{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:20:09Z","timestamp":1782951609384,"version":"3.54.5"},"reference-count":19,"publisher":"BMJ","issue":"3","license":[{"start":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T00:00:00Z","timestamp":1754870400000},"content-version":"unspecified","delay-in-days":41,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2025,7,23]]},"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:p>Introduction: Syndrome of undifferentiated recurrent fever (SURF) refers to a group of recurrent fevers without a clear monogenic cause. Clinical spectrum, treatment response predictors and management strategies remain unclear. <\/jats:p>\n               <jats:p>Objective: This study aims to longitudinally analyse a homogeneously selected cohort of 101 SURF patients, to identify factors associated with colchicine resistance and to evaluate the efficacy of interleukin-1 (IL-1) inhibitors. <\/jats:p>\n               <jats:p>Methods: Patients were enrolled in the Eurofever Registry, carefully excluding those with periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA); familial Mediterranean fever and other known monogenic recurrent fevers. Demographic, clinical and treatment data were analysed to identify predictors of colchicine resistance and define subgroups through cluster analysis. <\/jats:p>\n               <jats:p>Results: Common symptoms included fever, arthralgia, abdominal pain and myalgia, with PFAPA-like features (lymphadenopathy, tonsillitis, oral aphthae) observed in one-third of cases, sporadically. Colchicine efficacy, assessed in 77 patients, revealed complete response in the majority of patients (61%). Univariable analysis identified PFAPA-like features, including aphthous stomatitis (p=0.001), cervical lymphadenopathy (p=0.012) and exudative tonsillitis (p=0.004), as associated with colchicine resistance. Multivariable analysis confirmed aphthous stomatitis as an independent predictor of resistance (p=0.014). Tonsillectomy was ineffective. IL-1 inhibitors (anakinra, canakinumab) were beneficial in refractory cases. Cluster analysis revealed three distinct subgroups with varying symptoms and colchicine responses.<\/jats:p>\n               <jats:p>Conclusions: These findings provide new insights into SURF, identifying predictors of colchicine resistance and supporting the efficacy of IL-1 blockade. Cluster analysis suggests the heterogeneity within SURF, reinforcing the need for refined diagnostic criteria and personalised treatment strategies.<\/jats:p>","DOI":"10.1136\/rmdopen-2025-005874","type":"journal-article","created":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T02:36:01Z","timestamp":1754879761000},"page":"e005874","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Predictive factors for therapeutic response and cluster analysis in syndrome of undifferentiated recurrent fever (SURF)"],"prefix":"10.1136","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7670-6825","authenticated-orcid":false,"given":"Serena","family":"Palmeri","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy"},{"name":"Rheumatology and Autoinflammatory Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Ponzano","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University of Genoa, Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giada","family":"Recchi","sequence":"additional","affiliation":[{"name":"Rheumatology and Autoinflammatory Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Conti","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy"},{"name":"Rheumatology and Autoinflammatory Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1244-0789","authenticated-orcid":false,"given":"Saverio","family":"La Bella","sequence":"additional","affiliation":[{"name":"Rheumatology and Autoinflammatory Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Sutera","sequence":"additional","affiliation":[{"name":"Rheumatology and Autoinflammatory Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Bustaffa","sequence":"additional","affiliation":[{"name":"Rheumatology and Autoinflammatory Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Matucci-Cerinic","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy"},{"name":"Rheumatology and Autoinflammatory Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Bertelli","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics, IRCCS Istituto Giannina Gaslini, IRCCS Istituto Giannina Gaslini, Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Penco","sequence":"additional","affiliation":[{"name":"Rheumatology and Autoinflammatory Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignazia","family":"Prigione","sequence":"additional","affiliation":[{"name":"Rheumatology and Autoinflammatory Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9626-5470","authenticated-orcid":false,"given":"Riccardo","family":"Papa","sequence":"additional","affiliation":[{"name":"Rheumatology and Autoinflammatory Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella","family":"Ceccherini","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics and Genomics of Rare Diseases, IRCCS Istituto Giannina Gaslini, Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7129-868X","authenticated-orcid":false,"given":"Stefano","family":"Volpi","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy"},{"name":"Rheumatology and Autoinflammatory Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0131-7846","authenticated-orcid":false,"given":"Roberta","family":"Caorsi","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy"},{"name":"Rheumatology and Autoinflammatory Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0704-1916","authenticated-orcid":false,"given":"Marco","family":"Gattorno","sequence":"additional","affiliation":[{"name":"Rheumatology and Autoinflammatory Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, 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criteria (Eurofever\/PRINTO) in a real-life cohort","volume":"42","author":"\u00c7a\u011flayan","year":"2023","journal-title":"Clin Rheumatol"},{"key":"2025090312393450000_11.3.e005874.7","doi-asserted-by":"crossref","first-page":"152024","DOI":"10.1016\/j.semarthrit.2022.152024","article-title":"Clinical characterization, long-term follow-up, and response to treatment of patients with syndrome of undifferentiated recurrent fever (SURF)","volume":"55","author":"Sutera","year":"2022","journal-title":"Semin Arthritis Rheum"},{"key":"2025090312393450000_11.3.e005874.8","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1186\/s12969-024-00987-z","article-title":"Unravelling the clinical heterogeneity of undefined recurrent fever over time in the European registries on Autoinflammation","volume":"22","author":"Vyzhga","year":"2024","journal-title":"Pediatr Rheumatol"},{"key":"2025090312393450000_11.3.e005874.9","doi-asserted-by":"crossref","first-page":"103520","DOI":"10.1016\/j.autrev.2024.103520","article-title":"Disease phenotypes in adult patients with suspected undifferentiated autoinflammatory diseases and PFAPA syndrome: Clinical and therapeutic implications","volume":"23","author":"G\u00f3mez-Caverzaschi","year":"2024","journal-title":"Autoimmun Rev"},{"key":"2025090312393450000_11.3.e005874.10","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1002\/art.43065","article-title":"Clinical, Immunologic, and Genetic Characteristics in Patients With Syndrome of Undifferentiated Recurrent Fevers","volume":"77","author":"Macaraeg","year":"2025","journal-title":"Arthritis Rheumatol"},{"key":"2025090312393450000_11.3.e005874.11","doi-asserted-by":"crossref","DOI":"10.1007\/s10875-023-01649-7","article-title":"Pyrin Inflammasome Activation Defines Colchicine-Responsive SURF Patients from FMF and Other Recurrent 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