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.
- lupus erythematosus
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Handling editor David S Pisetsky
Twitter @none, @edvital
Deceased Ray Naden deceased on 16 August 2020
Contributors All authors were involved in the EULAR/ACR classification criteria exercises, contributed to the manuscript and critically read and approved the final version. This final version could unfortunately not be read and approved any more by RN, who died in early autumn of 2020, as referred to on the title page. He was intimately involved in the study and had been up to date with the manuscript until a few days before his death.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient and public involvement statement SLE patient representatives were involved at every stage of the EULAR/ACR classification criteria project.
Patient consent for publication Not required.
Ethics approval Ethics committee approval and subject consent were obtained as per local requirements.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement All data relevant to this study are included in this manuscript (including the supplementary information) or the previous two manuscripts on the EULAR/ACR classification criteria.
Author note We mourn Prof Ray Naden, who passed away on August 16th 2020. The authors wish to dedicate this article to his memory as a friend and colleague, and to highlight his efforts for these and other criteria.
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