# Concurrent Hemophagocytic Lymphohistiocytosis and Thrombotic Microangiopathy Induced by Cytomegalovirus and Epstein-Barr Virus Co-infection in an Immunocompetent Young Adult: A Case Report

**Authors:** Maha El Amani, Firdaous Belkaid, Soukaina Haidouri, Tarek Dendane, Khalid Abidi

PMC · DOI: 10.7759/cureus.92654 · Cureus · 2025-09-18

## TL;DR

A young healthy woman developed rare blood and immune disorders caused by two viruses, CMV and EBV, and recovered after intensive treatment.

## Contribution

This case report documents the rare co-occurrence of HLH and TMA in an immunocompetent individual due to CMV and EBV co-infection.

## Key findings

- A 19-year-old woman developed HLH and TMA following CMV and EBV co-infection.
- The patient met most HLH-2004 criteria and showed MAHA with normal ADAMTS13 activity.
- Multidisciplinary treatment led to clinical improvement and full recovery.

## Abstract

Hemophagocytic lymphohistiocytosis (HLH) and thrombotic microangiopathy (TMA) are rare and life-threatening conditions that can be triggered by viral infections, though their simultaneous occurrence remains exceptional, particularly in immunocompetent individuals.

We report the case of a previously healthy 19-year-old woman who developed severe anemia, thrombocytopenia, and fever, rapidly progressing to status epilepticus and multiorgan failure. Laboratory findings were consistent with microangiopathic hemolytic anemia (MAHA), with a normal ADAMTS13 activity, and brain imaging demonstrated diffuse cerebral vasculitis with microthrombi. Extensive workup excluded autoimmune, malignant, toxic, and other infectious causes, while polymerase chain reaction (PCR) testing revealed significant cytomegalovirus (CMV) and Epstein-Barr virus (EBV) viremia. In parallel, the patient fulfilled six of the eight HLH-2004 criteria, including persistent fever, bi-cytopenia, hepatosplenomegaly, hyperferritinemia, hypertriglyceridemia, and hemophagocytosis on bone marrow examination, with an HScore of 259 (>99% probability of HLH), confirming the diagnosis of secondary HLH. Treatment included corticosteroids, ganciclovir, rituximab, cyclophosphamide, anticoagulation, and supportive care, resulting in gradual clinical improvement and full recovery. This case illustrates the pathogenic synergy between CMV and EBV in precipitating both HLH and TMA in an immunocompetent host, and highlights the importance of early diagnosis and multidisciplinary management in such rare and aggressive presentations.

## Linked entities

- **Diseases:** Hemophagocytic lymphohistiocytosis (MONDO:0015540), Thrombotic microangiopathy (MONDO:0019737), Cytomegalovirus infection (MONDO:0005132), Epstein-Barr virus infection (MONDO:0005111), anemia (MONDO:0002280), thrombocytopenia (MONDO:0002049), multiorgan failure (MONDO:0043726)

## Full-text entities

- **Genes:** ADAMTS13 (ADAM metallopeptidase with thrombospondin type 1 motif 13) [NCBI Gene 11093] {aka ADAM-TS13, ADAMTS-13, C9orf8, VWFCP, vWF-CP}
- **Diseases:** viremia (MESH:D014766), TMA (MESH:D057049), MAHA (MESH:D000743), HLH (MESH:D051359), hypertriglyceridemia (MESH:D015228), viral infections (MESH:D014777), cerebral vasculitis (MESH:D020293), thrombocytopenia (MESH:D013921), fever (MESH:D005334), CMV (MESH:D003586), multiorgan failure (MESH:D051437), hyperferritinemia (MESH:D000085583), Epstein-Barr Virus (MESH:D020031), Co-infection (MESH:D060085), cytopenia (MESH:D006402), hepatosplenomegaly (MESH:C535727), anemia (MESH:D000740), status epilepticus (MESH:D013226)
- **Chemicals:** rituximab (MESH:D000069283), cyclophosphamide (MESH:D003520), ganciclovir (MESH:D015774)
- **Species:** Homo sapiens (human, species) [taxon 9606], Cytomegalovirus (genus) [taxon 10358]

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12535433/full.md

## References

19 references — full list in the complete paper: https://tomesphere.com/paper/PMC12535433/full.md

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Source: https://tomesphere.com/paper/PMC12535433