Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal immune disorder 
characterized by uncontrolled lymphocyte- and macrophage-activation. The 
resulting hypercytokinemia and cell infiltration of organs lead to the clinical 
and laboratory features of HLH. Viral infections and other triggers can induce 
both, inherited and acquired forms of HLH. Disease-causing mutations in the 
genes encoding perforin (PRF1, FHL2), munc13-4 (UNC13D, FHL3), syntaxin 11 
(STX11, FHL4), and munc18-2 (UNC18-2/STXBP2, FHL5) have been previously 
identified in Familial Hemophagocyic Lymphohistiocytosis (FHL), whereas mutation 
in RAB27A and LYST account for Griscelli syndome type 2 and Chediak-Higashi 
syndrome, respectively. These genes all encode proteins which are involved in 
the cytotoxic activity of lymphocytes. The inability of activated cytotoxic 
cells to clear antigen-presenting targets results in sustained immune 
stimulation, likely accounting for the unremitting polyclonal CD8 T-cell 
activation and hyperimmune reaction which characterizes FHL. Treatment of HLH 
consists of elimination of the trigger and immunosuppressive treatment in order 
to induce remission from the uncontrolled inflammation. Allogeneic hematopoietic 
stem cell transplantation can be indicated in the inherited forms of HLH.