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Gattorno, Marco; Hofer, Michael; Federici, Silvia; Vanoni, Federica; Bovis, Francesca; Aksentijevich, Ivona; Anton, Jordi; Arostegui, Juan Ignacio; Barron, Karyl; Ben-Cherit, Eldad; Brogan, Paul A; Cantarini, Luca; Ceccherini, Isabella; De Benedetti, Fabrizio; Dedeoglu, Fatma; Demirkaya, Erkan; Frenkel, Joost; Goldbach-Mansky, Raphaela; Gul, Ahmet; Hentgen, Veronique; Hoffman, Hal; Kallinich, Tilmann; Kone-Paut, Isabelle; Kuemmerle-Deschner, Jasmin; Lachmann, Helen J; Laxer, Ronald M; Livneh, Avi; Obici, Laura; Ozen, Seza; Rowczenio, Dorota; Russo, Ricardo; Shinar, Yael; Simon, Anna; Toplak, Nataša; Touitou, Isabelle; Uziel, Yosef; van Gijn, Marielle; Foell, Dirk; Garassino, Claudia; Kastner, Dan; Martini, Alberto; Sormani, Maria Pia; Ruperto, Nicolino
Annals of the rheumatic diseases, 08/2019, Volume: 78, Issue: 8Journal Article
Different diagnostic and classification criteria are available for hereditary recurrent fevers (HRF)-familial Mediterranean fever (FMF), tumour necrosis factor receptor-associated periodic fever syndrome (TRAPS), mevalonate kinase deficiency (MKD) and cryopyrin-associated periodic syndromes (CAPS)-and for the non-hereditary, periodic fever, aphthosis, pharyngitis and adenitis (PFAPA). We aimed to develop and validate new evidence-based classification criteria for HRF/PFAPA. Step 1: selection of clinical, laboratory and genetic candidate variables; step 2: classification of 360 random patients from the Eurofever Registry by a panel of 25 clinicians and 8 geneticists blinded to patients' diagnosis (consensus ≥80%); step 3: statistical analysis for the selection of the best candidate classification criteria; step 4: nominal group technique consensus conference with 33 panellists for the discussion and selection of the final classification criteria; step 5: cross-sectional validation of the novel criteria. The panellists achieved consensus to classify 281 of 360 (78%) patients (32 CAPS, 36 FMF, 56 MKD, 37 PFAPA, 39 TRAPS, 81 undefined recurrent fever). Consensus was reached for two sets of criteria for each HRF, one including genetic and clinical variables, the other with clinical variables only, plus new criteria for PFAPA. The four HRF criteria demonstrated sensitivity of 0.94-1 and specificity of 0.95-1; for PFAPA, criteria sensitivity and specificity were 0.97 and 0.93, respectively. Validation of these criteria in an independent data set of 1018 patients shows a high accuracy (from 0.81 to 0.98). Eurofever proposes a novel set of validated classification criteria for HRF and PFAPA with high sensitivity and specificity.
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