{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:31:53Z","timestamp":1791822713570,"version":"4.3.4"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2019,7,31]],"date-time":"2019-07-31T00:00:00Z","timestamp":1564531200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2019,7,31]],"date-time":"2019-07-31T00:00:00Z","timestamp":1564531200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Rheumatol Int"],"published-print":{"date-parts":[[2020,4]]},"DOI":"10.1007\/s00296-019-04393-7","type":"journal-article","created":{"date-parts":[[2019,7,31]],"date-time":"2019-07-31T10:02:45Z","timestamp":1564567365000},"page":"663-669","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Macrophage activation syndrome complicating rheumatic diseases in adults: case-based review"],"prefix":"10.1007","volume":"40","author":[{"given":"Mayan","family":"Gilboa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gil","family":"Bornstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilan","family":"Ben-Zvi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8400-8461","authenticated-orcid":false,"given":"Chagai","family":"Grossman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,7,31]]},"reference":[{"key":"4393_CR1","first-page":"2513","volume":"30","author":"AV Ramanan","year":"2003","unstructured":"Ramanan AV, Schneider R (2003) Macrophage activation syndrome\u2014what\u2019s in a name! J Rheumatol 30:2513\u20132516","journal-title":"J Rheumatol"},{"key":"4393_CR2","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1097\/01.all.0000246626.57118.d9","volume":"6","author":"AH Filipovich","year":"2006","unstructured":"Filipovich AH (2006) Hemophagocytic lymphohistiocytosis and related disorders. Curr Opin Allergy Clin Immunol 6:410\u2013415","journal-title":"Curr Opin Allergy Clin Immunol"},{"key":"4393_CR3","doi-asserted-by":"publisher","first-page":"e451","DOI":"10.1097\/MD.0000000000000451","volume":"94","author":"CB Bae","year":"2015","unstructured":"Bae CB, Jung JY, Kim HA, Suh CH (2015) Reactive hemophagocytic syndrome in adult-onset Still disease: clinical features, predictive factors, and prognosis in 21 patients. Medicine (Baltimore) 94:e451","journal-title":"Medicine (Baltimore)"},{"key":"4393_CR4","doi-asserted-by":"publisher","first-page":"3388","DOI":"10.1002\/art.24883","volume":"60","author":"A Parodi","year":"2009","unstructured":"Parodi A, Davi S, Pringe AB, Pistorio A, Ruperto N, Magni-Manzoni S et al (2009) Macrophage activation syndrome in juvenile systemic lupus erythematosus: a multinational multicenter study of thirty-eight patients. Arthritis Rheum 60:3388\u20133399","journal-title":"Arthritis Rheum"},{"key":"4393_CR5","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1097\/01.md.0000224708.62510.d1","volume":"85","author":"O Lambotte","year":"2006","unstructured":"Lambotte O, Khellaf M, Harmouche H, Bader-Meunier B, Manceron V, Goujard C et al (2006) Characteristics and long-term outcome of 15 episodes of systemic lupus erythematosus-associated hemophagocytic syndrome. Medicine (Baltimore) 85:169\u2013182","journal-title":"Medicine (Baltimore)"},{"key":"4393_CR6","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1002\/pbc.22630","volume":"55","author":"G Simonini","year":"2010","unstructured":"Simonini G, Pagnini I, Innocenti L, Calabri GB, De Martino M, Cimaz R (2010) Macrophage activation syndrome\/Hemophagocytic Lymphohistiocytosis and Kawasaki disease. Pediatr Blood Cancer 55:592","journal-title":"Pediatr Blood Cancer"},{"key":"4393_CR7","first-page":"1133","volume":"34","author":"EM Behrens","year":"2007","unstructured":"Behrens EM, Beukelman T, Paessler M, Cron RQ (2007) Occult macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis. J Rheumatol 34:1133\u20131138","journal-title":"J Rheumatol"},{"key":"4393_CR8","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1002\/art.22416","volume":"56","author":"J Bleesing","year":"2007","unstructured":"Bleesing J, Prada A, Siegel DM, Villanueva J, Olson J, Ilowite NT et al (2007) 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. Arthritis Rheum 56:965\u2013971","journal-title":"Arthritis Rheum"},{"key":"4393_CR9","first-page":"435","volume":"34","author":"A Albert","year":"1992","unstructured":"Albert A, Azgui Z, Buisine J, Ciaudo M, Fenneteau O, Fillola G et al (1992) Macrophage activation syndromes. Nouv Rev Fr Hematol 34:435\u2013441","journal-title":"Nouv Rev Fr Hematol"},{"key":"4393_CR10","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1002\/(SICI)1096-911X(199709)29:3<157::AID-MPO1>3.0.CO;2-C","volume":"29","author":"BE Favara","year":"1997","unstructured":"Favara BE, Feller AC, Pauli M, Jaffe ES, Weiss LM, Arico M et al (1997) Contemporary classification of histiocytic disorders. The WHO Committee On Histiocytic\/Reticulum Cell Proliferations. Reclassification Working Group of the Histiocyte Society. Med Pediatr Oncol 29:157\u2013166","journal-title":"Med Pediatr Oncol"},{"key":"4393_CR11","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1002\/pbc.21039","volume":"48","author":"JI Henter","year":"2007","unstructured":"Henter JI, Horne A, Arico M, Egeler RM, Filipovich AH, Imashuku S et al (2007) HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 48:124\u2013131","journal-title":"Pediatr Blood Cancer"},{"key":"4393_CR12","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1203\/00006450-199810000-00001","volume":"44","author":"KE Sullivan","year":"1998","unstructured":"Sullivan KE, Delaat CA, Douglas SD, Filipovich AH (1998) Defective natural killer cell function in patients with hemophagocytic lymphohistiocytosis and in first degree relatives. Pediatr Res 44:465\u2013468","journal-title":"Pediatr Res"},{"key":"4393_CR13","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation-2005.1.82","author":"G Janka","year":"2005","unstructured":"Janka G, zur Stadt U (2005) Familial and acquired hemophagocytic lymphohistiocytosis. Hematology Am Soc Hematol Educ Program. \nhttps:\/\/doi.org\/10.1182\/asheducation-2005.1.82","journal-title":"Hematology Am Soc Hematol Educ Program"},{"key":"4393_CR14","doi-asserted-by":"publisher","first-page":"994","DOI":"10.3899\/jrheum.141261","volume":"42","author":"F Minoia","year":"2015","unstructured":"Minoia F, Davi S, Horne A, Bovis F, Demirkaya E, Akikusa J et al (2015) Dissecting the heterogeneity of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis. J Rheumatol 42:994\u20131001","journal-title":"J Rheumatol"},{"key":"4393_CR15","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1016\/j.hoc.2015.06.010","volume":"29","author":"A Ravelli","year":"2015","unstructured":"Ravelli A, Davi S, Minoia F, Martini A, Cron RQ (2015) Macrophage activation syndrome. Hematol Oncol Clin N Am 29:927\u2013941","journal-title":"Hematol Oncol Clin N Am"},{"key":"4393_CR16","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1309\/AJCPUK8TLI2MLYOQ","volume":"143","author":"M Machaczka","year":"2015","unstructured":"Machaczka M, Klimkowska M (2015) Bone marrow assessment in the diagnosis of acquired hemophagocytic lymphohistiocytosis in adults. Am J Clin Pathol 143:308\u2013309","journal-title":"Am J Clin Pathol"},{"key":"4393_CR17","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1016\/j.semarthrit.2015.11.002","volume":"45","author":"A Lenert","year":"2016","unstructured":"Lenert A, Yao Q (2016) Macrophage activation syndrome complicating adult onset Still\u2019s disease: a single center case series and comparison with literature. Semin Arthritis Rheum 45:711\u2013716","journal-title":"Semin Arthritis Rheum"},{"key":"4393_CR18","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1093\/rheumatology\/keq218","volume":"50","author":"PM Miettunen","year":"2011","unstructured":"Miettunen PM, Narendran A, Jayanthan A, Behrens EM, Cron RQ (2011) Successful treatment of severe paediatric rheumatic disease-associated macrophage activation syndrome with interleukin-1 inhibition following conventional immunosuppressive therapy: case series with 12 patients. Rheumatology (Oxford) 50:417\u2013419","journal-title":"Rheumatology (Oxford)"},{"key":"4393_CR19","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1097\/RHU.0b013e318205092d","volume":"17","author":"N Bruck","year":"2011","unstructured":"Bruck N, Suttorp M, Kabus M, Heubner G, Gahr M, Pessler F (2011) Rapid and sustained remission of systemic juvenile idiopathic arthritis-associated macrophage activation syndrome through treatment with anakinra and corticosteroids. J Clin Rheumatol 17:23\u201327","journal-title":"J Clin Rheumatol"},{"key":"4393_CR20","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1038\/ncprheum0919","volume":"4","author":"A Kelly","year":"2008","unstructured":"Kelly A, Ramanan AV (2008) A case of macrophage activation syndrome successfully treated with anakinra. Nat Clin Pract Rheumatol 4:615\u2013620","journal-title":"Nat Clin Pract Rheumatol"},{"key":"4393_CR21","first-page":"2068","volume":"31","author":"AV Ramanan","year":"2004","unstructured":"Ramanan AV, Rosenblum ND, Feldman BM, Laxer RM, Schneider R (2004) Favorable outcome in patients with renal involvement complicating macrophage activation syndrome in systemic onset juvenile rheumatoid arthritis. J Rheumatol 31:2068\u20132070","journal-title":"J Rheumatol"},{"key":"4393_CR22","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1016\/S0140-6736(08)60454-7","volume":"371","author":"S Yokota","year":"2008","unstructured":"Yokota S, Imagawa T, Mori M, Miyamae T, Aihara Y, Takei S et al (2008) Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled, withdrawal phase III trial. Lancet 371:998\u20131006","journal-title":"Lancet"},{"key":"4393_CR23","doi-asserted-by":"publisher","first-page":"864","DOI":"10.3899\/jrheum.170955","volume":"45","author":"P Ruscitti","year":"2008","unstructured":"Ruscitti P, Iacono D, Ciccia F, Emmi G, Cipriani P, Grembiale RD et al (2008) Macrophage Activation Syndrome in Patients Affected by Adult-onset Still Disease: analysis of Survival Rates and Predictive Factors in the Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale Cohort. J Rheumatol 45:864\u2013872","journal-title":"J Rheumatol"},{"key":"4393_CR24","first-page":"84","volume":"59","author":"D Gupta","year":"2016","unstructured":"Gupta D, Jagani R, Mendonca S, Rathi KR (2016) Adult-onset Still\u2019s disease with myocarditis and hemophagocytic lymphohistiocytosis: rare manifestation with fatal outcome. Indian J Pathol Microbiol 59:84\u201386","journal-title":"Indian J Pathol Microbiol"},{"key":"4393_CR25","doi-asserted-by":"publisher","first-page":"478","DOI":"10.2177\/jsci.36.478","volume":"36","author":"Y Komiya","year":"2013","unstructured":"Komiya Y, Takenaka K, Nagasaka K (2013) Successful treatment of glucocorticoid and cyclosporine refractory adult-onset Still\u2019s disease complicated with hemophagocytic syndrome with plasma exchange therapy and tocilizumab : a case report. Nihon Rinsho Meneki Gakkai Kaishi 36:478\u2013483","journal-title":"Nihon Rinsho Meneki Gakkai Kaishi"},{"key":"4393_CR26","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1097\/MD.0b013e3181caf100","volume":"89","author":"A Hot","year":"2010","unstructured":"Hot A, Toh ML, Coppere B, Perard L, Madoux MH, Mausservey C et al (2010) Reactive hemophagocytic syndrome in adult-onset Still disease: clinical features and long-term outcome: a case-control study of 8 patients. Medicine (Baltimore) 89:37\u201346","journal-title":"Medicine (Baltimore)"},{"key":"4393_CR27","doi-asserted-by":"publisher","first-page":"1596","DOI":"10.1136\/ard.2005.046904","volume":"65","author":"JB Arlet","year":"2006","unstructured":"Arlet JB, Le TH, Marinho A, Amoura Z, Wechsler B, Papo T et al (2006) Reactive haemophagocytic syndrome in adult-onset Still\u2019s disease: a report of six patients and a review of the literature. Ann Rheum Dis 65:1596\u20131601","journal-title":"Ann Rheum Dis"},{"key":"4393_CR28","doi-asserted-by":"publisher","first-page":"1358","DOI":"10.1111\/imj.12002","volume":"42","author":"NK Loh","year":"2012","unstructured":"Loh NK, Lucas M, Fernandez S, Prentice D (2012) Successful treatment of macrophage activation syndrome complicating adult Still disease with anakinra. Intern Med J 42:1358\u20131362","journal-title":"Intern Med J"},{"key":"4393_CR29","doi-asserted-by":"publisher","first-page":"92","DOI":"10.3109\/s10165-010-0348-9","volume":"21","author":"M Kobayashi","year":"2011","unstructured":"Kobayashi M, Takahashi Y, Yamashita H, Kaneko H, Mimori A (2011) Benefit and a possible risk of tocilizumab therapy for adult-onset Still\u2019s disease accompanied by macrophage-activation syndrome. Mod Rheumatol 21:92\u201396","journal-title":"Mod Rheumatol"},{"key":"4393_CR30","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1007\/s10067-016-3178-0","volume":"35","author":"Y Zhang","year":"2016","unstructured":"Zhang Y, Yang Y, Bai Y, Yang D, Xiong Y, Zeng X (2016) Clinical characteristics and follow-up analysis of adult-onset Still\u2019s disease complicated by hemophagocytic lymphohistiocytosis. Clin Rheumatol 35:1145\u20131151","journal-title":"Clin Rheumatol"},{"key":"4393_CR31","doi-asserted-by":"publisher","first-page":"532","DOI":"10.3109\/s10165-011-0429-4","volume":"21","author":"H Tsuboi","year":"2011","unstructured":"Tsuboi H, Iwata H, Nampei A, Matsushita M, Shi K (2011) Hemophagocytic syndrome in a patient with rheumatoid arthritis. Mod Rheumatol 21:532\u2013535","journal-title":"Mod Rheumatol"},{"key":"4393_CR32","doi-asserted-by":"publisher","first-page":"655","DOI":"10.2169\/internalmedicine.51.5687","volume":"51","author":"Y Oda","year":"2012","unstructured":"Oda Y, Urushidani Y, Ooi S, Endoh A, Nakamura R, Adachi K et al (2012) Hemophagocytic lymphohistiocytosis in a rheumatoid arthritis patient treated with infliximab. Intern Med 51:655\u2013657","journal-title":"Intern Med"},{"key":"4393_CR33","doi-asserted-by":"publisher","first-page":"962","DOI":"10.3109\/14397595.2013.844402","volume":"25","author":"S Kaieda","year":"2015","unstructured":"Kaieda S, Yoshida N, Yamashita F, Okamoto M, Ida H, Hoshino T et al (2015) Successful treatment of macrophage activation syndrome in a patient with dermatomyositis by combination with immunosuppressive therapy and plasmapheresis. Mod Rheumatol 25:962\u2013966","journal-title":"Mod Rheumatol"},{"key":"4393_CR34","unstructured":"Wohlfarth P, Agis H, Gualdoni GA, Weber J, Staudinger T, Schellongowski P, et al (2017) Interleukin 1 Receptor Antagonist Anakinra, Intravenous Immunoglobulin, and Corticosteroids in the Management of Critically Ill Adult Patients With Hemophagocytic Lymphohistiocytosis. J Intensive Care Med 885066617711386"},{"key":"4393_CR35","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1016\/j.amjms.2017.04.016","volume":"354","author":"M Schaffner","year":"2017","unstructured":"Schaffner M, Rosenstein L, Ballas Z, Suneja M (2017) Significance of hyperferritinemia in hospitalized adults. Am J Med Sci 354:152\u2013158","journal-title":"Am J Med Sci"},{"key":"4393_CR36","doi-asserted-by":"publisher","first-page":"1659","DOI":"10.1002\/art.38398","volume":"66","author":"F Ortiz-Sanjuan","year":"2014","unstructured":"Ortiz-Sanjuan F, Blanco R, Calvo-Rio V, Narvaez J, Rubio Romero E, Olive A et al (2014) Efficacy of tocilizumab in conventional treatment-refractory adult-onset Still\u2019s disease: multicenter retrospective open-label study of thirty-four patients. Arthritis Rheumatol 66:1659\u20131665","journal-title":"Arthritis Rheumatol"},{"key":"4393_CR37","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1136\/ard.2008.088179","volume":"68","author":"M De Bandt","year":"2009","unstructured":"De Bandt M, Saint-Marcoux B (2009) Tocilizumab for multirefractory adult-onset Still\u2019s disease. Ann Rheum Dis 68:153\u2013154","journal-title":"Ann Rheum Dis"}],"container-title":["Rheumatology International"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00296-019-04393-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s00296-019-04393-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00296-019-04393-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,29]],"date-time":"2020-07-29T23:28:55Z","timestamp":1596065335000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s00296-019-04393-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,31]]},"references-count":37,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2020,4]]}},"alternative-id":["4393"],"URL":"https:\/\/doi.org\/10.1007\/s00296-019-04393-7","relation":{},"ISSN":["0172-8172","1437-160X"],"issn-type":[{"value":"0172-8172","type":"print"},{"value":"1437-160X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,31]]},"assertion":[{"value":"27 May 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 July 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 July 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"Mayan Gilboa declares she has no conflict of interest. Gil Bornstein declares he has no conflict of interest. Ilan Ben-Zvi declares he has no conflict of interest. Chagai Grossman declares he has no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and\/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}