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Background: Sjogren syndrome (SS) is a chronic systemic autoimmune disease and its pathogenesis often involves the participation of numerous immune cells and inflammatory factors. Despite increased researches and studies recently focusing on this area, it remains to be fully elucidated. We decide to incorporate genetic insight into investigation of the causal link between various immune cells, inflammatory factors and pathogenesis of Sjogren syndrome (SS). Methods: Our study leveraged the genetic variants of multi-omics statistics extracted from genome-wide association study (GWAS), the University of Bristol and the FinnGen study. We performed a bidirectional Mendelian randomization and mediation study based on randomly allocated instrumental variables to infer causality, followed by external validation with UK Biobank data and Bayesian colocalization. Results: We demonstrated that an elevated level of CD27 on IgD + CD24 + B cell, a subset of B cells expressing both IgD and CD24, was associated with a higher risk of SS (OR = 1.119, 95% CI: 1.061–1.179, P < 0.001), while CD3 on CD45RA + CD4 + Treg was a protective factor (OR = 0.917, 95%CI: 0.877–0.959, P < 0.001). Results of meta-analysis and colocalization further supported the significant results identified in the primary analysis. A total of 4 inflammatory cytokines and 7 circulating proteins exhibited potential causal relationships with SS despite no significant result achieved after FDR correction. Finally, results of mediation analysis indicated that CD40L receptor levels had significant mediating effects (β = 0.0314, 95% CI: 0.0004–0.0624, P = 0.0471) at a mediation proportion of 28% (95% CI: 0.364%-55.6%) in causal relationship between CD27 on IgD + CD24 + B cell and SS. Conclusions: By providing a novel genetic insight into unveiling the roles of autoimmunity and inflammation in Sjogren syndrome, our findings may potentially lead to identifying new clinical biomarkers for disease monitoring and therapeutic targets that offer more effective alternatives for treating this condition. Therefore, our study may provide valuable evidence for future clinical intervention and targeted immunotherapy. [ABSTRACT FROM AUTHOR]

Background: The EULAR Sjögren's syndrome (SS) disease activity index (ESSDAI) pulmonary domain is used to assess the activity of respiratory system involvement in Sjögren's disease (SjD). The most unfavorable form of respiratory involvement in SjD, after lymphomas, is interstitial lung disease (ILD). Objectives: The aim of the study was to assess the involvement of the respiratory system in SjD patients and the occurrence of ILD in high-resolution computed tomography (HRCT), depending on immunological markers, the influence of cigarette smoking, and the age of the patients. Design: Single-center, registry, cohort study. Methods: Among all SjD patients, a group with involvement in the pulmonary domain was distinguished. This group was later subjected to a detailed analysis of immunological and serological markers and chest imaging tests. Results: In all, 64 patients out of 299 with SjD had involvement in the pulmonary domain defined according to the ESSDAI definition. The most frequently reported clinical symptoms of respiratory system involvement included dryness and chronic cough (over 80% of patients), followed by shortness of breath. Nine percent of patients with changes in lungs were asymptomatic. Patients with pulmonary involvement were older (54 vs 48 years, p < 0.05). In the subpopulation of patients with SjD and pulmonary involvement, the presence of rheumatoid factor (73% vs 60%, p < 0.05), and hematological domain involvement according to ESSDAI (54% vs 37%, p < 0.05) were more common. In the group of 64 patients with a positive pulmonary domain, 34 (53%) had ILD on HRCT. A higher incidence of comorbidities was found in the population of patients with ILD. No correlation was found between the type of lung involvement and the immunological profile, inflammatory markers, age, and smoking habit. Conclusion: Involvement of the pulmonary domain is common in patients with SjD. However, the clinical picture is very heterogeneous, which determines the subsequent personalization of treatment. [ABSTRACT FROM AUTHOR]

Background: Sjogren's syndrome is an autoimmune disease that affects exocrine glands like sweat glands, salivary glands, and lacrimal glands. Dentists frequently encounter these patients and have an important role in establishing the diagnosis. It is mainly diagnosed by clinical features like xerostomia and xerophthalmia, along with anti-Sjögren's syndrome-related antigen A (anti-SSA/also called Ro antigen) and anti-Sjögren's syndrome-related antigen B (anti-SSB/ also called La antigen) antibodies in the patients. However, there is a subset of the population where autonuclear antibodies cannot be detected but are still present with all clinical features of Sjogren's syndrome. Such patients usually remain undiagnosed, and only symptomatic treatment is given in spite of repeated consultation with various medical specialists. Only after establishing a proper diagnosis can we initiate definitive treatment. Case presentation: Here, we report a case of seronegative Sjogren's syndrome in a patient with severe xerostomia without anti-SSA and anti-SSB antibodies. The focus score from the labial biopsy, co-relating with clinical presentation, helped us in establishing the diagnosis. After a definitive diagnosis, our patient is put on cholinergic therapy, which greatly reduced the symptoms of xerostomia. Conclusions: Physicians and dentists should refer such patients to an oral and maxillofacial surgeon for a labial biopsy to consider "seronegative Sjogren's syndrome." The "focus score" evaluation by the pathologist helps in establishing the diagnosis of "seronegative Sjogren's syndrome". [ABSTRACT FROM AUTHOR]

Background and objectives: Sjögren Syndrome (SS) is a chronic, systemic, and progressive autoimmune disease in which inflammatory processes play a role. Dry eyes or mouth are present in approximately 95–98% of patients with pSS. This study aimed to evaluate the relationship between SII level and disease activity as well as dry eye involvement in patients with pSS. Materials and methods: A cross-sectional design was employed, and a total of 28 female patients who were aged 18–65 years and were diagnosed with pSS were involved. The Sjögren Syndrome Disease Activity Index (ESSDAI) was calculated in patients. The Schirmer test was applied to all patients. The relationship between SII level and disease activity as well as dry eye involvement in pSS patients was evaluated. Results: In our study, a strong positive correlation was found between the SII value and pSS disease activity, while a negative correlation was found between the Schirmer test, which shows dry eye findings, and eye drying time, and a positive correlation was found with the OSDI. Conclusions: this study reported a correlation between hematological parameters and the development of dry eye in pSS. NLR, PLR, and SII showed statistically significant changes in pSS patients. [ABSTRACT FROM AUTHOR]

Introduction: In patients with Hereditary Angioedema (HAE) related to primary C1 inhibitor deficiency (C1INH), the defective clearance of immune complexes and apoptotic materials along with impairment of normal humoral response potentially leads to autoimmunity. Few studies report evidence on autoimmune diseases in C1INH-HAE, but no large population studies focus on rare connective tissue diseases (RCTDs). We aim at evaluating for the first time prevalence and distribution of RCTDs - Systemic Lupus Erytematosus (SLE), primary Sjogren Syndrome (SjS), primary antiphospholipid syndrome (APS), Systemic Sclerosis (SSc), and mixed connective tissue diseases (MCTD) in a large Italian cohort of C1INH-HAE patients. Methods: A multicenter observational study includes C1INH-HAE patients from ITACA Centers throughout Italy (time frame Sept 2023-March 2024). Inclusion criteria are i. a defined diagnosis of type I or type II C1INH-HAE; ii. age =15 years (puberty already occurred); iii. enrollment in the ITACA Registry. The diagnosis of SLE, primary SjS, primary APS, SSc, and MCTD are made in accordance with international classification criteria. Results: Data are collected from a total of 855 C1INH-HAE patients referring to 15 ITACA Centers. Patients with concomitant RCTDs were 18/855 (2.1%) with F:M ratio 3.5 and a prevalent type I C1INH-HAE diagnosis (87.2%). A diagnosis of SLE results in 44.5% of cases (n=8) while the remaining diagnoses are primary SjS (22.2%, n=4), primary APS (16.6%, n=3), SSc (11.2%, n=2), and a single case of MCTD (5.5%). The female gender is prevalent in all the RCTDs. Patients on long term prophylaxis (LTP) are significantly prevalent in RCTDs group than in the whole C1INH-HAE population (p<0.01). Conclusions: A relevant prevalence of RCTDs is documented in C1INH-HAE patients, mainly SLE. Patients with RCTDs are on LTP in a significant proportion supporting the idea of a bidirectional link between C1INH-HAE and autoimmunity. [ABSTRACT FROM AUTHOR]

Abstract Background Endoplasmic reticulum stress (ERS) and the unfolded protein response (UPR) are adaptive mechanisms for conditions of high protein demand, marked by an accumulation of misfolded proteins in the endoplasmic reticulum (ER). Rheumatic autoimmune diseases (RAD) are known to be associated with chronic inflammation and an ERS state. However, the activation of UPR signaling pathways is not completely understood in Sjögren’s disease (SD). This study evaluated the expression of ERS-related genes in glandular tissue of patients with primary SD (pSD), associated SD (aSD) with other autoimmune diseases, and non-Sjögren sicca syndrome (NSS). Methods In a cross-sectional study, minor salivary gland biopsies were obtained from 44 patients with suspected SD and 13 healthy controls (HC). Patients were classified as pSD, aSD, or NSS based on clinical, serological, and histological assessment. Histopathological analysis and mRNA expression analysis of genes associated with ERS and UPR (PERK, XBP1, ATF-6, ATF-4, CANX, CALR, CHOP, and BIP) were performed on the samples. Differences between groups (pSD, aSD, NSS, and HC) were assessed. The influence of chloroquine (CQ) on the ER was also investigated. Results Twenty-eight SD patients showed increased expression of PERK (p = 0.0117) and XBP1 (p = 0.0346), and reduced expression of ATF-6 (p = 0.0003) and CHOP (p = 0.0003), compared to the HC group. Increased expression of BIP (p

Thao Thi Do,1,&ast; Vy Thuy Nguyen,1,&ast; Ngoc Tran Nhu Nguyen,1 Kim Tran Thien Duong,1 Tri Ta Minh Nguyen,1 Duong Nguyen Thuy Le,1 Tin Hoang Nguyen2 1Oral Diagnosis and Periodontology Department, Faculty of Odonto-Stomatology, Can Tho University of Medicine and Pharmacy, Can Tho City, 900000, Vietnam; 2Department of Physiology, Faculty of Medicine, Can Tho University of Medicine and Pharmacy, Can Tho City, 900000, Vietnam&ast;These authors contributed equally to this workCorrespondence: Tin Hoang Nguyen, Department of Physiology, Faculty of Medicine, Can Tho University of Medicine and Pharmacy, 179 Nguyen Van Cu Street, An Khanh Ward, Ninh Kieu District, Can Tho City, 900000, Vietnam, Tel +84344895522, Email nhtin@ctump.edu.vnAbstract: The tight junction (TJ), a type of cell-cell junction, regulates the permeability of solutes across epithelial and endothelial cellular sheets and is believed to maintain cell polarity. However, recent studies have provided conflicting views on the roles of TJs in epithelial polarity. Membrane proteins, including occludin, claudin, and the junction adhesion molecule, have been identified as TJ components. TJs are predominantly found at the stratum granulosum and stratum corneum. Although it remains unclear whether the disruption of TJs is the cause or consequence of certain dental diseases, evidence suggests that TJ dysfunction may be a crucial factor in gingival epithelial barrier impairment and the progression of oral diseases. Bacterial infection is among the most specific factors we found that may contribute to the breakdown of the epithelial barrier formed by TJs in dental diseases. Bacteria and their products may weaken the epithelial barrier by directly destroying intercellular junctions or altering the expression of junctional proteins. Additionally, they may induce the production of inflammatory cytokines, which could lead to the downregulation of TJ proteins and, consequently, impair the epithelial barrier. This review introduces a novel perspective by exploring, for the first time, the role of TJs dysfunction in the breakdown of the oral epithelial barrier and its potential link to the progression of dental diseases such as gingivitis, periodontitis, Sjӧgren syndrome, and oral squamous cell carcinoma.Keywords: epithelial barrier, gingival inflammation, Sjӧgren syndrome, oral squamous cell carcinoma, periodontitis

Abstract Background Sjögren syndrome (SS) is a systemic autoimmune disease characterised by oral and ocular mucosal dryness. Objectives Our study focused on skin manifestations of SS. The differences between primary SS (pSS) and secondary SS (sSS) were investigated. Furthermore, we elucidated factors predicting internal organ involvement. Methods This was a single centre retrospective cohort study. We analysed clinical and laboratory data from 185 Ro‐SSA positive SS patients between January 2000 and December 2016. Results Skin manifestations were present in 74.9% (n = 137) of SS patients. Dermatitis and Lupus erythematosus (LE)‐specific skin manifestations were present in 34.1% (n = 63) and 21.6% (n = 40) of SS patients respectively. 65.9% (n = 122) of SS patients had internal organ involvement, with 53% (n = 98) presenting neuropsychiatric manifestations. Several risk factors for internal organ involvement were identified: presence of myalgia/arthralgia (odds ratio [OR] = 3.05, confidence interval [CI] 1.29−7.22), fatigue (OR = 2.53, CI 1.11−5.73) and age older than 50 years (OR = 2.23, CI 1.01−4.93). Conclusions Internal organ involvement is frequent in SS, however there is no significant difference between pSS and sSS concerning its occurrence.

Mucosa-associated lymphoid tissue (MALT) lymphoma commonly arises from chronic inflammation or autoimmune diseases, such as Sjögren syndrome (SjS). Although rare, amyloid deposition in MALT lymphoma has been reported. We present a rare case of parotid gland MALT lymphoma in a 49-year-old woman, in whom preoperative diagnosis was challenging due to atypical imaging findings resulting from amyloid deposits. MRI showed T2-hypointense and T1-iso- to slightly hyperintense masses in the left parotid gland and right sublingual gland, with predominant marginal contrast enhancement and no significant diffusion restriction. Additionally, atrophy and fatty replacement of the parenchyma were noted in bilateral parotid glands, suggesting SjS. Left superficial parotidectomy was performed and pathological findings confirmed MALT lymphoma with extensive amyloid deposition. Histopathological findings of the resected parotid gland parenchyma also suggested SjS. MALT lymphoma should be considered in the differential diagnosis of multiple salivary gland masses in patients with suspected SjS. If MRI reveals atypical imaging findings for malignant lymphoma, particularly T2-hypointensity with no significant diffusion restriction, the possibility of amyloid deposition in MALT lymphoma should be considered.

Abstract Background Salivary hypofunction leads to debilitating oral symptoms and has major complications for overall quality of life. Two of the most frequent causes of xerostomia are radiotherapy in the head and neck and Sjögren’s syndrome. Only symptomatic treatment is available today. An increasing number of both preclinical and clinical studies have suggested that mesenchymal stem cell (MSC) transplantation treatment can increase the salivary flow rate and ameliorate symptoms of xerostomia. However, both adipose-derived and bone marrow–derived MSCs are used, although they differ in important ways. The primary objective of this study is an indirect comparison of the change in the unstimulated salivary flow rate after intervention between patients treated with adipose-derived or bone marrow–derived MSCs. Methods This systematic review and network meta-analysis will search for eligible studies in the MEDLINE, EMBASE, and Cochrane CENTRAL register of Controlled Trials. Eligible studies are as follows: clinical studies including human patients with salivary hypofunction due to either radiotherapy or Sjogren’s syndrome who were subsequently treated with either adipose-derived MSCs or bone marrow–derived MSCs. Studies with no control group will be excluded. The search phrase has been peer-reviewed following the PRESS guidelines. The primary outcome is the change in the unstimulated salivary flow rate after treatment with either adipose-derived or bone marrow–derived MSCs. Secondary outcomes are as follows: change in patient reported outcomes, methods of intervention administration, number of injected MSCs, and safety. Data from included studies will be pooled and compared with a fixed-effects or random effects model dependent on signs of heterogeneity, presented with a forest plot, and indirectly compared with a meta-regression in a network meta-analysis. Risk of bias will be assessed with the tools ROBINS-I or RoB-2 depending on type of study. Discussion Both adipose-derived and bone marrow–derived MSCs are used today for experimental treatment of salivary hypofunction in humans as no direct or indirect comparisons have been made. Therefore, an evaluation of the effect of adipose-derived vs bone marrow–derived MSC treatment is needed to support future decision-making on the type of MSC used in a clinical trial. Systematic review registration PROSPERO ID CRD42024527183.

This study aimed to investigate whether patients with primary Sjögren syndrome (SjS) have different levels of 25 OH-D3 (vitamin D) when compared to healthy populations and whether differences in 25 OH-D3 correlated with disease activity or markers.

Background. Primary Sjögren’s syndrome (pSS) is an autoimmune epithelitis associated with various pulmonary manifestations, including PAH (pulmonary arterial hypertension), a severe complication often found in collagen tissue disorders. Case presentation. A 26-year-old female having chest pain and exertional dyspnea diagnosed with severe PAH associated with pSS is presented in this case study. Clinical, laboratory, and imaging findings supported the diagnosis, and treatment involved immunosuppressive therapy and standard PAH medications. Discussion and conclusion. The report highlights the complexities of diagnosing and treating PAH associated with pSS, emphasizing the importance of early intervention for improved long-term outcomes. The prognosis for PAH in connective tissue diseases, encompassing pSS, remains challenging, underscoring the need for accurate diagnosis and timely management with immunosuppressants and PAH-specific therapies.

Background: Psychiatric disorders, such as major depressive disorder (MDD), anxiety disorder (AD), bipolar disorder (BD), and schizophrenia (SCZ), are disturbances in brain activity that lead to disorders of cognition, behavior, and emotion regulation. Among Sjogren syndrome (SS) patients, psychiatric disorders are more prevalent than in the general population. Identifying associated risk factors can provide new evidence for clinical diagnosis and treatment. Methods: We selected genetic instruments based on published genome-wide association studies (GWASs) to determine predisposition. Then, we conducted a 2-sample bidirectional Mendelian randomization (MR) analysis to explore the potential causal associations between SS and four major psychiatric disorders. The primary analysis was performed using MR with the inverse-variance weighted method. Confirmation was achieved through Steiger filtering and testing to determine the causal direction. Sensitivity analyses were conducted using MR-Egger, MR-PRESSO, and "leave-one-out" method methods. Results: Our study showed that SS was linked to BD and SCZ, indicating that individuals with SS may have a reduced risk of developing BD (IVW: OR = 0.940, P=0.014) and SCZ (IVW: OR = 0.854, P=1.47*10-4), while there was no causal relationship between SS and MDD or AD. MR-Egger regression shows no evidence of pleiotropy (BD: intercept = 0.007, p = 0.774; SCZ: intercept = 0.051, p = 0.209). The same as the MR-PRESSO analysis (BD: global test p = 1.000; SCZ: global test p = 0.160). However, the results from the leave-one-out analysis demonstrated instability. Specifically, after excluding SNP rs3117581, the effects on BD and SCZ were found to be non-significant, suggesting the potential influence of unrecognized confounding factors. The results of the reverse MR show that four major psychiatric disorders had no causal effects on SS. Conclusions: Our research findings demonstrate a causal relationship between SS and SCZ, as well as between SS and BD. There are no causal effects between the four major psychiatric disorders and SS. These findings suggest that SS may have the potential to reduce the risk of both psychiatric disorders. This study provides new insight for their prevention and treatment. [ABSTRACT FROM AUTHOR]

Background: Rheumatological toxicity associated with immunotherapy, particularly Sjögren's syndrome (SjS), has been observed with variable incidence in patients treated with immune checkpoint inhibitors (ICIs). Although SjS is a well-known autoimmune disease, its occurrence as an immune-related adverse event (irAE) during cancer treatment is less well understood. Current literature documents a range of incidence rates and clinical manifestations of SjS in patients undergoing ICI therapy, highlighting the need for early diagnosis and multidisciplinary management. Case presentation: A 40-year-old woman underwent mammography, which revealed a 43 mm mass in the left breast. Core biopsy confirmed grade 3 infiltrating triple negative ductal carcinoma with high MIB-1. She received neoadjuvant chemotherapy, followed by surgery and radiotherapy. A CT scan in September 2022 showed lung nodules and lymph node involvement. A lung biopsy confirmed breast cancer metastasis. She started treatment with atezolizumab and nab-paclitaxel with evidence of a partial response. Nabpaclitaxel was discontinued due to side effects and atezolizumab was continued as maintenance therapy. After four cycles, the patient developed symptoms consistent with Sjögren's syndrome (SjS), which were confirmed by diagnostic tests. Treatment wi th prednisone, pilocarpine and hydroxychloroquine was initiated alongside ongoing immunotherapy. The patient continues to receive atezolizumab with stable disease and good quality of life. Conclusion: This case highlights the importance of recognizing SjS as a potential irAE in patients treated with ICIs, particularly those with TNBC. Multidisciplinary collaboration is essential for the prompt diagnosis and effective management of SjS to maintain both cancer control and patient quality of life. Given the recent emergence of these events and the lack of specific guidelines, our case report may provide valuable insights into the management of a little-known adverse event and pave the way for further real-world data collection on the management of these rare but significant toxicities that impact on patient quality of life. Further research is needed to optimize treatment protocols and outcomes for patients experiencing rheumatological irAEs during cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Salivary hypofunction leads to debilitating oral symptoms and has major complications for overall quality of life. Two of the most frequent causes of xerostomia are radiotherapy in the head and neck and Sjögren's syndrome. Only symptomatic treatment is available today. An increasing number of both preclinical and clinical studies have suggested that mesenchymal stem cell (MSC) transplantation treatment can increase the salivary flow rate and ameliorate symptoms of xerostomia. However, both adipose-derived and bone marrow–derived MSCs are used, although they differ in important ways. The primary objective of this study is an indirect comparison of the change in the unstimulated salivary flow rate after intervention between patients treated with adipose-derived or bone marrow–derived MSCs. Methods: This systematic review and network meta-analysis will search for eligible studies in the MEDLINE, EMBASE, and Cochrane CENTRAL register of Controlled Trials. Eligible studies are as follows: clinical studies including human patients with salivary hypofunction due to either radiotherapy or Sjogren's syndrome who were subsequently treated with either adipose-derived MSCs or bone marrow–derived MSCs. Studies with no control group will be excluded. The search phrase has been peer-reviewed following the PRESS guidelines. The primary outcome is the change in the unstimulated salivary flow rate after treatment with either adipose-derived or bone marrow–derived MSCs. Secondary outcomes are as follows: change in patient reported outcomes, methods of intervention administration, number of injected MSCs, and safety. Data from included studies will be pooled and compared with a fixed-effects or random effects model dependent on signs of heterogeneity, presented with a forest plot, and indirectly compared with a meta-regression in a network meta-analysis. Risk of bias will be assessed with the tools ROBINS-I or RoB-2 depending on type of study. Discussion: Both adipose-derived and bone marrow–derived MSCs are used today for experimental treatment of salivary hypofunction in humans as no direct or indirect comparisons have been made. Therefore, an evaluation of the effect of adipose-derived vs bone marrow–derived MSC treatment is needed to support future decision-making on the type of MSC used in a clinical trial. Systematic review registration: PROSPERO ID CRD42024527183. [ABSTRACT FROM AUTHOR]

Introduction: Sjogren's syndrome (SS) is an autoimmune chronic inflammatory disorder affecting women in their fourth to sixth decade, affecting gastrointestinal, and musculoskeletal systems. A 35-year-old female with SS with polymyositis (PM) presented with symptoms of weakness in all four limbs, difficulty in sitting, rising, swallowing solid foods, vomiting, and difficulty in climbing stairs. She was diagnosed with SS in 2018 and was treated with prednisolone, Vitamin D, calcium, pyridoxine, methylcobalamin, artificial tears, pilocarpine, and painkillers. However, a muscle biopsy was never done. Methods: The data were collected from the patient's file along with her consent when she came for follow-up. Results: A muscle biopsy was done at our center to confirm the diagnosis of PM. The patient was prescribed IV prednisolone and other symptomatic treatment until symptoms resolved and was discharged with oral drugs when they were manageable. Conclusion: The diagnosis of primary SS along with PM is a rare occurrence. Although it does not change the treatment plan much, its diagnosis is very important for managing any complications that may arise from it. Patients' noncompliance and loss of follow-up can create issues in the treatment. Such cases help in forming the guidelines for the future and restructuring the classification of autoimmune conditions. [ABSTRACT FROM AUTHOR]

Background: In vivo confocal microscopy (IVCM) is a vital tool in studying dry eye disease (DED), providing insights into morphological changes at ocular surface unit levels. This review presents the main differences in corneal structure between aqueous-deficient dry eye disease (AD-DED) and normal eyes. Methods: A comprehensive search of PubMed, Web of Science, Embase, and MEDLINE databases from January 2000 to December 2023 was conducted. The study selection process, as well as data selection and examination, were independently performed by two members of the review team. Results: The review reveals a consistent decrease in corneal surface epithelial cell density in AD-DED cases compared to a control group, but conflicting data on basal epithelial cell density. Notably, the abnormal hyperreflectivity of keratocytes in patients with Sjogren's syndrome was recorded, and there was a significant keratocyte density in AD-DED subjects compared to evaporative DED and control groups. Studies also found a decrease in sub-basal nerve density, increased tortuosity, and the fragmentation of nerve fibers. Dendritic cell density and dendritic cell dendrites increase in AD-DED patients compared to healthy subjects. Conclusions: IVCM is a powerful tool for enhancing our understanding of the pathophysiological mechanisms underlying DED. However, the review underscores the urgent need to standardize the terminology, analysis, and units used for accurate interpretation, a crucial step in advancing our knowledge of DED. [ABSTRACT FROM AUTHOR]

Sjogren's syndrome is an autoimmune disease characterized by lymphocytic infiltration of exocrine glands resulting in xerostomia and dry eyes affecting entire body. A 40-year-old woman presented with generalized weakness and shortness of breath. She had reduced muscle power (2/5) with reduced tone, and absent reflexes in four limbs. Further investigation revealed severe hypokalemia with metabolic acidosis. She was treated with intravenous potassium chloride and diagnosed with Sjogren's syndrome based on her serology profile. After treatment, her condition improved. Hypokalemia occurs due to increased renal excretions of potassium. Distal Renal Tubular Acidosis is a major cause of potassium loss in urine. Sjogren's Syndrome is an important cause of Distal Renal Tubular Acidosis, which can present as severe hypokalemia. Although it commonly presents with symptoms like dry eyes and dry mouth, it can rarely present as Distal Renal Tubular Acidosis and hypokalemia as the primary presentation. Sjogren's syndrome should be suspected in patients with hypokalemia with features of Distal Renal Tubular Acidosis.

Background/purpose: The diagnosis and treatment of Sjogren's syndrome (SS) are commonly conducted by rheumatologists and stomatologists. The purpose of this study was to compare the scientometric characteristics of SS publications by rheumatologists and stomatologists. Materials and methods: All the papers on cheilitis were comprehensively retrieved from the Scopus database, and divided into rheumatologists and stomatologists groups. Results: There were 3245 and 1209 papers on SS were published by rheumatologists and stomatologists, respectively. For the most-cited top-200 papers, the total citation count was 29,764 and the h index was 108 for SS publications by rheumatologists; whereas the count is 19,891 and h index is 81 for publications by stomatologists. Interestingly, we observed that accumulated citations of the publications by stomatologists cooperated with rheumatologists were larger than those by stomatologists alone during 2012–2022. The more common keywords such as saliva, salivation, minor salivary glands, parotid gland, submandibular gland, sialography, lip, dental caries, and hyposalivation were reported by stomatologists. The more frequent keywords such as rheumatoid factor, fatigue, lymphoma, interstitial lung disease, arthralgia, Raynaud phenomenon, lymphadenopathy, and vasculitis were reported by rheumatologists. Conclusion: This study firstly reports the scientometric characteristics of SS publications by rheumatologists and stomatologists. The scale and citations of rheumatologists' publications greatly outweigh those of stomatologists, suggesting stomatologists can cooperate more with rheumatologists regarding SS research.

The diagnosis and treatment of Sjogren's syndrome (SS) are commonly conducted by rheumatologists and stomatologists. The purpose of this study was to compare the scientometric characteristics of SS publications by rheumatologists and stomatologists. All the papers on cheilitis were comprehensively retrieved from the Scopus database, and divided into rheumatologists and stomatologists groups. There were 3245 and 1209 papers on SS were published by rheumatologists and stomatologists, respectively. For the most-cited top-200 papers, the total citation count was 29,764 and the h index was 108 for SS publications by rheumatologists; whereas the count is 19,891 and h index is 81 for publications by stomatologists. Interestingly, we observed that accumulated citations of the publications by stomatologists cooperated with rheumatologists were larger than those by stomatologists alone during 2012–2022. The more common keywords such as saliva, salivation, minor salivary glands, parotid gland, submandibular gland, sialography, lip, dental caries, and hyposalivation were reported by stomatologists. The more frequent keywords such as rheumatoid factor, fatigue, lymphoma, interstitial lung disease, arthralgia, Raynaud phenomenon, lymphadenopathy, and vasculitis were reported by rheumatologists. This study firstly reports the scientometric characteristics of SS publications by rheumatologists and stomatologists. The scale and citations of rheumatologists' publications greatly outweigh those of stomatologists, suggesting stomatologists can cooperate more with rheumatologists regarding SS research. [ABSTRACT FROM AUTHOR]

Background/Objectives: Sjögren's Syndrome (SS) is a chronic degenerative rheumatic disease. Because of its chronic nature, it significantly affects the quality of life of those who suffer from it. Methods: This qualitative study investigated disease experience among women suffering from SS to understand its impact on their overall well-being. In-depth interviews were conducted with 15 women who suffer from SS. Interviews were analyzed using the Grounded Theory methodology, using open, axial, and selective coding. Results: Three central phenomena of disease experience were identified: invisibility; uncontrollability; and unpredictability. Conclusions: SS disease experience has a strong imprint on emotional well-being and sense of self-control among middle-aged women. Understanding SS impacts on women's lives is important to better understand the disease and contribute to recognizing potential areas of management and social support in relevant windows of opportunity within the health-disease continuum. [ABSTRACT FROM AUTHOR]

BackgroundRheumatological toxicity associated with immunotherapy, particularly Sjögren’s syndrome (SjS), has been observed with variable incidence in patients treated with immune checkpoint inhibitors (ICIs). Although SjS is a well-known autoimmune disease, its occurrence as an immune-related adverse event (irAE) during cancer treatment is less well understood. Current literature documents a range of incidence rates and clinical manifestations of SjS in patients undergoing ICI therapy, highlighting the need for early diagnosis and multidisciplinary management.Case presentationA 40-year-old woman underwent mammography, which revealed a 43 mm mass in the left breast. Core biopsy confirmed grade 3 infiltrating triple negative ductal carcinoma with high MIB-1. She received neoadjuvant chemotherapy, followed by surgery and radiotherapy. A CT scan in September 2022 showed lung nodules and lymph node involvement. A lung biopsy confirmed breast cancer metastasis. She started treatment with atezolizumab and nab-paclitaxel with evidence of a partial response. Nab-paclitaxel was discontinued due to side effects and atezolizumab was continued as maintenance therapy. After four cycles, the patient developed symptoms consistent with Sjögren’s syndrome (SjS), which were confirmed by diagnostic tests. Treatment with prednisone, pilocarpine and hydroxychloroquine was initiated alongside ongoing immunotherapy. The patient continues to receive atezolizumab with stable disease and good quality of life.ConclusionThis case highlights the importance of recognizing SjS as a potential irAE in patients treated with ICIs, particularly those with TNBC. Multidisciplinary collaboration is essential for the prompt diagnosis and effective management of SjS to maintain both cancer control and patient quality of life. Given the recent emergence of these events and the lack of specific guidelines, our case report may provide valuable insights into the management of a little-known adverse event and pave the way for further real-world data collection on the management of these rare but significant toxicities that impact on patient quality of life. Further research is needed to optimize treatment protocols and outcomes for patients experiencing rheumatological irAEs during cancer immunotherapy.

Abstract Background Primary Sjogren’s syndrome (pSS) is a complex autoimmune disease featuring damage to salivary and lacrimal glands, with the possibility of manifestations across multiple organs. Antibody-producing B cells have long been appreciated to play a significant role in pSS pathogenesis, with a number of autoreactive antibody species having been identified to be elevated in pSS patients. While several studies have attempted to characterize the BCR repertoires of peripheral blood B cells in pSS patients, much remains unknown about the repertoire characteristics of gland-infiltrating B cells. Methods Through paired scRNAseq and scBCRseq, we profiled the BCR repertoires of both infiltrating and circulating B cells in a small cohort of patients. We further utilize receptor reconstruction analyses to further investigate repertoire characteristics in a wider cohort of pSS patients previously profiled through RNAseq. Results Via integrated BCR and transcriptome analysis of B cell clones, we generate a trajectory progression pattern for infiltrated memory B cells in pSS. We observe significant differences in BCR repertoires between the peripheral blood and labial gland B cells of pSS patients in terms of relative expansion, isotype usage, and BCR clustering. We further observe significant decreases in IgA2 isotype usage among pSS patient labial and parotid gland B cells these analyses relative to controls as well as a positive correlation between kappa/lambda light chain usage and clinical disease activity. Conclusions Through BCR repertoire analysis of pSS patient salivary glands, we identify a number of novel repertoire characteristics that may serve as useful indicators of clinical disease and disease activity. By collecting these BCR repertoires into an accessible database, we hope to also enable comparative analysis of patient repertoires in pSS and potentially other autoimmune disorders.

Introduction: The presence of three different entities in a single patient is usually of clinical interest and mostly anecdotal. The overlap of systemic sclerosis (SSc), Sjögren syndrome (SS), and ANCA-associated renal-limited vasculitis has been reported only once previously. Case Presentation: A 61-year-old female was evaluated at consultation with 2 years of symptomatology, presenting cardboard-like skin, sclerodactyly, limited oral opening, and dry skin and eyes. She was admitted for progressive renal failure (serum creatinine, 5.5 mg/dL). Her serology work-up showed positive anti-SCL-70, anti-Ro, anti-La, anti-MPO, and antinuclear antibodies. Renal biopsy was performed and confirmed histological findings for SSc, SS, and ANCA-associated vasculitis with active extracapillary glomerulonephritis with fibrous predominance (EUVAS-Berden sclerotic class), active tubulointerstitial nephritis, focal tubular injury, and moderate chronic arteriolopathy. Treatment with 6 monthly doses of methylprednisolone and cyclophosphamide was established. At the last follow-up, the patient maintained a stable serum creatinine level of 2.6 mg/dL and had decreased proteinuria, no erythrocyturia, and no requirement for renal replacement therapy. Conclusion: Systemic sclerosis is a rare autoimmune disease; nevertheless, overlap with Sjögren syndrome is relatively common, although its association with ANCA vasculitis is anecdotal. Diagnostic integration presents a challenge for nephrologists to define the prognosis and a specific treatment.

Purpose: Our study aimed to explore the correlation between Sjögren syndrome, sociodemographic factors, comorbid conditions, and optic neuritis. Methods: This retrospective, nationwide, population-based, matched case-control investigation involved 33,190 individuals diagnosed with optic neuritis, identified using the International Classification of Diseases, Ninth Revision, Clinical Modification codes 377.30 for optic neuritis or 377.32 for retrobulbar neuritis. Patient data were extracted from the Taiwan National Health Insurance Research Database. Demographic characteristics, the presence of Sjögren syndrome, and pre-existing comorbid conditions were analyzed using univariate logistic regression. Continuous variables were assessed with a paired t-test. Adjusted logistic regression was employed to compare the prognosis odds ratio (OR) of patients with optic neuritis to controls. Results: After adjusting for confounding variables, individuals with Sjögren syndrome exhibited a significantly higher likelihood of developing optic neuritis compared to controls (adjusted OR, 9.79; 95% confidence interval [CI], 7.28-12.98; p < 0.0001). Other conditions associated with increased odds of optic neuritis included rheumatoid arthritis, ankylosing spondylitis, multiple sclerosis, systemic lupus erythematosus, and granulomatous vasculitis (adjusted OR: 1.57, 95% CI: 1.33-1.86; adjusted OR: 2.02, 95% CI: 1.65-2.48; adjusted OR: 140.77, 95% CI: 35.02-565.85; adjusted OR: 2.38, 95% CI: 1.71-3.30; adjusted OR: 18.28, 95% CI: 2.21-151.45, respectively), as well as systemic infections such as human herpes viral infection and tuberculosis infection (adjusted OR: 1.50, 95% CI: 1.35-1.66; adjusted OR: 4.60, 95% CI: 3.81-5.56, respectively). Discussion: Our findings strongly support the existence of an association between Sjögren syndrome, rheumatoid arthritis, ankylosing spondylitis, multiple sclerosis, systemic lupus erythematosus, granulomatous vasculitis, human herpes viral infection, tuberculosis, and optic neuritis. [ABSTRACT FROM AUTHOR]

Background: The fetuses of pregnant women affected by anti-Ro/anti-La antibodies are at risk of developing complete atrioventricular heart block (CAVB) and other potentially life-threatening cardiac affections. CAVB can develop in less than 24 h. Treatment with anti-inflammatory drugs and immunoglobulins (IVIG) can restore the normal rhythm if applied in the transition period. Routine weekly echocardiography, as often recommended, will rarely detect emergent AVB. The surveillance of these pregnancies is controversial. Home-monitoring using a hand-held Doppler is a promising new approach. Methods: To obtain an overview of the current practice in Germany, we developed a web-based survey sent by the DEGUM (German Society of Ultrasound in Medicine) to ultrasound specialists. With the intention to evaluate practicability of home-monitoring, we instructed at-risk pregnant women to use a hand-held Doppler in the vulnerable period between 18 and 26 weeks at our university center. Results: There are trends but no clear consensus on surveillance, prophylaxis, and treatment of anti-Ro/La positive pregnant between specialists in Germany. Currently most experts do not offer home-monitoring but have a positive attitude towards its prospective use. Intensified fetal monitoring using a hand-held Doppler is feasible for pregnant women at risk and does not lead to frequent and unnecessary contact with the center. Conclusion: Evidence-based guidelines are needed to optimize the care of anti-Ro/La-positive pregnant women. Individual risk stratification could help pregnancy care of women at risk and is welcmed by most experts. Hand-held doppler monitoring is accepted by patients and prenatal medicine specialists as an option for intensified monitoring and can be included in an algorithm for surveillance. [ABSTRACT FROM AUTHOR]

(1) Objective: To determine the diagnostic accuracy of major salivary gland ultrasonography (SGUS) in primary Sjogren’s syndrome (SS), we used the Outcome Measures in Rheumatology Clinical Trials (OMERACT) scoring system on a large single-centre cohort of patients with sicca syndrome. (2) Method: We retrospectively collected the clinical, imaging and serological data of all the patients referred with a suspicion of SS who underwent SGUS and minor salivary glands biopsy. (3) Results: A total of 132 patients were included. The SGUS scores were correlated between the two sides (p < 0.001). The diagnostic cut-off for SS (AUROC: 0.7408) was 6 for the SGUS-global sum (sensitivity: 32.43%; specificity: 96.84%). The cut-off with the highest specificity for SS diagnosis was 7. In the patients with a final diagnosis of SS, the mean SGUS score was significantly higher (p < 0.001) than that of the non-SS patients (3.73 vs. 1.32 for the SGUS-global sum). A significant correlation was demonstrated between the SGUS scores and final SS diagnosis (p < 0.001), biopsy positivity (p < 0.001), ANA positivity (p = 0.016), Ro-SSA positivity (p = 0.01), and gland fibrosis (p = 0.02). (4) Conclusions: SGUS, using the OMERACT scoring system, has moderate sensitivity and high specificity for the diagnosis of SS. The scoring showed a strong and direct correlation with all the clinical hallmarks of SS diagnosis, such as the positivity of a labial salivary gland biopsy, ANA and Ro-SSA statuses, and salivary gland fibrosis. Because of its high specificity, a SGUS-global score > 6 could be therefore employed for the diagnosis of SS in the case of ANA negativity or the unavailability of a biopsy.

Abstract Background Dry eyes and mouth are symptoms of Sjogren syndrome, which can occur on its own and be referred to as primary Sjogren syndrome or in conjunction with other rheumatic diseases like rheumatoid arthritis and be referred to as secondary Sjogren syndrome. Anti-muscarinic type 3 receptors have been linked to neurological issues as well as secretory dysfunction in Sjogren patients. Consequently, the purpose of this study is to determine the serum level of muscarinic acetylcholine receptor subtype 3 (m3AChR)-specific autoantibodies in rheumatoid arthritis (RA) patients and evaluate its relationship to disease activity, functional disability, and to study its role in the development of secondary Sjogren syndrome manifestations in those patients. Methods In this cross-sectional study, 30 RA patients with secondary Sjogren syndrome signs and 30 RA patients without secondary Sjogren syndrome manifestations were included, along with 30 healthy volunteers who were aged, and sex matched as controls. All participants underwent thorough clinical examination, evaluation of disease activity using the DAS28 score, assessment of functional status using the modified health assessment questionnaire (MHAQ), and evaluation of the serum level of (m3AChR) by (ELISA). Results When compared to RA patients without secondary Sjogren syndrome and healthy controls (20.09 ± 4.24, 18.36 ± 3.59 ng/ml respectively), the serum level of m3AChR antibodies among 30 RA patients with secondary Sjogren syndrome considerably increased (mean 25.98 ± 4.81 ng/ml).Analysis of the m3AChR’s (ROC)-curve revealed that the three groups under study differed significantly (P 22.63ng/ml), sensitivity (73.33%), and specificity (86.67%) all exceeding the threshold. Additionally, there was a significant positive connection between the serum level of m3AChR and the following variables (P

Objectives: The role of autoimmune diseases on the risk for acute epiglottitis remains uncertain. This study aimed to delineate the association between epiglottitis and autoimmune diseases using population database. Methods: A population-based retrospective study was conducted to analyze claims data from Taiwan National Health Insurance Research Database collected over January, 2000, to December, 2013. Results: In total, 2339 patients with epiglottitis were matched with 9356 controls without epiglottitis by sex, age, socioeconomic status, and urbanization level. The correlation between autoimmune diseases and epiglottitis was analyzed by multivariate logistic regression. Compared with controls, patients with epiglottitis were much more likely to have preexisting Sjögren syndrome (adjusted odds ratio [aOR]: 2.37; 95% CI: 1.14-4.91; P =.021). In addition, polyautoimmunity was associated with increased risk of epiglottitis (aOR: 2.08; 95% CI: 1.14-3.80; P =.018), particularly in those aged >50 years (aOR: 2.61; 95% CI: 1.21-5.66; P =.015). Conclusions: Among autoimmune diseases, we verify the association between epiglottitis and Sjögren syndrome in Taiwan. Furthermore, we present the novel discovery that patients with epiglottitis have an increased risk of polyautoimmunity, particularly those aged >50 years. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to determine physical activity levels and understand the factors influencing an active lifestyle among patients with primary Sjögren's syndrome (pSS). Methods: Ninety-seven patients participated in this multicentric study. Physical activity levels were assessed using the International Physical Activity Questionnaire-Short Form (IPAQ-SF). The Inflammatory Arthritis Facilitators and Barriers (IFAB) questionnaire was used to evaluate perceived barriers and facilitators to physical activity. Results: Forty-six patients were physically inactive and the rest of them were moderately active. Commonly identified barriers included a lack of motivation, fatigue, and pain. Conversely, knowledge of the health and mood benefits for physical activity emerged as a key motivator. Patients with better scores on facilitators and lower scores on barriers exhibited higher physical activity levels (p<0.05). Notably, a high level of perceived facilitators of physical activity (odds ratio [OR]: 1.02; 95% confidence interval [CI], 1.00 -- 1.05) and reduced pain (OR: 0.81; 95% CI: 0.69 -- 0.95) were linked to an active lifestyle. Conclusions: This study emphasizes the role of motivation and awareness of the benefits of physical activity for health and mood in driving physical activity for patients with primary Sjögren's syndrome. Tailored physical activity programs that address psychological aspects and disease-related pain, and fatigue should be designed to counter sedentary lifestyles in pSS patients. [ABSTRACT FROM AUTHOR]

(1) Objective: To determine the diagnostic accuracy of major salivary gland ultrasonography (SGUS) in primary Sjogren's syndrome (SS), we used the Outcome Measures in Rheumatology Clinical Trials (OMERACT) scoring system on a large single-centre cohort of patients with sicca syndrome. (2) Method: We retrospectively collected the clinical, imaging and serological data of all the patients referred with a suspicion of SS who underwent SGUS and minor salivary glands biopsy. (3) Results: A total of 132 patients were included. The SGUS scores were correlated between the two sides (p < 0.001). The diagnostic cut-off for SS (AUROC: 0.7408) was 6 for the SGUS-global sum (sensitivity: 32.43%; specificity: 96.84%). The cut-off with the highest specificity for SS diagnosis was 7. In the patients with a final diagnosis of SS, the mean SGUS score was significantly higher (p < 0.001) than that of the non-SS patients (3.73 vs. 1.32 for the SGUS-global sum). A significant correlation was demonstrated between the SGUS scores and final SS diagnosis (p < 0.001), biopsy positivity (p < 0.001), ANA positivity (p = 0.016), Ro-SSA positivity (p = 0.01), and gland fibrosis (p = 0.02). (4) Conclusions: SGUS, using the OMERACT scoring system, has moderate sensitivity and high specificity for the diagnosis of SS. The scoring showed a strong and direct correlation with all the clinical hallmarks of SS diagnosis, such as the positivity of a labial salivary gland biopsy, ANA and Ro-SSA statuses, and salivary gland fibrosis. Because of its high specificity, a SGUS-global score > 6 could be therefore employed for the diagnosis of SS in the case of ANA negativity or the unavailability of a biopsy. [ABSTRACT FROM AUTHOR]

Introduction: The presence of three different entities in a single patient is usually of clinical interest and mostly anecdotal. The overlap of systemic sclerosis (SSc), Sjögren syndrome (SS), and ANCA-associated renal-limited vasculitis has been reported only once previously. Case Presentation: A 61-year-old female was evaluated at consultation with 2 years of symptomatology, presenting cardboard-like skin, sclerodactyly, limited oral opening, and dry skin and eyes. She was admitted for progressive renal failure (serum creatinine, 5.5 mg/dL). Her serology work-up showed positive anti-SCL-70, anti-Ro, anti-La, anti-MPO, and antinuclear antibodies. Renal biopsy was performed and confirmed histological findings for SSc, SS, and ANCA-associated vasculitis with active extracapillary glomerulonephritis with fibrous predominance (EUVAS-Berden sclerotic class), active tubulointerstitial nephritis, focal tubular injury, and moderate chronic arteriolopathy. Treatment with 6 monthly doses of methylprednisolone and cyclophosphamide was established. At the last follow-up, the patient maintained a stable serum creatinine level of 2.6 mg/dL and had decreased proteinuria, no erythrocyturia, and no requirement for renal replacement therapy. Conclusion: Systemic sclerosis is a rare autoimmune disease; nevertheless, overlap with Sjögren syndrome is relatively common, although its association with ANCA vasculitis is anecdotal. Diagnostic integration presents a challenge for nephrologists to define the prognosis and a specific treatment. [ABSTRACT FROM AUTHOR]

This study aimed to determine the role of IFN-1 gene signatures in SLE and their association with Sjögren syndrome (SS). Publicly available data from the Gene Expression Omnibus database were used to construct the models. The random forest tree model was used to screen key IFN-1 gene signatures, and consensus clustering algorithms were used for unsupervised cluster analysis of these signatures. CIBERSORT and gene set variation analyses were used to evaluate the relative immune cell infiltration and enriched molecular pathways of the samples, respectively. Weighted gene co-expression network analysis was used to identify the co-expression modules and hub genes. Finally, univariate and multivariate logistic regression models were used to evaluate differences in clinical and laboratory characteristics between the different groups. The role of IFN-1 gene signatures in SLE was comprehensively assessed, which revealed an IFN-1 gene signature including six genes that could easily distinguish SLE patients and healthy individuals and identified two distinct IFN-1 subtypes exhibiting significant differences in clinical characteristics, immune microenvironment, and biological functional pathways. The SLE disease activity index, lower lymphocyte count, nucleotide oligomerization domain (NOD)-like receptor signaling pathway, and dendritic cell activation were strongly correlated with the IFN-1 gene signatures. In addition, we found that IFN-1 gene signatures in SLE may be an important susceptibility factor for SS, and the NOD-like receptor signaling pathway was identified as a common pathway. This study provides a comprehensive evaluation of the IFN-1 gene signatures, which may provide a new direction for the understanding of SLE and SS and help in the selection of optimal strategies for personalized immunotherapy. [ABSTRACT FROM AUTHOR]

Abstract Background Tubulointerstitial nephritis with IgM-positive plasma cells (IgMPC-TIN) is a newer disease about which there are many unclear points. Glucocorticoid therapy is effective in many cases of IgMPC-TIN; however, relapse during glucocorticoid tapering has been reported. Relapse and its treatment are poorly defined. Case Presentation Case 1 was a 61-year-old man with renal dysfunction and proteinuria. Tubulointerstitial nephritis and IgM-positive plasma cells were observed in a renal biopsy. He was diagnosed with IgMPC-TIN accompanied by Fanconi syndrome and distal renal tubular acidosis (d-RTA). Prednisolone (PSL; 30 mg daily, 0.45 mg/kg/day) treatment was highly effective, and PSL was gradually tapered and discontinued after 1 year. However, 1 month after PSL discontinuation, therapeutic markers were elevated. Therefore, PSL (10 mg daily, 0.15 mg/kg/day) was administered, and the markers indicated improvement. Case 2 was a 43-year-old woman referred for renal dysfunction and proteinuria. Laboratory data revealed that she had primary biliary cholangitis (PBC), d-RTA, and Fanconi syndrome. A renal biopsy showed accumulation of IgM-positive plasma cells in the tubulointerstitium without any glomerular changes. A diagnosis of IgMPC-TIN was made and the patient was started on PSL (35 mg daily, 0.6 mg/kg/day). Therapeutic markers decreased immediately and PSL was discontinued after 1 year. Three months later, the proteinuria and Fanconi syndrome worsened. PSL treatment was restarted (20 mg daily, 0.35 mg/kg/day) and markers indicated improvement. Case 3 was a 45-year-old woman with renal dysfunction and proteinuria. Tubulointerstitial nephritis and IgM-positive plasma cells were observed in a renal biopsy. The patient had PBC, Sjögren syndrome, d-RTA, and Fanconi syndrome, and the diagnosis of IgMPC-TIN was made. The patient was started on PSL (30 mg daily, 0.4 mg/kg/day) and disease markers decreased immediately. However, when PSL was tapered to 15 mg daily (0.2 mg/kg/day), the patient’s serum IgM levels increased; therefore, we maintained the PSL at 15 mg daily (0.2 mg/kg/day). Conclusion We report three cases of relapsed IgMPC-TIN associated with reduction or discontinuation of glucocorticoid therapy. In these cases, elevation of serum IgM preceded that of other markers such as urinary β2-microglobulin, proteinuria, and glycosuria. We recommend monitoring serum IgM levels while tapering glucocorticoids; a maintenance dose of glucocorticoid should be considered if relapse is suspected or anticipated.

We present a case of acute external ophthalmoplegia, hypersomnolence, and ataxia occurring 5 days after an episode of SARS-CoV-2 upper respiratory tract infection. The patient's serum returned positive for anti-GD1a antibodies. Guided by precedent cases, she was empirically started on a course of intravenous (IV) immunoglobulin for possible para-infectious Bickerstaff brainstem encephalitis (BBE). However, she failed to respond and subsequently developed autoimmune hemolytic anemia as well as renal tubular acidosis (type 1). Corroborative history from her family elucidated constitutional and sicca symptoms and she was eventually diagnosed with primary Sjögren syndrome (pSS) complicated by brainstem and cerebellar involvement. She was treated with IV cyclophosphamide and rituximab, after which her neurological deficits completely resolved at two months. [ABSTRACT FROM AUTHOR]

Simple Summary: This paper characterizes the immunotherapy-related adverse effects in the oral tissues, in a large series of patients. This includes a description of the severity of oral symptoms, immediate clinical presentation, treatment, chronicity despite holding the immunotherapy, and the development of oral cancer. The management of these patients exemplified new diagnostic tools, detailed clinical presentation that may assist to differentiate between various oral irAEs and outlines unique adjustments in the topical treatment and inclusion of a new treatment modality for these irAEs. Lastly, this paper raises the awareness for second primary oral cancer and possible risk for oral malignant transformation. (1) Background: Immunotherapy-related adverse effects (irAEs) have been reported to manifest in oral tissues, mainly as lichenoid and non-lichenoid lesions and salivary gland dysfunction; however, the characterization of oral irAEs and their clinical impact is limited. (2) Methods: This is a retrospective clinical chart review of 14 patients with oral irAEs, describing the impact of the oral irAEs in terms of the immediate effect, treatment, chronicity of the irAEs and the development of oral cancer. (3) Results: Common symptoms were pain and dry mouth, causing no-to-severe pain and/or dry mouth sensation. The immediate sequala ranged from sensitivity to certain foods up to elimination of oral intake. Treatment included conventional palliation techniques with or without systemic steroids. Discontinuation of the immunotherapy agents was required in 6 patients. Innovative treatment modalities included photobiomodulation for oral mucosal pain relief, and salivary gland intraductal irrigations for relief of salivary gland hypofunction. Late sequala included the development of proliferative leukoplakia and oral cancer. (4) Conclusions: Patients treated with immunotherapy may develop debilitating oral irAEs. They should be followed for oral involvement so treatment may be initiated when the symptoms are mild to avoid discontinuation of the immunotherapy. Patients that develop oral lichenoid lesions should receive long-term follow-up, as they may have higher risk for oral cancer. [ABSTRACT FROM AUTHOR]

PurposeTo evaluate the ocular signs and tests for keratoconjunctivitis sicca (KCS) in the absence of a gold standard.MethodsCross-sectional study of participants from the Sjögren's International Collaborative Clinical Alliance (SICCA) registry. Participants had oral/ocular/rheumatologic examinations, blood/saliva samples collected, and salivary gland biopsy. Latent class analysis (LCA) identified clusters of patients based on 3 to 4 predictor variables relating to signs or tests of KCS. The resulting model-based "gold standard" classification formed the basis for estimated sensitivity and specificity associated with these predictors.ResultsA total of 3514 participants were enrolled into SICCA, with 52.9% classified as SS. LCA revealed a best-fit model with 2 groups. For the gold standard-positive group, an abnormal tear breakup time, ocular staining score (OSS), and Schirmer I had a sensitivity of 99.5%, 91.0%, and 47.4%, respectively. For the gold standard-negative group, an abnormal tear breakup time, OSS, and Schirmer I had a specificity of 32.0%, 84.0%, and 88.5%, respectively. OSS components (fluorescein and lissamine staining), exhibited a sensitivity of 82.6% and 90.5%, respectively, in the gold standard-positive group, whereas these signs in the gold standard-negative group had a specificity of 88.8% and 73.0%, respectively.ConclusionsOSS and its components (fluorescein and lissamine staining) differentiated 2 groups from each other better than other KCS parameters and had relatively high sensitivity and specificity.

Tomas Loureiro,1 Sandra Rodrigues-Barros,1 Ana Rita Carreira,1 Filipe Gouveia-Moraes,1 Pedro Carreira,1 Ana Vide Escada,1 Paul Campos,1 Ines Machado,1 Nuno Campos,1 Renato Ambrosio Jr,2 Timothy J Archer,3 Dan Z Reinstein3 1Ophthalmology Department, Hospital Garcia de Orta, Almada, Portugal; 2Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil; 3London Vision Clinic, London, UKCorrespondence: Tomas Loureiro, Ophthalmology Department, Hospital Garcia de Orta, Avenida Torrado da Silva, Almada, 2805-267, Portugal, Tel +351 913 513 175, Email loureiro.tomas@gmail.comPurpose: To evaluate the changes on epithelial thickness before and after topical treatment in primary Sjögren syndrome-associated dry eye disease (SS-DED).Methods: This was a prospective study that included referred women with SS-DED and healthy age-matched controls. Corneal epithelial thickness was evaluated using high-definition anterior segment optical coherence tomography (Cirrus 5000 HD-OCT) in the baseline first consultation, and four weeks after treatment with preservative free 1mg/1mL sodium hyaluronate. Schirmer test 1 (ST1), tear break-up time (TBUT), tear meniscus height (TMH), SICCA Ocular Surface Score (SICCA OSS) and Ocular Surface Disease Index (OSDI) were evaluated. Statistical significance was defined as p-value < 0.05.Results: The study included 40 eyes, 20 with SS-DED and 20 controls. At baseline, SS-DED patients had lower ST1 (11.1 ± 2.2mm vs 14.1 ± 3.1mm, p< 0.01), faster TBUT (9.1 ± 1.8s vs 13.2 ± 1.1s, p< 0.01) and lower TMH (211.2 ± 68.4 μm vs 217.2 ± 60.1μm; p< 0.01) than the control group, whereas SICCA OSS and OSDI were higher (p< 0.01). The superior epithelium was thinner in SS-DED group (41.1 ± 3.2 μm vs 43.1± 2.3 μm, p< 0.01). After treatment, ST1, TBUT, TMH, SICCA OSS, and OSDI improved (p< 0.01), and superior epithelium thickened (p< 0.01) in the SS-DED group.Conclusion: Treatment with sodium hyaluronate improved ST1, TBUT, TMH, SICCA-OSS, and OSDI score. Superior epithelium tends to be thinner in SS-DED but becomes thicker with treatment. Our results seem to illustrate the morphological changes in the corneal epithelium in DED, which could be further recognized as a clinical biomarker of SS-DED.Keywords: dry eye disease, Sjogren’s syndrome, epithelial thickness, AS-OCT

Sjogren’s syndrome (SSj) is a chronic autoimmune disease mainly targeting the exocrine glands, but sometimes associating extra-glandular manifestations. Xerosis, purpura, Raynaud’s phenomenon, cutaneous vasculitis, annular erythema are the main forms of skin involvement. A 26-year-old female patient was admitted for diffuse erythematous rash and angioedema, xerophthalmia and symmetrical arthralgia of hand joints. Anti-nuclear antibodies, anti-SSA and anti-Ro52 antibodies were identified, Schirmer’s test was positive, thus the diagnoses of primary SSj and associated urticarial vasculitis were established. Treatment with oral methylprednisolone, azathioprine and hydroxychloroquine was initiated, with favourable response over the next week. Patients with primary SSj that develop cutaneous vasculitis, lymphadenopathies or lymphopenia may be at risk for additional extra-glandular manifestations, including non-Hodgkin lymphoma.

Sjogren syndrome is a slowly progressive autoimmune disease with lymphocytic infiltration of exocrine glands, peri-epithelial and extra-epithelial tissues. In light of better diagnostic modalities and improved treatment options, patients with Sjogren syndrome are now commonly encountered by anaesthetist for various surgeries. Here, we would like to describe an anaesthetic management of a parturient with bad obstetric history who was diagnosed with Sjogren syndrome and was planned for caesarean delivery. This article also reviewed anaesthetic problems faced due to inherent disease pathology and concurrent alterations in treatment modalities.

Purpose: The objective of the study was to compare the efficacy and safety of two concentration of autologous serum (AS) 20% vs 50% in recalcitrant moderate-to-severe dry eye patients. Methods: A double-blind prospective, interventional, and randomized study was done on 44 patients (80 eyes) clinically diagnosed with moderate-to-severe dry eye disease (DED) that was refractory to conventional treatment, and all patients were treated with AS20% or AS50% for 12 weeks. We documented Ocular Surface Disease Index (OSDI), tear film breakup time (TBUT), OXFORD corneal staining score (OSS), and Schirmer test (ST) at baseline, 2,4,8, and 12 weeks. These parameters were compared in both groups and between the groups by using Student's t-test. The study included 11 males and 33 females. Results: Out of 80 eyes, 33 eyes had moderate and 47 had severe DED. The age of patients in AS20% was 44.73 ± 14.37 years, and in AS50% was 46.41 ± 14.47 years. The most common etiology associated with DED was secondary Sjogren syndrome. In moderate DED, both the groups showed significant improvement in both subjective and objective parameters. But in severe DED, the AS20% group failed to show any significant improvement objectively, though subjective improvement was present. Conclusion: In refractory severe DED patients, AS50% is better option for treatment and in moderate DED both concentrations of autologous serum are effective.

HIGHLIGHTS 1. Sjögren’s syndrome is a chronic autoimmune disease that attacks the exocrine glands, especially lacrimal and salivary glands. 2. Comprehensive management of pregnant women with Sjögren’s syndrome was described. 3. Clinical and laboratory examination, risk assessment and also preconception counseling before planning pregnancy are needed by women with Sjögren’s syndrome. ABSTRACT Objective: To illustrate the comprehensive management of pregnant women with Sjögren syndrome. Case Report: A 24 years old women came to Dr. Soetomo General Academic Hospital, Surabaya, Indonesia, due to Sjögren syndrome in 35/36 weeks of gestasional age for routine examination. She was first diagnosed with Sjögren syndrome in February 2018 because she complained of dry eyes and hair fall out. This was her first pregnancy. Laboratory result showed positive ANA test. The patient had hypertension with controlled blood preasure and dry eyes. The patient was diagnosed with primigravida 35-36 weeks of pregnancy, single live intrauterine, head presentation, IUGR, screening preeclampsia was positive, and there was complication with Sjögren’s syndrome. The patient was treated by multidisciplinary team consisting of obstetricians, internists, ophthalmologists and neonatologists. Conclusion: Sjögren’s syndrome is a chronic autoimmune disease that attacks the exocrine glands, especially lacrimal and salivary glands. The exact cause of Sjögren's syndrome is still not known. Women with Sjögren’s syndrome should have clinical and laboratory examination, risk assessment and also preconception counseling before planning pregnancy because Sjögren syndrome was a rare case during pregnancy. Close monitoring and proper management was imperative to detect the early complication.

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.

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. [ABSTRACT FROM AUTHOR]

Background: Tubulointerstitial nephritis with IgM-positive plasma cells (IgMPC-TIN) is a newer disease about which there are many unclear points. Glucocorticoid therapy is effective in many cases of IgMPC-TIN; however, relapse during glucocorticoid tapering has been reported. Relapse and its treatment are poorly defined. Case Presentation: Case 1 was a 61-year-old man with renal dysfunction and proteinuria. Tubulointerstitial nephritis and IgM-positive plasma cells were observed in a renal biopsy. He was diagnosed with IgMPC-TIN accompanied by Fanconi syndrome and distal renal tubular acidosis (d-RTA). Prednisolone (PSL; 30 mg daily, 0.45 mg/kg/day) treatment was highly effective, and PSL was gradually tapered and discontinued after 1 year. However, 1 month after PSL discontinuation, therapeutic markers were elevated. Therefore, PSL (10 mg daily, 0.15 mg/kg/day) was administered, and the markers indicated improvement. Case 2 was a 43-year-old woman referred for renal dysfunction and proteinuria. Laboratory data revealed that she had primary biliary cholangitis (PBC), d-RTA, and Fanconi syndrome. A renal biopsy showed accumulation of IgM-positive plasma cells in the tubulointerstitium without any glomerular changes. A diagnosis of IgMPC-TIN was made and the patient was started on PSL (35 mg daily, 0.6 mg/kg/day). Therapeutic markers decreased immediately and PSL was discontinued after 1 year. Three months later, the proteinuria and Fanconi syndrome worsened. PSL treatment was restarted (20 mg daily, 0.35 mg/kg/day) and markers indicated improvement. Case 3 was a 45-year-old woman with renal dysfunction and proteinuria. Tubulointerstitial nephritis and IgM-positive plasma cells were observed in a renal biopsy. The patient had PBC, Sjögren syndrome, d-RTA, and Fanconi syndrome, and the diagnosis of IgMPC-TIN was made. The patient was started on PSL (30 mg daily, 0.4 mg/kg/day) and disease markers decreased immediately. However, when PSL was tapered to 15 mg daily (0.2 mg/kg/day), the patient's serum IgM levels increased; therefore, we maintained the PSL at 15 mg daily (0.2 mg/kg/day). Conclusion: We report three cases of relapsed IgMPC-TIN associated with reduction or discontinuation of glucocorticoid therapy. In these cases, elevation of serum IgM preceded that of other markers such as urinary β2-microglobulin, proteinuria, and glycosuria. We recommend monitoring serum IgM levels while tapering glucocorticoids; a maintenance dose of glucocorticoid should be considered if relapse is suspected or anticipated. [ABSTRACT FROM AUTHOR]

This study aimed to compare tear film viscosity (TFV) in Sjögren and non-Sjögren dry eye diseases (DEDs). This was a cross-sectional observational study. A total of 68 DED patients were enrolled, including 32 patients with Sjögren syndrome (SS) and 36 without SS. TFV was assessed by a tear film analyzer and determined by the momentary moving speed (MMS; MMS (t) = α × t−β, t = time (s)) with its power-law fitting-derived parameters (α and β). Among the four indices of TFV (MMS (0.1 s), MMS (2.0 s), α, and β), the SS-DED patients had significantly lower MMS (0.1 s) (p = 2.01 × 10−5), α (p = 0.0375), and β (p = 0.0076). The SS-DED group also had significantly higher OSDI, lower central and nasal tear meniscus height (TMH), and higher OSS. MMS (0.1 s) was significantly correlated with nasal TMH and OSS (ρ = 0.2520, p = 0.0381 in nasal TMH; ρ = −0.3487, p = 0.0036 in OSS). Index β was not correlated with any non-TFV tests. In conclusion, MMS (0.1 s), α, and β are promising TFV indices in distinguishing SS-DED from non-SS-DED patients early. Among these TFV indices, lower MMS is the best alternative clue for detecting SS-DED. [ABSTRACT FROM AUTHOR]

Anti-aquaporin-4 antibody (AQP4-IgG)-positive neuromyelitis optica spectrum disorder (NMOSD) and Sjögren syndrome (SS) are likely comorbidities. However, the exact effects of age and disease duration on the positivity rates of serum anti-Ro/SSA and anti-La/SSB (anti-SSA/SSB) antibodies and the presence of sicca symptoms in patients with AQP4-IgG remain unknown. In the present study, we evaluated the data from patients with suspected NMOSD who had neurological episodes and tested for serum AQP4-IgG. Associations between the presence of serum AQP4-IgG and SS-related findings were evaluated. The presence of anti-SSA/SSB antibodies [odds ratio (OR), 7.34; 95% confidence interval (CI), 5.71-9.43; p < 0.0001] and that of sicca symptoms (OR, 2.08; 95% CI, 1.67-2.58; p < 0.0001) were both higher in patients with AQP4-IgG (n = 1,651) than in those without AQP4-IgG (n = 2,796). Meanwhile, neither age nor the elapsed time from neurological onset was linked to the prevalence of anti-SSA/SSB antibodies or sicca symptoms, and the prevalence rates of the SS-related factors were elevated since the onset of neurological episodes in those with AQP4-IgG. The frequency of sicca symptoms among those with anti-SSA/SSB antibodies was irrespective of AQP4-IgG (OR, 1.11; 95% CI, 0.67-1.85; p = 0.6892). The measured AQP4-IgG titers did not differ significantly according to the presence of anti-SSA/SSB antibodies (p = 0.2386; Mann-Whitney U test). In summary, age and duration of NMOSD were not the factors producing an elevated prevalence of anti-SSA/SSB antibodies and sicca symptoms in patients with AQP4-IgG, implying that the occurrence of comorbid SS is likely to temporarily precede or synchronize with the onset of AQP4-IgG-positive NMOSD. [ABSTRACT FROM AUTHOR]