Objectives To develop and validate an international set of classification criteria for primary Sjögren's syndrome (SS) using guidelines from the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR). These criteria were developed for use in individuals with signs and/or symptoms suggestive of SS.
Methods We assigned preliminary importance weights to a consensus list of candidate criteria items, using multi-criteria decision analysis. We tested and adapted the resulting draft criteria using existing cohort data on primary SS cases and non-SS controls, with case/non-case status derived from expert clinical judgement. We then validated the performance of the classification criteria in a separate cohort of patients.
Results The final classification criteria are based on the weighted sum of five items: anti-SSA/Ro antibody positivity and focal lymphocytic sialadenitis with a focus score of ≥1 foci/4 mm2, each scoring 3; an abnormal Ocular Staining Score of ≥5 (or van Bijsterveld score of ≥4), a Schirmer's test result of ≤5 mm/5 min and an unstimulated salivary flow rate of ≤0.1 mL/min, each scoring 1. Individuals with signs and/or symptoms suggestive of SS who have a total score of ≥4 for the above items meet the criteria for primary SS. Sensitivity and specificity against clinician-expert—derived case/non-case status in the final validation cohort were high, that is, 96% (95% CI92% to 98%) and 95% (95% CI 92% to 97%), respectively.
Conclusion Using methodology consistent with other recent ACR/EULAR-approved classification criteria, we developed a single set of data-driven consensus classification criteria for primary SS, which performed well in validation analyses and are well suited as criteria for enrolment in clinical trials.
- Sjøgren's Syndrome
- Disease Activity
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Handling editor Tore K Kvien
This article is published simultaneously in the January 2017 issue of Arthritis & Rheumatology.
Collaborators Members of the International Working Group on Sjögren’s Syndrome Classification Criteria, in addition to the authors, were as follows: Drs AM Heidenreich, H Lanfranchi and C Vollenweider (Argentina); Dr M. Schiødt (Denmark); Drs V. Devauchelle, JE Gottenberg and A Saraux and patient representative Maggy Pincemin (France); Dr T Dörner (Germany); Dr A Tzoufias (Greece); Drs C Baldini, S Bombardieri and S De Vita (Italy); Drs K Kitagawa, T Sumida and H Umehara (Japan); Drs H Bootsma, AA Kruize, TR Radstake and A Vissink (the Netherlands); Dr R Jonsson (Norway); Dr M Ramos-Casals (Spain); Dr E Theander (Sweden); Drs S Challacombe, B Fisher, B Kirkham, G Larkin, F Ng and S Rauz (UK) and Drs E Akpek, J Atkinson, AN Baer, S Carsons, N Carteron, T Daniels, B Fox, J Greenspan, G Illei, D Nelson, A Parke, S Pillemer, B Segal, K Sivils, EW St Clair, D Stone, F Vivino and A Wu and patient representative Kathy Hammitt (USA).
Contributors All authors were involved in drafting the article or revising it critically for important intellectual content and all authors approved the final version to be published. SCS had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study conception and design: CHS, SCS, RS, SJB and XM. Acquisition of data: CHS, SCS, RS, LAC, ML, TML, AR, HS, CV, SJB and XM. Analysis and interpretation of data: CHS, SCS, RS, LAC, ML, TML and AR.
Funding The patient cohorts involved in this research were funded by the NIH (grants from the National Institute of Dental and Craniofacial Research (NIDCR), the National Eye Institute and the Office of Research on Women's Health; contract N01-DE-32636 and NIDCR contract HHSN26S201300057C for the Sjögren's International Collaborative Clinical Alliance cohort and grants AR-053483, AR-050782, DE-018209, DE-015223, AI-082714, GM-104938 and 1P50-AR-060804). Support for the Oklahoma Medical Research Foundation cohort was provided by the Oklahoma Medical Research Foundation, the Phileona Foundation and the Sjögren's Syndrome Foundation.
Competing interests CHS has received consulting fees from the Pasteur Institute (less than $10 000). SCS has received textbook royalties from Springer Publishing (less than $10 000). ML has received consulting fees from Alcon, Allergan, MSD, Sanofi, Santen and Thea (less than $10 000 each). HS has received consulting fees from UCB and Eli Lilly (less than $10 000 each). SJB has received consulting fees from Celgene, Eli Lilly, Glenmark, GlaxoSmithKline, MedImmune, Novartis, Ono, Pfizer, Roche, Takeda and UCB (less than $10 000 each).
Provenance and peer review Not commissioned; internally peer reviewed.