Beyond the Usual Suspects: Cytomegalovirus-Driven Hemophagocytic Lymphohistiocytosis (HLH) in a Previously Healthy Adult.

Hemophagocytic lymphohistiocytosis (HLH) is a potentially life-threatening syndrome characterized by excessive immune activation and cytokine storm. While primary HLH is genetic and typically presents in childhood, secondary HLH is acquired and often triggered by malignancy, autoimmune disorders, or infections. Acute cytomegalovirus (CMV) infection is a known trigger, although it is rarely the primary cause in immunocompetent adults. We present the case of a healthy 33-year-old female presenting with three weeks of high-grade fever and flank pain following treatment for a presumed urinary tract infection. Despite multiple courses of antibiotics, her symptoms persisted. Evaluation revealed hepatitis, cytopenias, and splenomegaly. Testing confirmed acute CMV infection with a relatively low viral titer. However, the patient met the diagnostic criteria for HLH with a high H-score. She was successfully treated with antivirals, corticosteroids, and intravenous immunoglobulin (IVIG). This case highlights the necessity of considering HLH in the differential diagnosis of fever of unknown origin (FUO) and underscores that even mild CMV viremia can precipitate life-threatening HLH in immunocompetent adults.