{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:14:06Z","timestamp":1791976446951,"version":"4.4.0"},"reference-count":39,"publisher":"American Society of Hematology","issue":"1","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,12,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Hemophagocytic lymphohistiocytosis (HLH) is one of the life-threatening emergencies that a hematologist may be called upon to diagnose and manage. It is a hyperinflammatory process that develops in patients with genetic abnormalities, hematologic malignancies, chronic inflammatory states, or infections. The main clinical challenges are recognizing HLH, determining whether the immune response is aberrant or appropriate, and deciding upon therapy. Patients may present with fever, central nervous system symptoms, cytopenias, or elevated liver enzymes.<\/jats:p>\n               <jats:p>Recognizing HLH is challenging because its features overlap with numerous systemic disorders, thus requiring a high level of suspicion and timely investigations to confirm the diagnosis and detect the underlying trigger. Once HLH is diagnosed, careful consideration of immunosuppressive therapy's potential benefit versus harm is necessary. Such therapy can sometimes be tailored to the underlying trigger. In the acute setting, the competing pressures of completing a thorough diagnostic process (including evaluation for the presence of lymphoma and infection) and the need for expedited treatment must be balanced. During the management of an HLH patient, continuous vigilance for the presence of as-yet unrecognized disease triggers, monitoring response, and identifying emerging complications is critical. This review will discuss the recognition and management of HLH in the inpatient setting.<\/jats:p>","DOI":"10.1182\/hematology.2023000509","type":"journal-article","created":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T15:09:03Z","timestamp":1702048143000},"page":"259-266","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":25,"title":["Inpatient recognition and management of HLH"],"prefix":"10.1182","volume":"2023","author":[{"given":"Adi","family":"Zoref-Lorenz","sequence":"first","affiliation":[{"name":"1 Hematology Institute, Meir Medical Center, Kfar Saba, Israel"},{"name":"2 Division of Immunobiology, Cincinnati Children's Medical Center, Cincinnati, OH"},{"name":"3 School of Medicine, Tel Aviv University, Tel Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Ellis","sequence":"additional","affiliation":[{"name":"1 Hematology Institute, Meir Medical Center, Kfar Saba, Israel"},{"name":"3 School of Medicine, Tel Aviv University, Tel Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael B.","family":"Jordan","sequence":"additional","affiliation":[{"name":"2 Division of Immunobiology, Cincinnati Children's Medical Center, Cincinnati, OH"},{"name":"4 Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of\u2009Medicine, Cincinnati, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","published-online":{"date-parts":[[2023,12,8]]},"reference":[{"key":"2023120815055418900_hem2023000509C1","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1146\/annurev-med-042921-112837","article-title":"Cytokine storm syndrome","volume":"74","author":"Cron","year":"2023","journal-title":"Annu Rev Med"},{"issue":"17","key":"2023120815055418900_hem2023000509C2","doi-asserted-by":"crossref","first-page":"2337","DOI":"10.1182\/blood.2020009499","article-title":"T-cell activation profiles distinguish hemophagocytic lymphohistiocytosis and early sepsis","volume":"137","author":"Chaturvedi","year":"2021","journal-title":"Blood"},{"issue":"3","key":"2023120815055418900_hem2023000509C3","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1182\/blood.2021013549","article-title":"Expansion of CD4dimCD8+ T cells characterizes macrophage activation syndrome and other secondary HLH","volume":"140","author":"De Matteis","year":"2022","journal-title":"Blood"},{"issue":"5","key":"2023120815055418900_hem2023000509C4","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1016\/j.jaci.2022.02.028","article-title":"Distinguishing immune activation and inflammatory signatures of multisystem inflammatory syndrome in children (MIS-C) versus hemophagocytic lymphohistiocytosis (HLH)","volume":"149","author":"Kumar","year":"2022","journal-title":"J Allergy Clin Immunol"},{"issue":"17","key":"2023120815055418900_hem2023000509C5","doi-asserted-by":"crossref","first-page":"3457","DOI":"10.1182\/bloodadvances.2021004287","article-title":"IFN-\u03b3 signature in the plasma proteome distinguishes pediatric hemophagocytic lymphohistiocytosis from sepsis and SIRS","volume":"5","author":"Lin","year":"2021","journal-title":"Blood Adv"},{"issue":"13","key":"2023120815055418900_hem2023000509C6","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1182\/blood-2017-12-820852","article-title":"Interleukin-18 diagnostically distinguishes and pathogenically promotes human and murine macrophage activation syndrome","volume":"131","author":"Weiss","year":"2018","journal-title":"Blood"},{"issue":"3","key":"2023120815055418900_hem2023000509C7","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1182\/blood-2003-10-3413","article-title":"An animal model of hemophagocytic lymphohistiocytosis (HLH): CD8+ T cells and interferon gamma are essential for the disorder","volume":"104","author":"Jordan","year":"2004","journal-title":"Blood"},{"key":"2023120815055418900_hem2023000509C8","doi-asserted-by":"crossref","first-page":"1147603","DOI":"10.3389\/fimmu.2023.1147603","article-title":"Insights into the cellular pathophysiology of familial hemophagocytic lymphohistiocytosis","volume":"14","author":"Steen","year":"2023","journal-title":"Front Immunol"},{"issue":"2","key":"2023120815055418900_hem2023000509C9","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"},{"issue":"18","key":"2023120815055418900_hem2023000509C10","doi-asserted-by":"crossref","first-page":"2857","DOI":"10.1002\/cncr.30084","article-title":"Malignancy-associated hemophagocytic lymphohistiocytosis in adults: relation to hemophagocytosis, characteristics, and outcomes","volume":"122","author":"Tamamyan","year":"2016","journal-title":"Cancer"},{"issue":"11","key":"2023120815055418900_hem2023000509C11","doi-asserted-by":"crossref","first-page":"e27929","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"},{"issue":"9","key":"2023120815055418900_hem2023000509C12","doi-asserted-by":"crossref","first-page":"2613","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"},{"issue":"1","key":"2023120815055418900_hem2023000509C13","doi-asserted-by":"crossref","DOI":"10.3390\/jcm12010192","article-title":"Differential diagnosis of hyperferritinemia in critically ill patients","volume":"12","author":"Schuster","year":"2022","journal-title":"J Clin Med"},{"issue":"1","key":"2023120815055418900_hem2023000509C14","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1186\/s13054-020-02941-3","article-title":"Hemophagocytic lymphohistiocytosis in critically ill patients: diagnostic reliability of HLH-2004 criteria and HScore","volume":"24","author":"Knaak","year":"2020","journal-title":"Crit Care"},{"issue":"1","key":"2023120815055418900_hem2023000509C15","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1182\/blood-2017-11-814244","article-title":"Genetic and mechanistic diversity in pediatric hemophagocytic lymphohistiocytosis","volume":"132","author":"Chinn","year":"2018","journal-title":"Blood"},{"issue":"26","key":"2023120815055418900_hem2023000509C16","doi-asserted-by":"crossref","first-page":"3051","DOI":"10.1182\/blood.2020008206","article-title":"Contribution of clonal hematopoiesis to adult-onset hemophagocytic lymphohistiocytosis","volume":"136","author":"Miller","year":"2020","journal-title":"Blood"},{"issue":"5","key":"2023120815055418900_hem2023000509C17","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1007\/s12185-019-02623-z","article-title":"Hemophagocytic lymphohistiocytosis as a harbinger of aggressive lymphoma: a case series","volume":"109","author":"Pasvolsky","year":"2019","journal-title":"Int J Hematol"},{"issue":"12","key":"2023120815055418900_hem2023000509C18","doi-asserted-by":"crossref","first-page":"e27400","DOI":"10.1002\/pbc.27400","article-title":"Limitations of HLH-2004 criteria in distinguishing malignancy-associated hemophagocytic lymphohistiocytosis","volume":"65","author":"Gurunathan","year":"2018","journal-title":"Pediatr Blood Cancer"},{"issue":"7","key":"2023120815055418900_hem2023000509C19","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1182\/blood.2021012764","article-title":"An improved index for diagnosis and mortality prediction in malignancy-associated hemophagocytic lymphohistiocytosis","volume":"139","author":"Zoref-Lorenz","year":"2022","journal-title":"Blood"},{"issue":"5","key":"2023120815055418900_hem2023000509C20","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1007\/s00277-013-1925-8","article-title":"A high sIL-2R\/ferritin ratio is a useful marker for the diagnosis of lymphoma-associated hemophagocytic syndrome","volume":"93","author":"Tsuji","year":"2014","journal-title":"Ann Hematol"},{"issue":"23","key":"2023120815055418900_hem2023000509C21","doi-asserted-by":"crossref","first-page":"2465","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"},{"issue":"3","key":"2023120815055418900_hem2023000509C22","doi-asserted-by":"crossref","first-page":"e217","DOI":"10.1016\/S2352-3026(21)00366-5","article-title":"Malignancy-associated haemophagocytic lymphohistiocytosis","volume":"9","author":"Setiadi","year":"2022","journal-title":"Lancet Haematol"},{"issue":"1","key":"2023120815055418900_hem2023000509C23","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/s40425-019-0598-9","article-title":"Haemophagocytic lymphohistiocytosis in patients treated with immune checkpoint inhibitors: analysis of WHO global database of individual case safety reports","volume":"7","author":"Noseda","year":"2019","journal-title":"J Immunother Cancer"},{"issue":"24","key":"2023120815055418900_hem2023000509C24","doi-asserted-by":"crossref","first-page":"2469","DOI":"10.1182\/blood.2021011898","article-title":"Characterization of HLH-like manifestations as a CRS variant in patients receiving CD22 CAR T cells","volume":"138","author":"Lichtenstein","year":"2021","journal-title":"Blood"},{"issue":"7","key":"2023120815055418900_hem2023000509C25","doi-asserted-by":"crossref","first-page":"438.e1","DOI":"10.1016\/j.jtct.2023.03.006","article-title":"Immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome","volume":"29","author":"Hines","year":"2023","journal-title":"Transplant Cell Ther"},{"issue":"2","key":"2023120815055418900_hem2023000509C26","doi-asserted-by":"crossref","first-page":"269","DOI":"10.3324\/haematol.2018.198655","article-title":"Treatment outcomes and prognostic factors in adult patients with secondary hemophagocytic lymphohistiocytosis not associated with malignancy","volume":"104","author":"Yoon","year":"2019","journal-title":"Haematologica"},{"issue":"5","key":"2023120815055418900_hem2023000509C27","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1097\/CCM.0000000000005361","article-title":"Consensus-based guidelines for the recognition, diagnosis, and management of hemophagocytic lymphohistiocytosis in critically ill children and adults","volume":"50","author":"Hines","year":"2022","journal-title":"Crit Care Med"},{"issue":"5","key":"2023120815055418900_hem2023000509C28","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1016\/j.jaip.2018.05.031","article-title":"Recommendations for the use of etoposide-based therapy and bone marrow transplantation for the treatment of HLH: consensus statements by the HLH Steering Committee of the Histiocyte Society","volume":"6","author":"Ehl","year":"2018","journal-title":"J Allergy Clin Immunol Pract"},{"key":"2023120815055418900_hem2023000509C29","doi-asserted-by":"crossref","first-page":"614704","DOI":"10.3389\/fimmu.2021.614704","article-title":"Use of the JAK inhibitor ruxolitinib in the treatment of hemophagocytic lymphohistiocytosis","volume":"12","author":"Keenan","year":"2021","journal-title":"Front Immunol"},{"issue":"2","key":"2023120815055418900_hem2023000509C30","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1158\/2643-3230.BCD-21-0181","article-title":"Blockade or deletion of IFN\u03b3 reduces macrophage activation without compromising CAR T-cell function in hematologic malignancies","volume":"3","author":"Bailey","year":"2022","journal-title":"Blood Cancer Discov"},{"issue":"17","key":"2023120815055418900_hem2023000509C31","doi-asserted-by":"crossref","first-page":"3229","DOI":"10.1002\/cncr.30826","article-title":"A consensus review on malignancy-associated hemophagocytic lymphohistiocytosis in adults: malignancy-associated HLH in adults","volume":"123","author":"Daver","year":"2017","journal-title":"Cancer"},{"issue":"11","key":"2023120815055418900_hem2023000509C32","doi-asserted-by":"crossref","first-page":"3063","DOI":"10.1007\/s00432-020-03301-y","article-title":"Ruxolitinib combined with doxorubicin, etoposide, and dexamethasone for the treatment of the lymphoma-associated hemophagocytic syndrome","volume":"146","author":"Zhou","year":"2020","journal-title":"J Cancer Res Clin Oncol"},{"issue":"5","key":"2023120815055418900_hem2023000509C33","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1111\/ejh.13593","article-title":"Ruxolitinib as adjunctive therapy for secondary hemophagocytic lymphohistiocytosis: a case series","volume":"106","author":"Hansen","year":"2021","journal-title":"Eur J Haematol"},{"issue":"6","key":"2023120815055418900_hem2023000509C34","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1136\/ard-2022-223739","article-title":"Efficacy and safety of emapalumab in macrophage activation syndrome","volume":"82","author":"De Benedetti","year":"2023","journal-title":"Ann Rheum Dis"},{"issue":"16","key":"2023120815055418900_hem2023000509C35","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1182\/blood.2019000936","article-title":"Pediatric hemophagocytic lymphohistiocytosis","volume":"135","author":"Canna","year":"2020","journal-title":"Blood"},{"issue":"26","key":"2023120815055418900_hem2023000509C36","doi-asserted-by":"crossref","first-page":"5824","DOI":"10.1182\/blood-2010-04-282392","article-title":"Reduced-intensity conditioning significantly improves survival of patients with hemophagocytic lymphohistiocytosis undergoing allogeneic hematopoietic cell transplantation","volume":"116","author":"Marsh","year":"2010","journal-title":"Blood"},{"issue":"3","key":"2023120815055418900_hem2023000509C37","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1016\/j.jaci.2021.07.031","article-title":"Comparison of hematopoietic cell transplant conditioning regimens for hemophagocytic lymphohistiocytosis disorders","volume":"149","author":"Marsh","year":"2022","journal-title":"J Allergy Clin Immunol"},{"issue":"11","key":"2023120815055418900_hem2023000509C38","doi-asserted-by":"crossref","first-page":"2309","DOI":"10.1182\/bloodadvances.2022007012","article-title":"Favorable outcomes following allogeneic transplantation in adults with hemophagocytic lymphohistiocytosis","volume":"7","author":"Gooptu","year":"2023","journal-title":"Blood Adv"},{"issue":"3","key":"2023120815055418900_hem2023000509C39","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1136\/annrheumdis-2015-208982","article-title":"2016 Classification criteria for macrophage activation syndrome complicating systemic juvenile idiopathic arthritis: a European League Against Rheumatism\/American College of Rheumatology\/Paediatric Rheumatology International Trials Organisation Collaborative initiative","volume":"75","author":"Ravelli","year":"2016","journal-title":"Ann Rheum Dis"}],"container-title":["Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ashpublications.org\/hematology\/article-pdf\/2023\/1\/259\/2175509\/259zoreflorenz.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/ashpublications.org\/hematology\/article-pdf\/2023\/1\/259\/2175509\/259zoreflorenz.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T15:09:17Z","timestamp":1702048157000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/hematology\/article\/2023\/1\/259\/506435\/Inpatient-recognition-and-management-of-HLH"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,8]]},"references-count":39,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12,8]]},"published-print":{"date-parts":[[2023,12,8]]}},"URL":"https:\/\/doi.org\/10.1182\/hematology.2023000509","relation":{},"ISSN":["1520-4391","1520-4383"],"issn-type":[{"value":"1520-4391","type":"print"},{"value":"1520-4383","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,12,8]]},"published":{"date-parts":[[2023,12,8]]}}}