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Association between comorbidities and extraglandular manifestations in primary Sjögren’s syndrome: a multicenter cross-sectional study



Primary Sjögren’s syndrome (pSS) has been related to a higher risk of comorbidities, but studies examining comorbidities among patients with and without extraglandular manifestations are limited. The objectives of this study were to assess the prevalence of comorbidities in Chinese pSS patients and to determine the relationship between comorbidities and extraglandular manifestations.


This cross-sectional study was based on the multicenter pSS registry established by the Chinese Rheumatism Data Center. Patients fulfilling the 2002 American-European criteria or the 2016 classification criteria for pSS were enrolled from May 2016 to December 2018. Demographic data, disease characteristics, comorbidities (cardiovascular disease, thyroid disorder, malignancy, and fragility fracture), and extraglandular manifestations were collected. Multivariate analyses were used to assess the relationships between comorbidities and extraglandular manifestations.


A total of 4087 pSS patients were included (95.7% female and mean age of 51.2 ± 13.1 years). The baseline prevalence of comorbidities was 3.8% for cardiovascular diseases, 12.1% for thyroid disorders, 1.8% for malignancies, and 1.7% for fragility fractures. The presence of extraglandular manifestations was associated with more comorbidities. Patients with more than one extraglandular manifestation had a higher prevalence of cardiovascular disease (adjusted odds ratio [aOR] 2.004, 95% confidence interval [CI] 1.221–3.288), thyroid disorder (aOR 1.380, 95% CI 1.022–1.863), and fragility fracture (aOR 2.684, 95% CI 1.505–4.786) after adjustment for age, sex, disease duration, and the significant variables in the univariate analysis.


The presence of extraglandular manifestations in pSS was associated with an increased comorbidity burden, especially cardiovascular disease, thyroid disorder, and fragility fracture.

Key Points
This is the first study assessing the association between extraglandular manifestations and comorbidity burden based on the largest pSS registry in China.
Patients with multiple extraglandular manifestations tend to have increased comorbid cardiovascular disease, thyroid disorder, and fragility fracture.

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Data availability

The principal investigators, Dong Xu and Yan Zhao, had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.


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We acknowledged the contributions from all medical centers in the CRDC all over China and the HealthCloud Co., Ltd. as the system provider.


This work was financially supported by the Chinese National Key Technology R&D Program, Ministry of Science and Technology (2017YFC0907601, 2017YFC0907605).

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Authors and Affiliations



MTL, LYZ, JLZ, DX, YZ, and XFZ contributed to the conception and design of the study. LYZ, QL, JL, PTY, XDK, XWD, MJZ, XML, YFW, and JX contributed to data collection. YYZ and YHW participated in statistical analysis and interpretation. YYZ drafted the manuscript. MTL, YHW, EH, and DX revised the manuscript critically. DX, MTL, YZ, and XFZ supervised the study. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Dong Xu or Yan Zhao.

Ethics declarations

Written informed consent was obtained from all patients at enrollment. Ethics approval for the registry was obtained from the Medical Ethics Committee of Peking Union Medical College Hospital (PUMCH, JS-2038).



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Zhang, Y., Li, M., Zhang, L. et al. Association between comorbidities and extraglandular manifestations in primary Sjögren’s syndrome: a multicenter cross-sectional study. Clin Rheumatol 39, 2677–2688 (2020).

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  • Comorbidity
  • Extraglandular manifestation
  • Sjögren’s syndrome