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Familial <jats:styled-content style=\"fixed-case\">HLH<\/jats:styled-content> includes autosomal recessive and <jats:styled-content style=\"fixed-case\">X<\/jats:styled-content>\u2010linked disorders characterized by uncontrolled activation of <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content> cells and macrophages and overproduction of inflammatory cytokines, secondary to defects in genes encoding proteins involved in granule\u2010dependent cytolytic pathways. In older children and adults, <jats:styled-content style=\"fixed-case\">HLH<\/jats:styled-content> 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\u2010organ 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 <jats:styled-content style=\"fixed-case\">HLH<\/jats:styled-content>. The detection of gene defects has contributed considerably to our understanding of <jats:styled-content style=\"fixed-case\">HLH<\/jats:styled-content>, but the mechanisms leading to acquired <jats:styled-content style=\"fixed-case\">HLH<\/jats:styled-content> have yet to be fully determined.<\/jats:p>","DOI":"10.1111\/bjh.12293","type":"journal-article","created":{"date-parts":[[2013,4,12]],"date-time":"2013-04-12T09:13:21Z","timestamp":1365758001000},"page":"609-622","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":176,"title":["Advances in understanding the pathogenesis of <scp>HLH<\/scp>"],"prefix":"10.1111","volume":"161","author":[{"given":"G. 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