioprine on lymphoid cell populations in a double-blind trial in ulcerative colitis","volume":"24","author":"Campbell","year":"1976","journal-title":"Clin Exp Immunol"},{"key":"10.1016\/j.jpeds.2011.04.045_bib39","doi-asserted-by":"crossref","first-page":"45","DOI":"10.7326\/0003-4819-118-1-199301010-00009","article-title":"NIH conference. Epstein-Barr virus infections: biology, pathogenesis, and management","volume":"118","author":"Straus","year":"1993","journal-title":"Ann Intern Med"},{"key":"10.1016\/j.jpeds.2011.04.045_bib40","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/S0952-7915(99)80062-4","article-title":"The biology of Epstein-Barr virus: lessons learned from the virus and the host","volume":"11","author":"Cohen","year":"1999","journal-title":"Curr Opin Immunol"},{"key":"10.1016\/j.jpeds.2011.04.045_bib41","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1128\/CMR.1.3.300","article-title":"Epstein-Barr virus and human diseases: recent advances in diagnosis","volume":"1","author":"Okano","year":"1988","journal-title":"Clin Microbiol Rev"},{"key":"10.1016\/j.jpeds.2011.04.045_bib42","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1007\/s100249900093","article-title":"X-linked lymphoproliferative disease: pathology and diagnosis","volume":"2","author":"Maia","year":"1999","journal-title":"Pediatr Dev Pathol"},{"key":"10.1016\/j.jpeds.2011.04.045_bib43","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1097\/00062752-199901000-00005","article-title":"Epstein-Barr virus and lymphoproliferative disease","volume":"6","author":"Mosier","year":"1999","journal-title":"Curr Opin Hematol"},{"key":"10.1016\/j.jpeds.2011.04.045_bib44","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1067\/S0022-3476(03)00444-X","article-title":"Epidemiologic and clinical characteristics of children with newly diagnosed inflammatory bowel disease in Wisconsin: a statewide population-based study","volume":"143","author":"Kugathasan","year":"2003","journal-title":"J Pediatr"},{"key":"10.1016\/j.jpeds.2011.04.045_bib45","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1097\/00002281-200309000-00011","article-title":"Macrophage activation syndrome and reactive hemophagocytic lymphohistiocytosis: the same entities?","volume":"15","author":"Grom","year":"2003","journal-title":"Curr Opin Rheumatol"},{"key":"10.1016\/j.jpeds.2011.04.045_bib46","doi-asserted-by":"crossref","first-page":"2665","DOI":"10.1200\/JCO.2001.19.10.2665","article-title":"Requirement for etoposide in the treatment of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis","volume":"19","author":"Imashuku","year":"2001","journal-title":"J Clin Oncol"}],"container-title":["The Journal of Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022347611004525?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022347611004525?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2021,12,11]],"date-time":"2021-12-11T05:33:48Z","timestamp":1639200828000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0022347611004525"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,11]]},"references-count":46,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2011,11]]}},"alternative-id":["S0022347611004525"],"URL":"https:\/\/doi.org\/10.1016\/j.jpeds.2011.04.045","relation":{},"ISSN":["0022-3476"],"issn-type":[{"value":"0022-3476","type":"print"}],"subject":[],"published":{"date-parts":[[2011,11]]}}}