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ID PMID Title PublicationDate abstract
31652955 An Association of Gut Microbiota with Different Phenotypes in Chinese Patients with Rheuma 2019 Oct 24 We aimed to investigate the association of gut microbiota with disease activity, inflammatory parameters, and auto-antibodies profile in rheumatoid arthritis (RA). A total of 138 RA patients and 21 healthy controls (HC) were enrolled. Fecal samples were collected for bacterial DNA extraction and 16S ribosome (r)RNA sequencing, followed by analyses of gut microbiota composition. Serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-17A were determined by using ELISA. Our results indicated that RA patients had lower diversity index, which reflects both evenness and richness of gut microbiota, compared to HC. The alpha-diversity was lower in anti-citrullinated peptide antibodies (ACPA)-positive patients than in HC. The phylum Verrucomicrobiae and genus Akkermansia were more abundant in patients compared to HC. There was increased relative abundance of Enterobacteriaceae as well as Klebsiella, and less abundance of Bifidobacterium in patients with high levels of TNF-α or IL-17A compared to those who had low levels of these cytokines. In addition, ACPA-positive patients had higher proportions of Blautia, Akkermansia, and Clostridiales than ACPA-negative patients. Gut dysbiosis in RA patients was presented as different microbial composition and its association with inflammatory parameters as well as ACPA seropositivity. These findings support the involvement of gut microbiota in RA pathogenesis.
30886994 Real world long-term impact of intensive treatment on disease activity, disability and hea 2019 BACKGROUND: The emphasis on treating rheumatoid arthritis (RA) intensively reduces disease activity but its impact in routine care is uncertain. We evaluated temporal changes in disease activities and outcomes in a 10-year prospective observational cohort study of patients in routine care at one unit. METHODS: The Guy's and St Thomas' RA cohort was established in 2005. It involved most RA patients managed in this hospital. Clinical diagnoses of RA were made by rheumatologists. Patients were seen regularly in routine care. Each visit included measurement of disease activity scores for 28 joints (DAS28), health assessment questionnaire scores (HAQ) and EuroQol scores. Patients received intensive treatments targeting DAS28 remission. RESULTS: In 1693 RA patients mean DAS28 scores fell from 2005 to 15 by 11% from 4.08 (95% CI: 3.91, 4.25) in 2005 to 3.64 (3.34, 3.78); these falls were highly significant (p < 0.001). DAS28 components: swollen joint counts fell by 32% and ESR by 24%; in contrast tender joint counts and patient global assessments showed minimal or no reductions. The reduction in DAS28 scores was predominantly between 2005 and 2010, with no falls from 2011 onwards. Associated with falls in mean DAS28s, patients achieving remission increased (18% in 2005; 27% in 2015) and the number with active disease (DAS28 > 5.1) decreased (25% in 2005; 16% in 2015). In 752 patients seen at least annually for 3 years, persisting remission (68 patients) and intermittent remission (376 patients) were associated with less disability and better health related quality of life. Over time biologic use increased, but they were used infrequently in patients in persistent remission. CONCLUSIONS: Over 10 years an intensive management strategy in a routine practice setting increased combination DMARD and biologic use: disease activity levels declined; this association is in keeping with a causal relationship. Patients who achieved remission, even transiently, had better functional outcomes than patients never achieving remission.
31573949 Digital Tracking of Rheumatoid Arthritis Longitudinally (DIGITAL) Using Biosensor and Pati 2019 Sep 26 BACKGROUND: Rheumatoid arthritis (RA) is a condition with symptoms that vary over time. The typical 3- to 6-month interval between physician visits may lead to patients failing to recall or underreporting symptoms experienced during the interim. Wearable digital technology enables the regular passive collection of patients' biometric and activity data. If it is shown to be strongly related to data captured by patient-reported outcome (PRO) measures, information collected passively from wearable digital technology could serve as an objective proxy or be complementary to patients' subjective experience of RA symptoms. OBJECTIVE: The goal of this study is to characterize the extent to which digital measures collected from a consumer-grade smartwatch agree with measures of RA disease activity and other PROs collected via a smartphone app. METHODS: This observational study will last 6 months for each participant. We aim to recruit 250 members of the ArthritisPower registry with an RA diagnosis who will receive a smartwatch to wear for the period of the study. From the ArthritisPower mobile app on their own smartphone device, participants will be prompted to answer daily and weekly electronic PRO (ePRO) measures for the first 3 months. RESULTS: The study was launched in December 2018 and will require up to 18 months to complete. Study results are expected to be published by the end of 2021. CONCLUSIONS: The completion of this study will provide important data regarding the following: (1) the relationship between passively collected digital measures related to activity, heart rate, and sleep collected from a smartwatch with ePROs related to pain, fatigue, physical function, and RA flare entered via smartphone app; (2) determine predictors of adherence with smartwatch and smartphone app technology; and (3) assess the effect of study-specific reminders on adherence with the smartwatch. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/14665.
31100891 Gut Microbial Composition and Function Are Altered in Patients with Early Rheumatoid Arthr 2019 May 16 Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation of the joints and extra-articular manifestations. Recent studies have shown that microorganisms affect RA pathogenesis. However, few studies have examined the microbial distribution of early RA patients, particularly female patients. In the present study, we investigated the gut microbiome profile and microbial functions in early RA female patients, including preclinical and clinically apparent RA cases. Changes in microbiological diversity, composition, and function in each group were analyzed using quantitative insights into microbial ecology (QIIME) and phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt). The results revealed the dysbiosis due to decreased diversity in the early RA patients compared with healthy subjects. There were significant differences in the microbial distribution of various taxa from phylum to genus levels between healthy subjects and early RA patients. Phylum Bacteroidetes was enriched in early RA patients, while Actinobacteria, including the genus Collinsella, was enriched in healthy subjects. Functional analysis based on clusters of orthologous groups revealed that the genes related to the biosynthesis of menaquinone, known to be derived from gram-positive bacteria, were enriched in healthy subjects, while iron transport-related genes were enriched in early RA patients. Genes related to the biosynthesis of lipopolysaccharide, the gram-negative bacterial endotoxin, were enriched in clinically apparent RA patients. The obvious differences in microbial diversity, taxa, and associated functions of the gut microbiota between healthy subjects and early RA patients highlight the involvement of the gut microbiome in the early stages of RA.
31001257 Soluble CD83 Triggers Resolution of Arthritis and Sustained Inflammation Control in IDO De 2019 Interference with autoimmune-mediated cytokine production is a key yet poorly developed approach to treat autoimmune and inflammatory diseases such as rheumatoid arthritis. Herein, we show that soluble CD83 (sCD83) enhances the resolution of autoimmune antigen-induced arthritis (AIA) by strongly reducing the expression levels of cytokines such as IL-17A, IFNγ, IL-6, and TNFα within the joints. Noteworthy, also the expression of RANKL, osteoclast differentiation, and joint destruction was significantly inhibited by sCD83. In addition, osteoclasts which were cultured in the presence of synovial T cells, derived from sCD83 treated AIA mice, showed a strongly reduced number of multinuclear large osteoclasts compared to mock controls. Enhanced resolution of arthritis by sCD83 was mechanistically based on IDO, since inhibition of IDO by 1-methyltryptophan completely abrogated sCD83 effects on AIA. Blocking experiments, using anti-TGF-β antibodies further revealed that also TGF-β is mechanistically involved in the sCD83 induced reduction of bone destruction and cartilage damage as well as enhanced resolution of inflammation. Resolution of arthritis was associated with increased numbers of regulatory T cells, which are induced in a sCD83-IDO-TGF-β dependent manner. Taken together, sCD83 represents an interesting approach for downregulating cytokine production, inducing regulatory T cells and inducing resolution of autoimmune arthritis.
31170675 Multitarget-based cotreatment with cilostazol and celecoxib synergistically suppresses col 2019 Aug Cilostazol exerts potent anti-inflammatory effects and celecoxib, a COX-2 specific inhibitor, improves the unsatisfactory profile of NSAIDs. It was aimed to assess the anti-arthritic potential of celecoxib add-on for cilostazol therapy in collagen induced arthritis (CIA), and to elucidate the implication of interleukin (IL)-10 in the action of cilostazol and celecoxib cotreatment. Cotreatment of RAW 264.7 cells with 10 μM cilostazol and 0.3 μM celecoxib synergistically suppressed RANKL-induced increases in RANK mRNA and protein levels. When cultured in the presence of RANKL for 5 days, RANKL-stimulated expressions of osteoclastogenic genes (OSCAR, DC-STAMP, and cathepsin K mRNA) and the expression of RANK mRNA were markedly elevated. Furthermore, these gene expressions, including that of RANK, were significantly suppressed by cotreatment with cilostazol (10 μM) and celecoxib (0.3 μM). In addition, this co-treatment strongly down-regulated RANKL-induced NFATc1 protein and TRAP activity (key osteoclastogenic factors), and these down-regulations were significantly prevented by pretreating cells with IL-10 neutralizing antibody. Furthermore, increased osteoclast formation and extensive resorption pit formation by bone marrow-derived monocytes obtained from C57BL/6 mice cultured in the presence of M-CSF/RANKL were markedly suppressed by cilostazol and celecoxib cotreatment. Consequently, hindlimb paw thicknesses in DBA/1J CIA mice were significantly reduced by cilostazol (10 mg/kg/d) and celecoxib (5 mg/kg/d) cotreatment. These results were accompanied by synergistic suppression of cartilage depletion and bone erosion and reductions in arthritis scores in the CIA mice. In conclusion, serum IL-10 levels in these mice were markedly increased by cilostazol and celecoxib cotreatment, whereas elevated serum IL-1β levels were markedly reduced. Cotreatment with low-dose cilostazol and celecoxib may ensure the synergistic anti-arthritic potential.
31710871 Prognostic factors for primary Sjögren's syndrome-associated interstitial lung diseases. 2019 Nov OBJECTIVE: Interstitial lung disease (ILD) is a condition characterized by a higher mortality rate in primary Sjögren's syndrome (pSS). However, factors influencing the outcome of patients with pSS-associated ILD remain unclear. The aim of the present study was to evaluate predictive factors associated with a worse prognosis in pSS-ILD. METHODS: This retrospective study included 99 consecutive patients with pSS-ILD. Clinical characteristics, laboratory findings, and pulmonary function tests at the time of diagnosis were analyzed. Chest HRCT images were reviewed by two experienced chest radiologists. Prognostic factors were assessed by univariate and multivariate analyses, using Cox proportional hazards regression model. RESULTS: Median age was 68 years (73% women). In the total patient population, the 5- and 10-year survival rates were 89.8% and 79.0%, respectively. Univariate analysis revealed a significant association between prognosis and age, serum Krebs von den Lungen-6 (KL-6) levels, and %FVC. None of the chest HRCT findings were related to patient outcomes. Based on multivariate analyses adjusted by age and gender, lower levels of %FVC and higher levels of KL-6 were significantly associated with poor outcomes. Using optimal cutoff levels, according to receiver operating characteristic curve analyses, KL-6 > 800 U/mL were significantly associated with worse prognosis (HR: 2.91, 95% CI: 1.04-8.10). Patients with elevated serum KL-6 levels (>800 U/mL) showed a higher mortality rate than those without elevated serum KL-6 levels (p = 0.02). CONCLUSIONS: Lower %FVC and higher serum KL-6 levels are predictive factors for poor outcome in patients with pSS-ILD.
31214622 Sjogren's Syndrome and TAM Receptors: A Possible Contribution to Disease Onset. 2019 Sjogren's syndrome (SS) is a chronic, progressive autoimmune disease featuring both organ-specific and systemic manifestations, the most frequent being dry mouth and dry eyes resulting from lymphocytic infiltration into the salivary and lacrimal glands. Like the related autoimmune disease systemic lupus erythematosus (SLE), SS patients and mouse models display accumulation of apoptotic cells and a Type I interferon (IFN) signature. Receptor tyrosine kinases (RTKs) of the Tyro3, Axl, and Mer (TAM) family are present on the surface of macrophages and dendritic cells and participate in phagocytosis of apoptotic cells (efferocytosis) and inhibition of Type I IFN signaling. This review examines the relationship between TAM receptor dysfunction and SS and explores the potential contributions of TAM defects on macrophages to SS development.
31101054 Interleukin-1-related activity and hypocretin-1 in cerebrospinal fluid contribute to fatig 2019 May 17 BACKGROUND: Fatigue is a common and sometimes debilitating phenomenon in primary Sjögren's syndrome (pSS) and other chronic inflammatory diseases. We aimed to investigate how IL-1 β-related molecules and the neuropeptide hypocretin-1 (Hcrt1), a regulator of wakefulness, influence fatigue. METHODS: Hcrt1 was measured by radioimmunoassay (RIA) in cerebrospinal fluid (CSF) from 49 patients with pSS. Interleukin-1 receptor antagonist (IL-1Ra), IL-1 receptor type 2 (IL-1RII), IL-6, and S100B protein were measured by enzyme-linked immunosorbent assay (ELISA). Fatigue was rated by the fatigue visual analog scale (fVAS). RESULTS: Simple univariate regression and multiple regression analyses with fatigue as a dependent variable revealed that depression, pain, and the biochemical variable IL-1Ra had a significant association with fatigue. In PCA, two significant components were revealed. The first component (PC1) was dominated by variables related to IL-1β activity (IL-1Ra, IL-1RII, and S100B). PC2 showed a negative association between IL-6 and Hcrt1. fVAS was then introduced as an additional variable. This new model demonstrated that fatigue had a higher association with the IL-1β-related PC1 than to PC2. Additionally, a third component (PC3) became significant between low Hcrt1 concentrations and fVAS scores. CONCLUSIONS: The main findings of this study indicate a functional network in which several IL-1β-related molecules in CSF influence fatigue in addition to the classical clinical factors of depression and pain. The neuropeptide Hcrt1 seems to participate in fatigue generation, but likely not through the IL-1 pathway.
30403265 Association between systemic activity ındex and dry eye severity in patients with primary 2019 Jan PURPOSE: The aim of the present study was to compare the severity of ocular and systemic findings among patients with primary Sjögren syndrome. METHODS: The study followed a prospective controlled design and comprised two groups; the test group included 58 eyes of 58 patients newly diagnosed with primary Sjögren syndrome with poor dry eye test findings and the control group included 45 right eyes of 45 healthy age- and sex-matched individuals. The ocular surface disease index score, tear osmolarity, Schirmer I test without anesthesia, fluorescein tear breakup time, and cornea-conjunctiva staining with lissamine green (van Bijsterveld scoring) were used to examine tear function in the patients via a complete ophthalmological examination. The results were graded and classified on the basis of a Dry Eye WorkShop report and results of the corneal and conjunctival staining test, Schirmer's test, and fluorescein tear breakup time test. Discomfort, severity and frequency of symptoms, visual symptoms, conjunctival injection, eyelid-meibomian gland findings, and corneal-tear signs were interpreted. Disease activity was scored per the EULAR Sjögren's syndrome disease activity index (ESSDAI) via systemic examination and laboratory evaluations, and the EULAR Sjögren's syndrome patient-reported index (ESSPRI) assessed via a survey of patient responses. RESULTS: Mean patient age was 48.15 ± 16.34 years in the primary Sjögren syndrome group and 44.06 ± 9.15 years in the control group. Mean fluorescein tear breakup time was 4.51 ± 2.89s in the primary Sjögren syndrome group and 10.20 ± 2.39 s in the control group. Mean Schirmer I test result was 3.51 ± 3.18 mm/5 min in the primary Sjögren syndrome group and 9.77±2.30 mm/5 min in the control group. Mean ocular surface disease index score was 18.56 ± 16.09 in the primary Sjögren syndrome group, and 19.92 ± 7.16 in the control group. Mean osmolarity was 306.48 ± 19.35 in the primary Sjögren syndrome group, and 292.54 ± 10.67 in the control group. Mean lissamine green staining score was 2.17 ± 2.76 in the primary Sjögren syndrome group, and 0.00 in the control group. Statistically significant differences were found berween the primary Sjögren syndrome group and control group in terms of fluorescein tear breakup time, Schirmer's test, lissamine green staining, and osmolarity tests (p=0.036, p=0.041, p=0.001, and p=0.001 respectively). The Dry Eye WorkShop score was 2.15 ± 0.98, the EULAR Sjögren's syndrome disease activity index score was 11.18 ± 4.05, and the EULAR Sjögren's syndrome patient-reported index score was 5.20±2.63. When potential associations of the Dry Eye Workshop Study scores and osmolarity scores with the Eular Sjögren's syndrome disease activity index scores were evaluated, the results were found to be statistically significant (p=0.001, p=0.001 respectively). CONCLUSION: The results showed an association between dry eye severity and systemic activity index in primary Sjögren syndrome patients.
29458245 Impact of sleep quality on clinical features of primary Sjögren's syndrome. 2019 Sep BACKGROUND/AIMS: This study aimed to investigate the inf luence of poor sleep quality on clinical features of primary Sjögren's syndrome (pSS). METHODS: Sleep quality was cross-sectionally assessed using the Pittsburgh Sleep Quality Index (PSQI), and demographic, clinical, and laboratory data were collected from 115 Korean patients with pSS. The patients completed questionnaires on the European League Against Rheumatism (EULAR) SS Patient Reported Index (ESSPRI), quality of life (EuroQOL five dimensions questionnaire [EQ-5D]), fatigue (fatigue severity score [FSS]), and depression (Beck Depression Inventory [BDI] II]). Symptoms and patient global assessment (PGA) were evaluated with a 100-mm visual analogue scale (VAS). The EULAR sicca score (ESS), ESSPRI, and EULAR SS Disease Activity Index (ESSDAI) were calculated at study enrollment. RESULTS: Fifty-three patients (46.1%) had poor sleep quality and 32.4% of 71 patients without depression were poor sleepers. Poor sleepers had a significantly lower EQ-5D or ESSDAI and a significantly higher FSS, BDI-II, PGA, ESS, ESSPRI, or VAS scores for extra-glandular symptoms than good sleepers. Neutrophil and lymphocyte counts were significantly higher and immunoglobulin G levels tended to decrease in poor sleepers. Additionally, PSQI was negatively correlated with EQ-5D and ESSDAI and positively with ESS, FSS, BDI-II, PGA, VAS scores for their symptoms, and ESSPRI. Multivariate analysis revealed that poor sleep quality remained the independent determinants of the unsatisfactory symptom state (ESSPRI ≥ 5). CONCLUSION: Our results showed that poor sleep quality could significantly affect the patient-oriented outcomes and physician-reported activity index of pSS patients through the various effects of sleep quality on the psychological or somatic symptoms and the immune system.
31790331 Diagnostic approach for patients with unidentified fever according to the classical criter 2019 Dec Fever of unknown origin (FUO) is caused by various diseases, making differential diagnosis difficult. This study aimed to determine the clinical features of patients with FUO for use in daily medical practice. Medical records of patients who first visited our department for FUO between January 2008 and December 2017 were reviewed. We classified the diagnostic categories as infection, non-infectious inflammation, neoplasm, others, and unidentified through definitive diagnosis and compared the clinical characteristics of patients who fulfilled the criteria of classical FUO and those who did not. The most prevalent diseases in patients who fulfilled the criteria were adult-onset Still's disease, Behçet's disease (BD), and polymyalgia rheumatica, which do not have any specific image inspection or specific serological markers. BD and familial Mediterranean fever were most prevalent in patients who did not fulfill the criteria. All neoplasms fulfilled the criteria of classical FUO. The most useful diagnostic procedure was determined according to the criteria of each disease. The key factor that did not fulfill the criteria was periodic fever continuing for less than 3 weeks. When examining patients with FUO, we should strictly diagnose in accordance with the criteria of each disease and consider diseases that cause periodic fever.
31464665 Autoimmune epithelitis beyond the exocrine glands: an unusual case of anti-Ro/La and Scl-7 2019 May OBJECTIVES: Interstitial lung disease is a life-threatening complication of many systemic autoimmune diseases with diverse clinical and histopathological features. Among them, lymphocytic interstitial pneumonia (LIP) is mainly associated with primary Sjögren's syndrome (pSS). A case of a middle-aged man with LIP, anti-Ro/La, anti-Scl70 autoantibodies and overlapping histopathological features of pSS and systemic sclerosis (SSc) is presented and discussed. METHODS: A 65-year-old man complaining for easy fatigue and dry cough was evaluated. Physical examination revealed bibasilar crackles on auscultation. Imaging tests showed areas of centrilobular nodules with tree-in-bud sign on the medial lobe of the right lung. Pulmonary function tests demonstrated small airways disease. Laboratory evaluation revealed elevated ESR and CRP, ANA titre >1/320, positive Ro52, Ro60 and La autoantibodies but also, weakly positive anti Scl70 autoantibody. RESULTS: Right lobe lung biopsy showed diffuse fibrosis with altered alveolar architecture and diffuse infiltration of alveolar septa by lymphocytes and mast cells. Ectopic germinal centres were disclosed, adjacent to the small bronchi causing lumen obstruction and validated after the demonstration of CD23 expression, specific for follicular dendritic cells. Biopsy of minor salivary glands revealed intense periductal fibrosis with limited round cell infiltrates, not fulfilling the histopathological criteria for pSS. The diagnosis of LIP was established and the patient received corticosteroids with poor response. Subsequently he was treated with rituximab with satisfactory results. CONCLUSIONS: This case with LIP and disease-specific autoantibodies for pSS and SSc teaches the complexity and overlapping nature of both diseases, extending from autoimmune epithelitis with ectopic germinal centres to fibrosis-related SSc. It points out the significance of the affected tissue biopsy, which may uncover the different disease phenotypes. To this end, treatment with anti-CD20, acting at the crossroads of the pathogenetic mechanisms of both diseases may serve as a first choice therapy.
30053612 What is the best salivary gland ultrasonography scoring methods for the diagnosis of prima 2019 Mar OBJECTIVE: To evaluate the performance of salivary gland ultrasonography for the diagnosis of primary and secondary Sjögren's syndromes (pSS and sSS). METHOD: Multicenter cross-sectional study on 97 patients with clinical sicca symptoms. The pSS (n = 22) met the American-European Consensus Group (AECG) classification criteria. The control patients (n = 36) with sicca symptoms did not fulfill the AECG criteria. Four scores were used to evaluate the 4 major salivary gland echostructure: the Salaffi score (0-16), Jousse-Joulin score (0-4), Hocevar score (0-48) and Milic score (0-12). RESULTS: The medians of ultrasonographic (US) scores were higher in the pSS and sSS groups than in the control group (P < 0.001). The receiver-operating characteristic (ROC) curves and the positive likelihood ratio (LR+) of the four scores showed a good diagnostic performance for the US diagnosis of pSS and sSS. Respectively, for pSS and sSS, the AUC were 0.891 (95%CI 0.812-0.970) and 0.824 (95%CI 0.695-0.954) for Hocevar score, 0.885 (95%CI 0.804-0.965) and 0.808 (95%CI 0.673-0.943) for Milic score, 0.915 (95%CI 0.848-0.982) and 0.844 (95%CI 0.724-0.965) for Salaffi score, 0.897 (95%CI 0.821-0.973) and 0.851 (95%CI 0.735-0.968) for Jousse-Joulin score. This study showed an interesting inter-observer reproducibility (kappa = 0.714 ± 0.131) of the US evaluation with 85.7% agreement between reader to determine the pathological character of the salivary glands. CONCLUSION: Salivary gland US is a simple, non-invasive and performant imaging procedure for the diagnosis of pSS and sSS, with Salaffi, Milic and Jousse-Joulin scores.
31556344 Pulmonary involvement in primary Sjögren's syndrome, as measured by the ESSDAI. 2020 Jan Objective: Systemic features influence disease prognosis and choice of treatment in primary Sjögren's syndrome (pSS). Our aim was to investigate the prevalence of pulmonary involvement in pSS patients and to classify patients according to the pulmonary domain of the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI).Methods: This retrospective cohort study included consecutive pSS patients, fulfilling American-European Consensus Group/American College of Rheumatology classification criteria, who visited the Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, in 2015. Data on pulmonary complaints and pulmonary tests were obtained from electronic patient records. Pulmonary involvement was recorded if therapy was needed or follow-up was recommended, and when it was possibly or assumed to be related to pSS instead of coincidental factors.Results: Of the 262 included pSS patients, 88 (34%) had pulmonary complaints, mostly cough or dyspnoea on exertion. Pulmonary diagnostics were performed in 225 patients (86%). Pulmonary involvement was present and assumed to be related to pSS in 25 patients (10%) and possibly related to pSS in 14 (5%). Interstitial lung disease (ILD, n = 15), especially non-specific interstitial pneumonia (n = 7), was present most commonly. In total, 16 patients (6%) were scored as low (n = 4), moderate (n = 11), or high activity (n = 1) on the ESSDAI pulmonary domain.Conclusion: In this cross-sectional study in daily clinical practice, pulmonary involvement was present in 10-15% of pSS patients, of which ILD was most common. Of all pSS patients, 6% were scored as active on the pulmonary domain of the ESSDAI.
31275901 Concomitant Sjögren's Syndrome Was Not Associated with a Poorer Response or Outcomes in U 2019 AIM: Patients with primary biliary cholangitis (PBC) have at least 60% probability of having an autoimmune extrahepatic condition, with the most common being Sjögren's syndrome (SS). The impacts of SS on the response and outcomes in ursodeoxycholic acid (UDCA)-treated patients with PBC, however, remain unclear. The aim of this study was to document the biochemical responses and clinical outcomes of UDCA-treated patients with concomitant SS and to compare the findings to those of patients with PBC alone. METHODS: Data from consecutive patients with PBC who visited West China Hospital affiliated with Sichuan University between October 2013 and October 2017 were reviewed retrospectively. RESULTS: The study populations consisted of 226 patients with PBC alone and 56 with PBC/SS. The median ages, proportions of female patients, Fib-4 scores, and aspartate aminotransferase (AST)/platelet ratio index (APRI) at baseline in the two cohorts were similar. At presentation, patients with PBC/SS had higher serum IgG levels and positive rates for serum antinuclear antibody (ANA) than patients with PBC alone (all P < 0.05). There was no statistically significant difference between the rate of biochemical response to UDCA at 1 year in the PBC/SS and PBC alone groups. The UK-PBC risk scores and GLOBE scores in UDCA-treated patients in the two cohorts were also similar. During the follow-up period, the differences in the liver enzyme levels, Fib-4 scores, APRI, and incidence of liver-related adverse events were not significant. CONCLUSIONS: The results of this retrospective, single-center study suggest that the response and clinical outcomes of UDCA-treated patients with PBC are not adversely affected by concomitant SS.
31203680 Small-molecule inhibitors and the salivary gland epithelium in Sjögren's syndrome. 2019 Jul INTRODUCTION: The salivary gland (SG) in primary Sjögren's syndrome (pSS) is characterized by its lack of function (hyposalivation) and lymphocytic invasion. Small-molecule inhibitors (SMIs) are a new class of drugs, whose diminutive size permits diffusion into cells. SMIs targeting components of the immune system are eagerly being trialed for their potential therapeutic utility in pSS. Neglected until now, however, is a discussion of the potential effects of SMIs on the SG epithelium. AREAS COVERED: We begin by reminding the reader of the SG epithelial compartment, its complicity in inflammatory milieu formation in pSS, and categories of SMIs which merit attention. We discuss each SMI category, including pre-clinical data concerning pSS and likely consequences of their application on the SG epithelium. EXPERT OPINION: Recovery of saliva production in pSS requires restoring the function of the SG epithelium, not solely on inflammation resolution. Many SMIs, for example, those blocking JAK-STAT signaling, interfere with critical epithelial cell pathways, most notably EGF signaling. If the effect of SMIs on SG epithelium is ignored, recovery of SG function will be challenging. We predict that NFκB signaling blockade will impart the least SG epithelium damage whilst reducing inflammation and facilitating recovery from hyposalivation in pSS.
30674351 Fluocinolone acetonide intravitreal implant as a therapeutic option for severe Sjögren's 2019 Jan 24 BACKGROUND: In this report, we present the results of a severe case of Sjögren's syndrome-related keratopathy after fluocinolone acetonide 190-μg intravitreal implant (Iluvien®; Alimera Sciences Inc.) therapy. CASE PRESENTATION: A 52-year-old Caucasian woman with Sjögren's syndrome secondary to autoimmune hepatitis and primary sclerosing cholangitis was admitted to our emergency department owing to bilateral corneal ulcers and corneal perforation in the left eye following exposure keratopathy in an artificially induced coma. Within the following months, recurrent fulminant keratolysis with perforations required multiple penetrating keratoplasties and amniotic membrane transplants in both eyes. With new signs of severe keratolysis, an intravitreal fluocinolone acetonide implant was injected off-label in the left eye, and a third penetrating keratoplasty was performed 2 weeks later. In the 6 months of follow-up after the last penetrating keratoplasty, no more surgical interventions were needed in the eye with the fluocinolone acetonide implant. The corneal surface remained stable, and intraocular pressure was normal. During this time frame, two further penetrating keratoplasties, one vitrectomy, and five amniotic membrane transplants were performed in the fellow eye owing to relapsing keratolysis and perforations. CONCLUSIONS: To the best of our knowledge, this is the first report of fluocinolone acetonide intravitreal therapy in a patient with corneal disease. In the 6-month follow-up period, no surgical intervention was needed in the eye with the fluocinolone acetonide implant, whereas further penetrating keratoplasties and amniotic membrane transplants were performed in the fellow eye. Intravitreal fluocinolone acetonide may be considered as a treatment option in severe cases of autoimmune corneal disease.
31929838 The Utility of Major Salivary Gland Ultrasonographic Parameters in the Diagnosis of Sjögr 2019 OBJECTIVE: To investigate ultrasonographically the salivary glands and to correlate ultrasonographic parameters with focus score, serum beta-2-microglobulin, and stimulated salivary flow rate. MATERIAL AND METHODS: 32 patients with primary Sjögren's syndrome (pSS) and 32 healthy controls were enrolled in this case-control study, performed in the Department of Internal Medicine, Division of Rheumatology, "Victor Babeș" University of Medicine and Pharmacy, Timișoara, Romania. All the patients and controls were examined by salivary gland ultrasonography (B-mode, color and spectral Doppler, and sonoelastography), determining the following parameters: salivary gland ultrasonography (SGUS) score, resistive index (RI) of transverse facial artery, and shear wave velocity (SWV). Serum beta-2-microglobulin and stimulated saliva amount were determined in all the patients and controls. Minor salivary gland biopsy with focus score assessment was done in pSS patients. RESULTS: Patients with pSS presented higher SGUS score and parotid and submandibular SWV and reduced RI of transverse facial artery than controls (p < 0.0001). In pSS patients, statistically significant correlations were identified between assessed ultrasonographic parameters and focus score, serum beta-2-microglobulin, and respective stimulated saliva flow (p < 0.0001). CONCLUSIONS: This study highlighted statistically significant correlations between salivary gland ultrasonographic parameters and focus score, serum beta-2-microglobulin, and stimulated saliva flow.
31140693 World Workshop on Oral Medicine VII: Immunobiologics for salivary gland disease in Sjögre 2019 Jun OBJECTIVE: This systematic review evaluated the efficacy of immunobiologics for the management of oral disease in Sjögren's syndrome (SS). MATERIALS AND METHODS: MEDLINE(®) , Embase, Scopus, and the Cochrane Library were searched for evidence on the use of immunobiologics for management of glandular disease in SS. Primary outcomes were xerostomia and salivary gland dysfunction, assessed via visual analogue scales, disease-specific scales for SS, measurement of salivary flow, ultrasound data, and quality of life measures. RESULTS: Seventeen studies (11 randomized controlled trials and 6 observational studies) met inclusion criteria. Rituximab showed efficacy in improving salivary gland function but not xerostomia. Abatacept showed promise in improving both xerostomia and salivary flow. Belimumab exhibited long-term improvement of salivary flow and subjective measures. The novel agent CFZ533 improved both disease activity and patient-reported indexes. CONCLUSIONS: There is strong evidence pointing to the efficacy of rituximab in the management of oral disease in SS. Future controlled trials may elucidate the efficacy of belimumab and abatacept. The new drug CFZ533 is a promising alternative for the management of SS and its salivary gland involvement. In considering these agents, the promise of efficacy must be balanced against the harmful effects associated with biologic agents.