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European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) SLE classification criteria item performance
Open accessAbstract
Background/objectives The European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 classification criteria for systemic lupus erythematosus system showed high specificity, while attaining also high sensitivity. We hereby analysed the performance of the individual criteria items and their contribution to the overall performance of the criteria.Methods We combined the EULAR/ACR derivation and validation cohorts for a total of 1197 systemic lupus erythematosus (SLE) and n=1074 non-SLE patients with a variety of conditions mimicking SLE, such as other autoimmune diseases, and calculated the sensitivity and specificity for antinuclear antibodies (ANA) and the 23 specific criteria items. We also tested performance omitting the EULAR/ACR criteria attribution rule, which defines that items are only counted if not more likely explained by a cause other than SLE.Results Positive ANA, the new entry criterion, was 99.5% sensitive, but only 19.4% specific, against a non-SLE population that included other inflammatory rheumatic, infectious, malignant and metabolic diseases. The specific criteria items were highly variable in sensitivity (from 0.42% for delirium and 1.84% for psychosis to 75.6% for antibodies to double-stranded DNA), but their specificity was uniformly high, with low C3 or C4 (83.0%) and leucopenia <4.000/mm³ (83.8%) at the lowest end. Unexplained fever was 95.3% specific in this cohort. Applying the attribution rule improved specificity, particularly for joint involvement.Conclusions Changing the position of the highly sensitive, non-specific ANA to an entry criterion and the attribution rule resulted in a specificity of >80% for all items, explaining the higher overall specificity of the criteria set.
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“More recently, however, sensitivity (75.6%) and specificity (93.7%) characteristics of anti-dsDNA antibodies were published for the disease cohort used for establishing the new ACR/EULAR criteria, and compared with the ACR 1982 (67% and 92%, respectively) and SLICC 2012 (57.1% and 95.9%, respectively) cohorts [7,20].”
From Anti-dsDNA antibodies in the classification criteria of systemic lupus erythematosus (2022) · cites this paper as [7]
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“In a recent evaluation of the combined European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) derivation and validation cohorts (1197 SLE patients and 1074 non-SLE population), ANA had high sensitivity, but only 19.4% specificity.”
From Anti-dsDNA antibodies in the classification criteria of systemic lupus erythematosus (2022) · cites this paper as [7]
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“The position of ANA as entry criterion as opposed to ANA as separately valued (immunological) criterion in previous classification criteria, and the attribution rule (items count towards SLE only if there is no more likely alternative explanation) proved to be the key element to increase the specificity of the EULAR/ACR criteria [7].”
From Anti-dsDNA antibodies in the classification criteria of systemic lupus erythematosus (2022) · cites this paper as [7]
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The 1982 revised criteria for the classification of systemic lupus erythematosus
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Self-citationAringer, M., Costenbader, K., Daikh, D., Brinks, R., Mosca, M., Ramsey‐Goldman, R., Smolen, J. S., Wofsy, D., Boumpas, D. T., Kamen, D. L., et al. (2019) · Arthritis & Rheumatology · doi:10.1002/art.40930 · Cited by 2,677
Self-citation2019 update of the EULAR recommendations for the management of systemic lupus erythematosus
Fanouriakis, A., Kostopoulou, M., Alunno, A., Aringer, M., Bajema, I., Boletis, J. N., Cervera, R., Doria, A., Gordon, C., Govoni, M., et al. (2019) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2019-215089 · Cited by 2,011
Self-citationAringer, M., Costenbader, K., Daikh, D., Brinks, R., Mosca, M., Ramsey-Goldman, R., Smolen, J. S., Wofsy, D., Boumpas, D. T., Kamen, D. L., et al. (2019) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2018-214819 · Cited by 1,612
Self-citationLeuchten, N., Hoyer, A., Brinks, R., Schoels, M., Schneider, M., Smolen, J., Johnson, S. R., Daikh, D., Dörner, T., Aringer, M., et al. (2018) · Arthritis Care & Research · doi:10.1002/acr.23292 · Cited by 190
Self-citationClassification criteria in rheumatic diseases: A review of methodologic properties
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Self-citationTedeschi, S. K., Johnson, S. R., Boumpas, D., Daikh, D., Dörner, T., Jayne, D., Kamen, D., Lerstrøm, K., Mosca, M., Ramsey‐Goldman, R., et al. (2018) · Arthritis Care & Research · doi:10.1002/acr.23317 · Cited by 112
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Research works printed but not linked: 1
- Radin, 2020, Impact of the new 2019 EULAR/ACR classification criteria for systemic lupus erythematosus in a multicenter cohort study of 133 women with undifferentiated connective tissue disease, Arthritis Care Res
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Anti-dsDNA antibodies in the classification criteria of systemic lupus erythematosus
Infantino, M., Nagy, E., Bizzaro, N., Fischer, K., Bossuyt, X., & Damoiseaux, J. (2022) · Journal of Translational Autoimmunity · doi:10.1016/j.jtauto.2021.100139 · Cited by 38
Metadata
- Authors
- Aringer, M., Brinks, R., Dörner, T., Daikh, D., Mosca, M., Ramsey-Goldman, R., Smolen, J. S., Wofsy, D., Boumpas, D. T., Kamen, D. L., Jayne, D., Cervera, R., Costedoat-Chalumeau, N., Diamond, B., Gladman, D. D., Hahn, B., Hiepe, F., Jacobsen, S., Khanna, D., Lerstrøm, K., Massarotti, E., McCune, J., Ruiz-Irastorza, G., Sanchez-Guerrero, J., Schneider, M., Urowitz, M., Bertsias, G., Hoyer, B. F., Leuchten, N., Schmajuk, G., Tani, C., Tedeschi, S. K., Touma, Z., Anic, B., Assan, F., Chan, T. M., Clarke, A. E., Crow, M. K., Czirják, L., Doria, A., Graninger, W., Halda-Kiss, B., Hasni, S., Izmirly, P. M., Jung, M., Kumánovics, G., Mariette, X., Padjen, I., Pego-Reigosa, J. M., Romero-Diaz, J., Rúa-Figueroa, Í., Seror, R., Stummvoll, G. H., Tanaka, Y., Tektonidou, M. G., Vasconcelos, C., Vital, E. M., Wallace, D. J., Yavuz, S., Meroni, P. L., Fritzler, M. J., Naden, R., Costenbader, K., & Johnson, S. R.
- Affiliations
- Technische Universität Dresden (DE)
- Heinrich Heine University Düsseldorf (DE)
- Humboldt-Universität zu Berlin (DE)
- Portland VA Medical Center (US)
- University of Pisa (IT)
- Medical University of Vienna (AT)
- University of California, San Francisco (US)
- National and Kapodistrian University of Athens (GR)
- Medical University of South Carolina (US)
- University of Cambridge (GB)
- Hospital Clínic de Barcelona (ES)
- Sorbonne Paris Cité (FR)
- Feinstein Institute for Medical Research (US)
- University of Toronto (CA)
- University of California, Los Angeles (US)
- Rigshospitalet (DK)
- University of Michigan (US)
- LUPUS UK (GB)
- Brigham and Women's Hospital (US)
- University of Crete (GR)
- Christian-Albrechts-Universität zu Kiel (DE)
- San Francisco VA Medical Center (US)
- Université Paris-Sud (FR)
- University of Hong Kong (HK)
- University of Calgary (CA)
- Hospital for Special Surgery (US)
- University of Pecs (HU)
- University of Padua (IT)
- Medical University of Graz (AT)
- National Institutes of Health (US)
- New York University (US)
- University Hospital Centre Zagreb (HR)
- University of Occupational and Environmental Health Japan (JP)
- Universidade do Porto (PT)
- University of Leeds (GB)
- Cedars-Sinai Medical Center (US)
- IRCCS Istituto Auxologico Italiano (IT)
- McMaster University (CA)
- Corresponding author
- Aringer, Martin
- ORCID
- Aringer, Martin
- Brinks, Ralph
- Dörner, Thomas
- Mosca, Marta
- Smolen, Josef S
- Wofsy, David
- Boumpas, Dimitrios T
- Kamen, Diane L
- Jayne, David
- Cervera, R
- Costedoat-Chalumeau, Nathalie
- Diamond, Betty
- Gladman, Dafna D
- Hiepe, Falk
- Jacobsen, Søren
- Khanna, Dinesh
- Massarotti, Elena
- Ruiz-Irastorza, Guillermo
- Schneider, Matthias
- Urowitz, Murray
- Bertsias, George
- Hoyer, Bimba F
- Leuchten, Nicolai
- Schmajuk, Gabriela
- Tani, Chiara
- Tedeschi, Sara K
- Touma, Zahi
- Assan, Florence
- Chan, Tak Mao
- Clarke, Ann Elaine
- Crow, Mary K
- Doria, Andrea
- Graninger, Winfried
- Hasni, Sarfaraz
- Izmirly, Peter M
- Jung, Michelle
- Padjen, Ivan
- Rúa-Figueroa, Íñigo
- Tanaka, Yoshiya
- Tektonidou, Maria G
- Vasconcelos, Carlos
- Vital, Edward M
- Wallace, Daniel J
- Yavuz, Sule
- Meroni, Pier Luigi
- Fritzler, Marvin J
- Costenbader, Karen
- Johnson, Sindhu R
- Venue
- Annals of the Rheumatic Diseases
- Publisher
- Elsevier BV
- Published
- 2021-06
- Volume
- 80
- Issue
- 6
- Pages
- 775-781
- ISSN
- 0003-4967 (ISSN-L)
- PMC
- PMC13153727
- OpenAlex
- W3128254628
- Cited by
- 68
- References
- 23
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 17 · 2023: 8 · 2022: 15 · 2021: 10
- FWCI
- 9.42
- Type
- journal article
- Language
- en
- Open access
- green
- pmc.ncbi.nlm.nih.gov
- Locations
- Annals of the Rheumatic Diseases (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
- PubMed Central (submittedVersion)
- Istanbul Science University (Istanbul Bilim University) (submittedVersion)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- Padua Research Archive (University of Padova) (submittedVersion, other-oa)
- Apollo
- Funders
- National Institute for Health and Care Research (CS-2013-13-032, RTF/01/097, CL-2012-02-003)
- Academy of Medical Sciences (AMS-SGCL8-Vital)
- National Institutes of Health
- Medical Research Council (MR/M01665X/1)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (ZIAAR041232)
- Topics
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Health Sciences › Medicine › Rheumatology › Systemic Sclerosis and Related Diseases
- Health Sciences › Medicine › Rheumatology › Vasculitis and related conditions
- Keywords
- systemic lupus erythematosus, sensitivity and specificity, antinuclear antibodies, anti-dsDNA antibodies, complement C3 and C4, leukopenia, fever of unknown origin, joint involvement
- MeSH terms
- Antibodies, Antinuclear, Humans, Lupus Erythematosus, Systemic, Rheumatic Diseases, Rheumatology, Sensitivity and Specificity, United States, Cohort Studies
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