Hemophagocytic syndrome: primary forms and predisposing conditions

- HLH is a life-threatening hyperinflammatory syndrome.
- Genetic defects impairing lymphocyte cytotoxicity mainly cause primary HLH.
- Defects primary impairing macrophages activation are being increasingly recognized.
- Deciphering the other pathological pathways is a key challenge for the coming years.

Hemophagocytic lymphohistiocytosis (HLH, also referred to a hemophagocytic syndrome) is a life-threatening condition in which uncontrolled activation of lymphocytes and macrophages, and thus the secretion of large amounts of inflammatory cytokines, leads to a severe hyperinflammatory state. Over the last few decades, researchers have characterized primary forms of HLH caused by genetic defects that impair lymphocytes' cytotoxic machinery. Other genetic causes of HLH not related to impaired cytotoxicity have also recently been identified. Furthermore, the so-called 'acquired' forms of HLH are encountered in the context of severe infections, autoimmune and autoinflammatory diseases, malignancy, and metabolic disorders, and may also be associated with primary immunodeficiencies. This implies that a variety of disease mechanisms can lead to HLH. Today's research seeks to gain a better understanding of the various pathogenetic and environmental factors that converge to induce HLH.