Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of extreme, systemic immune activation characterized by prolonged fever, hepatosplenomegaly, cytopenias, and elevated markers of inflammation. This constellation of clinical and laboratory findings results from dysregulation of the pathways that govern the immune system’s inflammatory response, leading to persistent activation of lymphocytes and macrophages. The mortality rate is high, and prompt recognition and treatment initiation are essential for survival. However, diagnosis can be challenging because HLH is rare and can present with nonspecific clinical findings that overlap with other disease states, such as sepsis or malignancy.

HLH has been historically classified as primary/familial HLH, caused by a genetic mutation, or secondary, caused by an environmental or acquired trigger, such as infection, malignancy, or an autoimmune disorder. Today there is a growing understanding that this dichotomy does not fully capture the complex interactions between genetic predisposition and environmental factors that can lead to HLH or...

You do not currently have access to this content.