Clinical Characteristics and Treatment of Familial Hemophagocytic Lymphohistiocytosis.

Abstract

Familial hemophagocytic lymphohistiocytosis (fHLH) comprises a group of autosomal recessive disorders characterized by germline loss-of-function variants that negatively impact lymphocyte cytotoxicity. These disorders exhibit variable clinical presentations, most often in association with severe hyperinflammation. fHLH is diagnosed through clinical and laboratory assessments as well as genetic testing and immunologic assays. In the absence of therapy to control the hyperactive immune system, fHLH is generally fatal. Treatment has historically taken the form of cytotoxic chemotherapy and/or immunosuppressive therapy, although targeted inhibitors of inflammatory cytokines and their downstream signaling are increasingly being utilized. Definitive treatment requires allogeneic hematopoietic cell transplantation.