{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T02:03:28Z","timestamp":1793930608697,"version":"4.8.0"},"reference-count":60,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,5,10]],"date-time":"2021-05-10T00:00:00Z","timestamp":1620604800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,5,10]],"date-time":"2021-05-10T00:00:00Z","timestamp":1620604800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Institute for Maternal and Child Health IRCCS Burlo Garofolo","award":["24\/2017"],"award-info":[{"award-number":["24\/2017"]}]},{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"crossref","award":["RF-2016-02362384"],"award-info":[{"award-number":["RF-2016-02362384"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pediatr Rheumatol"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Recurrent aphthous stomatitis with systemic signs of inflammation can be encountered in inflammatory bowel disease, Beh\u00e7et\u2019s disease (BD), Systemic Lupus Erythematosus (SLE). In addition, it has been proposed that cases with very early onset in childhood can be underpinned by rare monogenic defects of immunity, which may require targeted treatments. Thus, subjects with early onset recurrent aphthous stomatitis receiving a clinical diagnosis of BD-like or SLE-like disease may deserve a further diagnostic workout, including immunologic and genetic investigations.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Objective<\/jats:title>\n                <jats:p>To investigate how an immunologic, genetic and transcriptomics assessment of interferon inflammation may improve diagnosis and care in children with recurrent aphthous stomatitis with systemic inflammation.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Subjects referred to the pediatric rheumatologist for recurrent aphthous stomatitis associated with signs of systemic inflammation from January 2015 to January 2020 were enrolled in the study and underwent analysis of peripheral lymphocyte subsets, sequencing of a 17-genes panel and measure of interferon score.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We enrolled 15 subjects (12 females, median age at disease onset 4\u2009years). The clinical diagnosis was BD in 8, incomplete BD in 5, BD\/SLE overlap in 1, SLE in 1. Pathogenic genetic variants were detected in 3 patients, respectively 2 <jats:italic>STAT1<\/jats:italic> gain of function variants in two patients classified as BD\/SLE overlap and SLE, and 1 <jats:italic>TNFAIP3<\/jats:italic> mutation (A20 haploinsufficiency) in patients with BD. Moreover 2 likely pathogenic variants were identified in <jats:italic>DNASE1L3<\/jats:italic> and <jats:italic>PTPN22,<\/jats:italic> both in patients with incomplete BD. Interferon score was high in the two patients with <jats:italic>STAT1<\/jats:italic> GOF mutations, in the patient with <jats:italic>TNFAIP3<\/jats:italic> mutation, and in 3 genetic-negative subjects. In two patients, the treatment was modified based on genetic results.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Although recurrent aphthous stomatitis associated with systemic inflammation may lead to a clinical diagnosis of BD or SLE, subjects with early disease onset in childhood deserve genetic investigation for rare monogenic disorders. A wider genetic panel may help disclosing the genetic background in the subset of children with increased interferon score, who tested negative in this study.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12969-021-00552-y","type":"journal-article","created":{"date-parts":[[2021,5,10]],"date-time":"2021-05-10T12:03:21Z","timestamp":1620648201000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Genetic and immunologic findings in children with recurrent aphthous stomatitis with systemic inflammation"],"prefix":"10.1186","volume":"19","author":[{"given":"Martina","family":"Girardelli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Valencic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Moressa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Margagliotta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6267-3794","authenticated-orcid":false,"given":"Alessandra","family":"Tesser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Pastore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ottavia","family":"Spadola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanouil","family":"Athanasakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni Maria","family":"Severini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Taddio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Tommasini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,5,10]]},"reference":[{"key":"552_CR1","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/S0022-3476(99)70321-5","volume":"135","author":"KT Thomas","year":"1999","unstructured":"Thomas KT, Feder HM Jr, Lawton AR, Edwards KM. Periodic fever syndrome in children. J Pediatr. 1999;135:15\u201321.","journal-title":"J Pediatr"},{"key":"552_CR2","doi-asserted-by":"publisher","first-page":"e721","DOI":"10.1542\/peds.2009-0088","volume":"124","author":"M Gattorno","year":"2009","unstructured":"Gattorno M, Caorsi R, Meini A, Cattalini M, Federici S, Zulian F, et al. Differentiating pfapa syndrome from monogenic periodic fevers. Pediatrics. 2009;124:e721\u20138.","journal-title":"Pediatrics."},{"key":"552_CR3","doi-asserted-by":"publisher","first-page":"2795","DOI":"10.1002\/art.39763","volume":"68","author":"NM Ter Haar","year":"2016","unstructured":"Ter Haar NM, Jeyaratnam J, Lachmann HJ, Simon A, Brogan PA, Doglio M, et al. The phenotype and genotype of mevalonate kinase deficiency: a series of 114 cases from the eurofever registry. Arthritis Rheumatol. 2016;68:2795\u2013805.","journal-title":"Arthritis Rheumatol"},{"key":"552_CR4","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/s12969-016-0070-z","volume":"14","author":"I Kone-Paut","year":"2016","unstructured":"Kone-Paut I. Behcet's disease in children, an overview. Pediatr Rheumatol Online J. 2016;14:10.","journal-title":"Pediatr Rheumatol Online J."},{"key":"552_CR5","doi-asserted-by":"publisher","first-page":"8571","DOI":"10.3748\/wjg.v19.i46.8571","volume":"19","author":"KB Lankarani","year":"2013","unstructured":"Lankarani KB, Sivandzadeh GR, Hassanpour S. Oral manifestation in inflammatory bowel disease: a review. World J Gastroenterol. 2013;19:8571\u20139.","journal-title":"World J Gastroenterol"},{"key":"552_CR6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1546-0096-13-1","volume":"13","author":"D Chiewchengchol","year":"2015","unstructured":"Chiewchengchol D, Murphy R, Edwards SW, Beresford MW. Mucocutaneous manifestations in juvenile-onset systemic lupus erythematosus: a review of literature. Pediatr Rheumatol Online J. 2015;13:1.","journal-title":"Pediatr Rheumatol Online J"},{"key":"552_CR7","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1182\/blood-2004-02-0675","volume":"105","author":"B Wolach","year":"2005","unstructured":"Wolach B, Scharf Y, Gavrieli R, de Boer M, Roos D. Unusual late presentation of x-linked chronic granulomatous disease in an adult female with a somatic mosaic for a novel mutation in cybb. Blood. 2005;105:61\u20136.","journal-title":"Blood."},{"key":"552_CR8","doi-asserted-by":"publisher","first-page":"967","DOI":"10.3389\/fimmu.2020.00967","volume":"11","author":"M Erdos","year":"2020","unstructured":"Erdos M, Jakobicz E, Soltesz B, Toth B, Bata-Csorgo Z, Marodi L. Recurrent, severe aphthous stomatitis and mucosal ulcers as primary manifestations of a novel stat1 gain-of-function mutation. Front Immunol. 2020;11:967.","journal-title":"Front Immunol"},{"key":"552_CR9","doi-asserted-by":"publisher","first-page":"1589","DOI":"10.1016\/j.jaci.2018.04.023","volume":"142","author":"L Pfajfer","year":"2018","unstructured":"Pfajfer L, Mair NK, Jimenez-Heredia R, Genel F, Gulez N, Ardeniz O, et al. Mutations affecting the actin regulator wd repeat-containing protein 1 lead to aberrant lymphoid immunity. J Allergy Clin Immunol. 2018;142:1589\u2013604 e11.","journal-title":"J Allergy Clin Immunol"},{"key":"552_CR10","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1038\/nature04702","volume":"441","author":"S Feske","year":"2006","unstructured":"Feske S, Gwack Y, Prakriya M, Srikanth S, Puppel SH, Tanasa B, et al. A mutation in orai1 causes immune deficiency by abrogating crac channel function. Nature. 2006;441:179\u201385.","journal-title":"Nature."},{"key":"552_CR11","doi-asserted-by":"publisher","first-page":"1350","DOI":"10.1172\/JCI37901","volume":"119","author":"K Huck","year":"2009","unstructured":"Huck K, Feyen O, Niehues T, Ruschendorf F, Hubner N, Laws HJ, et al. Girls homozygous for an il-2-inducible t cell kinase mutation that leads to protein deficiency develop fatal ebv-associated lymphoproliferation. J Clin Invest. 2009;119:1350\u20138.","journal-title":"J Clin Invest"},{"key":"552_CR12","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1002\/mgg3.237","volume":"4","author":"HS Sorte","year":"2016","unstructured":"Sorte HS, Osnes LT, Fevang B, Aukrust P, Erichsen HC, Backe PH, et al. A potential founder variant in carmil2\/rltpr in three norwegian families with warts, molluscum contagiosum, and t-cell dysfunction. Mol Genet Genomic Med. 2016;4:604\u201316.","journal-title":"Mol Genet Genomic Med"},{"key":"552_CR13","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1038\/s41586-019-1828-5","volume":"577","author":"N Lalaoui","year":"2020","unstructured":"Lalaoui N, Boyden SE, Oda H, Wood GM, Stone DL, Chau D, et al. Mutations that prevent caspase cleavage of ripk1 cause autoinflammatory disease. Nature. 2020;577:103\u20138.","journal-title":"Nature."},{"key":"552_CR14","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1038\/ng.3459","volume":"48","author":"Q Zhou","year":"2016","unstructured":"Zhou Q, Wang H, Schwartz DM, Stoffels M, Park YH, Zhang Y, et al. Loss-of-function mutations in tnfaip3 leading to a20 haploinsufficiency cause an early-onset autoinflammatory disease. Nat Genet. 2016;48:67\u201373.","journal-title":"Nat Genet"},{"key":"552_CR15","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.1093\/rheumatology\/key445","volume":"58","author":"C Papadopoulou","year":"2019","unstructured":"Papadopoulou C, Omoyinmi E, Standing A, Pain CE, Booth C, D'Arco F, et al. Monogenic mimics of behcet's disease in the young. Rheumatology (Oxford). 2019;58:1227\u201338.","journal-title":"Rheumatology (Oxford)"},{"key":"552_CR16","doi-asserted-by":"crossref","unstructured":"Demirkaya E, Sahin S, Romano M, Zhou Q, Aksentijevich I. New horizons in the genetic etiology of systemic lupus erythematosus and lupus-like disease: monogenic lupus and beyond. J Clin Med. 2020;9.","DOI":"10.3390\/jcm9030712"},{"key":"552_CR17","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1007\/s10875-015-0147-3","volume":"35","author":"GI Rice","year":"2015","unstructured":"Rice GI, Rodero MP, Crow YJ. Human disease phenotypes associated with mutations in trex1. J Clin Immunol. 2015;35:235\u201343.","journal-title":"J Clin Immunol"},{"key":"552_CR18","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1186\/s12969-019-0349-y","volume":"17","author":"I Tirosh","year":"2019","unstructured":"Tirosh I, Spielman S, Barel O, Ram R, Stauber T, Paret G, et al. Whole exome sequencing in childhood-onset lupus frequently detects single gene etiologies. Pediatr Rheumatol Online J. 2019;17:52.","journal-title":"Pediatr Rheumatol Online J."},{"key":"552_CR19","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1002\/eji.201847955","volume":"49","author":"E Kaleviste","year":"2019","unstructured":"Kaleviste E, Saare M, Leahy TR, Bondet V, Duffy D, Mogensen TH, et al. Interferon signature in patients with stat1 gain-of-function mutation is epigenetically determined. Eur J Immunol. 2019;49:790\u2013800.","journal-title":"Eur J Immunol"},{"key":"552_CR20","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1136\/annrheumdis-2019-215918","volume":"79","author":"DM Schwartz","year":"2020","unstructured":"Schwartz DM, Blackstone SA, Sampaio-Moura N, Rosenzweig S, Burma AM, Stone D, et al. Type i interferon signature predicts response to jak inhibition in haploinsufficiency of a20. Ann Rheum Dis. 2020;79:429\u201331.","journal-title":"Ann Rheum Dis"},{"key":"552_CR21","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1001\/jamadermatol.2018.5077","volume":"155","author":"N Zimmermann","year":"2019","unstructured":"Zimmermann N, Wolf C, Schwenke R, Luth A, Schmidt F, Engel K, et al. Assessment of clinical response to janus kinase inhibition in patients with familial chilblain lupus and trex1 mutation. JAMA Dermatol. 2019;155:342\u20136.","journal-title":"JAMA Dermatol"},{"key":"552_CR22","doi-asserted-by":"publisher","first-page":"4246965","DOI":"10.1155\/2018\/4246965","volume":"2018","author":"A Puccetti","year":"2018","unstructured":"Puccetti A, Fiore PF, Pelosi A, Tinazzi E, Patuzzo G, Argentino G, et al. Gene expression profiling in behcet's disease indicates an autoimmune component in the pathogenesis of the disease and opens new avenues for targeted therapy. J Immunol Res. 2018;2018:4246965.","journal-title":"J Immunol Res"},{"key":"552_CR23","doi-asserted-by":"publisher","first-page":"958","DOI":"10.1136\/annrheumdis-2015-208491","volume":"75","author":"I Kone-Paut","year":"2016","unstructured":"Kone-Paut I, Shahram F, Darce-Bello M, Cantarini L, Cimaz R, Gattorno M, et al. Consensus classification criteria for paediatric behcet's disease from a prospective observational cohort: Pedbd. Ann Rheum Dis. 2016;75:958\u201364.","journal-title":"Ann Rheum Dis"},{"key":"552_CR24","doi-asserted-by":"publisher","first-page":"1725","DOI":"10.1002\/art.1780400928","volume":"40","author":"MC Hochberg","year":"1997","unstructured":"Hochberg MC. Updating the american college of rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997;40:1725.","journal-title":"Arthritis Rheum"},{"key":"552_CR25","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1136\/annrheumdis-2018-214819","volume":"78","author":"M Aringer","year":"2019","unstructured":"Aringer M, Costenbader K, Daikh D, Brinks R, Mosca M, Ramsey-Goldman R, et al. 2019 European league against rheumatism\/American College of Rheumatology classification criteria for systemic lupus erythematosus. Ann Rheum Dis. 2019;78:1151\u20139.","journal-title":"Ann Rheum Dis"},{"key":"552_CR26","doi-asserted-by":"crossref","unstructured":"Pin A, Monasta L, Taddio A, Piscianz E, Tommasini A, Tesser A. An easy and reliable strategy for making type i interferon signature analysis comparable among research centers. Diagnostics (Basel). 2019;9.","DOI":"10.3390\/diagnostics9030113"},{"key":"552_CR27","doi-asserted-by":"publisher","first-page":"1159","DOI":"10.1016\/S1474-4422(13)70258-8","volume":"12","author":"GI Rice","year":"2013","unstructured":"Rice GI, Forte GM, Szynkiewicz M, Chase DS, Aeby A, Abdel-Hamid MS, et al. Assessment of interferon-related biomarkers in aicardi-goutieres syndrome associated with mutations in trex1, rnaseh2a, rnaseh2b, rnaseh2c, samhd1, and adar: a case-control study. Lancet Neurol. 2013;12:1159\u201369.","journal-title":"Lancet Neurol"},{"key":"552_CR28","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1038\/nmeth0410-248","volume":"7","author":"IA Adzhubei","year":"2010","unstructured":"Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, et al. A method and server for predicting damaging missense mutations. Nat Methods. 2010;7:248\u20139.","journal-title":"Nat Methods"},{"key":"552_CR29","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1038\/nprot.2009.86","volume":"4","author":"P Kumar","year":"2009","unstructured":"Kumar P, Henikoff S, Ng PC. Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat Protoc. 2009;4:1073\u201381.","journal-title":"Nat Protoc"},{"key":"552_CR30","doi-asserted-by":"publisher","first-page":"1553","DOI":"10.1101\/gr.092619.109","volume":"19","author":"S Chun","year":"2009","unstructured":"Chun S, Fay JC. Identification of deleterious mutations within three human gen- omes. Genome Res. 2009;19:1553\u201361.","journal-title":"Genome Res"},{"key":"552_CR31","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1038\/nmeth0810-575","volume":"7","author":"JM Schwarz","year":"2010","unstructured":"Schwarz JM, R\u00f6delsperger C, Schuelke M, Seelow D. MutationTaster evaluates disease-causing potential of sequence alterations. Nat Methods. 2010;7:575\u20136.","journal-title":"Nat Methods"},{"key":"552_CR32","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1038\/ng.2892","volume":"46","author":"M Kircher","year":"2014","unstructured":"Kircher M, Witten DM, Jain P, O'Roak BJ, Cooper GM, Shendure J. A general framework for estimating the relative pathogenicity of human genetic variants. Nat Genet. 2014;46:310\u20135.","journal-title":"Nat Genet"},{"key":"552_CR33","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1038\/nmeth0410-250","volume":"7","author":"GM Cooper","year":"2010","unstructured":"Cooper GM, Goode DL, Ng SB, Sidow A, Bamshad MJ, Shendure J, et al. Single-nucleotide evolutionary constraint scores highlight disease-causing mutations. Nat Methods. 2010;7:250\u20131.","journal-title":"Nat Methods"},{"key":"552_CR34","doi-asserted-by":"crossref","unstructured":"Carbonella A, Mancano G, Gremese E, Alkuraya FS, Patel N, Gurrieri F, et al. An autosomal recessive dnase1l3-related autoimmune disease with unusual clinical presentation mimicking systemic lupus erythematosus. Lupus. 2017;26:768\u201372.","DOI":"10.1177\/0961203316676382"},{"key":"552_CR35","unstructured":"Johannes Hartl, Robert M. Clancy, Peter M. Izmirly2, H. Michael Belmont1, Nicole Kaiden3, Nicole Bornkamp, et al. Dysfunction of the DNAS E1L3 Pathway and Antigen Accumulation in Lupus Nephritis [abstract]. 2018 ACR\/ARHP Annual Meeting."},{"key":"552_CR36","doi-asserted-by":"crossref","unstructured":"Liu L, Okada S, Kong XF, Kreins AY, Cypowyj S, Abhyankar A, et al. Gain-of-function human stat1 mutations impair il-17 immunity and underlie chronicmucocutaneous candidiasis. J Exp Med. 2011;208:1635\u201348.","DOI":"10.1084\/jem.20110958"},{"key":"552_CR37","doi-asserted-by":"crossref","unstructured":"Giovannozzi S, Lemmens V, Hendrix J, Gijsbers R, Schrijvers R. Live cell imaging demonstrates multiple routes toward a stat1 gain-of-function phenotype. Front Immunol. 2020;11:1114.","DOI":"10.3389\/fimmu.2020.01114"},{"key":"552_CR38","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1093\/rheumatology\/ket460","volume":"53","author":"M Hofer","year":"2014","unstructured":"Hofer M, Pillet P, Cochard MM, Berg S, Krol P, Kone-Paut I, et al. International periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis syndrome cohort: Description of distinct phenotypes in 301 patients. Rheumatology (Oxford). 2014;53:1125\u20139.","journal-title":"Rheumatology (Oxford)"},{"key":"552_CR39","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1007\/s00296-019-04257-0","volume":"39","author":"ED Batu","year":"2019","unstructured":"Batu ED. Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (pfapa) syndrome: Main features and an algorithm for clinical practice. Rheumatol Int. 2019;39:957\u201370.","journal-title":"Rheumatol Int"},{"key":"552_CR40","first-page":"437","volume":"33","author":"C De Pieri","year":"2015","unstructured":"De Pieri C, Taddio A, Insalaco A, Barbi E, Lepore L, Ventura A, et al. Different presentations of mevalonate kinase deficiency: a case series. Clin Exp Rheumatol. 2015;33:437\u201342.","journal-title":"Clin Exp Rheumatol"},{"key":"552_CR41","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1016\/j.jpeds.2017.08.078","volume":"192","author":"E Pehlivan","year":"2018","unstructured":"Pehlivan E, Adrovic A, Sahin S, Barut K, Kul Cinar O, Kasapcopur O. Pfapa syndrome in a population with endemic familial mediterranean fever. J Pediatr. 2018;192:253\u20135.","journal-title":"J Pediatr"},{"key":"552_CR42","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1007\/s10067-015-2890-5","volume":"35","author":"L Cantarini","year":"2016","unstructured":"Cantarini L, Vitale A, Bersani G, Nieves LM, Cattalini M, Lopalco G, et al. Pfapa syndrome and behcet's disease: a comparison of two medical entities based on the clinical interviews performed by three different specialists. Clin Rheumatol. 2016;35:501\u20135.","journal-title":"Clin Rheumatol"},{"key":"552_CR43","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1111\/pde.12577","volume":"32","author":"A Gurkan","year":"2015","unstructured":"Gurkan A, Ozlu SG, Altiaylik-Ozer P, Kurtul BE, Karacan CD, Senel S. Recurrent aphthous stomatitis in childhood and adolescence: a single-center experience. Pediatr Dermatol. 2015;32:476\u201380.","journal-title":"Pediatr Dermatol"},{"key":"552_CR44","doi-asserted-by":"publisher","first-page":"e20232","DOI":"10.1097\/MD.0000000000020232","volume":"99","author":"G Li","year":"2020","unstructured":"Li G, Li Y, Liu H, Shi Y, Guan W, Zhang T, et al. Genetic heterogeneity of pediatric systemic lupus erythematosus with lymphoproliferation. Medicine (Baltimore). 2020;99:e20232.","journal-title":"Medicine (Baltimore)"},{"key":"552_CR45","first-page":"61","volume":"2","author":"RR Sieving","year":"1975","unstructured":"Sieving RR, Kauffman CA, Watanakunakorn C. Deep fungal infection in systemic lupus erythematosus - three cases reported, literature reviewed. J Rheumatol. 1975;2:61\u201372.","journal-title":"J Rheumatol"},{"key":"552_CR46","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1097\/RHU.0b013e3181c41b84","volume":"15","author":"AM Wasserman","year":"2009","unstructured":"Wasserman AM, Sarantopoulos GP, Khanna D. Fungal leukocytoclastic vasculitis as a presentation of systemic vasculitis in a patient with systemic lupus erythematosus. J Clin Rheumatol. 2009;15:383\u20136.","journal-title":"J Clin Rheumatol"},{"key":"552_CR47","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1007\/s10067-012-1980-x","volume":"31","author":"GL Chen","year":"2012","unstructured":"Chen GL, Chen Y, Zhu CQ, Yang CD, Ye S. Invasive fungal infection in Chinese patients with systemic lupus erythematosus. Clin Rheumatol. 2012;31:1087\u201391.","journal-title":"Clin Rheumatol"},{"key":"552_CR48","doi-asserted-by":"publisher","first-page":"684","DOI":"10.1177\/0961203314525247","volume":"23","author":"M Fangtham","year":"2014","unstructured":"Fangtham M, Magder LS, Petri MA. Oral candidiasis in systemic lupus erythematosus. Lupus. 2014;23:684\u201390.","journal-title":"Lupus."},{"key":"552_CR49","doi-asserted-by":"publisher","first-page":"2296","DOI":"10.3899\/jrheum.150142","volume":"42","author":"MF Silva","year":"2015","unstructured":"Silva MF, Ferriani MP, Terreri MT, Pereira RM, Magalh\u00e3es CS, Bonf\u00e1 E, et al. A multicenter study of invasive fungal infections in patients with childhood-onset systemic lupus Erythematosus. J Rheumatol. 2015;42:2296\u2013303.","journal-title":"J Rheumatol"},{"key":"552_CR50","unstructured":"Chowdhry IA, Tan IJ, Mian N, Mackay M, Keiser H, Davidson A. Systemic lupus erythematosus presenting with features suggestive of human immunodeficiency virus infection. J Rheumatol. 2005;32:1365\u20138."},{"key":"552_CR51","doi-asserted-by":"crossref","unstructured":"Febronio MV, Pereira RMR, Bonfa E, Takiuti AD, Pereyra EAG, Silva CCA. Inflammatory cervicovaginal cytology is associated with disease activity in juvenile systemic lupus erythematosus. Lupus.2007;16:430\u20135.","DOI":"10.1177\/0961203307079298"},{"key":"552_CR52","doi-asserted-by":"crossref","unstructured":"Tsuchida N, Kirino Y, Soejima Y, Onodera M, Arai K, Tamura E, et al. Haploinsufficiency of a20 caused by a novel nonsense variant or entire deletion oftnfaip3 is clinically distinct from behcet's disease. Arthritis Res Ther. 2019;21:137.","DOI":"10.1186\/s13075-019-1928-5"},{"key":"552_CR53","doi-asserted-by":"crossref","unstructured":"Baechler EC, Batliwalla FM, Karypis G, Gaffney PM, Ortmann WA, Espe KJ, et al. Interferon-inducible gene expression signature in peripheral blood cells ofpatients with severe lupus. Proc Natl Acad Sci U S A. 2003;100:2610\u20135.","DOI":"10.1073\/pnas.0337679100"},{"key":"552_CR54","doi-asserted-by":"crossref","unstructured":"Aeschlimann FA, Batu ED, Canna SW, Go E, Gul A, Hoffmann P, et al. A20 haploinsufficiency (ha20): clinical phenotypes and disease course of patients with anewly recognised nf-kb-mediated autoinflammatory disease. Ann Rheum Dis. 2018;77:728\u201335.","DOI":"10.1136\/annrheumdis-2017-212403"},{"key":"552_CR55","doi-asserted-by":"crossref","unstructured":"Flint SM, Jovanovic V, Teo BW, Mak A, Thumboo J, McKinney EF, et al. Leucocyte subset-specific type 1 interferon signatures in sle and other immunemediated diseases. RMD Open. 2016;2:e000183.","DOI":"10.1136\/rmdopen-2015-000183"},{"key":"552_CR56","doi-asserted-by":"crossref","unstructured":"Bahrami T, Valilou SF, Sadr M, Soltani S, Salmaninejad A, Soltaninejad E, et al. Ptpn22 gene polymorphisms in pediatric systemic lupus erythematosus. Fetal Pediatr Pathol. 2020;39:13\u201320.","DOI":"10.1080\/15513815.2019.1630873"},{"key":"552_CR57","doi-asserted-by":"crossref","unstructured":"Tizaoui K, Kim SH, Jeong GH, Kronbichler A, Lee KS, Lee KH, et al. Association of ptpn22 1858c\/t polymorphism with autoimmune diseases: a systematic review and bayesian approach. J Clin Med. 2019;8.","DOI":"10.3390\/jcm8030347"},{"key":"552_CR58","doi-asserted-by":"crossref","unstructured":"Batu ED, Kosukcu C, Taskiran E, Sahin S, Akman S, Sozeri B, et al. Whole exome sequencing in early-onset systemic lupus erythematosus. J Rheumatol. 2018;45:1671\u20139.","DOI":"10.3899\/jrheum.171358"},{"key":"552_CR59","doi-asserted-by":"crossref","unstructured":"Al-Mayouf SM, Sunker A, Abdwani R, Abrawi SA, Almurshedi F, Alhashmi N, et al. Loss-of-function variant in dnase1l3 causes a familial form of systemic lupus erythematosus. Nat Genet. 2011;43:1186\u20138.","DOI":"10.1038\/ng.975"},{"key":"552_CR60","doi-asserted-by":"crossref","unstructured":"Ozcakar ZB, Foster J 2nd, Diaz-Horta O, Kasapcopur O, Fan YS, Yalcinkaya F, et al. Dnase1l3 mutations in hypocomplementemic urticarial vasculitis syndrome. Arthritis Rheum. 2013;65:2183\u20139.","DOI":"10.1002\/art.38010"}],"container-title":["Pediatric Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12969-021-00552-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12969-021-00552-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12969-021-00552-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T15:27:23Z","timestamp":1675265243000},"score":1,"resource":{"primary":{"URL":"https:\/\/ped-rheum.biomedcentral.com\/articles\/10.1186\/s12969-021-00552-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,10]]},"references-count":60,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["552"],"URL":"https:\/\/doi.org\/10.1186\/s12969-021-00552-y","relation":{},"ISSN":["1546-0096"],"issn-type":[{"value":"1546-0096","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,10]]},"assertion":[{"value":"27 October 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 April 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 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":"A signed informed consent was obtained from patients\u2019 parents\/guardians, according to an IRB approved protocol (RC 24\/17).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"An institutional consent form is available.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"None of the Authors has any conflict of interests regarding the matters treated in the manuscript.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"70"}}