{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:30:25Z","timestamp":1792794625187,"version":"4.5.0"},"reference-count":19,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Hemophagocytic lymphohistiocytosis (HLH) is a disorder characterized by dysregulated immune activation triggered by various etiologies, leading to excessive inflammatory responses, cytokine storm, and subsequent organ dysfunction. While the presence of hemophagocytic cells in septic shock is generally considered a physiological response that seldom requires specific intervention, the finding of abundant hemophagocytes along with\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    (\n                    <jats:italic>E. coli<\/jats:italic>\n                    ) on a bone marrow smear warrants careful assessment for possible HLH. We herein present a fatal case of HLH secondary to an E. coli urinary tract infection in a seronegative rheumatoid arthritis patient on low-dose methotrexate. The bone marrow smear not only demonstrated typical hemophagocytes but also revealed phagocytes containing ingested E. coli. In contrast to previously reported cases,\n                    <jats:italic>E. coli<\/jats:italic>\n                    in this patient not only caused severe bacteremia but was also demonstrated on the bone marrow aspirate, resulting in profound immunosuppression.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1863594","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T04:23:50Z","timestamp":1783916630000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Case Report: Hemophagocytic lymphohistiocytosis secondary to Escherichia coli infiltration of bone marrow in a patient with seronegative rheumatoid arthritis treated with low-dose methotrexate"],"prefix":"10.3389","volume":"17","author":[{"given":"Ziping","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory Medicine, The People\u2019s Hospital of Longhua","place":["Shenzhen, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengjian","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Medicine, The People\u2019s Hospital of Longhua","place":["Shenzhen, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunhong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Medicine, The People\u2019s Hospital of Longhua","place":["Shenzhen, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueyan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Medicine, The People\u2019s Hospital of Longhua","place":["Shenzhen, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)61048-X","article-title":"Adult haemophagocytic syndrome","volume":"383","author":"Ramos-Casals","year":"2014","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.27929","article-title":"Challenges in the diagnosis of hemophagocytic lymphohistiocytosis: Recommendations from the North American Consortium for Histiocytosis (NACHO)","volume":"66","author":"Jordan","year":"2019","journal-title":"Pediatr Blood Cancer"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.cn112140-20201111-01024","article-title":"Hemophagocytic lymphohistiocytosis: update on pathogenesis, diagnosis, and treatment","volume":"59","author":"Liu","year":"2021","journal-title":"Zhonghua Er Ke Za Zhi"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1097\/pcc.0b013e3181a1ae08","article-title":"Secondary hemophagocytic lymphohistiocytosis and severe sepsis\/ systemic inflammatory response syndrome\/multiorgan dysfunction syndrome\/macrophage activation syndrome share common intermediate phenotypes on a spectrum of inflammation","volume":"10","author":"Castillo","year":"2009","journal-title":"Pediatr Crit Care Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000001878","article-title":"The use of ferritin to identify critically ill patients with secondary hemophagocytic lymphohistiocytosis","volume":"44","author":"Grang\u00e9","year":"2016","journal-title":"Crit Care Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2022.102227","article-title":"Treatment of early rheumatoid arthritis: Methotrexate and beyond","volume":"64","author":"Garc\u00eda-Gonz\u00e1lez","year":"2022","journal-title":"Curr Opin Pharmacol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200007)43:7<1488::AID-ANR11>3.0.CO;2-G","article-title":"Inhibition of neutrophil migration soon after initiation of treatment with leflunomide or methotrexate in patients with rheumatoid arthritis: findings in a prospective, randomized, double-blind clinical trial in fifteen patients","volume":"43","author":"Kraan","year":"2000","journal-title":"Arthritis Rheum"},{"key":"B8","article-title":"Infections, drugs, and rheumatoid arthritis. What have we learned","volume":"35","author":"Coblyn","year":"2008","journal-title":"J\u00a0Rheumatol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1093\/ajcp\/85.5.616","article-title":"Quantitative urine culture in patients with urinary tract infection and bacteremia","volume":"85","author":"Roberts","year":"1986","journal-title":"Am J Clin Pathol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.15274","article-title":"How I treat primary haemophagocytic lymphohistiocytosis","volume":"182","author":"Marsh","year":"2018","journal-title":"Br J Haematol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/S2665-9913(23)00273-4","article-title":"Diagnosis and investigation of suspected haemophagocytic lymphohistiocytosis in adults: 2023 Hyperinflammation and HLH Across Speciality Collaboration (HiHASC) consensus guideline","volume":"6","author":"Cox","year":"2024","journal-title":"Lancet Rheumatol"},{"key":"B12","doi-asserted-by":"publisher","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":"B13","doi-asserted-by":"publisher","DOI":"10.1002\/art.38690","article-title":"Development and validation of the HScore, a score for the diagnosis of reactive hemophagocytic syndrome","volume":"66","author":"Fardet","year":"2014","journal-title":"Arthritis Rheumatol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"10529","DOI":"10.1038\/s41598-021-90046-4","article-title":"Analysis of the occurrence of hemophagocytic lymphohistiocytosis (HLH) features in patients with sepsis: a prospective study","volume":"11","author":"Bursa","year":"2021","journal-title":"Sci Rep"},{"key":"B15","article-title":"Pancytopenia secondary to hemophagocytic syndrome in rheumatoid arthritis treated with methotrexate and sulfasalazine","volume":"25","author":"Sibilia","year":"1998","journal-title":"J Rheumatol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keg187","article-title":"Haemophagocytic syndrome in a rheumatoid arthritis patient treated with infliximab","volume":"42","author":"Aouba","year":"2003","journal-title":"Rheumatol (Oxford)"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.51.5687","article-title":"Hemophagocytic lymphohistiocytosis in a rheumatoid arthritis patient treated with infliximab","volume":"51","author":"Oda","year":"2012","journal-title":"Intern Med"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2018894618","article-title":"Recommendations for the management of hemophagocytic lymphohistiocytosis in adults","volume":"133","author":"La Ros\u00e9e","year":"2019","journal-title":"Blood"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.12998\/wjcc.v7.i21.3394","article-title":"Efficient management of secondary haemophagocytic lymphohistiocytosis with intravenous steroids and \u03b3-immunoglobulin infusions","volume":"7","author":"Georgiadou","year":"2019","journal-title":"World J Clin cases"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1863594\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T04:23:53Z","timestamp":1783916633000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1863594\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,13]]},"references-count":19,"alternative-id":["10.3389\/fimmu.2026.1863594"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1863594","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,13]]},"article-number":"1863594"}}