{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T04:13:34Z","timestamp":1788149614160,"version":"build-2803163510"},"reference-count":79,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:00:00Z","timestamp":1787961600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Background\/Objectives: Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is the most frequently encountered periodic fever syndrome in pediatric populations. It is characterized by recurrent, stereotyped episodes of fever accompanied by pharyngitis, cervical lymphadenopathy, and aphthous stomatitis, sometimes with other additional nonspecific symptoms. Episodes usually last 3\u20137 days and recur at regular intervals of approximately 2\u20138 weeks. The etiopathogenesis of PFAPA remains incompletely understood. Accumulating evidence supports a central role of immune dysregulation with multiple genetic variants that contribute to disease susceptibility. Diagnosis is primarily based on clinical evaluation, although targeted genetic testing may be considered in selected cases particularly when overlapping with other monogenic autoinflammatory disorders. Management of PFAPA aims to decrease the frequency and intensity of febrile episodes. Acute flares are managed with antipyretics, corticosteroids, or, in selected cases, anti-interleukin-1 (IL-1) therapy, while preventive strategies include colchicine, cimetidine, or tonsillectomy. Adjunctive approaches such as vitamin D supplementation, probiotics, and other immunomodulatory interventions have also been investigated. This updated review summarizes current insights into the pathogenesis and therapeutic approaches of PFAPA. Methods: This narrative review was conducted using PubMed, and Scopus to identify English-language publications from 2010 to 2026 addressing PFAPA. Conclusions: Pediatricians should consider PFAPA in children with recurrent fevers and oropharyngeal symptoms, especially when standard treatments fail, to ensure proper management and avoid unnecessary antibiotic use.<\/jats:p>","DOI":"10.3390\/children13091167","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T02:08:58Z","timestamp":1788142138000},"page":"1167","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis (PFAPA) Syndrome: An Updated Review with Current Insights into Pathogenesis and Therapeutic Strategies"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1639-0723","authenticated-orcid":false,"given":"Abobakr","family":"Abdelgalil","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine, Cairo University, Cairo 12613, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1220-7215","authenticated-orcid":false,"given":"Doaa Mosad","family":"Mosa","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Rehabilitation, and Physical Medicine, Faculty of Medicine, Mansoura University Hospital, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghaidaa Faisal","family":"Albaz","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, King Abdulaziz University Hospital, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konooz Fahad","family":"Faisal","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, King Abdulaziz University Hospital, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7047-076X","authenticated-orcid":false,"given":"Ali","family":"Sobh","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine, Mansoura University Children\u2019s Hospital, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9534-6076","authenticated-orcid":false,"given":"Mohamed Hesham","family":"Mashali","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine, Cairo University, Cairo 12613, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1111\/apa.12069","article-title":"Incidence, clinical characteristics and outcome in Norwegian children with periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis syndrome: A population-based study","volume":"102","author":"Kristoffersen","year":"2013","journal-title":"Acta Paediatr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4337","DOI":"10.1007\/s00431-024-05703-3","article-title":"Exploring factors for predicting colchicine responsiveness in children with PFAPA","volume":"183","author":"Kaya","year":"2024","journal-title":"Eur. 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