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Extended report
EULAR definition of arthralgia suspicious for progression to rheumatoid arthritis
  1. Hanna W van Steenbergen1,
  2. Daniel Aletaha2,
  3. Liesbeth J J Beaart-van de Voorde1,
  4. Elisabeth Brouwer3,
  5. Catalin Codreanu4,
  6. Bernard Combe5,
  7. João E Fonseca6,7,
  8. Merete L Hetland8,9,
  9. Frances Humby10,
  10. Tore K Kvien11,
  11. Karin Niedermann12,
  12. Laura Nuño13,
  13. Sue Oliver14,
  14. Solbritt Rantapää-Dahlqvist15,
  15. Karim Raza16,17,
  16. Dirkjan van Schaardenburg18,
  17. Georg Schett19,
  18. Liesbeth De Smet1,
  19. Gabriella Szücs20,
  20. Jirí Vencovský21,
  21. Piotr Wiland22,
  22. Maarten de Wit23,
  23. Robert L Landewé24,
  24. Annette H M van der Helm-van Mil1,25
  1. 1Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  2. 2Department of Internal Medicine 3, Division of Rheumatology, Medical University Vienna, Vienna, Austria
  3. 3Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center, Groningen, The Netherlands
  4. 4Rheumatology Department, Center of Rheumatic Diseases, Bucharest, Romania
  5. 5Department of Rheumatology, Montpellier University Hospital, Montpellier, France
  6. 6Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal
  7. 7Rheumatology Department, Centro Hospitalar de Lisboa Norte, EPE, Hospital de Santa Maria, Lisbon Academic Medical Centre, Lisbon, Portugal
  8. 8DANBIO registry and Center for Rheumatology and Spine Diseases, Centre of Head and Orthopaedics, Rigshospitalet, Copenhagen, Denmark
  9. 9Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
  10. 10Queen Mary University of London, Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, London, UK
  11. 11Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway
  12. 12Institute of Physiotherapy, School of Health Professions, Zurich University of Applied Sciences, Winterthur, Switzerland
  13. 13Department of Rheumatology, Hospital Universitario La Paz-IdiPaz, Paseo de La Castellana, Madrid, Spain
  14. 14Independent Nurse Consultant, North Devon, UK
  15. 15Department of Public Health and Clinical Medicine/Rheumatology, University Hospital, Umeå, Sweden
  16. 16Rheumatology Research Group, Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
  17. 17Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, UK
  18. 18Amsterdam Rheumatology and immunology Center, locations Reade and Academic Medical Center, Amsterdam, The Netherlands
  19. 19Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen, Germany
  20. 20Department of Rheumatology, University of Debrecen Medical Center, Debrecen, Hungary
  21. 21Department of Rheumatology, First Faculty of Medicine, Institute of Rheumatology, Charles University, Prague, Czech Republic
  22. 22Department of Rheumatology and Internal Medicine, Wroclaw Medical University, Wroclaw, Poland
  23. 23EULAR Standing Committee of People with Arthritis/Rheumatism in Europe (PARE), Zurich, Switzerland
  24. 24Amsterdam Rheumatology and Immunology Center, Amsterdam, the Netherlands and Atrium Medical Center, Heerlen, The Netherlands
  25. 25Department of Rheumatology, Erasmus University Medical Center, Rotterdam, The Netherlands
  1. Correspondence to Dr Annette H M van der Helm-van Mil, Department of Rheumatology, Leiden University Medical Center, P.O. Box 9600, Leiden 2300 RC, The Netherlands; AvdHelm{at}


Background During the transition to rheumatoid arthritis (RA) many patients pass through a phase characterised by the presence of symptoms without clinically apparent synovitis. These symptoms are not well-characterised. This taskforce aimed to define the clinical characteristics of patients with arthralgia who are considered at risk for RA by experts based on their clinical experience.

Methods The taskforce consisted of 18 rheumatologists, 1 methodologist, 2 patients, 3 health professionals and 1 research fellow. The process had three phases. In phase I, a list of parameters considered characteristic for clinically suspect arthralgia (CSA) was derived; the most important parameters were selected by a three-phased Delphi approach. In phase II, the experts evaluated 50 existing patients on paper, classified them as CSA/no-CSA and indicated their level of confidence. A provisional set of parameters was derived. This was studied for validation in phase III, where all rheumatologists collected patients with and without CSA from their outpatient clinics.

Results The comprehensive list consisted of 55 parameters, of which 16 were considered most important. A multivariable model based on the data from phase II identified seven relevant parameters: symptom duration <1 year, symptoms of metacarpophalangeal (MCP) joints, morning stiffness duration ≥60 min, most severe symptoms in early morning, first-degree relative with RA, difficulty with making a fist and positive squeeze test of MCP joints. In phase III, the combination of these parameters was accurate in identifying patients with arthralgia who were considered at risk of developing RA (area under the receiver operating characteristic curve 0.92, 95% CI 0.87 to 0.96). Test characteristics for different cut-off points were determined.

Conclusions A set of clinical characteristics for patients with arthralgia who are at risk of progression to RA was established.

  • Early Rheumatoid Arthritis
  • Rheumatoid Arthritis
  • Outcomes research
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  • Handling editor Hans WJ Bijlsma

  • Contributors All authors contributed substantially to the conception and design of the work and acquisition and interpretation of the data. HWvS, AHMvdH-vM and RLL additionally analysed the data and drafted the initial version of the manuscript. All other authors revised the manuscript critically for important intellectual content and all authors gave approval of the final version to be published.

  • Funding This taskforce developing the presented definition was financially supported by EULAR Standing Committee on Clinical Affairs (ESCCA).

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval The medical ethics committee of the Leiden University Medical Centre obtained approval for the patient information used in phase I and phase II. In phase III, approval was obtained, if necessary, according to the local guidelines of the participating centres.

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

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