{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T17:36:26Z","timestamp":1788456986334,"version":"build-2803163510"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>This study aimed to define the etiologies and clinical features of pediatric Fever of unknown origin (FUO), focusing on periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) and the syndrome of undifferentiated recurrent fever (SURF), to guide clinical management.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively analyzed pediatric FUO cases at Fudan University Children\u2019s Hospital (2014\u20132024.6), assessing clinical characteristics, immune phenotypes, laboratory parameters, and treatment responses with at least one-year follow-up.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 442 children (64.7% male), the mean age at onset was 3.42years. Infectious diseases accounted for 20.6%, mainly EBV infection. Autoinflammatory diseases were predominant (n=291), including PFAPA (n=135), and SURF (n=72). PFAPA presented earlier (mean age, 2.25 years) with regular episodes (median interval, every 25 days). SURF showed variable intervals (range, 7\u2013120 days) and was classified as periodic (n = 38) or non-periodic (n = 34) subtypes. Isolated fever occurred in 21% of SURF periodic, whereas SURF non-periodic more often involved systemic symptoms (fatigue, headache, urticaria, and gastrointestinal complaints). During attacks, both PFAPA and SURF showed elevated CRP\/ESR with neutrophilia\/monocytosis and lymphopenia. Corticosteroids aborted PFAPA episodes in 90.9% but shortened afebrile intervals in 31.8%; tonsillectomy resulted in a 90.5% complete remission rate. Among non-surgical treatments, immunomodulation proved beneficial, with OM-85 yielding 45.0% complete remission and 65.0% overall clinical benefit. SURF treatment responses were heterogeneous: SURF periodic responded better to OM-85, whereas SURF non-periodic showed partial responses to colchicine or biologics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Autoinflammatory diseases, particularly PFAPA and SURF, were the leading causes of pediatric FUO, offering insights for management and treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1791904","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T06:34:16Z","timestamp":1774506856000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The etiological spectrum of pediatric FUO and clinical management of PFAPA\/SURF: a ten-year retrospective study"],"prefix":"10.3389","volume":"17","author":[{"given":"Chenchen","family":"Guan","sequence":"first","affiliation":[{"name":"Department of Clinical Immunology and Allergy, Children\u2019s Hospital of Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinhua","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology and Allergy, Children\u2019s Hospital of Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinqiao","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology and Allergy, Children\u2019s Hospital of Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Ying","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology and Allergy, Children\u2019s Hospital of Fudan 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Children\u2019s Hospital of Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luyao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology and Allergy, Children\u2019s Hospital of Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bijun","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology and Allergy, Children\u2019s Hospital of Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjie","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology and Allergy, Children\u2019s Hospital of Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaochuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of 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