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Evidence-based recommendations for genetic diagnosis of familial Mediterranean fever
  1. Gabriella Giancane1,
  2. Nienke M Ter Haar2,
  3. Nico Wulffraat1,
  4. Sebastiaan J Vastert1,
  5. Karyl Barron3,
  6. Veronique Hentgen4,
  7. Tilmann Kallinich5,
  8. Huri Ozdogan6,
  9. Jordi Anton7,
  10. Paul Brogan8,
  11. Luca Cantarini9,
  12. Joost Frenkel10,
  13. Caroline Galeotti11,
  14. Marco Gattorno12,
  15. Gilles Grateau13,
  16. Michael Hofer14,
  17. Isabelle Kone-Paut15,
  18. Jasmin Kuemmerle-Deschner16,
  19. Helen J Lachmann17,
  20. Anna Simon18,
  21. Erkan Demirkaya19,
  22. Brian Feldman20,
  23. Yosef Uziel21,
  24. Seza Ozen22
  1. 1Department of Pediatric Immunology, UMC, Utrecht, The Netherlands
  2. 2Laboratory for Translational Immunology, UMC, Utrecht, The Netherlands
  3. 3NIH, Bethesda, USA
  4. 4Reference Centre for Autoinflammatory Disorders (CEREMAI) Centre Hospitalier de Versailles, Le Chesnay Cedex, France
  5. 5Charite University Medicine, Berlin, Germany
  6. 6Cerrahpasa Ic Hastaliklari Klinigi, Istanbul, Turkey
  7. 7Hospital Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain
  8. 8Infection, Inflammation and Rheumatology Section, UCL Institute of Child Health, London, UK
  9. 9Policlinico Le Scotte, University of Siena, Siena, Italy
  10. 10Department of Pediatrics, UMC, Utrecht, The Netherlands
  11. 11Reference Centre for Autoinflammatory Disorders CEREMAI, Bicêtre Hospital, University of Paris SUD, Le Kremlin Bicêtre Cedex, France
  12. 12UO Pediatria II, G. Gaslini Institute, Genova, Italy
  13. 13Centre national de référence des amyloses d'origine inflammatoire et de la fièvre, Hôpital Tenon, AP-HP, Université Pierre-et-Marie-Curie, Paris, France
  14. 14Pediatric Rheumatology, Department of Pediatrics, University of Lausanne, Lausanne and University of Geneva, Geneva, Switzerland
  15. 15Division of Paediatric Rheumatology, Reference Centre for Autoinflammatory Disorders CEREMAI, Bicêtre Hospital, University of Paris SUD, Paris, France
  16. 16Klinik für Kinder- und Jugendmedizin, Abteilung für pädiatrische Rheumatologie, Autoinflammation Reference Center Tübingen, Universitätsklinikum Tübingen, Tübingen, Germany
  17. 17National Amyloidosis Centre, University College London Medical School, London, UK
  18. 18Department of Medicine, Division of General Internal Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
  19. 19Gulhane Military Medical Faculty, Institute of Health Sciences, R&D Center, Ankara, Turkey
  20. 20University of Toronto, The Hospital for Sick Children, Toronto, Canada
  21. 21Department of Pediatrics, Meir Medical Center, Kfar Saba, Tel Aviv University, Sackler School of Medicine, Tel Aviv, Israel
  22. 22Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey
  1. Correspondence to Dr Gabriella Giancane, Department of Pediatric Immunology, UMC, Utrecht 3508 AB, The Netherlands; ggiancan{at}; gabriella.giancane{at}


Familial Mediterranean fever (FMF) is a disease of early onset which can lead to significant morbidity. In 2012, Single Hub and Access point for pediatric Rheumatology in Europe (SHARE) was launched with the aim of optimising and disseminating diagnostic and management regimens for children and young adults with rheumatic diseases. The objective was to establish recommendations for FMF focusing on provision of diagnostic tools for inexperienced clinicians particularly regarding interpretation of MEFV mutations. Evidence-based recommendations were developed using the European League against Rheumatism standard operating procedure. An expert committee of paediatric rheumatologists defined search terms for the systematic literature review. Two independent experts scored articles for validity and level of evidence. Recommendations derived from the literature were evaluated by an online survey and statements with less than 80% agreement were reformulated. Subsequently, all recommendations were discussed at a consensus meeting using the nominal group technique and were accepted if more than 80% agreement was reached. The literature search yielded 3386 articles, of which 25 were considered relevant and scored for validity and level of evidence. In total, 17 articles were scored valid and used to formulate the recommendations. Eight recommendations were accepted with 100% agreement after the consensus meeting. Topics covered were clinical versus genetic diagnosis of FMF, genotype–phenotype correlation, genotype–age at onset correlation, silent carriers and risk of amyloid A (AA) amyloidosis, and role of the specialist in FMF diagnosis. The SHARE initiative provides recommendations for diagnosing FMF aimed at facilitating improved and uniform care throughout Europe.

  • Familial Mediterranean Fever
  • Amyloidosis
  • Fever Syndromes

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