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2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus
  1. Martin Aringer1,
  2. Karen Costenbader2,
  3. David Daikh3,
  4. Ralph Brinks4,
  5. Marta Mosca5,
  6. Rosalind Ramsey-Goldman6,
  7. Josef S Smolen7,
  8. David Wofsy8,
  9. Dimitrios T Boumpas9,10,
  10. Diane L Kamen11,
  11. David Jayne12,
  12. Ricard Cervera13,
  13. Nathalie Costedoat-Chalumeau14,
  14. Betty Diamond15,
  15. Dafna D Gladman16,
  16. Bevra Hahn17,
  17. Falk Hiepe18,
  18. Søren Jacobsen19,
  19. Dinesh Khanna20,
  20. Kirsten Lerstrøm21,
  21. Elena Massarotti22,23,
  22. Joseph McCune20,
  23. Guillermo Ruiz-Irastorza24,
  24. Jorge Sanchez-Guerrero25,26,
  25. Matthias Schneider27,
  26. Murray Urowitz28,
  27. George Bertsias29,
  28. Bimba F Hoyer18,30,
  29. Nicolai Leuchten1,
  30. Chiara Tani31,
  31. Sara K Tedeschi23,32,
  32. Zahi Touma33,
  33. Gabriela Schmajuk3,
  34. Branimir Anic34,
  35. Florence Assan35,
  36. Tak Mao Chan36,
  37. Ann Elaine Clarke37,
  38. Mary K Crow38,
  39. László Czirják39,
  40. Andrea Doria40,
  41. Winfried Graninger41,
  42. Bernadett Halda-Kiss39,
  43. Sarfaraz Hasni42,
  44. Peter M Izmirly43,
  45. Michelle Jung37,
  46. Gábor Kumánovics39,
  47. Xavier Mariette44,45,
  48. Ivan Padjen34,
  49. José M Pego-Reigosa46,
  50. Juanita Romero-Diaz47,
  51. Íñigo Rúa-Figueroa Fernández48,
  52. Raphaèle Seror35,
  53. Georg H Stummvoll49,
  54. Yoshiya Tanaka50,
  55. Maria G Tektonidou51,
  56. Carlos Vasconcelos52,
  57. Edward M Vital53,54,
  58. Daniel J Wallace55,
  59. Sule Yavuz56,
  60. Pier Luigi Meroni57,
  61. Marvin J Fritzler58,
  62. Ray Naden59,
  63. Thomas Dörner18,
  64. Sindhu R Johnson60,61
  1. 1 Medicine III, University Medical Center and Faculty of Medicine Carl Gustav Carus, TU Dresden, Dresden, Germany
  2. 2 Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
  3. 3 University of California at San Francisco and VA Medical Center, San Francisco, California, USA
  4. 4 Policlinic and Hiller Research Unit for Rheumatology, Medical Faculty, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany
  5. 5 Department of Clinical and Experimental Medicine, Azienda Ospedaliero Universitaria Pisana, University of Pisa, Pisa, Italy
  6. 6 Department of Medicine, Division of Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
  7. 7 Department of Rheumatology, Medicine III, Medical University of Vienna, Vienna, Austria
  8. 8 Department of Medicine, Russell/Engleman Rheumatology Research Center, University of California at San Francisco, San Francisco, California, USA
  9. 9 Joint Academic Rheumatology Program, Medical School, National and Kapodestrian University of Athens, and Biomedical Research Foundation of the Athens Academy, Athens, Greece
  10. 10 Departments of Internal Medicine and Rheumatology, Clinical Immunology and Allergy, Medical School, University of Cyprus, Nicosia, Cyprus
  11. 11 Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA
  12. 12 Department of Medicine, University of Cambridge, Cambridge, UK
  13. 13 Department of Autoimmune Diseases, Hospital Clínic, University of Barcelona, Barcelona, Spain
  14. 14 Medicine, Toronto Western Hospital, University Health Network, Mount Sinai Hospital, University of Toronto, Toronto Scleroderma Research Program, Toronto, Ontario, Canada
  15. 15 Center for Autoimmune, Musculoskeletal and Hematopoietic Diseases, The Feinstein Institute for Medical Research, Manhasset, New York, USA
  16. 16 Division of Rheumatology, Department of Medicine, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada
  17. 17 Division of Rheumatology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, USA
  18. 18 Department of Rheumatology and Clinical Immunology, Charité – Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
  19. 19 Copenhagen Lupus and Vasculitis Clinic, Center for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
  20. 20 Division of Rheumatology, University of Michigan, Ann Arbor, Michigan, USA
  21. 21 Lupus Europe, Co-Opted Trustee for Research, Essex, UK
  22. 22 Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
  23. 23 Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
  24. 24 Autoimmune Diseases Research Unit, Department of Internal Medicine, Biocruces Bizkaia Health Research Institute, Hospital Universitario Cruces, UPV/EHU, Bizkaia, The Basque Country, Spain
  25. 25 Division of Rheumatology, Department of Medicine, Mount Sinai Hospital/University Health Network, University of Toronto, Toronto, Ontario, Canada
  26. 26 Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
  27. 27 Policlinic and Hiller Research Unit for Rheumatology, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany
  28. 28 Center for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University of Toronto, Lupus Clinic, Toronto, Ontario, Canada
  29. 29 Rheumatology, Clinical Immunology and Allergy, University of Crete Medical School, Heraklion, Crete, Greece
  30. 30 Department of Medicine III, University of Schleswig-Holstein at Kiel, Kiel, Germany
  31. 31 Department of Clinical and Experimental Medicine, Rheumatology Unit, Azienda Ospedaliero Universitaria Pisana, University of Pisa, Pisa, Italy
  32. 32 Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
  33. 33 Division of Rheumatology, Department of Medicine, Toronto Western Hospital, Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
  34. 34 Division of Clinical Immunology and Rheumatology, University of Zagreb School of Medicine and University Hospital Centre Zagreb, Zagreb, Croatia
  35. 35 Department of Rheumatology, Université Paris Sud, Hôpitaux Universitaires Paris-Sud, AP-HP, INSERM UMR 1184, Le Kremlin-Bicêtre, France
  36. 36 Department of Medicine, University of Hong Kong, Hong Kong, China
  37. 37 Division of Rheumatology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
  38. 38 Hospital for Special Surgery, Ney York, New York, USA
  39. 39 Department of Rheumatology and Immunology, University of Pécs, Pécs, Hungary
  40. 40 Rheumatology Unit, Department of Medicine (DIMED), University of Padova, Padova, Italy
  41. 41 Internal Medicine, Medical University of Graz, Graz, Austria
  42. 42 Lupus Clinical Research Program, Office of the Clinical Director, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA
  43. 43 Rheumatology, New York University School of Medicine, New York, New York, USA
  44. 44 Rheumatology, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux universitaires Paris-Sud – Hôpital Bicêtre, Le Kremlin Bicêtre, France
  45. 45 Department of Rheumatology, Université Paris-Sud, Center for Immunology of Viral Infections and Auto-immune Diseases (IMVA), Institut pour la Santé et la Recherche Médicale (INSERM) UMR 1184, Université Paris-Saclay, Le Kremlin Bicêtre, France
  46. 46 Department of Rheumatology, University Hospital of Vigo, IRIDIS Group, Instituto de Investigación Sanitaria Galicia Sur (IISGS), Vigo, Spain
  47. 47 Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
  48. 48 Rheumatology, Doctor Negrín University Hospital, Las Palmas de Gran Canaria, Las Palmas, Spain
  49. 49 Rheumatology, Medical University of Vienna, Vienna, Austria
  50. 50 First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan
  51. 51 Medical School, National and Kapodistrian University of Athens, Athens, Greece
  52. 52 Clinical Immunology Unit, Centro Hospitalar do Porto, ICBAS, University of Porto, Porto, Portugal
  53. 53 Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK
  54. 54 NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK
  55. 55 Division of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, California, USA
  56. 56 Department of Rheumatology, Istanbul Bilim University, Istanbul, Turkey
  57. 57 Clinical Immunology and Rheumatology Unit, IRCCS Istituto Auxologico Italiano, Milan, Italy
  58. 58 Faculty of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
  59. 59 Maternal-Fetal Medicine, McMaster University Faculty of Health Sciences, Hamilton, Ontario, Canada
  60. 60 Internal Medicine Department, Centre de référence maladies auto-immunes et systémiques rares d'île deFrance, Cochin Hospital, Université Paris Descartes-Sorbonne Paris Cité, INSERM U1153, Center for Epidemiology and Statistics Sorbonne Paris Cité (CRESS), Paris, France
  61. 61 Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
  1. Correspondence to Martin Aringer, Medicine III, University Medical Center and Faculty of Medicine Carl Gustav Carus, TU Dresden, Dresden D-01307, Germany; martin.aringer{at}uniklinikum-dresden.de; Dr Sindhu R Johnson, Division of Rheumatology, Ground Floor, East Wing, Toronto Western Hospital, 399 Bathurst Street, Toronto, Ontario M5T 2S8, Canada; Sindhu.Johnson{at}uhn.ca

Abstract

Objective To develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR).

Methods This international initiative had four phases. (1) Evaluation of antinuclear antibody (ANA) as an entry criterion through systematic review and meta-regression of the literature and criteria generation through an international Delphi exercise, an early patient cohort and a patient survey. (2) Criteria reduction by Delphi and nominal group technique exercises. (3) Criteria definition and weighting based on criterion performance and on results of a multi-criteria decision analysis. (4) Refinement of weights and threshold scores in a new derivation cohort of 1001 subjects and validation compared with previous criteria in a new validation cohort of 1270 subjects.

Results The 2019 EULAR/ACR classification criteria for SLE include positive ANA at least once as obligatory entry criterion; followed by additive weighted criteria grouped in seven clinical (constitutional, haematological, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal) and three immunological (antiphospholipid antibodies, complement proteins, SLE-specific antibodies) domains, and weighted from 2 to 10. Patients accumulating ≥10 points are classified. In the validation cohort, the new criteria had a sensitivity of 96.1% and specificity of 93.4%, compared with 82.8% sensitivity and 93.4% specificity of the ACR 1997 and 96.7% sensitivity and 83.7% specificity of the Systemic Lupus International Collaborating Clinics 2012 criteria.

Conclusion These new classification criteria were developed using rigorous methodology with multidisciplinary and international input, and have excellent sensitivity and specificity. Use of ANA entry criterion, hierarchically clustered and weighted criteria reflect current thinking about SLE and provide an improved foundation for SLE research.

  • systemic lupus erythematosus
  • lupus
  • classification criteria
  • consensus methods
  • multi-criteria decision analysis
  • validation
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Footnotes

  • Permission This article is published simultaneously in the September 2019 issue of Arthritis & Rheumatology.

  • Handling editor David S Pisetsky

  • Contributors MA, SRJ, TD, KC, DD, RB, MM, RR-G, JSS, DW, DB, DLK, DJ and RN have been involved in the planning and execution of the project and in writing the manuscript. RC, NC-C, BD, DDG, BH, FH, SJ, DK, KL, EM, W. JM, GR-I, JS-G, MS, MU, GB, BFH, NL, CT, SKT, ZT, GS, BA, FA, TMC, AEC, MKC, LC, AD, WG, BH-K, SH, PMI, MJ,GK, XM, IP, JMP-R, JR-D, IR-F, RS, GHS, YT, MGT, CV, EMV, DJW, SY, PLM and MJF have each significantly contributed to the body of work of the project and involved in correcting and finalising the manuscript.

  • Funding This study was supported by American College of Rheumatology and European League Against Rheumatism.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval Local ethics committees where applicable for chart based review of data.

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

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