{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T12:32:21Z","timestamp":1790425941569,"version":"4.1.0"},"reference-count":89,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T00:00:00Z","timestamp":1621209600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T00:00:00Z","timestamp":1621209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100005743","name":"Universit\u00e0 Cattolica del Sacro Cuore","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005743","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Intern Emerg Med"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The innate immunity works as a defence bullwark that safeguards healthy tissues with the power of detecting infectious agents in the human body: errors in the context of innate immunity identify autoinflammatory disorders (AIDs), which arise as bouts of aberrant inflammation with little or no involvement of T and B cells and neither recognized infections, nor associated autoimmune phenomena. Hereditary AIDs tend to have a pediatric-onset heralded by stereotyped inflammatory symptoms and fever, while AIDs without an ascertained cause, such as systemic juvenile idiopathic arthritis, derive from the interaction of genetic factors with environmental noxae and are unevenly defined. A dysregulated inflammasome activation promotes the best-known family of AIDs, as well as several degenerative and metabolic disorders, but also nuclear factor \u03baB- and interferon-mediated conditions have been framed as AIDs: the zenith of inflammatory flares marks different phenotypes, but diagnosis may go unnoticed until adulthood due to downplayed symptoms and complex kaleidoscopic presentations. This review summarizes the main AIDs encountered in childhood with special emphasis on the clinical stigmata that may help establish a correct framework and blueprints to empower young scientists in the recognition of AIDs. The description focuses inflammasomopathies as paradigms of interleukinopathies, nuclear factor-\u03baB -related disorders and interferonopathies. The challenges in the management of AIDs during childhood have been recently boosted by numerous therapeutic options derived from genomically-based approaches, which have led to identify targeted biologic agents as rationalized treatments and achieve more tangible perspectives of disease control.<\/jats:p>","DOI":"10.1007\/s11739-021-02751-7","type":"journal-article","created":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T06:02:45Z","timestamp":1621231365000},"page":"1759-1770","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["The everchanging framework of autoinflammation"],"prefix":"10.1007","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1560-3907","authenticated-orcid":false,"given":"Raffaele","family":"Manna","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7032-7779","authenticated-orcid":false,"given":"Donato","family":"Rigante","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,5,17]]},"reference":[{"key":"2751_CR1","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1111\/j.1365-2249.2011.04535.x","volume":"167","author":"VU Ozkurede","year":"2012","unstructured":"Ozkurede VU, Franchi L (2012) Immunology in clinic review series; focus on autoinflammatory diseases: role of inflammasomes in autoinflammatory syndromes. Clin Exp Immunol 167:382\u2013390","journal-title":"Clin Exp Immunol"},{"key":"2751_CR2","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1111\/jebm.12377","volume":"13","author":"D Rigante","year":"2020","unstructured":"Rigante D (2020) When, how, and why do fevers hold children hostage? J Evid Based Med 13:85\u201388","journal-title":"J Evid Based Med"},{"key":"2751_CR3","doi-asserted-by":"publisher","first-page":"3293145","DOI":"10.1155\/2019\/3293145","volume":"2019","author":"C Gaggiano","year":"2019","unstructured":"Gaggiano C, Rigante D, Vitale A et al (2019) Hints for genetic and clinical differentiation of adult-onset monogenic autoinflammatory diseases. Mediators Inflamm 2019:3293145","journal-title":"Mediators Inflamm"},{"key":"2751_CR4","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1016\/j.cell.2010.01.040","volume":"140","author":"K Schroder","year":"2010","unstructured":"Schroder K, Tschopp J (2010) The inflammasomes. Cell 140:821\u2013832","journal-title":"Cell"},{"key":"2751_CR5","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1111\/jebm.12406","volume":"13","author":"D Rigante","year":"2020","unstructured":"Rigante D (2020) Phenotype variability of autoinflammatory disorders in the pediatric patient: a pictorial overview. J Evid Based Med 13:227\u2013245","journal-title":"J Evid Based Med"},{"key":"2751_CR6","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1177\/039463201102400402","volume":"24","author":"L Cantarini","year":"2011","unstructured":"Cantarini L, Lucherini OM, Frediani B et al (2011) Bridging the gap between the clinician and the patient with cryopyrin-associated periodic syndromes. Int J Immunopathol Pharmacol 24:827\u2013836","journal-title":"Int J Immunopathol Pharmacol"},{"key":"2751_CR7","first-page":"93","volume":"17","author":"L Cantarini","year":"2015","unstructured":"Cantarini L, Lopalco G, Cattalini M et al (2015) Interleukin-1: Ariadne\u2019s thread in autoinflammatory and autoimmune disorders. Isr Med Assoc J 17:93\u201397","journal-title":"Isr Med Assoc J"},{"key":"2751_CR8","doi-asserted-by":"publisher","first-page":"784","DOI":"10.1016\/j.cell.2010.03.002","volume":"140","author":"DL Kastner","year":"2010","unstructured":"Kastner DL, Aksentijevich I, Goldbach-Mansky R (2010) Autoinflammatory disease reloaded: a clinical perspective. Cell 140:784\u2013790","journal-title":"Cell"},{"key":"2751_CR9","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1038\/ncprheum0874","volume":"4","author":"B Neven","year":"2008","unstructured":"Neven B, Prieur AM, Quartier dit Maire P, (2008) Cryopyrinopathies: update on pathogenesis and treatment. Nat Clin Pract Rheumatol 4:481\u2013489","journal-title":"Nat Clin Pract Rheumatol"},{"key":"2751_CR10","doi-asserted-by":"publisher","first-page":"213","DOI":"10.3109\/s10165-009-0271-0","volume":"20","author":"T Kubota","year":"2010","unstructured":"Kubota T, Koike R (2010) Cryopyrin-associated periodic syndromes: background and therapeutics. Mod Rheumatol 20:213\u2013221","journal-title":"Mod Rheumatol"},{"key":"2751_CR11","first-page":"1","volume":"14","author":"D Rigante","year":"2010","unstructured":"Rigante D (2010) The protean visage of systemic autoinflammatory syndromes: a challenge for inter-professional collaboration. Eur Rev Med Pharmacol Sci 14:1\u201318","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"2751_CR12","doi-asserted-by":"publisher","first-page":"1410","DOI":"10.3389\/fimmu.2017.01410","volume":"8","author":"DM Rowczenio","year":"2017","unstructured":"Rowczenio DM, Gomes SM, Ar\u00f3stegui JI et al (2017) Late-onset cryopyrin-associated periodic syndromes caused by somatic NLRP3 mosaicism-UK single center experience. Front Immunol 8:1410","journal-title":"Front Immunol"},{"key":"2751_CR13","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1080\/03009740310003974","volume":"32","author":"G Federico","year":"2003","unstructured":"Federico G, Rigante D, Pugliese AL et al (2003) Etanercept induces improvement of arthropathy in chronic infantile neurological cutaneous articular (CINCA) syndrome. Scand J Rheumatol 32:312\u2013314","journal-title":"Scand J Rheumatol"},{"key":"2751_CR14","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1007\/s00381-006-1280-3","volume":"22","author":"D Rigante","year":"2006","unstructured":"Rigante D, Ansuini V, Caldarelli M et al (2006) Hydrocephalus in CINCA syndrome treated with anakinra. Childs Nerv Syst 22:334\u2013337","journal-title":"Childs Nerv Syst"},{"key":"2751_CR15","doi-asserted-by":"publisher","first-page":"1661","DOI":"10.1007\/s00296-010-1787-5","volume":"31","author":"D Rigante","year":"2011","unstructured":"Rigante D, Leone A, Marrocco R et al (2011) Long-term response after 6-year treatment with anakinra and onset of focal bone erosion in neonatal-onset multisystem inflammatory disease (NOMID\/CINCA). Rheumatol Int 31:1661\u20131664","journal-title":"Rheumatol Int"},{"key":"2751_CR16","doi-asserted-by":"publisher","first-page":"2007","DOI":"10.1007\/s10067-018-4145-8","volume":"37","author":"D Rigante","year":"2018","unstructured":"Rigante D, Manna R, Verrecchia E et al (2018) Resolution of femoral metaphyseal dysplasia in CINCA syndrome after long-term treatment with interleukin-1 blockade. Clin Rheumatol 37:2007\u20132009","journal-title":"Clin Rheumatol"},{"key":"2751_CR17","doi-asserted-by":"publisher","first-page":"380","DOI":"10.3389\/fphar.2016.00380","volume":"7","author":"A Vitale","year":"2016","unstructured":"Vitale A, Insalaco A, Sfriso P et al (2016) A snapshot on the on-label and off-label use of the interleukin-1 inhibitors in Italy among rheumatologists and pediatric rheumatologists: a nationwide multi-center retrospective observational study. Front Pharmacol 7:380","journal-title":"Front Pharmacol"},{"key":"2751_CR18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1017\/S1462399405009749","volume":"7","author":"S Stojanov","year":"2005","unstructured":"Stojanov S, McDermott MF (2005) The tumour necrosis factor receptor-associated periodic syndrome: current concepts. Expert Rev Mol Med 7:1\u201318","journal-title":"Expert Rev Mol Med"},{"key":"2751_CR19","doi-asserted-by":"publisher","first-page":"1197","DOI":"10.1007\/s10067-014-2722-z","volume":"33","author":"D Rigante","year":"2014","unstructured":"Rigante D, Lopalco G, Vitale A et al (2014) Key facts and hot spots on tumor necrosis factor receptor-associated periodic syndrome. Clin Rheumatol 33:1197\u20131207","journal-title":"Clin Rheumatol"},{"key":"2751_CR20","doi-asserted-by":"publisher","first-page":"485103","DOI":"10.1155\/2013\/485103","volume":"2013","author":"D Rigante","year":"2013","unstructured":"Rigante D, Frediani B, Galeazzi M et al (2013) From the Mediterranean to the sea of Japan: the transcontinental odyssey of autoinflammatory diseases. Biomed Res Int 2013:485103","journal-title":"Biomed Res Int"},{"key":"2751_CR21","doi-asserted-by":"publisher","first-page":"341","DOI":"10.3109\/07853890.2010.547212","volume":"43","author":"D Rigante","year":"2011","unstructured":"Rigante D, Cantarini L, Imazio M et al (2011) Autoinflammatory diseases and cardiovascular manifestations. Ann Med 43:341\u2013346","journal-title":"Ann Med"},{"key":"2751_CR22","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1086\/321976","volume":"69","author":"I Aksentijevich","year":"2001","unstructured":"Aksentijevich I, Galon J, Soares M et al (2001) The tumor-necrosis-factor receptor-associated periodic syndrome: new mutations in TNFRSF1A, ancestral origins, genotype-phenotype studies and evidence for further genetic heterogeneity of periodic fevers. Am J Hum Genet 69:301\u2013314","journal-title":"Am J Hum Genet"},{"key":"2751_CR23","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1007\/s11739-016-1570-z","volume":"12","author":"D Rigante","year":"2017","unstructured":"Rigante D (2017) Tumor necrosis factor inhibitors in tumor necrosis factor receptor-associated periodic syndrome: still a chance to work? Intern Emerg Med 12:269\u2013270","journal-title":"Intern Emerg Med"},{"key":"2751_CR24","doi-asserted-by":"publisher","first-page":"2233","DOI":"10.1007\/s10067-018-4119-x","volume":"37","author":"J Sota","year":"2018","unstructured":"Sota J, Vitale A, Insalaco A et al (2018) Safety profile of the interleukin-1 inhibitors anakinra and canakinumab in real-life clinical practice: a nationwide multicenter retrospective observational study. Clin Rheumatol 37:2233\u20132240","journal-title":"Clin Rheumatol"},{"key":"2751_CR25","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1080\/1744666X.2017.1280396","volume":"13","author":"D Rigante","year":"2017","unstructured":"Rigante D (2017) A systematic approach to autoinflammatory syndromes: a spelling booklet for the beginner. Expert Rev Clin Immunol 13:571\u2013597","journal-title":"Expert Rev Clin Immunol"},{"key":"2751_CR26","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1177\/039463201402700404","volume":"27","author":"S Esposito","year":"2014","unstructured":"Esposito S, Ascolese B, Senatore L et al (2014) Current advances in the understanding and treatment of mevalonate kinase deficiency. Int J Immunopathol Pharmacol 27:491\u2013498","journal-title":"Int J Immunopathol Pharmacol"},{"key":"2751_CR27","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1002\/art.22409","volume":"56","author":"D Rigante","year":"2007","unstructured":"Rigante D, Capoluongo E, Bertoni B et al (2007) First report of macrophage activation syndrome in hyperimmunoglobulinemia D with periodic fever syndrome. Arthritis Rheum 56:658\u2013661","journal-title":"Arthritis Rheum"},{"key":"2751_CR28","doi-asserted-by":"publisher","first-page":"664","DOI":"10.3109\/07853890.2011.598546","volume":"44","author":"L Cantarini","year":"2012","unstructured":"Cantarini L, Rigante D, Brizi MG et al (2012) Clinical and biochemical landmarks in systemic autoinflammatory diseases. Ann Med 44:664\u2013673","journal-title":"Ann Med"},{"key":"2751_CR29","doi-asserted-by":"publisher","first-page":"994","DOI":"10.1212\/01.WNL.0000115390.33405.F7","volume":"62","author":"A Simon","year":"2004","unstructured":"Simon A, Kremer HP, Wevers RA et al (2004) Mevalonate kinase deficiency: evidence for a phenotypic continuum. Neurology 62:994\u2013997","journal-title":"Neurology"},{"key":"2751_CR30","doi-asserted-by":"publisher","first-page":"1150","DOI":"10.3389\/fimmu.2020.01150","volume":"11","author":"J Jeyaratnam","year":"2020","unstructured":"Jeyaratnam J, Frenkel J (2020) Management of mevalonate kinase deficiency: a pediatric perspective. Front Immunol 11:1150","journal-title":"Front Immunol"},{"key":"2751_CR31","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1038\/ni.3457","volume":"17","author":"YH Park","year":"2016","unstructured":"Park YH, Wood G, Kastner DL et al (2016) Pyrin inflammasome activation and RhoA signaling in the autoinflammatory diseases FMF and HIDS. Nat Immunol 17:914\u2013921","journal-title":"Nat Immunol"},{"key":"2751_CR32","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1016\/j.jbspin.2008.08.004","volume":"76","author":"C Fonnesu","year":"2009","unstructured":"Fonnesu C, Cerquaglia C, Giovinale M et al (2009) Familial Mediterranean fever: a review for clinical management. Joint Bone Spine 76:227\u2013233","journal-title":"Joint Bone Spine"},{"key":"2751_CR33","doi-asserted-by":"publisher","first-page":"e2019027","DOI":"10.4084\/mjhid.2019.027","volume":"11","author":"R Manna","year":"2019","unstructured":"Manna R, Rigante D (2019) Familial Mediterranean fever: assessing the overall clinical impact and formulating treatment plans. Mediterr J Hematol Infect Dis 11:e2019027","journal-title":"Mediterr J Hematol Infect Dis"},{"key":"2751_CR34","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.autrev.2014.10.005","volume":"14","author":"L Cantarini","year":"2015","unstructured":"Cantarini L, Lopalco G, Selmi C et al (2015) Autoimmunity and autoinflammation as the yin and yang of idiopathic recurrent acute pericarditis. Autoimmun Rev 14:90\u201397","journal-title":"Autoimmun Rev"},{"key":"2751_CR35","doi-asserted-by":"publisher","first-page":"1447","DOI":"10.1002\/art.24458","volume":"61","author":"E Ben-Chetrit","year":"2009","unstructured":"Ben-Chetrit E, Touitou I (2009) Familial Mediterranean fever in the world. Arthritis Rheum 61:1447\u20131453","journal-title":"Arthritis Rheum"},{"key":"2751_CR36","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1016\/0002-9343(67)90167-2","volume":"43","author":"E Sohar","year":"1967","unstructured":"Sohar E, Gafni J, Pras M et al (1967) Familial Mediterranean fever. A survey of 470 cases and review of the literature. Am J Med 43:227\u2013253","journal-title":"Am J Med"},{"key":"2751_CR37","doi-asserted-by":"publisher","first-page":"1879","DOI":"10.1002\/art.1780401023","volume":"40","author":"A Livneh","year":"1997","unstructured":"Livneh A, Langevitz P, Zemer D et al (1997) Criteria for the diagnosis of familial Mediterranean fever. Arthritis Rheum 40:1879\u20131885","journal-title":"Arthritis Rheum"},{"key":"2751_CR38","first-page":"173","volume":"10","author":"D Rigante","year":"2006","unstructured":"Rigante D, La Torraca I, Avallone L et al (2006) The pharmacological basis of treatment with colchicine in children with familial Mediterranean fever. Eur Rev Med Pharmacol Sci 10:173\u2013178","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"2751_CR39","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.imlet.2016.10.007","volume":"180","author":"D Rigante","year":"2016","unstructured":"Rigante D, Manna R (2016) A position for tumor necrosis factor inhibitors in the management of colchicine-resistant familial Mediterranean fever? Immunol Lett 180:77\u201378","journal-title":"Immunol Lett"},{"key":"2751_CR40","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1097\/QCO.0b013e328329d15e","volume":"22","author":"G Guz","year":"2009","unstructured":"Guz G, Kanbay M, Ozturk MA (2009) Current perspectives on familial Mediterranean fever. Curr Opin Infect Dis 22:309\u2013315","journal-title":"Curr Opin Infect Dis"},{"key":"2751_CR41","doi-asserted-by":"publisher","first-page":"e2020059","DOI":"10.4084\/mjhid.2020.059","volume":"12","author":"MG Massaro","year":"2020","unstructured":"Massaro MG, Pompili M, Sicignano LL et al (2020) Improvement of liver involvement in familial Mediterranean fever after the introduction of canakinumab: a case report. Mediterr J Hematol Infect Dis 12:e2020059","journal-title":"Mediterr J Hematol Infect Dis"},{"key":"2751_CR42","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.jpeds.2019.02.039","volume":"209","author":"G Boursier","year":"2019","unstructured":"Boursier G, Hentgen V, Sarrabay G et al (2019) The changing concepts regarding the mediterranean fever gene: toward a spectrum of pyrin-associated autoinflammatory diseases with variable heredity. J Pediatr 209:12-16.e1","journal-title":"J Pediatr"},{"key":"2751_CR43","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1136\/annrheumdis-2019-215048","volume":"78","author":"M Gattorno","year":"2019","unstructured":"Gattorno M, Hofer M, Federici S et al (2019) Classification criteria for autoinflammatory recurrent fevers. Ann Rheum Dis 78:1025\u20131032","journal-title":"Ann Rheum Dis"},{"key":"2751_CR44","doi-asserted-by":"publisher","first-page":"1140","DOI":"10.1093\/rheumatology\/kei178","volume":"45","author":"B Tallon","year":"2006","unstructured":"Tallon B, Corkill M (2006) Peculiarities of PAPA syndrome. Rheumatology 45:1140\u20131143","journal-title":"Rheumatology"},{"key":"2751_CR45","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.imlet.2017.11.013","volume":"193","author":"D Rigante","year":"2018","unstructured":"Rigante D (2018) New mosaic tiles in childhood hereditary autoinflammatory disorders. Immunol Lett 193:67\u201376","journal-title":"Immunol Lett"},{"key":"2751_CR46","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1093\/rheumatology\/keh479","volume":"44","author":"MP Dierselhuis","year":"2005","unstructured":"Dierselhuis MP, Frenkel J, Wulffraat NM et al (2005) Anakinra for flares of pyogenic arthritis in PAPA syndrome. Rheumatology (Oxford) 44:406\u2013408","journal-title":"Rheumatology (Oxford)"},{"key":"2751_CR47","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1136\/jmg.2005.030759","volume":"42","author":"PJ Ferguson","year":"2005","unstructured":"Ferguson PJ, Chen S, Tayeh MK et al (2005) Homozygous mutations in LPIN2 are responsible for the syndrome of chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia (Majeed syndrome). J Med Genet 42:551\u2013557","journal-title":"J Med Genet"},{"key":"2751_CR48","doi-asserted-by":"publisher","first-page":"10894","DOI":"10.1074\/jbc.M112.342915","volume":"287","author":"M Valdearcos","year":"2012","unstructured":"Valdearcos M, Esquinas E, Meana C et al (2012) Lipin-2 reduces proinflammatory signaling induced by saturated fatty acids in macrophages. J Biol Chem 287:10894\u201310904","journal-title":"J Biol Chem"},{"key":"2751_CR49","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1038\/s41372-020-0744-8","volume":"41","author":"DU De Rose","year":"2021","unstructured":"De Rose DU, Coppola M, Gallini F et al (2021) Overview of the rarest causes of fever in newborns: handy hints for the neonatologist. J Perinatol 41:372\u2013382","journal-title":"J Perinatol"},{"key":"2751_CR50","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1007\/s11926-018-0749-x","volume":"20","author":"A Steiner","year":"2018","unstructured":"Steiner A, Harapas CR, Masters SL et al (2018) An update on autoinflammatory diseases: relopathies. Curr Rheumatol Rep 20:39","journal-title":"Curr Rheumatol Rep"},{"key":"2751_CR51","doi-asserted-by":"publisher","first-page":"1008","DOI":"10.1093\/rheumatology\/keu437","volume":"54","author":"CD Ros\u00e9","year":"2015","unstructured":"Ros\u00e9 CD, Pans S, Casteels I et al (2015) Blau syndrome: cross-sectional data from a multicentre study of clinical, radiological and functional outcomes. Rheumatology (Oxford) 54:1008\u20131016","journal-title":"Rheumatology (Oxford)"},{"key":"2751_CR52","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1080\/21678707.2018.1406797","volume":"6","author":"D Rigante","year":"2018","unstructured":"Rigante D (2018) A developing portrait of hereditary periodic fevers in childhood. Expert Opin Orphan Drugs 6:47\u201355","journal-title":"Expert Opin Orphan Drugs"},{"key":"2751_CR53","doi-asserted-by":"publisher","first-page":"117","DOI":"10.5606\/ArchRheumatol.2020.7060","volume":"35","author":"A Pa\u00e7 K\u0131saarslan","year":"2020","unstructured":"Pa\u00e7 K\u0131saarslan A, S\u00f6zeri B, \u015eahin N et al (2020) Blau syndrome and early-onset sarcoidosis: a six case series and review of the literature. Arch Rheumatol 35:117\u2013127","journal-title":"Arch Rheumatol"},{"key":"2751_CR54","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1016\/j.ajhg.2012.03.013","volume":"90","author":"CT Jordan","year":"2012","unstructured":"Jordan CT, Cao L, Roberson ED et al (2012) Rare and common variants in CARD14, encoding an epidermal regulator of NF-\u03baB, in psoriasis. Am J Hum Genet 90:796\u2013808","journal-title":"Am J Hum Genet"},{"key":"2751_CR55","doi-asserted-by":"publisher","first-page":"620","DOI":"10.1056\/NEJMoa1013068","volume":"365","author":"S Marrakchi","year":"2011","unstructured":"Marrakchi S, Guigue P, Renshaw BR et al (2011) Interleukin-36-receptor antagonist deficiency and generalized pustular psoriasis. N Engl J Med 365:620\u2013628","journal-title":"N Engl J Med"},{"key":"2751_CR56","doi-asserted-by":"publisher","first-page":"399","DOI":"10.3389\/fimmu.2017.00399","volume":"8","author":"I Aksentijevich","year":"2017","unstructured":"Aksentijevich I, Zhou Q (2017) NF-\u03baB pathway in autoinflammatory diseases: dysregulation of protein modifications by ubiquitin defines a new category of autoinflammatory diseases. Front Immunol 8:399","journal-title":"Front Immunol"},{"key":"2751_CR57","doi-asserted-by":"publisher","first-page":"10127","DOI":"10.1073\/pnas.1612594113","volume":"113","author":"Q Zhou","year":"2016","unstructured":"Zhou Q, Yu X, Demirkaya E et al (2016) Biallelic hypomorphic mutations in a linear deubiquitinase define otulipenia, an early-onset autoinflammatory disease. Proc Natl Acad Sci USA 113:10127\u201310132","journal-title":"Proc Natl Acad Sci USA"},{"key":"2751_CR58","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1080\/14397595.2020.1719595","volume":"31","author":"M Shimizu","year":"2021","unstructured":"Shimizu M, Matsubayashi T, Ohnishi H et al (2021) Haploinsufficiency of A20 with a novel mutation of deletion of exons 2\u20133 of TNFAIP3. Mod Rheumatol 31:493\u2013497","journal-title":"Mod Rheumatol"},{"key":"2751_CR59","doi-asserted-by":"publisher","first-page":"2628","DOI":"10.1056\/NEJMoa2026834","volume":"383","author":"DB Beck","year":"2020","unstructured":"Beck DB, Ferrada MA, Sikora KA et al (2020) Somatic mutations in UBA1 and severe adult-onset autoinflammatory disease. N Engl J Med 383:2628\u20132638","journal-title":"N Engl J Med"},{"key":"2751_CR60","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1186\/s13075-020-02160-9","volume":"22","author":"H Kim","year":"2020","unstructured":"Kim H, Gunter-Rahman F, McGrath JA et al (2020) Expression of interferon-regulated genes in juvenile dermatomyositis versus Mendelian autoinflammatory interferonopathies. Arthritis Res Ther 22:69","journal-title":"Arthritis Res Ther"},{"key":"2751_CR61","doi-asserted-by":"publisher","first-page":"102390","DOI":"10.1016\/j.autrev.2019.102390","volume":"18","author":"Y Jamilloux","year":"2029","unstructured":"Jamilloux Y, El Jammal T, Vuitton L et al (2029) JAK inhibitors for the treatment of autoimmune and inflammatory diseases. Autoimmun Rev 18:102390","journal-title":"Autoimmun Rev"},{"key":"2751_CR62","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1111\/ijd.12695","volume":"54","author":"A McDermott","year":"2015","unstructured":"McDermott A, Jacks J, Kessler M et al (2015) Proteasome-associated autoinflammatory syndromes: advances in pathogeneses, clinical presentations, diagnosis, and management. Int J Dermatol 54:121\u2013129","journal-title":"Int J Dermatol"},{"key":"2751_CR63","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1056\/NEJMoa1312625","volume":"371","author":"Y Liu","year":"2014","unstructured":"Liu Y, Jesus AA, Marrero B et al (2014) Activated STING in a vascular and pulmonary syndrome. N Engl J Med 371:507\u2013518","journal-title":"N Engl J Med"},{"key":"2751_CR64","doi-asserted-by":"publisher","first-page":"2111","DOI":"10.3390\/ijms17122111","volume":"17","author":"G Tarantino","year":"2016","unstructured":"Tarantino G, Esposito S, Andreozzi L et al (2016) Lung involvement in children with hereditary autoinflammatory disorders. Int J Mol Sci 17:2111","journal-title":"Int J Mol Sci"},{"key":"2751_CR65","first-page":"480373","volume":"2012","author":"L Rossi-Semerano","year":"2012","unstructured":"Rossi-Semerano L, Kon\u00e9-Paut I (2012) Is Still\u2019s disease an autoinflammatory syndrome? Int J Inflam 2012:480373","journal-title":"Int J Inflam"},{"key":"2751_CR66","doi-asserted-by":"publisher","first-page":"190","DOI":"10.3899\/jrheum.180168","volume":"46","author":"A Martini","year":"2019","unstructured":"Martini A, Ravelli A, Avcin T et al (2019) Toward new classification criteria for juvenile idiopathic arthritis: first steps, Pediatric Rheumatology International Trials Organization International consensus. J Rheumatol 46:190\u2013197","journal-title":"J Rheumatol"},{"key":"2751_CR67","first-page":"53","volume":"10","author":"A Stabile","year":"2006","unstructured":"Stabile A, Bertoni B, Ansuini V et al (2006) The clinical spectrum and treatment options of macrophage activation syndrome in the pediatric age. Eur Rev Med Pharmacol Sci 10:53\u201359","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"2751_CR68","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1016\/j.jbspin.2010.09.002","volume":"77","author":"P Quartier","year":"2010","unstructured":"Quartier P (2010) Current treatments for juvenile idiopathic arthritis. Joint Bone Spine 77:511\u2013516","journal-title":"Joint Bone Spine"},{"key":"2751_CR69","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1097\/INF.0000000000000346","volume":"33","author":"S Esposito","year":"2014","unstructured":"Esposito S, Bianchini S, Fattizzo M et al (2014) The enigma of periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome. Pediatr Infect Dis J 33:650\u2013652","journal-title":"Pediatr Infect Dis J"},{"key":"2751_CR70","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1080\/21678707.2017.1279049","volume":"5","author":"S Gentileschi","year":"2017","unstructured":"Gentileschi S, Vitale A, Frediani B et al (2017) Challenges and new horizons in the periodic fever, aphthous stomatitis, pharingitis and adenitis (PFAPA) syndrome. Expert Opin Orphan Drugs 5:165\u2013171","journal-title":"Expert Opin Orphan Drugs"},{"key":"2751_CR71","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1038\/s41577-018-0008-4","volume":"18","author":"C Scheiermann","year":"2018","unstructured":"Scheiermann C, Gibbs J, Ince L et al (2018) Clocking in to immunity. Nat Rev Immunol 18:423\u2013437","journal-title":"Nat Rev Immunol"},{"key":"2751_CR72","first-page":"444","volume":"19","author":"D Rigante","year":"2017","unstructured":"Rigante D, Gentileschi S, Vitale A et al (2017) Evolving frontiers in the treatment of periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis (PFAPA) syndrome. Isr Med Ass J 19:444\u2013447","journal-title":"Isr Med Ass J"},{"key":"2751_CR73","doi-asserted-by":"publisher","first-page":"109830","DOI":"10.1016\/j.ijporl.2019.109830","volume":"130","author":"D Rigante","year":"2020","unstructured":"Rigante D, Corina L (2020) Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome: a debate about diagnosis and treatment in children continues. Int J Pediatr Otorhinolaryngol 130:109830","journal-title":"Int J Pediatr Otorhinolaryngol"},{"key":"2751_CR74","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1007\/s10067-016-3317-7","volume":"36","author":"D Rigante","year":"2017","unstructured":"Rigante D, Vitale A, Natale MF et al (2017) A comprehensive comparison between pediatric and adult patients with periodic fever, aphthous stomatitis, pharyngitis, and cervical adenopathy (PFAPA) syndrome. Clin Rheumatol 36:463\u2013468","journal-title":"Clin Rheumatol"},{"key":"2751_CR75","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1007\/s12325-020-01576-8","volume":"38","author":"LL Sicignano","year":"2021","unstructured":"Sicignano LL, Rigante D, Moccaldi B et al (2021) Children and adults with PFAPA syndrome: similarities and divergences in a real-life clinical setting. Adv Ther 38:1078\u20131093","journal-title":"Adv Ther"},{"key":"2751_CR76","doi-asserted-by":"publisher","first-page":"S78","DOI":"10.1016\/j.injr.2015.07.010","volume":"10","author":"D Sharma","year":"2015","unstructured":"Sharma D, Singh S (2015) Kawasaki disease - A common childhood vasculitis. Indian J Rheumatol 10:S78\u2013S83","journal-title":"Indian J Rheumatol"},{"key":"2751_CR77","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/s13052-021-00962-4","volume":"47","author":"A Marchesi","year":"2021","unstructured":"Marchesi A, Rigante D, Cimaz R et al (2021) Revised recommendations of the Italian Society of Pediatrics about the general management of Kawasaki disease. Ital J Pediatr 47:16","journal-title":"Ital J Pediatr"},{"key":"2751_CR78","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1007\/s00296-009-1337-1","volume":"30","author":"D Rigante","year":"2010","unstructured":"Rigante D, Valentini P, Rizzo D et al (2010) Responsiveness to intravenous immunoglobulins and occurrence of coronary artery abnormalities in a single-center cohort of Italian patients with Kawasaki syndrome. Rheumatol Int 30:841\u2013846","journal-title":"Rheumatol Int"},{"key":"2751_CR79","doi-asserted-by":"publisher","first-page":"278","DOI":"10.3390\/ijms17030278","volume":"17","author":"D Rigante","year":"2016","unstructured":"Rigante D, Andreozzi L, Fastiggi M et al (2016) Critical overview of the risk scoring systems to predict non-responsiveness to intravenous immunoglobulin in Kawasaki syndrome. Int J Mol Sci 17:278","journal-title":"Int J Mol Sci"},{"key":"2751_CR80","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1111\/1756-185X.13218","volume":"21","author":"Y Onouchi","year":"2018","unstructured":"Onouchi Y (2018) The genetics of Kawasaki disease. Int J Rheum Dis 21:26\u201330","journal-title":"Int J Rheum Dis"},{"key":"2751_CR81","doi-asserted-by":"publisher","first-page":"e2020039","DOI":"10.4084\/mjhid.2020.039","volume":"12","author":"D Rigante","year":"2020","unstructured":"Rigante D (2020) Kawasaki disease as the immune-mediated echo of a viral infection. Mediterr J Hematol Infect Dis 12:e2020039","journal-title":"Mediterr J Hematol Infect Dis"},{"key":"2751_CR82","doi-asserted-by":"publisher","first-page":"R261","DOI":"10.1186\/gb-2007-8-12-r261","volume":"8","author":"S Popper","year":"2007","unstructured":"Popper S, Shimizu C, Shike H et al (2007) Gene-expression patterns reveal underlying biological processes in Kawasaki disease. Genome Biol 8:R261","journal-title":"Genome Biol"},{"key":"2751_CR83","doi-asserted-by":"publisher","first-page":"2605","DOI":"10.1161\/ATVBAHA.115.306475","volume":"35","author":"Y Lee","year":"2015","unstructured":"Lee Y, Wakita D, Dagvadorj J et al (2015) IL-1 signaling is critically required in stromal cells in Kawasaki disease vasculitis mouse model: role of both IL-1 alpha and IL-1 beta. Arterioscler Thromb Vasc Biol 35:2605\u20132616","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2751_CR84","doi-asserted-by":"publisher","first-page":"1542","DOI":"10.1161\/CIRCULATIONAHA.111.072769","volume":"125","author":"Y Lee","year":"2012","unstructured":"Lee Y, Schulte DJ, Shimada K et al (2012) IL-1\u03b2 is crucial for induction of coronary artery inflammation in a mouse model of Kawasaki disease. Circulation 125:1542\u20131550","journal-title":"Circulation"},{"key":"2751_CR85","doi-asserted-by":"publisher","first-page":"1898","DOI":"10.3390\/ijms20081898","volume":"20","author":"A Bettiol","year":"2019","unstructured":"Bettiol A, Lopalco G, Emmi G et al (2019) Unveiling the efficacy, safety, and tolerability of anti-interleukin-1 treatment in monogenic and multifactorial autoinflammatory diseases. Int J Mol Sci 20:1898","journal-title":"Int J Mol Sci"},{"key":"2751_CR86","doi-asserted-by":"publisher","first-page":"1333","DOI":"10.1007\/s10067-015-2923-0","volume":"34","author":"D Rigante","year":"2015","unstructured":"Rigante D, Emmi G, Fastiggi M et al (2015) Macrophage activation syndrome in the course of monogenic autoinflammatory disorders. Clin Rheumatol 34:1333\u20131339","journal-title":"Clin Rheumatol"},{"key":"2751_CR87","doi-asserted-by":"publisher","first-page":"e2018067","DOI":"10.4084\/mjhid.2018.067","volume":"10","author":"D Rigante","year":"2018","unstructured":"Rigante D (2018) The broad-ranging panorama of systemic autoinflammatory disorders with specific focus on acute painful symptoms and hematologic manifestations in children. Mediterr J Hematol Infect Dis 10:e2018067","journal-title":"Mediterr J Hematol Infect Dis"},{"key":"2751_CR88","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1136\/annrheumdis-2016-210092","volume":"76","author":"NM ter Haar","year":"2017","unstructured":"ter Haar NM, Annink KV, Al-Mayouf SM et al (2017) Development of the autoinflammatory disease damage index (ADDI). Ann Rheum Dis 76:821\u2013830","journal-title":"Ann Rheum Dis"},{"key":"2751_CR89","doi-asserted-by":"publisher","first-page":"948154","DOI":"10.1155\/2014\/948154","volume":"2014","author":"D Rigante","year":"2014","unstructured":"Rigante D, Lopalco G, Vitale A et al (2014) Untangling the web of systemic autoinflammatory diseases. Mediators Inflamm 2014:948154","journal-title":"Mediators Inflamm"}],"container-title":["Internal and Emergency Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11739-021-02751-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11739-021-02751-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11739-021-02751-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,10]],"date-time":"2021-10-10T16:53:55Z","timestamp":1633884835000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11739-021-02751-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,17]]},"references-count":89,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2021,10]]}},"alternative-id":["2751"],"URL":"https:\/\/doi.org\/10.1007\/s11739-021-02751-7","relation":{},"ISSN":["1828-0447","1970-9366"],"issn-type":[{"value":"1828-0447","type":"print"},{"value":"1970-9366","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,17]]},"assertion":[{"value":"10 March 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 April 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 May 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"There are no conflicts of interest to disclose.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interests"}},{"value":"This\u00a0review was conducted following the principles of ethical and professional conduct: the research did not involve human participants or animals.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Statement of human and animal rights"}},{"value":"Patient\u2019s parents gave their formal informed consent to publish their son\u2019s picture, corresponding to Fig.\u00a0.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}