Advances in Hemophagocytic Lymphohistiocytosis: Pathogenesis, Early Diagnosis/Differential Diagnosis, and Treatment

Hemophagocytic lymphohistiocytosis (HLH) is a histiocytic disorder characterized by a highly stimulated, but ineffective, immune response to antigens, which results in life-threatening cytokine storm and inflammatory reaction. Considerable progress has been made during the past 2 decades. Detection of molecular genetic abnormalities in genes involved in immune response pathways, such as PRF1, STX11, UNC13D, STXBP2, RAB27A, LYST, AP3B1, SH2D1A, and BIRC4, is confirmatory for the diagnosis. Clinical diagnosis is largely made according to HLH-2004 criteria. However, a new finding of the Th1/Th2 cytokine pattern (significant increase of IFN-γ and IL-10 with slightly increased or normal level of IL-6) is a useful biomarker for the early diagnosis, differential diagnosis, and the monitoring of the disease. Intensive immunosuppressive therapy is generally accepted as treatment for the relief of clinical symptoms/signs, while allogeneic hematopoietic stem cell transplantation is currently the only potentially curative therapy option for severe familial forms of HLH.