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Multinational evidence-based recommendations on how to investigate and follow-up undifferentiated peripheral inflammatory arthritis: integrating systematic literature research and expert opinion of a broad international panel of rheumatologists in the 3E Initiative
  1. P Machado1,2,
  2. I Castrejon3,
  3. W Katchamart4,
  4. R Koevoets2,
  5. B Kuriya4,5,
  6. M Schoels6,
  7. L Silva-Fernández7,
  8. K Thevissen8,
  9. W Vercoutere9,
  10. E Villeneuve10,
  11. D Aletaha11,
  12. L Carmona12,
  13. R Landewé13,
  14. D van der Heijde2,
  15. J W J Bijlsma14,
  16. V Bykerk4,
  17. H Canhão15,
  18. A I Catrina16,
  19. P Durez17,
  20. C J Edwards18,
  21. M D Mjaavatten19,
  22. B F Leeb20,
  23. B Losada21,
  24. E M Martín-Mola22,
  25. P Martinez-Osuna23,
  26. C Montecucco24,
  27. U Müller-Ladner25,
  28. M Østergaard26,
  29. B Sheane27,
  30. R M Xavier28,
  31. J Zochling29,
  32. C Bombardier30,31
  1. 1Rheumatology Department, Coimbra University Hospital, Coimbra, Portugal
  2. 2Rheumatology Department, Leiden University Medical Center, Leiden, The Netherlands
  3. 3Rheumatology Department, Hospital Universitario de La Princesa, Madrid, Spain
  4. 4Mount Sinai Hospital, Toronto, Ontario, Canada
  5. 5Harvard School of Public Health, Boston, Massachusetts, USA
  6. 6KH Hietzing, Vienna, Austria
  7. 7Rheumatology Department, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain
  8. 8Rheumatology Department, Maastricht University Medical Center, Maastricht, The Netherlands
  9. 9Rheumatology Department, Atrium Medical Centre Parkstad, Heerlen, The Netherlands
  10. 10Academic Unit of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, Leeds University, Leeds, UK
  11. 11Medical University, Vienna, Austria
  12. 12Research Unit, Fundación Española de Reumatología, Madrid, Spain
  13. 13Department of Internal Medicine/Rheumatology, Maastricht University Medical Center, Care and Public Health Research Institute, Maastricht, The Netherlands
  14. 14Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands
  15. 15Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Serviço de Reumatologia e Doenças Ósseas Metabólicas, Hospital de Santa Maria, Lisbon, Portugal
  16. 16Department of Rheumatology, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden
  17. 17Microbiology Department, Cliniques universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium
  18. 18Southampton University Hospital, Southampton, UK
  19. 19Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway
  20. 20State Hospital Stockerau, Center for Rheumatology, Lower Austria, Stockerau, Austria
  21. 21Hospital Universitario de Caracas, Ciudad Universitaria, Los Chaguaramos, Caracas, Venezuela
  22. 22Hospital Universitario La Paz, Department of Rheumatology, Universidad Autónoma, Madrid, Spain
  23. 23Rheumatology Unit, Centro de Investigación Farmacológica y Biotecnológica, Hospital y Fundación Clínica Médica Sur, México City, México
  24. 24Cattedra di Reumatologia, IRCCS Policlinico S. Matteo, Università di Pavia, Pavia, Italy
  25. 25Department of Rheumatology and Clinical Immunology, Justus-Liebig-University Gießen, Kerckhoff Clinic, Bad Nauheim, Germany
  26. 26Department of Rheumatology, Copenhagen University Hospitals at Hvidovre and Glostrup, Hvidovre, Denmark
  27. 27Department of Rheumatology, St James's Hospital, Dublin, Ireland
  28. 28Hospital de Clínicas de Porto Alegre, Faculdade de Medicina da Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
  29. 29Menzies Research Institute, University of Tasmania, Hobart, Australia
  30. 30Division of Rheumatology, University Health Network, Toronto, Ontario, Canada
  31. 31Department of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada
  1. Correspondence to Dr Pedro Machado, Department of Rheumatology, Coimbra University Hospital, Praceta Mota Pinto, 3000-075 Coimbra, Portugal; pedrommcmachado{at}


Objective To develop evidence-based recommendations on how to investigate and follow-up undifferentiated peripheral inflammatory arthritis (UPIA).

Methods 697 rheumatologists from 17 countries participated in the 3E (Evidence, Expertise, Exchange) Initiative of 2008–9 consisting of three separate rounds of discussions and modified Delphi votes. In the first round 10 clinical questions were selected. A bibliographic team systematically searched Medline, Embase, the Cochrane Library and ACR/EULAR 2007–2008 meeting abstracts. Relevant articles were reviewed for quality assessment, data extraction and synthesis. In the second round each country elaborated a set of national recommendations. Finally, multinational recommendations were formulated and agreement among the participants and the potential impact on their clinical practice was assessed.

Results A total of 39 756 references were identified, of which 250 were systematically reviewed. Ten multinational key recommendations about the investigation and follow-up of UPIA were formulated. One recommendation addressed differential diagnosis and investigations prior to establishing the operational diagnosis of UPIA, seven recommendations related to the diagnostic and prognostic value of clinical and laboratory assessments in established UPIA (history and physical examination, acute phase reactants, autoantibodies, radiographs, MRI and ultrasound, genetic markers and synovial biopsy), one recommendation highlighted predictors of persistence (chronicity) and the final recommendation addressed monitoring of clinical disease activity in UPIA.

Conclusions Ten recommendations on how to investigate and follow-up UPIA in the clinical setting were developed. They are evidence-based and supported by a large panel of rheumatologists, thus enhancing their validity and practical use.

This paper is freely available online under the BMJ Journals unlocked scheme, see

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  • PM, IC, WK, RK, BK, MS, LS-F, KT, WV and EV contributed equally to this work.

  • Funding This work was supported by Abbott with an unrestricted educational grant.

  • Competing interests None.

  • Provenance and peer review Not commissioned; externally peer reviewed.