{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T03:39:27Z","timestamp":1792813167495,"version":"4.5.0"},"reference-count":67,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,6]],"date-time":"2021-10-06T00:00:00Z","timestamp":1633478400000},"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. Med."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Adult hemophagocytic lymphohistiocytosis (HLH) is highly lethal in the ICU. The diagnostic and therapeutic emergency that HLH represents is compounded by its unknown pathophysiological mechanisms. Here, we report on a large cohort of adult HLH in the ICU (ICU-HLH). We analyzed prognostic factors associated with mortality to define the diagnostic and therapeutic challenges in this specific population.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> This retrospective study included adult patients diagnosed with HLH in four ICUs in Marseille, France between 2010 and 2020. Patients who fulfilled the HLH-2004 criteria (\u2265 4\/8) and\/or had an HScore \u2265 169 were diagnosed with HLH. HLH was categorized into four groups according to etiology: sepsis-associated HLH, intracellular infection-associated HLH, malignancy-associated HLH, and idiopathic HLH.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Two hundred and sixty patients were included: 121 sepsis-associated HLH (47%), 84 intracellular infection-associated HLH (32%), 28 malignancy-associated HLH (11%), and 27 idiopathic HLH (10%). The ICU mortality rate reached 57% (<jats:italic>n<\/jats:italic> = 147\/260) without a statistical difference between etiological groups. Independent factors associated with mortality in multivariate analysis included age (OR (5 years) = 1.31 [1.16\u20131.48], <jats:italic>p<\/jats:italic> &amp;lt; 0.0001), SOFA score at ICU admission (OR = 1.37 [1.21\u20131.56], <jats:italic>p<\/jats:italic> &amp;lt; 0.0001), degradation of the SOFA score between ICU arrival and HLH diagnosis (Delta SOFA) (OR = 1.47 [1.28\u20131.70], <jats:italic>p<\/jats:italic> &amp;lt; 0.0001), the presence of bone-marrow hemophagocytosis (OR = 5.27 [1.11\u201324.97], <jats:italic>p<\/jats:italic> = 0.04), highly severe anemia (OR = 1.44 [1.09\u20131.91], <jats:italic>p<\/jats:italic> = 0.01), and hypofibrinogenemia (OR = 1.21 [1.04\u20131.41], <jats:italic>p<\/jats:italic> = 0.02).<\/jats:p><jats:p><jats:bold>Conclusions:<\/jats:bold> In this large retrospective cohort study of critically ill patients, ICU-HLH in adults was associated with a 57% mortality rate, regardless of HLH etiology or specific treatment. Factors independently associated with prognosis included age, presence of hemophagocytosis in bone-marrow aspirates, organ failure at admission, and worsening organ failure during the ICU stay. Whether a rapid diagnosis and the efficacy of specific therapy improve outcome is yet to be prospectively investigated.<\/jats:p>","DOI":"10.3389\/fmed.2021.735796","type":"journal-article","created":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T10:12:39Z","timestamp":1633601559000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":43,"title":["High Mortality of HLH in ICU Regardless Etiology or Treatment"],"prefix":"10.3389","volume":"8","author":[{"given":"Amandine","family":"Bichon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00e9my","family":"Bourenne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00f4me","family":"Allardet-Servent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Papazian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sami","family":"Hraiech","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Guervilly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Pauly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"Kaplanski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Djamel","family":"Mokart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Gainnier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Carvelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,10,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.blre.2014.03.002","article-title":"Hemophagocytic syndromes\u2013an update","volume":"28","author":"Janka","year":"2014","journal-title":"Blood Rev."},{"key":"B2","doi-asserted-by":"crossref","first-page":"2918","DOI":"10.1182\/blood.V78.11.2918.2918","article-title":"Hypercytokinemia in familial hemophagocytic lymphohistiocytosis","volume":"78","author":"Henter","year":"1991","journal-title":"Blood."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1853","DOI":"10.1007\/s00134-017-4853-6","article-title":"From febrile pancytopenia to hemophagocytic lymphohistiocytosis-associated organ dysfunction","volume":"43","author":"Carcillo","year":"2017","journal-title":"Intensive Care Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1002\/pbc.21039","article-title":"Therapeutic guidelines for hemophagocytic lymphohistiocytosis","volume":"48","author":"Henter","year":"2007","journal-title":"Pediatr Blood Cancer."},{"key":"B5","doi-asserted-by":"publisher","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":"B6","doi-asserted-by":"publisher","first-page":"1957","DOI":"10.1126\/science.286.5446.1957","article-title":"Perforin gene defects in familial hemophagocytic lymphohistiocytosis","volume":"286","author":"Stepp","year":"1999","journal-title":"Science."},{"key":"B7","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1182\/blood-2017-11-814244","article-title":"Genetics and mechanistic diversity in pediatric hemophagocytic lymphohistiocytosis","volume":"132","author":"Chinn","year":"2018","journal-title":"Blood."},{"key":"B8","doi-asserted-by":"publisher","first-page":"2113","DOI":"10.1182\/blood-2015-12-688960","article-title":"Polygenic Mutations in the Cytotoxicity Pathway Increase Susceptibility to Develop HLH Immunopathology in Mice","volume":"127","author":"Sepulveda","year":"","journal-title":"Blood. 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