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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]

Sjögren Syndrome (SS) is a chronic inflammatory autoimmune disease characterized by lymphocytic infiltration of exocrine glands. This study, based on bioinformatics predictions, investigates the biological functions of ubiquitin specific peptidase 18 (USP18) and notch receptor 1 (NOTCH1) in T helper 17 (Th17) and regulatory T (Treg) cell imbalance and B cell activity in SS. USP18 and NOTCH1 were highly expressed in peripheral blood mononuclear cells (PBMCs) of SS patients and the PBMCs of NOD mice compared to the controls. Adenovirus-mediated knockdown of USP18 significantly enhanced the salivary flow rate of NOD mice while reducing lymphocyte infiltration in mouse salivary ligand tissues. In addition, it decreased the proportions of Th17 cells while increasing the proportions of Treg cells. USP18 enhanced NOTCH1 protein stability through de-ubiquitination modification. In the presence of USP18 knockdown, the NOTCH1 upregulation restored the predominance of Th17 cells in mice. In B cells isolated from PBMCs, the production of B cell autoantibodies was decreased by USP18 silencing but enhanced by NOTCH1 upregulation. In summary, this study demonstrates that USP18-mediated protein stabilization of NOTCH1 is correlated with Th17/Treg cell imbalance and B cell activity during SS development. [ABSTRACT FROM AUTHOR]

Purpose of Review: Sjögren Syndrome is a systemic autoimmune disorder that presents mainly with sicca symptoms, but frequently affects other body systems which can lead to a wide variety of manifestations. Understanding the neurological and psychiatric manifestations of Sjögren Syndrome can help with an earlier diagnosis of this disease and leads to better clinical outcomes. Recent Findings: We provide an updated overview of the central neurological manifestations, peripheral neurological manifestations and psychiatric manifestations and their diagnosis when associated with primary Sjögren Syndrome. The epidemiology and clinical features of the neurological and psychiatric manifestations are derived from different cohort studies and review articles that were selected from PubMed searches conducted between January 2024 and March 2024. Summary: The absence of diagnostic criteria and the scarcity of large, robust studies makes the recognition of the neurological and psychiatric manifestations of Sjögren Syndrome more difficult. Maintaining a high index of suspicion in clinical practice and a close collaboration between the Neurologist and the Rheumatologist will facilitate the diagnosis and management of these patients. [ABSTRACT FROM AUTHOR]

Hydroxychloroquine (HCQ) has been used to treat Sjögren's disease (SjD) patients. However, there are no studies evaluating drug adherence through HCQ blood levels, pharmacy refill (PR) and medication adherence questionnaires. The relationship of HCQ blood levels with glandular/extraglandular disease parameters was also poorly assessed. This cross-sectional observational study included 74 adult SjD patients, who were receiving a stable HCQ dose (4-5.5 mg/kg/day, actual weight) for at least 3 months before study inclusion. HCQ blood levels were quantified by high-performance liquid chromatography coupled to mass spectrometry. Adherence was assessed by PR and Medida de Adesão aos Tratamentos (MAT) questionnaire. The following parameters were evaluated: Xerostomia Inventory, Ocular Surface Disease Index, EULAR (European League Against Rheumatism) Sjögren's Syndrome Disease Activity Index, EULAR Sjögren's Syndrome Patient Reported Index, Schirmer's I test and non-stimulated/stimulated salivary flow rates. HCQ blood levels were 775.3(25.0–2,568.6)ng/mL. Eleven patients (14.9%) had HCQ blood levels < 200ng/mL (non-adherent group); 11(14.9%), 200-499ng/mL (sub-therapeutic levels group); and 52(70.2%), ≥ 500ng/mL (adherent group). PR classified incorrectly all non-adherent/sub-therapeutic patients and 2/52(3.9%) adherent patients. Using MAT, the overall misclassification was 24/52(46.2%) in the adherent group, and were correctly identified 9/11(81.8%) patients in non-adherent and 7/11(63.6%) in sub-therapeutic groups. MAT sensitivity and specificity to identify non-adherent/sub-therapeutic patients were 72.7% and 53.9%, respectively. The three groups were comparable regarding glandular/extraglandular disease parameters (p > 0.05). The assessment of HCQ blood levels is a promising tool for evaluating drug adherence in SjD. This is particularly crucial as one-third of patients exhibited non-adherence/sub-therapeutic levels, and neither PR nor MAT reliably identified these patients. [ABSTRACT FROM AUTHOR]

Background: Sjögren's Syndrome (SS) is also known as autoimmune exocrine gland disease. Previous studies have confirmed that adaptive immunity plays an important role in the development of this disease. But less is known about the role of the innate immune system. Methods: To identify the core pathways, and local infiltrated immune cells in the local immune microenvironment of SS. We verified the activation of these core genes and core signaling pathways in SS model mice by in vivo experiment and transcriptome sequencing. Results: Finally, we identified 6 core genes EPSTI1, IFI44L, MX1, CXCL10, IFIT3, and IFI44. All the 6 genes had good diagnostic value. Based on multi-omics sequencing results and experimental studies, we found that cGAS–STING signaling pathway is most relevant to the pathogenesis of SS. By in vivo experiments, we verified that autophagy is the key brake to limit the activation of cGAS–STING signaling pathway. Conclusions: Maladaptive activation of autophagy and cGAS–STING signaling pathway are central contributors to the SG pathogenesis of pSS patient. Regulating autophagy by rapamycin may be a possible treatment for Sjögren's syndrome in the future. [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]

Circulating endothelial progenitor cells (EPCs) were first described in 1997 by Asahara et al. as "putative endothelial cells" from human peripheral blood. The study of endothelial progenitors is also intensifying in several pathologies associated with endothelial damage, including diabetes, myocardial infarction, sepsis, pulmonary arterial hypertension, obstructive bronchopneumopathy and transplantation. EPCs have been studied in several autoimmune diseases with endothelial involvement such as systemic lupus erythematosus, thrombotic thrombocytopenic purpura, antineutrophil cytoplasmic antibodies, vasculitis, rheumatoid arthritis, Goujerot-Sjögren and antiphospholipid syndrome. Factors involved in endothelial damage are due to overexpression of pro-inflammatory cytokines and/or autoantibodies. Management of these pathologies, particularly the long-term use of glucocorticoids and methotrexate, promote atherosclerosis. A lack of standardized assessment of the number and function of EPCs represents a serious challenge for the use of EPCs as prognostic markers of cardiovascular diseases (CVD). The objective of this review was to describe EPCs, their properties and their involvement in several autoimmune diseases. [ABSTRACT FROM AUTHOR]

Introduction: Influenza A (H3N2) virus is the major cause of morbidity/mortality due to seasonal influenza over 50 years. Data about the safety/immunogenicity of influenza A/Singapore (H3N2) vaccine are scarce in primary Sjögren syndrome (pSS). Methods: Twenty-one consecutive pSS patients and 42 HC (healthy control individuals) were immunized with influenza A/Singapore/INFIMH-16–0019/2016 (H3N2)-like virus. Rates of SP (seroprotection) and SC (seroconversion), GMT (geometric mean titers), FI-GMT (factor increase in GMT), ESSDAI (EULAR Sjögren's Syndrome Disease Activity Index), and adverse events were appraised before and 4 weeks post-vaccination. Results: pSS and HC had similar mean age (51.2 ± 14.2 vs. 50.6 ± 12.1 years, p = 0.886). Pre-vaccination SP rates were high in pSS and HC (90.5% vs. 71.4%, p = 0.114), and GMT were higher in pSS [80.0 (52.4–160.0) vs. 40.0 (20.0–80.0), p = 0.001]. The percentage of influenza vaccination in the preceding two years was elevated and similar in pSS and HC (94.1% vs. 94.6%, p = 1.000). GMT values augmented in both groups four weeks after vaccination and persisted higher in the first group [160.0 (80.0–320.0) vs. 80.0 (40.0–80.0), p < 0.001] with equivalent FI-GMT [1.4 (1.0–2.8) vs. 1.4 (1.0–2.0), p = 0.410]. Both groups had low and similar SC rates (19.0% vs. 9.5%, p = 0.423). ESSDAI values persisted steadily during the study (p = 0.313). No serious adverse events have occurred. Conclusion: The novel demonstration that the influenza A/Singapore (H3N2) vaccine induces a different pattern of immunogenicity from other influenza A constituents in pSS, featured by a desirable high pre- and post-vaccination immunogenicity, is in line with reported differences in immune responses between strains in trivalent vaccines and may be related to pre-existing immunity. Clinicaltrials.gov: #NCT03540823. Key Points • This prospective study demonstrated a robust pre- and post-vaccination immunogenicity to influenza A/Singapore/INFIMH-16–0019/2016 (H3N2)-like virus in primary Sjögren's syndrome (pSS). • This high immunogenicity pattern may be related to pre-existing immunization, or else it is related to immunogenicity differences of each strain. • This vaccine had an adequate safety profile in pSS, with no impact on disease activity. [ABSTRACT FROM AUTHOR]

Objective: The study aims to evaluate the utility of major salivary gland ultrasonography for diagnosis of primary Sjögren's syndrome (pSS) and to assess its concordance with minor salivary gland biopsy (MSGB). Methods: A cross-sectional study of 72 patients with suspected pSS was performed. Demographic, clinical, and serological data were collected. MSGB was performed, as was ultrasonography. The ultrasound technician was blind to clinical, serological, and histological data. The validity of ultrasonography compared with MSGB, the American-European Consensus Group (AECG), and American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) criteria was assessed by calculating the percentage of agreement, sensitivity, specificity, positive and negative predictive values, and area under the curve (AUC). Results: Based on MSGB as the gold standard, the percentage of agreement between both tests was 78% (AUC 0.75). Based on the ACR/EULAR criteria, the percentage of agreement was 83% (AUC 0.78) for ultrasonography and 81% (AUC 0.83) for biopsy. Sensitivity and specificity were 90% and 67%, respectively, for ultrasonography and 76% and 90% for biopsy. The results were similar with the AECG criteria. The intra- and inter-observer variability was good (κ > 0.7). Significant differences were observed for positive anti-Ro52 values and hypergammaglobulinemia in pathological ultrasound scans. Conclusion: Diagnostic ultrasonography is as useful as MSGB in pSS. Therefore, it could be included in the classification criteria. In this cohort, it proved more sensitive than MSGB and could be used as an initial test for patients suspected of having pSS. MSGB could be used in cases where clinical and serological results are inconclusive. Key Points • Major salivary gland ultrasonography adds diagnostic value similar to that of MSGB, thus potentially enabling this invasive procedure to be avoided. • Ultrasonography could be included in the classification criteria for primary Sjögren's syndrome. • Given that ultrasonography is more sensitive and less specific than MSGB, it could be used as an initial diagnostic test in patients with suspected Sjögren's syndrome. • Biopsy should be performed in those cases where ultrasonography, clinical, and serological data are inconclusive. [ABSTRACT FROM AUTHOR]

Background: We investigated the safety and efficacy of short-term treatment with topical low-dose hydrocortisone sodium phosphate 0.335% (PFH) in patients with moderate to severe primary Sjögren syndrome (SS)-related dry eye disease (DED). Methods: A retrospective single-centre interventional study. All patients received PFH for 6 days with a pulsed posology: three times daily for 2 days, twice daily for 2 days, and once daily for 2 days. This scheme was repeated for 3 consecutive months and then alternated for 3 months. Data were collected at baseline, 3 months, and 6 months of follow-up. Results: A total of 40 SS patients were enrolled. Conjunctival hyperaemia and corneal-conjunctival stain significantly improved (p < 0.001). Ocular Surface Disease Index score reduced significantly between baseline and 3 months and between baseline and 6 months (p < 0.001). The tear film osmolarity lowered significantly in each eye from baseline to 3 months and from baseline to 6 months (p = 0.002 and p = 0.037, respectively). Comparing results at 3 and 6 months, the Ocular Surface Disease Index score (p = 1.000), the frequency of lacrimal substitutes installation (p = 0.632), and tear film osmolarity (right eye p = 0.518, left eye p = 1.000) did not change significantly. Intraocular pressure did not change during the study period. Conclusion: PFH eye drops with a pulsed posology improve signs and symptoms, not affecting the intraocular pressure in SS-related DED. Therefore, this pulsed treatment is safe and efficacious. [ABSTRACT FROM AUTHOR]

Sjögren syndrome (SS) is a multisystem autoimmune disease, primarily targeting salivary and lacrimal glands; skin, nasal and vaginal dryness, along with musculoskeletal pain and fatigue are the most commonly reported symptoms. Hearing loss is hypothesized to be frequent as well. The purpose of this systematic review was to estimate the prevalence of Hearing loss and its different subtypes in patients with Sjögren syndrome. PRISMA guidelines were followed to ensure highest quality for our systematic review. A random effects model meta-analysis and meta-regression was conducted using I2 as heterogeneity indicator. Eleven observational studies were included in this systematic review. Ten of them were cross-sectional, while one study was case–control. Studies were assessed for risk of bias: all were rated to a moderate level, except for two rated to a low level. Pooled prevalence of any type of hearing loss was 52.2%. After excluding studies rated to moderate bias, the pooled prevalence of hearing loss was 36.7%. We also conducted a subgroup analysis depending on type of hearing loss. Pooled prevalence of sensorineural hearing loss was 42.6%., while pooled prevalence of conductive hearing loss and mixed hearing loss were 5% and 2.3%, respectively. Meta-regression was conducted in an effort to identify possible variables capable to explain high heterogeneity between studies. Sample size and year of study were separately found to account for a portion of heterogeneity between studies of sensorineural hearing loss. Year of study was also found to account for a portion of heterogeneity between studies of conductive hearing loss. In conclusion, sensorineural hearing loss, is highly prevalent in patients with Sjögren syndrome. On this basis, early screening and follow-up of patients with Sjögren syndrome by pure tone audiometry is important. [ABSTRACT FROM AUTHOR]

10% of rheumatoid arthritis (RA) cases are associated to so-called secondary Sjögren's syndrome (SS). These RA cases have higher DAS, fewer remissions. Is this linked to a poor response to DMARDs (disease-modifying anti-rheumatic drugs)? No study has addressed this question to date. Does the association between secondary Sjögren's syndrome (SS) and rheumatoid arthritis (RA) affect the therapeutic response to DMARDs and long-term prognosis? We conducted a retrospective case–control study: 39 RA associated with SS was (anti-SSA antibodies and/or Chisolm stage III or IV) were compared to 39 isolated cases of erosive RA matched by age, duration of progression and gender. The DAS CRP was higher in the RA + SS group in patients with disease progression of 16 years: 2.6 (1.5–4.5) compared to the RA group: 1.6 (1.3–2.8) (p = 0.0001) while fewer patients were in remission: 61 vs. 92% (p = 0.002). A higher number of B DMARDs have been prescribed: RA + SS = 3.04 (1–7); RA = 1.7 (1–5) (p = 0.004). Anti-TNFs are less effective when RA is associated with SS: 30 vs. 70%. Conversely, Rituximab is more effective when RA is associated with SS: 80 vs. 30%. Erosive RA-related SS exacerbates the clinical course of the condition: higher DAS, fewer remissions. This is linked to reduced treatment efficacy: higher number of DMARDs prescribed, reduced efficacy of anti-TNF drugs. RA-related SS could modify sensitivity to biotherapies: lower percentage of remissions and resistance to anti-TNF drugs. [ABSTRACT FROM AUTHOR]

Background and aims: RFC1-CANVAS and primary Sjögren syndrome (pSS) are among the most frequent causes of sensory ganglionopathy (SG) and can present simultaneously in a given patient, sharing confounding signs and symptoms. We describe the clinical characteristics of patients with SG due to CANVAS who were suspected of having or had received a previous diagnosis of pSS. Methods: Patients with SG and a genetically confirmed RFC1-CANVAS followed in our centre were ascertained and their personal history of pSS was collected. Results: Among the 71 patients with CANVAS, six patients (all females) had been diagnosed with pSS by their clinicians. In these six patients, the mean age at onset of the SG was 61 years, four patients describing gait instability and positive sensory symptoms, one only gait instability and one only positive sensory symptoms. Five patients had a history of chronic cough; signs at examination included a cerebellar syndrome (n = 3), vestibulopathy (n = 2), pes cavus (n = 3) and dysautonomia (n = 2). On neurophysiological examination, SG was generally severe and symmetrical. All patients presented a sicca syndrome, but only four patients had a confirmed pSS as per 2016 ACR-EULAR classification criteria. Four patients were treated but did not respond to immunosuppressive therapy, one suffering from side effects. Interpretation: The suspicion or diagnosis of pSS in a patient with SG should not exclude RFC1 expansion analysis, as a CANVAS diagnosis may dissuade the clinician from initiating or continuing immunosuppressive therapy, especially in unconfirmed pSS patients. Importantly, a sicca syndrome may lead to pSS misdiagnosis. [ABSTRACT FROM AUTHOR]

Lung involvement in autoimmune diseases (AID) is uncommon, but may precede other organ manifestations. A diagnostic problem is chronicity presenting with lung fibrosis. A new category of interstitial pneumonia with autoimmune features for patients with clinical symptoms of AID and presenting with usual interstitial pneumonia (UIP) enables antifibrotic treatment for these patients. Hypersensitivity pneumonia (HP) and other forms of lung fibrosis were not included into this category. As these diseases based on adverse immune reactions often present with unspecific clinical symptoms, a specified pathological diagnosis will assist the clinical evaluation. We aimed to establish etiology-relevant differences of patterns associated with AID or HP combined with lung fibrosis. We retrospectively evaluated 51 cases of AID, and 29 cases of HP with lung fibrosis, and compared these to 24 cases of idiopathic pulmonary fibrosis (UIP/IPF). Subacute AID and HP most often presented with organizing pneumonia (OP), whereas chronicity was associated with UIP. Unspecified fibrosis was seen in a few cases, whereas NSIP pattern was rare. In 9 cases, the underlying etiology could not be defined. Statistically significant features differentiating chronic AID or HP from UIP/IPF are lymphocytic infiltrations into myofibroblastic/fibroblastic foci. Other features significantly associated with AID and HP were granulomas, isolated Langhans giant cells, and protein deposits, but seen in only a minority of cases. A combination of UIP with one of these features enabled a specific etiology-based diagnosis. Besides the antifibrotic drug regimen, additional therapies might be considered. [ABSTRACT FROM AUTHOR]

This study aimed to describe a patient with Sjögren syndrome who developed Plummer-Vinson syndrome, and to review the literature and describe shared aspects of this rare association. A systematic screening of articles was conducted in PubMed/MEDLINE, LILACS, SciELO, Scopus, Web of Science, and Cochrane, dating 1940 to 2020. All the articles included the association between Sjögren syndrome and Plummer-Vinson syndrome. No language restriction was applied. The following terms were used: "Sjögren syndrome" or "sicca syndrome" and "Plummer-Vinson syndrome" or "Paterson-Kelly syndrome." We performed our analysis by adding our present case, with a total of 4 cases. Three out of four were female (75%), age varied from 56 to 58 years old. In 2 cases, Sjögren syndrome preceded Plummer-Vinson syndrome diagnosis, and in 1 report, Plummer-Vinson syndrome appeared before Sjögren syndrome. Disease duration varied from 7 to 20 years. In two cases, autoantibodies were available, and antinuclear antibodies and anti-Ro/SS-A were positive in both, and anti-La/SS-B in one of them was associated with anti-dsDNA; however, no data regarding lupus was available in the article. Treatment involved iron supplementation in 3/3. Two out of three received parenteral iron supplementation, and in these two cases, mechanical esophageal dilatation was needless. In the other case, an additional endoscopic esophageal dilatation was necessary to receive the oral iron supplement. All 3 cases had a good outcome. This case illustrates a patient with Sjögren syndrome who developed the rare Plummer-Vinson syndrome. In Sjögren syndrome, the presence of iron-deficiency anemia, dysphagia, and weight loss should alert the physician to search for associated Plummer-Vinson syndrome. Highlights: Plummer-Vinson syndrome (PVS) is a sporadic disease characterized by the triad of dysphagia, iron-deficient anemia, and webs on the esophagus. There are only three previous cases of PVS in Sjögren syndrome. The parenteral iron supplementation treats PVS adequately and seems to preclude the need for endoscopic esophageal dilatation. [ABSTRACT FROM AUTHOR]

Background: To investigate the correlation between the duration of Sjögren syndrome (SS) and ocular surface parameters in patients with SS-related dry eye. Methods: We analyzed 108 eyes of 108 female patients with primary SS-related dry eye. All patients underwent rheumatoid serologic tests and ocular surface assessments. The ocular surface assessment included the Standard Patient Evaluation of Eye Dryness (SPEED) score, meibomian gland (MG) atrophy, lipid layer thickness (LLT), partial and total blinking, partial blinking rate, Schirmer's I test, non-invasive tear break-up time, and ocular surface staining score. Correlations between the duration of SS and ocular surface assessments were calculated. Results: The average age and SS duration of the participants were 56.7 ± 10.2 (range 21–78) years and 54.15 ± 41.10 (range 1–134) months, respectively. There was a strong positive correlation between SS duration and MG atrophy (r = 0.766, p < 0.001). The correlation between SS duration and MG atrophy rate remained significant after controlling for age (r = 0.559, p < 0.001). Average, maximum, and minimum LLTs showed weak negative correlations with SS duration (r = − 0.310, − 0.211, and–0.304, respectively, p = 0.014, 0.028, and 0.022, respectively) and MG atrophy (r = − 0.191, − 0.326, and − 0.299, respectively, p = 0.049, 0.002, and 0.009, respectively). SPEED score showed a weak positive correlation to SS duration (r = 0.303, p = 0.042) and a moderate positive correlation to MG atrophy (r = 0.450, p = 0.029). Conclusions: Longer duration of primary SS was related to more severe MG atrophy. Therefore, it is necessary to perform meibography in SS patients to verify MG atrophy status. A comparative study with non-SS dry eye patients is required to validate this study. [ABSTRACT FROM AUTHOR]

Over the last two decades, a large number of non-communicable/chronic disorders reached an epidemic level on a global scale such as diabetes mellitus type 2, cardio-vascular disease, several types of malignancies, neurological and eye pathologies—all exerted system's enormous socio-economic burden to primary, secondary, and tertiary healthcare. The paradigm change from reactive to predictive, preventive, and personalized medicine (3PM/PPPM) has been declared as an essential transformation of the overall healthcare approach to benefit the patient and society at large. To this end, specific biomarker panels are instrumental for a cost-effective predictive approach of individualized prevention and treatments tailored to the person. The source of biomarkers is crucial for specificity and reliability of diagnostic tests and treatment targets. Furthermore, any diagnostic approach preferentially should be noninvasive to increase availability of the biomaterial, and to decrease risks of potential complications as well as concomitant costs. These requirements are clearly fulfilled by tear fluid, which represents a precious source of biomarker panels. The well-justified principle of a "sick eye in a sick body" makes comprehensive tear fluid biomarker profiling highly relevant not only for diagnostics of eye pathologies but also for prediction, prognosis, and treatment monitoring of systemic diseases. One prominent example is the Sicca syndrome linked to a cascade of severe complications that include dry eye, neurologic, and oncologic diseases. In this review, protein profiles in tear fluid are highlighted and corresponding biomarkers are exemplified for several relevant pathologies, including dry eye disease, diabetic retinopathy, cancers, and neurological disorders. Corresponding analytical approaches such as sample pre-processing, differential proteomics, electrophoretic techniques, high-performance liquid chromatography (HPLC), enzyme-linked immuno-sorbent assay (ELISA), microarrays, and mass spectrometry (MS) methodology are detailed. Consequently, we proposed the overall strategies based on the tear fluid biomarkers application for 3P medicine practice. In the context of 3P medicine, tear fluid analytical pathways are considered to predict disease development, to target preventive measures, and to create treatment algorithms tailored to individual patient profiles. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the perspective of Romanian patients with Sjögren syndrome (SS) on various aspects of the disease during the SARS-CoV-2 outbreak, including both the impact of COVID-19 on the disease itself as well as the effects of vaccination against SARS-CoV-2 in this group of patients. The study is an online questionnaire-based survey. We received responses from 137 SS patients. Regarding the general emotional status, 33 patients (24.0%) and 47 patients (34.3%) declared to have been sadder/depressive and more agitated/anxious during the SARS-CoV2 outbreak, respectively. During the lockdown, 49 (33.7%) patients strictly and 77 patients (56.2%) did their best to respect the home isolation measures. The income was unchanged for most of the patients (94 patients, 68.6%). Regarding access to healthcare providers, 27 patients (18.7%) postponed the consultation for fear of getting SARS-CoV2. In our study group, 31 patients (22.6%) responded that they have had COVID-19. Only one patient was completely asymptomatic, while the most frequently declared symptom was weakness (84.0%). In 17 patients among the respondents (68%) the symptoms lasted for at least 2 weeks; the most frequent long-lasting symptoms were fatigue (40.0%) and weakness (36.0%). Out of all the respondents, 53 patients (41.4%) were vaccinated against SARS-CoV2 with at least one dose. After the first dose, the most prevalent side effect was pain at the site of injection (89.2%), followed by weakness (25.0%) and myalgias (21.4%). This information will be useful for developing special programs dedicated to SARS-CoV2 infection and vaccination in patients with SS and other autoimmune diseases. [ABSTRACT FROM AUTHOR]

Purpose: Demodex mites infestation, typically asymptomatic, is a problem for patients with weakened immune systems because it often takes the form of symptomatic, massive infection. The Demodex mites play an important role in the occurrence of a range of eye surface diseases such as Demodex blepharitis, Meibomian gland dysfunctions, conjunctivitis and corneal changes. The ocular infection is closely related to the systemic invasion. Our goal was to minimize infestation and alleviate the symptoms of massive demodicosis so as to prevent further damage to the cornea. Methods: Our research note involves a 61-year old woman diagnosed with secondary Sjögren syndrome due to rheumatoid arthritis. On the background of the autoimmune disease, corneal perforation of the left eye occurred that was cured by surgery. Then during the follow-up visit the patient was found (microscopically) massively infected with Demodex mites and the developed symptoms were particularly severe. Results: Adequate dry eye syndrome and massive demodicosis therapy significantly reduced the number of Demodex mites and improved the patient's condition. Conclusion: We would like to draw the attention of the physicians of different specialties that special care should be taken with respect to the therapy of dry eye syndrome and ocular demodicosis in patients with immunological disorders to achieve therapeutic success and avoid particularly dangerous consequences of these diseases. [ABSTRACT FROM AUTHOR]

Background: Neuromyelitis optica spectrum disorders (NMOSD) are autoimmune neurological diseases of the central nervous system, which are characterized by the presence of serum anti-aquaporin-4 autoantibodies (AQP4-IgG). An association between Sjögren syndrome (SjS) and AQP4-IgG-positive NMOSD has been proposed, but the rate of coexistence has not been determined. Methods: In this study, 4,447 patients suspected of having NMOSD with acute neurological episodes were evaluated for the positivity of serum AQP4-IgG, serum SS-A/Ro antibody, and the presence of SjS-related symptoms (dry eye, dry mouth). Results: Of the 4,447 patients, 1,651 were positive for serum AQP4-IgG, and the remaining 2,796 were negative. A significantly higher proportion of AQP4-IgG-positive patients were positive for serum anti-SSA/Ro antibody (26.3 vs. 4.5%; p < 0.0001) and anti-SSB/La antibody (7.2 vs. 1.2%; p < 0.0001) and had dry eye (9.1 vs.4.9%; p < 0.0001) and dry mouth symptoms (8.9 vs. 3.7%; p < 0.0001). More than 80% of the patients with SjS with acute neurological events such as myelitis or optic neuritis were AQP4-IgG positive. AQ4-IgG-positive patients with comorbid SjS showed a higher female rate (97.1 vs. 89.0%; p = 0.0062), a higher positivity rate for oligoclonal bands (15.4 vs. 7.5%; p = 0.029), and a higher relapse frequency (p = 0.027) than AQP4-IgG-positive patients without comorbid SjS. Conclusions: The prevalence of SjS is higher among AQP4-IgG-positive than AQP4-IgG-negative patients, with the potential prevalence of 10–20% at the diagnosis of AQP4-IgG-positive NMOSD. Comorbid SjS is more prevalent in females, and it has a higher relapse frequency among AQP4-IgG-positive patients. [ABSTRACT FROM AUTHOR]

This article discusses a case of Adie's tonic pupil in a 37-year-old Asian woman with primary Sjögren syndrome. The patient presented with symptoms of dry eyes, dry mouth, bilateral dilated pupils, and blurred vision. Further examination revealed irregular shaped pupils and a sluggish response to light. The presence of Adie's tonic pupil was confirmed through pharmacological testing. The article emphasizes the importance of recognizing this rare manifestation of Sjögren syndrome for early diagnosis and proper management. [Extracted from the article]

Chikungunya virus (CHIKV) infection is caused by an arbovirus prevalent in various parts of the world. The virus can induce autoantibodies and rheumatic diseases, such as rheumatoid arthritis and spondylarthritis. However, until now, no case of Sjögren syndrome (SS) was described associated with CHIKV. In this article, we describe a 49-year-old female with polyarthralgia and a temporary rash on her trunk and arms. Her physical examination showed polyarthritis of her ankles and wrists. Serologies for CHIKV were interpreted as positive with IgM 6.5 (normal range < 0.8) and negative for IgG. Antinuclear antibodies were positive at a titer of 1:640 as well as anti-Ro/SS-A. The diagnosis of subacute CHIKV infection was determined. The Schirmer test, Rose Bengal, and salivary scintigraphy were positive and the diagnosis of SS was confirmed. She was treated with hydroxychloroquine, methotrexate, and a single dose of betamethasone depot. This is the first report on CHIKV associated with SS. Sequence analysis of the CHIKV proteome versus SS autoantigens showed an extensive peptide sharing between the virus and numerous SS autoantigens, thus supporting the hypothesis that autoimmune cross-reactivity might causally link CHIKV to SS. [ABSTRACT FROM AUTHOR]

Objective: The diagnostic utility of labial salivary gland (LSG) biopsy for IgG4-related sialadenitis remains undetermined. The purpose of the present study was to determine whether submandibular gland biopsy could be replaced by LSG biopsy for diagnosing IgG4-RS. Patients and methods: Medical records of two groups of patients were reviewed. Group A contained 45 patients suspected to have IgG4-RS who underwent both SMG and LSG biopsies. Group B contained 25 patients who were clinically and pathologically diagnosed with Sjögren syndrome (SS). Biopsy samples were stained using hematoxylin and eosin (HE) and immunohistochemical techniques and observed under an optical microscope. Relevant data describing histopathological characteristics were collected and analyzed. Results: SMG of IgG4-RS patients presented typical histopathological characteristics of fibrosis and IgG4-positive plasmacytic infiltration, while LSG showed varied characteristics. The sensitivity and accuracy of SMG for diagnosing IgG4-RS were greater than those of LSG (100% and 100% versus 55.3% and 75.7%, respectively, P < 0.05). Conclusions: Biopsy of SMG showed greater sensitivity and specificity, whereas LSG biopsy showed varied histopathological and immunohistochemical characteristics; thus, SMG biopsy cannot be replaced by LSG biopsy for diagnosis of IgG4-RS. Key Point • Biopsy of SMG showed greater sensitivity and specificity than LSG biopsy for diagnosis of IgG4-RS. [ABSTRACT FROM AUTHOR]

Background and Objective: Autoimmune longitudinal extensive transverse myelitis (LETM) is often combined with connective tissue disorders (CTD). The purpose of this study was to compare the clinical characteristics of autoimmune LETM with and without CTD.Methods: Ninety-two patients diagnosed with autoimmune LETM were enrolled from our clinical database and divided into two groups depending on whether they had a concomitant diagnosis of CTD. Differences in clinical, serological, and imaging characteristics between the two groups were evaluated and compared.Results: Fifty-nine LETM patients without CTD and 33 LETM patients with CTD were included. LETM patients with CTD had higher Kurtzke Expanded Disability Status Scale at nadir and more severe sensory dysfunction (p < 0.05) than those without CTD. It was also found that LETM patients with CTD, compared with those without CTD, had elevated levels of immune inflammation markers such as IgG, IgA, and globulins (p < 0.05). These abovementioned characteristics were more prominent in patients with aquaporin-4 antibodies (AQP4-ab) than in those without them. In addition, the most common type of CTD in LETM was Sjögren syndrome (SS), which was usually diagnosed at the time of LETM or later.Conclusion: LETM patients with CTD, especially those with AQP4-ab, had greater sensory dysfunction and higher levels of inflammatory markers than did LETM patients without CTD. Multicenter cooperation and long-term follow-up are necessary to further study the inherent implications and prognosis of the disease. [ABSTRACT FROM AUTHOR]

Introduction: The risk factors for systemic autoimmune diseases (SAD) in gastric disease patients with proton pump inhibitor (PPI) use are still unclear. This study discussed this relationship in an Asian population. Methods: Patients without a prior history of SAD were identified from Taiwan's National Health Insurance Research Database between January 1, 2000, and December 31, 2010. Cox regression models were applied to estimate the hazard ratio (HR) with 95% confidence interval [CI] of SAD. The cumulative PPI dosage was stratified by quartiles of defined daily doses and adjusted for baseline disease risk score which served as the primary variables compared against no PPI use. Results: We analyzed the data of 51,291 participants aged 18 years or older and free of SAD at baseline. PPI users (n = 17,938) had a significantly increased risk of SAD over non-PPI users. There was a significantly higher risk of developing SAD in older age groups. A significant dose-dependent association was observed between cumulative PPI use and the risk of SAD. Female PPI users had significantly higher risk of developing SAD. In patients who received PPI, the autoimmune disease with significantly higher incidence was Sjögren syndrome (SjS) (adjusted HR [aHR] 1.82, 95% CI, 1.02–3.27) and rheumatoid arthritis (RA) (aHR, 2.19, 95% CI, 1.19–4.01). Conclusion: This study found PPI users to be associated with an increased risk of SAD. Older age or cumulative PPI use was significantly associated with SAD, and the highest incidence was SjS and RA among gastric disease patients who received PPI. Key Points • This nationwide long-term cohort study found PPI users to be associated with an increased risk of rheumatoid arthritis and Sjögren syndrome in Taiwan. • This finding may help with clinical risk evaluation and will inform further investigation of the pathogenesis between autoimmune diseases and PPI use. [ABSTRACT FROM AUTHOR]

Purpose: Patients with obstructive sleep apnea (OSA) have a higher risk of Behçet's disease (BD) and Sjögren syndrome (SS). However, the bidirectional relationship between these autoimmune diseases and OSA is unclear. We investigated the relationship between autoimmune diseases (SS and BD) and OSA. Methods: SS and BD patients were identified through the Taiwan National Health Insurance Research Database from 2002 to 2012. Patients with SS or BD were matched according to age and sex with a control group in a ratio of 1:4. The study included 12,926 patients with SS and 51,704 non-SS controls. Similarly, 1221 patients with BD were matched with 4884 non-BD controls. We used a Cox regression model, stratified by age, gender, and comorbidities, to assess the risk of OSA. Results: OSA was diagnosed in 0.61% of the SS cohort and 1.23% of the BD cohort. The higher overall risk for OSA was observed significantly in patients with SS than in controls (adjusted hazard ratio [HR] = 2.48, 95% confidence interval [CI] = 1.89–3.24). The higher risk was also observed significantly in BD patients than in controls (HR = 1.99, 95% CI = 1.06–3.72). Furthermore, men with SS or BD exhibited HR of 2.62 (95% CI 1.89 to 3.62) and 6.40 (95% CI 2.96 to 13.84) for developing OSA, respectively. Conclusion: Risk of OSA was significantly elevated in SS or BD patients compared with controls. Further study is warranted to elucidate underlying mechanisms. [ABSTRACT FROM AUTHOR]

This study aimed at determining socio-demographic and clinical factors of primary Sjögren syndrome (pSS) associated with osteoporosis (OP) and fragility fracture. SJOGRENSER is a cross-sectional study of patients with pSS, classified according to American European consensus criteria developed in 33 Spanish rheumatology departments. Epidemiological, clinical, serological and treatment data were collected and a descriptive analysis was conducted. Bivariate and multivariate analyses were performed using a binomial logistic regression to study the factors associated with OP and fragility fracture in pSS. 437 patients were included (95% women, with a median age of 58.6 years). 300 women were menopausal (76.4%). Prevalence of OP was 18.5% [in men (N = 21) this measured 19%]. A total of 37 fragility fractures were recorded. In the multivariate analysis, there was an association between OP and age: in the 51–64 age range (menopausal women), the OR measured 9.993 (95% CI 2301–43,399, p = 0.002); In the age > 64 years group, OR was 20.610 (4.679–90.774, p < 0.001); between OP and disease duration, OR was 1.046 (1.008–1085, p = 0.017); past treatment with corticosteroids, OR 2.548 (1.271–5.105, p = 0.008). Similarly, an association was found between fragility fractures and age: in the 51–64 age group, OR measured 5.068 (1.117–22,995, p = 0.035), age > 64 years, OR was 7.674 (1.675–35,151, p < 0.009); disease duration, OR 1.049 (CI 1.003–1097, p < 0.036) and the ESSDAI index, OR 1.080 (1.029–1134, p = 0.002). Patients with pSS can develop osteoporosis and fragility fractures over the course of the disease. Age, corticosteroids treatment and disease duration were associated with the development of OP. Disease duration and ESSDAI were associated with the development of fractures in patients with pSS. [ABSTRACT FROM AUTHOR]

The objective of this study is to review the ocular surface changes and complications of patients with Sjögren syndrome and assess their visual impact. A retrospective, cross-sectional, observational, and descriptive study of patients with Sjögren syndrome diagnosed according to the American–European Consensus Group criteria was designed. Data including age, gender, the reason for consultation, associated systemic disease, visual acuity, and ocular complications were recorded. Dry eye tests including tear meniscus thickness; tear film break-up time; ocular surface staining (fluorescein and lissamine green); and Schirmer I test were performed. A total of 249 patients, 233 women (93.6%) and 16 men (6.4%) were studied. Meibomian gland dysfunction was found in 46% (n = 229 eyes) patients; shortened tear film break-up time in 44% (n = 220 eyes); decreased tear meniscus in 49% (n = 243 eyes); significant superficial punctate keratopathy in 49% (n = 242 eyes); a mean ocular surface staining score of 5.92 points; and a low score for Schirmer I test (mean = 5.4 mm). Eyes with a 4 + corneal fluorescein score showed the worst BCVA (mean = 0.63 ± 0.66 LogMAR, ≤ 20/80 Snellen eq., 95% CI 0.29–0.97), compared to 1 + to 3 + scores (mean = 0.211 ± 0.37 LogMAR, 20/32 Snellen eq., 95% CI 0.53–1.15). Ten eyes (4.0%) presented central corneal ulceration with a mean visual acuity of 20/500 (96% visual loss). Ocular surface alterations related to severe dry eye and complications from Sjögren syndrome may have a significant impact on visual acuity. Secondary Sjögren syndrome to rheumatoid arthritis had the worse dry eye prognosis, visual outcome, and ocular complications. [ABSTRACT FROM AUTHOR]

This study aims to investigate ultrasound (US) findings on salivary glands (SG) in patients with Sjögren syndrome (SS) vs. other connective tissue diseases (CTDs) and to assess the relationship of SGUS abnormalities with autoantibody profile in both groups. We enrolled 81 patients, 45 diagnosed with SS (39 with primary SS, 6 with secondary SS) and 36 diagnosed with other CTDs. All patients underwent a prospective evaluation of sicca symptoms, a Schirmer's test, and a B-mode US assessment of the parotid and submandibular glands, all blinded to the diagnosis. Each SG was semi-quantitatively scored 0–3; a grade ≥ 2 was considered pathological. SGUS involvement was classified as normal or pathological at the patient level and for each pair at the gland level. In addition, a total SGUS score of 0–12 and a parotid/submandibular score of 0–6 were calculated for each patient. Autoimmunity laboratory data were also obtained. All SGUS scores were higher in SS patients than in those with CTD (p < 0.001) and significantly more SS patients showed a pathological global (p < 0.001), parotid (p < 0.001), or submandibular (p = 0.001) US score compared with CTD patients. In SS patients, the presence of autoantibodies was significantly associated with pathological SGUS and higher scores, particularly at the parotid level, while in CTD patients, xerostomia and a pathological Schirmer's test were associated with pathological US and higher scores at the submandibular level (p < 0.05). SGUS showed a different grade of abnormality, site involvement, and associated autoantibody profile in SS patients as compared with other CTD. Key Points: • Patients with SS and other CTDs showed different grades of SGUS abnormality. • Patients with SS and other CTDs showed different gland involvement and associated autoantibody profiles. • Anti-Ro60 and anti-Ro52 Ro60 positivity were associated with the severity of parotid involvement in SS patients. [ABSTRACT FROM AUTHOR]

Primary Sjögren's syndrome (pSS) is a chronic autoimmune disorder associated with a variety of systemic presentations. Varied neurological dysfunctions of newly diagnosed adult patients with pSS have been observed in recent years. We aimed to describe a rare case of acute bilateral facial paralysis diagnosed with pSS for the first time and review the previous studies including similar cases. A 69-year-old female, who had experienced ocular and oral dryness for more than 10 years, presented with bilateral facial palsy. Her laboratory test results showed positive anti-Ro (SSA) and anti-Ro-52 antibodies. Ophthalmic examination and test of saliva secretion verified xerophthalmia and xerostomia, respectively. Other possibilities of Lyme disease, Möbius syndrome, tumor, bilateral temporal bone fracture, Guillain–Barré syndrome, central nervous system lymphoma and HIV infection were ruled out. A diagnosis of pSS associated with bilateral facial paralysis was made. The literature review revealed one article describing a similar patient. Our case was the only one suffering from acute bilateral facial palsy without other nerve involvement. The presence of such patients reveals that pSS is an underlying cause of acute bilateral facial paralysis. [ABSTRACT FROM AUTHOR]

Lymphoepithelial salivary gland cysts are rarely seen in autoimmune diseases particularly Sjogren syndrome as well as in HIV for which medical management is advocated. To study the morphology of these cysts, correlate with the disease process and assess the final outcome. Case series. Fine needle aspiration clinic. HIV-infected and autoimmune disease patients with lymphoepithelial cysts. Antiretroviral therapy for HIV-patients and anti-inflammatory drugs for Sjogren syndrome. Three HIV-infected patients (two children and one adult) and three middle aged female patients presented with parotid and submandibular cysts, two of which were bilateral along with submandibular (one each in the HIV and the autoimmune group). In the adult HIV-patient, the cyst was found at the inception of the disease while the other pediatric HIV-patients just crossed a decade. Of the other three cases of Sjogren syndrome, two were primary and one, secondary to rheumatoid arthritis. All the cysts regressed completely with treatment of the respective diseases which was confirmed by ultrasonograms. Lymphoepithelial cysts are produced by release of serous secretion by the acinar and ductal cells within the epithelial islands in the process of their destruction. Possibly, antibody mediated increased secretion in the initial stages also plays a role. Lymphoepithelial cysts of HIV patients may occur in the course of treatment, not necessarily in the beginning, though it resolves spontaneously. Lymphoepithelial cysts of primary or secondary Sjogren syndrome may be repressed sufficiently by anti-inflammatory/immunosuppressant treatment. [ABSTRACT FROM AUTHOR]

An association of polymorphic marker rs2228262 in the THBS1 gene with the risk of developing dry eye in Sjögren syndrome was revealed. Confocal microscopy data suggest that this polymorphic marker is responsible for the high probability of corneal nerve fiber lesion in Sjögren syndrome even in the absence of clinical and functional signs of dry eye syndrome. A significant correlation was established between polymorphic markers rs1478604, rs2228262 in THBS1 gene and the coefficients of anisotropy and orientation symmetry of corneal nerve fibers. These results allow considering these polymorphic markers as a genetic factor of predisposition to dry eye syndrome in patients with Sjögren syndrome. [ABSTRACT FROM AUTHOR]

To analyze the clinical spectrum, laboratory characteristics, and outcomes of monoclonal gammopathy (MG) in patients with rheumatic diseases. Screening for the presence of MG was performed in 872 inpatients with rheumatic diseases from January 2010 to July 2017. A total of 41 patients were enrolled. Their clinical and biological features in addition to outcomes were described. For each patient with primary Sjögren syndrome (pSS), 2 age- and sex-matched pSS patients without MG were selected as controls. Risk factors for the presence of MG and malignant hematological neoplasias were assessed. MG was observed in patients with SS, rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, primary biliary cirrhosis, polymyositis, hypomyopathic dermatomyositis, psoriatic arthritis, ANCA-associated vasculitis, polyarteritis nodosa, and polymyalgia rheumatic, with SS the most frequent type. Serum M protein was detected in 37 patients. The monoclonal bands identified in serum were 16 IgG (5 κ, 11 λ), 11 IgA (6 κ, 5 λ), 6 IgM (5 κ, 1 λ), and 4 free λ chains. M components were observed in urine in the other 4 patients. High ESR, albumin/globulin inversion, rheumatoid factor positivity, hypergammaglobulinemia, and hypocomplementemia were common features, presented in more than half of the 41 patients. Patients with pSS, when complicated with MG, showed a higher rate of abnormal urine NAG (71.4 vs 15.8%, P = 0.025), higher levels of ESR [55.0 (53.5) mm/h vs 21.0 (31.8) mm/h, P = 0.001], ESSDAI [26.0 (25.0) vs 12.0 (9.0), P = 0.006], and ClinESSDAI scores [24.0 (25.0) vs 10.5 (10.0), P = 0.011]. Multivariate analysis revealed that the disease activity, assessed by either ESSDAI [adjusted OR 1.127 (95%CI 1.015-1.251), P = 0.025] or ClinESSDAI [adjusted OR 1.121 (95%CI 1.011-1.242), P = 0.030], was the only independent risk factor for the presence of MG. During the follow-up, 2 patients had transient serum M protein, 2 had isotype switch, 1 progressed to multiple myeloma (MM), and another 2 experienced renal injuries attributed by monoclonal or polyclonal plasma cell interstitial infiltration. Seven (17.1%) of the 41 MG patients presented hematological neoplasias, 4 with MM, 2 with smoldering multiple myeloma, and 1 with B cell lymphoma of mucosa-associated lymphoid tissue (MALT) type. The presence of light-chain MG was associated with the development of MM [OR 17.5 (95%CI 1.551-197.435), P = 0.041], but not with an increased risk of lymphoma or SMM. MG was observed in patients with various rheumatic disorders, with SS being the most common type. The presence of MG might be associated with higher disease activity. The development of hematological neoplasias including MM and lymphoma was seen in this setting. Therefore, we recommend the screening for MG and close monitoring for potential malignant transformation in patients with rheumatic diseases as needed. [ABSTRACT FROM AUTHOR]

The aim of this study is to evaluate the hearing behavior of rheumatoid arthritis (RA) and primary Sjögren syndrome (PSS) patients and compare them with a healthy control group and with each other. A comparative cross-sectional study was performed with a group of 117 female RA patients, a group of 60 female PSS patients, and a 251 female healthy control group. Every subject underwent a series of studies including high-frequency audiometry, speech audiometry, and tympanometry. The high-frequency audiometry measured 250 to 16,000 Hz. The 117 patients with RA and the 60 with PSS were diagnosed according to American College of Rheumatology criteria / ACR 2010, and the validated classification of the American-European Consensus Group. Hearing loss was present in 36.8% of the RA group in 500-3000 Hz, 68.4% in 4000-8000 Hz, and 94.9% in 10,000-16,000 Hz. Hearing loss was present in 60% of the PSS group in 500-3000 Hz, 70% in 4000-8000 Hz, and 100% in 10,000-16,000 Hz. The hearing impairment prevalence of both groups was significantly different ( p < 0.05) when compared with the healthy control group. We also compared the hearing thresholds between RA and PSS patients, finding a significant hearing threshold increase in 500-3000 Hz of the PSS group. This study consolidates the association between RA and PSS with hearing impairment. A deeper hearing loss was reported in PSS than in RA patients, demonstrating a greater auditory and speech recognition repercussion. [ABSTRACT FROM AUTHOR]

Flammer syndrome (FS) is a term to blanket a cluster of vascular and nonvascular signs and symptoms linked to primary vascular dysregulation (PVD), increased sensitivity to various stimuli (stress, drugs, etc.) and altered sense regulation such as pain, smell and thirst perception. On one hand, disruption of blood barrier and homeostasis of the body are the main targets of vascular irregularity. Inflammation and immune disorders including autoimmunity are considered as a consequence of the abnormal vascular regulation processes. On the other hand, decreased thirst feeling typical for FS-affected individuals may lead to extensive body dehydration resulting in dry eye appearance and breast cancer (BC) risk, amongst others. To this end, recent research demonstrated FS as linked to BC development and progression into the metastatic disease. On the other side, Sjögren syndrome (SS) is an autoimmune disease characterised by a progressive sicca syndrome associated with the dry eye symptoms, specific immunologic complex and/or significant infiltrate at minor salivary gland biopsy. SS is relatively frequent, with a clinical diagnosis predominantly amongst women. Its physiopathology is a complex battery of both environmental and genetic factors. If left untreated, SS may be associated with and/or resulted in severe arthritis and the development of B cell lymphoma. In this mini-review, we summarise the facts and hypotheses connecting FS and SS symptoms together and mechanisms potentially overlapping in both syndromes. Unraveling the common denominators between these two syndromes not only providing more evidence for interaction between altered sense regulation, vascular dysregulation, immune system dysfunction but also focusing on the individual outcomes in terms of severity grade and potential complications exploring novel diagnostic, prognostic and treatment modalities. Multi-professional considerations presented here are an example how to effectively enter the new era of preventive, predictive and personalised medicine benefiting the patients and healthcare system as the whole. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS) are systemic autoimmune diseases with complex symptoms and pathogenesis that are still not completely understood. Several studies showed that the trace element homeostasis and also the levels of antioxidant plasma proteins are changed in autoimmune disorders; however, these results are controversial. In this study, the potassium (K), calcium (Ca), magnesium (Mg), copper (Cu), zinc (Zn), and iron (Fe) concentrations of the serum and proteins-immunoglobulin G (IgG), transferrin (Trf), albumin (Alb), and ceruloplasmin (Cp)-separated from serum samples by affinity chromatography were determined in patients with SLE and SS. Ca and K levels were found to be decreased in the case of both disorders compared to the control group, and the competitive antagonism of Cu and Zn was also observed: elevated Cu concentration together with a lower Zn concentration was measured in the sera of patients with autoimmune diseases. After fractionation, the trace element concentration of protein containing fractions altered to that of the control group. In case of the autoimmune disorders, the highest Cu concentration was determined in the Alb-containing protein fractions while the Zn level decreased in the Alb and increased in the Cp as well as in the IgG- and Trf-containing fractions compared to the healthy samples. Changes have also been found in the level and distribution of K and Ca. [ABSTRACT FROM AUTHOR]

Anti-Ro/SS-A is one specific type of antinuclear antibodies. They are in the majority of cases associated with primary Sjögren syndrome (SS) but also in Systemic Lupus Erythematosus (SLE), rheumatoid arthritis (RA), and in healthy people. During pregnancy, they are mainly associated to congenital heart block (CHB) and neonatal lupus (NL). The aim of this study was to compare the rate of maternal and fetal complications between a series of anti-Ro/SS-A positive pregnant women prospectively followed. Forty-two anti-Ro/SSA antibodies positive pregnant women that were referred to our hospital between 2011 and 2015. Data about pregnancy follow-up and outcomes were prospectively recorded from electronic databases. Data included demographic characteristics of the patients and their diseases (type, treatments, profile of anti-Ro/SSA, and antiphospholipid antibodies), pregnancy complications (CHB, preeclampsia, preterm delivery), ultrasound examinations and conditions, and mode of delivery. Maternal age was 35.22 ± 3.42 years and most of them were either SLE ( n = 16, 40%) or Sjögren syndrome ( n = 15, 37.5%). The rest of them were asymptomatic carriers ( n = 8; 20%), and there was only one case of rheumatoid arthritis ( n = 1; 2.5%). The incidence of anti-Ro52 and anti-Ro60 positive was n = 13, 82.4% and n = 16, 100%, respectively. Anti-La/SSB antibodies were present in n = 17, 48,6% of the patients. Half of the patients were taking hydroxycloroquine ( n = 18, 45%). Seven pregnancies were complicated by fetal anti-Ro-related cardiac disease (17.9%) including four cases (57.1%) of second-degree heart block, two cases of third degree heart block (28.6%) and one case (14.3%) of intense and diffuse hyperechogenicity in atrioventricular valves without heart block. Gestational age at diagnosis of these conditions was 23.2 ± 3.5 weeks. One of the 18 patients having hydroxychloroquine (5.6%) compared with the six of them in women not having this medication (6/22, 27.3%) ( p = 0.10). Concerning about Doppler evaluation, the Z score of umbilical pulsatility index (PI) was significantly higher in the SLE patients ( p = 0.02). There were no cases of preeclampsia. Labor was induced in 21 cases (52.5%) and cesarean section rate was 45%. Gestational age at birth was 39 (37-40) weeks, and the general prematurity rate was 20% ( n = 8). Birthweight was 2985 g (2425-3185 g) and 2850 (12.25-52.50) centiles for gestational age. The rate of small for gestational age (SGA) infants was 31.3% for SLE patients (5/16), 13.3% for Sjögren syndrome (2/15), and 12.5% for asymptomatic women (1/8). The rate of neonatal acidosis (pH < 7.20) was 20% (8/34) and it was higher in the SLE cases (6/15, 40%) when delivered after 38 weeks. The main pregnancy complication associated to anti-Ro/SS-A antibodies is CHB. The prevalence of CHB in patients taking hydroxychloriquine is lower without distinguishing between high or low risk patients. Preterm delivery occurs in anti-Ro/SS-A patients at the same rate as in the general population if no complications such as CHB or intrauterine growth restriction (IUGR) occur. The SGA rate also is higher probably because of SLE not because anti-Ro/SS-A antibodies. Finally, the finding of high umbilical artery PI will allow to predict fetus at risk of adverse pregnancy outcomes. Highlights: •Anti-Ro/SS-A and anti-La/SS-B are clinically very relevant during pregnancy mainly because of their association to congenital heart block and neonatal lupus. •In our cohort, the prevalence of congenital heart block detected in patients taking hydroxycloroquine is much lower than in patients not taking it without distinguishing between high and low risk patients. •High umbilical artery pulsatility index in Doppler scans studies has been detected in our anti-Ro/SSA population (basely in SLE patients) demonstrated this measurement as a predictor of SGA and adverse pregnancy outcomes in general population such as cesarean section for fetal distress. The small for gestational age rate is higher probably because of SLE not because anti-Ro/SS-A •Preterm delivery happens in anti-Ro/SS-A patients at the same rate as in the general population if no complications such as congenital heart block or intrauterine growth restriction occur. [ABSTRACT FROM AUTHOR]

Introduction: Interstitial lung disease (ILD), which is the most common form of respiratory involvement of Sjȍgren syndrome (SS), is highly associated with postoperative pulmonary complications after surgery. We report the successful anesthetic management of a cervical cancer patient with SS and ILD under combined spinal-epidural anesthesia (CSE) to avoid postoperative pulmonary complications. Case description: A 41-year-old woman with SS complicated by recently progressive ILD was scheduled for an elective radical hysterectomy under the diagnosis of cervical cancer. We performed CSE with separate needle technique (SNT) using two different interspaces. An epidural catheter was inserted at T11-T12 before administration of spinal medication at L3-L4. We could achieve successful anesthetic management for radical hysterectomy, maintaining stable hemodynamic variables. Postoperative analgesia, using epidural catheter, was effective and devoid of any postoperative pulmonary morbidity. Discussion and Evaluation: CSE could offer a high level of sensory blockade, profound muscular blockade, longer duration of surgical anesthesia, excellent postoperative pain control, and reduction in the incidence of pulmonary morbidity. Therefore it would be excellent anesthetic option for the patients with pulmonary impairment. Conclusion: CSE with SNT may be particularly advantageous in patients with pulmonary impairment such as progressive ILD when general anesthesia is associated with high risk of postoperative complications. [ABSTRACT FROM AUTHOR]

Primary Sjögren's syndrome (pSS) can be complicated by distal renal tubular acidosis (dRTA), which may contribute to low bone mineral density (BMD). Our objective was to evaluate BMD in pSS patients with and without dRTA as compared with healthy controls. BMD of lumbar spine (LS) and femoral neck (FN) was measured in 54 pSS patients and 162 healthy age- and sex-matched controls by dual-energy X-ray absorptiometry (DXA). dRTA was defined as inability to reach urinary pH <5.3 after an ammonium chloride (NH4Cl) test. LS- and FN-BMD were significantly higher in pSS patients compared with controls (1.18 ± 0.21 g/cm(2) for patients vs. 1.10 ± 0.18 g/cm(2) for controls, P = 0.008 and 0.9 ± 0.16 g/cm(2) for patients vs. 0.85 ± 0.13 g/cm(2) for controls, P = 0.009, respectively). After adjustment for BMI and smoking, the LS- and FN-BMD remained significantly higher. Patients with dRTA (N = 15) did not have a significantly different LS- and FN-BMD compared with those without dRTA (N = 39) after adjustment for BMI, age, and gender. Thirty-seven (69 %) pSS patients were using hydroxychloroquine (HCQ). Unexpectedly, pSS patients had a significantly higher LS- and FN-BMD compared with healthy controls. Patients with dRTA had similar BMD compared with patients without dRTA. We postulate that an explanation for the higher BMD in pSS patients may be the frequent use of HCQ. [ABSTRACT FROM AUTHOR]

Autoimmune diseases such as rheumatoid arthritis (RA) and Sjögren syndrome (SS) ameliorate during pregnancy, through dampening (immunotolerance) of the maternal immune system which protects the fetus from rejection. A large number of studies have shown that human chorionic gonadotropin (hCG) contributes to this tolerance. Studies on animal models have reaffirmed that hCG treatment mimics the benefits of pregnancy. Based on the scientific evidence, randomized clinical trials comparing hCG with current therapies and/or placebo are recommended for RA, SS, and for other autoimmune diseases such as, type 1 diabetes and ankylosing spondylitis, which also get better during pregnancy and hCG treatment seems to help. [ABSTRACT FROM AUTHOR]

Sjögren syndrome is a chronic, systemic, and autoimmune disorder that targets exocrine glands by remarkable B cell hyperactivity. Eventually, it is associated with extra-glandular clinical manifestations that affect essentially any organ system, including pulmonary involvement. Interstitial lung disease is one of the most serious pulmonary complications, and the early diagnosis is essential to initiate a prompt therapy. On the other hand, Sjögren syndrome could present concomitantly with several rheumatologic diseases such as systemic lupus erythematosus or rheumatoid arthritis. Pulmonary Langerhans Histiocytosis is a rare clonal proliferative disease characterized by pulmonary involvement by cells phenotypically similar to Langerhans cells. We describe the case of a nonsmoker 62-year-old woman with Sjögren syndrome who presented concomitantly a Pulmonary Langerhans Histiocytosis mimicking a pulmonary complication of its Sjögren. Fortunately, she had a well response to corticosteroids and azathioprine regimen. The aim of the paper is to emphasize the importance of the good differential diagnosis related to the pulmonary involvement. To the best of our knowledge, this is the first description of these two entities in the literature. [ABSTRACT FROM AUTHOR]

The objective of this study was to describe the clinical and immunological characteristics of maternal autoimmune-mediated fetal congenital heart block (CHB) in a cohort of pregnant women from an autoimmune disease pregnancy clinic. This is a retrospective observational study of all women presenting with CHB in our autoimmune disease pregnancy clinic from January 1997 to December 2014. In addition, perinatal outcome is also described. Fourteen patients accounting for 18 fetuses with CHB were identified. The median age was 32.5 years (range, 22-40). Seven (50 %) patients had Sjögren's syndrome, and the remaining seven were asymptomatic carriers of autoantibodies. All patients had anti-Ro/SSA antibodies, and 11/13 (85 %) had anti-La/SSB antibodies. The median gestational age at the time of CHB was 22 weeks (range 18-28). Complete third degree CHB was detected in 12 (67 %). Seven cases of CHB were treated with dexamethasone, two with ritodrine, and one with the association of dexamethasone, ritodrine, and terbutaline. In 9 (50 %) cases that presented with, or developed, very poor prognosis factors, such as a ventricular rate below 50-55 bpm and/or the presence of fetal hydrops, parents opted for the termination of pregnancy, after dedicated counseling. Finally, there were nine newborns (seven males [78 %]) with median age at delivery of 37 weeks (range, 32-39). A definitive epicardial pacemaker was placed in six newborns, four of them within 2 weeks of life. CHB is a severe complication related to maternal anti-Ro/SSA and anti-La/SSB antibodies. Our results confirm previous data showing that therapy is ineffective, and most of the surviving patients will require neonatal pacemaker. [ABSTRACT FROM AUTHOR]

Introduction: Hepatitis C virus (HCV) infections are associated with extrahepatic manifestations in 40-75 % of cases. Sialitis and secondary Sjögren syndrome are well characterized complications of chronic HCV infections but the mechanisms (primary or secondary) leading to xerostomia are not understood. Similarly, brain lesions due to HCV can be primary or secondary but the pathology of primary HCV-related brain lesions is not well described. Case report: We report the postmortem case of a 60-year old patient initially presenting with sicca syndrome and dementia. HCV was identified in the brain but not in the salivary glands using transcription-mediated amplification (TMA). Focal sialitis was found in submandibular glands. Neuropathological examination revealed the presence of multiple dot-sized demyelination foci. Conclusion: Sicca syndrome is a common concern in chronic HCV infections and may be due to secondary immune mechanisms (we could not isolate HCV in salivary gland tissues). TMA had never been applied to the detection of viruses in salivary glands and neural tissues and proves to be a promising technique. Neuropathological reports in HCV infections are rare and the lesions we report may be the first characterization of the direct effect of HCV on brain cells. More cases are needed to define the full spectrum of lesions potentially caused by the direct action of the HCV on salivary glands and neural tissues. [ABSTRACT FROM AUTHOR]

Primary Sjögren syndrome (pSS) is a systemic autoimmune disease characterized by lymphocytic infiltration of the salivary and tear glands, and autoantibody secretion, in the absence of other systemic autoimmune disorder. Among autoimmune diseases, it is a relatively common disease, but the burden of central nervous system (CNS) involvement is controversial. This retrospective study evaluates the prevalence, clinical patterns and outcomes of CNS involvement in a cohort of patients with primary Sjögren syndrome. We evaluated 93 patients with pSS diagnosed according to American-European Consensus Group criteria. Fourteen patients (15.1 %) had CNS involvement. All were women with an average age of onset of the disease of 42.1 ± 14.7 years (average ± SD) and an average age of onset of neurological involvement of 47.29 ± 16 years. Three had parkinsonian syndrome, two epilepsy, two motor and sensory deficits, two headache with brain magnetic resonance abnormalities, two neuromyelitis optica, two chronic progressive myelitis and one aseptic meningitis. Neurological involvement preceded Sjögren syndrome diagnosis in nine of the patients (64 %), and neurological outcome was good in 11 patients (78.6 %). Central nervous involvement was not as rare as expected, and the frequency was similar to the frequency of peripheral nervous system involvement. In half of the patients, this was the first symptom of the disease, emphasizing the importance of considering this diagnosis, especially in young female with neurological symptoms without other evident cause. [ABSTRACT FROM AUTHOR]

To identify risk and predictors of lymphoma or lymphoproliferative disease in patients with primary Sjögren syndrome. Articles were identified through a comprehensive search strategy in Medline, Embase and Cochrane CENTRAL. Studies had to investigate primary Sjögren syndrome patients, 18 years of age or older, with the goal of examining potential clinical, immunological and hematological risk factors for lymphoma or lymphoproliferative disease. The quality of the studies was graded using the Oxford Levels of Evidence Scale. Whenever possible, the authors created evidence tables and performed meta-analysis. Of 900 studies identified, 18 were selected for inclusion. These studies provided data from over 15,000 patients (90 % female) for analysis. Lymphadenopathy, parotid enlargement, palpable purpura, low C4 serum levels and cryoglobulins were the most consistent non-Hodgkin´s lymphoma/lymphoproliferative disease predictors. Additionally, some of the studies identified splenomegaly, low C3 serum levels, lymphopenia and neutropenia as significant prognostic factors. The detection of germinal center-like lesions in primary Sjögren Syndrome diagnostic salivary biopsies was also proposed as highly predictive of non-Hodgkin´s lymphoma. In contrast, anemia, anti-Ro, anti-La, antinuclear antibodies, rheumatoid factor, male gender and hypergammaglobulinemia were not associated with lymphoma or lymphoproliferative disease. Patients with primary Sjögren syndrome have an increased risk of lymphoma or lymphoproliferative disease compared to the general population. Ascertaining relevant and reliable predictors in this patient population would greatly facilitate the identification of patients at elevated risk for closer monitoring in the context of limited resources. [ABSTRACT FROM AUTHOR]

Until recently, relatively little was known about the background risk of malignancy in pediatric rheumatic diseases. Worrying reports about the development of malignancies in children treated with new biologic agents have prompted rigorous studies of the incidence of malignancy associated with juvenile idiopathic arthritis (JIA). These studies reveal that JIA is likely to be associated with an increased risk of incident malignancy, irrespective of treatment with new biologic agents. A preliminary study indicates that the background risk of malignancy is also elevated in pediatric-onset systemic lupus erythematosus. On the basis of simple observation, the background risk of malignancy among children with Sjögren syndrome and dermatomyositis seems much lower than the markedly elevated risk found in adults with the same diagnoses. Clearly, the background risk of malignancy must be considered in any evaluation of the safety of new therapeutic agents. [ABSTRACT FROM AUTHOR]

Anti-cyclic citrullinated peptide antibody (anti-CCP) is a specific marker for the diagnosis of rheumatoid arthritis. However, this antibody can be detected in other rheumatic diseases and even in healthy people. This study aims to determine the prevalence and the clinical significance of anti-CCP in patients with primary Sjögren syndrome (pSS). We analyzed the clinical and laboratory data of 95 patients with pSS by retrospective review of their medical records. Anti-CCP was measured by ELISA kit. Anti-CCP, rheumatoid factor (RF), anti-nuclear antibody, anti-Ro and anti-La antibodies, and clinical data were investigated. We analyzed clinical and serologic characteristics of anti-CCP-positive patients. Twenty-one patients (22.1%) had positive anti-CCP (mean titer 61.6 ± 15.6 U/ml) and 40 patients (42.1%) had positive RF (mean titer 98.8 ± 22.7 IU/ml). Seventy-nine patients (83.1%) had arthralgia, and 31 patients (32.6%) had non-erosive arthritis on physical examination and radiologic images. Anti-CCP-positive patients had more frequently positive RF (71.4% vs. 41.8%, P = 0.01) and anti-Ro antibody (85.7% vs. 60.8%, P = 0.03). Anti-CCP-positive patients had non-erosive arthritis more frequently than anti-CCP-negative patients (76.1% vs. 21.6%, P < 0.01). The prevalence of anti-CCP was 22.1% in pSS, and anti-CCP was associated with non-erosive arthritis, and positivity of RF and anti-Ro antibody. [ABSTRACT FROM AUTHOR]