AUTHOR=Bichon Amandine , Bourenne Jérémy , Allardet-Servent Jérôme , Papazian Laurent , Hraiech Sami , Guervilly Christophe , Pauly Vanessa , Kaplanski Gilles , Mokart Djamel , Gainnier Marc , Carvelli Julien 

TITLE=High Mortality of HLH in ICU Regardless Etiology or Treatment

JOURNAL=Frontiers in Medicine

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2021.735796

DOI=10.3389/fmed.2021.735796

ISSN=2296-858X

ABSTRACT=<p><bold>Background:</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.</p><p><bold>Methods:</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 (≥ 4/8) and/or had an HScore ≥ 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.</p><p><bold>Results:</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% (<italic>n</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 [1.16–1.48], <italic>p</italic> &lt; 0.0001), SOFA score at ICU admission (OR = 1.37 [1.21–1.56], <italic>p</italic> &lt; 0.0001), degradation of the SOFA score between ICU arrival and HLH diagnosis (Delta SOFA) (OR = 1.47 [1.28–1.70], <italic>p</italic> &lt; 0.0001), the presence of bone-marrow hemophagocytosis (OR = 5.27 [1.11–24.97], <italic>p</italic> = 0.04), highly severe anemia (OR = 1.44 [1.09–1.91], <italic>p</italic> = 0.01), and hypofibrinogenemia (OR = 1.21 [1.04–1.41], <italic>p</italic> = 0.02).</p><p><bold>Conclusions:</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.</p>