Format

Send to

Choose Destination
Ann Rheum Dis. 2019 Aug;78(8):1025-1032. doi: 10.1136/annrheumdis-2019-215048. Epub 2019 Apr 24.

Classification criteria for autoinflammatory recurrent fevers.

Author information

1
UOSD Centro Malattie Autoinfiammatorie e Immunodeficienze, IRCCS Istituto Giannina Gaslini, Genoa, Italy marcogattorno@gaslini.org.
2
Department of Paediatrics, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
3
University Hospital of Geneva, Geneva, Switzerland.
4
Clinica Pediatrica e Reumatologia, IRCCS Istituto Giannina Gaslini, Genova, Italy.
5
Department of Pediatrics, Ospedale Regionale di Bellinzona e Valli, Bellinzona, Switzerland.
6
Department of Health Sciences (DISSAL), University of Genova, Genova, Italy.
7
Inflammatory Disease Section, National Human Genome Research Institute, Bethesda, Maryland, USA.
8
Hospital Sant Joan de Déu, Universitat de Barcelona, Barcelona, Catalunya, Spain.
9
Immunology Department, CDB, Hospital Clínic/IDIBAPS, Barcelona, Spain.
10
Division of Intramural Research, NIH-NIAID, Bethesda, Maryland, USA.
11
Rheumatology Unit, Hadassah-Hebrew University Hospital, Ein Kerem, Jerusalem, Israel.
12
Institute of Child Health, University College London, London, UK.
13
Department of Medical Sciences, University of Siena, Siena, Italy.
14
Genetica Medica, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
15
Division of Rheumatology, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy.
16
Pediatric Rheumatology, Harvard University Children's Hospital, Boston, Massachusetts, USA.
17
Unit of Pediatric Rheumatology, Western University Children's Hospital, London, Ontario, Canada.
18
Department of Pediatrics, Wilhelmina Kinderziekenhuis, Utrecht, The Netherlands.
19
Translational Autoinflammatory Disease Studies Unit, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA.
20
Division of Rheumatology, Istanbul University, Istanbul Faculty of Medicine, Istanbul, Turkey.
21
National Referral Centre of Auto-Inflammatory Diseases and Inflammatory Amyloidosis, CEREMAIA, Versailles Hospital, Le Chesnay (Paris), France.
22
Department of Pediatrics, University of California at San Diego, San Diego, California, USA.
23
Pediatric Pneumology and Immunology, Charite University Medicine Berlin, Berlin, Germany.
24
Department of Paediatric Rheumatology and CEREMAI, Hôpital de Bicêtre, National Reference Centre for Auto-Inflammatory Diseases, Le Kremlin-Bicêtre, Paris, France.
25
Department of Pediatrics, University Hospital Tuebingen, Tuebingen, Germany.
26
Division of Medicine, UCL Medical School, Royal Free Campus, National Amyloidosis Centre, London, UK.
27
Unit of Pediatric Rheumatology, Hospital for Sick Children, Toronto, Ontario, Canada.
28
Sheba Medical Center, Heller Institute, Ramat Gan, Israel.
29
Fondazione IRCCS Policlinico San Matteo, Centro per lo Studio e la Cura delle Amiloidosi Sistemiche, Pavia, Italy.
30
Department of Pediatrics, Hacettepe University, Ankara, Turkey.
31
Servicio de Inmunología/Reumatología, Hospital de Pediatria Juan P Garrahan, Buenos Aires, Argentina.
32
Heller Institute of Medical Research, Sheba Medical Center, Ramat Gan, Israel.
33
Department of General Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.
34
Department of Allergology, Rheumatology and Clinical Immunology, University Children's Hospital, Ljubljana, Slovenia.
35
National Referral Centre of Auto-Inflammatory Diseases and Inflammatory Amyloidosis, CEREMAIA, Centre Hospitalier Regional Universitaire de Montpellier, Montpellier, France.
36
Department of Pediatrics, Meir Medical Centre, Kfar Saba, Israel.
37
Tel Aviv University, Tel Aviv, Israel.
38
Department of Genetics, University Medical Centre Utrecht, Utrecht, The Netherlands.
39
Department of Pediatrics, Universitätsklinikum Münster, Münster, Germany.
40
IRCCS Istituto Giannina Gaslini, Genoa, Italy.
41
Ospedale Policlinico San Martino IRCCS, Genoa, Italy.
42
Clinica Pediatrica e Reumatologia, PRINTO, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
#
Contributed equally

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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).

CONCLUSION:

Eurofever proposes a novel set of validated classification criteria for HRF and PFAPA with high sensitivity and specificity.

KEYWORDS:

CAPS; PFAPA; TRAPS; classification criteria; inherited periodic fevers; mevalonate kinase deficiency

Conflict of interest statement

Competing interests: None declared.

Publication type

Publication type

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center