Infections Associated With the Hemophagocytic Syndrome

Abstract

The hemophagocytic syndrome (HPS) is an unusual but potentially fatal disease resulting from dysregulated activation and proliferation of natural killer (NK) cells and cytotoxic T cells. The term hemophagocytosis describes the pathological finding of activated macrophages, engulfing erythrocytes, leukocytes, platelets, and their precursor cells. The clinical appearance of the syndrome is heterogeneous, characterized by hemophagocytosis in bone marrow, liver, or lymph nodes, variable cytopenias, hyperferritinenia, hypercytokinemia, high fever, coagulation disorders, hepatosplenomegaly and lymphadenopathy. The syndrome can be either primary or secondary. Until recently, we believed that symptoms of HPS due to genetic causes generally arose during infancy and early childhood. The truth is that the first episode of HPS can occur throughout life, from prenatal to the seventh decade. With the availability of genetic testing, distinctions between primary (genetically determined) and secondary (acquired) forms of HPS have become increasingly blurred. Secondary or reactive HPS is associated with infections, autoimmune diseases, or malignancies. This review summarizes the pathogenesis, clinical and diagnostic features and management of HPS in the context of specific infections. It is important to realize that both primary and secondary syndromes can be precipitated by an infection, particularly Epstein-Barr virus (EBV) and other herpes viruses, human immunodeficiency virus (HIV), influenza, parvovirus, hepatitis viruses, as well as bacterial, fungal, and parasitic infections.