Primary Sjogren's Syndrome Research Articles

Shared biomarkers of multi-tissue origin for primary Sjogren's syndrome and their importance in immune microenvironment alterations

With the recent advancement in omics and molecular techniques, a wealth of new molecular biomarkers have become available for the diagnosis and classification of primary Sjögren's syndrome (pSS) patients. However, whether these biomarkers are universal is of great interest to us. In this study, we used various methods to obtain shared biomarkers derived from multiple tissue in pSS patients and to explore their relationship with immune microenvironment alterations. First we identified differentially expressed genes (DEGs) between pSS and healthy controls utilizing nine mRNA microarray datasets obtained from the Gene Expression Omnibus (GEO). Then, shared biomarkers were filtered out using robust rank aggregation (RRA), data integration analysis, weighted gene co-expression network analysis (WGCNA), and least absolute selection and shrinkage operator (LASSO) regression; their roles in pSS and association with changes in the immune microenvironment were also analyzed. In addition, these biomarkers were further confirmed with both the testing set and immunohistochemistry (IHC). As a result, ten biomarkers, i.e., EPSTI1, IFI44, IFIT1, IFIT2, IFIT3, MX1, OAS1, PARP9, SAMD9L and TRIM22, were identified. Receiver operating characteristic (ROC) curves showed that the ten genes could discriminate pSS from controls. Gene set enrichment analysis (GSEA) showed that the enrichment of immune-related gene sets was significant in pSS patients with high expression of either biomarker. Furthermore, the association between some immunocytes and these biomarkers was identified. In the two distinct molecular patterns of pSS patients based on the expressions of these biomarkers, the proportions of immunocytes were significantly different. Our study identified shared biomarkers of multi-tissue origin and revealed their relationship with altered immune microenvironment in pSS patients. These markers not only have diagnostic implications but also provide potential immunotherapeutic targets for the clinical treatment of pSS patients.

The characteristics of chest HRCT and pulmonary function tests in lung-onset primary sjogren's syndrome.

Interstitial lung disease (ILD) can manifest before the diagnosis of primary Sjögren's syndrome (pSS), however, the underlying mechanisms remain unclear. The aim of this study is to investigate the characteristics of lung-onset pSS using chest high-resolution computerized tomography (HRCT) and pulmonary function tests (PFTs). The data of 102 patients with pSS-ILD were retrospectively analyzed. The patients were divided into two groups: lung-onset group and the nonlung-onset group. The chest HRCT, PFTs, and clinical and laboratory data were evaluated and compared. Among the 102 patients with pSS-ILD, 59 (57.8%) were lung-onset and 43 (42.2%) were nonlung-onset. Chest HRCT in the lung-onset group showed higher percentage of usual interstitial pneumonia and nonspecific interstitial pneumonia, the difference did not reach statistical significance. The total HRCT score was higher in the lung-onset group, compared with the nonlung-onset group (2 [2, 3], vs. 2 [1, 2], p = .014). Total lung capacity (TLC) (%pred) [(75.4 ± 16.2) versus (82.8 ± 19.4), p = .049] and forced vital capacity (FVC) (%pred) [(82.2 ± 19.9) versus (91.6 ± 28.3), p = .050] were significantly lower in the lung-onset group, compared with the nonlung-onset group.Residual volume (RV)/TLC (%) significantly increased more than 40% in the lung-onset group (p = .015). Restricted ventilation disorder, small airway obstruction and reduced diffusing capacity of the lung for carbon monoxide/alveolar volume (%Pred) were more common in the lung-onset group (p = .038, p = .050, and p = .050, respectively). Correlation analysis showed that HRCT score was positively correlated with the interval between the onset of pulmonary symptoms and the diagnosis of ILD, serum CA125, and serum CEA. TCL (%pred), VC (%pred), FVC (%pred) were negatively correlated with serum CA125. Lung-onset is common in pSS patients with more severe lung function impairments. Serum biomarkers, such CA125, CEA, and ALB, were associated with the severity of lung damage.

Pulmonary Hypertension in Autoimmune Diseases – A Review of New Concepts in Screening, Diagnosis and Therapeutic Management

Pulmonary hypertension (PH) has gained more and more attention in the last years given the increased mortality and morbidity rate and in particular pulmonary arterial hypertension associated with autoimmune diseases (a specific subgroup of PH), entities with an increasing incidence and prevalence globally. Among these, systemic sclerosis is of particular interest, being the most common among connective tissue diseases (CTDs) with PH as a major complication. Other CTDs such as mixed connective tissue disease (MCTD), systemic lupus erythematosus (SLE), primary Sjogren's syndrome, and dermatomyositis may also develop PH as a complication of these severe and complex conditions, which can have a major impact on prognosis and quality of life. PH has also been reported in rheumatoid arthritis and ankylosing spondylitis but further studies are necessary. Several studies have shown that the 3-year survival rate for patients with systemic sclerosis-associated with pulmonary hypertension (SSc-PH) is between 31% and 52%, while the 5-year survival rate is below <50%. Therefore, an early and accurate diagnosis as well as subsequent management of PH in these conditions is mandatory, since survival remains suboptimal despite treatment advances. The aim of this article is to provide an overview of different autoimmune diseases associated with PH and to provide an easy reference source on current best practices.

Association Between Bruton's Tyrosine Kinase Gene Overexpression and Risk of Lymphoma in Primary Sjögren's Syndrome.

We undertook this study to analyze whole blood gene expression and to investigate the role of B cell genes in primary Sjögren's syndrome-related non-Hodgkin lymphoma (primary SS-NHL). Peripheral whole blood samples were collected from 345 well-phenotyped patients with primary SS enrolled in the prospective Assessment of Systemic Signs and Evolution in Sjögren's Syndrome (ASSESS) cohort. Transcriptomic analysis was performed using human Clariom S Arrays (Affymetrix). In our primary analysis, we considered patients with incident lymphoma (i-primary SS-NHL) as the case group and all patients without lymphoma as the comparison group. In our sensitivity analyses, we considered all patients with primary SS-NHL, including those with a history of lymphoma (h-primary SS-NHL), as the case group and primary SS patients without lymphoma, stratified on their risk factors of lymphoma, as the comparison group. Twenty-one patients with primary SS-NHL (including 8 with i-primary SS-NHL and 13 h-primary SS-NHL) were eligible for transcriptomic analysis; we compared these patients to 324 primary SS controls without lymphoma, including 110 with moderate to severe disease activity and 61 with no risk factor of lymphoma. Functional clustering analyses revealed an enrichment of genes related to innate and adaptive immunity, including B cell-related genes. Bruton's tyrosine kinase (BTK) and a proliferation-inducing ligand (APRIL) genes were overexpressed before the occurrence of lymphoma in patients with incident lymphoma compared with patients without lymphoma. In sensitivity analyses, BTK was consistently up-regulated across all comparisons performed. BTK expression was associated with risk of lymphoma on multivariate analyses, which considered 9 validated predictors of lymphoma in primary SS. BTK and APRIL were overexpressed in the peripheral blood of primary SS patients prior to lymphoma. The association between BTK, APRIL, and primary SS-NHL requires confirmation in other prospective cohorts.

Proteomics profiling and lysine malonylation analysis in primary Sjogren’s syndrome

Primary Sjogren's Syndrome (pSS) is a chronic autoimmune disease, with unclear pathogenies. Lysine-malonylation (Kmal) as a novel post-translational modification (PTMs) was found associated with metabolic, immune, and inflammatory processes. For purpose of investigating the proteomic profile and functions of kmal in pSS, liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based analysis and bioinformatics analysis are performed based on twenty-eight pSS patients versus twenty-seven healthy controls (HCs). A total of 331 down-regulated proteins and 289 up-regulated proteins are observed in differentially expressed proteins (DEPs) of pSS. We discover the expression of transforming growth factor beta-1 (TGFB1) and CD40 ligand downregulate which enriches in the inflammatory associated pathway. Expression of signal transducer and activator of transcription 1-alpha/beta (STAT1) show upregulation and enrich in type I interferon signaling pathway and IL-27-mediated signaling pathway. In differentially malonylated proteins (DMPs) of pSS, we identify 3 proteins are down-regulated in 7 sites and 18 proteins are up-regulated in 19 sites. Expression of malonylated integrin-linked kinase (ILK) significantly enrich in the focal adhesion pathway. Together, our data provide evidence that downregulation of TGFB1 and CD40LG play a critical role in the inflammatory process of pSS, while upregulation of STAT1 may be associated with IL-27 immunity and pSS immune dysfunction. Moreover, kmal modification at the kinase domain of ILK may destabilize ILK that thus contributing to pSS pathogenies by regulating the focal adhesion pathway. SignificanceOur research offered the first characterization of Kmal, a newly identified form of lysine acylation in pSS, as well as proteomic data on individuals with pSS. In this study, we found that several key DMPs were associated with focal adhesion pathway, which contributes to the development of pSS. The present results provide an informative dataset for the future exploration of Kmal in pSS.

Depression in Sjögren's syndrome mediates the relationship between pain, fatigue, sleepiness, and overall quality of life.

Sjögren's syndrome (SS) includes many extra-glandular symptoms such as fatigue, pain, sleepiness and depression, which impact on quality of life (QoL). These symptoms also influence each other and could be linked by autonomic nervous system (ANS) dysregulation. Our aim was to model the role of putative predictive variables, including depression in the relationships between ANS function, fatigue, and QoL in SS. Cross-sectional analysis of self-reported data from the multicentre UK primary SS registry. The Composite Autonomic Symptom Scale (COMPASS) was used to assess autonomic function, the Hospital Anxiety and Depression Scale (HADS) to assess anxiety and depression and the EuroQol-5 Dimension (EQ-5D) to assess QoL. Validated scales were used for other clinical variables. Using multiple regression analysis and structural equation modelling (SEM), we investigated how the QoL of people with SS is impacted by the direct and indirect effects of fatigue, sleepiness, depression, symptom burden and ANS function, and their interactions. Data was obtained for 1046 people with SS, 56% COMPASS completers. Symptoms of ANS dysregulation were common. Participants with ANS dysregulation had more severe depression, anxiety, dryness, fatigue, pain, sleepiness and QoL (P < 0.01 for all). Depression, anxiety, dryness, and pain were independent predictors of ANS function in the multiple regression model (P < 0.05 for all). ANS function could not be included in the SEM. The SEM model had good fit to the data (comparative fit index = 0.998) and showed that, in people with SS, depression mediates the effects of pain, fatigue and sleepiness on QoL. Our results show that diagnosing and treating depression in people with SS could have direct positive impact on QoL, and significantly ameliorate the impact of fatigue and pain.

Impairment of oral health and its impact on the quality of life of patients with Sjögren's syndrome

AbstractObjectivesThis study aimed to describe the clinical profile and the oral health status and their impact on the quality of life of patients with Sjögren's syndrome (SS).MethodsThrough a cross‐sectional study, patients with SS were compared with those with dry symptoms with no conclusive diagnosis of SS (non‐SS) and patients without complaints of dryness, matched for sex and age (control group). Data related to classification of SS, focus score, unstimulated whole salivary flow (UWSF), dental plaque index, periodontal screening and recording (PSR), decayed, missing and filled teeth (DMFT), and clinical signs of candidiasis were assessed. Colony‐forming units (CFU) of Candida spp were assessed and saliva biochemical analysis was also performed. The Xerostomia Inventory (XI) and Oral Health Impact Profile 14 (OHIP‐14) questionnaire were applied to assess the severity of xerostomia and quality of life.ResultsThirty‐three patients with primary SS, 22 with secondary SS, nine non‐SS, and 23 from control group were included. Patients with primary SS, secondary SS and non‐SS had lower UWSF and higher rates of plaque, PSR and DMFT than the control group. Candida spp. count was also higher in SS groups. Osmolality, buffering capacity and protein concentration in saliva were similar between groups. The scores of XI and OHIP‐14 were higher in the SS and non‐SS groups and showed positive correlation with PSR and DMFT and negative correlation with UWSF.ConclusionSS is associated with poor oral health, mainly related to dental and periodontal problems, which exert a negative impact on quality of life.

Phenotypic and proteomic analysis of plasma extracellular vesicles highlights them as potential biomarkers of primary Sjögren syndrome.

Sjögren syndrome (SjS) is an autoimmune disease characterized by the destruction of the exocrine gland epithelia, causing a dryness of mucosa called sicca symptoms, and whose main life-threatening complication is lymphoma. There is a need for new biomarkers in this disease, notably diagnostic biomarkers for patients with genuine sicca symptoms that do not meet current criteria, and prognostic biomarkers for patients at risk of lymphoma. Plasma extracellular vesicles (EVs) are promising biomarker candidates in several diseases, but their potential has not yet been explored in SjS. In this proof-of-concept study, we characterized EVs from primary SjS patients (pSS, n=12) at the phenotypic and proteomic levels, compared to EVs from healthy donor (HD, n=8) and systemic lupus erythematosus patients (SLE, n=12). Specific plasma EVs subpopulations, derived from neutrophils, endothelial, and epithelial cells, were found increased in pSS. We also identified a pSS proteomic signature in plasma EVs, including neutrophil-, epithelial-, and endothelial-related proteins, such as integrin alpha M (ITGAM), olfactomedin-4 (OLFM4), Ras-related protein RAB10, and CD36. Overall, our results support the relevance of plasma EVs as biomarkers in SjS.

Salivary ultrasonography and histopathologic evaluation of secondary Sjögren’s syndrome in rheumatoid arthritis patients

Novel modalities, such as salivary ultrasonography (SGUS) and shear wave elastography (SWE), have previously been introduced to evaluate Sjögren’s syndrome (SS). However, in secondary SS (sSS), the diagnostic performance of SGUS and its relationship with clinicopathological characteristics have not yet been clearly defined. In this study, we aimed to investigate sSS in RA patients using SGUS and SWE and sought to determine its pathological correlations. Thirty-one RA patients who presented with sicca symptoms were included to be evaluated on SS, and were compared with 18 primary SS (pSS) patients. All subjects were assessed through SGUS, SWE, and conventional diagnostic approaches for SS, including minor salivary gland biopsy (MSGB). In SGUS evaluation, two separate scoring systems, suggested by Hocevar and OMERACT, were used. Among 31 RA patients with sicca symptoms, 19 (61.2%) were diagnosed as sSS. Similar to pSS, SGUS showed good diagnostic performance (sensitivity 68.4% and 78.9%, and specificity 91.7% and 75.0% for Hocever and OMERACT, respectively) in differentiating sSS from RA patients with simple sicca symptoms. The sSS and pSS patients exhibited significantly higher lymphoid infiltration areas in MSGB than RA patients without SS. Focus score and lymphoid infiltration areas correlated well with sonographic severity. Severity of fibrosis in MSGB showed better positive correlation with SWE than with SGUS. Similar to pSS, SGUS shows good diagnostic performance for sSS in RA patients. SWE reflects histopathologic chronicity of MSGB well in both pSS and sSS.

Mitochondria-related genes and metabolic profiles of innate and adaptive immune cells in primary Sjögren's syndrome.

Primary Sjogren's syndrome (pSS) is a prototypical systemic autoimmune disease characterised by lymphocyte infiltration and immune-complex deposition in multiple organs. The specific distribution of immune cell populations and their relationship with mitochondria remain unknown. Histological analysis was performed to assess the specific distribution of innate and adaptive immune cell populations in labial salivary gland (LSG) samples from 30 patients with pSS and 13 patients with non-pSS. The ultrastructural morphometric features of mitochondria within immune cells were observed under the transmission electron microscope (TEM). RNA sequencing was performed on LSG samples from 40 patients with pSS and 7 non-pSS patients. The Single-sample Gene Set Enrichment Analysis (ssGSEA), ESTIMATE, and CIBERSORT algorithms and Pearson correlation coefficients were used to examine the relationship between mitochondria-related genes and immune infiltration. Weighted Gene Co-expression Network Analysis (WGCNA) was used to identify the mitochondria-specific genes and the related pathways based on the immune cell types. HE staining revealed a massive infiltration of plasma cells with abundant immunoglobulin protein distributed around phenotypically normal-appearing acinar and ductal tissues of patients with pSS. Immunohistochemical analyses revealed that innate immune cells (macrophages, eosinophils and NK cells) were distributed throughout the glandular tissue. Dominant adaptive immune cell infiltration composed of B cells, CD4+T cells and CD8+ T cells or ectopic lymphoid follicle-like structures were observed in the LSGs of patients with pSS. TEM validated the swelling of mitochondria with disorganised cristae in some lymphocytes that had invaded the glandular tissue. Subsequently, bioinformatic analysis revealed that innate and adaptive immune cells were associated with different mitochondrial metabolism pathways. Mitochondrial electron transport and respiratory chain complexes in the glandular microenvironment were positively correlated with innate immune cells, whereas amino acid and nucleic acid metabolism were negatively correlated with adaptive immune cells. In addition, mitochondrial biogenesis and mitochondrial apoptosis in the glandular microenvironment were closely associated with adaptive immune cells. Innate and adaptive immune cells have distinct distribution profiles in the salivary gland tissues of patients with pSS and are associated with different mitochondrial metabolic pathways, which may contribute to disease progression.

Risk factors and prognosis of interstitial lung disease for primary Sjögren syndrome patients: A retrospective case‒control study.

To determine the prevalence, clinical features, risk factors, and prognosis of interstitial lung disease (ILD) in patients with primary Sjogren's syndrome (pSS). Data from 274 pSS patients from August 2013 to August 2022 were reviewed. The clinical features of pSS with ILD were revealed. Logistic regression was used to determine risk factors for ILD in pSS patients. Survival analysis and Cox regression were used to analyse the prognosis and prognostic factors of pSS patients. In pSS patients, the prevalence of ILD was 22.3% (61/274). The pSS patients with ILD were characterized by a late onset and long disease course, with a nonspecific interstitial pneumonia (NSIP) pattern as the predominant high-resolution computed tomography (HRCT) finding. Logistic regression results indicated that an age over 50years old (OR 4.786, 95% CI 1.602-14.299; P = 0.005), purpuric rash (OR 4.695, 95% CI 1.537-14.339; P = 0.007), AMA-M2 antibody positivity (OR 2.582, 95% CI 1.166-5.722; P = 0.019), and diabetes (OR 2.514, 95% CI 1.025-6.167; P = 0.044) were risk factors for ILD in pSS patients. Cox regression results showed that advanced age (HR 1.240, 95% CI 1.088-1.413; P = 0.001) and cancer history (HR 8.411, 95% CI 1.771-39.934; P = 0.007) were risk factors for pSS patient survival. This study showed that pSS patients with ILD tended to have a late onset and long course of pSS. An age over 50years, purpuric rash, AMA-M2 antibody positivity, and diabetes were risk factors for ILD in pSS patients. Advanced age and cancer history were prognostic factors in pSS patients. Key Points • This study showed that pSS patients with ILD tended to have a late-onset and lengthy course of pSS, with the NSIP pattern as the predominant lung image. • The risk factors for ILD in pSS patients determined in this study were an age over 50years, purpuric rash, AMA-M2 antibody positivity, and diabetes. • The prognostic risk factors for pSS patients were advanced age and cancer history.

Potential risk genes for primary Sjogren's syndrome from a meta-analysis by linear regression and random forest classification

Potential risk genes for primary Sjogren's syndrome from a meta-analysis by linear regression and random forest classification

Single-cell clonal tracing of glandular and circulating T cells identifies a population of CD9+ CD8+ T cells in primary Sjogren's syndrome.

Primary Sjogren's syndrome (pSS) is a complex chronic autoimmune disease in which local tissue damage in exocrine glands is combined with broader systemic involvement across the body in tissues including the skin. These combined manifestations negatively impact patient health and quality of life. While studies have previously reported differences in immune cell composition in the peripheral blood of pSS patients relative to healthy control subjects, a detailed immune cell landscape of the damaged exocrine glands of these patients remains lacking. Through single-cell transcriptomics and repertoire sequencing of immune cells in paired peripheral blood samples and salivary gland biopsies, we present here a preliminary picture of adaptive immune response in pSS. We characterize a number of points of divergence between circulating and glandular immune responses that have been hitherto underappreciated, and identify a novel population of CD8+ CD9+ cells with tissue-residential properties that are highly enriched in the salivary glands of pSS patients. Through comparative analyses with other sequencing data, we also observe a potential connection between these cells and the tissue-resident memory cells found in cutaneous vasculitis lesions. Together, these results indicate a potential role for CD8+ CD9+ cells in mediating glandular and systemic effects associated with pSS and other autoimmune disorders.

Recent Advances on Primary Sjogren's Syndrome and Depression Relationship

Primary Sjogren's syndrome is a chronic autoimmune disorder that affects the exocrine glands, leading to dryness of the eyes, mouth, and other mucous membranes. Depression is a common comorbidity in patients with primary Sjogren's syndrome, and it can have a significant impact on patients' quality of life. This review paper provides an overview of the clinical presentation and prevalence of primary Sjogren's syndrome and depression, as well as a summary of the research progress on the relationship between these two conditions. The proposed mechanisms underlying the relationship between primary Sjogren's syndrome and depression, including neuroendocrine and immune system dysregulation, proinflammatory cytokines, stress and coping mechanisms, psychological factors, and other factors, are also discussed. Additionally, various treatment options for depression in patients with primary Sjogren's syndrome are reviewed, including pharmacological and non-pharmacological interventions. While there are some limitations to the current research, understanding the relationship between primary Sjogren's syndrome and depression is important for improving the care and quality of life of patients with this condition.

Neurological injury in primary Sjogren's syndrome.

Forty-eight patients with primary Sjogren's syndrome, attending outpatient clinics at Damascus Hospital between January 2020 and January 2022 in this cross-sectional study at the outpatient clinics, were interviewed and examined, and the necessary laboratory and radiological examinations were demanded. Information was collected on disease duration, onset time, and patterns of neurological symptoms. Forty-eight patients, including 42 females, aged 56.1±10.3 years were enroled.Central nervous system involvement was found in 34 patients. 85% of patients had generalized nerve manifestations, while local nerve manifestations were found in 77,5% of patients. The common neurological manifestation was headaches, then cognitive disorders, and the most common pattern of headache was migraine. Beck Depression Index showed a significant increase in the apathy evaluation scale.The study of cognitive changes showed a significant increase in the Mini-Mental State Examination (MMSE) index.Carotid Doppler showed the presence of injury in 42.4% of patients. The magnetic resonance imaging showed positive findings in 21 patients and positive evoked potentials in 52% of patients. Studies showing the prevalence of Sjogren's neurological injury patterns are insufficient, but this was changed when the criteria for diagnosing Sjogren's syndrome was modified, and the definition of neurological traits in the context of the syndrome was expanded.The presence of a high rate of headaches, cognitive changes, and fatigue confirms that generalized nervous system injuries are more common than local injuries. Migraine was the most common pattern of headache found in patients with the syndrome compared with other patterns such as tension headaches and headaches due to medications, especially analgesics.This was associated with the presence of anti-SSA antibodies and Raynaud's phenomenon, which suggest that the headache mechanism may be due to vascular endothelial dysfunction or an immune-mediated inflammation injury of the neurovascular system.The changes that appeared on the MRI images suggested premotor cortex involvement rather than mesolimbic cortical impairment, and its presence was also associated with SSA antibody positivity, and it is caused by inflammation. Primary Sjogren's syndrome should be considered as having any unspecified or specific neurological disorder.

Mortality risk factors in primary Sjögren syndrome: areal-world, retrospective, cohort study.

What baseline predictors would be involved in mortality in people with primary Sjögren syndrome (SjS) remains uncertain. This study aimed to investigate the baseline characteristics collected at the time of diagnosis of SjS associated with mortality and to identify mortality risk factors for all-cause death and deaths related to systemic SjS activity measured by the ESSDAI score. In this international, real-world, retrospective, cohort study, we retrospectively collected data from 27 countries on mortality and causes of death from the Big Data Sjögren Registry. Inclusion criteria consisted of fulfilling 2002/2016 SjS classification criteria, and exclusion criteria included chronic HCV/HIV infections and associated systemic autoimmune diseases. A statistical approach based on a directed acyclic graph was used, with all-cause and Sjögren-related mortality as primary endpoints. The key determinants that defined the disease phenotype at diagnosis (glandular, systemic, and immunological) were analysed as independent variables. Between January 1st, 2014 and December 31, 2023, data from 11,372 patients with primary SjS (93.5% women, 78.4% classified as White, mean age at diagnosis of 51.1 years) included in the Registry were analysed. 876 (7.7%) deaths were recorded after a mean follow-up of 8.6 years (SD 7.12). Univariate analysis of prognostic factors for all-cause death identified eight Sjögren-related variables (ocular and oral tests, salivary biopsy, ESSDAI, ANA, anti-Ro, anti-La, and cryoglobulins). The multivariate CPH model adjusted for these variables and the epidemiological features showed that DAS-ESSDAI (high vs no high: HR=1.68; 95% CI, 1.27-2.22) and cryoglobulins (positive vs negative: HR=1.72; 95% CI, 1.22-2.42) were independent predictors of all-cause death. Of the 640 deaths with available information detailing the specific cause of death, 14% were due to systemic SjS. Univariate analysis of prognostic factors for Sjögren-cause death identified five Sjögren-related variables (oral tests, clinESSDAI, DAS-ESSDAI, ANA, and cryoglobulins). The multivariate competing risks CPH model adjusted for these variables and the epidemiological features showed that oral tests (abnormal vs normal results: HR=1.38; 95% CI, 1.01-1.87), DAS-ESSDAI (high vs no high: HR=1.55; 95% CI, 1.22-1.96) and cryoglobulins (positive vs negative: HR=1.52; 95% CI, 1.16-2) were independent predictors of SjS-related death. The key mortality risk factors at the time of SjS diagnosis were positive cryoglobulins and a high systemic activity scored using the ESSDAI, conferring a 2-times increased risk of all-cause and SjS-related death. ESSDAI measurement and cryoglobulin testing should be considered mandatory when an individual is diagnosed with SjS. Novartis.

Prevalence and comorbidities of Sjogren's syndrome patients in the Community of Madrid: A population-based cross-sectional study.

To estimate the prevalence, sociodemographic characteristics and comorbidities of Sjogren's syndrome (SS) patients in the Community of Madrid. A population-based cross-sectional cohort of SS patients was derived from the information system for rare diseases in the Community of Madrid (SIERMA) and confirmed by a physician. The prevalence per 10,000 inhabitants among people aged ≥18years in June 2015 was calculated. Sociodemographic data and accompanying disorders were recorded. Univariate and bivariate analyses were performed. A total of 4,778 SS patients were confirmed in SIERMA; 92.8% were female, with a mean age of 64.3 (standard deviation=15.4) years. A total of 3,116 (65.2%) patients were classified as primary SS (pSS), and 1,662 (34.8%) as secondary SS (sSS). The prevalence of SS among people aged ≥18 years was 8.4/10,000 (95%Confidence interval [CI]=8.2-8.7). The prevalence of pSS was 5.5/10,000 (95%CI=5.3-5.7), and that of sSS was 2.8/10,000 (95%CI=2.7-2.9), with rheumatoid arthritis (20.3%) and systemic lupus erythematosus (8.5%) being the most prevalent associated autoimmune diseases. The most common comorbidities were hypertension (40.8%), lipid disorders (32.7%), osteoarthritis (27.7%) and depression (21.1%). The most prescribed medications were nonsteroidal anti-inflammatory drugs (31.9%), topical ophthalmic therapies (31.2%) and corticosteroids (28.0%). The prevalence of SS in the Community of Madrid was similar to the overall prevalence worldwide observed in previous studies. SS was more frequent in women in their sixth decade. Two out of every three SS cases were pSS, while one-third were associated predominantly with rheumatoid arthritis and systemic lupus erythematosus.

Cardiac Manifestations of Sjogren's Syndrome: A Review of Literature.

Sjogren's syndrome (SS) is a chronic inflammatory disorder of the exocrine glands. It is characterized by a lymphocytic infiltrate in the lacrimal and salivary glands causing keratoconjunctivitis sicca and xerostomia. Extra-glandular involvement may be present in about one-third of patients with primary Sjogren's syndrome (pSS).The most commonly affected organs are the thyroid, lungs, gastrointestinal tract, kidneys, skin, and nervous system.Cardiac manifestations of Sjogren's syndrome are rare and not well-described in the current literature. Most of the evidence is present in the form of case reports and small case series.However, recent studies have shown that patients with Sjogren's syndrome (SS) seem to have a greater overall risk of cardiovascular (CV) events. Although not conventionally considered a feature of the disease, cardiac manifestations can lead to increased morbidity and mortality in this patient population.In this review article, we study the association between cardiac diseases and primary Sjogren's syndrome.

Utilisation of primary healthcare services by Sjögren's syndrome patients in the Community of Madrid and associated factors: a population-based cross-sectional study.

To describe the utilisation of primary health care (PHC) services and factors associated with its use by patients diagnosed with Sjögren's syndrome (SS). Population-based cross-sectional cohort of SS patients in Madrid, Spain (SIERMA). Sociodemographic, diagnostic, clinical and PHC service utilisation variables were studied by bivariate analyses and regression models. A total of 4,778 SS patients were included, 65.2% classified as primary SS (pSS), while 34.8% associated with another autoimmune disease (associated SS). Mean age was 64.3 years, and 92.8% of the patients were women. A total of 87.5% used PHC services, with a mean of 19.8 consultations/year. The general practitioner was the most visited health professional, with a mean of 10.9 consultations/year, followed by the nurse, with a mean of 5.7. Characteristics associated with a greater use of PHC services in SS patients were associated SS, higher adjusted morbidity groups (AMG) risk level and older age. Additional factors included symptoms such as dry mouth, fatigue, dry vagina and joint and muscle pain; comorbidities such as atrial fibrillation, diabetes, hypertension, solid malignant neoplasms, coronary heart disease and chronic obstructive pulmonary disease; and treatments such as sterile saline solution, corticosteroids, opioids and biologic disease-modifying anti-rheumatic drugs. Most SS patients used PHC services during the study period, and the mean number of consultations was remarkably high. Utilisation was mainly associated with AMG risk level, ageing, glandular and extra-glandular symptoms, substantial comorbidities and various treatments. An optimised design of PHC policies will facilitate early diagnosis, improved management and better quality of life for SS patients.

Virgin Coconut Oil in Paste Form as Treatment for Dyspareunia and Vaginal Dryness in Patients With and Without Rheumatic Autoimmune Diseases: An Efficacy and Safety Assessment Pilot Study.

Introduction The use of virgin coconut oil (VCO) as an over-the-counter (OTC) treatment for vaginal dryness and dyspareunia (VDD) in the general population has increased worldwide despite the absence of evidence-based studies supporting its efficacy. The principal objective of our pilot study was to scientifically validate the significant benefits and safety of using intra- and peri-vaginal application of VCO in paste form (VCOPF)for the treatment of VDDin patients with and without rheumatic autoimmune diseases (RAD). Additionally, multiple psychosocial, sexuality, and disease activity variables were also assessed. Methods A survey study of patients with chronic VDD, with and without RAD, treated with a single proprietary brand of VCOPF via the 'CocoRelief' protocolcontinuously for at least six months in an outpatient rheumatology practice setting. We evaluated the comparison of group characteristics, treatment outcomes, and satisfaction questions by Fisher's exact test or chi-square test for independence for categorical variablesand two-sample t-tests for continuous variables. Results Of the 53 respondents, 31 (58%) had an RAD and 22 (42%) did not. Rheumatoid arthritis and primary Sjogren's syndrome comprised 75% of the RAD group. The non-RAD cohort had both a higher baseline mean of intercourse pain (on a scale of 0-5) before VCOPF use (4.4 (SD 1.1) vs 3.9 (SD 1.0)(p = 0.094)) and a higher mean intercourse pain after VCOPF (2.0 (SD 1.3) vs 1.3 (SD 1.1) (p = 0.039)). VDD decreased by 55% in the non-RAD and 66% in the RAD population. Although not statistically significant (p = 0.195), VCOPF was at worst comparable to estrogen-containing therapies (ECT). No adverse events (AE) were documented. Conclusion A high percentage of women with VDD, with and without RAD, needlessly continue to experience quality-of-life-altering physical and psychosocial morbidity due to the underutilization and lack of awareness of VCO-containing therapy. The small sample size, non-blinded, non-randomized, pilot platform, and the use of a non-validated assessment toolrepresentthe principal limiting factors. This study revealed that VCOPF, when used in paste form via the CocoReliefprotocol, provided statistically significant long-term VDD-related efficacy not inferior to ECT without AE in patients with and without RAD. VCOPF is, therefore, likely to be a useful, cost-effective alternative in a substantial percentage of patients with and without RAD, particularly in women hesitant to utilize ECT due to cost and/or fear of adverse effects.