title: Macrophage activation syndrome in the era of biologic therapy.
abstract: Macrophage activation syndrome (MAS) refers to acute overwhelming inflammation caused by a 'cytokine storm'. Although increasingly recognized as a life-threatening complication of various rheumatic diseases, clinically, MAS is strikingly similar to primary and secondary forms of haemophagocytic lymphohistiocytosis (HLH). Not surprisingly, many rheumatologists prefer the term secondary HLH rather than MAS to describe this condition, and efforts to change the nomenclature are in progress. The pathophysiology of MAS remains elusive, but observations in animal models, as well as data on the effects of new anticytokine therapies on rates and clinical presentations of MAS in patients with systemic juvenile idiopathic arthritis (sJIA), provide clues to the understanding of this perplexing clinical phenomenon. In this Review, we explore the latest available evidence and discuss potential diagnostic challenges in the era of increasing use of biologic therapies.
authors.affiliation: Division of Rheumatology, ML 4010, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA.
authors.forename: Alexei A
authors.initials: AA
authors.lastname: Grom
authors.affiliation: Department of Women's and Children's Health, Karolinska University Hospital, Karolinska vägen, 171 76 Solna, Stockholm, Sweden.
authors.forename: AnnaCarin
authors.initials: A
authors.lastname: Horne
authors.affiliation: Division of Rheumatology, Ospedale Pediatrico Bambino Gesù, Piazza Sant'Onofrio, 4, Rome, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: De Benedetti
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001171:Arthritis, Juvenile / Q000188:drug therapy / Q000276:immunology; D001688:Biological Products / Q000627:therapeutic use; D004195:Disease Models, Animal; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use; D020382:Interleukin-18 / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology*; D051359:Lymphohistiocytosis, Hemophagocytic / Q000188:drug therapy / Q000276:immunology*; D055501:Macrophage Activation Syndrome / Q000188:drug therapy / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D001688:Biological Products; D053590:Interleukin 1 Receptor Antagonist Protein; D020382:Interleukin-18; D053583:Interleukin-1beta; D015850:Interleukin-6; D011993:Recombinant Fusion Proteins; C541220:canakinumab; D007371:Interferon-gamma; C531377:rilonacept; C502936:tocilizumab