Report of Two Contrasting Cases of Epstein–Barr Virus–Associated Hemophagocytic Lymphohistiocytosis: Comparison to Infectious Mononucleosis and Flow Cytometric Analysis of Bone Marrow

Abstract

Purpose

This study aims to investigate the characteristics of Epstein–Barr virus associated-hemophagocytic lymphohistiocytosis (EBV-HLH) and HLH caused by a severe form of infectious mononucleosis (IM-HLH) compared to IM by EBV, and thus also to assist in early diagnosis and providing appropriate treatment.

Methods

Data for this analysis were collected from patients at the Department of General Medicine, Nara Medical University, between April 1, 2012, and August 1, 2020. EBV infection was diagnosed using clinical presentation and laboratory tests. HLH diagnosis followed the HLH-2004 protocol, supplemented by plasma EBV DNA detection. A range of clinical and laboratory parameters were collected, including age, sex, clinical outcomes, blood cell counts, hemoglobin, platelets, and various serum values. Plasma EBV DNA levels and flow cytometric analysis (FCM) of bone marrow were performed for HLH cases.

Results

Among 1850 hospitalized patients, 14 cases were identified, including 2 HLH cases and 12 IM cases. Comparative analysis revealed distinctive features of HLH, including lower lymphocyte and platelet counts and higher levels of ferritin, soluble interleukin 2 receptor (sIL-2R), and D dimer compared to IM. Notably, one HLH case responded well to corticosteroid monotherapy, while the other case did not, resulting in a fatal outcome. Detection of a cluster of CD5-CD7 lymphocytes in bone marrow is a hallmark of EBV-HLH and useful to distinguish from IM-HLH.

Conclusion

This study underscores the importance of early differentiation among EBV-HLH, IM-HLH, and IM in adults to guide appropriate treatment strategies. While specific laboratory markers help distinguish HLH from IM, a more detailed analysis of FCM is crucial for precise diagnosis of HLH cases and tailored therapeutic interventions.

Keywords:

• hemophagocytic lymphohistiocytosis
• Epstein–Barr virus infection
• Epstein–Barr virus–associated hemophagocytic lymphohistiocytosis
• diagnosis of EBV-HLH
• flow cytometric analysis of bone marrow

Patient Consent for Publication

We obtained written informed consent from two patients of HLH case for the publication of this report. This study was also approved by the Ethical Committee of Nara Medical University (approval number: 2695). The signed consent forms are retained by the corresponding author.

Disclosure

All authors report no conflict of interest for this study.