Influenza as a Less Commonly Recognized Cause of Hemophagocytic Lymphohistiocytosis: A Systematic Review of Case Reports and Case Series
Department
Internal Medicine
Additional Department
Oncology and Hematology
Document Type
Article
Publication Title
European Journal of Haematology
Abstract
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyper-inflammatory condition that can be triggered by viral infections. However, influenza is not commonly recognized as a cause of HLH, and there is no comprehensive synthesis of influenza-associated HLH in the literature to guide clinicians. We conducted a systematic search of Pubmed and Embase to identify case reports and case series on influenza-associated HLH, and included 29 articles involving 47 patients. Their age ranged from 2 months to 72 years. 67% were males. Influenza A accounted for 91.3% of the cases, predominantly H1N1 (90.2%). All patients had fever, 60% had anemia, 69.7% had thrombocytopenia, 46.6% had leukopenia, 61.3% had splenomegaly, 71.4% had hypertriglyceridemia, and 94.7% had elevated ferritin levels. 97.6% had hemophagocytosis on biopsy. Antiviral therapy was administered in 89.5% of patients. HLH-directed therapy included corticosteroids (77%), intravenous immunoglobulin (36%), and etoposide (23.1%). Intensive care was required in 95.2% of cases. Overall survival was 53.2%. Survival rate was 50% among patients who received either antiviral therapy alone or HLH-directed therapy alone, compared with 65.4% among those who received both. Further studies are necessary to establish standardized diagnostic and therapeutic protocols for influenza-associated HLH.
First Page
1044
Last Page
1051
DOI
10.1111/ejh.70241
Volume
117
Issue
4
Publication Date
10-1-2026
Medical Subject Headings
Humans; Lymphohistiocytosis, Hemophagocytic; Influenza, Human; Male; Female; Child, Preschool; Adolescent; Infant; Middle Aged; Child; Aged; Adult; Antiviral Agents; Treatment Outcome; Immunoglobulins, Intravenous
PubMed ID
42306884
Recommended Citation
Balusu, K., Abdelhay, A., Payal, F., & Kouides, P. A. (2026). Influenza as a Less Commonly Recognized Cause of Hemophagocytic Lymphohistiocytosis: A Systematic Review of Case Reports and Case Series. European Journal of Haematology, 117 (4), 1044-1051. https://doi.org/10.1111/ejh.70241