{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T17:36:27Z","timestamp":1788456987768,"version":"build-2803163510"},"reference-count":18,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T00:00:00Z","timestamp":1770854400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012151","name":"Sanming Project of Medicine in Shenzen Municipality","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012151","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis syndrome (PFAPA) is characterized by recurrent febrile episodes associated with one or more of the symptoms described by the acronym, and easily misdiagnosed as other infectious diseases, especially tonsillitis. We aimed to describe the clinical, laboratory parameters and cytokine profiles in patients with PFAPA and to explore indicators to distinguish children with PFAPA from bacterial infection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients with PFAPA and bacterial infection, who had cytokine panels performed by Flowcytomix technique during the febrile episodes (prior to any treatments), were retrospectively enrolled from January 2020 to June 2024 in Shenzhen Children\u2019s Hospital. Clinical data were collected from inpatient medical records. Serum levels of cytokines and other laboratory parameters were compared between patients with PFAPA and those with identified bacterial infection. Multivariate regression analysis and a receiver operating characteristic (ROC) curve analysis were performed to construct a diagnostic model to assess the potential role of serum cytokines and laboratory parameters in the diagnosis of PFAPA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      67 patients with PFAPA and 160 patients with identified bacterial infection were included in this study. The level of serum IFN-\u03b3, and the IFN-\u03b3\/IL-6 ratio in PFAPA patients were significantly higher than those in identified bacterial infection (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.0001). The cutoff value of serum IFN-\u03b3\/IL-6 ratio for differentiating PFAPA from bacterial infection was\u2009&amp;gt; 0.43, and the area under the receiver operating characteristic curve (AUC) was 0.79, with a sensitivity of 70.15% and a specificity of 71.88%. A diagnosis model combined IL-10, platelet and IFN-\u03b3\/IL-6 ratio was built, and the AUC was 0.95, with the sensitivity and specificity as 90.3% and 89.6%, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The IFN-\u03b3\/IL-6 ratio during febrile episodes may be useful in the early diagnosis of PFAPA by differentiating this disease from bacterial infection. The combined model based on IFN-\u03b3\/IL-6, IL-10, and PLT optimizes the diagnosis efficiency.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1683221","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T06:50:45Z","timestamp":1770879045000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Cytokine profiles and laboratory parameters as indicators to distinguish children with PFAPA and bacterial infection"],"prefix":"10.3389","volume":"17","author":[{"given":"Xiaona","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingyan","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.wjorl.2021.05.004","article-title":"Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome: A review","volume":"7","author":"Wang","year":"2021","journal-title":"World J Otorhinolaryngol Head Neck Surg"},{"key":"B2","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1186\/s12969-022-00737-z","article-title":"Epidemiology and clinical features of PFAPA: a retrospective cohort study of 336 patients in western Sweden","volume":"20","author":"Rydenman","year":"2022","journal-title":"Pediatr Rheumatol Online J"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1111\/apa.17269","article-title":"Antibiotic prescriptions to children with periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis","volume":"113","author":"Rydenman","year":"2024","journal-title":"Acta Paediatr"},{"key":"B4","doi-asserted-by":"publisher","first-page":"38","DOI":"10.2152\/jmi.68.38","article-title":"Differential cytokine profiles in pediatric patients with PFAPA syndrome and recurrent tonsillitis","volume":"68","author":"Nakano","year":"2021","journal-title":"J Med Invest"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2019-215048","article-title":"Classification criteria for autoinflammatory recurrent fevers","volume":"78","author":"Gattorno","year":"2019","journal-title":"Ann Rheum Dis Aug"},{"key":"B6","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1186\/s12969-020-00424-x","article-title":"Consensus treatment plans for periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome (PFAPA): a framework to evaluate treatment responses from the childhood arthritis and rheumatology research alliance (CARRA) PFAPA work group","volume":"18","author":"Amarilyo","year":"2020","journal-title":"Pediatr Rheumatol Online J"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.958473","article-title":"Challenges in the diagnosis of periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome in developing countries-A decade of experience from North India","volume":"13","author":"Banday","year":"2022","journal-title":"Front Immunol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/ket460","article-title":"International periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis syndrome cohort: description of distinct phenotypes in 301 patients","volume":"53","author":"Hofer","year":"2014","journal-title":"Rheumatol (Oxford). 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