{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T03:22:12Z","timestamp":1774408932046,"version":"3.50.1"},"reference-count":15,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,6,9]],"date-time":"2020-06-09T00:00:00Z","timestamp":1591660800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,6,9]],"date-time":"2020-06-09T00:00:00Z","timestamp":1591660800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ann Clin Microbiol Antimicrob"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>Adult-onset hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening condition, which is often triggered by certain types of infection, cancer and numerous autoimmune diseases; however, of the numerous infectious triggers associated with HLH, the consequences of <jats:italic>Bartonella henselae<\/jats:italic> infection have been rarely reported.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Case presentation<\/jats:title>\n<jats:p>A 48-year-old female presented with a 20-day history of intermittent fever accompanied by systemic rash, fatigue, anorexia and weight loss later she developed shock and unconsciousness. Blood tests showed a reduction of leukocyte, anemia and thrombocytopenia, and pathological results of a bone marrow biopsy confirmed hemophagocytic activity. Metagenomic next-generation sequencing (mNGS) analysis of the lymph node detected the presence of <jats:italic>B. henselae<\/jats:italic>. Whole exome sequencing revealed two gene variants, STXBP2 and IRF5, in this adult patient with secondary HLH. Then, she received minocycline and rifampin combination anti-infective therapy. Intravenous immunoglobulin for 5\u00a0days followed by a high dose of methylprednisolone were also administered. The patient was successfully discharged from the intensive care unit and remained in good condition after 2\u00a0months of follow-up.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>mNGS served crucial roles in obtaining an etiological diagnosis, which suggested that screening for <jats:italic>B. henselae<\/jats:italic> should be considered in patients with HLH, especially those with a cat at home. In addition, the genetic defects were discovered to not only be present in primary HLH, but also in secondary HLH, even in the elderly.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s12941-020-00370-2","type":"journal-article","created":{"date-parts":[[2020,6,9]],"date-time":"2020-06-09T12:03:02Z","timestamp":1591704182000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Hemophagocytic lymphohistiocytosis is associated with Bartonella henselae infection in a patient with multiple susceptibility genes"],"prefix":"10.1186","volume":"19","author":[{"given":"Tianjun","family":"Yang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Mei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhendong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunyan","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaowei","family":"Fang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shike","family":"Geng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3853-3879","authenticated-orcid":false,"given":"Aijun","family":"Pan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,6,9]]},"reference":[{"issue":"2","key":"370_CR1","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1002\/pbc.21039","volume":"48","author":"JI Henter","year":"2007","unstructured":"Henter JI, Horne A, Aric\u00f3 M, Egeler RM, Filipovich AH, Imashuku S, Ladisch S, McClain K, Webb D, Winiarski J, Janka G. HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007;48(2):124\u201331.","journal-title":"Pediatr Blood Cancer"},{"issue":"6","key":"370_CR2","doi-asserted-by":"publisher","first-page":"804","DOI":"10.1093\/cid\/civ999","volume":"62","author":"A Le Joncour","year":"2016","unstructured":"Le Joncour A, Bidegain F, Ziol M, Galicier L, Oksenhendler E, Mechai F, Boutboul D, Bouchaud O. Hemophagocytic lymphohistiocytosis associated with Bartonella henselae infection in an HIV-infected patient. Clin Infect Dis. 2016;62(6):804\u20136.","journal-title":"Clin Infect Dis"},{"issue":"3","key":"370_CR3","doi-asserted-by":"publisher","first-page":"E83","DOI":"10.1111\/petr.12235","volume":"18","author":"A Poudel","year":"2014","unstructured":"Poudel A, Lew J, Slayton W, Dharnidharka VR. Bartonella henselae infection inducing hemophagocytic lymphohistiocytosis in a kidney transplant recipient. Pediatr Transplant. 2014;18(3):E83\u20137.","journal-title":"Pediatr Transplant"},{"issue":"5","key":"370_CR4","doi-asserted-by":"publisher","first-page":"e0155908","DOI":"10.1371\/journal.pone.0155908","volume":"11","author":"H Deng","year":"2016","unstructured":"Deng H, Lu Q, Xu H, Deng X, Yuan L, Yang Z, Guo Y, Lin Q, Xiao J, Guan L, Song Z. Identification of a novel missense FBN2 mutation in a Chinese family with congenital contractural arachnodactyly using exome sequencing. PLoS ONE. 2016;11(5):e0155908.","journal-title":"PLoS ONE"},{"key":"370_CR5","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.mcp.2016.10.006","volume":"32","author":"E Parra","year":"2017","unstructured":"Parra E, Segura F, Tijero J, Pons I, Nogueras MM. Development of a real-time PCR for Bartonella spp. detection, a current emerging microorganism. Mol Cell Probes. 2017;32:55\u20139.","journal-title":"Mol Cell Probes."},{"issue":"1","key":"370_CR6","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1186\/s12941-018-0294-5","volume":"17","author":"J Cheng","year":"2018","unstructured":"Cheng J, Hu H, Kang Y, Chen W, Fang W, Wang K, Zhang Q, Fu A, Zhou S, Cheng C, Cao Q, Wang F, Lee S, Zhou Z. Identification of pathogens in culture-negative infective endocarditis cases by metagenomic analysis. Ann Clin Microbiol Antimicrob. 2018;17(1):43.","journal-title":"Ann Clin Microbiol Antimicrob."},{"issue":"2","key":"370_CR7","doi-asserted-by":"publisher","first-page":"125","DOI":"10.4067\/S0716-10182013000200001","volume":"30","author":"K Abarca","year":"2013","unstructured":"Abarca K, Winter M, Marsac D, Palma C, Contreras AM, Ferres M. Accuracy and diagnostic utility of IgM in Bartonella henselae infections. Revista Chilena De Infectologia Organo Oficial De La Sociedad Chilena De Infectologia. 2013;30(2):125\u20138.","journal-title":"Revista Chilena De Infectologia Organo Oficial De La Sociedad Chilena De Infectologia"},{"issue":"4","key":"370_CR8","first-page":"92","volume":"25","author":"WI Farouk","year":"2018","unstructured":"Farouk WI, Hassan NH, Ismail TR, Daud IS, Mohammed F. Warthin-Starry staining for the detection of Helicobacter pylori in gastric biopsies. Malays J Med Sci. 2018;25(4):92\u20139.","journal-title":"Malays J Med Sci."},{"issue":"3","key":"370_CR9","first-page":"261","volume":"14","author":"M Bagheri","year":"2015","unstructured":"Bagheri M, Dong Y, Ono M. Molecular diversity of macrophages in allergic reaction: comparison between the allergenic modes; Th1- and -Th2-derived immune conditions. Iran J Allergy Asthma Immunol. 2015;14(3):261\u201372.","journal-title":"Iran J Allergy Asthma Immunol."},{"issue":"Suppl 2","key":"370_CR10","doi-asserted-by":"publisher","first-page":"S61","DOI":"10.1136\/thorax.55.suppl_2.S61","volume":"55","author":"WJ Pichler","year":"2000","unstructured":"Pichler WJ, Yawalkar N. Allergic reactions to drugs: involvement of T cells. Thorax. 2000;55(Suppl 2):S61\u20135.","journal-title":"Thorax"},{"issue":"9","key":"370_CR11","doi-asserted-by":"publisher","first-page":"1281","DOI":"10.1111\/j.1349-7006.2007.00549.x","volume":"98","author":"HC Chuang","year":"2007","unstructured":"Chuang HC, Lay JD, Hsieh WC, Su IJ. Pathogenesis and mechanism of disease progression from hemophagocytic lymphohistiocytosis to Epstein\u2013Barr virus-associated T-cell lymphoma: nuclear factor-kappa B pathway as a potential therapeutic target. Cancer Sci. 2007;98(9):1281\u20137.","journal-title":"Cancer Sci"},{"issue":"9","key":"370_CR12","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1136\/jmg.2009.075341","volume":"47","author":"V Cetica","year":"2010","unstructured":"Cetica V, Santoro A, Gilmour KC, Sieni E, Beutel K, Pende D, Marcenaro S, Koch F, Grieve S, Wheeler R, Zhao F, zur Stadt U, Griffiths GM, Aric\u00f2 M. STXBP2 mutations in children with familial haemophagocytic lymphohistiocytosis type 5. J Med Genet. 2010;47(9):595\u2013600.","journal-title":"J Med Genet."},{"issue":"8","key":"370_CR13","doi-asserted-by":"publisher","first-page":"e0159454","DOI":"10.1371\/journal.pone.0159454","volume":"11","author":"L Yang","year":"2016","unstructured":"Yang L, Tang Y, Xiao F, Xiong J, Shen K, Liu Y, Zhang W, Zheng L, Zhou J, Xiao M. Hemophagocytic lymphohistocytosis in the Chinese Han population may be associated with an STXBP2 Gene polymorphism. PLoS ONE. 2016;11(8):e0159454.","journal-title":"PLoS ONE"},{"issue":"2","key":"370_CR14","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1016\/j.jid.2019.06.147","volume":"140","author":"HN Thynn","year":"2020","unstructured":"Thynn HN, Chen XF, Hu WX, Duan YY, Zhu DL, Chen H, Wang NN, Chen HH, Rong Y, Lu BJ, Yang M, Jiang F, Dong SS, Guo Y, Yang TL. An allele-specific functional SNP associated with two systemic autoimmune diseases modulates IRF5 expression by long-range chromatin loop formation. J Investig Dermatol. 2020;140(2):348\u201360.","journal-title":"J Investig Dermatol."},{"issue":"6","key":"370_CR15","doi-asserted-by":"publisher","first-page":"946","DOI":"10.1007\/s10875-011-9583-x","volume":"31","author":"M Yanagimachi","year":"2011","unstructured":"Yanagimachi M, Goto H, Miyamae T, Kadota K, Imagawa T, Mori M, Sato H, Yanagisawa R, Kaneko T, Morita S, Ishii E, Yokota S. Association of IRF5 polymorphisms with susceptibility to hemophagocytic lymphohistiocytosis in children. J Clin Immunol. 2011;31(6):946\u201351.","journal-title":"J Clin Immunol"}],"container-title":["Annals of Clinical Microbiology and Antimicrobials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12941-020-00370-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12941-020-00370-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12941-020-00370-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,8]],"date-time":"2021-06-08T23:26:51Z","timestamp":1623194811000},"score":1,"resource":{"primary":{"URL":"https:\/\/ann-clinmicrob.biomedcentral.com\/articles\/10.1186\/s12941-020-00370-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,9]]},"references-count":15,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["370"],"URL":"https:\/\/doi.org\/10.1186\/s12941-020-00370-2","relation":{},"ISSN":["1476-0711"],"issn-type":[{"value":"1476-0711","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,9]]},"assertion":[{"value":"17 March 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 May 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 June 2020","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":"Written informed consent was obtained from the patient for publication of this case and the accompanying images.","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"}}],"article-number":"28"}}