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Extended report
The phenotype of TNF receptor-associated autoinflammatory syndrome (TRAPS) at presentation: a series of 158 cases from the Eurofever/EUROTRAPS international registry
  1. H J Lachmann1,
  2. R Papa2,
  3. K Gerhold3,
  4. L Obici4,
  5. I Touitou5,
  6. L Cantarini6,
  7. J Frenkel7,
  8. J Anton8,
  9. I Kone-Paut9,
  10. M Cattalini10,
  11. B Bader-Meunier11,
  12. A Insalaco12,
  13. V Hentgen13,
  14. R Merino14,
  15. C Modesto15,
  16. N Toplak16,
  17. R Berendes17,
  18. S Ozen18,
  19. R Cimaz19,
  20. A Jansson20,
  21. P A Brogan21,
  22. P N Hawkins1,
  23. N Ruperto2,
  24. A Martini22,
  25. P Woo21,
  26. M Gattorno2
  27. for the Paediatric Rheumatology International Trials Organisation (PRINTO), the EUROTRAPS and the Eurofever Project
  1. 1National Amyloidosis Centre, Royal Free Campus, University College Medical School, London, UK
  2. 2Pediatria II, Istituto Giannina Gaslini, Genova, Italy
  3. 3Pediatric Pneumology and Immunology, Charité—Universitätsmedizin Berlin, Berlin, Germany
  4. 4Biotechnology Research Laboratories, Amyloid Centre, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
  5. 5Unit of Autoinflammatory Diseases, CHU Montpellier, UM1, INSERM U844, Montpellier, France
  6. 6Rheumatology Unit, Policlinico le Scotte, University of Siena, Siena, Italy
  7. 7Department of Paediatrics, University Medical Center Utrecht, Utrecht, Netherlands
  8. 8Hospital Sant Joan de Déu, Universitat de Barcelona, Esplugues (Barcelona), Spain
  9. 9Centre 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. 10Dipartimento di Pediatria, Unità di Immunologia e Reumatologia Pediatrica, Clinica Pediatrica dell'Università di Brescia, Spedali Civili, Brescia, Italy
  11. 11Unité 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. 12Reumatologia, Ospedale Pediatrico Bambin Gesù, Roma, Italy
  13. 13Service de pediatrie generale, Hopital A Mignot, Centre de référence national des maladies auto-inflammatoires, Le Chesnay (Paris), France
  14. 14Unidad De Reumatologia Pediatrica, Hospital Universitario La Paz, Madrid, Spain
  15. 15Reumatologia, Hospital Valle de Hebron, Barcelona, Spain
  16. 16Department of Allergology, Rheumatology and Clinical Immunology, University Children's Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia
  17. 17Kinderkrankenhaus St. Marien, Landshut, Germany
  18. 18Department of Pediatric Nephrology and Rheumatology, Hacettepe University, Ankara, Turkey
  19. 19Dept di Pediatria, Ospedale A Meyer, Firenze, Italy
  20. 20Rheumatology & Immunology, Dr von Hauner Children's Hospital, Ludwig-Maximilians-University Munich, Munich, Germany
  21. 21Center of Paediatric and Adolescent Rheumatology—UCL, Institute of Child Health and Great Ormond Street Hospital NHS Foundation Trust, London, UK
  22. 22Istituto Giannina Gaslini, Pediatria II and Università degli Studi di Genova, Genova, Italy
  1. Correspondence to Dr Helen J Lachmann, Division of Medicine, National Amyloidosis Centre, UCL Medical School, Royal Free Campus, Rowland Hill Street, London NW3 2PF, UK; h.lachmann{at}ucl.ac.uk

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.

  • Fever Syndromes
  • Inflammation
  • Amyloidosis

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/

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