{
  "abstract": "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. 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. 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. 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.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.",
  "authors": [
    {
      "affiliations": [
        "Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy",
        "Rheumatology and Autoinflammatory Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy"
      ],
      "name": "Serena Palmeri"
    },
    {
      "affiliations": [
        "Department of Health Sciences, University of Genoa, Genoa, Italy"
      ],
      "name": "Marta Ponzano"
    },
    {
      "affiliations": [
        "Rheumatology and Autoinflammatory Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy"
      ],
      "name": "Giada Recchi"
    },
    {
      "affiliations": [
        "Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy",
        "Rheumatology and Autoinflammatory Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy"
      ],
      "name": "Chiara Conti"
    },
    {
      "affiliations": [
        "Rheumatology and Autoinflammatory Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy"
      ],
      "name": "Saverio La Bella"
    },
    {
      "affiliations": [
        "Rheumatology and Autoinflammatory Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy"
      ],
      "name": "Diana Sutera"
    },
    {
      "affiliations": [
        "Rheumatology and Autoinflammatory Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy"
      ],
      "name": "Marta Bustaffa"
    },
    {
      "affiliations": [
        "Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy",
        "Rheumatology and Autoinflammatory Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy"
      ],
      "name": "Caterina Matucci-Cerinic"
    },
    {
      "affiliations": [
        "Laboratory of Human Genetics, IRCCS Istituto Giannina Gaslini, IRCCS Istituto Giannina Gaslini, Genoa, Italy"
      ],
      "name": "Roberta Bertelli"
    },
    {
      "affiliations": [
        "Rheumatology and Autoinflammatory Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy"
      ],
      "name": "Federica Penco"
    },
    {
      "affiliations": [
        "Rheumatology and Autoinflammatory Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy"
      ],
      "name": "Ignazia Prigione"
    },
    {
      "affiliations": [
        "Rheumatology and Autoinflammatory Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy"
      ],
      "name": "Riccardo Papa"
    },
    {
      "affiliations": [
        "Laboratory of Genetics and Genomics of Rare Diseases, IRCCS Istituto Giannina Gaslini, Genoa, Italy"
      ],
      "name": "Isabella Ceccherini"
    },
    {
      "affiliations": [
        "Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy",
        "Rheumatology and Autoinflammatory Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy"
      ],
      "name": "Stefano Volpi"
    },
    {
      "affiliations": [
        "Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy",
        "Rheumatology and Autoinflammatory Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy"
      ],
      "name": "Roberta Caorsi"
    },
    {
      "affiliations": [
        "Rheumatology and Autoinflammatory Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy"
      ],
      "name": "Marco Gattorno"
    }
  ],
  "title": "Predictive factors for therapeutic response and cluster analysis in syndrome of undifferentiated recurrent fever (SURF)",
  "uid": "7654d682-f9e0-51b4-bda6-8b166a46f809"
}