title: Evidence-based provisional clinical classification criteria for autoinflammatory periodic fevers.
abstract: The objective of this work was to develop and validate a set of clinical criteria for the classification of patients affected by periodic fevers. Patients with inherited periodic fevers (familial Mediterranean fever (FMF); mevalonate kinase deficiency (MKD); tumour necrosis factor receptor-associated periodic fever syndrome (TRAPS); cryopyrin-associated periodic syndromes (CAPS)) enrolled in the Eurofever Registry up until March 2013 were evaluated. Patients with periodic fever, aphthosis, pharyngitis and adenitis (PFAPA) syndrome were used as negative controls. For each genetic disease, patients were considered to be 'gold standard' on the basis of the presence of a confirmatory genetic analysis. Clinical criteria were formulated on the basis of univariate and multivariate analysis in an initial group of patients (training set) and validated in an independent set of patients (validation set). A total of 1215 consecutive patients with periodic fevers were identified, and 518 gold standard patients (291 FMF, 74 MKD, 86 TRAPS, 67 CAPS) and 199 patients with PFAPA as disease controls were evaluated. The univariate and multivariate analyses identified a number of clinical variables that correlated independently with each disease, and four provisional classification scores were created. Cut-off values of the classification scores were chosen using receiver operating characteristic curve analysis as those giving the highest sensitivity and specificity. The classification scores were then tested in an independent set of patients (validation set) with an area under the curve of 0.98 for FMF, 0.95 for TRAPS, 0.96 for MKD, and 0.99 for CAPS. In conclusion, evidence-based provisional clinical criteria with high sensitivity and specificity for the clinical classification of patients with inherited periodic fevers have been developed.
authors: UO Pediatria II-Reumatologia, Istituto Giannina Gaslini, Genova, Italy.
authors: Silvia
authors: S
authors: Federici
authors: Unità di Biostatistica, DISSAL, University of Genoa, Genova, Italy.
authors: Maria Pia
authors: MP
authors: Sormani
authors: Department of Pediatric Rheumatology, Hacettepe University, Ankara, Turkey.
authors: Seza
authors: S
authors: Ozen
authors: National Amyloidosis Centre, University College London, London, UK.
authors: Helen J
authors: HJ
authors: Lachmann
authors: National Pediatric Familial Mediterranean Fever Centre, Institute of Child and Adolescent Health, Yerevan, Armenia.
authors: Gayane
authors: G
authors: Amaryan
authors: Center of Paediatric and Adolescent Rheumatology, UCL, London, UK.
authors: Patricia
authors: P
authors: Woo
authors: Centre de référence national des maladies auto-inflammatoires, CEREMAI, rhumatologie pédiatrique, CHU Le Kremlin Bicêtre (APHP, University of Paris SUD), Paris, France.
authors: Isabelle
authors: I
authors: Koné-Paut
authors: Pediatric Rheumatology Unit of Western Switzerland, CHUV, University of Lausanne, Lausanne, and HUG, Geneva, Switzerland.
authors: Natacha
authors: N
authors: Dewarrat
authors: Rheumatology Unit, Policlinico le Scotte, University of Siena, Siena, Italy.
authors: Luca
authors: L
authors: Cantarini
authors: Division of Rheumatology, Department of Pediatric Medicine, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors: Antonella
authors: A
authors: Insalaco
authors: Department of Pediatrics, Meir Medical Centre, Kfar Saba, Israel.
authors: Yosef
authors: Y
authors: Uziel
authors: Department of Pediatrics, Università Cattolica Sacro Cuore, Roma, Italy.
authors: Donato
authors: D
authors: Rigante
authors: Université Paris-Descartes, Hôpital Necker-Enfants Malades, Centre de référence national pour les Arthrites Juveniles, Unité d'Immunologie, Hématologie et Rhumatologie Pédiatrique, Université Descartes, Sorbonne Paris Cité, Institut IMAGINE, Paris, France.
authors: Pierre
authors: P
authors: Quartier
authors: Gulhane Military Medical Faculty, FMF Arthritis Vasculitis and Orphan Disease Research Center (FAVOR), Ankara, Turkey.
authors: Erkan
authors: E
authors: Demirkaya
authors: Department of Pediatrics, Aarhus University Hospital, Pediatric Rheumatology Clinic, Aarhus, Denmark.
authors: Troels
authors: T
authors: Herlin
authors: Dipartimento di Pediatria, Unità di Immunologia e Reumatologia Pediatrica, Clinica Pediatrica dell'Università di Brescia, Brescia, Italy.
authors: Antonella
authors: A
authors: Meini
authors: Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Clinica Pediatrica II De Marchi, Milano, Italia.
authors: Giovanna
authors: G
authors: Fabio
authors: Kinderklinik, Rheumatologie, Charite University Hospital Berlin, Berlin, Germany.
authors: Tilmann
authors: T
authors: Kallinich
authors: Dipartimento di Scienze Pediatriche e dell'Adolescenza, Clinica Pediatrica Universita' di Torino, Torino, Italy.
authors: Silvana
authors: S
authors: Martino
authors: Department of Pediatrics, Rambam Medical Center, Haifa, Israel.
authors: Aviel Yonatan
authors: AY
authors: Butbul
authors: Dipartimento di Pediatria F Fede, Seconda Universita' degli Studi di Napoli, Napoli, Italia.
authors: Alma
authors: A
authors: Olivieri
authors: Universitatsklinik fur Kinderheilkunde und Jugendmedizin, Tübingen, Germany.
authors: Jasmin
authors: J
authors: Kuemmerle-Deschner
authors: Université Paris-Descartes, Hôpital Necker-Enfants Malades, Centre de référence national pour les Arthrites Juveniles, Unité d'Immunologie, Hématologie et Rhumatologie Pédiatrique, Université Descartes, Sorbonne Paris Cité, Institut IMAGINE, Paris, France.
authors: Benedicte
authors: B
authors: Neven
authors: Department of General Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors: Anna
authors: A
authors: Simon
authors: Ic Hastaliklari ABD, Romatoloji BD, Cerrahpasa Tip Fakultesi, Istanbul, Turkey.
authors: Huri
authors: H
authors: Ozdogan
authors: Unit of autoinflammatory diseases, Montpellier, UM1, INSERM U844, Montpellier, France.
authors: Isabelle
authors: I
authors: Touitou
authors: Department of Paediatrics, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Joost
authors: J
authors: Frenkel
authors: Pediatric Rheumatology Unit of Western Switzerland, CHUV, University of Lausanne, Lausanne, and HUG, Geneva, Switzerland.
authors: Michael
authors: M
authors: Hofer
authors: Istituto Giannina Gaslini, Pediatria II and Università degli Studi di Genova, Genova, Italy.
authors: Alberto
authors: A
authors: Martini
authors: UO Pediatria II-Reumatologia, Istituto Giannina Gaslini, Genova, Italy.
authors: Nicolino
authors: N
authors: Ruperto
authors: UO Pediatria II-Reumatologia, Istituto Giannina Gaslini, Genova, Italy.
authors: Marco
authors: M
authors: Gattorno
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D056587:Cryopyrin-Associated Periodic Syndromes / Q000145:classification / Q000175:diagnosis; D019317:Evidence-Based Medicine; D010505:Familial Mediterranean Fever / Q000145:classification / Q000175:diagnosis; D005260:Female; D005334:Fever; D056660:Hereditary Autoinflammatory Diseases / Q000145:classification / Q000175:diagnosis*; D006801:Humans; D007223:Infant; D008297:Male; D054078:Mevalonate Kinase Deficiency / Q000145:classification / Q000175:diagnosis; D008875:Middle Aged; D012372:ROC Curve; D012042:Registries; D012680:Sensitivity and Specificity; D055815:Young Adult
keywords: Familial Mediterranean Fever; Fever Syndromes; Inflammation