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Ann Rheum Dis. 2014 Dec;73(12):2160-7. doi: 10.1136/annrheumdis-2013-204184. Epub 2013 Aug 21.

The phenotype of TNF receptor-associated autoinflammatory syndrome (TRAPS) at presentation: a series of 158 cases from the Eurofever/EUROTRAPS international registry.

Author information

1
National Amyloidosis Centre, Royal Free Campus, University College Medical School, London, UK.
2
Pediatria II, Istituto Giannina Gaslini, Genova, Italy.
3
Pediatric Pneumology and Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
4
Biotechnology Research Laboratories, Amyloid Centre, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
5
Unit of Autoinflammatory Diseases, CHU Montpellier, UM1, INSERM U844, Montpellier, France.
6
Rheumatology Unit, Policlinico le Scotte, University of Siena, Siena, Italy.
7
Department of Paediatrics, University Medical Center Utrecht, Utrecht, Netherlands.
8
Hospital Sant Joan de Déu, Universitat de Barcelona, Esplugues (Barcelona), Spain.
9
Centre de référence national des maladies auto-inflammatoires, CEREMAI, rhumatologie pediatrique, CHU Le Kremlin Bicetre (University of Paris SUD, APHP), Le kremlin Bicetre (Paris), France.
10
Dipartimento di Pediatria, Unità di Immunologia e Reumatologia Pediatrica, Clinica Pediatrica dell'Università di Brescia, Spedali Civili, Brescia, Italy.
11
Unité d'Immunologie, Hématologie et Rhumatologie Pediatrique, Université Paris-Descartes, Hôpital Necker-Enfants Malades, Centre de référence national pour les Arthrites Juveniles, APHP, IHU Imagine, Paris, France.
12
Reumatologia, Ospedale Pediatrico Bambin Gesù, Roma, Italy.
13
Service de pediatrie generale, Hopital A Mignot, Centre de référence national des maladies auto-inflammatoires, Le Chesnay (Paris), France.
14
Unidad De Reumatologia Pediatrica, Hospital Universitario La Paz, Madrid, Spain.
15
Reumatologia, Hospital Valle de Hebron, Barcelona, Spain.
16
Department of Allergology, Rheumatology and Clinical Immunology, University Children's Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia.
17
Kinderkrankenhaus St. Marien, Landshut, Germany.
18
Department of Pediatric Nephrology and Rheumatology, Hacettepe University, Ankara, Turkey.
19
Dept di Pediatria, Ospedale A Meyer, Firenze, Italy.
20
Rheumatology & Immunology, Dr von Hauner Children's Hospital, Ludwig-Maximilians-University Munich, Munich, Germany.
21
Center of Paediatric and Adolescent Rheumatology-UCL, Institute of Child Health and Great Ormond Street Hospital NHS Foundation Trust, London, UK.
22
Istituto Giannina Gaslini, Pediatria II and Università degli Studi di Genova, Genova, Italy.

Abstract

OBJECTIVE:

To evaluate the genetic findings, demographic features and clinical presentation of tumour necrosis factor receptor-associated autoinflammatory syndrome (TRAPS) in patients from the Eurofever/EUROTRAPS international registry.

METHODS:

A web-based registry collected retrospective data on patients with TNFRSF1A sequence variants and inflammatory symptoms. Participating hospitals included paediatric rheumatology centres and adult centres with a specific interest in autoinflammatory diseases. Cases were independently validated by experts in the disease.

RESULTS:

Complete information on 158 validated patients was available. The most common TNFRSF1A variant was R92Q (34% of cases), followed by T50M (10%). Cysteine residues were disrupted in 27% of cases, accounting for 39% of sequence variants. A family history was present in 19% of patients with R92Q and 64% of those with other variants. The median age at which symptoms began was 4.3 years but 9.1% of patients presented after 30 years of age. Attacks were recurrent in 88% and the commonest features associated with the pathogenic variants were fever (88%), limb pain (85%), abdominal pain (74%), rash (63%) and eye manifestations (45%). Disease associated with R92Q presented slightly later at a median of 5.7 years with significantly less rash or eye signs and more headaches. Children were more likely than adults to present with lymphadenopathy, periorbital oedema and abdominal pains. AA amyloidosis has developed in 16 (10%) patients at a median age of 43 years.

CONCLUSIONS:

In this, the largest reported case series to date, the genetic heterogeneity of TRAPS is accompanied by a variable phenotype at presentation. Patients had a median 70 symptomatic days a year, with fever, limb and abdominal pain and rash the commonest symptoms. Overall, there is little evidence of a significant effect of age or genotype on disease features at presentation.

KEYWORDS:

Amyloidosis; Fever Syndromes; Inflammation

PMID:
23965844
PMCID:
PMC4251160
DOI:
10.1136/annrheumdis-2013-204184
[Indexed for MEDLINE]
Free PMC Article

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