{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T16:56:32Z","timestamp":1778864192089,"version":"3.51.4"},"reference-count":11,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,8,20]],"date-time":"2020-08-20T00:00:00Z","timestamp":1597881600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,8,20]],"date-time":"2020-08-20T00:00:00Z","timestamp":1597881600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pediatr Rheumatol"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>Deficiency of the natural antagonist of interleukin-1 was first described in 2009 and so far 20 patients has been reported. In Brazil just two cases have been reported both carrying the same homozygous 15\u2009bp deletion. Blocking interleukin-1 has changed rate survival for DIRA patients. The use of anakinra and rilonacept has been reported safe and efficient, whereas the selective blockade of interleukin-1 beta, using the monoclonal antibody canakinumab has been reported in a single case only.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Case presentation<\/jats:title>\n<jats:p>Here we report a case of a 7\u2009years old Brazilian boy that presented with recurrent episodes of systemic inflammation with severe disabling osteomyelitis with mild pustular skin rash. A Next Generation Sequencing gene panel allowed to detect two pathogenic mutations in the IL1RN gene, described in compound heterozygosity. Corticosteroids was effective in controlling inflammation and anti-IL1 beta blocker triggered disease flare. Complete clinical control could be achieved using IL-1 receptor antagonist.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>DIRA is a severe, life threatening autoinflammatory condition with low numbers of patients described all over the world. The mutation p.Asp72_Ile76del in IL1RN is presented in all Brazilian DIRA patients already described and p.Q45* (rs1019766125) is a new mutation affecting the IL1RN gene. Following the pathogenesis of DIRA, blocking both subunits of interleukin one as well as antagonizing the receptor using anakinra or rilonacept seems to be effective. There is just one report using canakinumab for the treatment of DIRA and this is the first report of disease flare using this drug.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s12969-020-00454-5","type":"journal-article","created":{"date-parts":[[2020,8,20]],"date-time":"2020-08-20T11:02:57Z","timestamp":1597921377000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["A case report of a novel compound heterozygous mutation in a Brazilian patient with deficiency of Interleukin-1 receptor antagonist (DIRA)"],"prefix":"10.1186","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7533-1937","authenticated-orcid":false,"given":"Leonardo Oliveira","family":"Mendon\u00e7a","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alice","family":"Grossi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Caroli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robson Aguiar","family":"de Oliveira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge","family":"Kalil","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabio Fernandes Morato","family":"Castro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Pontillo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabella","family":"Ceccherini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Myrthes Anna Maragna Toledo","family":"Barros","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Gattorno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,8,20]]},"reference":[{"issue":"1","key":"454_CR1","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/ng0997-25","volume":"17","author":"FMF French","year":"1997","unstructured":"French FMF. Consortium; A candidate gene for familial mediterranean fever. Nat Genet. 1997;17(1):25\u201331.","journal-title":"Nat Genet"},{"issue":"23","key":"454_CR2","doi-asserted-by":"publisher","first-page":"2426","DOI":"10.1056\/NEJMoa0807865","volume":"360","author":"I Aksentijevich","year":"2009","unstructured":"Aksentijevich I, Masters SL, Ph D, Ferguson PJ, Dancey P, Frenkel J, et al. An autoinflammatory disease with deficiency of the Interleukin-1-receptor antagonist autoinflammatory disease : recurrent episodes of inflammatory. N Engl J Med. 2009;360(23):2426\u201337.","journal-title":"N Engl J Med"},{"key":"454_CR3","doi-asserted-by":"crossref","unstructured":"de Jesus, Adriana Almeida De\u2019; osman, mazen; silva, clovis a.; kim, peter w.; pham, tuyet-hang; gadina, massino; yang, barbara; bertola, debora r.; carneiro-sampaio, magda; ferguson, polly j.; renshaw, blair r.; schooley, ben; brown, michael; ai-dosari, asma hatem. A novel mutation of IL1RN in the deficiency of Interleukin-1 receptor antagonist syndrome: description of two unrelated cases from Brazil. Arthritis Rheum; 2011;63(12):4007\u20134017.","DOI":"10.1002\/art.30588"},{"key":"454_CR4","doi-asserted-by":"publisher","first-page":"1550","DOI":"10.1136\/annrheumdis-2015-207701","volume":"75","author":"M Rusmini","year":"2016","unstructured":"Rusmini M, Federici S, Caroli F, et al. Next-generation sequencing and its initial applications for molecular diagnosis of systemic auto-inflammatory diseases. Ann Rheum Dis. 2016;75:1550\u20137.","journal-title":"Ann Rheum Dis"},{"key":"454_CR5","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1016\/j.rdc.2013.05.002","volume":"39","author":"SM Stern","year":"2013","unstructured":"Stern SM, Ferguson PJ. Autoinflammatory bone diseases. Rheum Dis Clin N Am. 2013;39:735\u201349.","journal-title":"Rheum Dis Clin N Am"},{"issue":"12","key":"454_CR6","doi-asserted-by":"publisher","first-page":"4018","DOI":"10.1002\/art.30565","volume":"63","author":"M Stenerson","year":"2011","unstructured":"Stenerson M, Dufendach K, Aksentijevich I, Brady J, Austin J, Reed AM. The first reported case of compound heterozygous IL1RN mutations causing deficiency of the Interleukin-1 receptor antagonist. Arthritis Rheum. 2011;63(12):4018\u201322.","journal-title":"Arthritis Rheum"},{"key":"454_CR7","first-page":"16","volume":"2","author":"M Garg","year":"2017","unstructured":"Garg M, de Jesus AA, Chapelle D, Dancey P, Herzog R, Rivas-Chacon R, Muskardin TLW, Reed A, Reynolds JC, Goldbach-Mansky R, GAM S. Rilonacept maintains long-term inflammatory remission in patients with deficiency of the IL-1 receptor antagonist. J Clin Invest. 2017;2:16.","journal-title":"J Clin Invest"},{"issue":"9","key":"454_CR8","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1186\/s13256-015-0618-4","volume":"June","author":"E Ulusoy","year":"2015","unstructured":"Ulusoy E, Karaca NE, El-Shanti H, Kilicoglu E, Aksu G, Kutukculer N. Interleukin-1 receptor antagonist deficiency with a novel mutation: late onset and successful treatment with canakinumab: a case report. J Med Case Rep. 2015;June(9):145.","journal-title":"J Med Case Rep"},{"issue":"5","key":"454_CR9","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1007\/s10875-017-0399-1","volume":"37","author":"LO Mendon\u00e7a","year":"2017","unstructured":"Mendon\u00e7a LO, Malle L, Donavan FX, Chandrasekharappa SC, Montealegre GA, Chapelle D, Suri D, Mansky G, de Jesus AA. Deficiency of Interleukin-1 Receptor Antagonist (DIRA): Report of the First Indian Patient and a Novel Deletion Affecting IL1RN. J Clin Immunol. 2017;37(5):445\u201351.","journal-title":"J Clin Immunol"},{"key":"454_CR10","doi-asserted-by":"crossref","unstructured":"Kuemmerle-Deschner J.B.; Reicherter, K; Schlipf S; Hansmann S; Hospach A; Tsiflikas I; Liu X; Benseler S; Weber A; New variant in the IL1RN-gene associated with late onset and atypical presentation of DIRA \u2013 follow-up; Pediatr Rheumatol 2019, 17(Suppl 1):P1041.","DOI":"10.1136\/annrheumdis-2018-eular.5620"},{"key":"454_CR11","doi-asserted-by":"crossref","unstructured":"Necil Kutukculer, Anne Puel, Sanem Eren Akarcan, et al., \u201cDeficiency of Interleukin-1 Receptor Antagonist: A Case with Late Onset Severe Inflammatory Arthritis, Nail Psoriasis with Onychomycosis and Well Responsive to Adalimumab Therapy,\u201d Case Reports in Immunology, vol. 2019, Article ID 1902817, 6 pages, 2019.","DOI":"10.1155\/2019\/1902817"}],"container-title":["Pediatric Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12969-020-00454-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12969-020-00454-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12969-020-00454-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T23:30:26Z","timestamp":1629415826000},"score":1,"resource":{"primary":{"URL":"https:\/\/ped-rheum.biomedcentral.com\/articles\/10.1186\/s12969-020-00454-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,20]]},"references-count":11,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["454"],"URL":"https:\/\/doi.org\/10.1186\/s12969-020-00454-5","relation":{},"ISSN":["1546-0096"],"issn-type":[{"value":"1546-0096","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,20]]},"assertion":[{"value":"28 November 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 August 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 August 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The study is approved at the Hospital das Cl\u00ednicas, University of S\u00e3o Paulo, School of Medicine. The number of study approval is CAAE 74305817.0.0000.0068.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Written informed consent for publication was obtained from all included in the study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"LOM receives fees from Novartis Brazil as speaker and received an award from the European Society for Primary Immunodeficiencies; MG receives fees as speaker and consultancies from Novartis and Sobi","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"67"}}