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Background: Primary Sjogren's syndrome (pSS) is a systemic autoimmune disease involving multiple organ systems. The Janus kinase/signal transduction and activator of transcription (JAK/STAT) signaling pathway is a key pathway involving the pathogenesis of pSS. Baricitinib, a selective JAK1 and JAK2 inhibitor, has been approved for treatment of active rheumatoid arthritis and reported in treatment of some other autoimmune diseases including systemic lupus erythematosus. We have found that baricitinib might be effective and safe in pSS in a pilot study. However, there is no published clinical evidence of baricitinib in pSS. Hence, we conducted this randomized study to further explore the efficacy and safety of baricitinib in pSS. Methods: This is a multi-center, prospective, open-label, randomized study to compare the efficacy of baricitinib + hydroxychloroquine (HCQ) with HCQ alone in pSS patients. We plan to involve 87 active pSS patients with European League Against Rheumatism pSS disease activity index (ESSDAI) ≥ 5 from eight different tertiary centers in China. Patients will be randomized (2:1) to receive baricitinib 4 mg per day + HCQ 400 mg per day or HCQ 400 mg per day alone. We will switch HCQ to baricitinib + HCQ if the patient in the latter group has no ESSDAI response at week 12. The final evaluation will be at week 24. The primary endpoint is the percentage of ESSDAI response, or minimal clinically important improvement (MCII), which was defined as an improvement of ESSDAI at least three points at week 12. The secondary endpoints include EULAR pSS patient-reported index (ESSPRI) response, change of Physician's Global Assessment (PGA) score, serological activity parameters, salivary gland function test, and focus score on labial salivary gland biopsy. Discussion: This is the first randomized controlled study to evaluate the clinical efficacy and safety of baricitinib in pSS. We hope that the result of this study can provide more reliable evidence of the efficacy and safety of baricitinib in pSS. Trial registration: ClinicalTrials.gov NCT05016297. Registered on 19 Aug 2021. [ABSTRACT FROM AUTHOR]

Objectives: To characterize the clinical features and outcomes of childhood-onset primary Sjögren's syndrome (pSS). Methods: Patients less than 18 years old who were diagnosed with pSS by paediatric rheumatologists were included, and all patients were applied the 2002 American-European Consensus Group (ACEG) criteria, the 2016 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria for pSS, or the 1999 proposed juvenile pSS criteria. The electronic medical records of patients with pSS from 2013 to 2020 were collected and analysed. Results: Thirty-nine patients were included. Of them, 27 (69.2%), 38 (97.4%) and 35 (89.7%) patients fulfilled the AECG criteria, ACR/EULAR criteria and proposed juvenile pSS criteria, respectively. The female:male ratio was 3.9:1. The median ages at first signs or symptoms and at diagnosis were 9.2 (4.7, 14.5) years and 10.9 (6.3, 15.0) years, respectively. The main clinical manifestations were rash or purpura (20, 51.3%), followed by fever (12, 30.8%), glandular enlargement/recurrent parotitis (10, 25.6%), and dry mouth and/or dry eyes (9, 23.1%). Twenty-eight (56.4%) patients had systemic damage, the most common of which was haematological involvement (14, 35.9%), followed by hepatic (13, 33.3%) and renal involvement (8, 20.5%). Thirty-eight (97.4%) patients underwent labial minor salivary gland biopsy, and all exhibited focal lymphocytic sialadenitis. All patients had a global ESSDAI score ≥ 1 at diagnosis, and the median total score at diagnosis was 8 (2, 31). Thirty-six (92.3%) patients were followed up for a median time of 23.6 (7.9, 79.5) months, and three patients developed systemic lupus erythematosus (SLE) at follow-up times of 13.3, 38.8 and 63.8 months. Conclusions: The presentation of childhood-onset pSS is atypical, and extraglandular manifestations and systemic involvement are more common than in adult-onset pSS. Labial salivary gland biopsy is vital for patients with probable pSS. Some patients may develop SLE over time. [ABSTRACT FROM AUTHOR]

Background: Autoimmune gastritis (AIG) and Primary Sjögren's syndrome (pSS) are both autoimmune diseases with low prevalence in China. Subacute combined degeneration (SCD) of the spinal cord is the most common neurological manifestation of vitamin B12 deficiency. Until now, a patient with pSS and complications of AIG including SCD has not been reported. Case Presentation: A 69-year-old woman presented with palpitations and symmetrical and progressive numbness in her hands and feet. The patient had a sense of stepping on cotton and could not write or walk without help. We reviewed the patient's history and analyzed her blood tests, imaging, gastroscopic findings, and pathological results. The patient fulfilled the criteria of AIG, pSS, spinal cord SCD and early pernicious anemia (PA) simultaneously. Although pSS can lead to reduction of vitamin B12, this is the first overlapping case of pSS with spinal cord SCD. After symptomatic treatment, the patient returned to a normal life. Conclusions: This first report about the coexistence of pSS and complications of AIG including SCD and PA will promote a better understanding of the relationship between these diseases. [ABSTRACT FROM AUTHOR]

Introduction: Patients with Primary Sjögren's syndrome (pSS) are at a higher risk of thyroid disorders than the general population. This retrospective analysis of 202 patients with pSS was conducted to uncover risk factors associated with thyroid involvement and to create a predictive model for this condition., Methods: We analyzed 202 patients with pSS from Guang'anmen Hospital, China Academy of Chinese Medical Sciences, with 105 cases of thyroid involvement and 97 without. The Least Absolute Shrinkage and Selection Operator method was used to identify key variables for our risk model. These variables were then subjected to multivariate logistic regression to develop the model. The accuracy of the model was assessed through the C-index, receiver operating characteristic curves, calibration plots, and decision curve analysis, with internal validation via bootstrapping., Results: High-sensitivity C-reactive protein (HCRP), pulmonary disease, pharyngeal dryness, forgetfulness, night sweats, hyperuricemia, nasal dryness, anxiety, Ro52, and aspartate aminotransferase (AST) were incorporated into the nomogram. The model showed robust discrimination and calibration abilities. Decision curve analysis indicated the clinical utility of our nomogram in intervening on the probability thresholds of thyroid disease., Conclusion: By integrating HCRP, pulmonary disease, pharyngeal dryness, forgetfulness, night sweats, hyperuricemia, nasal dryness, anxiety, Ro52, and AST, our thyroid risk nomogram can predict the risk of thyroid involvement in patients with pSS, aiding in more informed treatment strategies., Competing Interests: The authors declare the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yang, Du, Ren, Mei, Jiang, Liu, Zhang and Cui.)

Aim: This study aimed to evaluate the long-term survival, causes of death, and prognostic factors in Chinese patients with primary Sjögren syndrome (pSS)., Methods: We included patients with pSS registered in the Chinese Rheumatism Data Centre between May 2016 and December 2021, and collected baseline clinical, laboratory, and treatment data. Survival and standard mortality rates were calculated using general population mortality data. Factors related to mortality were identified using Cox proportional hazards regression., Results: Among the 8588 patients included, 274 died during a median follow-up of 4.0 years. The overall standardized mortality ratio was 1.61 (95% CI: 1.43-1.81). Overall survival rates were 98.2% at 5 years and 93.8% at 10 years. The predominant causes of death were comorbidities, including cardiovascular diseases, tumors, and infections, while the most frequent pSS-related causes of death were interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH). Male sex, older age, ILD, PAH, and high EULAR Sjögren's syndrome disease activity index (ESSDAI), thrombocytopenia, anemia, high immunoglobulin A (IgA) level, and glucocorticoid treatment independently increased the mortality risk, while using hydroxychloroquine was a protective factor., Conclusion: Mortality rates have significantly increased in Chinese patients with pSS. Comorbidities, rather than pSS-related organ damage, were the main causes of death. All-cause mortality was associated with male sex, older age, ILD, PAH, high ESSDAI, thrombocytopenia, anemia, high IgA level, and glucocorticoid treatment, whereas hydroxychloroquine use might improve the long-term survival., (© 2024 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

• The levels of multiple immune markers, antibodies, and inflammatory markers in pSS patients with dyslipidemia were significantly higher than those without. • pSS dyslipidemia is associated with multiple cellular inflammatory cytokines such as TNF-a and IL-2R levels. • Traditional cardiovascular risk factors contribute to the advancement of atherosclerotic disease in patients with pSS; besides, non-traditional cardiovascular risk factors also influence the development of complications associated with lipids. To investigate the relationship between the lipid profiles of patients with primary Sjögren's syndrome (pSS) and other clinical characteristics, laboratory examination, disease activity, and inflammatory factors. In addition, the risk factors for hyperlipidemia-related complications of pSS and the effect of hydroxychloroquine (HCQ) usage on the lipid profile were incorporated into this study. This is a single-center, retrospective study that included 367 patients who were diagnosed with pSS at Tongji Hospital, School of Medicine, Tongji University, China from January 2010 to March 2022. Initially, demographic information, clinical characteristics, medication records, and complications of the patients were gathered. A case-control analysis compared the 12 systems involvement (ESSDAI domain), clinical symptoms, and laboratory tests between pSS patients with and without dyslipidemia. A simple linear regression model was employed to investigate the relationship between serum lipid profile and inflammatory factors. Logistics regression analysis was performed to assess variables for hyperlipidemia-related complications of pSS. The paired t-test was then used to evaluate the improvement in lipid profile among pSS patients. 48.7 % of all pSS patients had dyslipidemia, and alterations in lipid levels were related to gender, age, and smoking status but not body mass index (BMI). Dyslipidemia is more prevalent in pSS patients who exhibit heightened autoimmunity and elevated levels of inflammation. Higher concentrations of multiple highly inflammatory factors correlate with a more severe form of dyslipidemia. Non-traditional cardiovascular risk factors may contribute to hyperlipidemia-related complications of pSS, such as increased, low complement 3 (C3) and low C4. According to our study, HCQ usage may protect against lipid-related disease in pSS. Attention should be paid to the dyslipidemia of pSS. This research aims to clarify the population portrait of pSS patients with abnormal lipid profiles and provides insights into the correlation between metabolism and inflammation in individuals with pSS and the potential role they play in the advancement of the disease. These findings provide novel avenues for further understanding the underlying mechanisms of pSS pathogenesis. [ABSTRACT FROM AUTHOR]

Purpose: Previous evidence has shown that psychological stress can trigger the onset of autoimmune disease. This study aimed to investigate the prevalence of stressful life events preceding the onset of symptoms in female primary Sjogren's syndrome (pSS) in China compared to controls and the possible associations of stressful life events with disease activity. Patients and Methods: This was a hospital-based retrospective case–control study. Sixty-seven consecutive female pSS patients and an equal number of age-matched (± 3 years) healthy controls were recruited for assessment using the related Stressful Life Events Scale. The pSS disease activity was measured by the EULAR Sjogren's syndrome disease activity index. Data were analyzed by SPSS, version 23, using chi-square, univariate logistic regression, multiple logistic regression, and partial correlation. Results: A higher number of negative stressful life events before disease onset in pSS patients compared with healthy controls suggest that these play a role in increasing the risk of disease occurrence (OR = 2.59, 95% CI: 1.87– 3.58, p < 0.05). The number of positive life events did not differ between the two groups. Both the number and severity of the negative stressful life events were also significantly correlated with disease activity. Conclusion: Patients with pSS experienced more negative stressful life events in the year preceding the onset of symptoms than controls. Negative stressful life events before symptom onset may be risk factors for pSS and may affect pSS disease activity. [ABSTRACT FROM AUTHOR]

Aim: Sleep disturbances are common in primary Sjögren's syndrome (pSS) patients and may lead to disease aggravation and decreased health‐related quality of life (HRQoL). There are currently no known reported studies related to the prevalence, correlates, and impact of sleep disturbance in pSS patients from China. Therefore, this study aims to assess the sleep quality in Chinese pSS patients and evaluate its relationship with the disease activity, quality of life and mood disorders. Methods: A self‐report survey was administered to 221 pSS patients and 198 healthy individuals using the Pittsburgh Sleep Quality Index (PSQI) for sleep quality. Disease activity and damage were evaluated with the European League Against Rheumatism Sjögren's syndrome disease activity index (ESSDAI). Independent samples t tests, Chi‐square analysis, logistic regression were used to analyze these data. Results: Our results found that the prevalence of poor sleep (PSQI ≥ 6) was 57.5% and the mean global score of PSQI was 6.57 (SD 3.19) in patients, which were significantly higher than the controls (32.3% and 4.93 [SD 2.86], respectively). When trying to fall asleep, patients with pSS had some sleep disturbances, reduced sleep efficiency, increased number of awakenings than controls. There were significant correlations among dryness, ocular surface disease, HRQoL, pain, disease activity, anxiety/depression and sleep quality in pSS patients. Meanwhile, logistic regression models identified depression and Short Form‐36 mental composite score as predictors of poor sleep quality. Conclusions: Sleep disturbances are commonly reported in pSS patients and sleep quality is lower in pSS patients than in healthy controls. The data suggested the need for holistic assessment and management of pSS patients. [ABSTRACT FROM AUTHOR]

Objective: To analyze the clinical characteristics of primary Sjögren's syndrome (pSS) combined with interstitial lung disease (ILD), so as to provide a theoretical basis for the early diagnosis, treatment and prevention of PSS-ILD., Methods: From October 2017 to January 2022, patients with pSS who were admitted to the Department of Rheumatology at Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine were included in this retrospective study. Patients were divided into the pSS-ILD (102 cases) and pSS-non-ILD groups (154 cases) based on the presence or absence of ILD on high-resolution computed tomography (HRCT). Demographics information, clinical symptoms, laboratory indicators and HRCT features were compared, and the logistic regression analysis was utilized to identify the risk factors., Results: A total of 256 patients were included. Patients with pSS-ILD were more often female, and their age and disease duration were significantly higher than those in the pSS-non-ILD group ( p < 0.05). The HRCT imaging classification included ground glass-like shadow (78.4%) and patchy solid shadow (17.6%), and Non-specific interstitial pneumonitis (NSIP) (72.5%) was the predominant typology. Regarding the laboratory indexes, the positive rates of erythrocyte sedimentation rate, C-reactive protein, white blood cell count, neutrophil/lymphocyte ratio, triglycerides, total cholesterol, and anti-SS-A52 antibodies were significantly higher in the pSS-ILD patients than in the pSS-non-ILD group, while the positive rates of anti-synaptic antibodies were lower than in the pSS-non-ILD group, and the differences between two groups were statistically significant ( p < 0.05). Logistic regression showed that age >60 years, longer duration of disease, higher triglycerides, and cholesterol were risk factors for pSS-ILD patients., Conclusion: The clinical features of pSS-ILD patients were xerophthalmia, cough and shortness of breath, and HRCT can help to diagnose the disease at an early stage. Age over 60 years, chronic course of disease, and elevated lipid levels are risk factors for ILD in pSS patients, and the relationship between autoimmune antibody levels and the occurrence of ILD needs to be further confirmed in follow-up studies with large sample sizes. These findings have the potential to provide useful information for early diagnosis, treatment, and prevention of the development of pSS-ILD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yang, Zhao, Shan and Wang.)

Background: Detection of IgG subclasses (IgGSc) is vital for the diagnosis and management of disease, especially IgG4-related diseases (IgG4-RD). This study aimed to evaluate the performances of the chemiluminescent immunoassay (CLIA) for detecting IgGSc and diagnosing IgG4-RD by IgGSc., Methods: A total of 40 individuals with IgG4-RD, 40 with primary Sjogren's syndrome (pSS), and 40 healthy controls (HCs) were enrolled. Serum samples were collected for the simultaneous detection of IgG1, IgG2, IgG3, and IgG4 by the Siemens immunonephelometric assay and the CLIA. The correlation analysis was performed, and diagnostic value was analyzed by the receiver operating characteristic (ROC) curve., Results: Patients with IgG4-RD had higher IgG4 (p < 0.001) and lower IgG1 (p < 0.001) than those with pSS, and HC. The results by the Siemens immunonephelometric assay and the CLIA showed a strong correlation in detecting IgG1, IgG2, IgG3, and IgG4 (r = 0.937, r = 0.847, r = 0.871, r = 0.990, all p < 0.001, respectively). The sum of IgG1, IgG2, IgG3, and IgG4 using two assays strongly correlated with total IgG by the IMMAGE 800 (r = 0.866, r = 0.811, both p < 0.001, respectively). For discriminating IgG4-RD from pSS and HC, no significant differences were observed in CLIA IgG4 and Siemens immunonephelometric assay IgG4 (z = 0.138, p = 0.891), which provided the area under the curves (AUCs) of 0.951 (p < 0.001) and 0.950 (p < 0.001), respectively. The AUCs of CLIA IgG1 and Siemens immunonephelometric assay IgG1 in distinguishing pSS from IgG4-RD and HC were 0.761 (p < 0.001) and 0.765 (p < 0.001), respectively, with no significant differences (z = 0.228, p = 0.820)., Conclusions: The CLIA and the Siemens immunonephelometric assay appeared to have good consistency with comparable diagnostic value in detecting IgGSc, especially IgG4, and IgG1 that can accurately identify IgG4-RD or pSS in clinical practice., (© 2024 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Objective: The main purpose of this study was to investigate the current situation of primary Sjögren's syndrome (pSS) patients with interstitial lung disease (ILD) in China. The relationships between social demography, disease activity, psychological status, clinical variables, and ILD were analyzed. Besides that, the quality of life (QoL) in pSS with ILD was also analyzed. Methods: In the cross-sectional study, 101 pSS patients participated in this study. Under the guidance of the researchers, the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI), EULAR Sjögren's Syndrome Patient-Reported Index (ESSPRI), the Short-Form 36 health survey (SF-36), Hospital Anxiety and Depression Scale (HADS), Pittsburgh sleep quality index (PSQI), Summated Xerostomia Inventory (SXI), and other related questionnaires were completed. Independent sample t tests, Mann-Whitney U test, chi-square test, and correlational analysis were used. Results: The data showed that 28 (30.1%) pSS people with ILD. The occurrence and development of ILD were associated with disease duration, fatigue, alanine aminotransferase (ALT), neutrophils, albumin, and use of hormone. The survey also found that the QoL of pSS-ILD was significantly lower than non-ILD, especially the score in the dimension of role physical function. Conclusions: ILD was very common in pSS. ILD had a significant negative impact on the QoL of patients. Therefore, it is of great significance to strengthen the early intervention and drug treatment of pSS patients to prevent ILD and improve their QoL. Key Points • This cross-sectional study finds that the incidence of ILD in patients with pSS is 30.1%. • The occurrence and development of ILD is associated with disease duration, fatigue, alanine aminotransferase (ALT), neutrophils, albumin, and use of hormone. •The study also finds that the QoL of pSS-ILD is significantly lower than in patients with non-ILD, especially the score in the dimension of role physical function. [ABSTRACT FROM AUTHOR]

Background: We established a multi-centre online registry for primary Sjögren's syndrome (pSS) in China, and compared Chinese patients with those from other countries. Methods: Data were from 87 rheumatology centres in 27 provinces. All 2986 patients had pSS according to the 2002 American-European Consensus Group or the 2016 American College of Rheumatology/European League Against Rheumatism. All centres used the same methods. Data on demographics, clinical parameters, laboratory results, disease activity and treatments were examined. Results: The female:male ratio was 22.9:1, and the mean age at onset was 46.31 years. A total of 332 (11.1%) patients had thyroid disease, including hyperthyroidism (1.2%), hypothyroidism (6.0%) and subacute thyroiditis (3.9%). Dry eye had a prevalence of 68.59% in Chinese patients, 93.7–96% in European patients and 97.3% in American patients. Dry mouth had a prevalence of 86.5% in Chinese patients, 93.2–96% in European patients and 97.9% in American patients. Fewer Chinese than European patients had arthritis (6.9% vs. 15–19.3%). ANA positivity was 90.7% in Chinese, 81.3% in European and 77.6% in American patients. Anti-SSA antibody positivity was 84.6% in Chinese, 71% in European and 68.2% in American patients. The most commonly used drugs in Chinese patients were hydroxychloroquine (n = 1818; 67.5%), glucocorticoids (n = 1720; 63.9%) and total glucosides of paeony (n = 1120; 41.7%). Conclusions: This study provided information on the phenotypes of Chinese patients with pSS, and identified several differences with patients from other geographical regions. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether primary Sjögren's syndrome (pSS) patients with hyperglobulinemia have an increased risk of all-cause mortality., Methods: Patients who registered in the Chinese Rheumatism Data Centre from May 2016 to July 2021 and met the 2002 American European Consensus Group criteria or 2016 American College of Rheumatology /European League Against Rheumatism classification criteria for Sjögren's syndrome were included. Hyperglobulinemia was defined as any elevated serum levels of immunoglobulin G (IgG), immunoglobulin A (IgA), or immunoglobulin M (IgM). The primary outcome was all-cause death. Data for demographic and clinical characteristics, laboratory results, disease activity, damage scores, and treatments were evaluated., Results: A total of 9527 pSS patients were included in the analysis, of whom 4236 (44.5%) had at least one kind of elevated immunoglobulin level among IgG, IgA, and IgM. Patients with hyperglobulinemia had a significantly increased risk of death (crude hazard ratio 2.60; 95% confidence interval 1.91-3.55; adjusted hazard ratio 1.90; 95% confidence interval 1.20-3.01). The risk of death was positively correlated with IgG level (P trend <.001). The 5-, 10-, and 15-year survival rates of patients with hyperglobulinemia were 96.9%, 92.3%, and 87.9%, respectively, and significantly lower than the corresponding rates of 98.8%, 97.9%, and 96.4% in patients without hyperglobulinemia., Conclusions: Hyperglobulinemia is an independent risk factor for increased all-cause mortality in pSS patients. The risk of death is positively correlated with IgG level., (© Japan College of Rheumatology 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Pulmonary arterial hypertension (PAH) is a rare and severe complication of primary Sjögren's syndrome (pSS). Cohort studies indicate that the underlying diseases of PAH associated with connective tissue disease (CTD-PAH) in Asian countries are different from that in the United States and in Europe. This study investigated the clinical characteristics, survival, and prognostic factors of pSS-PAH in Chinese patients. We enrolled 29 patients with pSS-PAH who visited our referral center during August 2007 and May 2015. PAH was confirmed by right heart catheterization (RHC). Baseline demographic data, clinical manifestations, laboratory tests, autoantibody results, hemodynamics data, and treatment regimens were analyzed. All patients were followed up at the Department of Rheumatology, Peking Union Medical College Hospital (PUMCH) every three to six months. All patients were female. Mean age of pSS onset was 34.4±11.1 years. Mean age of PAH diagnosed by RHC was 40.6±9.0 years. There was no significant difference in age, disease duration, and hemodynamic findings between the survivors and the non-survivors in this cohort. The overall one-, three-, and five-year survival rates were 80.2%, 74.8%, and 67.4%, respectively. Prognostic factors of mortality were time between pSS onset and PAH onset (HR 1.102, 95% CI 1.017-1.185, p=0.018) and cardiac index<2 l/min/m2 (HR 5.497, 95% CI 1.063-28.434, p=0.042). In contrast, the use of immunosuppressants (HR 0.110, 95% CI 0.024-0.495, p=0.004) was related to better survival. This study demonstrates that the predictors of mortality in patients with pSS-PAH include delayed onset of PAH in pSS and worse cardiac function. Immunosuppressants can improve the prognosis of pSS-PAH. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this article was to systematically review the literature to identify the impact of primary Sjögren's syndrome (pSS) on specific health-related quality of life (HRQoL) domains. Methods: A meta-analysis was performed, and the related articles were searched in Medline, Embase, Cochrane Library, China National Knowledge Infrastructure, China Biology Medicine, and Web of Science databases and in reference lists of articles and systematic reviews. Score of the Short Form 36 (SF-36) questionnaire was used as the outcome measurement, and mean differences (MD) with 95% confidence intervals (CIs) were calculated. Results: Seven studies were included, comprising 521 patients with pSS and 9,916 healthy controls. The SF-36 questionnaire score of each domain (physical function, role physical [RP] function, emotional role function, vitality, mental health, social function, body pain, general health, physical component scale, mental component scale) was lower in patients with pSS than in healthy controls, especially the score in the dimension of RP function. Conclusion: This meta-analysis showed that patients had lower pSS score in each dimension of the SF-36, mostly in the RP function. This demonstrated that targeted interventions should be carried out to improve the HRQoL of pSS patients. [ABSTRACT FROM AUTHOR]

Background A retrospective analysis of clinical data from primary Sjogren's syndrome ( pSS) patients with lung cancer was conducted in order to guide further clinical work. Methods From January 1993 to December 2010, 10 pSS patients with lung cancer were hospitalized at the Peking Union Medical College Hospital. One hundred and three p SS patients were recruited as the controls. Patients' clinical data was retrospectively analyzed. Result The incidence rate of lung cancer in pSS patients was 0.477%. The duration from diagnosis of pSS to lung cancer in the 10 patients was 0.92∼42 years. The pSS patients with lung cancer were significantly older than those without lung cancer (60.8 ± 8.9 vs. 44.9 ± 12.1, P < 0.001). Eight of the pSS patients with lung cancer (80%) were female nonsmokers; five pSS patients with lung cancer (50%) had lung involvement, exhibiting diffuse parenchymal lung disease. Adenocarcinoma was the most common pathological type of lung cancer (90%). Tumor node metastasis staging of lung cancer included: four cases of Ib (40%), one case of IIIb (10%), four cases of IV (40%) and one case undetermined (10%). Conclusion The incidence rate of lung cancer in pSS patients was higher with respect to the normal population. Physicians should closely observe lung cancer incidence during the pSS follow-up period. Adenocarcinoma was the most frequently seen lung cancer pathology in pSS patients. Clinical stages and individualized treatment for pSS patients with lung cancer should be carefully determined. [ABSTRACT FROM AUTHOR]

Objective: To observe the effect of Chinese herbal medicine for nourishing yin, supplementing qi, and activating blood on the expression of interferon-γ (IFN-γ)/interleukin-4 (IL-4) in peripheral blood and disease activity in primary Sjogren's syndrome (pSS) patients, and to study the relationship between the immune balance of Th1/Th2 and the disease activity. Methods: A total of 66 pSS patients were randomized with tossing coins method into two groups: the integrative therapy group (34 cases) and the control group (32 cases); and 28 healthy subjects were taken as the normal group. The integrative therapy group was treated by Chinese herbal medicines for nourishing yin, supplementing qi, and activating blood combined with hydroxychloroquine sulfate tablets and the control group was treated with hydroxychloroquine sulfate tablets. The treatment course was 3 months for both groups. The levels of serum immunoglobulin G (IgG), erythrocyte sedimentation rate (ESR), IFN-γ and IL-4 in peripheral blood were measured before and after treatment. Results: Compared with the normal group, the levels of IgG, ESR, IFN-γ and IL-4 were significantly increased in pSS patients ( P<0.05). Remarkably, after 3 months of treatment, these levels were dramatically decreased in both the integrative therapy group and the control group, although still higher than the normal group. The levels of IgG, ESR, IFN-γ and IL-4 in the integrative therapy group were lower than the control group and the same group before treatment ( P<0.05). The ratio of IFN-γ/IL-4 also significantly decreased after treatment. Moreover, the level of IFN-γ and the ratio of IFN-γ/IL-4 in the integrative theraphy group were significantly lower than the control group ( P<0.05). For all patients the ratio of IFN-γ/IL-4 before and after treatment was positive correlated with the levels of IgG and ESR. Conclusion: Chinese herbal medicine for nourishing yin, supplementing qi, and activating blood can alleviate the disease activity of pSS by regulating the immune balance of Th1/Th2. [ABSTRACT FROM AUTHOR]

Objective To evaluate the sensitivity and specificity of international classification criteria (2002) for primary Sjögren's syndrome (pSS) and the role of lower lip biopsy in diagnosis of pSS in Chinese patients. Methods Patients who were diagnosed by the experts/rheumatologists as pSS during 1990-2002 from the Department of Rheumatology, Peking Union Medical College Hospital were retrospectively collected as experimental group. Patients who were diagnosed as non-pSS connective tissue diseases or non-connective tissue diseases served as control group. Those with a history of head-neck radiation, hepatitis C virus infection, AIDS, lymphoma, sarcoidosis, graft versus host disease (GVHD), and anti-acetylcholine drug use were exempted. Both groups were required to complete questionnaires about symptoms such as dry eyes and dry mouth, and complete the objective tests of keratoconjunctivitis and xerostomia including Schirmer test, corneal staining, unstimulated salivary flow, sialography, lower lip biopsy, and antinuclear antibodies (including anti-SSA/SSB antibodies) test. Results A total of 330 pSS patients were included in experimental group and 185 non-pSS patients in control group. The mean age of both groups matched (47.8±10.9 years vs. 46.2±13.6 years, P> 0.05). The sensitivities of the criteria in pSS patients with lower lip biopsy and in pSS patients without lower lip biopsy were 89.2% and 87.2%, respectively; the overall sensitivity was 88.5%. The specificity was 97.3%. A total of 11.3% pSS patients with negative anti-SSA/SSB antibodies were diagnosed as pSS by lower lip biopsy. Conclusion The international classification criteria (2002) for pSS is feasible in Chinese patients. It has high sensitivity and specificity, and may serve as diagnosis criteria in routine clinical practice. [ABSTRACT FROM AUTHOR]

Introduction: There is currently no established effective treatment for primary Sjögren's syndrome (pSS). Traditional Chinese Medicine (TCM) is widely used in China and is reported to improve patient symptoms. This study compare the clinical efficacy and safety of herbal decoction CheReCunJin alone and combined with hydroxychloroquine for the treatment of pSS., Methods: Seventy pSS patients without visceral involvement were randomly assigned in equal numbers to oral administration of CheReCunJin decoction only (group 1) or CheReCunJin decoction combined with hydroxychloroquine (group 2), Efficacy was evaluated after 3 months of treatment by the TCM syndrome and total effectiveness scores, European League Against Rheumatism (EULAR) Sjögren's Syndrome Patient Reported Index (ESSPRI), and Sjögren's Syndrome Disease Activity Index (ESSDAI), Schirmer's test, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and immunoglobulin G (IgG) levels. Safety was assessed., Results: There were no differences in the baseline characteristics of the two groups. Compared with baseline values, the TCM syndrome, ESSPRI and ESSDAI scores, ESR, CRP, and Schirmer's test results improved significantly in both groups after treatment (p < 0.05). There was no significant difference in the TCM syndrome total effectiveness rate between the two groups (p = 0.31). Between-group differences in the changes in ESSPRI, ESSDAI, ESR, CRP, Schirmer's test, and IgG after treatment were not significant (all p> 0.05). Adverse reactions were reported in 5.88% of group 1 and 3.33% of group 2 participants (p = 0.83)., Conclusion: CheReCunJin decoction alone was effective and safe for the treatment of pSS., Trial Registration: Chinese Clinical Trial Registry: ChiCTR1800016471., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Patients with primary Sjögren's syndrome (pSS) reportedly believe that their symptoms worsen on extreme weather days due to variations in environmental conditions. However, few studies have assessed the acute effects of environmental exposure on the onset of pSS. This study aimed to evaluate the exposure-response relationship between extreme environmental conditions and pSS outpatient visits., Method: We obtained data on pSS outpatient visits from two provincial general hospitals in Hefei, China, during 2014-2019. A distributed lag non-linear model was used to estimate the exposure-lag-response relationship between environmental variables and pSS., Results: We detected significant and non-linear associations between extreme environments and pSS. The estimated relative risk (RR) for a lag of 3 days was 1.11 (95% CI: 1.03 to 1.19) for extreme cold and for a lag of 21 days was 1.07 (95% CI: 1.01 to 1.12) for extreme dampness. Long sunshine duration was positively correlated with pSS (lag 11, 1.05, 95% CI: 1.01 to 1.08). Moreover, female patients were more susceptible to these effects. Patients older than 65 years old were more vulnerable to frigid environments (lag 3, RR = 1.30, 95% CI: 1.09 to 1.54), while younger patients were more vulnerable to extreme dampness (lag 21, RR = 1.10, 95% CI: 1.03 to 1.16). Extreme cold and high humidity were negatively correlated with the same-day outpatient visits., Conclusions: Our findings suggest a potential relationship between exposure to extreme environmental conditions and increased risk of pSS outpatient visits. We therefore suggest that policymakers and doctors aim to further our understanding of environmental effects on pSS and adopt adequate measures to alleviate pSS symptoms. Key Points • Extreme cold, extreme dampness, and long sunshine duration increased the risk of pSS outpatient visits, especially for females. • Young pSS patients are more susceptible to a rise in humidity. • Elderly pSS patients are more sensitive to extreme cold weather., (© 2021. International League of Associations for Rheumatology (ILAR).)

Background: Interstitial lung disease (ILD) is a serious complication in patients with Sjögren's syndrome (SS). Most studies on primary SS (pSS) with ILD are limited in sample size, and studies on secondary SS (sSS) with ILD are rare. This study aimed to elucidate both primary and secondary SS-associated ILD (SS-ILD) based on a large cohort., Methods: The medical records of hospitalized patients diagnosed with SS at the Second Xiangya Hospital of Central South University from January 2010 to May 2020 were retrospectively reviewed. Clinical manifestations, medical history, biological results and imaging data were collected., Results: Of the 735 SS patients enrolled in this study, 563 (76.6%) were diagnosed with pSS, 172 (23.4%) were diagnosed with sSS. Additionally, 316 (43.0%) were diagnosed with SS-ILD. No significant difference was found between the pSS and sSS groups concerning the incidence of ILD ( p  = .718). Factors associated with SS-ILD were older age ( p  < .001), male sex ( p  = .032), female sex at menopause ( p  = .002), Raynaud's phenomenon ( p  < .001), low levels of albumin ( p  = .010) and respiratory symptoms ( p  < .001). The SS-ILD group showed higher counts of platelets ( p  < .001). The three most frequent high-resolution CT (HRCT) findings of SS-ILD were irregular linear opacities (42.7%), grid shadows (30.7%) and pleural thickening (28.5%). NSIP (56.3%) was the most frequent HRCT pattern. Compared with pSS patients with ILD (pSS-ILD) patients, sSS patients with ILD (sSS-ILD) patients had a higher incidence of proteinuria ( p  < .001) and hypercreatinaemia ( p  = .013), a higher level of erythrocyte sedimentation rate (ESR) ( p  = .003), low levels of complement 3 (C3) ( p  = .013), lymphocytes ( p  = .009) and leukocytes ( p  = .024), and worse DLCO (%Pred) ( p  = .035)., Conclusions: ILD is a common pulmonary involvement in both pSS patients and sSS patients. Older age, male sex, female sex at menopause, Raynaud's phenomenon, low albumin levels and respiratory symptoms are risk factors associated with SS-ILD. NSIP is important HRCT feature of SS-ILD. sSS-ILD patients showed worse laboratory results and pulmonary function.KEY MESSAGEOlder age, male sex, female sex at menopause, Raynaud's phenomenon, low albumin levels and respiratory symptoms are risk factors associated with SS-ILD.SS-ILD patients show higher counts of platelets and less purpura.sSS-ILD patients have worse laboratory results and pulmonary function.

Objective: This study explored differences between primary Sjögren's syndrome-associated interstitial lung disease (pSS-ILD) patients with and without ILD progression, and analyzed the factors affecting the progression and prognosis of pSS-ILD., Methods: This study is a retrospective cohort study which enrolled 113 pSS-ILD patients hospitalized between 2011 and 2017., Results: The 3-year survival rate of the pSS-ILD patients was 91.15%, and the 5-year survival rate was 84.07%. Univariate analysis showed that Raynaud's syndrome, hypoproteinemia, extensive lung involvement, possible usual interstitial pneumonia pattern were risk factors for the progression of ILD in patients with pSS-ILD, and cyclophosphamide was a protective factor for the progression of ILD in patients with pSS-ILD. Multiple logistic regression analysis showed that extensive lung involvement (odds ratio 4.143, 95% CI: 1.203-14.267, P < .05) was an independent risk factor for the progression of pSS-ILD. Cox hazard analysis showed that pSS-ILD with hypoproteinemia (hazard ratio [HR] 17.758, 95% CI: 4.753-66.340, P <- .05) and extensive lung involvement (HR 3.450, 95% CI: 1.419-8.390, P < .05) were associated with worse survival of patients., Conclusion: Extensive lung involvement is an independent risk factor for the progression of ILD in patients with pSS-ILD. Hypoproteinemia and extensive lung involvement are independent risk factors for mortality in patients with pSS-ILD, after controlling for potentially influential variables., (© 2020 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Objective: We aimed at investigating the expression level of vascular endothelial growth factor-A (VEGF-A) in patients with primary Sjögren's Syndrome (pSS) and evaluating the relationship between serum VEGF-A and the laboratory indicators that are associated with it in pSS., Methods: The VEGF-A levels were measured by ELISA in a total of 88 participants, including 58 patients with pSS and 30 healthy people. The VEGF-A levels between two groups were analyzed., Results: The serum levels of VEGF-A in pSS and control groups were 175.50 (112.00,296.50) pg/mL and 181.50 (155.25,288.50) pg/mL, without statistically significant difference. The associations were found between serum levels of VEGF-A with C reactive protein (CRP) (r=0.265, P <0.05), white blood cells (WBC) (r=0.302, P<0.05), neutrophils (NEUT) (r=0.349, P <0.05), platelets(PLT) (r=0.276, P <0.05), complement 3 (C3) (r=0.477, P<0.05), complement 4 (C4) (r=0.387, P <0.05) and CA19-9 (r=0.392, P <0.05). Among these laboratory indicators, VEGF-A was correlated with platelets and complement 4 in patients with pSS., Conclusions: In patients with pSS, the levels of VEGF-A were independently influenced by the levels of platelet and complement 4, which indicated the intermodulation between the growth factor and immune system in the autoimmune disease., (© 2020 by the Association of Clinical Scientists, Inc.)

Objectives: This study aims to characterize the expression profiles of circRNAs in primary Sjogren's Syndrome (pSS) and examine the potential of noninvasive circular RNAs (circRNAs) as biomarkers of pSS., Methods: We performed RNA sequencing of minor salivary gland (MSG) biopsies from four pSS and four non-pSS individuals (subjects undergoing MSG biopsies but not meeting 2012 or 2016 ACR classification criteria for SS). Differentially expressed circRNAs were identified by DESeq2, and confirmed by quantitative real-time PCR in the MSGs as well as in plasma exosomes in 37 pSS and 14 non-pSS subjects. Discriminatory capacity testing using receiver operating characteristic analysis was used to evaluate the performance of circRNAs as diagnostic biomarkers for pSS., Results: Circ-IQGAP2 and circ-ZC3H6 had significantly upregulated expression in the MSGs of pSS patients, and this elevated expression was confirmed by quantitative real-time PCR of plasma exosome RNA. The expression of these circRNAs also showed significant correlation with both clinical features, serum IgG level and MSG focus scores. Receiver operating characteristic analysis showed that the indices comprised of both the two circRNAs and clinical features were better able to distinguish pSS from non-pSS subjects with high mean areas under the curve of 0.93 in the MSGs and 0.92 in the plasma exosomes., Conclusion: This study indicated the potential roles of circ-IQGAP2 and circ-ZC3H6 as noninvasive biomarkers for the diagnosis of pSS., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Sjögren's syndrome is a chronic systemic autoimmune disease characterized by lymphocyte proliferation and progressive exocrine gland damage. In China, standardized diagnosis and treatment for Sjögren's syndrome lags behind other common rheumatic diseases, such as rheumatoid arthritis and systemic lupus erythematosus. Based on the evidence and guidelines from China and other countries, Chinese Sjögren's Syndrome Collaborative Research Group together with stomatologist and ophthalmologist developed Standardization of diagnosis and treatment of primary Sjögren's syndrome. The purposes are: (1) to standardize the detection and interpretation of key indicators for the diagnosis of Sjögren's syndrome, including serum anti SSA antibody and labial gland pathology; (2) to suggest using widely accepted disease activity index in evaluation of the disease; (3) to standardize rational management for Sjögren's syndrome patients with topical and systemic diseases.

Aim: This study aimed to retrospectively describe 15 new primary Sjögren's syndrome-pulmonary arterial hypertension (pSS-PAH) cases confirmed by right heart catheterization (RHC). Demographic and clinical characteristics were analyzed and risk factors for PAH in pSS were explored., Method: We retrospectively described 15 new pSS-PAH cases confirmed by RHC referred to our institution between January 2013 and March 2018. We present PAH and pSS characteristics, hemodynamic evaluations, medical management, and outcomes. A matched case control study was carried out to determine the risk factors of PAH in pSS compared with pSS-non-PAH patients., Results: All patients were female with a mean age at PAH diagnosis of 52.9 ± 14.6 years. The delay between the first symptom and PAH diagnosis was 18.7 ± 19.7 months. The most common primary manifestation at PAH onset was exertional dyspnea (13/15). At diagnosis of PAH, PAH was severe with a mean pulmonary artery pressure of 48.8 ± 13.7 mm Hg (range, 27-72 mm Hg) and a mean cardiac index of 2.3 ± 0.6 L/min/m 2 (range, 1.47-3.41 L/min/m 2 ). Compared with the pSS-PAH without pericardial effusion, pSS-PAH with pericardial effusion had larger right arterial (53 [45-56.75] vs 38 [35.5-46.5], P = .018) and right ventricular sizes (47 [42.75-51.25] vs 36 [32.5-41], P = .007). Compared with the pSS non-PAH group, we identified 2 risk factors for PAH in pSS: pericardial effusion (odds ratio [OR] [95% CI], 14.29 [1.14-166.67], P = .039) and liver involvement (OR [95% CI], 14.71 [1.14-166.67], P = .035)., Conclusion: For pSS patients, PAH can be the first manifestation. We believe that systemic evaluation, especially in patients with pericardial effusion and liver involvement, is important to identify high-risk patients for PAH, improving their prognosis., (© 2019 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Background: Prevalence of anxiety and depression is high in people with Primary Sjögren's syndrome (pSS). However, there are currently no known reported studies about anxiety/depression in pSS patients from China. Our aim was to compare anxiety/depression in pSS patients and healthy controls; to investigate the prevalence of anxiety and/or depression among pSS patients in China; to evaluate its relationship with the disease activity, fatigue, pain, education, ocular surface disease, oral health, swallowing disorders, employment status, European League Against Rheumatism Sjögren's Syndrome Patient Reported Index(ESSPRI) as well as to analyze potential determinants of anxiety and depression. Methods: In this study, 160 pSS patients and 170 age- and sex- matched healthy controls were included. Participants completed self-administered questionnaires, Hospital Anxiety and Depression Scale (HADS) and so on. Independent samples t-tests, χ2 analyses and multivariable stepwise logistic regression modeling were used to analyze the data. Results: We found 33.8% pSS patients were anxiety, and 36.9% had depression, which were significantly higher than controls. And there were significant correlations among education, employment status, disease activity, fatigue, ocular surface disease, ESSPRI, oral health, swallowing disorders and anxiety/depression. Meanwhile, logistic regression analysis revealed that oral health and swallowing disorders were significantly associated with anxiety in pSS patients; as well as fatigue was significantly associated with depression. Conclusions: The prevalence of depression and anxiety was high in adult pSS patients. Interestingly, oral health and swallowing disorders were the most important predictors of anxiety in pSS patients. Therefore, rheumatologists should pay attention to the potential mental comorbidities while managing patients with pSS and provide the basis for mental health providers in order to identify effective strategies for preventing and treating depression and anxiety among adult pSS patients. Simultaneously, rheumatologists should also focus on the oral health and swallowing disorders in pSS patients. [ABSTRACT FROM AUTHOR]

Pulmonary arterial hypertension (PAH) is a severe complication and leading cause of mortality in patients with primary Sjogren's syndrome (pSS). This study was to investigate the overall survival rates and the utility of red blood cell distribution width (RDW) as a potential prognostic factor of pSS-PAH. This cohort study retrospectively enrolled 55 patients with pSS-PAH who were followed up at the Department of Rheumatology of Peking Union Medical College Hospital (PUMCH) between August 2007 and May 2017. The patients were stratified according to the level of RDW (≤ 15.0 and > 15.0%). Baseline demographics, laboratory results, pulmonary function conditions, hemodynamic assessments, and treatment regimens were analyzed. Cox proportional hazards regression analysis was used to identify whether RDW level is a factor related to adverse outcome. A total of 55 patients were recruited, with an average age of 38.9 ± 9.3 years. Fifty-four were female (98.2%), and the average duration at the time of PAH diagnosis was 25.5 ± 33.2 months. Higher RDW levels were found in patients who deceased in follow-up (13.8 ± 2.6 vs 16.5 ± 1.6%, p = 0.003) and with higher NYHA classes (13.8 ± 1.8 vs 16.5 ± 2.9%, p < 0.001). Patients with RDW > 15% had a significantly worse overall survival than patients with RDW ≤ 15% (3-year survival rate 59.5 vs. 88.7% log-rank p = 0.015). Cox regression analysis identified RDW > 15% as a prognostic factor for adverse outcome (HR 1.786, 95% CI 1.137-2.803, p = 0.012). RDW can serve as a potential negative prognostic factor of pSS-PAH.

In order to evaluate autoantibody to SP-1 as an early biomarker in pSS, we investigated autoantibody to SP-1 in Chinese patients with primary Sjögren's syndrome (pSS). Autoantibodies to SP-1 are significantly increased in pSS patients compared to RA patients, SLE patients, and healthy people without secondary SS. The presence of anti SP-1 antibodies was negatively correlated with the focus score (FS), RF, and salivary gland function. It was positively correlated with FS=0, RF≤20, and normal salivary gland function. In further studies, the autoantigen SP-1 was identified in ductal epithelia of salivary glands in il14α TG mice by IIF. SP-1 mRNAs expression increased with growing age in il14α TG mice. SP-1 mRNA was also identified in labial biopsies of patients with pSS. In conclusion, autoantibody to SP-1 is an early marker in pSS. It is useful to diagnose pSS patients who lack RF or antibodies to Ro/La., (Copyright © 2017. Published by Elsevier Inc.)

Aim: To assess the clinical and laboratory features of primary Sjogren's syndrome (pSS) in a large teaching hospital in China., Methods: Three hundred and fifteen pSS patients diagnosed according to American-European Classification Criteria and consecutively admitted to Anhui Provincial Hospital from 1 January 1999 to 30 September 2012 were retrospectively selected in this study., Results: The median age was 46.8 ± 14.4 years (range 13-83 years) and the majority of patients were female (96.5%). The common clinical features at initial presentations were dry mouth (50.2%), dry eyes (31.4%) and joint pain (24.8%); 92.6% of patients had positive anti-SSA antibody and 49.2% patients had positive anti-SSB antibody. One hundred and eighteen patients underwent labial salivary gland biopsy. According to Chisholm grading criteria, grade 3 to 4 was present in 58.5% of the patients. The frequency of interstitial lung disease (ILD) occurred (20.9%) in the patients with systemic extraglandular manifestations. The patients with ILD were frequently associated with positive anti-SSA (P = 0.005) and low levels of C3. The most common impairment of lung function was small airway function abnormalities. Sixty-six pSS patients with ILD (pSS-ILD) were diagnosed with high-resolution computed tomography and treated with corticosteroids and/or immunosuppressants, in which 18 patients had improved pulmonary function., Conclusion: Labial salivary gland biopsy and anti-nuclear antibodies spectrum were important to the diagnosis of pSS. The pSS patients had high percentage of ILD, especially small airway function abnormalities. The combination of corticosteroids and immunosuppressants appears to be effective in treatment of pSS patients with ILD., (© 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.)