History of Hemophagocytic Lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) is a severe cytokine storm syndrome (CSS), which until the turn of the century, was barely known but is now receiving increased attention. The history of HLH dates back to 1939 when it was first described in adults, to be followed in 1952 by the first description of its primary, familial form in children. Secondary forms of HLH are far more frequent and occur with infections, malignancies, metabolic diseases, iatrogenic immune suppression, and autoinflammatory/autoimmune diseases. Identification of the genetic defects leading to the defective function of natural killer (NK) cells and cytotoxic T cells as well as the corresponding mouse models have revolutionized our understanding of HLH and of immune function. Diagnosis relies on clinical and laboratory criteria; functional and genetic tests can help separate primary from secondary forms. Treatment with immunochemotherapy and hematopoietic stem cell transplantation has considerably improved survival in children with primary HLH, a formerly uniformly fatal disease.