Secondary hemophagocytic lymphohistiocytosis following blood transfusion in the absence of an identifiable trigger

Hemophagocytic lymphohistiocytosis is a life-threatening inflammatory syndrome resulting from uncontrolled immune activation. Secondary hemophagocytic lymphohistiocytosis is typically triggered by infection, malignancy, or autoimmune disease, though diagnosis is often difficult due to nonspecific findings. We present the case of a 55-year-old man with pancytopenia and fever following a blood transfusion. There were no clear infectious, malignant, or autoimmune triggers identified. Bone marrow biopsy showed no hemophagocytosis, but laboratory workup revealed hypertriglyceridemia, hyperferritinemia, and elevated soluble IL-2 receptor. He met six hemophagocytic lymphohistiocytosis-2004 criteria and had a high H-score. He was treated with dexamethasone and etoposide, with rapid clinical improvement. This is a unique case of secondary hemophagocytic lymphohistiocytosis after a blood transfusion without other identifiable triggers, which has not yet been reported in the literature. This case underscores the importance of maintaining high clinical suspicion for hemophagocytic lymphohistiocytosis in adults with persistent fever and cytopenias, even in the absence of known triggers.