{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T22:23:41Z","timestamp":1785018221964,"version":"3.55.0"},"reference-count":11,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,3,21]],"date-time":"2022-03-21T00:00:00Z","timestamp":1647820800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,3,21]],"date-time":"2022-03-21T00:00:00Z","timestamp":1647820800000},"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":["Discov Onc"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hemophagocytic\u00a0lymphohistiocytosis\u00a0(HLH) is a rare disease resulting from the overactivation of the immune system due to under regulation of cytotoxic lymphocytes, macrophages and natural killer (NK) cells. HLH is associated with malignancies, infections, autoimmune disorders and rarely AIDS and is rapidly fatal.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>This case report identified a 53\u00a0year old male with acquired immunodeficiency syndrome (AIDS) who presented with neutropenic fever of unknown origin. He had two previous hospitalizations prior to the hospitalization diagnosing HLH. The first led to a diagnosis of drug fevers in the setting of treatment for thrombotic thrombocytopenic purpura and subsequent hospitalization led to empiric treatment of hospital acquired pneumonia after workup for intermittent fevers was negative. He was discharged but readmitted 10 days after for recurrence of neutropenic fevers. During this final hospitalization, he was found to have elevated liver enzymes, ferritin, triglycerides and soluble IL-2 receptor with persistent fevers, new splenomegaly and bicytopenia meeting the 2004 HLH criteria. Bone marrow biopsy confirmed the diagnosis of HLH as well as EBV associated large B-cell lymphoma. The patient improved on treatment with steroids, rituximab, tocilizumab, and chemotherapy but ultimately passed away due to refractory septic shock from multi-drug resistant Klebsiella pneumoniae.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This novel case highlights a patient diagnosed with HLH in the setting of several risk factors for the disease, including AIDS, B-cell lymphoma and EBV. Additionally, this case highlights the importance of early consideration of HLH in the setting of neutropenic fever without clear infectious etiology and search for malignancy associated reasons for HLH especially in immunocompromised patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s12672-022-00476-3","type":"journal-article","created":{"date-parts":[[2022,3,21]],"date-time":"2022-03-21T00:15:47Z","timestamp":1647821747000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Hemophagocytic lymphohistiocytosis: a rare disease unveiling the diagnosis of EBV-related large B cell lymphoma in a patient with HIV"],"prefix":"10.1007","volume":"13","author":[{"given":"Alexandra","family":"Noveihed","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiochee","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Glotfelty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibiyonu","family":"Lawrence","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,3,21]]},"reference":[{"key":"476_CR1","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.mmcr.2018.01.001","volume":"20","author":"S Asanad","year":"2018","unstructured":"Asanad S, Cerk B, Ramirez V. Hemophagocytic\u00a0lymphohistiocytosis\u00a0(HLH) secondary to disseminated histoplasmosis in the setting of\u00a0acquired immunodeficiency syndrome\u00a0(AIDS). Med Mycol Case Rep. 2018;20:15\u20137. https:\/\/doi.org\/10.1016\/j.mmcr.2018.01.001.","journal-title":"Med Mycol Case Rep."},{"issue":"3","key":"476_CR2","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1002\/ajh.23911","volume":"90","author":"ZK Otrock","year":"2015","unstructured":"Otrock ZK, Eby CS. Clinical characteristics, prognostic factors, and outcomes of adult patients with hemophagocytic lymphohistiocytosis. Am J Hematol. 2015;90(3):220\u20134. https:\/\/doi.org\/10.1002\/ajh.23911.","journal-title":"Am J Hematol"},{"key":"476_CR3","doi-asserted-by":"publisher","first-page":"7634760","DOI":"10.1155\/2019\/7634760","volume":"2019","author":"OE Emiloju","year":"2019","unstructured":"Emiloju OE, Gupta S, Arguello-Guerra V, Dourado C. Hemophagocytic\u00a0Lymphohistiocytosis\u00a0in an AIDS patient with kaposi sarcoma: a treatment dilemma. Case Rep Hematol. 2019;2019:7634760. https:\/\/doi.org\/10.1155\/2019\/7634760.","journal-title":"Case Rep Hematol."},{"issue":"11","key":"476_CR4","doi-asserted-by":"publisher","first-page":"2199","DOI":"10.1111\/jdv.13212","volume":"29","author":"F Skowron","year":"2015","unstructured":"Skowron F, Bensaid B, Balme B, et al. Drug reaction with eosinophilia and systemic symptoms (DRESS): clinicopathological study of 45 cases. J Eur Acad Dermatol Venereol. 2015;29(11):2199\u2013205. https:\/\/doi.org\/10.1111\/jdv.13212.","journal-title":"J Eur Acad Dermatol Venereol"},{"issue":"15","key":"476_CR5","doi-asserted-by":"publisher","first-page":"4041","DOI":"10.1182\/blood-2011-03-278127","volume":"118","author":"MB Jordan","year":"2011","unstructured":"Jordan MB, Allen CE, Weitzman S, Filipovich AH, McClain KL. How I treat hemophagocytic lymphohistiocytosis. Blood. 2011;118(15):4041\u201352. https:\/\/doi.org\/10.1182\/blood-2011-03-278127.","journal-title":"Blood"},{"key":"476_CR6","doi-asserted-by":"publisher","first-page":"71","DOI":"10.3389\/fped.2019.00071","volume":"7","author":"WY Kim","year":"2019","unstructured":"Kim WY, Montes-Mojarro IA, Fend F, Quintanilla-Martinez L. Epstein\u2013Barr virus-associated T and NK-cell lymphoproliferative diseases. Front Pediatr. 2019;7:71\u201371. https:\/\/doi.org\/10.3389\/fped.2019.00071.","journal-title":"Front Pediatr"},{"issue":"9927","key":"476_CR7","doi-asserted-by":"publisher","first-page":"1503","DOI":"10.1016\/S0140-6736(13)61048-X","volume":"383","author":"M Ramos-Casals","year":"2014","unstructured":"Ramos-Casals M, Brito-Zer\u00f3n P, L\u00f3pez-Guillermo A, Khamashta MA, Bosch X. Adult haemophagocytic syndrome. Lancet (British edition). 2014;383(9927):1503\u201316. https:\/\/doi.org\/10.1016\/S0140-6736(13)61048-X.","journal-title":"Lancet (British edition)"},{"issue":"5446","key":"476_CR8","doi-asserted-by":"publisher","first-page":"1957","DOI":"10.1126\/science.286.5446.1957","volume":"286","author":"SE Stepp","year":"1999","unstructured":"Stepp SE, Dufourcq-Lagelouse R, Le Deist F, et al. Perforin gene defects in familial hemophagocytic lymphohistiocytosis. Science. 1999;286(5446):1957\u20139. https:\/\/doi.org\/10.1126\/science.286.5446.1957.","journal-title":"Science"},{"key":"476_CR9","unstructured":"Hippensteel JA, Neumeier A. Secondary hemophagocytic lymphohistiocytosis in AIDS associated EBV+ diffuse large B-cell lymphoma. B46 Crit Care Case Rep Hematol Oncol Rheumatol Immunol. 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