Advances in understanding the pathogenesis of HLH
Department of Pediatrics; Department of Pathology
Medical Subject Headings
Hemic and Lymphatic Diseases | Pathology
Haemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory disorder resulting from immune dysfunction reflecting either primary immune deficiency or acquired failure of normal immune homeostasis. Familial HLH includes autosomal recessive and X-linked disorders characterized by uncontrolled activation of T cells and macrophages and overproduction of inflammatory cytokines, secondary to defects in genes encoding proteins involved in granule-dependent cytolytic pathways. In older children and adults, HLH is associated more often with infections, malignancies, autoimmune diseases, and acquired immune deficiencies. HLH, macrophage activation syndrome, sepsis, and systemic inflammatory response syndrome are different clinical entities that probably represent a common immunopathological state, termed cytokine storm. These conditions may be clinically indistinguishable; all include massive inflammatory response, elevated serum cytokine levels, multi-organ involvement, haemophagocytic macrophages, and often death. Tissues of haematopoietic and lymphoid function are directly involved; other organs are secondarily damaged by circulating cytokines and chemokines. Haemophagocytic disorders are now increasingly diagnosed in the context of severe inflammatory reactions to viruses, malignancies and systemic connective tissue diseases. Many of these cases may reflect underlying genetic predispositions to HLH. The detection of gene defects has contributed considerably to our understanding of HLH, but the mechanisms leading to acquired HLH have yet to be fully determined.
Rights and Permissions
Citation: Br J Haematol. 2013 Jun;161(5):609-22. doi: 10.1111/bjh.12293. Epub 2013 Apr 12. Link to article on publisher's site
Usmani, G. Naheed; Woda, Bruce A.; and Newburger, Peter E., "Advances in understanding the pathogenesis of HLH" (2013). University of Massachusetts Medical School Faculty Publications. 3.