{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T12:28:55Z","timestamp":1790684935795,"version":"4.1.0"},"reference-count":120,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2014,4,1]],"date-time":"2014-04-01T00:00:00Z","timestamp":1396310400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"content-domain":{"domain":["bprclinrheum.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Best Practice &amp; Research Clinical Rheumatology"],"published-print":{"date-parts":[[2014,4]]},"DOI":"10.1016\/j.berh.2014.03.002","type":"journal-article","created":{"date-parts":[[2014,6,26]],"date-time":"2014-06-26T09:47:32Z","timestamp":1403776052000},"page":"277-292","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":143,"title":["Macrophage activation syndrome and cytokine-directed therapies"],"prefix":"10.1016","volume":"28","author":[{"given":"Grant S.","family":"Schulert","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexei A.","family":"Grom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.berh.2014.03.002_bib1","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/S0022-3476(85)80072-X","article-title":"Acute hemorrhagic, hepatic, and neurologic manifestations in juvenile rheumatoid arthritis: possible relationship to drugs or infection","volume":"106","author":"Hadchouel","year":"1985","journal-title":"Journal of Pediatrics"},{"key":"10.1016\/j.berh.2014.03.002_bib2","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1016\/S0022-3476(96)70160-9","article-title":"Efficacy of cyclosporine A in the treatment of macrophage activation syndrome in juvenile arthritis: report of five cases","volume":"129","author":"Mouy","year":"1996","journal-title":"Journal of Pediatrics"},{"key":"10.1016\/j.berh.2014.03.002_bib3","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1016\/S0022-3476(96)70140-3","article-title":"Macrophage activation syndrome in systemic juvenile rheumatoid arthritis","volume":"129","author":"Grom","year":"1996","journal-title":"Journal of Pediatrics"},{"key":"10.1016\/j.berh.2014.03.002_bib4","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/S0022-3476(96)70408-0","article-title":"Macrophage activation syndrome in systemic juvenile rheumatoid arthritis successfully treated with cyclosporine","volume":"128","author":"Ravelli","year":"1996","journal-title":"Journal of Pediatrics"},{"key":"10.1016\/j.berh.2014.03.002_bib5","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1093\/rheumatology\/40.11.1285","article-title":"Reactive haemophagocytic syndrome in children with inflammatory disorders. A retrospective study of 24 patients","volume":"40","author":"Stephan","year":"2001","journal-title":"Rheumatology"},{"key":"10.1016\/j.berh.2014.03.002_bib6","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1136\/adc.85.5.421","article-title":"Macrophage activation syndrome: a potentially fatal complication of rheumatic disorders","volume":"85","author":"Sawhney","year":"2001","journal-title":"Arch Dis Child"},{"key":"10.1016\/j.berh.2014.03.002_bib7","first-page":"121","article-title":"Is macrophage activation syndrome a new entity?","volume":"20","author":"Athreya","year":"2002","journal-title":"Clin Exp Rheumatol"},{"key":"10.1016\/j.berh.2014.03.002_bib8","first-page":"401","article-title":"Macrophage activation syndrome following initiation of etanercept in a child with systemic onset juvenile rheumatoid arthritis","volume":"30","author":"Ramanan","year":"2003","journal-title":"J\u00a0Rheumatol"},{"key":"10.1016\/j.berh.2014.03.002_bib9","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1002\/(SICI)1096-911X(199709)29:3<157::AID-MPO1>3.0.CO;2-C","article-title":"Contemporary classification of histiocytic disorders. The WHO Committee on Histiocytic\/Reticulum Cell Proliferations. Reclassification Working Group of the Histiocyte Society","volume":"29","author":"Favara","year":"1997","journal-title":"Med Pediatr Oncol"},{"key":"10.1016\/j.berh.2014.03.002_bib10","doi-asserted-by":"crossref","first-page":"S82","DOI":"10.1016\/j.bbmt.2009.11.014","article-title":"Histiocytic disorders: recent insights into pathophysiology and practical guidelines","volume":"16","author":"Filipovich","year":"2010","journal-title":"Biol Blood Marrow Transplant"},{"key":"10.1016\/j.berh.2014.03.002_bib11","doi-asserted-by":"crossref","first-page":"4041","DOI":"10.1182\/blood-2011-03-278127","article-title":"How I treat hemophagocytic lymphohistiocytosis","volume":"118","author":"Jordan","year":"2011","journal-title":"Blood"},{"key":"10.1016\/j.berh.2014.03.002_bib12","first-page":"702","article-title":"Hemophagocytic lymphohistiocytosis in adults","volume":"56","author":"Zhang","year":"2011","journal-title":"Pediatr Blood Cancer"},{"key":"10.1016\/j.berh.2014.03.002_bib13","doi-asserted-by":"crossref","first-page":"3388","DOI":"10.1002\/art.24883","article-title":"Macrophage activation syndrome in juvenile systemic lupus erythematosus: a multinational multicenter study of thirty-eight patients","volume":"60","author":"Parodi","year":"2009","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.berh.2014.03.002_bib14","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/j.jpeds.2005.12.070","article-title":"Macrophage activation syndrome as the presenting manifestation of rheumatic diseases in childhood","volume":"148","author":"Avcin","year":"2006","journal-title":"Journal of Pediatrics"},{"key":"10.1016\/j.berh.2014.03.002_bib15","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1097\/MPH.0b013e3181dccbf4","article-title":"Macrophage activation syndrome in the acute phase of Kawasaki disease","volume":"32","author":"Latino","year":"2010","journal-title":"J\u00a0Pediatr Hematol Oncol"},{"key":"10.1016\/j.berh.2014.03.002_bib16","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1002\/pbc.22630","article-title":"Macrophage activation syndrome\/Hemophagocytic Lymphohistiocytosis and Kawasaki disease","volume":"55","author":"Simonini","year":"2010","journal-title":"Pediatr Blood Cancer"},{"key":"10.1016\/j.berh.2014.03.002_bib17","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1007\/s10067-012-1998-0","article-title":"Clinical analysis of macrophage activation syndrome in pediatric patients with autoimmune diseases","volume":"31","author":"Lin","year":"2012","journal-title":"Clin Rheumatol"},{"key":"10.1016\/j.berh.2014.03.002_bib18","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1002\/art.11368","article-title":"Reactive hemophagocytic syndrome in adult systemic disease: report of twenty-six cases and literature review","volume":"49","author":"Dhote","year":"2003","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.berh.2014.03.002_bib19","first-page":"1414","article-title":"Haemophagocytic syndrome in rheumatic patients. A systematic review","volume":"16","author":"Atteritano","year":"2012","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"10.1016\/j.berh.2014.03.002_bib20","first-page":"459","article-title":"The incidence of macrophage activation syndrome in children with rheumatic disorders","volume":"63","author":"Moradinejad","year":"2011","journal-title":"Minerva Pediatr"},{"key":"10.1016\/j.berh.2014.03.002_bib21","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1002\/art.22416","article-title":"The diagnostic significance of soluble CD163 and soluble interleukin-2 receptor alpha-chain in macrophage activation syndrome and untreated new-onset systemic juvenile idiopathic arthritis","volume":"56","author":"Bleesing","year":"2007","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.berh.2014.03.002_bib22","first-page":"1133","article-title":"Occult macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis","volume":"34","author":"Behrens","year":"2007","journal-title":"J\u00a0Rheumatol"},{"key":"10.1016\/j.berh.2014.03.002_bib23","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1002\/pbc.21039","article-title":"HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis","volume":"48","author":"Henter","year":"2007","journal-title":"Pediatr Blood Cancer"},{"key":"10.1016\/j.berh.2014.03.002_bib24","first-page":"271","article-title":"Toward an understanding of the long-term outcome of juvenile idiopathic arthritis","volume":"22","author":"Ravelli","year":"2004","journal-title":"Clin Exp Rheumatol"},{"key":"10.1016\/j.berh.2014.03.002_bib25","doi-asserted-by":"crossref","first-page":"764","DOI":"10.3899\/jrheum.100996","article-title":"An international consensus survey of diagnostic criteria for macrophage activation syndrome in systemic juvenile idiopathic arthritis","volume":"38","author":"Davi","year":"2011","journal-title":"J\u00a0Rheumatol"},{"key":"10.1016\/j.berh.2014.03.002_bib26","doi-asserted-by":"crossref","first-page":"1957","DOI":"10.1126\/science.286.5446.1957","article-title":"Perforin gene defects in familial hemophagocytic lymphohistiocytosis","volume":"286","author":"Stepp","year":"1999","journal-title":"Science"},{"key":"10.1016\/j.berh.2014.03.002_bib27","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/S0092-8674(03)00855-9","article-title":"Munc13-4 is essential for cytolytic granules fusion and is mutated in a form of familial hemophagocytic lymphohistiocytosis (FHL3)","volume":"115","author":"Feldmann","year":"2003","journal-title":"Cell"},{"key":"10.1016\/j.berh.2014.03.002_bib28","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1093\/hmg\/ddi076","article-title":"Linkage of familial hemophagocytic lymphohistiocytosis (FHL) type-4 to chromosome 6q24 and identification of mutations in syntaxin 11","volume":"14","author":"zur Stadt","year":"2005","journal-title":"Hum Mol Genet"},{"key":"10.1016\/j.berh.2014.03.002_bib29","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1084\/jem.20062447","article-title":"Jinx, an MCMV susceptibility phenotype caused by disruption of Unc13d: a mouse model of type 3 familial hemophagocytic lymphohistiocytosis","volume":"204","author":"Crozat","year":"2007","journal-title":"J\u00a0Exp Med"},{"key":"10.1016\/j.berh.2014.03.002_bib30","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.ajhg.2009.09.005","article-title":"Familial hemophagocytic lymphohistiocytosis type 5 (FHL-5) is caused by mutations in Munc18-2 and impaired binding to syntaxin 11","volume":"85","author":"zur Stadt","year":"2009","journal-title":"Am J Hum Genet"},{"key":"10.1016\/j.berh.2014.03.002_bib31","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1186\/ar3843","article-title":"Recent advances in the diagnosis and treatment of hemophagocytic lymphohistiocytosis","volume":"14","author":"Bode","year":"2012","journal-title":"Arthritis Res Ther"},{"key":"10.1016\/j.berh.2014.03.002_bib32","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1067\/mpd.2003.110","article-title":"Natural killer cell dysfunction in patients with systemic-onset juvenile rheumatoid arthritis and macrophage activation syndrome","volume":"142","author":"Grom","year":"2003","journal-title":"Journal of Pediatrics"},{"key":"10.1016\/j.berh.2014.03.002_bib33","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1002\/art.23199","article-title":"Mutations of the hemophagocytic lymphohistiocytosis-associated gene UNC13D in a patient with systemic juvenile idiopathic arthritis","volume":"58","author":"Hazen","year":"2008","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.berh.2014.03.002_bib34","doi-asserted-by":"crossref","first-page":"2892","DOI":"10.1002\/art.23734","article-title":"Macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis is associated with MUNC13-4 polymorphisms","volume":"58","author":"Zhang","year":"2008","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.berh.2014.03.002_bib35","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1093\/rheumatology\/kep418","article-title":"Mutations in the perforin gene can be linked to macrophage activation syndrome in patients with systemic onset juvenile idiopathic arthritis","volume":"49","author":"Vastert","year":"2010","journal-title":"Rheumatology"},{"key":"10.1016\/j.berh.2014.03.002_bib36","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1182\/blood-2003-10-3413","article-title":"An animal model of hemophagocytic lymphohistiocytosis (HLH): CD8+ T cells and interferon gamma are essential for the disorder","volume":"104","author":"Jordan","year":"2004","journal-title":"Blood"},{"key":"10.1016\/j.berh.2014.03.002_bib37","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1002\/emmm.200900009","article-title":"Neutralization of IFNgamma defeats haemophagocytosis in LCMV-infected perforin- and Rab27a-deficient mice","volume":"1","author":"Pachlopnik Schmid","year":"2009","journal-title":"EMBO Mol Med"},{"key":"10.1016\/j.berh.2014.03.002_bib38","doi-asserted-by":"crossref","first-page":"3219","DOI":"10.1002\/eji.200838488","article-title":"A\u00a0Griscelli syndrome type 2 murine model of hemophagocytic lymphohistiocytosis (HLH)","volume":"38","author":"Pachlopnik Schmid","year":"2008","journal-title":"Eur J Immunol"},{"key":"10.1016\/j.berh.2014.03.002_bib39","doi-asserted-by":"crossref","first-page":"6582","DOI":"10.1182\/blood-2011-01-329607","article-title":"Disruption of MyD88 signaling suppresses hemophagocytic lymphohistiocytosis in mice","volume":"117","author":"Krebs","year":"2011","journal-title":"Blood"},{"key":"10.1016\/j.berh.2014.03.002_bib40","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1084\/jem.20050473","article-title":"Role of interleukin-1 (IL-1) in the pathogenesis of systemic onset juvenile idiopathic arthritis and clinical response to IL-1 blockade","volume":"201","author":"Pascual","year":"2005","journal-title":"J\u00a0Exp Med"},{"key":"10.1016\/j.berh.2014.03.002_bib41","doi-asserted-by":"crossref","first-page":"3793","DOI":"10.1002\/art.22981","article-title":"Gene expression profiling of peripheral blood from patients with untreated new-onset systemic juvenile idiopathic arthritis reveals molecular heterogeneity that may predict macrophage activation syndrome","volume":"56","author":"Fall","year":"2007","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.berh.2014.03.002_bib42","doi-asserted-by":"crossref","first-page":"2264","DOI":"10.1172\/JCI43157","article-title":"Repeated TLR9 stimulation results in macrophage activation syndrome-like disease in mice","volume":"121","author":"Behrens","year":"2011","journal-title":"J\u00a0Clin Invest"},{"key":"10.1016\/j.berh.2014.03.002_bib43","doi-asserted-by":"crossref","first-page":"2918","DOI":"10.1182\/blood.V78.11.2918.2918","article-title":"Hypercytokinemia in familial hemophagocytic lymphohistiocytosis","volume":"78","author":"Henter","year":"1991","journal-title":"Blood"},{"key":"10.1016\/j.berh.2014.03.002_bib44","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1002\/(SICI)1096-911X(199607)27:1<21::AID-MPO5>3.0.CO;2-W","article-title":"Elevated circulating levels of interleukin-1 receptor antagonist but not IL-1 agonists in hemophagocytic lymphohistiocytosis","volume":"27","author":"Henter","year":"1996","journal-title":"Med Pediatr Oncol"},{"key":"10.1016\/j.berh.2014.03.002_bib45","doi-asserted-by":"crossref","DOI":"10.1182\/blood-2010-08-300046","article-title":"Gene expression profiling of peripheral blood mononuclear cells from children with active hemophagocytic lymphohistiocytosis","volume":"117","author":"Sumegi","year":"2011","journal-title":"Blood"},{"key":"10.1016\/j.berh.2014.03.002_bib46","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.cyto.2012.05.003","article-title":"Compensated inflammation in systemic juvenile idiopathic arthritis: role of alternatively activated macrophages","volume":"60","author":"Shimizu","year":"2012","journal-title":"Cytokine"},{"key":"10.1016\/j.berh.2014.03.002_bib47","doi-asserted-by":"crossref","first-page":"4100","DOI":"10.1182\/blood.V89.11.4100","article-title":"Cytokine production regulating Th1 and Th2 cytokines in hemophagocytic lymphohistiocytosis","volume":"89","author":"Osugi","year":"1997","journal-title":"Blood"},{"key":"10.1016\/j.berh.2014.03.002_bib48","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1189\/jlb.0105015","article-title":"Phenotypic and functional profiling of human proinflammatory type-1 and anti-inflammatory type-2 macrophages in response to microbial antigens and IFN-gamma- and CD40L-mediated costimulation","volume":"79","author":"Verreck","year":"2006","journal-title":"J\u00a0Leukoc Biol"},{"issue":"Suppl. 1","key":"10.1016\/j.berh.2014.03.002_bib49","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1186\/ar3907","article-title":"IL-10-producing regulatory B cells (B10 cells) in autoimmune disease","volume":"15","author":"Kalampokis","year":"2013","journal-title":"Arthritis Res Ther"},{"key":"10.1016\/j.berh.2014.03.002_bib50","doi-asserted-by":"crossref","first-page":"351","DOI":"10.3389\/fimmu.2013.00351","article-title":"The central role of anti-IL-1 blockade in the treatment of monogenic and multi-factorial autoinflammatory diseases","volume":"4","author":"Federici","year":"2013","journal-title":"Front Immunol"},{"key":"10.1016\/j.berh.2014.03.002_bib51","doi-asserted-by":"crossref","first-page":"4415","DOI":"10.1002\/pmic.201000298","article-title":"Plasma profiles in active systemic juvenile idiopathic arthritis: biomarkers and biological implications","volume":"10","author":"Ling","year":"2010","journal-title":"Proteomics"},{"key":"10.1016\/j.berh.2014.03.002_bib52","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1002\/art.23437","article-title":"The pattern of response to anti-interleukin-1 treatment distinguishes two subsets of patients with systemic-onset juvenile idiopathic arthritis","volume":"58","author":"Gattorno","year":"2008","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.berh.2014.03.002_bib53","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1002\/art.30128","article-title":"Anakinra as first-line disease-modifying therapy in systemic juvenile idiopathic arthritis: report of forty-six patients from an international multicenter series","volume":"63","author":"Nigrovic","year":"2011","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.berh.2014.03.002_bib54","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1097\/RHU.0b013e3181a4f459","article-title":"Anakinra for systemic juvenile arthritis: the Rocky Mountain experience","volume":"15","author":"Zeft","year":"2009","journal-title":"J\u00a0Clin Rheumatol"},{"key":"10.1016\/j.berh.2014.03.002_bib55","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1136\/ard.2010.134254","article-title":"A\u00a0multicentre, randomised, double-blind, placebo-controlled trial with the interleukin-1 receptor antagonist anakinra in patients with systemic-onset juvenile idiopathic arthritis (ANAJIS trial)","volume":"70","author":"Quartier","year":"2011","journal-title":"Ann Rheum Dis"},{"key":"10.1016\/j.berh.2014.03.002_bib56","doi-asserted-by":"crossref","first-page":"2396","DOI":"10.1056\/NEJMoa1205099","article-title":"Two randomized trials of canakinumab in systemic juvenile idiopathic arthritis","volume":"367","author":"Ruperto","year":"2012","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.berh.2014.03.002_bib57","doi-asserted-by":"crossref","first-page":"1794","DOI":"10.1002\/art.21061","article-title":"Rapid responses to anakinra in patients with refractory adult-onset Still's disease","volume":"52","author":"Fitzgerald","year":"2005","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.berh.2014.03.002_bib58","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1002\/art.1780340912","article-title":"Correlation of serum interleukin-6 levels with joint involvement and thrombocytosis in systemic juvenile rheumatoid arthritis","volume":"34","author":"de Benedetti","year":"1991","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.berh.2014.03.002_bib59","doi-asserted-by":"crossref","first-page":"e20014","DOI":"10.1371\/journal.pone.0020014","article-title":"Role of IL-1 beta in the development of human T(H)17 cells: lesson from NLPR3 mutated patients","volume":"6","author":"Lasiglie","year":"2011","journal-title":"PLoS One"},{"key":"10.1016\/j.berh.2014.03.002_bib60","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.1182\/blood-2004-08-2997","article-title":"Macrophage activation syndrome: characteristic findings on liver biopsy illustrating the key role of activated, IFN-gamma-producing lymphocytes and IL-6- and TNF-alpha-producing macrophages","volume":"105","author":"Billiau","year":"2005","journal-title":"Blood"},{"key":"10.1016\/j.berh.2014.03.002_bib61","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1016\/j.jpeds.2011.11.046","article-title":"Diagnostic accuracy of a specific cytokine pattern in hemophagocytic lymphohistiocytosis in children","volume":"160","author":"Xu","year":"2012","journal-title":"Journal of Pediatrics"},{"key":"10.1016\/j.berh.2014.03.002_bib62","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1002\/art.33496","article-title":"Amplification of the response to toll-like receptor ligands by prolonged exposure to interleukin-6 in mice: implication for the pathogenesis of macrophage activation syndrome","volume":"64","author":"Strippoli","year":"2012","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.berh.2014.03.002_bib63","doi-asserted-by":"crossref","first-page":"2385","DOI":"10.1056\/NEJMoa1112802","article-title":"Randomized trial of tocilizumab in systemic juvenile idiopathic arthritis","volume":"367","author":"De Benedetti","year":"2012","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.berh.2014.03.002_bib64","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.cyto.2012.02.006","article-title":"Tocilizumab masks the clinical symptoms of systemic juvenile idiopathic arthritis-associated macrophage activation syndrome: the diagnostic significance of interleukin-18 and interleukin-6","volume":"58","author":"Shimizu","year":"2012","journal-title":"Cytokine"},{"key":"10.1016\/j.berh.2014.03.002_bib65","doi-asserted-by":"crossref","first-page":"367","DOI":"10.2165\/11532610-000000000-00000","article-title":"Tumor necrosis factor inhibitors in the management of juvenile idiopathic arthritis: an evidence-based review","volume":"12","author":"Shenoi","year":"2010","journal-title":"Paediatr Drugs"},{"key":"10.1016\/j.berh.2014.03.002_bib66","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1007\/s11882-013-0351-2","article-title":"Update on the treatment of juvenile idiopathic arthritis","volume":"13","author":"Harris","year":"2013","journal-title":"Curr Allergy Asthma Rep"},{"key":"10.1016\/j.berh.2014.03.002_bib67","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.1093\/rheumatology\/keq133","article-title":"Distinct cytokine profiles of systemic-onset juvenile idiopathic arthritis-associated macrophage activation syndrome with particular emphasis on the role of interleukin-18 in its pathogenesis","volume":"49","author":"Shimizu","year":"2010","journal-title":"Rheumatology (Oxford)"},{"key":"10.1016\/j.berh.2014.03.002_bib68","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1038\/pr.2013.187","article-title":"Advances in the pathogenesis and treatment of systemic juvenile idiopathic arthritis","volume":"75","author":"Correll","year":"2014","journal-title":"Pediatr Res"},{"key":"10.1016\/j.berh.2014.03.002_bib69","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1002\/acr.21625","article-title":"Consensus treatment plans for new-onset systemic juvenile idiopathic arthritis","volume":"64","author":"DeWitt","year":"2012","journal-title":"Arthritis Care Res (Hoboken)"},{"key":"10.1016\/j.berh.2014.03.002_bib70","doi-asserted-by":"crossref","first-page":"239","DOI":"10.3389\/fimmu.2012.00239","article-title":"Protection from inflammatory organ damage in a murine model of hemophagocytic lymphohistiocytosis using treatment with IL-18 binding protein","volume":"3","author":"Chiossone","year":"2012","journal-title":"Front Immunol"},{"key":"10.1016\/j.berh.2014.03.002_bib71","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1016\/j.immuni.2006.09.010","article-title":"Perforin and granzymes have distinct roles in defensive immunity and immunopathology","volume":"25","author":"van Dommelen","year":"2006","journal-title":"Immunity"},{"key":"10.1016\/j.berh.2014.03.002_bib72","doi-asserted-by":"crossref","first-page":"967","DOI":"10.3899\/jrheum.090662","article-title":"Cytokine profiles of macrophage activation syndrome associated with rheumatic diseases","volume":"37","author":"Maruyama","year":"2010","journal-title":"J\u00a0Rheumatol"},{"key":"10.1016\/j.berh.2014.03.002_bib73","first-page":"443","article-title":"Etanercept for therapy-resistant macrophage activation syndrome","volume":"65","author":"Makay","year":"2006","journal-title":"Ann Rheum Dis"},{"key":"10.1016\/j.berh.2014.03.002_bib74","first-page":"2120","article-title":"Etanercept in the treatment of macrophage activation syndrome","volume":"28","author":"Prahalad","year":"2001","journal-title":"J\u00a0Rheumatol"},{"key":"10.1016\/j.berh.2014.03.002_bib75","first-page":"414","article-title":"Inhibition of the TNF-pathway: use of infliximab and etanercept as remission-inducing agents in cases of therapy-resistant chronic inflammatory disorders","volume":"132","author":"Aeberli","year":"2002","journal-title":"Swiss Med Wkly"},{"key":"10.1016\/j.berh.2014.03.002_bib76","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1097\/00124743-200108000-00013","article-title":"Worsening of macrophage activation syndrome in a patient with adult onset Still's disease after initiation of etanercept therapy","volume":"7","author":"Stern","year":"2001","journal-title":"J\u00a0Clin Rheumatol"},{"key":"10.1016\/j.berh.2014.03.002_bib77","doi-asserted-by":"crossref","first-page":"2256","DOI":"10.1073\/pnas.96.5.2256","article-title":"Gene expression, synthesis, and secretion of interleukin 18 and interleukin 1 beta are differentially regulated in human blood mononuclear cells and mouse spleen cells","volume":"96","author":"Puren","year":"1999","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.berh.2014.03.002_bib78","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.semnephrol.2006.09.013","article-title":"Interleukin-18 and the pathogenesis of inflammatory diseases","volume":"27","author":"Dinarello","year":"2007","journal-title":"Semin Nephrol"},{"key":"10.1016\/j.berh.2014.03.002_bib79","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1023\/A:1020600230977","article-title":"Plasma levels of interleukin-18 and interleukin-18 binding protein are elevated in patients with chronic liver disease","volume":"22","author":"Ludwiczek","year":"2002","journal-title":"J\u00a0Clin Immunol"},{"key":"10.1016\/j.berh.2014.03.002_bib80","doi-asserted-by":"crossref","first-page":"3483","DOI":"10.1182\/blood-2005-05-1980","article-title":"Severe imbalance of IL-18\/IL-18BP in patients with secondary hemophagocytic syndrome","volume":"106","author":"Mazodier","year":"2005","journal-title":"Blood"},{"key":"10.1016\/j.berh.2014.03.002_bib81","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1002\/art.20268","article-title":"Increased interleukin-18 expression in bone marrow of a patient with systemic juvenile idiopathic arthritis and unrecognized macrophage-activation syndrome","volume":"50","author":"Maeno","year":"2004","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.berh.2014.03.002_bib82","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1002\/1529-0131(200103)44:3<550::AID-ANR103>3.0.CO;2-5","article-title":"Levels of interleukin-18 and its binding inhibitors in the blood circulation of patients with adult-onset Still's disease","volume":"44","author":"Kawashima","year":"2001","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.berh.2014.03.002_bib83","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1006\/cyto.2001.0914","article-title":"A\u00a0novel IL-18BP ELISA shows elevated serum IL-18BP in sepsis and extensive decrease of free IL-18","volume":"14","author":"Novick","year":"2001","journal-title":"Cytokine"},{"key":"10.1016\/j.berh.2014.03.002_bib84","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.cyto.2009.07.435","article-title":"High circulating levels of free interleulkin-18 in patients with active SLE in the presence of elevated levels of interleukin-18 binding protein","volume":"48","author":"Novick","year":"2009","journal-title":"Cytokine"},{"key":"10.1016\/j.berh.2014.03.002_bib85","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1111\/j.1749-6632.2009.04742.x","article-title":"IL-18 activity in systemic lupus erythematosus","volume":"1173","author":"Favilli","year":"2009","journal-title":"Ann N Y Acad Sci"},{"key":"10.1016\/j.berh.2014.03.002_bib86","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1007\/s10875-008-9217-0","article-title":"Interleukin-18 binding protein in the Sera of patients with Wegener's granulomatosis","volume":"29","author":"Novick","year":"2009","journal-title":"J\u00a0Clin Immunol"},{"key":"10.1016\/j.berh.2014.03.002_bib87","doi-asserted-by":"crossref","first-page":"2782","DOI":"10.1002\/art.24750","article-title":"Defective phosphorylation of interleukin-18 receptor beta causes impaired natural killer cell function in systemic-onset juvenile idiopathic arthritis","volume":"60","author":"de Jager","year":"2009","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.berh.2014.03.002_bib88","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1007\/BF03402053","article-title":"Lack of interferon-gamma production despite the presence of interleukin-18 during cutaneous wound healing","volume":"6","author":"Kampfer","year":"2000","journal-title":"Mol Med"},{"key":"10.1016\/j.berh.2014.03.002_bib89","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0008663","article-title":"Failure of interferon gamma to induce the anti-inflammatory interleukin 18 binding protein in familial hemophagocytosis","volume":"5","author":"Nold-Petry","year":"2010","journal-title":"Plos One"},{"key":"10.1016\/j.berh.2014.03.002_bib90","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1189\/jlb.0603252","article-title":"Interferon-gamma: an overview of signals, mechanisms and functions","volume":"75","author":"Schroder","year":"2004","journal-title":"J\u00a0Leukoc Biol"},{"key":"10.1016\/j.berh.2014.03.002_bib91","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1189\/jlb.0602325","article-title":"The many faces of macrophage activation","volume":"73","author":"Mosser","year":"2003","journal-title":"J\u00a0Leukoc Biol"},{"key":"10.1016\/j.berh.2014.03.002_bib92","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.it.2004.09.015","article-title":"The chemokine system in diverse forms of macrophage activation and polarization","volume":"25","author":"Mantovani","year":"2004","journal-title":"Trends Immunol"},{"key":"10.1016\/j.berh.2014.03.002_bib93","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1084\/jem.20102538","article-title":"Hemophagocytosis causes a consumptive anemia of inflammation","volume":"208","author":"Zoller","year":"2011","journal-title":"J\u00a0Exp Med"},{"key":"10.1016\/j.berh.2014.03.002_bib94","doi-asserted-by":"crossref","first-page":"453","DOI":"10.2741\/2692","article-title":"Macrophage activation and polarization","volume":"13","author":"Martinez","year":"2008","journal-title":"Front Biosci"},{"key":"10.1016\/j.berh.2014.03.002_bib95","doi-asserted-by":"crossref","first-page":"3799","DOI":"10.1002\/art.34604","article-title":"The limited role of interferon-gamma in systemic juvenile idiopathic arthritis cannot be explained by cellular hyporesponsiveness","volume":"64","author":"Sikora","year":"2012","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.berh.2014.03.002_bib96","doi-asserted-by":"crossref","first-page":"1954","DOI":"10.1002\/art.22644","article-title":"Specific gene expression profiles in systemic juvenile idiopathic arthritis","volume":"56","author":"Ogilvie","year":"2007","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.berh.2014.03.002_bib97","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.immuni.2009.09.002","article-title":"Cross-regulation of signaling pathways by interferon-gamma: implications for immune responses and autoimmune diseases","volume":"31","author":"Hu","year":"2009","journal-title":"Immunity"},{"key":"10.1016\/j.berh.2014.03.002_bib98","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1046\/j.1365-2249.2003.02237.x","article-title":"Increased serum levels of interferon-gamma-inducible protein 10 and monokine induced by gamma interferon in patients with haemophagocytic lymphohistiocytosis","volume":"133","author":"Takada","year":"2003","journal-title":"Clin Exp Immunol"},{"key":"10.1016\/j.berh.2014.03.002_bib99","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1002\/ajh.21082","article-title":"Soluble TWEAK is markedly elevated in hemophagocytic lymphohistiocytosis","volume":"83","author":"Nagasawa","year":"2008","journal-title":"Am J Hematol"},{"key":"10.1016\/j.berh.2014.03.002_bib100","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1111\/j.1749-6632.2011.06307.x","article-title":"Inherited defects causing hemophagocytic lymphohistiocytic syndrome","volume":"1246","author":"de Saint Basile","year":"2011","journal-title":"Ann N Y Acad Sci"},{"key":"10.1016\/j.berh.2014.03.002_bib101","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1038\/gene.2012.3","article-title":"Macrophage activation syndrome as part of systemic juvenile idiopathic arthritis: diagnosis, genetics, pathophysiology and treatment","volume":"13","author":"Ravelli","year":"2012","journal-title":"Genes Immun"},{"key":"10.1016\/j.berh.2014.03.002_bib102","article-title":"Differences between systemic-onset juvenile idiopathic arthritis and macrophage activation syndrome from the standpoint of the proinflammatory cytokine profile","volume":"50","author":"Imagawa","year":"2004","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.berh.2014.03.002_bib103","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1128\/CVI.00306-10","article-title":"Serum neopterin levels as a diagnostic marker of hemophagocytic lymphohistiocytosis syndrome","volume":"18","author":"Ibarra","year":"2011","journal-title":"Clin Vaccin Immunol"},{"key":"10.1016\/j.berh.2014.03.002_bib104","first-page":"508","article-title":"Successful treatment of juvenile rheumatoid arthritis associated haemophagocytic syndrome by cyclosporin A with transient exacerbation by conventional-dose G-CSF","volume":"97","author":"Quesnel","year":"1997","journal-title":"Br J Haematol"},{"key":"10.1016\/j.berh.2014.03.002_bib105","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1097\/MPH.0b013e3181923cb4","article-title":"Experience with hemophagocytic lymphohistiocytosis\/macrophage activation syndrome at a single institution","volume":"31","author":"Gupta","year":"2009","journal-title":"J\u00a0Pediatr Hematol Oncol"},{"key":"10.1016\/j.berh.2014.03.002_bib106","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1097\/00043426-200210000-00011","article-title":"Adverse outcomes in primary hemophagocytic lymphohistiocytosis","volume":"24","author":"Sung","year":"2002","journal-title":"J\u00a0Pediatr Hematol Oncol"},{"key":"10.1016\/j.berh.2014.03.002_bib107","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.clim.2009.02.005","article-title":"Macrophage activation syndrome: serological markers and treatment with anti-thymocyte globulin","volume":"132","author":"Coca","year":"2009","journal-title":"Clin Immunol"},{"key":"10.1016\/j.berh.2014.03.002_bib108","doi-asserted-by":"crossref","DOI":"10.1542\/peds.2006-3164","article-title":"Immunotherapy of familial hemophagocytic lymphohistiocytosis with antithymocyte globulins: a single-center retrospective report of 38 patients","volume":"120","author":"Mahlaoui","year":"2007","journal-title":"Pediatrics"},{"key":"10.1016\/j.berh.2014.03.002_bib109","doi-asserted-by":"crossref","first-page":"401","DOI":"10.3109\/10428199509112197","article-title":"Hemophagocytic syndrome in Epstein-Barr virus-associated T-lymphoproliferative disorders: disease spectrum, pathogenesis, and management","volume":"19","author":"Su","year":"1995","journal-title":"Leuk Lymphoma"},{"key":"10.1016\/j.berh.2014.03.002_bib110","first-page":"74","article-title":"Successful treatment of thymoma-associated pure red cell aplasia with intravenous immunoglobulins","volume":"65","author":"Larroche","year":"2000","journal-title":"Med Pediatr Oncol"},{"key":"10.1016\/j.berh.2014.03.002_bib111","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1097\/01.rhu.0000081259.61370.eb","article-title":"Macrophage activation syndrome in a patient with systemic onset rheumatoid arthritis \u2013 rescue with intravenous immunoglobulin therapy","volume":"9","author":"Tristano","year":"2003","journal-title":"JCR J Clin Rheumatol"},{"key":"10.1016\/j.berh.2014.03.002_bib112","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1097\/MPH.0b013e3180f61be3","article-title":"Use of rituximab in conjunction with immunosuppressive chemotherapy as a novel therapy for Epstein Barr virus-associated hemophagocytic lymphohistiocytosis","volume":"29","author":"Balamuth","year":"2007","journal-title":"J\u00a0Pediatr Hematol Oncol"},{"key":"10.1016\/j.berh.2014.03.002_bib113","first-page":"364","article-title":"The role of rituximab in a case of EBV-related lymphoproliferative disease presenting with haemophagocytosis","volume":"67","author":"Bosman","year":"2009","journal-title":"Neth J Med"},{"key":"10.1016\/j.berh.2014.03.002_bib114","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1038\/ncprheum0919","article-title":"A\u00a0case of macrophage activation syndrome successfully treated with anakinra","volume":"4","author":"Kelly","year":"2008","journal-title":"Nat Clin Pract Rheumatol"},{"key":"10.1016\/j.berh.2014.03.002_bib115","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1093\/rheumatology\/keq218","article-title":"Successful treatment of severe paediatric rheumatic disease-associated macrophage activation syndrome with interleukin-1 inhibition following conventional immunosuppressive therapy: case series with 12 patients","volume":"50","author":"Miettunen","year":"2011","journal-title":"Rheumatology (Oxford)"},{"key":"10.1016\/j.berh.2014.03.002_bib116","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1097\/RHU.0b013e318205092d","article-title":"Rapid and sustained remission of systemic juvenile idiopathic arthritis-associated macrophage activation syndrome through treatment with anakinra and corticosteroids","volume":"17","author":"Bruck","year":"2011","journal-title":"J\u00a0Clin Rheumatol"},{"key":"10.1016\/j.berh.2014.03.002_bib117","doi-asserted-by":"crossref","first-page":"879","DOI":"10.3899\/jrheum.091046","article-title":"Macrophage activation syndrome treated with anakinra","volume":"37","author":"Durand","year":"2010","journal-title":"J\u00a0Rheumatol"},{"key":"10.1016\/j.berh.2014.03.002_bib118","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1016\/S0140-6736(08)60454-7","article-title":"Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled, withdrawal phase III trial","volume":"371","author":"Yokota","year":"2008","journal-title":"Lancet"},{"key":"10.1016\/j.berh.2014.03.002_bib119","doi-asserted-by":"crossref","first-page":"92","DOI":"10.3109\/s10165-010-0348-9","article-title":"Benefit and a possible risk of tocilizumab therapy for adult-onset Still's disease accompanied by macrophage-activation syndrome","volume":"21","author":"Kobayashi","year":"2011","journal-title":"Mod Rheumatol"},{"key":"10.1016\/j.berh.2014.03.002_bib120","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/1546-0096-10-30","article-title":"Risk of significant cytopenias after treatment with tocilizumab in systemic juvenile arthritis patients with a history of macrophage activation syndrome","volume":"10","author":"Kessler","year":"2012","journal-title":"Pediatr Rheumatol Online J"}],"container-title":["Best Practice &amp; Research Clinical Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1521694214000199?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1521694214000199?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T01:41:07Z","timestamp":1716860467000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1521694214000199"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,4]]},"references-count":120,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2014,4]]}},"alternative-id":["S1521694214000199"],"URL":"https:\/\/doi.org\/10.1016\/j.berh.2014.03.002","relation":{},"ISSN":["1521-6942"],"issn-type":[{"value":"1521-6942","type":"print"}],"subject":[],"published":{"date-parts":[[2014,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Macrophage activation syndrome and cytokine-directed therapies","name":"articletitle","label":"Article Title"},{"value":"Best Practice & Research Clinical Rheumatology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.berh.2014.03.002","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2014 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}]}}