Sjögren's Syndrome Research Articles

Sjögren’s Disease and Gastroesophageal Reflux Disease: What Is Their Evidence-Based Link?

Sjögren’s disease (SjD), or primary Sjögren’s syndrome (pSS), is a heterogeneous chronic autoimmune disorder with multiple clinical manifestations that can develop into non-Hodgkin’s lymphoma in mucosa-associated lymphoid tissue. SjD is one of the autoimmune diseases with the maximum delayed diagnosis due to its insidious onset, heterogeneous clinical features and varied course. It is increasingly recognized that extraglandular manifestations represent a clinical challenge for patients with SjD. The European League Against Rheumatism (EULAR) Sjögren’s Syndrome (SS) Disease Activity Index (ESSDAI) is a systemic disease activity index designed to measure disease activity in patients with primary Sjogren’s syndrome. It consists of 12 domains: cutaneous, pulmonary, renal, articular, muscular, peripheral nervous system, central nervous system, hematological, glandular, constitutional, lymphadenopathy and lymphoma, biological. More than a quarter of patients with pSS may have systemic features that are not included in the ESSDAI classification, i.e., various cardiovascular, ophthalmic, ENT, and other systemic or organ involvement that increase the magnitude of the systemic phenotype in the disease. The ESSDAI also excludes the gastrointestinal (GI) tract, and unfortunately, GI manifestations are not routinely assessed. Gastroesophageal reflux disease (GERD) is one of the most prevalent gastrointestinal disorders, impairing quality of life and consuming a large volume of medical resources. Recently carried out the Mendelian randomized trial confirmed the causal link between SjD and gastroesophageal reflux disease (GERD) and showed that GERD is a risk factor for SjD. This review aims to provide an overview of the research describing evidenced based links between Sjögren’s disease and gastroesophageal reflux disease, with the intention of ensuring that any systemic pathology in Sjögren’s disease is properly assessed and that management of the disease is directed towards the patient. A comprehensive literature search was carried out on PubMed, Web of Science, Scopus and the Cochrane Library databases. Two researchers searched for published studies indexed from inception to 1 September 2024 using the keywords ‘Sjögren’s syndrome’ OR ‘Sjögren’s disease’ AND ‘gastroesophageal reflux disease’ AND ‘microbiota’ OR microbiota dysbiosis’. We limited our search for scientific articles to human studies, and only included articles in English. Overall, there is a lack of evidence-based studies assessing the association between GERD and Sjögren’s disease and the changes in the microbiota associated with GERD in a multidisciplinary setting. Such studies are needed for the future, as this will improve the early diagnosis of Sjögren’s disease and the personalized management of the disease.

The Relationship Between Systemic Immune Inflammatory Level and Dry Eye in Patients with Sjögren’s Syndrome

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.

Efficacy of combined administration of Baekhogainsam-Tang and low-dose pilocarpine on frequent intractable xerostomia: Study protocol for a randomized controlled trial.

Intractable xerostomia is defined as the subjective perception of dry mouth and persistent salivary gland hypofunction. Pilocarpine is an approved salivary sialagogue that is frequently prescribed for the treatment of intractable xerostomia; however, it often exhibits more side effects at high-doses and limited effectiveness at low-doses. Baekhogainsam-Tang (BIT) is a common herbal formula used by patients complaining of sore throats and thirst. It seems that BIT can compensate for the insufficient effect of low-dose pilocarpine. However, no clinical trials have studied the efficacy of combined administration of BIT and low-dose pilocarpine for intractable xerostomia. We aim to assess the non-inferior efficacy and fewer side effects of combined administration of BIT and low-dose pilocarpine compared with the administration of high-dose pilocarpine. A randomized, open-label, parallel-group, multi-center trial will be conducted. A total of 120 patients with Sjogren's syndrome having an unstimulated salivary flow rate (SFR) ≤0.1 mL/min or who have undergone radiotherapy to the head and neck with an unstimulated SFR ≤0.25 mL/min will be recruited competitively. They will be randomly allocated to either the experimental or control groups. The experimental group will receive BIT herbal granules three times and pilocarpine (2.5-mg) four times daily; meanwhile, the control group will receive only 5-mg pilocarpine four times daily for 12 weeks. The primary outcome is unstimulated SFR after 12 weeks of treatment. Secondary outcomes are stimulated SFR after 12 weeks of medication, as well as differences and mean percentage changes in unstimulated and stimulated SFR, visual analog scale, salivary scintigraphy, and questionnaires for both oral symptoms and quality of life during the clinical trial. An independent T test or Mann-Whitney U test will be performed to compare values between the two groups. The Paired T test or Wilcoxon signed-rank test will be performed to compare intragroup continuous values. This trial will be significant evidence on the efficacy and safety of combined use of BIT and low-dose pilocarpine to treat intractable xerostomia. The Clinical Research Information Service of the Republic of Korea (ISRCTN, KCT0005982). Registered on 10 February 2021.

A descriptive analysis of 21 patients with pulmonary amyloidosis: An observational study.

Pulmonary amyloidosis is an extremely rare disease, often detected incidentally because of its asymptomatic nature and potential to result in fatal outcomes. In this study, we aimed to present the clinical and radiological features of patients diagnosed with pulmonary amyloidosis by biopsy. This descriptive study included 21 patients with pathologically diagnosed pulmonary amyloidosis. Pulmonary amyloidosis was classified as diffuse alveolar-septal amyloidosis (DASA), cystic amyloidosis (CPA), tracheobronchial amyloidosis (TBA), nodular amyloidosis (NPA), and extraparenchymal pulmonary amyloidosis (pleural and mediastinal lymph node). Clinical, bronchoscopic, and radiological specific characteristics were presented in detail to be used for differential diagnosis. The median age of the patients was 63 (40-83) years, and 14 (66.7%) were male. Twenty patients (95.2%) presented with at least 1 comorbidity. All patients diagnosed with tracheobronchial amyloidosis were symptomatic at presentation, whereas those diagnosed with NPA/extraparenchymal amyloidosis were often asymptomatic. The patients included 1 case of DASA, 1 case of CPA, 10 cases of NPA, 6 cases of TBA, and 3 cases of extraparenchymal amyloidosis involving the mediastinal lymph node and pleura. Sixteen patients (76.2%) were classified as localized amyloidosis, while 5 patients (23.8%) were classified as systemic amyloidosis following the diagnosis of multiple myeloma, monoclonal gammopathy of undetermined significance, systemic lupus erythematosus, Sjogren's syndrome, and B-cell lymphoma. Bronchoscopic biopsies were sufficient for diagnosis, and notably, even transbronchial needle aspiration could be a useful diagnostic method. During the follow-up, we observed that the disease remained stable without progression. However, it is important to note that patients with concurrent malignancies experience fatal outcomes. In conclusion, it is crucial to distinguish pulmonary amyloidosis from other pulmonary diseases such as malignancies, infectious diseases, and interstitial lung diseases, which may have similar clinical and radiological findings. Bronchoscopic diagnostic methods are usually sufficient for the diagnosis. Although patients with pulmonary involvement mostly remain stable during long-term follow-up without progression, it is important to consider the risk of malignancy.

Classification of salivary gland biopsies in Sjögren's syndrome by a convolutional neural network using an auto-machine learning platform.

The histopathological analysis of minor salivary gland biopsies, particularly through the quantification of the Focus Score (FS), is pivotal in the diagnostic workflow for Sjögren's Syndrome (SS). AI-based image recognition using deep learning models has demonstrated potential in enhancing diagnostic accuracy and efficiency in preclinical research. The primary aim of this investigation was to utilize an auto-machine learning (autoML) platform for the automated segmentation and quantification of FS on histopathological slides, aiming to augment diagnostic precision and speed in SS. A cohort comprising 86 patients with sicca syndrome (37 diagnosed with SS based on the 2016 ACR/EULAR Classification Criteria and 49 non-SS) was selected for an in-depth histological examination. A repository of 172 slides (two per patient) was assembled, encompassing 74 slides meeting the classificatory thresholds for SS (FS ≥ 1, indicative of lymphocytic infiltration) and 98 slides showcasing normal salivary gland histology. The autoML platform utilized (Giotto, L2F, Lausanne Switzerland) employed a Convolutional Neural Network (CNN) architecture (ResNet-152) for the training and validation phases, using a dataset of 172 slides. The developed model exhibited a reliability score of 0.88, proficiently distinguishing SS cases, with a sensitivity of 89.47% (95% CI: 66.86% to 98.70%) and a specificity of 88.24% (95% CI: 63.56% to 98.54%). The model found histological slides of suboptimal quality (e.g., those compromised during fixation or staining processes) to be the most challenging for accurate classification. AutoML platforms offer a rapid and flexible approach to developing machine learning models, even with smaller datasets, as demonstrated in this study for SS. These platforms hold significant potential for enhancing diagnostic precision and efficiency in both clinical and research settings. Multicentric studies with larger patient cohorts are essential for thorough evaluation and validation of this innovative diagnostic approach.

Characterization of anti-EBNA-1 antibodies and exploration of their molecular mimicry potential in an EBV-infected Sjögren's syndrome patient

There is a potential link between autoimmune diseases and Epstein-Barr virus (EBV) infections, with EBV playing a substantial role in the onset of Sjögren's syndrome (SjS). Some EBV proteins could mimic host self-antigens post-infection, leading to molecular mimicry. This similarity may cause the immune system to attack its tissues mistakenly. Among the various proteins associated with EBV, nuclear antigen 1 (EBNA-1) is essential for the latent replication of infected cells and is prevalent in all EBV-related diseases. In the study, single-chain variable fragment (scFv) antibodies targeting EBNA-1 were isolated using phage display technology from a primary SjS patient who also had a chronic active EBV infection. The specific clones were enriched after panning, and the binding activity of selected scFvs targeting EBNA-1 was confirmed. Sequence analysis indicated that the scFvs exhibiting positive signals could be grouped into five clones, all of which used homologous heavy chain V regions derived from germline Vh4-39, and two types of light chain V regions stemming from germline Vλ1-44 and Vλ3-15. These scFvs were found to exhibit a high degree of somatic mutations, likely indicative of antigen selection. Of the scFvs, P1-3 demonstrated the strongest binding affinity to EBNA-1, exhibiting a determined value of 7.3 x 10-8 M, and showed cross-reactivity to the SjS associated La/SSB self-antigen. The experimental results combined with AlphaFold 3 predictions revealed a potential epitope for scFv P1-3 binding to EBNA-1. Additionally, scFv P1-3 could also cross-bind to the modeled structure of La/SSB. We inferred a possible structural correlation between EBNA-1 and La/SSB involving an X2AX6PG epitope motif. This research contributes to our understanding of the structural basis of the interactions between antibodies and EBNA-1, shedding light on the VH and VL gene usage of anti-EBNA-1 antibodies in EBV-infected SjS patients and the potential origins of autoantibodies.

Sjögren's syndrome positive for isolated anti-Ro52/SS-A antibody and anti-centromere antibody.

This current case report describes a Japanese woman in her 80s with xerostomia who presented with salivary gland dysfunction. She was positive for isolated anti-Ro52/SS-A antibody as determined by a chemiluminescent enzyme immunoassay and positive on a fluorescence enzyme immunoassay that recognizes both Ro52 and Ro60 antigens. A high serum concentration of anti-Ro52/SS-A antibody was determined by an enzyme-linked immunosorbent assay. A high anti-centromere antibodies (ACA) titre was also observed. Although Raynaud's phenomenon or a high serum immunoglobulin G concentration were not observed, Masson-trichrome staining of the patient's labial salivary glands showed considerable fibrosis. Her serum type I and type II interferon concentrations were normal. The present patient is the first with Sjögren's syndrome (SS) to exhibit isolated anti-Ro52/SS-A antibody and ACA without anti-Ro60/SS-A antibody. This current case report presents her case together with those of four other SS patients who were positive for isolated anti-Ro52/SS-A antibody. The SS literature also includes cases positive for ACA and describes clinical characteristics. The other four SS patients with isolated anti-Ro52/SS-A antibody described here had no ACA; interstitial pneumonia and polyneuropathy were observed in these cases, although there was no consistent tendency regarding types I and II interferon.

Hypertension and Cardiovascular Outcomes in Inflammatory and Autoimmune Diseases: A Systematic Review and Meta-analysis.

This review aimed to investigate the prevalence of hypertension and cardiovascular (CV) complications in various inflammatory and autoimmune diseases (IAD). Despite recent improvements in the management of IAD, patients with IAD still have an increased CV mortality and CV complications, mostly related to CV risk factors such as hypertension and inflammation. We systematically searched MEDLINE and EMBASE libraries for controlled studies involving hypertension and CV complications in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), psoriasis including psoriatic arthritis (PsA), Sjogren's syndrome (SS), or antineutrophil cytoplasmic antibody-associated vasculitis (AAV) between January 2000 and March 2022. We extracted data on the prevalence of hypertension and CV complications. Then, random-effects meta-analyses and exploratory multivariate meta-regression were performed to explore factors related to the prevalence of hypertension.Of 2726 studies screened, 122 were selected for the meta-analysis. The prevalence of hypertension was higher among patients with IAD than controls, with an overall unadjusted odds ratio (OR) [95% confidence interval] of 1.67 [1.58-1.76] and an adjusted OR of 1.36 [1.24-1.50]. All diseases were found to be associated with increased risk of hypertension: SLE, adjusted OR 3.40 [1.93-6.00]; psoriasis, OR 1.32 [1.16-1.51]; PsA, OR 1.49 [1.15-1.94]; RA, OR 1.28 [1.04-1.58]; SS, OR 2.02 [1.19-3.44]. Age and female sex were significantly associated with hypertension in patients with IAD. The risk of CV complications was increased: ischemic heart disease, adjusted OR 1.38 [1.21-1.57]; cerebrovascular disease, OR 1.37 [1.03-1.81]; heart failure, OR 1.28 [1.05-1.55]; atherosclerotic plaques presence, OR 2.46 [1.84-3.29].The prevalence of hypertension and CV complications is higher among patients with IAD. Screening and management of hypertension appears to be of paramount importance in these patients.

A Stratification Approach Based on Salivary Gland Ultrasonography for Assessing Secretory Function in Sjögren's Disease.

Our aim was to develop an ultrasonographic scoring model for staging hypofunction of salivary gland (SG) in patients suffering from Sjögren's disease (SjD). The assessment of SG secretory hypofunction was conducted by measuring whole salivary flows. B-mode ultrasonography was performed bilaterally on the parotid and submandibular glands to evaluate the Gland score and OMERACT score quantitatively. The correlation between these scores and SG secretory function in SjD patients was analyzed, leading to the development of an ultrasonographic scoring model for staging SG hypofunction. A one-center derivation cohort comprising 164 SjD patients and a double-center validation cohort consisting of 107 SjD patients were included. Both ultrasonographic scores demonstrated excellent discriminatory ability between SjD patients with hypofunction and those with normal function (both AUC>0.8, p<0.001). A novel ultrasonographic scoring model revealed that low total OMERACT scores (<5) indicated initial-stage SG hypofunction, while high scores (>9) suggested end-stage hypofunction. Conversely, patients with moderate-level total OMERACT scores (5~9) require further stratification using total Gland scores. The incidence of SG hypofunction among all 271 SjD patients was found to be 18% in the initial stage, 58% in the progressive stage, and 100% in the end stage (p<0.001). Furthermore, the incidence of lacrimal gland involvement and hyperglobulinemia (IgG>16 IU/mL) was significantly lower in the initial-stage patients compared to those at other stages (all p<0.001). The novel ultrasonographic scoring model incorporates precise definitions for each stage, providing a robust and clinically significant approach to stratify salivary gland secretory hypofunction in SjD.

Etiology, Diagnosis And Therapy Of Burning Mouth Syndrome In Denture Wearers - Review

Background: The Burning Month Syndrome (BMS) is an oral mucosa pain - with or without inflammatory signs - without any specific lesion. Burning mouth syndrome (BMS) is multifactorial in origin which is typically characterized by burning and painful sensation in an oral cavity. The cause of BMS is not known, therefore a complex association of biological, psychological and neurophatic factors has been identified. BMS is classified as an idiopathic (nociplastic) orofacial pain with or without somatosensory changes by International Classification of Orofacial Pain (ICOP 2020). The aim of this study was to understand the etiological factors (local, systemic, and psychosocial) which may be responsible for oral burning associated with BMS, and to offer the prosthodontic practitioners possibilities for treatment generally at all patients, especially at denture wearers in solving this problem. Matherials and methods: Review of literature was used to analyze the etiological factors for BMS, pain characteristics, diagnostic criteria and treatment possibilities for BMS condition at patients with dentures. Results: BMS can be divided into three types depending on the intensity of pain. There are also few possible theories behind the cause of BMS. Local oral factors are: denture acrylic allergies, poorly fitting dentures, para functional activities, salivary gland dysfunction, taste dysfunction, infectious agents, periodontal diseases, peripheral nerve damage. Systemic factors are: nutritional deficiency/anemia, central nervous system disorders, psychological disorders, hormonal changes and diabetes mellitus, xerostomia and Sjogren's syndrome. Discussion: Problems with dentures are important factors in the burning symptoms. Inadequate denture retention and stability can induce abnormal tongue activity and become a habit to retain the denture extensions and in adequate freeway space increase load on the denture bearing areas which results of burning mouth sensation. It is clinically helpful if patients find that removal of the denture reliefs their symptoms. Although the short‐term follow‐up studies may show potential symptomatic improvement with treatment in patients with BMS, the long‐ term outcomes for BMS remain unclear. In perspective, complete understanding of the etiology and pathogenesis is imperative to the development of novel and efficacious therapeutic strategies and will guide overall prognosis of the disease in the future. Conclusion: Although different etiological theories have been proposed to explain primary burning mouth syndrome, none have received universal acceptance to date. BMS is a difficult and challenging problem for the dental practitioner. It is a clinical diagnosis made via the exclusion of all other causes. No universally accepted diagnostic criteria, laboratory tests, imaging studies or other modalities definitively diagnose or exclude BMS. The key to successful management is a good diagnostic work-up and coordination between the prosthodontic practitioners and appropriate physicians and psychologists. All this together will help prosthodontics practitioners to better diagnose and treat the BMS.

Causal associations of Sjögren's syndrome with cardiovascular disease: A two-sample Mendelian randomization study

Study objectivesObservational and cohort studies have associated Sjögren's syndrome (SS) with various types of cardiovascular disease (CVD), yet causal relationships have not been established. We employed Mendelian randomization (MR) to investigate potential causal links between SS and CVD in the general population. MethodsWe conducted a two-sample MR analysis using data from four distinct sources for 11 genome-wide significant single nucleotide polymorphisms (SNPs) associated with SS and data for 13 types of CVD sourced from FinnGen, IEU OpenGWAS, and GWAS catalog. The inverse variance weighted method was selected as the primary analytical approach, complemented by various sensitivity analyses. ResultsMR analyses provide evidence of a significantly increased risk of ischemic stroke associated with genetically predicted SS (odds ratio [OR], 1.0237; 95 % CI, 1.0096 to 1.0379; p = 0.0009), as well as suggestive evidence of a potential causal relationship between SS and an increased risk of chronic heart failure (OR, 1.0302; 95 % CI, 1.0020 to 1.0592; p = 0.0355). Sensitivity analyses reinforced these associations, demonstrating robustness and consistency across multiple statistical methods. The secondary analysis, conducted after outlier correction using MR-PRESSO and RadialMR methods, reaffirmed these associations and also indicated a suggestive causal link between SS and non-rheumatic valvular heart disease (OR, 1.0251; 95 % CI, 1.0021 to 1.0486; p = 0.0323). ConclusionsThis study demonstrates that genetically predicted SS is a potential causative risk factor for ischemic stroke, chronic heart failure, and non-rheumatic valvular heart disease on a large-scale population. However, further research incorporating ancestral diversity is required to confirm a causal relationship between SS and CVD.

Possible involvement of Toll-like receptor 8-positive monocytes/macrophages in the pathogenesis of Sjögren's disease.

Sjögren's disease (SjD) is an autoimmune disease marked by lymphocytic infiltration of salivary and lacrimal glands, leading to glandular dysfunction, where CD4-positive helper T (Th) cells and their cytokines are crucial in the pathogenesis. Recent studies have demonstrated that Toll-like receptors (TLRs), particularly those recognizing immune complexes containing DNA and RNA, contribute to Th cell activation in various autoimmune diseases. This study explores the expression and function of these TLRs in SjD. DNA microarray analysis of salivary gland tissue from six SjD patients and real-time PCR (n = 32) was used to identify overexpressed TLRs. Single-cell RNA sequencing (scRNA-seq) was performed using tissue lesions and integrated with published scRNA-seq data from tissues and peripheral blood mononuclear cells to examine gene expression in macrophages and monocytes. Finally, multi-color immunofluorescence staining was conducted to confirm TLR8 expression and function in SjD lesions (n = 19). DNA microarray analysis revealed the up-regulation of TLR8, along with other TLRs and innate immune response genes in SjD. Real-time PCR showed significant up-regulation of TLR7 and TLR8. TLR8 up-regulated in both analyses. In scRNA-seq analysis, the TLR8-expressing cluster comprised macrophages and monocytes, which also produced T cell activation genes like CD86. TLR8-positive macrophages infiltrated inflammatory sites and frequently expressed CD86 in quantitative imaging approaches. These results suggest that infiltrating monocytes and macrophages may produce cytokines and chemokines through TLR8 stimulation, potentially enhancing B7 molecule expression, promoting the adaptive immune response, and contributing to SjD pathogenesis.

A Dual Diagnosis of Myasthenia Gravis and Sjogren’s Syndrome in a Hispanic Patient: A Case-based Discussion of Clinical Findings, Therapeutic Implications, and Culturally Competent Care

The co-occurrence of myasthenia gravis (MG) and Sjogren's syndrome (SS) in a young, Hispanic, female patient underscores the diagnostic and therapeutic complexities inherent in autoimmune disorders. MG, a rare neuromuscular disorder characterized by autoantibodies impairing neuromuscular transmission, leads to variable muscle weakness and fatigue, notably affecting ocular and bulbar muscles. SS, an autoimmune condition with systemic manifestations, primarily affects secretory glands, resulting in symptoms such as xerostomia and xerophthalmia. Both conditions have higher prevalence rates in females, with MG particularly affecting young women under 40. Herein we present a case report and case-based discussion on diagnostic and management challenges of these two autoimmune conditions while highlighting issues specific to the Hispanic and underrepresented populations. Our goal is to highlight the intricate interplay between these two autoimmune pathologies to allow for more rapid recognition and reduce delay in diagnosis.

Evaluation of traditional Chinese medicine tea bag TBDESJS in patients with Sjögren's syndrome and dry eye syndrome: A phase II pilot study.

Sjögren's syndrome (SJS) and dry eye syndrome (DES) are characterized by ocular dryness from inadequate tear production or excessive evaporation. To evaluate the effectiveness of TBDESJS (Chun-Yu-Ching-Hua-Yin, CYCHY), a TCM tea bag, in treating SJS and DES patients compared with healthy controls (NHC). This phase II pilot study included 100 participants (60 SJS, 30 DES, 10 NHC) across 8 weeks, assessing changes in Schirmer's test, OSDI, ESSPRI, PSQI, FIRST, and artificial tear usage, using repeated measurement ANOVA and Tukey's honestly significant difference (HSD) for analysis. Total 97 subjects completed the trial, for the left eye (OS) of Schirmer's test, significant improvements at 4, and 8 weeks were observed in SJS (0.13 ± 0.43-5.77 ± 2.87, and 7.60 ± 4.84 mm) and DES (0.21 ± 0.41-6.21 ± 2.97, and 7.86 ± 3.47 mm) (all p < .001). For the right eye (OD), significant improvements were observed in SJS (0.13 ± 0.39-6.77 ± 4.53, and 8.79 ± 5.92 mm) and DES (0.34 ± 0.55-6.59 ± 2.50, and 8.24 ± 3.42 mm) (all p < .001). Secondary outcomes showed reduced the dryness of ESSPRI scores in SJS (6.37 ± 1.97-5.57 ± 1.79, p < .001) and DES (6.10 ± 1.97-5.28 ± 2.23, p < .05). PSQI global scores improved significantly in all groups at 8 weeks (p < .05). Artificial tear usage decreased in SJS (4.93 ± 2.45-1.00 ± 0.82 times/day), DES (4.47 ± 1.99-0.66 ± 0.67 times/day) (all p < .001). No serious adverse events in this study. TBDESJS significantly improved tear production, ocular dryness, and sleep quality, indicating potential neural regulation, anti-inflammatory and immunomodulatory benefits. These findings advocate for TBDESJS (Chun-Yu-Ching-Hua-Yin, CYCHY)'s comprehensive therapeutic value in SJS and DES treatment, emphasizing the need for further research to understand long-term effects and mechanisms.

Loss of STIM1 and STIM2 in salivary glands disrupts ANO1 function but does not induce Sjogren's disease.

Ca2+ signaling via the store operated Ca2+ entry (SOCE) mediated by STIM1 and STIM2 proteins and the ORAI1 Ca2+ channel is important in saliva fluid secretion and has been associated with Sjogren's disease (SjD). However, there are no studies addressing STIM1/2 dysfunction in salivary glands or SjD in animal models. We report that mice lacking Stim1 and Stim2 (Stim1/2K14Cre(+)) in salivary glands exhibited reduced Ca2+ levels and hyposalivate. SOCE was functionally required for the activation of the Ca2+ activated Cl- channel ANO1. Ageing Stim1/2K14Cre(+) mice showed no evidence of lymphocytic infiltration or increased levels of autoantibodies characteristic of SjD, possibly associated with a downregulation of toll-like receptor 8 (Tlr8) expression. Salivary gland biopsies of SjD patients showed increased expression of STIM1 and TLR7/8. Our study shows that SOCE activates ANO1 function and fluid secretion in salivary glands and highlights a potential link between SOCE and TLR signaling in SjD.

Pulmonary Progressive Fibrosis in Rheumatoid Arthritis and Primary Sjogren Syndrome: Similarities and Differences.

Background: Progressive pulmonary fibrosis (PPF) has been associated with a worse prognosis, even when interstitial lung disease (ILD) is related to rheumatic diseases. Since many differences are detectable among rheumatic diseases in prevalence and features of ILD, we aimed to investigate features of PPF in different rheumatic diseases, namely rheumatoid arthritis (RA) and primary Sjogren's syndrome (pSS). Methods: In an Italian multicentre cross-sectional study, consecutive pSS or RA patients with a diagnosis of ILD from at least two years were enrolled. For each patient, demographic, clinical, and serological data, other than chest high-resolution computed tomography and lung function tests, were recorded at the enrolment and after 2 years. Results: Among 232 patients, namely 156 RA-ILD and 76 pSS-ILD, a PPF was recorded in 38.8% of cases, without differences between the two diseases. Analysing patients with a PPF, usual interstitial pneumonia was significantly more frequent in RA than pSS (71.4% and 44.4%, respectively; p = 0.019), while ILD preceded the diagnosis of the rheumatic disease in 29.1% of RA and 89.5% of pSS (p < 0.001). Finally, RA patients were significantly younger than pSS at the diagnosis of the rheumatic disease (p < 0.001). Conclusions: In conclusion, although there is a similar prevalence of PPF in RA-ILD and pSS-ILD, we demonstrated for the first time that the two conditions differ in terms of radiological patterns and demographic and clinical features, suggesting that specific factors related to such diseases might influence the lung involvement over time. Prospective studies could investigate if these specificities could induce different responses to the treatment.

Warning values of serum total kappa/lambda ratio for M-proteinemia

BackgroundTo introduce the serum total kappa/lambda ratio (K/L) in humoral immunity testing reports to improve the detection rate of M-proteinemia.Methods156 M protein-positive and 5464 M protein-negative samples confirmed by serum immunofixation electrophoresis(sIFE) were accumulated from January 2021 to December 2023 in the First Affiliated Hospital of Soochow University and the contents of immunoglobulins (IgG, IgA, IgM, kappa and lambda) were tested by Beckman IMMAGE800. All the samples were divided into two groups by time: the modeling group and the validation group. The K/L values in the modeling group were analyzed by SPSS 27.0 to get the receiver operating characteristic curve (ROC). Furthermore, a more in-depth analysis was conducted to verify the reliability of the optimal cutoff values in the validation group. In addition, the levels of immunoglobulins of another group including 106 patients with definite diagnosis of monoclonal gammopathy ranging from January 2021 to June 2024 were traced back to improve the diagnostic efficiency.ResultsThe optimal cutoff values of K/L were 2.31 and 1.43 corresponding to K-type and L-type M-proteinemia respectively by ROC analysis. The sensitivity and specificity were validated as 76.14% and 77.42%. False positives were mainly found in samples with systemic sclerosis (36.84%), hypohepatia (28.71%) and sicca syndrome (27.27%). While false negatives were mainly found in IgA monoclonal gammopathy (38.39%) and IgM monoclonal gammopathy (28.57%). Combining with the detection rules of IgG, IgA and IgM, the sensitivities for the diagnosis of immunoglobulin light chain amyloidosis(AL) and monoclonal gammopathy of undetermined significance(MGUS) can be increased to 83.33% and 85%.ConclusionsK/L > 2.31 and K/L < 1.43 can be used as warning values for M-proteinemia. In addition, the content of the heavy chain in IgA- or IgM-type M-proteinemia may be considered to improve the detection rate.

Removable dental prostheses for patients with Sjögren's syndrome

Sjögren's syndrome (SS) is a chronic autoimmune condition primarily affecting the salivary and lacrimal glands, leading to pronounced dry mouth (xerostomia) and dry eyes. These symptoms create unique challenges for SS patients requiring removable dental prostheses, as the lack of saliva significantly impacts the retention, comfort, and overall effectiveness of these devices. Without adequate saliva, prosthetic retention diminishes, and patients frequently experience issues such as mucosal irritation and increased susceptibility to infections. To address these issues, tailored material choices are critical in designing effective prosthetic solutions. Soft liners, moisture-retentive acrylics, and antimicrobial coatings are among the innovations improving both retention and comfort for SS patients. The aesthetic and functional outcomes of prosthetic solutions are also essential considerations. Enhanced retention mechanisms, such as implant-supported overdentures, not only improve masticatory performance but also aid in preserving the patient’s facial profile and lip support. Advanced materials offering translucency and color stability contribute to a more natural appearance, which is critical for patient satisfaction. The maintenance of these prostheses requires specific care routines to mitigate microbial buildup and tissue irritation. Specialized cleaning agents and salivary substitutes help maintain hygiene and reduce discomfort, while regular follow-up visits enable timely adjustments to accommodate tissue changes and extend the prosthesis lifespan. Implementing a comprehensive approach that considers material selection, functional and aesthetic outcomes, and maintenance strategies can greatly enhance the quality of life for SS patients. By understanding and addressing the specific needs associated with xerostomic conditions, dental professionals can provide prosthetic solutions that offer both reliability and comfort in this challenging context. Regular patient education and diligent care routines remain essential to ensure the long-term success and durability of removable dental prostheses for individuals with SS.

Primary headache in SLE –systematic review and meta-analysis

ObjectivesTo systematically review and synthesize literature on: 1) the overall prevalence of primary headaches and specifically migraines, in patients with lupus since previous systematic review published in 2004; 2) the risk factors associated with primary headaches in patients with lupus; 3) the association of primary headaches with structural brain changes; and 4) “lupus headaches”. MethodsThis review used (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) PRISMA guidelines and literature searches in four databases: Ovid-based Medline, Embase, PsycINFO, and Cochrane Database of Systematic Reviews from inception until 4/2022. Papers on primary headaches in patients with lupus were identified. Included studies were critically appraised and analyzed. Since a systematic review on this topic was published in 2004, only papers published in 2004 and later were included in this review. Statistical and publication bias was assessed using funnel plots. ResultsA total of 5096 references were identified, 189 were selected for detailed review and 11 papers were included in the final analysis. 1) The pooled prevalence of primary headaches in lupus was 26.8 % (95 %CI 25.1–28.6). The prevalence of primary headaches was similar between patients with lupus and healthy controls, odds ratio (OR) 2.14, 95 %CI 0.97–4.76, p value=0.06, however publication bias was significant according to the Egger test. Lupus patients seem to have a higher prevalence of primary headaches compared to patients with rheumatoid arthritis (RA) and primary Sjogren's syndrome (pSS), OR 2.5, 95 % CI 1.56–4, p < 0.0001. Regarding the prevalence of migraines specifically, no difference was found between patients with lupus compared to healthy controls and patients with RA or pSS. 2) Primary headaches seem to be associated with depression and impaired health related quality of life rather than lupus activity or damage. There is insufficient data to conclude whether specific lupus treatments affected primary headaches in lupus, however, one study did suggest hydroxychloroquine reduced the frequency of primary headaches. Raynaud phenomenon was associated with migraines. 3) One study which examined MRI scans of patients with lupus compared to healthy controls did suggest that larger gray matter volumes reduced the odds for headaches in general (OR 0.98, p = 0.048) and for migraines in particular (OR 0.95, p = 0.004), and larger white matter volumes increased the odds for migraine (OR 1.04, p = 0.007). However, these findings might reflect disease activity or damage, therefore further studies are required to clarify this issue. 4) The only study which specifically addressed the prevalence of “lupus headaches” is Hanly's study from 2013 of the SLICC cohort. In this large cohort, only 1.5 % of patients had "lupus headaches", as defined by SLE Disease Activity Index-2000 (SLEDAI-2 K). Therefore “Lupus headache” is a rare entity in SLE and should be suspected after excluding other possible explanations for headaches, especially when there is no known prior history of primary headaches. ConclusionsPatients with lupus seem to have a similar prevalence of primary headaches, and specifically migraines, compared to healthy controls. These primary headaches are associated with depression and Raynaud phenomenon and not with disease activity nor damage. Scarce data is published regarding structural changes associated with primary headaches. Currently is seems “lupus headaches” are a distinct rare manifestation of lupus and more data are needed.

Clinical characteristics, treatment and outcome of subacute cutaneous lupus erythematosus induced by PD-1/PD-L1 inhibitors.

PD-1/PD-L1 inhibitors have increasingly been associated with the occurrence of subacute cutaneous lupus erythematosus (SCLE), but the clinical characteristics and outcomes remain under-explored. Literature on PD-1/PD-L1 inhibitors induced SCLE was retrieved from Chinese and English databases until June 31, 2024, and clinical data of patients were extracted for retrospective analysis. Twenty-nine patients participated, with a median age of 63 years (range 43, 80). The most frequently reported drugs were Nivolumab (51.7%) and pembrolizumab (31.0%). The median time from treatment initiation to SCLE onset was 3 months (range 0.5, 47). Cutaneous manifestations presented primarily as papulosquamous lesions (65.5%) and erythema annulare (31.0%), predominantly occurring on the trunk (51.7%) and arms (51.7%). Serological analysis revealed positive anti-Ro antibodies in 91.7% of patients, positive antinuclear antibodies in 75.0%, and positive anti-La antibodies in 50.0%. Skin biopsies showed interface dermatitis in 65.5% of cases and lymphocyte infiltration in 82.8%. Treatment with topical corticosteroids, systemic corticosteroids, and hydroxychloroquine led to gradual improvement or resolution of the rash, with a median recovery time of 1 month (range 0.5, 11). As the use of PD-1/PD-L1 inhibitors in oncology increases, SCLE should be recognized as a rare cutaneous adverse effect. Histological and serological evaluations play a critical role in diagnosing SCLE. Typically, SCLE resolves on its own with appropriate local and systemic treatment.