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Epidemiology of primary Sjögren's syndrome: A systematic review and meta-analysis

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Abstract

Objective: Epidemiological studies of primary Sjögren's syndrome (pSS) are crucial for describing the burden to society and the public medical system and for shedding light on aetiology. Previous reports of the epidemiology of pSS show variable outcomes. We conducted a systematic review of the epidemiology of pSS to assess the prevalence rates (PRs) and incidence rates (IRs), and to investigate possible geographic variations in pSS. Methods: A systematic literature search of PubMed and Embase (updated to 22 October 2013) was performed to identify all published reports on the epidemiology of pSS. The incidence and prevalence rates of pSS were summarised with IRs or PRs and 95% CIs. Results: The literature search yielded 1880 related citations. Only 21 fulfilled the inclusion criteria. According to a random-effects model, the pooled IR for pSS was 6.92 (95% CI 4.98 to 8.86) per 100 000 person-years. The overall PR was 60.82 (95% CI 43.69 to 77.94) cases per 100 000 inhabitants with a slightly lower estimate of Baodong Qin is BDQ, Jiaqi Wang is JQW, Zaixing Yang is ZXY, Renqian Zhong is RQZ. 43.03 (25.74 to 60.31) cases per 100 000 inhabitants when only considering population-based studies. The female/male ratio in incidence data was 9.15 (95% CI 3.35 to 13.18). The female/male ratio in prevalence data was 10.72 (95% CI 7.35 to 15.62). The overall age of pSS patients was 56.16 years (95% CI 52.54 to 59.78). Conclusions: Incidence and prevalence rates of pSS vary widely around the world. The results help us better understand the global epidemiology of pSS. Large population-based studies combining meticulous case-finding and case-ascertainment strategies are needed.

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... It has been estimated that 10% of patients with dry eye disease (DED) suffer from SS. However, two-thirds of these patients remain undiagnosed, and a median diagnostic delay of 10 years is reported [73]. Several factors may explain the underdiagnosis of SS: ...
... Dry eye and dry mouth are highly prevalent, making it difficult for clinicians to identify patients with underlying SS [73]. ...
... [28] However, around a third of patients with SS will develop systemic complications, contributing to a diminished quality of life and increased morbidity and mortality. The SS is associated with an alarmingly high risk of lymphoma development, which is a particularly concerning complication among the various systemic complications that may arise [3,73]. Early detection of SS may prevent complications and allow for clinical surveillance for the development of serious systemic manifestations. ...
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Sjögren's syndrome is a chronic and insidious auto-immune disease characterized by lymphocyte infiltration of exocrine glands. The patients typically present with ocular surface diseases related to dry eye and other systemic manifestations. However, due to the high prevalence of dry eye disease and the lack of objective and clinically reliable diagnostic tools, discriminating Sjögren's syndrome dry eye (SSDE) from non-Sjögren's syndrome dry eye (NSSDE) remains a challenge for clinicians. Diagnosing SS is important to improve the quality of life of patients through timely referral for systemic workups, as SS is associated with serious systemic complications such as lymphoma and other autoimmune diseases. The purpose of this article is to describe the current molecular understanding of Sjögren's syndrome and its implications for novel diagnostic modalities on the horizon. A literature review of the pre-clinical and clinical studies published between 2016 and 2022 was conducted. The SSDE pathophysiology and immunology pathways have become better understood in recent years. Novel diagnostic modalities, such as tear and saliva proteomics as well as exosomal biomarkers, provide hope on the horizon.
... Advances in Rheumatology *Correspondence: aysapinheiro@hotmail.com when it is called primary Sjogren's Syndrome, or in conjunction with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), or other rheumatic diseases, when it is called secondary Sjogren's Syndrome [2]. Primary Sjogren's Syndrome (pSS) is a common disease that affects 0.04% to 0.08% of people worldwide and has a female to male ratio of 9-14 to 1 [3]. As the process leads to progressively reduced or absent glandular secretion, along with mucosal dryness, Sjogren's Syndrome (SS) is characterized by symptoms ranging from xerophthalmia, xerostomia, fatigue, myalgias, and arthralgia to severe systemic symptoms with cutaneous, vascular, renal, pulmonary, or neurological involvement [2,4]. ...
... Chronic viral disease, mainly because of HCV, was the main cause of liver involvement in SS, with a prevalence of 13%, nearly 3 times higher than autoimmune liver involvement (5%). Patients with autoimmune liver disease had higher ESR and gamma globulin values and a higher prevalence of ANA, antimitochondrial, anti-smooth muscle, anti-Ro, and anti-La antibodies, while patients with chronic viral liver disease had a higher frequency of cryoglobulinemia and hypocomplementemia [3]. ...
... Hepatic stiffness was analyzed by elastography. Twelve patients (11.9%) had significant liver fibrosis and their predictors were leukopenia ≤ 4000/ mm [3], serum albumin ≤ 3.8 mg/dL, and aspartate aminotransferase ≥ 27 [8]. ...
Article
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Sjogren's syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration of the exocrine glands and other organs, associated with sicca syndrome but also with systemic involvement with varying degrees of severity. Despite their importance, some systemic manifestations, mainly liver, gastrointestinal, and pancreatic are not routinely evaluated. To address these manifestations, the Sjögren' s Syndrome Committee of the Brazilian Society of Rheu-matology conducted a broad systematic review of the literature on studies investigating prevalence and diagnosis of these symptoms in Sjogren´s patients and made recommendations based on the findings. Agreement between the experts was achieved using the Delphi method. This is the second part of this guideline, providing 6 recommendations for liver, gastrointestinal, and pancreatic care of SS patients.
... The disease mainly affects women, with the average female to male ratio of 9:1, and is one of the most common rheumatic disorders [2]. Incidence and prevalence rates of pSS vary widely around the world. ...
... The prevalence is estimated at 43 per 100,000 people [2]. Although pSS phenotype may vary as a function of geolocation and ethnicity, objective findings of salivary and/or lacrimal glands destruction were found in most patients. ...
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Introduction: Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease that mainly affects salivary and lacrimal glands leading to their progressive destruction. Objectives: The primary aim of this study was to verify whether shear wave elastography (SWE) of lacrimal glands can be used to differentiate primary Sjögren's syndrome patients from healthy controls. The secondary aim was to demonstrate if there are any associations between SWE result, results of other ocular tests included in pSS diagnosis (Schirmer's test, ocular staining score - OSS) and subjective symptoms of eye dryness. Patients and methods: The study included 45 pSS patients (41 females and 4 males) and 108 healthy controls (104 females and 4 males). All pSS patients met the 2016 ACR/EULAR pSS classification criteria. All subjects underwent bilateral SWE of the lacrimal glands with the results expressed in kilopascals. Schirmer's test was performed in all the patients and OSS was calculated only in the pSS group. Results: Patients with pSS had significantly higher SWE values for the lacrimal glands than the control group. No significant differences in the elastography results were observed between the group of pSS patients with or without eye dryness confirmed by Schirmer's test and OSS result, and pSS patients with or without subjective symptoms of dryness. The optimal cut-off point for the diagnosis of pSS in the case of the average result of lacrimal gland elastography is > 7.2 kPa (sensitivity 88.9%, specificity 88.0%). The result of lacrimal SWE may be a good classifier for the diagnosis of pSS, with AUC 89.8 (95% CI 81.5 - 98.1%). Conclusions: Shear wave elastography of lacrimal glands is a non-invasive, quantitative method that seems to be a reliable additional examination tool to support the diagnosis of pSS. Its role among functional tests has not yet been well defined. To confirm the suitability of SWE for pSS diagnosis, a standardized and widely accepted study protocol should be defined first.
... GM dysbiosis may break the balance and lead to primary Sjögren's syndrome (pSS), which may be connected with chronic local gut mucosal inflammation, molecular mimicry, and other mechanisms [10] . pSS is a systemic autoimmune disease most common in middle-aged women [11] . It affects exocrine glands and often causes dryness of the eyes or mouth, often affecting other organs such as the kidneys and lungs [12] . ...
... Cano-Ortiz, 2020 [24] Spain individuals. A correlation was observed between GM diversity and dry eye symptom severity [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]23] . As a possible indicator of GM dysbiosis [25][26] , the Firmicutes/Bacteroidetes (F/B) ratio is often observed to be decreased in patients with autoimmune diseases [27][28] . ...
Article
The recognition of the profound impact of the human gastrointestinal microbiome (GM) on human autoimmune diseases has gradually increased thanks to deeper research efforts. As a systemic autoimmune disease, primary Sjögren’s syndrome (pSS) cannot be completely cured. Human studies have revealed that GM species and diversity are altered in patients with pSS compared with healthy individuals. Animal studies have provided possible mechanisms for the association between pSS and GM. The potential role of GM in pSS is exerted through several mechanisms. GM dysbiosis leads to increased intestinal permeability, which increases the risk of GM antigen exposure and activates specific autoreactive T lymphocytes via “molecular mimicry”. In addition, GM antigen exposure and intestinal immune tolerance loss caused by GM dysbiosis together induce chronic local gut mucosal inflammation, which deteriorates to systemic chronic non-specific inflammation with the circulation of pro-inflammatory lymphocytes and cytokines. These factors eventually activate autoreactive B lymphocytes and lead to pSS. If GM plays a key role in the pathogenesis of pSS, clarifying the underlying mechanisms will be helpful for the development of new therapies targeting GM for dry eye associated with pSS. This review summarizes the latest knowledge about the relationship between GM and pSS, with the aim of contributing to future research and to the development of new clinical applications.
... characterized by the infiltration of leukocytes into the exocrine glands, particularly the salivary and lachrymal glands [1,2]. It is much more common in females than in males, particularly in middle-aged women [3]. The pSS prevalence rate in China is approximately 0.33%-0.77%, ...
... Several previous studies have reported dysbiotic salivary microbiota in pSS patients [17][18][19][20][21][22][23]. Intestinal dysbiosis has recently been considered a possible environmental influence in pSS etiology [1][2][3]24]. To our knowledge, pSS patient characteristics in Northern China have never been reported. ...
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This study analyzes and compares the structure and diversity of gut microbiota in patients with primary Sjögren’s syndrome (pSS) in Northern China to healthy individuals to identify clinical features associated with dysbiosis. We included 60 Chinese pSS patients and 50 age- and gender-matched healthy controls. DNA was extracted from stool samples and subjected to 16S ribosomal RNA gene analysis (V3-V4) for intestinal dysbiosis. In addition, patients were examined for laboratory and serological pSS features. A Spearman’s correlation analysis was performed to assess correlations between individual bacteria taxa and clinical characteristics. The alpha-diversity (Chao1 and Shannon Index) and beta-diversity (unweighted UniFrac distances) of the gut microbiota differed significantly between pSS patients and healthy controls. Further analysis showed that several gut opportunistic pathogens ( Bacteroides , Megamonas , and Veillonella ) were significantly more abundant in pSS patients and positively correlated with their clinical indicators. In contrast, some probiotic genera ( Collinsella , unidentified_ Ruminococcaceae , Romboutsia , and Dorea ) were significantly decreased in pSS patients and negatively correlated with their clinical indicators. Therefore, pSS patients in Northern China showed a dysbiotic intestinal microbiome enriched for potentially pathogenic genera that might be associated with autoimmune disease.
... [3,7] SS is a lymphoproliferative disease with autoimmune features characterized by mononuclear cell infiltration of exocrine glands, notably the lacrimal and salivary glands. [3,8,9] It is named after the Swedish ophthalmologist Henrik Sjögren (1899-1986). As SS is a multisystem disorder that is heterogenous in its presentation, course, and outcome, there is still no single clinical, laboratory, pathological, or radiological feature that could serve as a "gold standard" for the diagnosis YMS and YK contributed equally to this work. ...
... The estimated worldwide incidence of SS is seven cases per 100,000 population, with higher rates reported in Europe and Asia. [8] The pulmonary manifestation of SS is variable. The airways are likely the most frequently involved area of the respiratory system in SS, including the nasal mucosa, trachea (xerotrachea), bronchi (xerobronchitis), or bronchioles. ...
Article
Rationale: Pulmonary manifestations of Sjögren syndrome (SS) are variable and may involve the airway or lung parenchyma and increase the risk of vascular and malignant disease. However, to date, only one case of pulmonary arteriovenous malformation (AVM) has been reported in a patient with SS. Here, we report a rare case of recurrent pulmonary AVMs with aggravating multiple cysts in a patient with SS during a period of 14 years. Patient concerns: A 45-year-old woman was diagnosed with SS and pulmonary AVM in the right lung. Her AVMs were embolized successfully and she was followed up annually for 14 years. Eleven years after the initial treatment, her chest computed tomography showed new pulmonary AVMs in the left lung with aggravating multiple cysts. Diagnosis: We diagnosed her with SS according to the American-European consensus group criteria of 2010. Chest computed tomography and angiographic findings confirmed the recurrence of pulmonary AVMs. Interventions: The patient's recurrent pulmonary AVMs were successfully treated by embolization. Outcomes: Although her multiple cystic lung lesions had been aggravating during 14 years, she received embolization for the pulmonary AVMs twice and developed no complication related to these procedures. Currently, the patient is 56 years old and still alive with good performance state. Lessons: To date, only one case of pulmonary AVM has been reported in a patient with SS. The patient died 2.5 years after the diagnosis without recurrence of AVM. Here, we present a rare case of recurrent pulmonary AVMs associated with aggravating multiple cysts in both lungs, which were observed during long-term follow-up, in a patient with SS.
... Various serological markers are associated with the phenotypic expression of this disease, principally anti-Ro (SS-A) and anti-La (SS-B) antibodies (2). pSS is currently considered the most prevalent systemic autoimmune rheumatic illness after rheumatoid arthritis (1), with an estimated prevalence of 60.82 cases per 100,000 inhabitants (3). This disease predominantly affects women (≅ 10:1), with an incidence peak between 40 and 60 years-old (3). ...
... pSS is currently considered the most prevalent systemic autoimmune rheumatic illness after rheumatoid arthritis (1), with an estimated prevalence of 60.82 cases per 100,000 inhabitants (3). This disease predominantly affects women (≅ 10:1), with an incidence peak between 40 and 60 years-old (3). pSS pathophysiology is not fully understood, however abnormal functions of plasmacytoid dendritic cells, B and T lymphocytes and activated salivary gland epithelial cells promoting the production of numerous cytokines and autoantibodies are cardinal findings (4). ...
Article
Objectives: Primary Sjögren's syndrome (pSS) is an inflammatory chronic disorder that mainly affects exocrine glands. Additionally, oral infections can aggravate the glandular dysfunction. However, data on primary dental care (PDC) treatment in pSS are scarce. This study aimed to appraise the impact of PDC on Xerostomia Inventory (XI), unstimulated/stimulated salivary flow rates and salivary cytokine profile in pSS. Methods: Fifty-two pSS patients and 52 sex-/age-matched control participants without systemic autoimmune diseases were comprised in a prospective study. At inclusion, all participants were assessed through a standardized protocol, measurement of salivary pro-inflammatory cytokines, and underwent PDC. Dental procedures included: oral hygiene guidance, restorative treatment of caries, surgical removal of residual roots and impacted or partially erupted teeth, cysts, supra and subgingival periodontal scaling and treatment of soft tissue disorders (removal of lesions and treatment of opportunistic infections). After 3 months, the clinical/laboratorial assessments were repeated. Results: At inclusion, Decayed, Missing and Filled Teeth (DMFT) index was higher in pSS patients than in control group (13.3±8.2 vs. 8.6±6.2, p=0.002), whereas periodontal parameters were comparable in both groups (p>0.05). After PDC, 26.9% of pSS patients showed reduction of at least 6 points (clinical improvement) in XI, but mean XI remained unchanged (p=0.285). PDC resulted in increase in mean unstimulated (p<0.001) and stimulated (p=0.001) salivary flow rates in pSS, without change in salivary cytokine profile (p≥0.05). Conclusions: PDC promoted improvement in unstimulated and stimulated salivary flow rates in pSS. This novel finding reinforces the recommendation of this strategy for pSS patients. Clinicaltrials: gov (Identifier: NCT03711214).
... or 1 person in 400 [2]. A systematic review and meta-analysis showed a female/male ratio in prevalence data of 10.72 (95% CI 7.35 to 15.62) and the overall age of pSS patients of 56.16 years (95% CI 52.54 to 59.78) [3]. ...
... Among the limitations of the study is the size of the sample, which does not allow the generalization of the results. The fact that the participants present other associated rheumatological diseases make it difficult or impossible to attribute the experiences of illness only to SS, since these other diseases may be affecting their perception of the disease and altering their quality of life; however, when these diseases occur together, they can be considered part of the same phenomenon; this study included only female participants, which on the one hand limits the global understanding of the disease but gives a gender perspective to the study, highlighting how SS affects the role of women; it should be taken into consideration that this disease affects women in a greater proportion, female/male ratio reported was 10.72 [3]. ...
Article
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Sjögren’s syndrome (SS) is a disease with autoimmune features that affects mainly women and compromises the health-related quality of Life (HRQoL); it is important to evaluate illness experience for a better understanding of the life situation of the patient. The aim of the study was to summarize the individual life experiences and determine the impact of HRQoL and oral health-related quality of life (OHRQoL) and their correlation with health self-assessment in women with SS. The life experiences evaluation employed a concept mapping design to structure qualitative content obtained from semi-structured interviews. Hierarchical cluster analysis was used to analyze the patient’s experiences. EQ-5D-5L and OHIP-14Sp were used. The correlation between appreciation of the general health status and OHIP-14 was evaluated. The experience classification by patients were analyzed and a dendrogram was obtained, identifying 10 clusters of disease experiences of SS, being limitations, pain and difficulties, coping and attitudes towards treatment the most common. Pain/discomfort in EQ-5D-5L and physical pain and psychological discomfort in OHIP-14 were the most affected dimensions in the patients. The results support the theoretical perspective that the experience of illness is relevant to describing the main difficulties of patients with SS and how it affects their quality of life.
... The prevalence of primary Sjogren's syndrome less often happens, occurring in 61/100.000 of populations, with the highest prevalence being in Europe (Qin et al., 2015). Meanwhile, secondary Sjogren's syndrome happens more often, assumed at least in 0.4% of populations (Qin et al., 2015;Stefanski et al., 2017). ...
... The prevalence of primary Sjogren's syndrome less often happens, occurring in 61/100.000 of populations, with the highest prevalence being in Europe (Qin et al., 2015). Meanwhile, secondary Sjogren's syndrome happens more often, assumed at least in 0.4% of populations (Qin et al., 2015;Stefanski et al., 2017). ...
Article
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An autoimmune disorder is an abnormality that causes a disease. One of the autoimmune diseases is Sjogren's syndrome, which affects the salivary and lacrimal glands and causes dry mouth, dry eyes, and dry skin.
... It is characterized by lymphocyte infiltration of the exocrine glands (mainly salivary glands and lacrimal glands), which can lead to dry eyes and dry mouth. Its prevalence is 0.1-1% [1]. The central nervous system is involved in 6-48% of PSS patients, and the peripheral nervous system is involved in 2-60% of patients [2,3]. ...
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Objective To observe the clinical features and efficacy of immunosuppressive therapy in patients with primary Sjögren's syndrome (PSS) combined with peripheral neuropathy (PN) syndrome and to explore the risk factors for PN in patients with PSS. Methods Sixty consecutive patients with PSS admitted to the Department of Rheumatology and Immunology, Wuhan No. 1 Hospital, from January 2014 to June 2020 were analysed retrospectively. Patients were divided into a PN group (N = 15) and a non-PN group (N = 45). The clinical characteristics of the two groups were compared, and the independent risk factors for PN combined with PSS were analysed by multivariate logistic regression. The patients with PSS combined with PN were followed up to observe the effect of immunosuppressive therapy. Results The patients with PN had a longer course of disease than those without PN (z = − 3.225, P = 0.001), and the incidence of Raynaud's phenomenon, anti-SSB antibody, rheumatoid factor and hyperglobulinaemia was higher (all P < 0.05) in patients with PN than in those without PN. Multivariate logistic regression analysis showed that hyperglobulinaemia, RF and anti-SSB antibodies were independent risk factors for PN with PSS (P < 0.05). Fourteen patients with PSS-PN were treated with immunosuppressants. The clinical symptoms of 10 patients were relieved, and mRS scores of 10 patients were decreased. Conclusion PN is a common complication in PSS patients. Patients with PSS combined with PN have a longer course of disease and a significantly higher percentage of Raynaud's phenomenon, positive anti-SSB antibody, positive RF and hyperglobulinaemia. Immunosuppressive therapy was effective for partial remission of PN with PSS.
... Incidence and prevalence rates of pSS vary widely around the world. The prevalence rate of pSS was 43.03 cases per 100,000 inhabitants across a series of population-based studies in which the overall age of patients was 56.16 years (14). It is worth mentioning that increasing incidences of oligoptyalism in patients with Sjogren's syndrome have been reported, which affects the removal of dental plaque and ultimately may lead to periodontal diseases. ...
Article
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Background The relationship between periodontal diseases and Sjogren’s syndrome were found inconsistent in current studies. Our objective is to clarify the relationship between periodontal diseases and Sjogren’s syndrome. Methods A systematic review was performed and reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Electronic databases (EMBASE, PubMed, Web of Science, and Cochrane Library, from inceptions until 24 November 2021) were searched. The Newcastle-Ottawa Scale (NOS) and Agency for Healthcare Research and Quality (AHRQ) were applied to evaluate the quality of studies. Quality assessment of the certainty of evidence was performed based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guidelines. When the output is the ratio, Odds ratio (OR) of periodontal diseases with Sjogren’s syndrome were calculated. When the output is the mean, weighted mean difference (WMD) of periodontal diseases with Sjogren’s syndrome was calculated. We conducted meta-analysis and estimated the pool sensitivity. Begg’s test was used to test the possibility of publication bias. We also carried out meta-regression to clarify the source of heterogeneity (I2 > 50%). Finally, we performed a trial sequential analysis (TSA) to identify the false positive or false negative outcomes that might occur during repeated updates. Results 21 studies were included in this systematic review, with a total of 11435 subjects. Meta-analysis of 5 studies showed that there is a positive correlation between periodontitis and Sjogren’s syndrome (OR = 2.12, 95% CI = 1.43–3.17; 5 studies, 6927 participants; low certainty of evidence). Meta-analysis of 16 studies showed that the periodontal condition of patients with Sjogren’s syndrome was worse compared with the control group, and the scores of clinical periodontal parameters were relatively high. Conclusion Sjogren’s syndrome patients seem to be more likely to be diagnosed with periodontal diseases. However, our results should be interpreted with caution considering the high heterogeneity. Systematic review registration [ https://www.crd.york.ac.uk/prospero/ ], identifier [CRD42021261322].
... As much as 10% of patients suffering from dry eye disease (DED) are diagnosed with SS. However, two-thirds of these patients remain undiagnosed, and a median diagnostic delay of 10 years is reported [2]. Diagnosis of SS remains challenging due to the variable course of this condition and wide spectrum of non-specific clinical manifestations. ...
Article
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Sjögren’s syndrome is a chronic and insidious autoimmune disease characterized by lymphocyte infiltration of exocrine glands. Patients typically present with dry eye, dry mouth, and other systemic manifestations. Currently, the available molecules and drug-delivery systems for the treatment of Sjögren’s syndrome dry eye (SSDE) have limited efficacy since they are not specific to SSDE but to dry eye disease (DED) in general. The current treatment modalities are based on a trial-and-error approach using primarily topical agents. However, this approach gives time for the vicious cycle of DED to develop which eventually causes permanent damage to the lacrimal functional unit. Thus, there is a need for more individualized, specific, and effective treatment modalities for SSDE. The purpose of this article is to describe the current conventional SSDE treatment modalities and to expose new advances in ocular drug delivery for treating SSDE. A literature review of the pre-clinical and clinical studies published between 2016 and 2022 was conducted. Our current understanding of SSDE pathophysiology combined with advances in ocular drug delivery and novel therapeutics will allow the translation of innovative molecular therapeutics from the bench to the bedside.
... The clinical features can be divided into glandular and extra-glandular symptoms, which include dryness of the mouth and eyes, fatigue, and joint pain. This disease predominately occurs in females with a female-to-male ratio of 9:1 [152,153]. Ramos-Casals and colleagues proposed the term "SS secondary to HCV" for subgroups of HCV patients who develop SS [154]. ...
Article
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Hepatitis C virus (HCV) is a significant cause of chronic liver diseases worldwide and is associated with negative consequences, including cirrhosis, hepatic decompensation, hepatocellular carcinoma, and increased risk of mortality. In addition to liver-related morbidities, HCV is also associated with several extrahepatic manifestations, including mixed cryoglobulinemia, diabetes mellitus, cardiocerebrovascular disease, lymphoma, and autoimmune diseases. These non-liver-related complications of HCV increase the complexity of this disease and can contribute to the economic burden, morbidity, quality of life, and mortality throughout the world. Therefore, understanding how this virus can contribute to each extrahepatic manifestation is worth investigating. Currently, the advancement of HCV treatment with the advent of direct-acting anti-viral agents (DAAs) has led to a high cure rate as a result of sustained virologic response and tremendously reduced the burden of extrahepatic complications. However, HCV-associated extrahepatic manifestations remain a relevant concern, and this review aims to give an updated highlight of the prevalence, risk factors, associated burdens, and treatment options for these conditions.
... McCoy et al. performed the largest study to date to evaluate sex hormone exposure with pSS, and their findings suggested that female sex hormones might be protective for pSS (16), or conversely, that reduced female sex hormones might be associated with pSS. This would be consistent with the epidemiology of pSS, in that onset typically occurs during perimenopause when estrogen and progesterone levels drop [51]. Lu et al. found a remarkable increased risk of pSS in female patients with irregular menstrual cycles, especially those in their mid-forties to mid-fifties [18]. ...
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Objectives The aim of this study was to analyze the risk factors for primary Sjögren’s Syndrome (pSS) by conducting a meta-analysis of observational studies. Methods Four electronic databases were searched from inception to August 2022. The search strategy included medical subject headings (MeSH) and text words. Outcomes were calculated and reported as the odds ratio (OR) and 95% confidence interval (CI). Results Twelve studies consisting of nine case–control and three cohort studies were analyzed. Significant positive relationships between infection, a family history of autoimmune disease in first-degree relatives, negative stressful life events, CGGGG insertion/deletion polymorphisms in the IRF5 gene and the onset of pSS were found, with pooled ORs and 95% CIs of 2.73 (1.93, 3.86), 5.93 (3.34, 10.52), 1.69 (1.27, 2.24) and 2.69 (1.97, 3.66), respectively. In contrast, the results showed that a history of smoking was not associated with the onset of pSS, with a pooled OR and 95% CI of 1.39 (0.76, 2.53). However, a statistically significant negative association between current smoking and pSS was detected, with a pooled OR and 95% CI of 0.4 (0.29, 0.83). Conclusions Our research indicated that infection, a family history of autoimmune disease in first-degree relatives, negative stressful life events and CGGGG insertion/deletion polymorphisms in the IRF5 gene might be risk factors for pSS. In contrast, our study demonstrated that a history of smoking was not associated with the onset of pSS, whereas current smoking was negatively associated with pSS onset. Systematic review registration We registered this review on INPLASY ( https://inplasy.com/ ) under registration number INPLASY202230005.
... The major clinical manifestations of these patients include dryness of the mouth and eyes, joint pain, and fatigue, which seriously affect the life quality of SS patients (1). Moreover, these patients also exhibit other clinical manifestations involving multiple systems, such as the nervous system, musculoskeletal system, kidney, blood vessels, skin, and lung (2). However, the potential pathogenesis of SS has not been fully elucidated. ...
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Objective Numerous researches have reported the role of air pollution in the development of autoimmune diseases. However, few have evaluated the relationship between inhalable particulate matter (PM) exposure and Sjögren’s syndrome (SS). This study aimed to analyze the association between exposure to two particulate pollutants (PM 2.5 , PM 10 ) and SS-related hospitalizations. Methods Daily data were obtained on PM 2.5 and PM 10 , meteorological factors, and hospital hospitalizations for SS between 2016 and 2021. The daily data on PM 2.5 and PM 10 , meteorological factors, and the number of SS hospitalizations were collected between 2016 and 2021. A distributed lag non-linear model and a generalized linear model were established to explore the association between PM 2.5 and PM 10 exposure and hospitalizations for SS. Stratified analyses were performed to explore possible gender-, age-, and season-related differences in PM 2.5 and PM 10 effects. Results Exposure to PM 2.5 was related to the evaluated risk of hospitalizations for SS ( RR =1.015, 95% CI : 1.001-1.029, lag 3 day), similarly, PM 10 exposure had a statistically significant positive association with SS hospitalizations ( RR =1.013, 95% CI : 1.001-1.026, lag 3 day). Stratified analyses found that exposure to PM 2.5 and PM 10 exhibited higher impact on SS-related hospitalizations in female patients and exposure to PM 2.5 was also associated with the higher risk of SS-related hospitalizations in patients aged ≥ 65 years. In addition, exposure to PM 2.5 , PM 10 in colder season were more likely to increase SS-related hospitalizations. Conclusion Our findings suggested that exposure to PM 2.5 and PM 10 were significantly linked to an elevated risk of hospitalizations for SS.
... Primary Sjögren's syndrome (pSS) is a chronic systemic autoimmune disease characterised by B-cell hyperactivity and lymphocytic infiltration of exocrine glands, that presents as sicca syndrome (1). It affects 0.3-1 per 1000 of the general population with a peak incidence at approximately 50 years of age (2). The clinical phenotype of pSS varies from a benign glandular disorder to aggressive systemic involvement, and approximately 30% to 40% of patients have systemic manifestations such as interstitial lung disease (ILD) (3). ...
Article
Objectives: To study the clinical characteristics of primary Sjögren's syndrome (pSS) with different onset age, and perform a review of the literature to confirm if the clinical phenotypes are affected by onset age in patients with pSS. Methods: Data of 742 patients with pSS were retrospectively analysed. Patients were divided into three groups according to onset age: young-onset pSS (YopSS, <35 years), adult-onset pSS (AopSS, ≥35 and ≤65 years), and elderly-onset pSS (EopSS, >65 years). Clinical characteristics were compared among three groups and further multiple comparisons were conducted by Bonferroni adjustment. The Chi-squared test for linear-by-linear association was used to explore variation tendency. Results: This study included 105 (14.2%), 533 (71.8%), and 104 (14.0%) cases of YopSS, AopSS, and EopSS, respectively. YopSS demonstrated lower prevalence of dry mouth, abnormal Schirmer I tests, and interstitial lung disease (ILD), but higher proportions of low C3 and C4 levels, and ANA, anti-SSA, anti-SSB, and rheumatoid factor (RF) positivity than AopSS and EopSS. The proportions of dry mouth (p=0.004), abnormal Schirmer I tests (p=0.002), and ILD (p<0.001) tended to increase with the increase of onset age, while the prevalence of leukopenia (p=0.011), low C3 (p=0.001), low C4 (p=0.001), and ANA (p<0.001), anti-SSA (p<0.001), anti-SSB (p<0.001) and RF (p<0.001) positivity tended to decrease with an increase in onset age. Conclusions: YopSS demonstrated less dryness and ILD, but more immunologic disorders. ILD prevalence were directly proportional to onset age of pSS; however, leukopenia, hypocomplementaemia, and autoantibody positivity showed opposite trends.
... Estimate of incidence of primary SS in adults is 3.9-5.3 cases per 100,000 persons with estimated prevalence of 43-282 per 100,000 persons in Europe [1]. Primary SS is more common in women than men with estimates of 9-13 to 1. ...
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Background Sjogren’s syndrome (SS) is a rare chronic autoimmune disease involving exocrine glands presenting with sicca syndrome, recurrent parotitis and other extraglandular stigmata. SS is well characterized in the adult population with classification criteria; however, primary SS presenting in childhood is poorly defined and rare in males. Recurrent parotitis is the most common presenting symptom in children with primary SS; however, clinical phenotype in children appears more variable than in adults. The lungs are a common extraglandular location for manifestations of primary SS. However, interstitial lung disease (ILD) is rare in children with primary SS. There are only four published reports of ILD associated with primary SS in female children. Here, we present a very rare case of primary SS in a pediatric male with pulmonary manifestations and review of the literature on ILD in childhood-onset primary SS. Case presentation A 14-year-old White male with a history of chronic severe asthma, recurrent parotitis and idiopathic intracranial hypertension was referred to pediatric rheumatology for evaluation of a positive ANA. In early childhood, he was diagnosed with persistent asthma recalcitrant to therapy. At age 8, he developed recurrent episodes of bilateral parotitis despite multiple treatments with sialoendoscopy. At age 14, respiratory symptoms significantly worsened prompting reevaluation. Lab workup was notable for positive ANA and Sjogren’s Syndrome A and B antibodies. Pulmonary function tests showed only a mild obstructive process. Computed tomography of chest was significant for small airway disease, and lung biopsy was positive for mild interstitial lymphocytic inflammation presenting a conflicting picture for ILD. The constellation of findings led to the diagnosis of primary SS with associated pulmonary manifestations. He was treated with hydroxychloroquine, mycophenolate mofetil and oral corticosteroids with resolution of symptoms. Conclusions Primary SS is a rare disease in the pediatric population that is poorly characterized. This case is the very rare presentation of childhood-onset primary SS with pulmonary manifestations in a male patient. ILD associated with primary SS is also very rare with only four pediatric patients reported in the literature. Collaborative effort is needed to develop pediatric specific diagnostic and treatment guidelines in this rare condition.
... Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease, second to rheumatoid arthritis (RA), with a prevalence of 60.8 (95% CI: 43.7 to 77.9) cases per 100,000 inhabitants (1). pSS commonly affects the exocrine glands, in particular the salivary and lacrimal glands, resulting in a sensation of dry eyes (keratoconjunctivitis sicca) and dry mouth (xerostomia) (2). ...
Article
Ultrasound is a promising diagnostic method when it comes to assessing the involvement of major salivary glands in patients with primary Sjögren's syndrome (pSS). A matter of debate is whether ultrasound of the major salivary glands (SGUS) can replace a salivary gland biopsy in the diagnosis or classification of pSS. The intra- and inter-observer reliability of SGUS was found to be good, especially when focusing on hypoechogenic areas and homogeneity, and comparable to the reliability of histopathologic characteristics of salivary gland biopsies of pSS patients. However, replacing salivary gland biopsy by SGUS led to substantial decrease of the accuracy of the 2016 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria with clinical diagnosis as the gold standard. When SGUS was added as an additional item to the criteria, the accuracy of the criteria remained high, offering at the same time the clinicians a wider array of tools to assess patients. Combination of SGUS and anti-SSA antibodies was shown to be highly predictive of the classification of a patient suspected of pSS, making routine salivary gland biopsy debatable.
... person-years in the general population. Noteworthy the incidence rate nearly doubles in the female population [1]. Similarly to most autoimmune diseases, its cause remains unknown. ...
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Sjögren syndrome (SS) is a multisystem autoimmune disease, primarily targeting salivary and lacrimal glands; skin, nasal and vaginal dryness, along with musculoskeletal pain and fatigue are the most commonly reported symptoms. Hearing loss is hypothesized to be frequent as well. The purpose of this systematic review was to estimate the prevalence of Hearing loss and its different subtypes in patients with Sjögren syndrome. PRISMA guidelines were followed to ensure highest quality for our systematic review. A random effects model meta-analysis and meta-regression was conducted using I² as heterogeneity indicator. Eleven observational studies were included in this systematic review. Ten of them were cross-sectional, while one study was case–control. Studies were assessed for risk of bias: all were rated to a moderate level, except for two rated to a low level. Pooled prevalence of any type of hearing loss was 52.2%. After excluding studies rated to moderate bias, the pooled prevalence of hearing loss was 36.7%. We also conducted a subgroup analysis depending on type of hearing loss. Pooled prevalence of sensorineural hearing loss was 42.6%., while pooled prevalence of conductive hearing loss and mixed hearing loss were 5% and 2.3%, respectively. Meta-regression was conducted in an effort to identify possible variables capable to explain high heterogeneity between studies. Sample size and year of study were separately found to account for a portion of heterogeneity between studies of sensorineural hearing loss. Year of study was also found to account for a portion of heterogeneity between studies of conductive hearing loss. In conclusion, sensorineural hearing loss, is highly prevalent in patients with Sjögren syndrome. On this basis, early screening and follow-up of patients with Sjögren syndrome by pure tone audiometry is important.
... syndrome (SS) varies widely according to the study design and the classification criteria used. A large populationbased study carried out in Catalonia has recently estimated that SS may affect 1 in 400 people (1), with an incidence rate of seven new diagnoses per 100,000 person-years (2). Considering that the European Union defines a disease or condition as rare if it affects fewer than 1 in 2,000 people in the general population, SS is far from being a rare disease. ...
Article
More than 90 years have passed since Hendrik Sjögren began to consider that behind the dryness that several of his patients presented, there could be a systemic disease potentially linked to abnormal immune responses. For many years, the disease was mostly considered a minor syndrome compared with other systemic autoimmune diseases such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and vasculitis, and advances in its understanding were slow and little recognised. The irruption of new technologies at the end of the 20th century rapidly promoted the development of international projects with a wide impact and diffusion. In the last 20 years, a significant improvement has been achieved in epidemiological determinants, pathogenic mechanisms, diagnostic accuracy, and a standardised therapeutic approach for patients with Sjögren's syndrome (SS). These developments have provided the tools for an early diagnosis and personalised management for most patients. However, a significant number of early myths and ongoing controversies are still making the appropriate management of SS difficult in daily clinical practice. This review provides a selection of pearls, myths, and mistakes that may serve as practical diagnostic tips for the Sjögren Clinic in four specific scenarios: defining the appropriate epidemiological background, enabling the earliest diagnostic suspicion as possible, improving the systemic characterisation of the disease, and designing an optimal follow-up of patients.
... Background Primary Sjögren Syndrome (pSS) is a rare (0.1-1/10000) autoimmune systemic disease characterized by impaired secretory functions of the exocrine [1,2]. pSS is characterized by association of a symptomatic triad (dryness, pain and fatigue) with various systemic manifestations. ...
Article
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Background Primary Sjögren Syndrome is a rare autoimmune systemic disease characterized by impaired secretory functions of the exocrine gland. One of the main clinical features is dry mouth and subsequent oral diseases, which are also found in patients with Sicca. This leads to a marked deterioration in the quality of life and the patient’s search for information and solutions. Many patients turn to patients’ associations that offer moments of sharing to their members, especially through online discussion forums. Today, these forums represent quality material for a sociological or biomedical analysis of patients' concerns, as close as possible to their daily lives. Our objective is to analyze the concerns of patients with SS or Sicca regarding their dry mouth especially dental care. Methods In this cross-sectional observation study, a quantitative analysis of the Mouth-Nose online forum discussion of the French Association of Patients with Gougerot-Sjögren’s Syndromes and Dryness have been performed. After reading and re-reading, initial request themes, topics, and subtopics were established and coding was performed. Then, the 885 threads were classified depending the initial request, pragma-linguistic indices and the main topic discussed in the thread. After identifying the threads dealing with dental care, we looked at which types of care were most discussed and classified the discussions according to whether or not the patient was satisfied with their care at the dentist. Results The majority of the initial requests are posts for experiences sharing and/or advice. The topic of “dental care” is one of the main concerns of the forum users. Among the threads that concern dental care, requests to share experience with implants are in the majority. Finally, the majority of the posts on dental care relate to care in private dental practice, deals with dental implants and prevention and resulted mainly in patient satisfaction. Conclusions Analysis of the forum reveals importance of patient concerns about prevention, and care costs due to implant treatment, which add to disease burden. Most of messages relate favorable experiences with their dentists, which is in line with the approach of sharing experiences and support characteristic of a forum.
... According to published epidemiological studies, the prevalence of pSS in the elderly is 5-8 times higher than in other age groups. [10][11][12] In the elderly, SS diagnosis comes up against a whole series of critical points. 13,14 The aim of our review article is to discuss the most relevant of them, looking for useful tips in everyday clinical practice. ...
Article
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Primary Sjögren's syndrome (pSS) is a systemic autoimmune rheumatic disease where xerophthalmia, xerostomia and presence of anti-SSA and anti-SSB antibodies are typical features. Its prevalence is higher in over-65 aged population than in other age groups. In the elderly, pSS diagnosis comes up against a whole series of critical points that may favor its misdiagnosis. The aim of our article is to discuss the most relevant of them: the frequent occurrence of a seroneg-ative subset, the presence of systemic features not related to sicca syndrome, the sicca syndrome as iatrogenic manifestation and the possibility of a biopsy false negative of labial salivary glands.
... Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease that occurs mostly in middle-aged women and is characterized by impaired glandular function and the appearance of autoantibodies caused by infiltrating exocrine glands with lymphocytes, with an estimated prevalence of 0.3-3/1000 in the general population (1,2). PSS is a heterogeneous disease; approximately 5% to 35% of the population has dry eye, approximately 20% of patients have dry mouth, and up to 34% of patients have parotid gland swelling (3)(4)(5). ...
Article
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Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease characterized by exocrine gland dysfunction and inflammation. Patients often have dry mouth and dry eye symptoms, which seriously affect their lives. Improving dry mouth and eye symptoms has become a common demand from patients. For this reason, researchers have conducted many studies on external secretory glands. In this paper, we summarize recent studies on the salivary glands of pSS patients from the perspective of the immune microenvironment. These studies showed that hypoxia, senescence, and chronic inflammation are the essential characteristics of the salivary gland immune microenvironment. In the SG of pSS, genes related to lymphocyte chemotaxis, antigen presentation, and lymphocyte activation are upregulated. Interferon (IFN)-related genes, DNA methylation, sRNA downregulation, and mitochondrial-related differentially expressed genes are also involved in forming the immune microenvironment of pSS, while multiple signaling pathways are involved in regulation. We further elucidated the regulation of the salivary gland immune microenvironment in pSS and relevant, targeted treatments.
... Most SS patients are middle-aged women. 2,3 The pathogenesis and underlying mechanism of SS are still unclear. Therefore, screening and identifying genes associated with SS is necessary to understand its complex pathogenesis. ...
Article
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Abstract Background Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect multiple systems. Sjögren's syndrome (SS) is an autoimmune disease that may be primary SS (pSS) or occur together with other autoimmune diseases, including SLE. This study aimed to explore the shared gene signatures in SLE and pSS. Methods Gene expression data sets of SLE (GSE50772 and GSE81622) and pSS (GSE84844 and GSE48378) were obtained and analyzed for differentially expressed genes (DEGs) in peripheral blood mononuclear cells (PBMCs). A protein–protein interaction (PPI) network was constructed. Gene ontology (GO) and KEGG pathway enrichment analysis were carried out for the DEGs. Results We screened 232 and 110 DEGs from the SLE and pSS data sets, respectively. We found 32 shared DEGs, which were all upregulated in patients compared with controls. Among these 32 DEGs, 11 genes showed a more than twofold change in all data sets (IFI27, IFI44L, RSAD2, IFIT1, IFI44, USP18, IFI6, HERC5, EPSTI1, OAS1, and OAS3). PPI analysis showed that 29 genes interacted with each other. GO analysis showed that these 32 shared DEGs were mainly enriched in biological processes associated with the type I interferon signaling pathway, defense response to viruses, response to viruses, negative regulation of viral genome replication, and the immune response. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that these 32 DEGs were related to virus infection. Conclusion This study showed that alterations to biological processes associated with the response to virus infection play critical roles in both SLE and pSS.
... Women (F) develop Sjögren syndrome more frequently than men (M), and actually the SS incidence range, as referred to the sex F/M difference, is between 9:1 and 19:1 8 . The mean age at time of first diagnosis of pSS is 56 years, with another peak occurring between 20 and 40 years 13,14 . ...
Article
Objective: Sjögren syndrome (SS) is an autoimmune disorder, affecting about 16,000 individuals in Italy, yet lacking a standardized therapy protocol and a plain inclusion in the reimbursed healthcare services. This raises many controversial issues about how managing the SS patient, to relief pain and discomfort and improve patients' health and social life. The ozone therapy resulted successful in previous reports, and therefore, it was used in this case report. Case presentation: A 69-years old female outpatient, showing positivity to Schirmer's test, was previously diagnosed as a primary Sjögren syndrome, who later developed an autoimmune thyroiditis and showed the presence of rheumatoid factors. The patient suffered from a marked ocular dryness, subsequently to a purported endothelitis, alongside with fatigue and pain. Laboratory tests showed a positive ANA 1:320 in a speckled pattern with negative anti-SSA and anti-SSB tests. From December 2020 to January 2021 she underwent 2 routes of three sessions of oxygen-ozone autohemotherapy (O2-O3 AHT), as described below and improved, with only 2 sessions, her symptomatology and clinical outcome, as ocular dryness, fatigue and pain, rapidly disappeared. Conclusions: The use of ozone in the therapy of SS is a straightforward, affordable and feasible approach to treat primary Sjögren syndrome without significant side effects.
... Firstly, a small number of patients diagnosed with pSS who also underwent MRI exams were included. This is explained by the relatively low prevalence of this disease in the general population (0.06% worldwide) [32] and the fact that the study was monocentric. However, the monocentric nature of this study allowed all examinations to be performed on the same machine, which resulted in a higher degree of homogeneity of the selected images and, therefore, a more adequate extraction of textural analysis parameters. ...
Article
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This study aimed to assess the effectiveness of MRI-based texture features of the lacrimal glands (LG) in augmenting the imaging differentiation between primary Sjögren’s Syndrome (pSS) affected LG and healthy LG, as well as to emphasize the possible importance of radiomics in pSS early-imaging diagnosis. The MRI examinations of 23 patients diagnosed with pSS and 23 healthy controls were retrospectively included. Texture features of both LG were extracted from a coronal post-contrast T1-weighted sequence, using a dedicated software. The ability of texture features to discriminate between healthy and pSS lacrimal glands was performed through univariate, multivariate, and receiver operating characteristics analysis. Two quantitative textural analysis features, RunLengthNonUniformityNormalized (RLNonUN) and Maximum2DDiameterColumn (Max2DDC), were independent predictors of pSS-affected glands (p < 0.001). Their combined ability was able to identify pSS LG with 91.67% sensitivity and 83.33% specificity. MRI-based texture features have the potential to function as quantitative additional criteria that could increase the diagnostic accuracy of pSS-affected LG.
... pSS clinical manifestation and management. Primary Sjögren's syndrome (pSS) affects approximately 0.4% of the general population with a female to male reported predominance ranging anywhere from 9:1 to 20:1 [1][2][3] . Although the disease presents largely within the salivary and lacrimal glands, major systemic complications can occur, which include nephritis, cryoglobulinemic vasculitis, and lymphoma 2,4 . ...
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Primary Sjögren’s syndrome (pSS) patients exhibit enhanced degradation of the salivary epithelium initially through MMP9 overexpression. We assessed the expression of MMP9 and an associated transcription factor, ETS1, in primary salivary gland epithelial cells (SGECs) and investigated potential regulatory mechanism(s) in immortalized SGECs. SGECs and iSGECs were derived from pSS and/or xerostomic “sicca” patients. siRNA knockdown of ETS1 in iSGECs was performed to determine MMP9 mRNA (qRT-PCR) and protein expression (ELISA). ETS1 binding to MMP9 promoter was assessed by luciferase activity and binding confirmed by mutagenesis and ChIP. Effects of ETS1 overexpression on progenitor and Epithelial-Mesenchymal transition (EMT) associated markers were determined by Western blot. Expression of ETS1 and its phosphorylated form in iSGECs was determined by immunofluorescence microscopy. ETS1 and MMP9 were overexpressed in SGECs of pSS and non-pSS sicca patients with salivary gland lymphocytic infiltration compared to non-pSS sicca patients without infiltration. ETS1 siRNA knockdown reduced both MMP9 mRNA and protein levels. ETS1 overexpression affected the expression of EMT and progenitor cell markers. Lastly, ETS1 bound the MMP9 promoter within the DNA region of −296 bp to −339 bp. ETS1 may impair salivary function through direct transcriptional control of the MMP9 promoter. ETS1 upregulation may also affect other factors involved in repair of the dysfunctional pSS salivary epithelium.
Article
Systemic diseases (connective disease, granulomatosis) may be associated with peripheral neuropathies. The diagnosis can be complex when the neuropathy is the presenting manifestation of the disease, requiring close collaboration between neurologists and internists. Conversely, when the systemic disease is already known, the main question remaining is its imputability in the neuropathy. Regardless of the situation, the positive diagnosis of neuropathy is based on a systematic and rigorous electro-clinical investigation, specifying the topography, the evolution and the mechanism of the nerve damage. Certain imaging examinations, such as nerve and/or plexus MRI, or other more invasive examinations (skin biopsy, neuromuscular biopsy) enable to specify the topography and the mechanism of the injury. The imputability of the neuropathy in the course of a known systemic disease is based mainly on its electro-clinical pattern, on which the alternatives diagnoses depend. In the case of an inaugural neuropathy, a set of arguments orients the diagnosis, including the underlying terrain (young subject), possible associated systemic manifestations (inflammatory arthralgias, polyadenopathy), results of first-line laboratory tests (lymphopenia, hyper-gammaglobulinemia, hypocomplementemia), autoantibodies (antinuclear, anti-native DNA, anti-SSA/B) and sometimes invasive examinations (neuromuscular biopsy).
Article
El síndrome de Sjögren es un trastorno crónico autoinmune que afecta a las glándulas secretoras, principalmente salivales y lagrimales; además, puede presentar manifestaciones sistémicas extraglandulares. El objetivo de esta revisión fue revisar la literatura sobre los aspectos generales del síndrome de Sjögren, para lo cual se realizó una búsqueda en bases de datos entre el 15 de enero y el 15 de marzo del 2020, en donde se obtuvieron 29 artículos sobre los cuales se hizo la revisión. El síndrome de Sjögren tiene una importante prevalencia entre las enfermedades autoinmunes más comunes, caracterizada por presentar xerostomía y xeroftalmia. Los criterios diagnósticos tienen alta sensibilidad y especificidad y su tratamiento es sintomático.
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Introduction The initial presentations of childhood-onset primary Sjögren’s syndrome (C-pSS) vary, making diagnosis challenging. We aimed to improve the diagnosis and evaluation of C-pSS by summarizing its clinical and laboratory features. Methods A total of 49 patients with C-pSS between July 2015 and August 2022 in the Department of Rheumatology and Immunology of Shanghai Children's Medical Centre were enrolled in this study. Their clinical manifestations and laboratory examinations of these patients were compared based on the presence or absence of thrombocytopenia and parotitis and whether the immunological markers, including anti-nuclear antibodies (ANA), rheumatoid factor (RF), anti-Ro52/SSA antibodies (anti-SSA/Ro52), anti-Ro60/SSA antibodies (anti-SSA/Ro60), and anti-Ro/SSB antibodies (anti-SSB), were positive. Results The mean age at C-pSS diagnosis was 10.34 ± 3.45 years, and the ratio of boys to girls was 1:6. In the thrombocytopenia group, parotitis ( P = 0.044), organ involvement except for hematology ( P = 0.002), positive anti-SSB ( P = 0.004), and positive RF ( P = 0.001) were less frequently observed. Complement C4 ( P = 0.038) and white blood cells ( P = 0.002) levels decreased and increased significantly, respectively. Anti-SSB ( P = 0.010) and RF ( P = 0.004) positivity were independent potential protective factors against thrombocytopenia in patients with C-pSS. In the parotitis group, higher ANA titers ( P = 0.027), higher focus scores on labial gland biopsy ( P = 0.024), and positive RF ( P = 0.001), anti-SSA/Ro60 ( P = 0.003), and anti-SSB ( P = 0.001) were observed more frequently. Furthermore, positive anti-SSB ( P = 0.012) and positive RF ( P = 0.028) were independent risk factors for parotitis in patients with C-pSS. The hemoglobin level was significantly lower in patients with positive anti-SSA/Ro52 and positive anti-SSA/Ro60 results ( P = 0.022 and P = 0.029, respectively), while immunoglobulin G level was significantly higher in patients in the same group ( P = 0.048 and P = 0.007, respectively). Conclusions Positive anti-SSB and positive RF values may be independent potential protective factors of thrombocytopenia in patients with C-pSS. In contrast, positive anti-SSB and positive RF were independent risk factors of parotitis in patients with C-pSS. More studies are needed to reveal the diagnostic role and pathogenic mechanism of immunological markers in C-pSS.
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Zusammenfassung Zielsetzung Es erfolgt eine aktualisierte Schätzung der Prävalenz entzündlich rheumatischer Erkrankungen (ERE) in Deutschland. Methodik Mit einer systematischen Literaturrecherche in PubMed und Web of Science (letzte Suche am 08.11.2022) wurden Originalartikel (regionale und bundesweite Surveys und Routinedatenanalysen für Arthritiden, Kollagenosen und Vaskulitiden) zur Prävalenz von ERE für den Zeitraum 2014 bis 2022 identifiziert. Datenquellen, Erhebungszeitraum, Diagnosedefinition und das Risiko einer Verzerrung werden berichtet. Die Prävalenzen wurden anhand der verfügbaren Daten unter Berücksichtigung internationaler Angaben geschätzt. Ergebnisse Die Suche durch 2 Autorinnen ergab 263 Treffer, von denen 18 Routinedatenanalysen und 2 Surveys die Einschlusskriterien erfüllten. Die Prävalenzangaben lagen bei 0,42–1,85 % (rheumatoide Arthritis), 0,32–0,5 % (ankylosierende Spondylitis), 0,11–0,32 % (Psoriasisarthritis), 0,037–0,14 % (systemischer Lupus erythematodes), 0,07–0,77 % (Sjögren/Sicca-Syndrom), 0,14–0,15 % (Polymyalgia rheumatica, ab 40 Jahre), 0,04–0,05 % (Riesenzellarteriitis, ab 50 Jahre) und 0,015–0,026 % (ANCA-assoziierte Vaskulitis). Das Bias-Risiko war in 13 Studien moderat, in 7 Studien hoch. Anhand dieser Ergebnisse schätzen wir die Prävalenz von ERE in Deutschland auf 2,2–3,0 %. Dies entspricht in etwa 1,5 bis 2,1 Mio. Betroffenen. Die Prävalenz der juvenilen idiopathischen Arthritis wurde mit ca. 0,10 % (0,07–0,13 %) der 0‑ bis 18-Jährigen angegeben, was etwa 14.000 Kindern und Jugendlichen in Deutschland entspricht. Schlussfolgerung Dieses systematische Review zeigt einen Anstieg der Prävalenzen von ERE in Deutschland, basiert jedoch fast ausschließlich auf Routinedatenanalysen. In Ermangelung mehrstufiger Bevölkerungsstudien sind die vorliegenden Daten bei moderat bis hohem Verzerrungsrisiko insgesamt unsichere Quellen für Prävalenzschätzungen.
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About 2% of mothers with Sjögren’s syndrome and about 1% of mothers with systemic lupus erythematosus deliver a baby with a congenital heart block (CHB). This is thought to be as a result of the maternal autoantibodies that cross the placenta and cause congenital lupus in the fetus/neonate. Among patients with a 2nd or 3rd degree atrioventricular block, the mortality rate in the neonatal period is about 10%, and most neonates who survive require a pacemaker into adulthood. Despite the compelling mortality and morbidity, the data on the optimal preventive treatments are meager and not well-established. In addition to pharmaceutical therapy, one potentially effective therapy is plasmapheresis. Plasmapheresis is safe in pregnancy, well tolerated, and is effective in removing the offending substances in the serum which may cause disease. We review this literature, in order to educate the reader and to motivate interest in studying this condition in the future.
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Introduction Primary Sjögren's syndrome (pSS) is associated with an increased prevalence of traditional risk factors and cardiovascular diseases (CVDs). The study aimed to identify specific risk factors for CVD in pSS patients. Methods PSS patients with and without CVD were compared. All patients fulfilled the EULAR/ACR classification criteria. Patients with CVD presented at least one of the following manifestations: myocardial infarction, transient ischemic attacks, ischemic or hemorrhagic stroke, peripheral artery disease, coronary artery disease, and carotid plaques. Data were collected by a standardized protocol and review of medical records. Results 61/312 (19.6%) pSS patients presented with CVD. Traditional risk factors such as hypertension, hypercholesterinemia and diabetes ( p < 0.05), pSS manifestations, in particular vasculitis ( p = 0.033) and Raynaud's phenomenon ( p = 0.018) were associated with CVD. Among patients with ischemic events (28/312, 9%), particularly cerebrovascular disease ( n = 12/28, 42.9%), correlations with increased EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) ( p = 0.039) and EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) ( p = 0.048) were observed. Age at first cerebrovascular event was 55.2 [48.9–69.6] years. Multivariate analysis confirmed hypertension [odds ratio (OR) 3.7, 95% confidence interval (CI) 1.87–7.18, p < 0.001], hypercholesterinemia (OR 3.1, 95% CI 1.63–5.72, p < 0.001), male gender (OR 0.4, 95% CI 0.17–0.78, p = 0.009), Raynaud's phenomenon (OR 2.5, 95% CI 1.28–4.82, p = 0.007), and CNS involvement (OR 2.7, 95% CI 1.00–7.15, p = 0.048) as independent CVD predictors. Conclusion Raynaud's phenomen as well as vasculitis and high ESSDAI have shown a significant association to CVD. PSS patients with cerebrovascular events were younger than expected. Knowledge about risk factors may help clinicians to identify pSS patients at risk for CVD. After diagnosis of pSS, patients should be screened for risk factors such as hypertension and receive appropriate therapy to prevent or at least reduce sequelae such as infarction. However, further investigations are necessary in order to achieve a reliable risk stratification for these patients.
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Objective Sjögren’s disease (SjD) is an autoimmune disease characterised by inflammatory destruction of exocrine glands. Patients with autoantibodies to Ro/SSA (SjD Ro+ ) exhibit more severe disease. Long non-coding RNAs (lncRNAs) are a functionally diverse class of non-protein-coding RNAs whose role in autoimmune disease pathology has not been well characterised. Methods Whole blood RNA-sequencing (RNA-seq) was performed on SjD cases (n=23 Ro/SSA negative (SjD Ro− ); n=27 Ro/SSA positive (SjD Ro+ ) and healthy controls (HCs; n=27). Bioinformatics and pathway analyses of differentially expressed (DE) transcripts (log 2 fold change ≥2 or ≤0.5; p adj <0.05) were used to predict lncRNA function. LINC01871 was characterised by RNA-seq analyses of HSB-2 cells with CRISPR-targeted LINC01871 deletion ( LINC01871 −/ ⁻ ) and in vitro stimulation assays. Results Whole blood RNA-seq revealed autoantibody-specific transcription profiles and disproportionate downregulation of DE transcripts in SjD cases relative to HCs. Sixteen DE lncRNAs exhibited correlated expression with the interferon (IFN)-regulated gene, RSAD2 , in SjD Ro+ (r≥0.65 or ≤−0.6); four antisense lncRNAs exhibited IFN-regulated expression in immune cell lines. LINC01871 was upregulated in all SjD cases. RNA-seq and pathway analyses of LINC01871 −/ ⁻ cells implicated roles in cytotoxic function, differentiation and IFNγ induction. LINC01871 was induced by IFNγ in a myeloid cell line and regulated by calcineurin/NFAT pathway and T cell receptor (TCR) signalling in primary human T cells. Conclusion LINC01871 influences expression of many immune cell genes and growth factors, is IFNγ inducible, and regulated by calcineurin signalling and TCR ligand engagement. Altered LINC01871 expression may influence the dysregulated T cell inflammatory pathways implicated in SjD.
Article
Objectives To investigate the compositional and functional characteristics of the gut microbiota in primary Sjögren's syndrome (pSS) and compare them with those in systemic lupus erythematosus (SLE). Methods Stool samples from 78 treatment naïve pSS patients and 78 matched healthy controls were detected by shotgun metagenomic sequencing and compared with those from 49 treatment naïve SLE patients. The virulence loads and mimotopes of the gut microbiota were also assessed by sequence alignment. Results The gut microbiota of treatment naïve pSS patients had lower richness and evenness and showed a different community distribution than that of healthy controls. The microbial species enriched in the pSS-associated gut microbiota included Lactobacillus salivarius, Bacteroides fragilis, Ruminococcus gnavus, Clostridium bartlettii, Clostridium bolteae, Veillonella parvula, and Streptococcus parasanguinis. Lactobacillus salivarius was the most discriminating species in the pSS patients, especially in those with interstitial lung disease (ILD). Among the differentiating microbial pathways, the superpathway of l-phenylalanine biosynthesis was also further enriched in pSS complicated with ILD. There were more virulence genes carried by the gut microbiota in pSS patients, most of which encoded peritrichous flagella, fimbriae, or curli fimbriae, three types of bacterial surface organelles involved in bacterial colonization and invasion. Five microbial peptides with the potential to mimic pSS-related autoepitopes were also enriched in the pSS gut. SLE and pSS shared significant gut microbial traits, including the community distribution, altered microbial taxonomy and pathways, and enriched virulence genes. However, Ruminococcus torques was depleted in pSS patients but enriched in SLE patients compared to that in healthy controls. Conclusions The gut microbiota in treatment naïve pSS patients was disturbed and shared significant similarity with that in SLE patients.
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Interstitial lung diseases (ILD) are a group of heterogeneous progressive pulmonary disorders, characterised by tissue remodelling and/or fibrotic scarring of the lung parenchyma. ILD patients experience lung function decline with progressive symptoms, poor response to treatment, reduced quality of life and high mortality. ILD can be idiopathic or associated with systemic or connective tissue diseases (CTD) but idiopathic pulmonary fibrosis (IPF) is the most common form. While IPF has a male predominance, women are affected more greatly by CTD and therefore associated ILDs. The mechanisms behind biological sex differences in these progressive lung diseases remain unclear. However, differences in environmental exposures, variable expression of X-chromosome related inflammatory genes and sex hormones play a role. Here, we will outline sex-related differences in the incidence, progression and mechanisms of action of these diseases and discuss existing and novel cellular and pre-clinical studies. Furthermore, we will highlight how sex-differences are not adequately considered in pre-clinical disease models, how gender bias exists in clinical diagnosis and how women are underrepresented in clinical trials. Future action on these observations will hopefully shed light on the role of biological sex in disease development, identify potential targets for intervention and increase female participant numbers in clinical trials.
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Background Little is known about the disposition to autoimmune diseases (ADs) among children diagnosed with JIA. In this study, we provide a comprehensive overview of the prevalence of and factors associated with ADs in parents of children with juvenile idiopathic arthritis (JIA). Methods Prevalence rates of ADs and 95% Poisson confidence intervals were calculated for parents of JIA patients from the international Pharmachild registry and compared with general population prevalence rates as reported in the literature. Demographic, clinical and laboratory features were compared between JIA patients with and without a family history of AD using χ² and Mann-Whitney U tests. Results Eight thousand six hundred seventy three patients were included and the most common familial ADs were psoriasis, autoimmune thyroid disease, rheumatoid arthritis and ankylosing spondylitis. The prevalence of several ADs was higher in parents of the included JIA patients than in the general population. Clinical Juvenile Arthritis Disease Activity Scores at study entry and last follow-up were not significantly different between patients with (n = 1231) and without a family history of AD (n = 7442). Factors associated with familial AD were older age at JIA onset (P < 0.01), Scandinavian residence (P < 0.01), enthesitis-related arthritis, psoriatic arthritis and undifferentiated arthritis (P < 0.01), ANA positivity (P = 0.03) and HLA-B27 positivity (P < 0.01). Conclusions Familial AD proves to be a risk factor for JIA development and certain diseases should therefore not be overlooked during family health history at the diagnosis stage. A family history of AD is associated with the JIA category but does not influence the severity or disease course.
Article
Resumen El síndrome de Sjögren primario es una exocrinopatía autoinmunitaria caracterizada por la asociación de queratoconjuntivitis seca, xerostomía y manifestaciones sistémicas de naturaleza inmunoinflamatoria. Existe un claro predominio femenino con una frecuencia máxima alrededor de los 50 años, pero se encuentran formas que comienzan antes de los 35 años. Si bien la tríada que asocia síndrome seco, dolor difuso y fatiga es frecuente, el síndrome seco puede aparecer a veces varios años después de determinadas manifestaciones extraglandulares, en particular reumáticas. La presencia de anticuerpos antinucleares es frecuente, especialmente del tipo anti-Sjögren's-syndrome-related antigens A and B autoantibodies (anti-SSA y SSB). La biopsia de glándulas salivales accesorias es uno de los elementos clave del diagnóstico. Además del tratamiento sintomático del síndrome seco, la corticoterapia y los inmunosupresores pueden estar indicados en las formas graves con manifestaciones extraglandulares. A largo plazo, el riesgo de linfoma es mayor que en la población general.
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Objective The pathogenesis of primary Sjögren’s syndrome (pSS) remains incompletely understood. The N6-methyladenosine (m6A) RNA modification, the most abundant internal transcript modification, has close associations with multiple diseases. This study aimed to investigate the role of m6A in patients with pSS. Materials and methods This study enrolled 44 patients with pSS, 50 age- and gender-matched healthy controls (HCs), and 11 age- and gender-matched patients with non-SS sicca. We detected the messenger RNA (mRNA) levels of m6A elements (including METTL3, WTAP, RBM15, ALKBH5, FTO, YTHDF1, YTHDF2, YTHDF3, YTHDC1, and YTHDC2), ISG15, and USP18 in peripheral blood mononuclear cells (PBMCs) from patients with pSS, patients with non-SS sicca, and HCs. The clinical characteristics and laboratory findings of patients with pSS and patients with non-SS sicca were also collected. We used binary logistic regression to determine if m6A elements were risk factors for pSS. Results The mRNA levels of m6A writers (METTL3 and RBM15), erasers (ALKBH5 and FTO), and readers (YTHDF1, YTHDF2, YTHDF3, YTHDC1, and YTHDC2) were all significantly higher in PBMCs from patients with pSS than in HCs. The mRNA levels of m6A writers (METTL3 and WTAP) and readers (YTHDF2, YTHDF3, and YTHDC2) were lower in PBMCs from patients with pSS compared to patients with non-SS sicca. The expression of METTL3, RBM15, FTO, YTHDF1, YTHDF2, YTHDC1, and YTHDC2 was positively correlated with the level of C-reactive protein (CRP) of patients with pSS. The mRNA level of YTHDF1 in PBMCs from patients with pSS was negatively correlated with the EULAR Sjögren’s syndrome disease activity index (ESSDAI) score. In patients with pSS, FTO, YTHDC1, and YTHDC2 were also related to white blood cells (WBCs), neutrophils, lymphocytes, and monocytes. Increased mRNA level of ALKBH5 in PBMCs was a risk factor for pSS, as determined by binary logistic regression analysis. The mRNA level of ISG15 was positively correlated with that of FTO, YTHDF2, YTHDF3, and YTHDC2 in patients with pSS. Conclusion Compared with HCs, the expression of METTL3, RBM15, ALKBH5, FTO, YTHDF1, YTHDF2, YTHDF3, YTHDC1, and YTHDC2 was considerably higher in PBMCs from patients with pSS. In comparison with patients with non-SS sicca, the expression of METTL3, WTAP, YTHDF2, YTHDF3, and YTHDC2 was reduced in PBMCs from patients with pSS. The m6A elements correlating with clinical variables may indicate the disease activity and inflammation status of pSS. Elevated expression of ALKBH5 was a risk factor for pSS. The dynamic process of m6A modification is active in pSS. m6A elements (FTO, YTHDF2, YTHDF3, or YTHDC2) might target ISG15, stimulate the expression of ISG15, and activate the type I IFN signaling pathway, playing an active role in initiating the autoimmunity in pSS.
Article
This study aims to determine the prevalence and risk factors associated with lymphoma in primary Sjögren's syndrome (pSS). We conducted a cross‐sectional study on pSS patients who were registered into the Integrated Data Repository (IDR) at the University of Florida (UF) Health Shands Hospital. The parameters, such as age, sex, race, and smoking status, were included. Lymphoma types in pSS were categorized. The clinical and laboratory features were compared between pSS patients with and those without lymphoma by utilizing the items in the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI). Among 1,211,343 patients, we found 6,799 patients (0.56%) with lymphomas and 2,562 patients (0.21%) with pSS. Out of the 2,562 pSS patients, 67 patients (2.6%) were diagnosed with lymphoma. The difference in the clinical and laboratory features listed under the ESSDAI domains between pSS patients with lymphomas and pSS without it was significant (p<0.05 or 0.01): fever, weight loss, lymphadenopathy, splenomegaly, lacrimal gland diseases, cough, shortness of breath, hematuria, cerebrovascular accident diseases, peripheral nerve involvement due to vasculitis, neutropenia, and thrombocytopenia. We report 2.6% of lymphoma prevalence in pSS, lower than previously reported in literature.
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Macroautophagy/autophagy is critically involved in the process of salivary gland (SG) diseases such as xerostomia, which has a serious impact on quality of life. KRT14+ progenitor cells are found to be the main progenitors for maintaining the ductal homeostasis of the submandibular SGs. In this study, we investigated the role of ATG5 in SG KRT14+ cells in mice and humans. Human labial salivary glands (LSG) from primary Sjogren's syndrome (pSS) and non‐pSS patients (normal), and submandibular glands (SMG) from Atg5flox/flox; Krt14‐Cre (cKO) mice were used. ATG5+KRT14+ and p62+KRT14+ cells were detected by immunofluorescence staining in LSG. TUNEL, immunofluorescence, immunohistochemistry, and western blot were performed to detect cell death in SMG. Saliva was collected in 12‐week‐old (12 W) and 32‐week‐old (32 W) mice, then the concentration of calcium and buffering capacity were detected to analyze the function of SG. We found that LSG from pSS patients showed increased p62 and decreased ATG5 in KRT14+ cells. We further revealed that in 32 W, (1) the function of salivary glands was significantly impaired in cKO mice, (2) cell death increased in cKO mice, but cl‐Caspase 3 was not significantly changed, and (3) cleaved gasdermin D increased and was highly expressed in KRT14+ cells of cKO mice. After applying a pyroptosis inhibitor to 32 W mice, the reduced saliva flow rate was rescued. In addition, pyroptosis was also found in KRT14+ cells of pSS patients. Collectively, our results indicate that Atg5 deficiency would induce pyroptosis in mice SG, which could lead to functional impairments of SG.
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In this study, we report that AZD6738 (Ceralasertib), a novel potent ataxia telangiectasia and Rad3-related (ATR) kinase inhibitor, can decrease intraocular pressure (IOP) and inhibits fibrotic response in the trabecular meshwork (TM). We established mice TGF-β2-induced high IOP model and revealed that AZD6738 could effectively decrease IOP in the mice model and reduce TGF-β2-induced hyperplasia, collagen production, fibrosis, and extracellular matrix (ECM) remodeling in the TM by downregulating checkpoint kinase 1 (CHK1) level. Further, we demonstrated that AZD6738 reduces cell viability and migration, and inhibit the expression of fibrosis-related factors including fibronectin (FN), α-smooth muscle actin (α-SMA), laminin subunit beta 1 (LAMB1), matrix metallopeptidase (MMP) family including MMP2 and MMP9, collagen Ⅰ (COL1), and collagen Ⅳ (COL4), reduce gap junctions, altered cytoskeleton and nitric oxide production in TGF-β1-induced human trabecular meshwork cells (HTMCs) through the CHK1/P53 pathway, which were affected aqueous humor (AH) production and outflow pathway. In addition, we preliminarily verified the safety of the AZD6738 in topical ophthalmic use. Hence, our results demonstrate that AZD6738 may become a potential therapeutic option for anti-glaucoma.
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Objectives: Sjögren's Disease (SjD) is a chronic and systemic autoimmune disease characterized by lymphocytic infiltration and the development of dry eyes and dry mouth resulting from the secretory dysfunction of the exocrine glands. SARS-CoV-2 may trigger the development or progression of autoimmune diseases, as evidenced by increased autoantibodies in patients and the presentation of cardinal symptoms of SjD. The objective of the study was to determine whether SARS-CoV-2 induces the signature clinical symptoms of SjD. Methods: The ACE2-transgenic mice were infected with SARS-CoV-2. SJD profiling was conducted. COVID-19 patients' sera were examined for autoantibodies. Clinical evaluations of convalescent COVID-19 subjects, including minor salivary gland (MSG) biopsies, were collected. Lastly, monoclonal antibodies generated from single B cells of patients were interrogated for ACE2/spike inhibition and nuclear antigens. Results: Mice infected with the virus showed a decreased saliva flow rate, elevated antinuclear antibodies (ANAs) with anti-SSB/La, and lymphocyte infiltration in the lacrimal and salivary glands. Sera of COVID-19 patients showed an increase in ANA, anti-SSA/Ro52, and anti-SSB/La. The male patients showed elevated levels of anti-SSA/Ro52 compared to female patients, and female patients had more diverse ANA patterns. Minor salivary gland biopsies of convalescent COVID-19 subjects showed focal lymphocytic infiltrates in four of six subjects, and 2 of 6 subjects had focus scores >2. Lastly, we found monoclonal antibodies produced in recovered patients can both block ACE2/spike interaction and recognize nuclear antigens. Conclusion: Overall, our study shows a direct association between SARS-CoV-2 and SjD. Hallmark features of SjD salivary glands were histologically indistinguishable from convalescent COVID-19 subjects. The results potentially implicate that SARS-CoV-2 could be an environmental trigger for SjD. Key messages: What is already known about this subject?SAR-CoV-2 has a tropism for the salivary glands. However, whether the virus can induce clinical phenotypes of Sjögren's disease is unknown.What does this study add?Mice infected with SAR-CoV-2 showed loss of secretory function, elevated autoantibodies, and lymphocyte infiltration in glands.COVID-19 patients showed an increase in autoantibodies. Monoclonal antibodies produced in recovered patients can block ACE2/spike interaction and recognize nuclear antigens.Minor salivary gland biopsies of some convalescent subjects showed focal lymphocytic infiltrates with focus scores.How might this impact on clinical practice or future developments?Our data provide strong evidence for the role of SARS-CoV-2 in inducing Sjögren's disease-like phenotypes.Our work has implications for how patients will be diagnosed and treated effectively.
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There is a well-known association between the connective tissue disorders (CTDs) and lung disease. In addition to interstitial lung disease, the CTDs may affect the air spaces and pulmonary vasculature. Imaging tests are important not only in diagnosis but also in management of these complex disorders. In the present review, key aspects of the imaging of CTD-reated diseases are discussed.
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The cystic lung diseases (CLD) are characterized by the presence of multiple, thin-walled, air-filled spaces in the pulmonary parenchyma. Cyst formation may occur with congenital, autoimmune, inflammatory, infectious, or neoplastic processes. Recognition of cyst mimics such as emphysema and bronchiectasis is important to prevent diagnostic confusion and unnecessary evaluation. Chest CT can be diagnostic or may guide the workup based on cyst number, distribution, morphology, and associated lung, and extrapulmonary findings. Diffuse CLD (DCLDs) are often considered those presenting with 10 or more cysts. The more commonly encountered DCLDs include lymphangioleiomyomatosis, pulmonary Langerhans' cell histiocytosis, lymphoid interstitial pneumonia, Birt-Hogg-Dubé syndrome, and amyloidosis/light chain deposition disease.
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A síndrome de Sjögren primária (SSp) é uma doença inflamatória e crônica que pode apresentar manifestações glandulares e sistêmicas (presentes entre 20% e 40% dos casos). Para melhor avaliação dos pacientes com essa doença, métricas que avaliam essas manifestações podem ser utilizadas, dentre elas temos o EULAR Sjögren’s syndrome patient report index (ESSPRI), que avalia sintomas de secura, fadiga e dor articular; o EULAR Sjögren’s syndrome disease activity index (ESSDAI), que avalia atividade sistêmica da doença, resposta ao tratamento e prognóstico; já os índices de dano são representados pelo Sjögren’s syndrome disease damage index (SSDDI) e o Sjögren’s syndrome damage index (SSDI). Também podemos nos utilizar de testes subjetivos e objetivos de avaliação de olho seco (questionário de xeroftalmia, teste de Schirmer, tempo de ruptura lacrimal e Ocular Surface Disease Index – OSDI); os testes subjetivos e objetivos de boca seca (questionário de xerostomia, fluxo salivar não estimulado e estimulado, cintilografia de glândulas salivares, ultrassonografia de glândulas salivares maiores e biópsia de glândula salivar menor) e outros índices ou métricas que podem ser específicos ou não da SSp, como os que avaliam fadiga e qualidade de vida. Unitermos: Síndrome de Sjögren. Métricas. Questionários. Olho seco. Boca seca.
Chapter
Sjogren’s syndrome (SS) is a connective tissue disease targeting the exocrine glands with subsequent sicca symptoms mainly in eyes and mouth. Respiratory symptoms may be the most frequent extraglandular manifestation following fatigue and pain. Mucosal dysfunction may affect the upper and lower airways, being the small airways more frequently involved. Parenchymal disease carries most of the morbidity and mortality. Nonspecific interstitial pneumonia (NSIP) is the most common radiographic feature, whereas the fibrotic NSIP type is the most reported finding in biopsies. Pulmonary lymphoma may arise from bronchial-associated lymphoid tissue lesions, and although rare, it is prevalent in SS. Chronic hypertrophic bronchial wall changes may ascribe to the various cystic lesions. Under their presence, possible lymphocytic interstitial pneumonia, amyloidosis, and lymphoma should be explored. Pulmonary arterial hypertension may present as frequently as in lupus, especially in Asian populations. Advanced knowledge in the pathogenesis has helped in understanding the various presentations within the respiratory system, contrasting with the scarce therapeutic options to treat both the airway and parenchymal disease. Anti-fibrotic parenchymal lung therapy offers promising outcomes. The pulmonary involvement in SS may associate with a decline in quality of life and reduced life expectancy. Subsequently, clinicians should know these facts for a timely intervention.
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Mesenchymal stem cell (MSC) transplantation has been proven to be an effective treatment for Sjögren’s syndrome (SS) to improve salivary gland pathology and exocrine function, but the mechanism remains unclear. A recently reported inhibitory receptor, Tim-3, also appears to be closely related to autoimmune diseases. Here, we aimed to explore the roles of Tim-3 in the pathogenesis of SS and MSC treatment. The results showed that Tim-3 was downregulated in T cells of SS patients and nonobese diabetic (NOD) mice, which is correlated with SS pathogenesis. MSC transplantation ameliorated SS-like symptoms and pathological changes in the submandibular glands with modulated Tim-3 expression, resulting in attenuation of localized inflammation, fibrosis, and epithelial-mesenchymal transition. Furthermore, Tim-3 is crucial for the inhibitory effect of MSCs on PBMC proliferation in vitro. Therefore, our work has demonstrated that MSC transplantation effectively mitigates the pathological changes of SS by regulating Tim-3 expression, which provides a novel mechanism of MSC treatment and indicates a brand-new perspective of the combination of inhibitory-receptor-targeted treatment and MSC therapy in SS.
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To define the prevalence of Sjögren's syndrome (SS) through an epidemiological survey in a closed rural community. The classification of SS is based on the validated criteria reported by a multicentre study performed in Europe and supported by the Epidemiology Committee of the European Community (EEC-COMAC Epidemiology). The population under study consisted of 837 women aged 18 years or older, residing in the Astakos community of Aitoloakarnania, Greece. The study protocol was subdivided in two parts. In part I, an exhaustive epidemiological survey of these women was conducted in July and August of 1992. The validated questionnaire used in the survey assesses both ocular and oral involvement. In part II, 45 of the women reporting symptoms of both dry eye and dry mouth were approached for a full examination based on the validated set of classification criteria of SS. The full complement of the diagnostic tests was performed on 35 of these women. A subject is classified as a definite primary SS case if at least four of six items of the subject's test items are positive. If three of six items are positive the subject is classified as a probable primary SS case. The classification criteria for definite primary SS were satisfied by five women. This number corresponds to an estimated prevalence of 0.60% (exact 95% CI 0.19%, 1.39%). Probable primary SS was diagnosed for 25 women (prevalence = 2.99%). Because of the loss of follow up (10 of 45) and the use of slightly stricter criteria for inclusion of possible SS cases in part II of the study, we consider our estimate of the prevalence of SS to be conservative. This study concurring with other recent reports, suggests that SS is more prevalent than previously thought.
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Because of the pressure for timely, informed decisions in public health and clinical practice and the explosion of information in the scientific literature, research results must be synthesized. Meta-analyses are increasingly used to address this problem, and they often evaluate observational studies. A workshop was held in Atlanta, Ga, in April 1997, to examine the reporting of meta-analyses of observational studies and to make recommendations to aid authors, reviewers, editors, and readers. Twenty-seven participants were selected by a steering committee, based on expertise in clinical practice, trials, statistics, epidemiology, social sciences, and biomedical editing. Deliberations of the workshop were open to other interested scientists. Funding for this activity was provided by the Centers for Disease Control and Prevention. We conducted a systematic review of the published literature on the conduct and reporting of meta-analyses in observational studies using MEDLINE, Educational Research Information Center (ERIC), PsycLIT, and the Current Index to Statistics. We also examined reference lists of the 32 studies retrieved and contacted experts in the field. Participants were assigned to small-group discussions on the subjects of bias, searching and abstracting, heterogeneity, study categorization, and statistical methods. From the material presented at the workshop, the authors developed a checklist summarizing recommendations for reporting meta-analyses of observational studies. The checklist and supporting evidence were circulated to all conference attendees and additional experts. All suggestions for revisions were addressed. The proposed checklist contains specifications for reporting of meta-analyses of observational studies in epidemiology, including background, search strategy, methods, results, discussion, and conclusion. Use of the checklist should improve the usefulness of meta-analyses for authors, reviewers, editors, readers, and decision makers. An evaluation plan is suggested and research areas are explored.
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There has been no previous prevalence study about of Sjögren's syndrome (SS) in Brazil. The aim was to evaluate the SS prevalence in a general population in Vitória, ES, Brazil. This was an epidemiological, observational, and cross-sectional study conducted on 1,205 randomized people, aged 18-65 years, who lived in Vitória. The subjects were screened for xerostomia and xerofphthalmia through home interviews. Those with sicca symptoms were asked to report to a hospital for further medical evaluation, unstimulated salivary flow, Schirmer I test, blood analysis and minor labial salivary biopsy. Sicca symptoms were found in 18% (217 subjects) of the sample. Of the 217 subjects with sicca symptoms, 127 (58%) were available for examination. In this sample, 61.7% were female and 46.8% were under medication. Sicca syndrome was confirmed in 12% by at least one examination (salivary flow or Schirmer I). Two patients (0.17%) matched four criteria according to American-European Criteria (95% CI = 0.020-0.5983).
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Studies on the epidemiology of primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC) show variable outcome. We aimed at systematically reviewing the incidence and prevalence rates, as well as geographical distribution and temporal trends of PSC and PBC. A systematic search of literature was performed in Medline and EMBASE (search last conducted January 10th, 2011). Population-based epidemiological studies reporting incidence and/or prevalence rates for PSC or PBC in a defined geographical area of at least 100,000 adult inhabitants were considered relevant. Study area, study period, number of patients, number of inhabitants, incidence per 100,000 inhabitants per year, prevalence per 100,000 inhabitants, method of case-finding, method of case-ascertainment, male/female ratio and in case of PSC, occurrence of inflammatory bowel diseases (IBD) were extracted from retrieved articles. The literature search yielded 2286 abstracts of which 31 articles fulfilled all inclusion criteria. Studies varied in size from 10 to 770 patients in catchment areas from 100,312 to 19,230,000 inhabitants. The incidence and prevalence rates for PSC range from 0 to 1.3 per 100,000 inhabitants/year and 0-16.2 per 100,000 inhabitants, respectively. PBC incidence rates range from 0.33 to 5.8 per 100,000 inhabitants/year and prevalence rates range from 1.91 to 40.2 per 100,000 inhabitants; prevalence rates are increasing in time. Incidence and prevalence rates of both PSC and PBC vary widely and seem to be increasing. True population-based studies are scarce and therefore large population-based studies combining meticulous case-finding and case-ascertainment strategies are necessary.
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The limited availability of prevalence data based on a representative sample of the general population, and the limited number of diseases considered in studies about co-morbidity are the critical factors in study of autoimmune diseases. This paper describes the prevalence of 12 autoimmune diseases in a representative sample of the general population in the South of Sardinia, Italy, and tests the hypothesis of an overall association among these diseases. Data were obtained from 21 GPs. The sample included 25,885 people. Prevalence data were expressed with 95% Poisson C.I. The hypothesis of an overall association between autoimmune diseases was tested by evaluating the co-occurrence within individuals. Prevalence per 100,000 are: 552 rheumatoid arthritis, 124 ulcerative colitis, 15 Crohn's disease, 464 type 1 diabetes, 81 systemic lupus erythematosus, 124 celiac disease, 35 myasthenia gravis, 939 psoriasis/psoriatic arthritis, 35 systemic sclerosis, 224 multiple sclerosis, 31 Sjogren's syndrome, and 2,619 autoimmune thyroiditis. An overall association between autoimmune disorders was highlighted. The comparisons with prevalence reported in current literature do not show outlier values, except possibly for a few diseases like celiac disease and myasthenia gravis. People already affected by a first autoimmune disease have a higher probability of being affected by a second autoimmune disorder. In the present study, the sample size, together with the low overall prevalence of autoimmune diseases in the population, did not allow us to examine which diseases are most frequently associated with other autoimmune diseases. However, this paper makes available an adequate control population for future clinical studies aimed at exploring the co-morbidity of specific pairs of autoimmune diseases.
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Rheumatic diseases are a major health and financial burden for societies. The prevalence of rheumatic diseases may change over time, and therefore, we sought to estimate the prevalence of rheumatic diseases in an adult population of central Greece. In this prospective cross-sectional population survey, a random sample of adult population was drawn from poll catalogues of a region in central Greece. A postal questionnaire was sent to 3,528 people for the presence of any rheumatic disease. All positive cases were further confirmed by clinical examination using the American College of Rheumatoloy criteria. Multiple regression analysis was used to assess risk factors for rheumatic diseases. The response rate was 48.3% (1,705 answers). Four hundred and twenty individuals (24.6%) had a rheumatic disease. The prevalence of rheumatoid arthritis was 0.58% (95% confidence interval [CI], 0.32-0.87), of psoriatic arthritis was 0.35% (95% CI, 0.33-1.13), of ankylosing spondylitis was 0.29% (95% CI, 0.28-0.94), of primary Sjögren's syndrome was 0.23% (95% CI, 0.22-0.75) and of systemic lupus erythematosus was 0.11% (95% CI, 0.11-0.37). One individual had systemic sclerosis (prevalence, 0.058%), 1 individual had dermatomyositis (prevalence, 0.058%; 95% CI, 0.05-0.18), 2 individuals had vasculitis (prevalence 0.11%; 95% CI, 0.11-0.37), 81 individuals had gout (prevalence, 4.75%; 95% CI, 4.41-5.13), and 304 individuals had osteoarthritis (OA) (prevalence 17.82%; 95% CI, 16.50-19.34). Gout was associated with male gender, diabetes mellitus, and hypertension, and OA was associated with age, female gender, and hypertension. Rheumatic diseases are common in central Greece, affecting nearly a quarter of adult population. OA and gout are the most common joint disorders.
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To assess the recently proposed preliminary criteria for the classification of Sjögren's syndrome (SS) in a multicentre European study of a new series of clinically defined cases. The criteria included six items: I = ocular symptoms; II = oral symptoms; III = evidence of keratoconjunctivitis sicca; IV = focal sialoadenitis by minor salivary gland biopsy; V = instrumental evidence of salivary gland involvement; VI = presence of autoantibodies. Each centre was asked to provide five patients with primary SS, five with secondary SS, five with connective tissue diseases (CTD) but without SS, and five controls (patients with ocular or oral features that may simulate SS). The preliminary six item classification criteria set was applied to both the SS patients and the non-SS controls, and the performance of the criteria in terms of sensitivity and specificity was tested. The criteria set was tested on a total of 278 cases (157 SS patients and 121 non-SS controls) collected from 16 centres in 10 countries. At least four of the six items in the criteria set (limiting item VI to the presence of Ro(SS-A) or La(SS-B) antibodies) were present in 79 of 81 patients initially classified as having primary SS (sensitivity 97.5%), but in only seven of 121 non-SS controls (specificity 94.2%). When the presence of item I or II plus any two of items III-V of the criteria set was considered as indicative of secondary SS, 97.3% (71 of 73) of the patients initially defined as having this disorder and 91.8% (45 of 49) of the control patients with CTD without SS were correctly classified. This prospective study confirmed the high validity and reliability of the classification criteria for SS recently proposed by the European Community Study Group.
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Using the European Community (EC) criteria for classification Vitali et al. Arthritis Rheum 1993;36:340 7, we report the prevalence estimates of Sjogren's syndrome (SS) from a general population and present the first population data to assess the impact of the syndrome. A cross-sectional population-based survey performed on 1000 adults, aged 18-75 yr, randomly selected from a population register. Responders to the initial postal phase were invited for an interview. The five criteria measured at interview were: (1) the reporting of subjective oral symptoms lasting for > 3 months; (2) the reporting of subjective ocular symptoms lasting for >3 months; (3) Schirmer-I test; (4) unstimulated salivary flow; (5) autoantibodies [Ro (SS-A), La (SS-B), rheumatoid factor (RF), antinuclear antibodies (ANA)]. SS was diagnosed if at least four of these five criteria were positive. The MOS Short-form 36 (SF-36), General Health Questionnaire (GHQ) and the Health and Fatigue Questionnaire (HFQ) were completed by subjects after the interview, and scores were compared between those with and without a diagnosis of SS. A total of 341 subjects completed both the postal questionnaire and home visit. A diagnosis of SS could be given to 13 subjects. After adjusting for the presence of possible bias due to non-response, our best estimate of the prevalence of SS in the study population was 33 per 1000 subjects (95% CI 22 44). The prevalence of the disorder was higher in females (38; 95% CI 27-52) and for those subjects aged > or = 55 yr (46; 95% CI 34-61). Those subjects diagnosed positively were more impaired for each of the eight dimensions of the SF-36 than those without a diagnosis, and also suffered from higher levels of depression and fatigue. SS affects approximately 3-4% of adults and in the general population appears to be associated with a clinically significant impairment of a subject's health and well-being.
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The aim of our study was to determine the prevalence of Sjögren's syndrome (SS) in Slovenia. A total of 889 randomly selected adults were invited to take part in our study. The classification of SS was based on the validated criteria reported by a multicentre study performed in Europe. The participants were asked six simple questions for assessing both ocular and oral involvement. Information on co-morbidities and related treatment was collected at the same time. All participants were subjected to a Schirmer-I test, an unstimulated salivary flow test, as well as serological studies (rheumatoid factor, antinuclear antibodies, anti-Ro/SS-A and anti-La/SS-B antibodies). When indicated, Rose Bengal score, salivary scintigraphy and histopathological investigation of the minor salivary glands were carried out until three out of the six European classification criteria for SS were shown to be negative or until SS was diagnosed. Out of the 889 invited subjects, 332 (37.3%) participated in our study: 183 females, mean age (+/- S.D.) 52.2 +/- 13.7 yr (range 20-84) and 149 males, mean age (+/- S.D.) 56.3 +/- 12.9 yr (range 23-84). After the first visit, 244 of the 332 (73.5%) participants proved to be negative for three out of the six above-mentioned criteria, and were eliminated from further tests. The remaining 88 participants were consecutively subjected to Rose Bengal score, salivary scintigraphy and minor salivary gland biopsy. Fifteen participants refused to perform either one or more of the proposed tests at the second study stage. Two females of the 332 study participants [0.60% (exact 95% CI 0.07%, 2.16%)] fulfilled the criteria for primary SS. The estimated prevalence of definite SS in Slovenia is 0.60%.
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Cochrane Reviews have recently started including the quantity I 2 to help readers assess the consistency of the results of studies in meta-analyses. What does this new quantity mean, and why is assessment of heterogeneity so important to clinical practice? Systematic reviews and meta-analyses can provide convincing and reliable evidence relevant to many aspects of medicine and health care.1 Their value is especially clear when the results of the studies they include show clinically important effects of similar magnitude. However, the conclusions are less clear when the included studies have differing results. In an attempt to establish whether studies are consistent, reports of meta-analyses commonly present a statistical test of heterogeneity. The test seeks to determine whether there are genuine differences underlying the results of the studies (heterogeneity), or whether the variation in findings is compatible with chance alone (homogeneity). However, the test is susceptible to the number of trials included in the meta-analysis. We have developed a new quantity, I 2, which we believe gives a better measure of the consistency between trials in a meta-analysis. Assessment of the consistency of effects across studies is an essential part of meta-analysis. Unless we know how consistent the results of studies are, we cannot determine the generalisability of the findings of the meta-analysis. Indeed, several hierarchical systems for grading evidence state that the results of studies must be consistent or homogeneous to obtain the highest grading.2–4 Tests for heterogeneity are commonly used to decide on methods for combining studies and for concluding consistency or inconsistency of findings.5 6 But what does the test achieve in practice, and how should the resulting P values be interpreted? A test for heterogeneity examines the null hypothesis that all studies are evaluating the same effect. The usual test statistic …
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To determine the annual incidence of primary Sjögren's syndrome (pSS) in Slovenia. All patients admitted to our department of rheumatology or referred to our outpatient clinic between 1 January 2000 and 31 December 2002 owing to sicca symptoms or because of a suspicion of SS were examined. Our rheumatological department is the only tertiary referral centre for the Ljubljana region, which has a population of 599 895 Caucasian people. All patients were evaluated by the validated European criteria for SS. The exact 95% confidence interval (CI) based on binomial distribution was created for the incidence estimate. 248 patients were examined; 71 of them (28.6%; 65 women, 6 men) were diagnosed as having pSS. Their mean (SD) age was 51.3 (14.5) years (range 19-78). The average annual incidence for pSS in our study population was calculated as 3.9 cases per 100 000 inhabitants (95% CI 1.1 to 10.2). The estimated annual incidence of pSS in Slovenia is 3.9/100 000.
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To investigate the incidence and prevalence, as well as the mortality and survival rates, of primary Sjögren's syndrome (pSS) in a defined area of north-west Greece with a population of about 500 000 inhabitants. Cases were recorded from the following sources: (i) in- and out-patients referred to the rheumatology clinics of the Ioannina University Hospital and the Ioannina General Hospital; and (ii) patients referred to private rheumatologists practising in the study area. All patients diagnosed between 1 January 1982 and 31 December 2003 who were resident in the study area were included as incident cases. Diagnosis was based on the American-European consensus criteria for SS. Incidence and prevalence rates were calculated as numbers of cases per 10(5) inhabitants. Population data were based on the National Censuses of 1981, 1991 and 2001. A total of 422 incident cases were identified for the study period 1982-2003. Age-adjusted mean annual incidence rate for this period was 5.3 (95% confidence interval [CI] 4.5-6.1) cases per 10(5) adult inhabitants. The female/male ratio of incident cases was about 20/1. The age-adjusted prevalence rate for the adult population was 92.8 (95% CI 83.7-101.9) cases per 10(5) inhabitants on 31 December 2003. The 5-yr survival rate in the incidence cohort was 96.6% and the 10-yr survival rate 92.8%. The standardized mortality ratio in comparison with the general population of the study area was 1.02 (95% CI 0.4-2.0). The main causes of death were cardiovascular diseases and cancer. The occurrence of the disease shows a slightly decreasing, but not statistically significant, trend with time. The estimated incidence and prevalence of pSS in this study were slightly higher in comparison with data from other studies based on physician-diagnosed cases. The prevalence was significantly lower when compared with the findings of studies based on the examination of a sample of the general population. Mortality rates did not differ significantly between pSS patients and the general population.
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The aim of this study was to determine the prevalence of primary Sjögren's syndrome (pSS) according to European criteria (1993) and to the US-European Consensus Group (US-EU) criteria (2002) in adult women in Bornova, Izmir, Turkey. The study was designed as a two-phase cross-sectional survey consisting of a baseline questionnaire and collection of blood samples and clinical examination. In the initial phase, positivity for autoantibodies Ro(SS-A), La(SS-B), rheumatoid factor (RF), and anti-nuclear antibodies (ANA) was determined, and in the clinical phase, clinical examination, salivary and ocular tests were performed. Minor salivary gland biopsy was performed for those who had at least three of these five criteria positive. In our sample the prevalence of SS was 1.56% [95% confidence interval (CI) 0.92-2.66] according to the European criteria and 0.72% (95% CI 0.33-1.57) according to the US-EU criteria. To prevent the loss in diagnosis of pSS, the addition of ANA, RF, and tear break-up time (BUT) tests to US-EU criteria would be appropriate.
Article
Objective. Different sets of diagnostic criteria have been proposed for Sjögren's syndrome (SS), but none have been validated with a large series of patients or in a multicenter study. We conducted the present study involving 26 centers from 12 countries (11 in Europe, plus Israel), with the goals of reaching a consensus on the diagnostic procedures for SS and defining classification criteria to be used in epidemiologic surveys and adopted by the scientific community. Methods. The study protocol was subdivided into two parts. For part I, questionnaires regarding both ocular and oral involvement were developed; they included 13 questions and 7 questions, respectively. For part II a limited set of diagnostic tests was selected, and the exact procedure to be followed in performing these tests was defined. Part I of the study ipcluded 240 patients with primary SS and 240 age- and sex-matched controls. Two hundred forty-six patients with primary SS, 201 with secondary SS, 113 with connective tissue diseases but without associated SS, and 133 control patients were studied in part II. Results. The study resulted in (a) the validation of a simple 6-item questionnaire for determination of dry eyes and dry mouth, which showed good discriminant power between patients and controls, to be used in the initial screening for sicca syndrome; and (b) the definition of a new set of criteria for the classification of SS. The sensitivity and specificity of the criteria in correctly identifying patients with either the primary or the secondary variant of SS were also determined. Conclusion. Using the findings of this prospective multicenter European study, general agreement can be reached on the diagnostic procedures to be used for patients with SS. Final validation of the preliminary classification criteria for SS is underway.
Article
Objective To describe the epidemiology of primary Sjogren's syndrome (SS) in a multiracial/multiethnic population. MethodsA cross-sectional study with 5 case-retrieval sources identified adults with primary SS living in the Greater Paris area (population 1,172,482 adults) in 2007. Diagnoses were verified by the American-European Consensus Group (AECG) criteria and study-specific enlarged criteria based on the presence of 3 of 4 AECG items among subjective oral or ocular dryness, anti-SSA/SSB positivity, and positive minor salivary gland biopsy results. Prevalence estimates were standardized to those for the world population and a 5-source capture-recapture analysis (CRA) was used. Racial/ethnic differences in primary SS features were evaluated. ResultsIn all, 133 subjects met the AECG criteria and 203 met the enlarged criteria. The 2007 prevalence of primary SS was 1.02 cases per 10,000 adults (95% confidence interval [95% CI] 0.85-1.22) for the AECG criteria and 1.52 cases per 10,000 adults (95% CI 1.30-1.76) for the enlarged criteria. The CRA indicated completeness of case findings of approximate to 90%. Compared to subjects with European backgrounds, those with non-European backgrounds had 2.1-2.3 times higher primary SS prevalence and were younger (P < 0.0001) and were more likely to have polyclonal hypergammaglobulinemia (P < 0.0001) and anti-SSA/SSB antibodies (P = 0.0005 and P < 0.0001 for the AECG and enlarged criteria, respectively). Conclusion The figure of 1.02-1.52 cases per 10,000 adults we found and estimates from the few other population-based census surveys support that the prevalence of diagnosed primary SS is between 1 and 9 cases per 10,000 people (0.01-0.9%) in the general population. Non-European race/ethnicity may be associated with increased primary SS risk and a distinct disease profile.
Article
The purpose of this study was to estimate the sex- and age-specific incidence rates of major autoimmune rheumatic diseases (ARDs) in Taiwan using a population longitudinal database. A health insurance database containing the records of 1,000,000 beneficiaries of Taiwan National Health Insurance from 2005 to 2009 was used. Between 2005 and 2009, the overall incidence rate of the major ARDs was 29.8 (95% CI = 28.3-31.3) per 100,000 person-years. Among the ARDs studied, the incidence of rheumatoid arthritis (RA; per 100,000 person-years) was highest (17.2, 95% CI = 16.1-18.4) and was followed by Sjögren's syndrome (11.8, 95% CI = 10.8-12.7), systemic lupus erythematosus (SLE; 7.2, 95% CI = 6.5-8.0), systemic sclerosis (SS; 1.1, 95% CI = 0.8-1.4), vasculitis (1.0, 95% CI = 0.7-1.3), Behçet disease (0.9, 95% CI = 0.6-1.1), dermatomyositis (DM; 0.7, 95% CI = 0.5-1.0), and polymyositis (PM; 0.6, 95% CI = 0.4-0.8). Females had a higher incidence ratio than did males, but a significant female/male incidence ratio was only observed for SLE (8.5, 95% CI = 6.1-12.0), Sjögren's syndrome (6.0, 95% CI = 4.8-7.6), RA (3.0, 95% CI = 2.6-3.5), and SS (2.6, 95% CI = 1.4-4.6). ARDs are three to four times more common among women than among men in the Chinese population of Taiwan. The incidence of RA was the highest, followed by Sjögren's syndrome and SLE, while the incidence of Behçet disease was the lowest in this study. This nationwide, population-based, longitudinal epidemiological study of ARDs in Taiwan provides data for future global comparisons and may provide clues as to the etiology of these diseases.
Article
Objective. The aim of our study was to determine the prevalence of Sjogren's syndrome (SS) in Slovenia. Methods. A total of 889 randomly selected adults were invited to take part in our study. The classification of SS was based on the validated criteria reported by a multicentre study performed in Europe. The participants were asked six simple questions for assessing both ocular and oral involvement. Information on co-morbidities and related treatment was collected at the same time. All participants were subjected to a Schirmer-I test, an unstimulated salivary flow test, as well as serological studies (rheumatoid factor, antinuclear antibodies, anti-Ro/SS-A and anti-La/SS-B antibodies). When indicated, Rose Bengal score, salivary scintigraphy and histopathological investigation of the minor salivary glands were carried out until three out of the six European classification criteria for SS were shown to be negative or until SS was diagnosed. Results. Out of the 889 invited subjects, 332 (37.3%) participated in our study: 183 females, mean age (± S.D.) 52.2 ± 13.7 yr (range 20-84) and 149 males, mean age (± S.D.) 56.3 ± 12.9 yr (range 23-84). After the first visit, 244 of the 332 (73.5%) participants proved to be negative for three out of the six above-mentioned criteria, and were eliminated from further tests. The remaining 88 participants were consecutively subjected to Rose Bengal score, salivary scintigraphy and minor salivary gland biopsy. Fifteen participants refused to perform either one or more of the proposed tests at the second study stage. Two females of the 332 study participants [0.60% (exact 95% CI 0.07%, 2.16%)] fulfilled the criteria for primary SS. Conclusions. The estimated prevalence of definite SS in Slovenia is 0.60%.
Article
Introduction: Primary Sjögren syndrome (SS) is a chronic systemic autoimmune disease characterized by sicca features and systemic manifestations, and requires a multidisciplinary therapeutic approach. Areas covered: Treatment of sicca manifestations is symptomatic and is based on the administration of topical therapies (saliva substitutes and preservative-free artificial tears). In severe cases of keratoconjunctivitis sicca, topical cyclosporine A may be used. For patients with residual salivary gland function, stimulation of salivary flow with a sialogogue (pilocarpine or cevimeline) is the treatment of choice. The management of extraglandular features must be tailored to the specific organ(s) involved. Hydroxychloroquine may be appropriate for patients with fatigue, arthralgia and myalgia, while glucocorticoids and immunosuppressive agents should be reserved for severe systemic involvement (although no controlled trials in primary SS guide their use). RCTs have demonstrated the lack of efficacy of antitumor necrosis factor agents and promising results for B-cell depleting agents. Expert opinion: The overall low level of evidence in therapeutic studies in primary SS suggests that much larger trials of the most promising therapies are necessary. The use of drugs targeting molecules and receptors involved in the etiopathogenesis of primary SS may open up a new era in the therapeutic management of the disease, but the potential risks and benefits of these agents must be weighed carefully.
Article
The purpose of this study was to determine the prevalence, incidence, and mortality rates of autoimmune rheumatic diseases (ARDs) by using a population-based database. We used the longitudinal health insurance database (comprising 1,000,000 beneficiaries) of the Taiwan National Health Insurance from 2000 to 2008 and the National Death Registry of Taiwan from 2000 to 2008. The overall prevalence of major ARDs was 101.3 (95% confidence interval [95% CI] 27.5–107.9) per 100,000 populations; the prevalence was 165.1 (95% CI 44.8–177.1) in women and 40.1 (95% CI 10.9–46.1) in men. The prevalences of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjögren's syndrome, progressive systemic sclerosis, polymyositis/dermatomyositis, vasculitis, and Behçet's disease were 52.4 (95% CI 14.2–57.2), 37.0 (95% CI 10.0–41.0), 16.0 (95% CI 4.3–18.7), 3.8 (95% CI 1.0–5.3), 2.9 (95% CI 0.8–4.2), 5.7 (95% CI 1.6–7.4), and 1.4 (95% CI 0.4–2.3) per 100,000 persons, respectively. Between 2001 and 2008, the incidence rates (per 100,000 person-years) for these diseases were 17.3, 8.4, 10.6, 1.5, 1.5, 1.2, and 0.8, respectively. The incident cases with ARDs had a higher risk of mortality, with the standardized mortality ratio (SMR) ranging from 1.3 to 3.7. In 2000, the prevalence of major ARDs was 1.4–52.4 per 100,000 persons in Taiwan. Between 2000 and 2008, the incidence rates of various ARDs were 0.8–17.3 per 100,000 person-years. The prevalence and incidence of RA were the highest, followed by SLE and Sjögren's syndrome, and those of Behçet's disease were the lowest. Patients with different types of ARDs had higher mortality and SMR than those of the general population.
Article
Although the key inciting events that drive the progression from autoantibodies to clinical disease remain to be clarified, new light has been shed on the factors contributing to disease susceptibility and the role of genetic factors in determining Sjögren's syndrome (SS) disease phenotypes. The purpose of this article is to provide an update on the role of genetic markers in the susceptibility to and pathogenesis of SS. This article also discusses how genomic and proteomic technology can help in the design of specific therapeutics. Recent evidence suggests that inflammatory genes associated with interferon pathways, and specific regulatory genes that control the maturation and proliferation of B cells, contribute to the pathogenesis of SS. Both gene expression profiling technology and gene association studies have been used to identify these key biological pathways. Molecularly, defined subsets of pSS patients are also being revealed by these studies. Previously, identified gene loci that predispose to multiple autoimmune disorders have been confirmed supporting the paradigm of "general" autoimmune disease genes. Association of SS with many additional susceptibility loci are likely to be established through ongoing genome-wide association scans (GWAS). Clues from genetic studies suggest that targeting B cells will prove to be an effective way of reducing the systemic manifestations of pSS and are supported by early clinical trials. Genome-wide technologies are likely to identify new genes and molecular pathways in the pathogenesis of SS that will be useful not only to identify patients at risk for SS, but also to identify subsets of patients at risk for variable levels of disease severity. In the future, these studies could identify novel biomarkers that will lead to significant advances in management by providing the means to tailor therapeutic strategies to individual patients.
Article
Unlabelled: Incidence studies of primary sclerosing cholangitis (PSC) are important for describing the disease's burden and for shedding light on the disease's etiology. The purposes of this study were to conduct a systematic review of the incidence studies of PSC with a meta-analysis and to investigate possible geographic variations and temporal trends in the incidence of the disease. A systematic literature search of MEDLINE (1950-2010) and Embase (1980-2010) was conducted to identify studies investigating the incidence of PSC. The incidence of PSC was summarized with an incidence rate (IR) and 95% confidence intervals. The test of heterogeneity was performed with the Q statistic. Secondary variables extracted from the articles included the following: the method of case ascertainment, the country, the time period, the age, the male/female incidence rate ratio (IRR), and the incidence of PSC subtypes (small-duct or large-duct PSC and inflammatory bowel disease). Stratified and sensitivity analyses were performed to explore heterogeneity between studies and to assess effects of study quality. Time trends were used to explore differences in the incidence across time. The search retrieved 1669 potentially eligible citations; 8 studies met the inclusion criteria. According to a random-effects model, the pooled IR was 0.77 (0.45-1.09) per 100,000 person-years. However, significant heterogeneity was observed between studies (P < 0.001). Sensitivity analyses excluding non-population-based studies increased the overall IR to 1.00 (0.82-1.17) and eliminated the heterogeneity between studies (P = 0.08). The IRR for males versus females was 1.70 (1.34-2.07), and the median age was 41 years (35-47 years). All studies investigating time trends reported an overall increase in the incidence of PSC. Conclusion: The incidence of PSC is similar in North American and European countries and continues to increase over time. Incidence data from developing countries are lacking, and this limits our understanding of the global incidence of PSC.
Article
To estimate the incidence and mortality of treated primary Sjögren's syndrome (pSS) by sex and age group in Taiwan. We used claims data of the Bureau of National Health Insurance (NHI) of Taiwan from 2005 to 2007 for analysis. According to the NHI, pSS is classified as one of the financially catastrophic illnesses and patients with pSS could be exempted from copayment of all medical costs. To obtain a catastrophic illness certificate (CIC) for pSS, patients are required to meet the criteria of the American-European Consensus Group for pSS, and are reviewed by a committee. Patients approved for receipt of a CIC for pSS for the first time were defined as incident cases of treated pSS. A total of 3352 incident cases occurred between 2005 and 2007. The estimated mean annual incidence was 6.0 per 100,000 inhabitants (95% CI 5.8-6.2) for both sexes, 11.0 (95% CI 10.6-11.4) for women and 1.1 (95% CI 1.0-1.2) for men, with a female/male ratio of 9.9 (95% CI 8.8-11.1). Incidence increased with age, peaking at age 55-64 years in women and 65-74 years in men. The mortality rate was 33.4 per 1000 case person-years for men and 11.4 for women, with a male/female rate ratio of 2.9 (95% CI 1.7-5.3). The incidence of treated pSS in women is 10 times that in men. Nevertheless, pSS mortality in men is 3 times that in women.
Article
Primary Sjögren's syndrome (PSS) is a chronic autoimmune inflammatory disease characterized by exocrine gland inflammation producing clinical symptoms such as dryness of the mouth and eyes. The reported prevalence of PSS is variable, probably because of different classification criteria used and selection bias. The aim of this study was to determine the prevalence of PSS in a well-defined Norwegian Caucasian population using the revised American-European Consensus Group (AECG) criteria. Three hospitals and three private rheumatology practices provide all of the rheumatology services to the local population in Hordaland and Rogaland counties, which included 852 342 Caucasian inhabitants as of 1 January 2009. Patients on file fulfilling the new revised AECG criteria for PSS were included, and patients with incomplete data were invited to a screening visit. A total of 424 PSS patients were identified. Their mean age was 61.6 ± 13.2 years; 28 (7%) were men and 396 (93%) were women. The point estimate for the proportion of PSS was 0.050% [95% confidence interval (CI) 0.048-0.052]. The prevalence of PSS in this Norwegian population of Caucasians is lower than previously reported when less stringent criteria for identifying PSS were used, but is in line with more recent studies using the same criteria and methods as in this study.
Article
To determine the prevalence rate of primary Sjögren's syndrome (SS) in a community population of 2066 adults in a Beijing suburban village, and 100 inpatients, who were not necessarily admitted for rheumatic diseases. Questionnaire and serological studies of antinuclear antibodies, rheumatoid factor, and anti-SSA, anti-SSB antibodies were done. Possible positive subjects were given eye and oral examinations for objective evidence of xerostomia and keratoconjunctivitis sicca. According to the Copenhagen criteria, the prevalence rate of primary Sjögren's syndrome in China was 0.77%, and it was 0.33% by modified San Diego criteria. In 100 inpatients, we found 4 cases of primary Sjögren's syndrome by Copenhagen criteria, and one case by modified San Diego criteria. Primary Sjögren's syndrome is not a rare disease in China, but most cases are overlooked or misdiagnosed.
Article
To estimate the incidence of physician-diagnosed primary Sjögren syndrome (SS) among residents of Olmsted County, Minnesota, in the setting of usual medical care and to determine how often objective criteria are available in the medical records of such patients. We reviewed all medical records of residents in Olmsted County with physician-diagnosed SS from 1976 to 1992 to determine whether they had undergone objective tests for keratoconjunctivitis sicca, salivary dysfunction, or serologic abnormality. Confounding illnesses were excluded. To identify misclassified cases, all records from patients with xerostomia or keratoconjunctivitis sicca were also reviewed. The average annual SS incidence rates were calculated by considering the entire population to be at risk. Of 75 patients with onset of SS during the study period, 53 had primary SS. All patients were white, 51 (96.2%) were women, and the mean +/- SD age was 59+/-15.8 years. The age- and sex-adjusted annual incidence was 3.9 per 100,000 population (95% confidence interval, 2.8-4.9) for patients with primary SS. Eleven patients (20.8%) with physician-diagnosed SS had no documentation of objective eye, mouth, or laboratory abnormalities. Objective evaluations performed most frequently were laboratory and ocular tests and least often were investigations of xerostomia. The average annual incidence rate for physician-diagnosed primary SS in Olmsted County is about 4 cases per 100,000 population. These data probably underestimate the true incidence because they are based on usual medical care of patients with SS in a community setting, rather than on a case-detection survey. In the future, a true incidence may be possible with a higher index of suspicion, greater attention to objective tests, and increased awareness of new classification criteria for SS. For epidemiological studies based on existing data, application of current criteria may not be feasible, and consensus on criteria for such studies would be useful.
Article
Classification criteria for Sjögren's syndrome (SS) were developed and validated between 1989 and 1996 by the European Study Group on Classification Criteria for SS, and broadly accepted. These have been re-examined by consensus group members, who have introduced some modifications, more clearly defined the rules for classifying patients with primary or secondary SS, and provided more precise exclusion criteria.
Article
The extent of heterogeneity in a meta-analysis partly determines the difficulty in drawing overall conclusions. This extent may be measured by estimating a between-study variance, but interpretation is then specific to a particular treatment effect metric. A test for the existence of heterogeneity exists, but depends on the number of studies in the meta-analysis. We develop measures of the impact of heterogenei