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Ann Rheum Dis. 2015 May;74(5):799-805. doi: 10.1136/annrheumdis-2014-206580. Epub 2015 Jan 30.

Evidence-based provisional clinical classification criteria for autoinflammatory periodic fevers.

Author information

1
UO Pediatria II-Reumatologia, Istituto Giannina Gaslini, Genova, Italy.
2
Unità di Biostatistica, DISSAL, University of Genoa, Genova, Italy.
3
Department of Pediatric Rheumatology, Hacettepe University, Ankara, Turkey.
4
National Amyloidosis Centre, University College London, London, UK.
5
National Pediatric Familial Mediterranean Fever Centre, Institute of Child and Adolescent Health, Yerevan, Armenia.
6
Center of Paediatric and Adolescent Rheumatology, UCL, London, UK.
7
Centre de référence national des maladies auto-inflammatoires, CEREMAI, rhumatologie pédiatrique, CHU Le Kremlin Bicêtre (APHP, University of Paris SUD), Paris, France.
8
Pediatric Rheumatology Unit of Western Switzerland, CHUV, University of Lausanne, Lausanne, and HUG, Geneva, Switzerland.
9
Rheumatology Unit, Policlinico le Scotte, University of Siena, Siena, Italy.
10
Division of Rheumatology, Department of Pediatric Medicine, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
11
Department of Pediatrics, Meir Medical Centre, Kfar Saba, Israel.
12
Department of Pediatrics, Università Cattolica Sacro Cuore, Roma, Italy.
13
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.
14
Gulhane Military Medical Faculty, FMF Arthritis Vasculitis and Orphan Disease Research Center (FAVOR), Ankara, Turkey.
15
Department of Pediatrics, Aarhus University Hospital, Pediatric Rheumatology Clinic, Aarhus, Denmark.
16
Dipartimento di Pediatria, Unità di Immunologia e Reumatologia Pediatrica, Clinica Pediatrica dell'Università di Brescia, Brescia, Italy.
17
Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Clinica Pediatrica II De Marchi, Milano, Italia.
18
Kinderklinik, Rheumatologie, Charite University Hospital Berlin, Berlin, Germany.
19
Dipartimento di Scienze Pediatriche e dell'Adolescenza, Clinica Pediatrica Universita' di Torino, Torino, Italy.
20
Department of Pediatrics, Rambam Medical Center, Haifa, Israel.
21
Dipartimento di Pediatria F Fede, Seconda Universita' degli Studi di Napoli, Napoli, Italia.
22
Universitatsklinik fur Kinderheilkunde und Jugendmedizin, Tübingen, Germany.
23
Department of General Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.
24
Ic Hastaliklari ABD, Romatoloji BD, Cerrahpasa Tip Fakultesi, Istanbul, Turkey.
25
Unit of autoinflammatory diseases, Montpellier, UM1, INSERM U844, Montpellier, France.
26
Department of Paediatrics, University Medical Center Utrecht, Utrecht, The Netherlands.
27
Istituto Giannina Gaslini, Pediatria II and Università degli Studi di Genova, Genova, Italy.

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.

KEYWORDS:

Familial Mediterranean Fever; Fever Syndromes; Inflammation

PMID:
25637003
DOI:
10.1136/annrheumdis-2014-206580
[Indexed for MEDLINE]

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