SYSTEMATIC REVIEW article
Front. Med.
Sec. Intensive Care Medicine and Anesthesiology
Volume 12 - 2025 | doi: 10.3389/fmed.2025.1622770
Hemophagocytic Lymphohistiocytosis in the Adult Critically Ill: a narrative review of case reports and case series
Provisionally accepted
Giorgia Montrucchio1,2
Riccardo Traversi1*Gabriele Arrigo1Chiara Bonetto2Gabriele Sales1,2
Alessandro Busca3
Vito Fanelli1,2
Claudia Filippini4
LUCA BRAZZI1,2- 1Department of Surgical Sciences, University of Turin, Turin, Italy
- 2Anestesia e Rianimazione 1U, AOU Città della Salute e della Scienza, Torino, Italy
- 3SSCVD Trapianto e Cellule Staminali, AOU Città della Salute e della Scienza, Torino, Italy
- 4Department of Surgical Scieces, University of Turin, Turin, Italy
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METHODS: Patients' data were extracted from a literature search performed on PubMed (MEDLINE) and EMBASE using the following search terms: "Hemophagocyitic Lymphohistiocytosis" OR "HLH" OR "MACROPHAGE ACTIVATING SYNDROME" OR "MAS" AND "Intensive Care Unit" OR "Critical Care" OR "ICU". Search was limited to articles published after 2014, when HScore was proposed. RESULTS: We found 126 case reports and case series for a total of 148 patients with an overall mortality of 47.5%. Main triggers were infections (111 patients; 88.1%) followed by dysimmune disorders (29 patients; 19.7%) and hematological malignancies (20 patients; 13.6%). The following factors were associated with increased ICU mortality: viral infection (76 patients; 52.8%) p=0.0071 and p=0.0086 at multivariate analysis for SARS-CoV-2, hematological malignancies (p=0.0035 at univariate analysis; p=0.0083 at multivariate analysis), invasive mechanical ventilation (116 patients; 83.3%) p=0.0060 at univariate analysis not confirmed in multivariate analysis (p=0.0599). Corticosteroids were associated with reduced ICU mortality at univariate analysis (86 patients; 59.7% p=0.0250) not confirmed at multivariate analysis (p=0.7196). CONCLUSION: evidence from our analysis confirms the severity and rapid evolution of HLH, suggesting the importance of prompt clinical suspicion. Since HLH can be found in different hospital settings, including ICU, we believe that this syndrome should be considered in differential diagnosis for all patients presenting with MOD with unclear etiology. Development of specific diagnostic and therapeutic schemes should be considered a priority.
Keywords: septic shock, Immune dysregulation, Hematology critical care, Hemophagocytic lymphohistiocytosis (HLH), Hemophagocytic syndromes (HPS), Critical Care, HLH-2004 criteria, HScore
Received: 20 May 2025; Accepted: 13 Aug 2025.
Copyright: © 2025 Montrucchio, Traversi, Arrigo, Bonetto, Sales, Busca, Fanelli, Filippini and BRAZZI. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Riccardo Traversi, Department of Surgical Sciences, University of Turin, Turin, Italy
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