Critical Connections: Diagnosis of Epstein-Barr Virus (EBV)-Positive Nasopharyngeal Carcinoma-Associated Hemophagocytic Lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) is a rare and potentially fatal condition associated with Epstein-Barr virus (EBV) in children and adults. We report a case of a 65-year-old male with a history of EBV-positive nasopharyngeal carcinoma in remission presenting with fever, altered mental status, abdominal pain, and generalized weakness. Labs showed pancytopenia, hyponatremia, hypochloremia, acute-on-chronic kidney injury, and hypoalbuminemia. The patient was started on empiric broad-spectrum antimicrobials, intravenous crystalloids, and red blood cell transfusions. HLH was suspected, and laboratory evaluation demonstrated elevated EBV viral load, ferritin, and soluble interleukin-2 receptor levels. He met diagnostic criteria for HLH and was started on etoposide and methylprednisolone. However, due to rapid deterioration, the family requested hospice care, and the patient passed away four days later. This case highlights severe presentations of HLH and the importance of considering HLH in the differential diagnosis of patients with nasopharyngeal carcinoma presenting with undifferentiated multisystem syndromes.