Causal association between autoimmune liver disease and Sjögren's syndrome: A Mendelian randomization study.

BACKGROUND: Observational studies have found an association between autoimmune liver disease (AILD) and Sjögren's syndrome (SS). However, the causal relationship between the two remains unknown. Clinical guidelines indicate that the coexistence of AILD with other autoimmune diseases may impact prognosis and quality of life; hence, early recognition and management of extrahepatic autoimmune diseases is particularly crucial. Against this backdrop, this study aimed to utilize Mendelian randomization (MR) methods to investigate the potential causal relationship between AILD and SS. METHODS: We extracted summary statistics on AILD and SS from publicly available genome-wide association studies (GWAS) databases to identify appropriate instrumental variables (IVs). The inverse-variance weighted (IVW) method was utilized as the primary approach, with the weighted median (WM) method and MR-Egger method employed as supplementary methods to evaluate the potential causal relationship between the two conditions. Sensitivity analyses, including Cochran's Q test, MR-polynomial residuals and outliers (MR-PRESSO), MR-Egger intercept test, and the leave-one-out test, were performed to assess the stability of the results. RESULTS: The MR study results indicate a significant causal relationship between PBC and PSC with the risk of SS in the European population (IVW: odds ratio [OR] = 1.155, 95% confidence interval [CI]: 1.092-1.222, p < .001; IVW: OR = 1.162, 95% CI: 1.051-1.284, p = .003). A series of sensitivity analyses have confirmed the reliability of the results. CONCLUSIONS: Our study indicates that the presence of both PBC and PSC increases the susceptibility to SS. However, no reliable causal relationship was found between SS and the risk of PBC or PSC. These findings contribute to elucidating the potential pathogenic mechanisms of the disease and are of significant importance for the management of patients with PBC and PSC.

Celebrities influence on rheumatic diseases interest: a Google Trends analysis.

Celebrity-related events have influenced public interest in diseases like cancer, but their impact on rheumatic diseases is poorly investigated. We aimed to investigate whether celebrity-related events may account for atypical interest among Google users in rheumatic diseases. We used Google Trends to generate the relative search volume of 24 adult rheumatic diseases. We visually analyzed global time trends and recorded all dates with unusual spikes of interest. Finally, we used the Google search engine to detect media news related to rheumatic disease that may explain the spikes. The majority of atypical spikes in global interest were attributable to celebrity-related events, such as diagnosis, flare, or death due to rheumatic disease. Examples include Venus Williams with Sjögren's syndrome, Lady Gaga with fibromyalgia, Selena Gomez with lupus, Phil Mickelson with psoriatic arthritis, and Ashton Kutcher with vasculitis. Celebrity-related events may have a substantial influence on global interest in rheumatic diseases among Google users. These findings suggest that leveraging the attention generated by celebrities can be a powerful tool in raising awareness and promoting research efforts for rheumatic diseases. Future studies could leverage Google Trends to gauge the influence of celebrity events or health campaigns on rheumatic disease awareness.

Impact of gender and age at onset on Sjögren's syndrome presentation and outcome: state of the art.

Sjögren's syndrome (SS) is a complex and heterogeneous disease that typically affects middle-aged women. However, while it is rare, the disease may occur in male patients and in females during their childhood/adolescence or in the elderly. Contrasting data have been reported on these three subgroups clinical features and long-term outcomes. Notably, recent studies have pinpointed the severity of the disease in male patients and in both the early and the late-onset subgroups.The aim of this review is, therefore, to summarise the available evidence from the recent literature on these phenotypes. The focus will be on the clinical and laboratory features, and on the lymphoma risk observed in the three subgroups distinct phenotypes: of male patients as well as young-onset SS and elderly-onset SS. Ultimately, an accurate phenotypic stratification may represent the first step towards individualised medical approaches.

Clinical characteristics and risk factors of Helicobacter pylori infection-associated Sjogren's syndrome.

OBJECTIVE: Although infectious pathogens are predominant factors for inducing and maintaining immune system disorders, there exist few reports establishing the significant correlation between Helicobacter pylori (H. pylori) infection and Sjogren's syndrome. This study aims to demonstrate the correlation between Sjogren's syndrome and H. pylori infection in patients, highlighting various clinical characteristics and risk factors. METHODS: A single-center retrospective observational study was conducted in patients (n = 224) admitted from January 1, 2012, to February 10, 2021, in the First Affiliated Hospital of Wenzhou Medical University (Wenzhou, China). All the recruited subjects with Sjogren's syndrome and H. pylori infection were only included by validating the available medical records online. RESULTS: In this study, a total of 224 patients from January 1, 2012, to February 10, 2021, were diagnosed with Sjogren's syndrome. Among them, 94 patients (41.96%) with Sjogren's syndrome were infected with H. pylori. Accordingly, the clinical manifestations, serological and immunological characteristics, as well as gastroscopic biopsy outcomes of the recruited patients with primary Sjogren's syndrome (pSS) were reported. The multivariable analysis of the dry syndrome patients infected with H. pylori displayed hypergammaglobulinemia (odds ratio [OR], 0.354; 95% confidence interval [CI], 0.189-0.663), total cholesterol (OR, 1.158; 95% CI, 0.856-1.550), hypertension (OR, 0.227; 95% CI, 0.114-0.455), Female sex (OR, 5.778; 95% CI, 1.458-22.9), anti-SSA/Ro60 positive (OR, 2.384; 95% CI, 233-4.645), γ-GT (OR, 0.99; 95% CI, 0.99-1.00) and alkaline phosphatase (ALP, OR, 1.00; 95% CI, 0.99-1.00) levels. CONCLUSION: Together, our findings demonstrated that hypergammaglobulinemia could be the independent risk factors of H. pylori infection in patients with Sjogren's syndrome, requiring the physician's advice in the future.

Comparison between primary Sjögren's disease patients with high or low level of dryness.

OBJECTIVES: To describe primary Sjögren's disease (SjD) patients presenting no or low level of dryness and to compare them with SjD patients with oral or ocular dryness features. METHODS: All patients diagnosed with SjD according to AECG or ACR/EULAR criteria in our tertiary reference centre were included. Patients with high or low subjective symptoms or objective signs of dryness were compared. RESULTS: Overall, 509 patients were included for the comparison of patients with high (n=456) or low (n=53) level of subjective dryness and 472 for the comparison of patients with (n=359) or without (n=113) high objective dryness. Compared with patients with subjective dryness, patients without high subjective dryness were significantly younger (median 49 (39-62) years vs 58 (47-67) years, p<0.01), diagnosed earlier (median time from first symptoms to diagnosis 2 (0.5-4.5) years vs 4 (1-9.25), p=0.0056), more frequently anti-SSA positive ((83% vs 64%, p=0.008) and had less focal sialadenitis in minor salivary gland biopsy (69% vs 83%, p=0.02).The patients without high level of objective dryness (n=113) were also younger (51 (41-60) vs 58 (47-67) years, p<0.001) and were more frequently anti-SSA positive (79% vs 63%, p=0.002).In both groups, no difference was observed regarding disease activity. CONCLUSIONS: Among the patients with SjD, those without high subjective or objective dryness features had a younger profile, a faster diagnosis which may result from a more acute onset, were more frequently anti-SSA positive than patients with high dryness features.

Increased prevalences of head and neck cancers in patients with Sjögren's syndrome.

OBJECTIVE: This study aimed to investigate prevalences of head and neck cancers in patients with and those without Sjögren's syndrome using a population-based dataset. METHODS: We retrieved sampled patients from Taiwan's Longitudinal Health Insurance Database. This study included 38 930 patients with Sjögren's syndrome and 155 720 propensity-score matched comparison patients without Sjögren's syndrome. RESULTS: Chi-squared tests revealed that there was a statistically significant difference in the prevalences of head and neck cancers between patients with Sjögren's syndrome and comparison patients (1.77% vs. 1.22%, p < 0.001). The odds ratio for head and neck cancers for patients with Sjögren's syndrome relative to the comparison group was 1.452 (95% CI = 1.325-1.592). CONCLUSIONS: Our study demonstrated that patients with Sjögren's syndrome face increased odds of head and neck cancers, encompassing several sites including the oral cavity, oropharynx, nasopharynx, and thyroid.

Causal associations of Sjögren's syndrome with cancers: a two-sample Mendelian randomization study.

BACKGROUND: Several observational studies have explored the associations between Sjögren's syndrome (SS) and certain cancers. Nevertheless, the causal relationships remain unclear. Mendelian randomization (MR) method was used to investigate the causality between SS and different types of cancers. METHODS: We conducted the two-sample Mendelian randomization with the public genome-wide association studies (GWASs) summary statistics in European population to evaluate the causality between SS and nine types of cancers. The sample size varies from 1080 to 372,373. The inverse variance weighted (IVW) method was used to estimate the causal effects. A Bonferroni-corrected threshold of P < 0.0031 was considered significant, and P value between 0.0031 and 0.05 was considered to be suggestive of an association. Sensitivity analysis was performed to validate the causality. Moreover, additional analysis was used to assess the associations between SS and well-accepted risk factors of cancers. RESULTS: After correcting the heterogeneity and horizontal pleiotropy, the results indicated that patients with SS were significantly associated with an increased risk of lymphomas (odds ratio [OR] = 1.0010, 95% confidence interval [CI]: 1.0005-1.0015, P = 0.0002) and reduced risks of prostate cancer (OR = 0.9972, 95% CI: 0.9960-0.9985, P = 2.45 × 10-5) and endometrial cancer (OR = 0.9414, 95% CI: 0.9158-0.9676, P = 1.65 × 10-5). Suggestive associations were found in liver and bile duct cancer (OR = 0.9999, 95% CI: 0.9997-1.0000, P = 0.0291) and cancer of urinary tract (OR = 0.9996, 95% CI: 0.9992-1.0000, P = 0.0281). No causal effect of SS on other cancer types was detected. Additional MR analysis indicated that causal effects between SS and cancers were not mediated by the well-accepted risk factors of cancers. No evidence of the causal relationship was observed for cancers on SS. CONCLUSIONS: SS had significant causal relationships with lymphomas, prostate cancer, and endometrial cancer, and suggestive evidence of association was found in liver and bile duct cancer and cancer of urinary tract, indicating that SS may play a vital role in the incidence of these malignancies.

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

OBJECTIVES: To describe the utilisation of primary health care (PHC) services and factors associated with its use by patients diagnosed with Sjögren's syndrome (SS). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

French national diagnostic and care protocol for Sjögren's disease.

Sjögren's disease (SD), also known as Sjögren's syndrome (SS) or Gougerot-Sjögren's syndrome in France, is a rare systemic autoimmune disease in its primary form and is characterised by tropism for the exocrine glandular epithelia, particularly the salivary and lacrimal glands. The lymphocytic infiltration of these epithelia will clinically translate into a dry syndrome which, associated with fatigue and pain, constitutes the symptom triad of the disease. In about one third of patients, SD is associated with systemic complications that can affect the joints, skin, lungs, kidneys, central or peripheral nervous system, and lymphoid organs with an increased risk of B-cell lymphoma. SD affects women more frequently than men (9/1). The peak frequency is around the age of 50. However, the disease can occur at any age, with paediatric forms occurring even though they remain rare. SD can occur alone or in association with other systemic autoimmune diseases. In its isolated or primary form, the prevalence of SD is estimated to be between 1 per 1000 and 1 per 10,000 inhabitants. The most recent classification criteria were developed in 2016 by EULAR and ACR. The course and prognosis of the disease are highly variable and depend on the presence of systemic involvement and the severity of the dryness of the eyes and mouth. The current approach is therefore to identify at an early stage those patients most at risk of systemic complications or lymphoma, who require close follow-up. On the other hand, regular monitoring of the ophthalmological damage and of the dental status should be ensured to reduce the consequences.

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

OBJECTIVE: To determine the prevalence, clinical features, risk factors, and prognosis of interstitial lung disease (ILD) in patients with primary Sjogren's syndrome (pSS). METHODS: 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. RESULTS: 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 50 years 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. CONCLUSION: This study showed that pSS patients with ILD tended to have a late onset and long course of pSS. An age over 50 years, 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 50 years, purpuric rash, AMA-M2 antibody positivity, and diabetes. • The prognostic risk factors for pSS patients were advanced age and cancer history.

Assessment of depression, stress, anxiety and oral health-related quality of life in individuals with sjögren's syndrome: case control pilot study / Evaluación de la depresión, el estrés, la ansiedad y la calidad de vida relacionada con la salud bucal en personas con síndrome de Sjögren: estudio piloto de casos y controles

Objective: Sjögren's syndrome (SS) is a chronic auto-immune inflammatory systemic disease, in which the infiltration of mo-nonuclear cells in the exocrine glands leads to physiological and morphological changes. This pilot case-control study aims to describe the profile, evaluate the oral condition, quality of life (QoL) and psychological condition, through complete clinical examination, OHIP-14 and DASS-21 questionnaires. Materials and Methods: The study was conducted with seven individuals with a final diagnosis of SS (case group [CG]), and seven individuals with symptoms of dry mouth (control group [GCO]), consulting at the institution from January to November 2021. participants were selected by free demand and those previously seen at the institution with a diagnosis of SS between 19 and 70 years of age. The questionnaire OHIP-14 was applied to assess the patient's quality of life, where seven dimensions are assessed, subdivided into 14 questions through the Lickert scale (0 to 4) assigned by the individual and which quantifies the impact of oral health on QoL. The questionnaire DASS-21 assessed the psychological condition of the patient, which presents seven questions for each emotional state (depression, anxiety, and stress), totaling 21 questions. The general clinical condition, evolution of SS, oral clinical condition, and the profile of this population were related to QoL factors and psychological conditions, using these assessment instruments. Results: There was no statistically significant difference between the groups regarding stimulated salivary flow. The only symptom with a statistically significant difference in the CG was difficulty in phonation (p< 0.001). The dimensions related to functional limitation and physical pain showed the most expressive results (p=0.004) (p=0.025), showing a strong negative impact on the QoL of the CG individuals, and the dimension related to disability was the least affected (p=0.684). The analysis of depression, anxiety, and stress did not show statistically significant results between the groups; however, in the CG, 5 (71.42%) individuals showed a severe degree of depression, anxiety, and stress. Conclusions: Individuals in the case group showed some changes, with a strong negative impact on QoL compared to the control group.

Objetivo: El síndrome de Sjögren (SS) es una enfermedad inflamatoria sistémica crónica autoinmune, en la que la infiltración de células mononucleares en las glándulas exocrinas provoca cambios fisiológicos y morfológicos. Este estudio piloto de casos y controles tiene como objetivo describir el perfil, evaluar la condición bucal, calidad de vida (CdV) y condición psicológica, mediante examen clínico completo, cuestionarios OHIP-14 y DASS-21. Materiales y Métodos: El estudio se realizó con 7 individuos con diagnóstico final de SS, grupo de casos (CG) y 7 individuos con síntomas de sequedad bucal, grupo control (GCO) atendidos en la institución de enero a noviembre de 2021. Los participantes fueron seleccionados por libre demanda y entre los atendidos previamente en la institución con diagnóstico de SS entre 19 y 70 años de edad. Para evaluar la calidad de vida del paciente se aplicó el cuestionario OHIP-14, donde se evalúan siete dimensiones, sub-divididas en 14 preguntas a través de la escala de Likert (0 a 4) asignada por el individuo y que cuantifica el impacto de la salud bucal en la calidad de vida. El cuestionario DASS-21 evaluó la condición psicológica del paciente, el cual presenta siete preguntas para cada estado emocional (depresión, ansiedad y estrés), totalizando 21 preguntas. El estado clínico general, la evolución del SS, el estado clínico bucal y el perfil de esta población se relacionaron con factores de calidad de vida y condiciones psicológicas, mediante estos instrumentos de evaluación. Resultados: En cuanto al flujo salival estimulado, no hubo diferencias estadísticamente significativas entre los grupos. El único síntoma que mostró diferencia estadísticamente significativa en el CG fue la dificultad en la fonación (p< 0,001). Las dimensiones relacionadas con limitación funcional y dolor físico mostraron los resultados más expresivos (p=0,004) (p=0,025), mostrando un fuerte impacto negativo en la CdV de los individuos del GC, y la dimensión relacionada con discapacidad fue la menos afectada (p=0,684). El análisis de depresión, ansiedad y estrés no mostró resultados estadísticamente significativos entre los grupos; sin embargo, en el GC, 5 (71,42%) individuos presentaron un grado severo de depresión, ansiedad y estrés. Conclusión: Se puede concluir que los individuos del grupo de casos mostraron algunos cambios, con un fuerte impacto negativo en la calidad de vida en comparación con el grupo de control.

Prevalence of Sjögren's syndrome according to 2016 ACR-EULAR classification criteria in patients with systemic lupus erythematosus.

BACKGROUND: Diagnosis of SS is a complex task, as no symptom or test is unique to this syndrome. The American-European Consensus Group (AECG 2002) and the American-European classification criteria of 2016 (ACR/EULAR 2016) emerged through a search for consensus. This study aims to assess the prevalence of Sjögren's Syndrome (SS) in patients with Systemic Lupus Erythematosus (SLE), according to AECG 2002 and ACR-EULAR 2016 classifications, as well as clinical and histopathological features in this overlap. To date, there is no study that has evaluated SS in SLE, using the two current criteria. METHODS: This cross-sectional study evaluated 237 SLE patients at the outpatient rheumatology clinic between 2016 and 2018. Patients were submitted to a dryness questionnaire, whole unstimulated salivary flow (WUSF), "Ocular Staining Score" (OSS), Schirmer's test I (ST-I), and labial salivary gland biopsy (LSGB). RESULTS: After verifying inclusion and exclusion criteria, a total of 117 patients were evaluated, with predominance of females (94%) and mixed ethnicity (49.6%). The prevalence of SS was 23% according to AECG 2002 and 35% to ACR-EULAR 2016. Kappa agreement between AECG 2002 and ACR-EULAR 2016 were 0.7 (p < 0.0001). After logistic regression, predictors for SS were: anti/Ro (OR = 17.86, p < 0.05), focal lymphocytic sialadenitis (OR = 3.69, p < 0.05), OSS ≥ 5 (OR = 7.50, p < 0.05), ST I positive (OR = 2.67, p < 0.05), and WUSF ≤ 0.1 mL/min (OR = 4.13, p < 0.05). CONCLUSION: The prevalence of SS in SLE was 23% (AECG 2002) and 35% (ACR-EULAR 2016). The presence of glandular dysfunction, focal lymphocytic sialadenitis, and anti/Ro were predictors of SS in SLE. The greatest advantage of the new ACR-EULAR 2016 criteria is to enable an early diagnosis and identify the overlapping of these two diseases. ACR-EULAR 2016 criteria is not yet validated for secondary SS and this study is a pioneer in investigating prevalence based on the new criteria.

Childhood-onset primary Sjögren's syndrome in a tertiary center in China: clinical features and outcome.

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

Risk factors for primary Sjögren's Syndrome: a systematic review and meta-analysis.

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.

A lower prevalence of malignant lymphoma in Sjögren's syndrome patients: A cross-sectional study.

OBJECTIVE: This study aims to determine the prevalence and risk factors associated with lymphoma in primary Sjögren's syndrome (pSS). METHODS: 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). RESULTS: Among 1,211,343 patients, we found 6799 patients (0.56%) with lymphomas and 2562 patients (0.21%) with pSS. Out of the 2562 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. CONCLUSION: We report 2.6% of lymphoma prevalence in pSS, lower than previously reported in the literature.

Relationship of chronic rhinosinusitis with Sjogren's syndrome, systemic lupus erythematosus, and ankylosing spondylitis.

BACKGROUND: Several studies have demonstrated the association between chronic rhinosinusitis (CRS) and autoimmune diseases. However, there are few long-term longitudinal studies on this relationship. Therefore, we investigated the association between CRS and the risk of a subgroup of autoimmune disease using a representative nationwide cohort sample. METHODOLOGY: We investigated the association between CRS and autoimmune diseases, including Sjogren's syndrome, systemic lupus erythematosus, and ankylosing spondylitis. A total of 15,130 CRS patients and 30,260 patients without CRS were enrolled after 1:2 propensity score matching. A Cox proportional hazards model was used to analyse the hazard ratio (HR) of CRS for autoimmune disease. RESULTS: The incidence of Sjogren's syndrome, systemic lupus erythematosus, and ankylosing spondylitis was 0.55, 0.10, and 0.48 per 1000 person-years, respectively. Among autoimmune diseases, the risk of Sjogren's syndrome in CRS patients was significantly increased to an adjusted HR (aHR) of 1.70, whereas we could not detect any significant risk of developing systemic lupus erythematosus or ankylosing spondylitis. In the subgroup analysis according to CRS phenotype, the adjusted HR of developing Sjogren's syndrome was greater in CRS patients without nasal polyps) than in CRS patients with nasal polyps. CONCLUSIONS: Our study suggests that CRS without nasal polyps is associated with an increased incidence of Sjogren's syndrome diagnosis compared to CRS without nasal polyps. Additionally, there was no association between CRS and systemic lupus erythematosus or ankylosing spondylitis, regardless of CRS phenotype.

Autoimmune disorders in oral lichen planus: A systematic review and meta-analysis.

OBJECTIVES: The association of OLP with other autoimmune processes points to the possibility that OLP-affected patients are actually developing an autoimmune status that predisposes them to autoaggression against different targets. This systematic review and meta-analysis aim to evaluate the current evidence on the prevalence of autoimmune disorders in patients with OLP and their magnitude of association. METHODS: We searched PubMed, Embase, Web of Science, Scopus databases for the studies published before May 2021, with no limitation in regards to their publication date or language. We evaluated the quality of studies, carried out meta-analyses and performed heterogeneity, subgroups, meta-regression, and small-study effects analyses. RESULTS: Inclusion criteria were met by 153 studies (23,327 patients). Our results indicate the existence of high prevalence and a frequent association between OLP and some autoimmune disorders, especially in regards to thyroid disease (PP = 7.96%, 95% CI = 6.32-9.75; OR = 1.99, 95% CI = 1.60-2.49, p < 0.001) and diabetes mellitus (PP = 9.41%,95% CI = 8.16-10.74; OR = 1.64, 95% CI = 1.34-2.00, p < 0.001). CONCLUSIONS: Our study demonstrates the existence of a comorbidity between autoimmune thyroid diseases as well as between diabetes mellitus and OLP respectively. Quality of evidence should be upgraded on other autoimmune diseases (fibromyalgia, gastrointestinal disorders, rheumatic diseases, Sjogren's syndrome, lupus erythematosus, and dermatological diseases) for which the current data do not allow us to know whether they are really associated with OLP.

Polyautoimmunity in systemic lupus erythematosus: secondary Sjogren syndrome.

BACKGROUND: Sjogren's syndrome (SS) is a chronic autoimmune disease characterized by lymphocytic infiltration of the exocrine glands. It can be associated with other connective tissue diseases, including systemic lupus erythematosus (SLE). OBJECTIVE: This study aimed to determine the incidence of secondary SS (sSS) in patients diagnosed with SLE (SLE-SS) and compare the clinical and serological features of SLE-SS to SLE only. METHODS: A retrospective observational study including patients diagnosed with SLE (SLICC criteria) seen at the Rheumatology Department between 1990 and 2020 was performed. A total of 453 SLE patients were assessed for fulfilment of the criteria for SS using the European questionnaire and Schirmer test, fluorescein staining/non-stimulated whole-salivary flow, anti-Ro/La antibodies, and lip biopsy. Anti-Ro/SSA and anti-La/SSB antibodies and rheumatoid factor (RF) were measured at entry and at SS assessment. SLE-SS was defined according to the American-European Consensus Criteria (AECC). SLE-SS was defined as a case that initially only fulfilled SLE classification criteria but which exhibited disease progression during follow-up and then met classification criteria for sSS. RESULTS: SLE-SS occurred in 11% of the SLE patients. In comparison to SLE-only patients, the SLE-SS group was older at inclusion and onset, and had a longer disease course. Sicca syndrome, oral ulcers, pulmonary involvement, and peripheral neuropathy were more frequent. Anti-SSA, anti-SSB, RF, and total IgG were higher in the SLE-SS group. CONCLUSION: SLE-SS appears to be a subgroup of patients with distinct clinical and serologic features. The frequency of SLE-SS increases with age. Patients with SLE-SS have a higher frequency of oral ulcers, anti-Ro and anti-La antibodies, and a lower frequency of renal disease, anti-dsDNA antibodies, anti-SM, and lower C3 and C4 hypocomplementemia.

Characterisation of the coexistence between sarcoidosis and Sjögren's syndrome. Analysis of 43 patients.

OBJECTIVES: To characterise the key epidemiological, clinical, immunological, imaging, and pathological features of the coexistence between sarcoidosis and Sjögren's syndrome (SS). METHODS: All centres included in two large multicentre registries (the Sjögren Syndrome Big Data Consortium and the Sarco-GEAS-SEMI Registry) were contacted searching for potential cases of coexistence between SS and sarcoidosis seen in daily practice. Inclusion criteria were the fulfilment of the current classification criteria both for SS (2016 ACR/EULAR) and sarcoidosis (WASOG). The following features were considered for evaluating a coexisting immunopathological scenario between the two diseases: non-caseating granulomas (NCG), focal lymphocytic sialadenitis (FLS) and positive anti-Ro antibodies. RESULTS: We identified 43 patients who fulfilled the inclusion criteria (38 women, with a mean age of 53 years at diagnosis of SS and of 52 years at diagnosis of sarcoidosis). In 28 (65%) cases, sarcoidosis was diagnosed concomitantly with SS, or during the follow-up of patients with an already diagnosed SS, while in the remaining 15 (35%), SS was diagnosed during the follow-up of an already diagnosed sarcoidosis. Patients in whom sarcoidosis was diagnosed first showed a lower mean age (43.88 vs. 55.67 years, p=0.005) and were less frequently women (73% vs. 96%, p=0.04) in comparison with those in whom sarcoidosis was diagnosed concomitantly with SS, or during the follow-up of an already diagnosed SS. We identified the following immunopathological scenarios: a combination of NCG involving extrasalivary tissues and anti-Ro antibodies in 55% of patients, a coexistence of both pathological scenarios (extrasalivary NCG and FLS in MSGB) in 42% (with positive anti-Ro antibodies in two thirds of cases), and NCG involving salivary glands and anti-Ro antibodies in 3% of cases. CONCLUSIONS: We have characterised the largest reported series of patients who fulfilled the current classification criteria for both SS and sarcoidosis. This implies that sarcoidosis (and not just the presence of isolated NCG on salivary gland biopsy) may, like other systemic autoimmune diseases, coexist with SS, and that a sarcoidosis diagnosis does not preclude the development of SS in the future.

The risk of cancer in patients with primary Sjögren syndrome: a single-center study from Turkey.

BACKGROUND: The aim of this study is to determine the risk of cancer in patients with primary Sjögren syndrome (pSS) from a single center in Turkey. METHODS: Clinical data of the subjects with pSS were retrospectively analyzed. The incidence of cancer for general population was obtained from GLOBOCAN 2018. Age- and sex-specific standardized incidence ratios (SIR) of solid and hematological cancers were calculated compared with the general population. RESULTS: Four hundred thirty patients with pSS were included in the study. The majority of the patients were female (n = 396, 92.1%), and the mean age was 58.6 ± 12.0 years. Thirty-four patients (7.9 %) were diagnosed with cancer (26 solid and 8 hematological) during follow-up. The SIR for all cancers was 2.45 (95% CI, 1.625-3.275). The SIR was 2.42 (95% CI, 1.542-3.298) for solid cancers and 8.42 (95% CI, 2.394 - 14.446) for hematological cancers. The most diagnosed malignancies were breast cancer (n = 6), ovarian cancer (n = 6), and non-Hodgkin lymphoma (NHL) (n = 4). There was an increased risk for ovarian cancer (SIR 12.76, 95% CI, 2.545-22.975). The SIR values were 2.08 (95% CI, 0.419-3.741) and 10.81 (95% CI, 0.216-21.404) for breast cancer and NHL, respectively. DISCUSSION: The risk of hematological and solid cancers was higher in the patients with pSS when compared to general population. In our pSS cohort, the risk for ovarian cancer was found to be increased, which has not been previously reported in the literature.