The Virology of Hemophagocytic Lymphohistiocytosis

The hemophagocytic lymphohistiocytosis (HLH) syndrome encompasses a group of disorders with a similar clinical and laboratory presentation, most frequently with the pathologic finding of hemophagocytosis within the bone marrow. The disease exists in genetic and spontaneous forms, resulting in dysregulation of the immune system, specifically the inflammatory response through various mechanisms. The syndrome can be incited by many different events and underlying conditions such as hematologic malignancies, rheumatic and immunologic disorders, medications, and infections. This includes several viral pathogens. Given the tropism of certain viruses toward the bone marrow and immune cells, the herpesviruses, particularly Epstein-Barr, are frequently associated with this disease along with many others. This chapter will review the current understanding of the HLH syndrome and review the role of viruses in HLH as well as proposed virologic mechanisms and current therapies.