{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T08:42:13Z","timestamp":1761986533289,"version":"3.37.3"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,5,10]],"date-time":"2019-05-10T00:00:00Z","timestamp":1557446400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,5,10]],"date-time":"2019-05-10T00:00:00Z","timestamp":1557446400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Infect Dis"],"published-print":{"date-parts":[[2019,12]]},"DOI":"10.1186\/s12879-019-4022-3","type":"journal-article","created":{"date-parts":[[2019,5,10]],"date-time":"2019-05-10T10:04:44Z","timestamp":1557482684000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["A nearly fatal primary Epstein-Barr virus infection associated with low NK-cell counts in a patient receiving azathioprine: a case report and review of literature"],"prefix":"10.1186","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8288-9442","authenticated-orcid":false,"given":"Minna","family":"Honkila","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riitta","family":"Niinim\u00e4ki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mervi","family":"Taskinen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Outi","family":"Kuismin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaisa","family":"Kettunen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janna","family":"Saarela","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sami","family":"Turunen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marjo","family":"Renko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Terhi","family":"Tapiainen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,5,10]]},"reference":[{"key":"4022_CR1","doi-asserted-by":"publisher","first-page":"1505","DOI":"10.1086\/491740","volume":"192","author":"HH Balfour Jr","year":"2005","unstructured":"Balfour HH Jr, Holman CJ, Hokanson KM, et al. A prospective clinical study of Epstein-Barr virus and host interactions during acute infectious mononucleosis. J Infect Dis. 2005;192:1505\u201312.","journal-title":"J Infect Dis"},{"key":"4022_CR2","doi-asserted-by":"publisher","first-page":"R94","DOI":"10.1186\/gb-2011-12-9-r94","volume":"12","author":"AM Sulonen","year":"2011","unstructured":"Sulonen AM, Ellonen P, Almusa H, et al. Comparison of solution-based exome capture methods for next generation sequencing. Genome Biol. 2011;12:R94.","journal-title":"Genome Biol"},{"key":"4022_CR3","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1016\/j.crohns.2012.05.002","volume":"7","author":"MP Fitzgerald","year":"2013","unstructured":"Fitzgerald MP, Armstrong L, Hague R, Russell RK. A case of EBV driven haemophagocytic lymphohistiocytosis complicating a teenage Crohn's disease patient on azathioprine, successfully treated with rituximab. J Crohns Colitis. 2013;7:314\u20137.","journal-title":"J Crohns Colitis"},{"key":"4022_CR4","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1016\/j.jpeds.2011.04.045","volume":"159","author":"VF Biank","year":"2011","unstructured":"Biank VF, Sheth MK, Talano J, et al. Association of Crohn's disease, thiopurines, and primary epstein-barr virus infection with hemophagocytic lymphohistiocytosis. J Pediatr. 2011;159:808\u201312.","journal-title":"J Pediatr"},{"key":"4022_CR5","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1097\/MPG.0b013e3181e80410","volume":"52","author":"D Gidrewicz","year":"2011","unstructured":"Gidrewicz D, Lehman D, Rabizadeh S, Majlessipour F, Dubinsky M. Primary EBV infection resulting in lymphoproliferative disease in a teenager with Crohn disease. J Pediatr Gastroenterol Nutr. 2011;52:103\u20135.","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"4022_CR6","doi-asserted-by":"publisher","first-page":"E1","DOI":"10.1002\/ibd.21278","volume":"17","author":"E Angelucci","year":"2011","unstructured":"Angelucci E, Cesarini M, Caturelli E, Vernia P. EBV hepatitis in a young Crohn's disease patient on prolonged remission with azathioprine. Inflamm Bowel Dis. 2011;17:E1.","journal-title":"Inflamm Bowel Dis"},{"key":"4022_CR7","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1097\/MPG.0b013e3181d893c6","volume":"51","author":"S Ross","year":"2010","unstructured":"Ross S, Rajwal SK, Sugarman I, et al. Epstein-Barr virus-associated lymphoproliferative disorder in Crohn disease treated with azathioprine. J Pediatr Gastroenterol Nutr. 2010;51:229\u201331.","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"4022_CR8","doi-asserted-by":"publisher","first-page":"174","DOI":"10.3109\/10428190903402029","volume":"51","author":"S Courby","year":"2010","unstructured":"Courby S, Fabre B, Salameire D, et al. Multifocal polyclonal Epstein-Barr virus-associated B-cell lymphoproliferative disorder secondary to azathioprine therapy successfully treated with rituximab. Leuk Lymphoma. 2010;51:174\u20137.","journal-title":"Leuk Lymphoma"},{"key":"4022_CR9","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1002\/ibd.21104","volume":"16","author":"T Moreira","year":"2010","unstructured":"Moreira T, Lago P, Salgado M, Pimentel R. Epstein-Barr virus and parvovirus B19 coinfection in a Crohn's disease patient under azathioprine. Inflamm Bowel Dis. 2010;16:905\u20136.","journal-title":"Inflamm Bowel Dis"},{"key":"4022_CR10","doi-asserted-by":"publisher","first-page":"1252","DOI":"10.1128\/JCM.02052-08","volume":"47","author":"Y N'guyen","year":"2009","unstructured":"N'guyen Y, Andreoletti L, Patey M, et al. Fatal Epstein-Barr virus primo infection in a 25-year-old man treated with azathioprine for Crohn's disease. J Clin Microbiol. 2009;47:1252\u20134.","journal-title":"J Clin Microbiol"},{"key":"4022_CR11","doi-asserted-by":"publisher","first-page":"1449","DOI":"10.1002\/ibd.20823","volume":"15","author":"C Serrate","year":"2009","unstructured":"Serrate C, Silva-Moreno M, Dartigues P, et al. Epstein-Barr virus-associated lymphoproliferation awareness in hemophagocytic syndrome complicating thiopurine treatment for Crohn's disease. Inflamm Bowel Dis. 2009;15:1449\u201351.","journal-title":"Inflamm Bowel Dis"},{"key":"4022_CR12","doi-asserted-by":"publisher","first-page":"1613","DOI":"10.1002\/ibd.20856","volume":"15","author":"S Hagel","year":"2009","unstructured":"Hagel S, Bruns T, Kantowski M, Fix P, Seidel T, Stallmach A. Cholestatic hepatitis, acute acalculous cholecystitis, and hemolytic anemia: primary Epstein-Barr virus infection under azathioprine. Inflamm Bowel Dis. 2009;15:1613\u20136.","journal-title":"Inflamm Bowel Dis"},{"key":"4022_CR13","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1097\/MPG.0b013e31816a30b9","volume":"47","author":"KA Francolla","year":"2008","unstructured":"Francolla KA, Altman A, Sylvester FA. Hemophagocytic syndrome in an adolescent with Crohn disease receiving azathioprine and infliximab. J Pediatr Gastroenterol Nutr. 2008;47:193\u20135.","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"4022_CR14","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1136\/gut.36.2.311","volume":"36","author":"EF Posthuma","year":"1995","unstructured":"Posthuma EF, Westendorp RG, Van der Sluys Veer A, Kluin-Nelemans JC, Kluin PM, Lamers CB. Fatal infectious mononucleosis: a severe complication in the treatment of Crohn's disease with azathioprine. Gut. 1995;36:311\u20133.","journal-title":"Gut."},{"key":"4022_CR15","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1056\/NEJM199409293311321","volume":"331","author":"L Larvol","year":"1994","unstructured":"Larvol L, Soule JC, Le TA. Reversible lymphoma in the setting of azathioprine therapy for Crohn's disease. N Engl J Med. 1994;331:883\u20134.","journal-title":"N Engl J Med"},{"key":"4022_CR16","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1016\/j.molimm.2013.01.015","volume":"54","author":"G Bouma","year":"2013","unstructured":"Bouma G, Baggen JM, van Bodegraven AA, et al. Thiopurine treatment in patients with Crohn's disease leads to a selective reduction of an effector cytotoxic gene expression signature revealed by whole-genome expression profiling. Mol Immunol. 2013;54:472\u201381.","journal-title":"Mol Immunol"},{"key":"4022_CR17","doi-asserted-by":"publisher","first-page":"3240","DOI":"10.3748\/wjg.v23.i18.3240","volume":"23","author":"JD Lord","year":"2017","unstructured":"Lord JD, Shows DM. Thiopurine use associated with reduced B and natural killer cells in inflammatory bowel disease. World J Gastroenterol. 2017;23:3240\u201351.","journal-title":"World J Gastroenterol"},{"key":"4022_CR18","doi-asserted-by":"publisher","first-page":"2533","DOI":"10.1182\/blood-2014-01-553024","volume":"124","author":"T Azzi","year":"2014","unstructured":"Azzi T, L\u00fcnemann A, Murer A, et al. Role for early-differentiated natural killer cells in infectious mononucleosis. Blood. 2014;124:2533\u201343.","journal-title":"Blood."},{"key":"4022_CR19","doi-asserted-by":"publisher","first-page":"1489","DOI":"10.1016\/j.celrep.2013.11.041","volume":"5","author":"O Chijioke","year":"2013","unstructured":"Chijioke O, M\u00fcller A, Feederle R, et al. Human natural killer cells prevent infectious mononucleosis features by targeting lytic Epstein-Barr virus infection. Cell Rep. 2013;5:1489\u201398.","journal-title":"Cell Rep"},{"key":"4022_CR20","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.blre.2014.03.002","volume":"28","author":"GE Janka","year":"2014","unstructured":"Janka GE, Lehmberg K. Hemophagocytic syndromes--an update. Blood Rev. 2014;28:135\u201342.","journal-title":"Blood Rev"},{"key":"4022_CR21","doi-asserted-by":"publisher","first-page":"1617","DOI":"10.1016\/S0140-6736(09)61302-7","volume":"374","author":"L Beaugerie","year":"2009","unstructured":"Beaugerie L, Brousse N, Bouvier AM, et al. Lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study. Lancet. 2009;374:1617\u201325.","journal-title":"Lancet."},{"key":"4022_CR22","doi-asserted-by":"publisher","first-page":"3331","DOI":"10.1182\/blood-2016-01-628982","volume":"127","author":"CM Bollard","year":"2016","unstructured":"Bollard CM, Heslop HE. T cells for viral infections after allogeneic hematopoietic stem cell transplant. Blood. 2016;127:3331\u201340.","journal-title":"Blood."}],"container-title":["BMC Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12879-019-4022-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12879-019-4022-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12879-019-4022-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,19]],"date-time":"2020-05-19T09:38:24Z","timestamp":1589881104000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcinfectdis.biomedcentral.com\/articles\/10.1186\/s12879-019-4022-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,10]]},"references-count":22,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["4022"],"URL":"https:\/\/doi.org\/10.1186\/s12879-019-4022-3","relation":{},"ISSN":["1471-2334"],"issn-type":[{"type":"electronic","value":"1471-2334"}],"subject":[],"published":{"date-parts":[[2019,5,10]]},"assertion":[{"value":"7 February 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 April 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 May 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Both the patient and her legal guardian gave their written consent to the publication of this case history.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Publisher\u2019s Note"}}],"article-number":"404"}}