Adult-Onset Hemophagocytic Lymphohistiocytosis Associated With Epstein-Barr Virus, Lyme Disease, and Anaplasmosis

Adult-onset hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome characterized by dysregulated immune activation. Diagnosing HLH poses significant challenges due to its nonspecific clinical presentation, which often mimics infections, malignancies, and autoimmune diseases. Early recognition and prompt initiation of immunosuppressive therapy are crucial, as delayed treatment is associated with a high risk of mortality. We present a unique case of HLH triggered by a combination of Epstein-Barr virus (EBV), Lyme disease, and anaplasmosis, underscoring the complexity of diagnosing and managing this condition. The patient initially presented with fever, hypotension, and altered mental status, raising concerns for septic shock. However, a comprehensive diagnostic workup, including infectious disease testing, hematologic evaluation, and bone marrow biopsy, revealed HLH with evidence of EBV viremia, Borrelia burgdorferi exposure, and anaplasmosis infection. This case highlights the importance of maintaining a broad differential diagnosis when confronted with a sepsis-like presentation, particularly in endemic regions where tick-borne diseases and viral infections coexist. A multidisciplinary approach involving infectious disease specialists, hematologists, and intensivists was essential in achieving the diagnosis and formulating a treatment plan. The patient responded favorably to immunosuppressive therapy, including corticosteroids, intravenous immunoglobulins, and targeted antimicrobial therapy, resulting in clinical stabilization and recovery. Our report emphasizes the need for heightened clinical awareness of HLH and the challenges posed by its overlapping features with other systemic illnesses. Furthermore, it illustrates the significance of early intervention and individualized care in managing HLH triggered by multiple infectious agents.