{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T07:04:17Z","timestamp":1743577457885},"reference-count":11,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,10,5]],"date-time":"2022-10-05T00:00:00Z","timestamp":1664928000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,10,5]],"date-time":"2022-10-05T00:00:00Z","timestamp":1664928000000},"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"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) is a clinical syndrome of unclear etiology. PFAPA has generally been considered a non-hereditary fever syndrome; however, this has been called into question with recent reports of family clustering. Few reports have been published describing siblings with PFAPA. To our knowledge, this is the first report of siblings with near simultaneous onset of disease followed by synchronous disease flares.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Case Presentation:<\/jats:title>\n                <jats:p>We describe the case of near simultaneous onset of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis in siblings followed by synchronous disease flares of clear frequency and nearly identical character. Flares were characterized predominantly by fever, aphthous ulceration, cervical lymphadenitis, and the absence of infection. The fever episodes demonstrated a robust response to glucocorticoids and recurred in the same staggered manner every four weeks, with complete absence of symptoms and normal growth and development between episodes. Nine months after onset, the older sibling, a 5-year-old female, underwent tonsillectomy resulting in dramatic resolution of episodes. At the same time, her 2-year-old sister experienced resolution of her fever episodes, though she did not undergo tonsillectomy herself.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>This is an unusual case of simultaneous onset PFAPA followed by synchronous disease flares. PFAPA is an uncommon clinical syndrome, and it is rarely diagnosed in siblings. The etiology of PFAPA remains unclear. Though the disease is classically considered sporadic, there is a growing body of evidence to suggest that PFAPA may be heritable.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12969-022-00744-0","type":"journal-article","created":{"date-parts":[[2022,10,5]],"date-time":"2022-10-05T05:02:38Z","timestamp":1664946158000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Synchronous disease onset and flares in siblings with PFAPA"],"prefix":"10.1186","volume":"20","author":[{"given":"Kristen L.","family":"Dammeyer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda","family":"Schneider","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Max M.","family":"April","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip J.","family":"Kahn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,10,5]]},"reference":[{"issue":"1","key":"744_CR1","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/S0022-3476(87)80285-8","volume":"110","author":"GS Marshall","year":"1987","unstructured":"Marshall GS, Edwards KM, Butler J, Lawton AR. Syndrome of periodic fever, pharyngitis, and aphthous stomatitis. J Pediatr. 1987;110(1):43\u20136.","journal-title":"J Pediatr"},{"issue":"1","key":"744_CR2","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(1):15\u201321.","journal-title":"J Pediatr"},{"key":"744_CR3","doi-asserted-by":"crossref","unstructured":"Gattorno M, Hofer M, Federici S, Vanoni F, Bovis F, Aksentijevich I, et al. Ann Rheum Dis. 2019 Aug; 78(8):1025\u20131032.","DOI":"10.1136\/annrheumdis-2019-215048"},{"key":"744_CR4","doi-asserted-by":"publisher","first-page":"10200","DOI":"10.1038\/srep10200","volume":"5","author":"SA Di Gioia","year":"2015","unstructured":"Di Gioia SA, Bedoni N, von Scheven-G\u00eate A, Vanoni F, Superti-Furga A, Hofer M, et al. Analysis of the genetic basis of periodic fever with aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome. Sci Rep. 2015;5:10200.","journal-title":"Sci Rep"},{"issue":"1","key":"744_CR5","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1186\/s12969-016-0101-9","volume":"14","author":"F Vanoni","year":"2016","unstructured":"Vanoni F, Theodoropoulou K, Hofer M. PFAPA syndrome: a review on treatment and outcome. Pediatr Rheumatol Online J. 2016;14(1):38.","journal-title":"Pediatr Rheumatol Online J"},{"key":"744_CR6","doi-asserted-by":"crossref","unstructured":"Manthiram K, Nesbitt E, Morgan T, Edwards KM. Family History in Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis (PFAPA) Syndrome. Pediatrics. 2016;138(3).","DOI":"10.1542\/peds.2015-4572"},{"issue":"10","key":"744_CR7","doi-asserted-by":"publisher","first-page":"1984","DOI":"10.1093\/rheumatology\/keq187","volume":"49","author":"M Cochard","year":"2010","unstructured":"Cochard M, Clet J, Le L, Pillet P, Onrubia X, Gu\u00e9ron T, et al. PFAPA syndrome is not a sporadic disease. Rheumatology (Oxford). 2010;49(10):1984\u20137.","journal-title":"Rheumatology (Oxford)"},{"issue":"12","key":"744_CR8","doi-asserted-by":"publisher","first-page":"1563","DOI":"10.1007\/s00431-011-1479-5","volume":"170","author":"P Ant\u00f3n-Mart\u00edn","year":"2011","unstructured":"Ant\u00f3n-Mart\u00edn P, Ortiz Movilla R, Guill\u00e9n Mart\u00edn S, Allende LM, Cuesta Rubio MT, L\u00f3pez Gonz\u00e1lez MF, et al. PFAPA syndrome in siblings. Is there a genetic background? Eur J Pediatr. 2011;170(12):1563\u20138.","journal-title":"Eur J Pediatr"},{"issue":"3","key":"744_CR9","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1097\/INF.0b013e31818c8ea5","volume":"28","author":"IC Sampaio","year":"2009","unstructured":"Sampaio IC, Rodrigo MJ, Monteiro Marques JG. Two siblings with periodic fever, aphthous stomatitis, pharyngitis, adenitis (PFAPA) syndrome. Pediatr Infect Dis J. 2009;28(3):254\u20135.","journal-title":"Pediatr Infect Dis J"},{"issue":"10","key":"744_CR10","doi-asserted-by":"publisher","first-page":"1235","DOI":"10.1007\/s10067-009-1222-z","volume":"28","author":"PM Valenzuela","year":"2009","unstructured":"Valenzuela PM, Majerson D, Tapia JL, Talesnik E. Syndrome of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) in siblings. Clin Rheumatol. 2009;28(10):1235\u20137.","journal-title":"Clin Rheumatol"},{"issue":"1","key":"744_CR11","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.jpeds.2010.09.054","volume":"158","author":"M Adachi","year":"2011","unstructured":"Adachi M, Watanabe A, Nishiyama A, Oyazato Y, Kamioka I, Murase M, et al. Familial cases of periodic fever with aphthous stomatitis, pharyngitis, and cervical adenitis syndrome. J Pediatr. 2011;158(1):155\u20139.","journal-title":"J Pediatr"}],"container-title":["Pediatric Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12969-022-00744-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12969-022-00744-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12969-022-00744-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,5]],"date-time":"2022-10-05T05:03:20Z","timestamp":1664946200000},"score":1,"resource":{"primary":{"URL":"https:\/\/ped-rheum.biomedcentral.com\/articles\/10.1186\/s12969-022-00744-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,5]]},"references-count":11,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["744"],"URL":"https:\/\/doi.org\/10.1186\/s12969-022-00744-0","relation":{},"ISSN":["1546-0096"],"issn-type":[{"value":"1546-0096","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,5]]},"assertion":[{"value":"19 April 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 August 2022","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 September 2022","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 October 2022","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Per NYU Langone Health\u2019s Institutional Review Board at the NYU Grossman School of Medicine, anecdotal reports on a single patient seen in one\u2019s own practice and a comparison of these patients to existing reports in the literature does not require IRB approval.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approve and consent to participate"}},{"value":"Parental consent for publication was obtained.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"KD \u2013 Medical student, NYU Grossman School of Medicine, New York, NY.AS \u2013 Pediatric Allergist and Immunologist, Hassenfeld Children\u2019s Hospital, New York, NY.MA \u2013 Pediatric Otolaryngologist, Hassenfeld Children\u2019s Hospital, New York, NY.PK \u2013 Pediatric Rheumatologist, Hassenfeld Children\u2019s Hospital, New York, NY.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Author\u2019s information"}}],"article-number":"87"}}