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

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.