Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
32541072 Disease Activity Score in 28 Joints Using GGT Permits a Dual Evaluation of Joint Activity 2020 Dec 1 OBJECTIVE: To identify the factors potentially associated with serum gamma-glutamyltransferase (GGT) elevation in patients with rheumatoid arthritis (RA). METHODS: This is a cross-sectional monocentric study including RA patients over a 12-month period. Data on liver function, RA disease activity, and hepatotoxic and cardiovascular (CV) risk factors were systematically collected. To provide a simple tool to evaluate both joint disease activity and CV risk factors, we constructed the Disease Activity Score in 28 joints (DAS28)-GGT composite index by replacing erythrocyte sedimentation rate (ESR) with GGT. RESULTS: Among the 129 included patients, 32 (25%) had isolated GGT increase. GGT correlated with age, C-reactive protein (CRP) levels, and body weight and were significantly increased in patients with alcohol intake, type 2 diabetes mellitus, hypertension, dyslipidemia, and metabolic syndrome. GGT levels also gradually increased with the number of CV risk factors and correlated with the Framingham CV risk score. The composite index DAS28-GGT remained a reliable marker of RA disease activity and accurately detected patients with CV risk factors. Conversely to the DAS28 and the DAS28-CRP, the DAS28-GGT steadily increased according to the number of CV risk factors and had an increased diagnostic value compared to the DAS28 and DAS28-CRP for the presence of at least 2 CV risk factors and a Framingham CV risk score greater than 10%. CONCLUSION: GGT may be considered as a marker of systemic inflammation and CV risk in patients with RA. Based on these findings, we herein propose an original index, the DAS28-GGT, which is able to evaluate both joint disease activity and CV risk. This index will deserve further validation in prospective cohorts.
31911367 Systematic review of the efficacy of commonly prescribed pharmacological treatments for pr 2020 Feb Sleep disturbances are commonly reported by patients with autoimmune disease, and are negatively related to both disease activity and quality of life. Despite the potential for sleep disturbance to exacerbate inflammatory pathways, acute management of sleep disturbance with pharmacological aids is not well understood in this patient group. The objective of this review was to determine the efficacy of pharmacological treatments for sleep disturbance to improve sleep outcomes in adult patients with diagnosed autoimmune disease. Four databases and grey literature were searched for randomized controlled trials which used a pharmacological treatment specifically to treat sleep disturbance in patients with diagnosed autoimmune disease, both in hospitalized and non-hospitalized settings. A sleep outcome was required to be the primary endpoint of the study. Of the 409 studies identified, a total of six were included in the systematic review. Risk of bias across the studies was largely unclear, making an assessment challenging; meta-analysis was not undertaken due to clinical and methodological heterogeneity between studies. While there appeared to be perceived improvement in self-reported sleep quantity and quality in existing studies with pharmacological treatment, there was also evidence of placebo effect on some measures. Relatively small numbers of patients have undergone gold-standard polysomnographic (PSG) recording of sleep which limits our knowledge of objectively determined sleep quantity and quality in patients with autoimmune disease receiving pharmacological treatment for sleep disturbance. Presently there is insufficient evidence to determine whether pharmacological treatment of sleep disturbance is beneficial for improving sleep quantity and quality in this patient group beyond rheumatoid arthritis.
31046542 The in vitro effect of antirheumatic drugs on platelet function. 2020 Several antirheumatic drugs lower the cardiovascular risk among rheumatoid arthritis patients. It is, however, unknown whether inhibition of platelet function contributes to this risk reduction. Only few studies have investigated the potential role of platelets as a target of antirheumatic drugs. In this study, platelet function was tested in vitro in samples from 24 healthy individuals spiked with antirheumatic drugs in clinically relevant concentrations or vehicle. Platelet aggregation was tested with 96-well light transmission aggregometry (LTA), and when an effect ≥20% compared to vehicle was observed, flow cytometric platelet aggregation and activation were evaluated and closure time was measured by Platelet Function Analyzer (PFA-200). When evaluated by LTA, teriflunomide (the active metabolite of leflunomide), tocilizumab, and prednisolone reduced ADP- and collagen-induced platelet aggregation ≥20%, while adalimumab increased TRAP-induced platelet aggregation ≥20%. Using flow cytometry, agonist-induced platelet aggregation with teriflunomide or vehicle was mean ± standard deviation (SD); 30.7% ± 5.8 vs. 41.7% ± 6.5, p = 0.02 using ADP, and 34.7% ± 13.9 vs. 55.8% ± 3.9, p = 0.01 using collagen. Results indicate that teriflunomide, prednisolone, and tocilizumab inhibit, and adalimumab increases platelet aggregation. The study suggests that the majority of antirheumatic drugs mainly reduced cardiovascular risk through indirect effects (e.g., reducing inflammation).
32161846 Successful long-term remission through tapering tocilizumab infusions: a single-center pro 2020 BACKGROUND: Strategic drug therapy for rheumatoid arthritis (RA) patients with prolonged remission is not well defined. According to recent guidelines, tapering biological Disease-Modifying Anti-Rheumatic Drugs (bDMARDs) may be considered. We aimed to evaluate the effectiveness of long-term maintenance of tocilizumab (TCZ) treatment after the progressive tapering of infusions. METHODS: We conducted an exploratory, prospective, single-center, open-label study, on RA patients with sustained remission of at least 3 months and treated with TCZ infusions every 4 weeks. The initial re-treatment interval was extended to 6 weeks for the first 3 months. Thereafter, the spacing between infusions was determined by the clinician. Successful long-term maintenance following the tapering of TCZ infusions was defined by patients still treated after two years by TCZ with a minimum dosing interval of 5 weeks. RESULTS: Thirteen patients were enrolled in the study. Eight out of thirteen were still treated by TCZ after two years. Successful long-term maintenance was possible in six patients, with four patients maintaining a re-treatment interval of 8-weeks or more. We observed 5 patients with TCZ withdrawal: one showing adverse drug reaction (neutropenia) and four with secondary failure. Patients achieving successful long-term maintenance with TCZ were significantly younger than those with secondary failure (p < 0.05). In addition, RA patients with positive rheumatoid factor and anti-citrullinated peptide antibodies, experienced a significantly greater number of flares during our 2-year follow-up (p < 0.01). CONCLUSIONS: A progressive tapering of TCZ infusions may be possible for many patients. However, larger studies, including more patients, are needed to confirm this therapeutic option. TRIAL REGISTRATION: NCT02909998. Date of registration: October 2008.
32383727 Protective effects of Bifidobacterium adolescentis on collagen-induced arthritis in rats d 2020 May 1 Emerging studies have addressed the role of probiotics in inflammation modulation via modifying gut microbiota. Perturbed gut microbiota is recognized as a pivotal trigger in the pathogenesis of rheumatoid arthritis (RA), and manipulating gut microbiota at the early phase may be helpful to alleviate the disease based on the fact that dysbiosis occurred prior to clinical arthritis. The current study compared the effects of preventive and therapeutic treatment with Bifidobacterium adolescentis on collagen induced arthritis (CIA) in rats. Early B. adolescentis administration before CIA modelling performed better than late B. adolescentis treatment in reducing the clinical symptoms, rebalancing the pro- and anti-inflammatory responses and maintaining the fecal concentration of short chain fatty acids (SCFAs), as well as restoring the intestinal dysbiosis. Preventive B. adolescentis treatment restored the gut microbiota to a normal level while late B. adolescentis fed rats showed clearly different gut microbial profiles. In addition, there were slight discrepancies between early- and late- treatment of B. adolescentis in the production of specific auto-antibodies and tight junction proteins. All those results highlighted that early treatment of probiotics in arthritis might be a better timing for alleviating arthritis.
32141013 Appraisal of disease-modifying potential of amlodipine as an anti-arthritic agent: new ind 2020 Aug Amlodipine, a second-generation calcium channel blocker, exhibits documented anti-inflammatory potential. Thereby, present investigation was accomplished with an aim to explore anti-arthritic potential of amlodipine, giving a second chance to an existing drug. For validation of anti-arthritic potential of amlodipine, some in vitro models comprised of bovine serum albumin- and egg albumin-induced protein denaturation along with membrane stabilization of red blood cell was being conducted. In vivo models comprised of formaldehyde-provoked acute arthritis and CFA-instigated chronic arthritic. Paw edema, arthritic index, body weight alterations, biochemical and hematological parameters, and ankle joint histological and radiographic investigations were appraised. Moreover, RT-PCR was conducted to evaluate the levels of several inflammatory markers. Molecular docking was being conducted targeting TNF-α, IL-1β and IL-6 to establish the correlation between experimental and theoretical results. Amlodipine provides significant protection against denaturation being provoked by heating egg albumin and BSA along with stabilizing membrane of red blood cell, thereby proving in vitro anti-arthritic effect. A significant (p < 0.001) reduction in paw swelling was being observed with amlodipine in case of formaldehyde-instigated arthritis especially at the dose of 20 mg/kg. In case of CFA-provoked arthritis, reduction in paw volume and arthritic score while preservation of body weight loss and normal hematological and biochemical parameters in comparison to arthritic control were being manifested by amlodipine at the dose of 20 mg/kg. Gene expression level of TNF-α, IL-6 and IL-1β was significantly reduced by amlodipine while an increase in expression level of IL-4 and IL-10 was evident in animals treated with piroxicam and amlodipine. Molecular docking analysis demonstrated strong binding interaction of amlodipine with TNF-α, IL-6 and IL-1β thus providing a good correlation between experimental and theoretical results. Thus, current study is suggestive that amlodipine exhibits strong anti-arthritic potential and thus can be considered as a candidate for drug repurposing as anti-arthritic agent.
33094270 Factors associated with disability in patients with rheumatoid arthritis with persistent m 2020 BACKGROUND: Many patients with rheumatoid arthritis (RA) do not attain remission/low disease activity, remaining in a moderate disease activity state (MDAS) with ongoing disability and impaired quality of life (QoL). If patients in persistent MDAS with poor future outcomes could be prospectively identified, they could arguably be treated more intensively. We evaluated baseline factors predicting function (Health Assessment Questionnaire-Disability Index [HAQ-DI] scores) and QoL (3-level EuroQol-5 dimensions questionnaire [EQ-5D-3L] index scores) at 12 months in patients with RA in persistent MDAS in a real-world setting. METHODS: Patients with persistent MDAS (Disease Activity Score for 28-joint count based on erythrocyte sedimentation rate [DAS28-ESR] 3.2-5.1 on at least two consecutive outpatient appointments over 12 months) were identified retrospectively from Guy's Hospital RA Centre and analysed in two groups: (1) biologic naïve at baseline or (2) receiving/ever received biologics. The baseline timepoint was the second-visit MDAS DAS28-ESR score; the endpoint was the closest visit to 12 months. Linear regression analyses evaluated relationships between baseline variables and (1) 12-month HAQ-DI scores, (2) 12-month rank-transformed EQ-5D-3L index scores, (3) 12-month changes in HAQ-DI scores, and (4) 12-month changes in EQ-5D-3L index scores. RESULTS: The analysis included 207 biologic-naïve and 188 biologic-experienced patients. All patients had moderate disability (mean HAQ-DI 1.21 and 1.46) and impaired QoL (mean EQ-5D-3L index scores 0.52 and 0.50). Many reported moderate/severe pain (93 and 96%) and showed little change in HAQ-DI and EQ-5D-3L index scores over 12 months. In both biologic-naïve and biologic-experienced groups, multivariate analysis revealed a significant association between baseline HAQ-DI scores and endpoint HAQ-DI scores (β = 0.67, P < 0.001 and β = 0.76, P < 0.001, respectively), 12-month changes in HAQ-DI scores (both β = - 0.21, P < 0.001), and 12-month EQ-5D-3L index scores (β = - 0.57, P < 0.001 and β = - 0.29, P = 0.004, respectively). Baseline EQ-5D-3L index scores were significantly associated with 12-month changes in EQ-5D-3L index scores in both groups (β = - 0.73, P < 0.001 and β = - 0.40, P = 0.003, respectively). CONCLUSIONS: Patients with RA in persistent MDAS experience substantial ongoing physical disability, poor QoL, and pain. HAQ-DI is an important predictor of future disability and reduced QoL, supporting current national recommendations to measure HAQ-DI in routine care.
33274030 Clinical Outcomes after Reverse Total Shoulder Arthroplasty According to Primary Diagnosis 2020 Dec BACKGROUND: To compare the clinical outcomes of reverse total shoulder arthroplasty (RTSA) according to the primary diagnosis. METHODS: In 98 shoulders (97 patients), RTSA was performed for cuff tear arthropathy (45), massive rotator cuff tear without glenohumeral arthritis (31), posttraumatic arthritis (9), primary osteoarthritis (6), rheumatoid arthritis (4), and arthritis due to infection sequelae (3). The average age of the patients at surgery was 68.9 years (range, 46-84 years). The mean follow-up duration was 48.4 months (range, 24-85 months). RESULTS: In the overall series, the mean subjective pain score (visual analog scale) during motion decreased from 5.2 preoperatively to 1.8 at 2 years of follow-up. There were significant improvements in active forward flexion (preoperatively 51.5° to 121.8° at 2 years of follow-up). The average Constant score improved from 35.4 points to 57.8 points and UCLA score improved from 13.4 points to 28.8 points. The Constant score and UCLA score were 60.8 and 31.0 points, respectively, in patients with rheumatoid arthritis. The Constant score and UCLA score were 58.4 and 29.1 points, respectively, in patients with cuff tear disease and 55.7 and 27.7 points, respectively, in patients with posttraumatic arthritis. Patients' subjective satisfaction was 86.8 points in the overall series; highest in the patients with arthritis by infection sequelae (96.7 points) and lowest in the patients with posttraumatic arthritis (82.2 points). In terms of complications, there were 17 cases (17.3%) of scapular notching and 2 patients with suprascapular nerve irritation symptom, but no patients with permanent neuropathy. CONCLUSIONS: The range of forward flexion and abduction motion, pain relief, and functionality were improved after RTSA in not only patients with cuff tear disease but also those with other arthritic diseases. There was no difference in the clinical outcomes of RTSA between patients with cuff tear disease and those with other arthritic diseases.
32711507 Sjogren's syndrome is associated with higher rate of non-home discharge after primary hip 2020 Jul 25 BACKGROUND: To assess whether Sjogren's Syndrome (SS) is associated with outcomes after total knee or hip arthroplasty (TKA/THA). METHODS: We used the 1998-2014 U.S. National Inpatient Sample data. We performed multivariable-adjusted logistic regression analyses to assess the association of SS with healthcare utilization (hospital charges, length of hospital stay, discharge to non-home setting), and in-hospital complications (implant infection, revision, transfusion, mortality), controlling for important covariates and confounders. In sensitivity analyses, we additionally adjusted the main models for hospital location/teaching status, bed size, and region. RESULTS: We examined 4,116,485 primary THAs and 8,127,282 primary TKAs performed from 1998 to 2014; 12,772 (0.2%) primary TKAs and 6222 (0.2%) primary THAs were done in people with SS. In multivariable-adjusted models, SS was associated with a statistically significant higher odds ratio (OR; 95% confidence interval (CI)) of discharge to a rehabilitation/inpatient facility post-THA, 1.13 (1.00, 1.28), but not post-TKA, 0.93 (0.86, 1.02). We noted no differences in the length of hospital stay or hospital charges. SS was associated with significantly higher adjusted odds of in-hospital transfusion post-THA, 1.37 (1.22, 1.55) and post-TKA, 1.21 (1.10, 1.34). No significant differences by SS diagnosis were seen in hospital stay, hospital charges implant infection, implant revision or mortality rates. CONCLUSIONS: People with SS had higher transfusion rate post-TKA/THA, and higher rate of discharge to non-home setting post-THA. The lack of association of SS with post-arthroplasty complications should reassure patients, surgeons and policy-makers about the utility of TKA/THA in people with SS undergoing these procedures.
31902032 Characteristics of patients with primary Sjögren's syndrome associated interstitial lung 2020 May OBJECTIVE: To investigate characteristics of patients with primary Sjögren's syndrome (pSS)-associated interstitial lung disease (ILD) and relevant features of ILD progression. METHOD: Patients with pSS were retrospectively reviewed, and pSS-ILD and pSS non-ILD were identified. Clinical data, laboratory parameters, pulmonary high-resolution CT (HRCT), and pulmonary function tests (PFTs) were collected. pSS-ILD patients were further categorized into subgroups according to HRCT patterns or PFTs. RESULTS: Eighty-five pSS-ILD patients and 85 pSS non-ILD patients were included. The average age at disease onset and median disease duration were significantly higher in pSS-ILD patients than those in pSS non-ILD patients (p < 0.001). Fever, xerostomia, xerophthalmia, and numbness were more frequent, and white blood cells, C reactive protein, and immunoglobulin G (IgG) levels were higher in pSS-ILD patients when compared to pSS non-ILD patients (p < 0.01). More male patients, older age at disease onset, and less frequent anti-Ro52 antibody were noted in patients with CT-usual interstitial pneumonia (UIP) pattern. In 49 patients with pSS-ILD, who repeated PFTs 6 months from the baseline, 79.6% were stable while 20.4% progressed, with ESR and CT-UIP pattern related with disease progression. CONCLUSIONS: Patients with pSS-ILD were characterized by more frequent fever, xerophthalmia, and elevated IgG levels, while male, older age at disease onset, and less frequent anti-Ro52 antibody were related with CT-UIP pattern. ESR and CT-UIP pattern were potential predictors for ILD progression.Key Points• pSS-ILD patients are characterized by more frequent fever, xerophthalmia and elevated IgG.• Anti-Ro52 antibody is less frequent in patients with CT-UIP pattern compared to non-UIP patterns.• ESR and CT-UIP pattern are associated with pSS-ILD progression.
31244376 Effectiveness of resistance exercise in functional fitness in women with primary Sjögren' 2020 Jan Objective: The purpose of this study was to analyse the effectiveness of resistance exercise in functional fitness in women with primary Sjögren's syndrome (pSS).Method: This is a randomized controlled clinical trial with 51 volunteers: 26 allocated to the exercise group (GEX) and 25 to the control group. The GEX underwent a supervised resistance-training programme for 16 weeks, with two sessions per week. The outcomes measured were: functional capacity (FC), by the Fullerton Functional Fitness Test; Daily Motor Activity Index (DMAI), evaluated by an actigraph; disease activity, by the ESSDAI; and quality of life, by the 36-item Short Form Health Survey (SF-36). The evaluations were performed by a blind evaluator at baseline (TØ) and after 16 weeks (T16wk).Results: In the GEX, all FC parameters demonstrated improvement, except for the upper limb flexibility test (p = 0.866): upper and lower limb strength, flexibility, aerobic capacity, and agility (all p < 0.01). A similar situation occurred in the SF-36, where all domains demonstrated improvement except for the emotional aspect (p = 0.710): FC, physical aspects limitation, general health status, vitality, social aspects, and mental health (all p < 0.01). The DMAI (p = 0.2) and EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) (p = 0.284) did not change. No significant improvement was observed in the control group.Conclusion: The supervised resistance exercise programme did not worsen the DMAI or disease activity, demonstrating the safety of the intervention, and was effective in improving FC and quality of life in women with pSS.Registry identifier (clinical trials.gov): NCT03130062.
33005412 CD163 deficiency facilitates lipopolysaccharide-induced inflammatory responses and endotox 2020 OBJECTIVES: Septic (or endotoxin) shock is a severe systemic inflammatory disease caused by bacteraemia or endotoxaemia. Although it is known that increased serum levels of CD163 are observed in septic/endotoxin shock patients, the exact function and significance of CD163 in macrophage activation remain unclear. Therefore, in the current study, we tested whether CD163 contributes to the pathogenesis of endotoxin shock in mice. METHODS AND RESULTS: In samples obtained from autopsy, the number of CD163-positive macrophages was increased in the kidney, liver, heart, bone marrow and spleen of patients who had died from septic/endotoxin shock when compared to patients who had died from other causes. The animal study revealed a significantly lower survival rate in CD163-deficient mice after lipopolysaccharide (LPS) injection. Several cytokines and oxidative stress-related molecules were significantly elevated in the sera of LPS-induced endotoxin shock mice models. Higher concentrations of IL-6, TNF-α, IL-1β, nitrite ( NO2- ) and nitrate ( NO3- ) and a lower concentration of IL-10 were observed in CD163-deficient mice treated with LPS. Similar results were observed in CD163-deficient LPS-stimulated macrophages. Furthermore, in an antitype II collagen antibody-induced arthritis (CAIA), rheumatoid arthritis model, inflammation and bone erosion scores as well as the expression of IL-6 and IL-1β were significantly increased in CD163-deficient mice. CONCLUSIONS: CD163 was suggested to be involved in the regulation of inflammatory cytokine expression in septic/endotoxin shock and CAIA.
33264685 Cicatrizing conjunctivitis as an uncommon manifestation of primary Sjögren's syndrome. 2021 Jan PURPOSE: To report occurrence of cicatrizing conjunctivitis as an extraglandular ocular manifestation of primary Sjögren's syndrome (SS). METHODS: Medical charts of all patients with SS evaluated at two tertiary ophthalmological referral centers were reviewed. Patients who demonstrated clinical findings of cicatrizing conjunctivitis were included in this review. Patient and disease-related data including ocular complications, therapies and outcomes were collected. RESULTS: Eight patients with a diagnosisis of SS were noted to have cicatrizing conjunctivitis findings over a period of 11 years (between 2009 and 2020). Mean age of patients was 79. All patients had a negative immunoreactant deposition in conjunctival biopsy. Mean follow-up time was 6 years (range, 18-197 months). Three patients had progression of conjunctival scarring. Worsening of vision occurred in 4 patients due to corneal complications, including ulceration, perforation and scarring. CONCLUSIONS: SS is an under-recognized etiology of severe progressive cicatrizing conjunctivitis that can lead to ocular morbidity and loss of vision without appropriate management.
33070375 Cytokine profiles and clinical characteristics in primary Sjögren´s syndrome patient gro 2021 Feb BACKGROUND: Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by a lymphocytic infiltrate in salivary glands driving to epithelial damage. The pSS patients present heterogenic clinical and serological characteristics. This heterogenicity could be due to the cytokine microenvironment. Cytokine levels have been analyzed and reported individually, showing controversial results; for that reason, we considered essential to evaluate a cluster of cytokines and relate them with antibody levels and clinical characteristics to find pSS subgroups. METHODS: Ninety-nine pSS patients, diagnosed by the 2016 ACR/EULAR classification criteria, and 76 control subjects (CS) were included. Cytokine quantification was performed by Multiplex assay. Principal component analysis (PCA) was realized, and the K-mean test was used to identify clusters/groups. Groups were analyzed by the Kruskal-Wallis test and the Bonferroni test. RESULTS: Higher IFN-γ, IL-17F, IL-21, IL-23, IL-4, and IL-31 levels were observed in pSS patients in comparison with control subjects. PCA analysis showed three groups. The severe group was characterized by higher cytokine concentrations as well as an increase in clinical parameters such as antibody levels, damage index score, and others. The moderate group presented intermediate severity; meanwhile, the mild group presented the lowest severity. CONCLUSION: Cluster analysis revealed three groups that were different in cytokine levels and clinical parameters in which the mild group was defined by lower severity, the moderate group with intermediate severity, and the severe group with higher severity. This analysis could help subclassify the primary Sjögren syndrome patients for a better understanding of the clinical phenotype that impacts the treatment approach.
31969226 Risk of non-Hodgkin's lymphoma and thyroid cancer in primary Sjögren's syndrome measured 2020 Jul OBJECTIVES: The aim of this study was to evaluate the incidence and risk of non-Hodgkin's lymphoma (NHL) and thyroid cancer in patients with primary Sjögren's syndrome (pSS) using the Korean National Health Insurance Service (NHIS) claims database. METHODS: pSS was identified using the Korean NHIS medical claims database between 2007 and 2017. The case definition required more than one visit based on the SS diagnostic code and the registration system for rare and incurable diseases. We included all admissions with a primary diagnosis of lymphoma and thyroid cancer. RESULTS: The pSS incidence was 1.88 cases/100,000 inhabitants. Female patients had a higher incidence than male patients, with a female-to-male ratio of 7.65:1. Of those, we identified 18 (0.34%), 1 (0.02%) and 29 (0.56%) patients with NHL, Hodgkin's disease and thyroid cancer, respectively. For pSS, the standardised incidence ratios for NHL and thyroid cancer were 6.32 (95% confidence interval [CI] 4.09-9.38) and 1.23 (95% CI 0.88-1.68), respectively. Compared with the general population, female patients with pSS had a 6.95-fold higher risk of developing NHL, while the male patients did not. Patients with pSS did not have a higher risk of developing thyroid cancer. CONCLUSIONS: Although pSS is associated with a higher risk of developing NHL, the risk of NHL appears to have decreased compared with that in previous studies. Our study suggests that the risk of NHL or thyroid cancer with SS is not higher than that reported in previous studies.
32628345 Cognitive impairment in patients with Neuro-Sjögren. 2020 Aug OBJECTIVE: Extraglandular neurological manifestations of Sjögren's syndrome are increasingly recognized, defining the disease entity of Neuro-Sjögren. Neuropsychological assessment of patients with Sjögren's syndrome has hitherto been performed on predominantly rheumatological cohorts. These studies revealed a wide variety of prevalence rates for cognitive impairment (22-80%), while variable cut-off criteria for detection of cognitive impairment were applied. Attentional functions have not yet been thoroughly investigated in these patients, although they clearly represent relevant aspects of cognitive functioning in daily life. METHODS: We therefore conducted extensive neuropsychological assessment based on two neuropsychological test batteries [i.e., the extended German version of the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Assessment Battery (CERAD-PLUS), and the test battery for attentional performance (TAP) as a well-established assessment of attentional functions in the German-speaking part of Europe]. RESULTS: Sixty-four patients with Neuro-Sjögren, who were treated at our university hospital between December 2016 and January 2019, were included. Evidence for the presence of cognitive impairment was found in 55% of patients with Neuro-Sjögren. The degree of cognitive impairment ranged from mild (38%) to severe (17%). Attentional and mnemonic subtests showed pronounced cognitive impairment in patients with Neuro-Sjögren. INTERPRETATION: Our results suggest that a substantial proportion of patients with Neuro-Sjögren suffer from cognitive impairment, putatively as a corollary of attentional deficits, which might exert adverse effects on occupational abilities, other cognitive functions, and social role functioning.
32028422 Dyskeratotic cells in persistent pruritic skin lesions as a prognostic factor in adult-ons 2020 Feb Adult-onset Still disease (AOSD), a systemic inflammatory disorder, is characterized by high fever, evanescent rash, arthritis, and hyperferritinaemia. AOSD is also reported to be associated with other skin lesions, including persistent pruritic papules and plaques. This study aimed to assess the significance of dyskeratotic skin lesions in Japanese AOSD patients.We retrospectively assessed the histology of persistent pruritic skin lesions and evanescent rashes and the relationship between dyskeratotic cells, serum markers, and outcomes in 20 Japanese AOSD patients, comparing AOSD histology with that of dermatomyositis (DM), drug eruptions, and graft-versus-host disease (GVHD).As the results, Persistent pruritic lesions were characterized by scattered single keratinocytes with an apoptotic appearance confined to the upper layer of the epidermis and horny layer without inflammatory infiltrate. In contrast to AOSD, the histology of DM, drug eruption, and GVHD demonstrated dyskeratotic cells in all layers of the epidermis with inflammatory infiltrate. AOSD with evanescent rash showed no dyskeratotic cells. The dyskeratotic cells in pruritic AOSD lesions stained positive for ssDNA and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling, indicating apoptosis. Serum IL-18 was significantly higher in AOSD patients with dyskeratotic cells than those without, and generally required higher doses of glucocorticoids, immunosuppressants, and biologic agents. Two of ten AOSD patients with dyskeratotic cells died from hemophagocytic lymphohistiocytosis.In conclusion, Persistent pruritic AOSD skin lesions are characterized by dyskeratotic cells with apoptotic features, involving the upper layers of the epidermis. There may be a link to elevated IL-18. This dyskeratosis may be a negative prognostic indicator.
31303456 Application of classification criteria of Sjogren syndrome in patients with sicca symptoms 2020 Jan BACKGROUND: Patients who have symptoms of sicca, such as dry eyes and mouth, may have Sjögren's syndrome (SS). However, the conservative culture makes patients hesitate to undergo an invasive biopsy, which contributes to the difficulty of confirming a diagnosis. We aimed to identify the characteristics of patients with sicca symptoms to develop a better predictive value for each item included in the three different diagnostic criteria for SS and clarify the best diagnostic tools for the local population. METHODS: This is a single-center retrospective case-control study from January 2016 to December 2017. Patients who underwent sialoscintigraphy because of clinical symptoms of xerostomia and xerophthalmia at one medical center were reviewed via the patients' electronic medical records. RESULTS: Of 515 patients enrolled, the severity of results for sialoscintigraphy and Schirmer's test was correlated with a diagnosis of SS and generated receiver operator characteristic curve. The area under curve (AUC) was 0.603 for positive Schirmer's test, 0.687 for positive anti-Ro/La results, 0.893 for a positive salivary gland biopsy. The AUC was 0.626 and 0.602 for Schirmer's test which is redefined as <10 mm/5 minutes in either eye and according to 2016 the American College of Rheumatology/ European League Against Rheumatism criteria, respectively. CONCLUSION: Our results indicate the cut-off point for defining a positive test result in the Schirmer's test is worth modified to <10 mm/5 minutes in either eye.
31963817 Mechanisms of Disease in Sjögren Syndrome-New Developments and Directions. 2020 Jan 19 Sjögren Syndrome (SS) is an autoimmune disease that affects the exocrine glands, mainly salivary and lacrimal glands [...].
32159602 Correlation of sleep quality with fatigue and disease activity among patients with primary 2020 Mar BACKGROUND: Fatigue is a frequent symptom in patients with primary Sjögren's syndrome (pSS) and can be a cause of or be associated with sleep disorders. OBJECTIVE: To assess the sleep quality of pSS patients and its relationship with fatigue and disease activity. DESIGN AND SETTING: Analytical observational study conducted at an exercise psychobiology laboratory. METHODS: Sleep quality was evaluated using the Pittsburg sleep quality index (PSQI) and actigraphy. Fatigue was evaluated through the Profile of Fatigue and Discomfort - Sicca Symptoms Inventory (PROFAD-SSI-SF) and a visual analogue scale for fatigue (VAS-fatigue). Disease activity was evaluated using a visual analogue scale for pain (VAS-pain), EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) and Disease Activity Index (ESSDAI). We summarized the data through descriptive statistics. RESULTS: A total of 50 female patients with pSS, of average age 56.4 years, were included in the study; 80% presented low disease activity. The total PSQI score showed that 74% had poor sleep. The actigraphy showed mean sleep latency of 26.2 minutes and mean nightly awakening of 48.2 minutes (duration of wakings after sleep onset, WASO). There were correlations between PSQI and VAS-pain, VAS-fatigue, PROFAD-SSI and ESSPRI. Actigraphy showed a correlation between the duration of WASO and ESSDAI. CONCLUSION: The present study provides important information regarding correlations between sleep disorders and disease activity. There is a need for proper control over disease activity and for development of strategies to help patients to sleep better in order to diminish their fatigue.