{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T13:46:49Z","timestamp":1790344009563,"version":"4.1.0"},"reference-count":16,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,12,1]],"date-time":"2019-12-01T00:00:00Z","timestamp":1575158400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,12,21]],"date-time":"2019-12-21T00:00:00Z","timestamp":1576886400000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pediatr Rheumatol"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Fibrodysplasia ossificans progressiva (FOP) is the most catastrophic form of heterotopic ossification, due to ongoing intracellular signaling through the bone morphogenic protein pathway. The paroxysmal appearance of inflammatory lumps and elevated inflammatory markers during flares, suggest that FOP is an auto-inflammatory disease. Based on evidence, demonstrating a role for interleukin-1\u03b2 (IL-1\u03b2) in other forms of heterotopic ossification, we hypothesized that treating FOP patients with anti-IL-1 agents could help lower the rate of FOP paroxysms and\/or limit the symptoms and residual lesions.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Case presentation<\/jats:title>\n                <jats:p>A 13.5-year-old Arab boy was diagnosed with FOP. Treatment with anti-inflammatory drugs did not change the disease course. New lumps appeared in a rate of approximately one every 8\u2009days. Treatment with the anti-IL-1 agents anakinra and canakinumab resulted in significantly lower rate of paroxysms (every 22\u201325\u2009days, of which almost all involved only 2 existing lumps), as well as shorter duration. High levels of IL-1\u03b2 were found in the patient\u2019s plasma samples, collected during a paroxysm that appeared 8\u2009weeks after the last canakinumab dose. In contrast, IL-1\u03b2 plasma levels were undetectable in the previous three plasma samples, obtained while he was treated with anti-IL-1 agents.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Our data demonstrate the efficacy of anti-IL-1 agents in the treatment of a patient with FOP. Results showing the marked increase in IL-1\u03b2 plasma levels during a paroxysm support a role for IL-1\u03b2 in the pathogenesis of FOP and further provide the rationale for the use of anti-IL-1 agents in FOP treatment.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12969-019-0386-6","type":"journal-article","created":{"date-parts":[[2019,12,21]],"date-time":"2019-12-21T12:02:29Z","timestamp":1576929749000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Is fibrodysplasia ossificans progressiva an interleukin-1 driven auto-inflammatory syndrome?"],"prefix":"10.1186","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1077-1939","authenticated-orcid":false,"given":"Ruby","family":"Haviv","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Moshe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"De Benedetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giusi","family":"Prencipe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noa","family":"Rabinowicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosef","family":"Uziel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,12,21]]},"reference":[{"issue":"1","key":"386_CR1","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1186\/s13023-017-0674-5","volume":"12","author":"G Baujat","year":"2017","unstructured":"Baujat G, Choquet R, Bou\u00e9e S, et al. Prevalence of fibrodysplasia ossificans progressiva (FOP) in France: an estimate based on a record linkage of two national databases. Orphanet J Rare Dis. 2017;12(1):123.","journal-title":"Orphanet J Rare Dis"},{"issue":"5","key":"386_CR2","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1038\/ng1783","volume":"38","author":"EM Shore","year":"2006","unstructured":"Shore EM, Xu M, Feldman GJ, et al. A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva. Nat Genet. 2006;38(5):525\u20137.","journal-title":"Nat Genet"},{"key":"386_CR3","doi-asserted-by":"publisher","first-page":"2489","DOI":"10.1002\/jbmr.3235","volume":"32","author":"J Upadhyay","year":"2017","unstructured":"Upadhyay J, Xie L, Huang L, et al. Expansion of heterotopic bone in Fibrodysplasia Ossificans Progressiva is Activin A-dependent. J Bone Miner Res. 2017;32:2489\u201399.","journal-title":"J Bone Miner Res"},{"key":"386_CR4","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1016\/j.bone.2017.06.011","volume":"109","author":"DM Alessi Wolken","year":"2018","unstructured":"Alessi Wolken DM, Idone V, Hatsell SJ, et al. The obligatory role of Activin a in the formation of heterotopic bone in Fibrodysplasia Ossificans Progressiva. Bone. 2018;109:210\u20137.","journal-title":"Bone"},{"key":"386_CR5","doi-asserted-by":"publisher","first-page":"242","DOI":"10.5582\/irdr.2017.01055","volume":"6","author":"Z Qi","year":"2017","unstructured":"Qi Z, Luan J, Zhou X, et al. Fibrodysplasia ossificans progressiva: basic understanding and experimental models. Intractable Rare Dis Res. 2017;6:242\u20138.","journal-title":"Intractable Rare Dis Res"},{"key":"386_CR6","first-page":"1","volume":"4","author":"FS Kaplan","year":"2011","unstructured":"Kaplan FS, Shore EM, Pignolo RJ, et al. (The international clinical consortium on fibrodysplasia ossificans progressiva). The medical management of fibrodysplasia ossificans progressiva: current treatment considerations. Clin Proc Intl Clin Consort FOP. 2011;4:1\u2013100.","journal-title":"Clin Proc Intl Clin Consort FOP"},{"issue":"6","key":"386_CR7","doi-asserted-by":"publisher","first-page":"1180","DOI":"10.1111\/bcp.13823","volume":"85","author":"Kelly L. Wentworth","year":"2019","unstructured":"Wentworth KL, Masharani U, Hsiao EC. Therapeutic advances for blocking heterotopic ossification in fibrodysplasia ossificans progressiva. Br J Clin Pharmacol. 2018. https:\/\/doi.org\/10.1111\/bcp.13823.","journal-title":"British Journal of Clinical Pharmacology"},{"key":"386_CR8","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1007\/s00296-018-4179-x","volume":"39","author":"K Gencer-Atalay","year":"2019","unstructured":"Gencer-Atalay K, Ozturk EC, Yagci I, et al. Challenges in the treatment of fibrodysplasia ossificans progressiva. Rheumatol Int. 2019;39:69\u2013576.","journal-title":"Rheumatol Int"},{"key":"386_CR9","doi-asserted-by":"publisher","first-page":"686","DOI":"10.2106\/JBJS.I.00705","volume":"92","author":"FS Kaplan","year":"2010","unstructured":"Kaplan FS, Zasloff MA, Kitterman JA, et al. Early mortality and cardiorespiratory failure in patients with fibrodysplasia ossificans progressiva. J Bone Joint Surg Am. 2010;92:686\u201391.","journal-title":"J Bone Joint Surg Am"},{"key":"386_CR10","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.semcdb.2015.12.013","volume":"49","author":"FS Kaplan","year":"2016","unstructured":"Kaplan FS, Pignolo RJ, Shore EM. Granting immunity to FOP and catching heterotopic ossification in the act. 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