Hemophagocytic lymphohistiocytosis: review of etiologies and management

George, Melissa R

Much has been learned about HLH in the 75 years since it was first discovered. One of the earliest descriptions of the disease was in 1939 when Scott and Robb-Smith 1 described a disorder featuring erythrophagocytosis by proliferating histiocytes in the lymphoreticular system and called it "histiocytic medullary reticulosis" or HMR. It was later classified among malignant histiocytosis. Later in 1952, the familial form of HLH, FHL, was more fully described by Farquhar and Claireaux 2 with the cases of two siblings who succumbed to HLH, and later in 1958, another sibling from this same family presented in the same manner. 3 Risdall was among the first to describe a viral association with HLH and proposed that the condition be called virus-associated HLH, distinct from malignant histiocytosis. 4 In the years since, researchers have recognized the wide scope of this disease and the fact that infection often triggers both primary and secondary HLH. Regardless of cause, physiologically, HLH is characterized by defective cytotoxic cell function coupled with unbridled macrophage activity, leading to excessive cytokine production, subsequent immune dysregulation, and tissue damage. Left untreated, the dysregulated inflammatory response causes severe neutropenia, and patients often die from bacterial or fungal infections. The condition carries high morbidity and mortality. 5 Long-term survival in 1983 was estimated to be as low as 4%. 6 The median survival without treatment is estimated at ,2 months. 6