• Hemophagocytic lymphohistiocytosis (HLH) is an aggressive and life-threatening hyperinflammatory syndrome, which requires prompt and aggressive treatment
  • It is termed macrophage activation syndrome (MAS) when associated with rheumatic disease and secondary HLH (sHLH) when associated with other triggers, including malignancy and infection
  • HLH represents a group of conditions with different pathogenetic roots but a shared common final pathway
  • It most frequently affects infants up to 18 months of age but can be seen in children and adults of all ages
  • Defined by the presence of intact hematopoietic cells (erythrocytes or leukocytes) within the cytoplasm of phagocytic macrophages (histiocytes) in any tissue
  • The identification of hemophagocytic histiocytes in bone marrow is a fundamental diagnostic feature of HLH:
    • However, the diagnosis can be made even without the presence of haemophagocytosis in biopsied tissue (non-sensitive)
    • Other causes can lead to the presence of haemophagocytosis, including prolonged sepsis, infection (viral, fungal, parasitic) and malignancy