Immune Hyperactivation in Epstein-Barr Virus (EBV)-Driven T-cell Lymphoproliferation: A Pediatric Case of Hemophagocytic Syndrome.

Hemophagocytic lymphohistiocytosis (HLH) triggered by Epstein-Barr virus (EBV)-associated T-cell lymphoproliferation represents a rare, aggressive complication in immunocompetent children, often mimicking lymphoma and leading to cytokine storm and multiorgan failure.​ This case report describes a six-year-old girl presenting with fever, cervical mass, hepatosplenomegaly, and cytopenias. Diagnostic evaluation included imaging (CT scans), serology, EBV polymerase chain reaction (PCR) (viral load 545,238 copies/mL), lymph node biopsy showing cytotoxic T-cell proliferation, and serial labs confirming HLH-2004 criteria (fever, splenomegaly, hypertriglyceridemia, cytopenias, hyperferritinemia >500 ng/mL, and hypofibrinogenemia). Treatment involved antibiotics, rituximab, chemotherapy, and HLH-2004 protocol (etoposide, corticosteroids, and cyclosporine).​ Initial antibiotic therapy addressed Serratia superinfection, but the disease progressed with worsening cytopenias (hemoglobin (Hb) 7.2 g/dL, platelets 33,000/μL), ferritin 5,010 ng/mL, and multiorgan lesions on follow-up CT. HLH protocol induced transient remission (ferritin 206 ng/mL, normalized counts), but two relapses during tapering (recurrent fever, cytopenias, and rising ferritin) preceded fatal hematemesis in June 2025, after six months since the beginning of illness. This pediatric case underscores EBV's rare T-cell tropism in non-Asian contexts, diagnostic pitfalls from biopsy mimicry, and familial hints of underlying immunodeficiency. Despite multidisciplinary intervention, poor prognosis highlights the need for early HLH recognition and potential hematopoietic stem cell transplantation (HSCT). Rapid immunosuppression controls progression, but relapses remain common.