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ID PMID Title PublicationDate abstract
27788684 Protein oxidation, nitration and glycation biomarkers for early-stage diagnosis of osteoar 2016 Oct 27 BACKGROUND: There is currently no blood-based test for detection of early-stage osteoarthritis (OA) and the anti-cyclic citrullinated peptide (CCP) antibody test for rheumatoid arthritis (RA) has relatively low sensitivity for early-stage disease. Morbidity in arthritis could be markedly decreased if early-stage arthritis could be routinely detected and classified by clinical chemistry test. We hypothesised that damage to proteins of the joint by oxidation, nitration and glycation, and with signatures released in plasma as oxidized, nitrated and glycated amino acids may facilitate early-stage diagnosis and typing of arthritis. METHODS: Patients with knee joint early-stage and advanced OA and RA or other inflammatory joint disease (non-RA) and healthy subjects with good skeletal health were recruited for the study (n = 225). Plasma/serum and synovial fluid was analysed for oxidized, nitrated and glycated proteins and amino acids by quantitative liquid chromatography-tandem mass spectrometry. Data-driven machine learning methods were employed to explore diagnostic utility of the measurements for detection and classifying early-stage OA and RA, non-RA and good skeletal health with training set and independent test set cohorts. RESULTS: Glycated, oxidized and nitrated proteins and amino acids were detected in synovial fluid and plasma of arthritic patients with characteristic patterns found in early and advanced OA and RA, and non-RA, with respect to healthy controls. In early-stage disease, two algorithms for consecutive use in diagnosis were developed: (1) disease versus healthy control, and (2) classification as OA, RA and non-RA. The algorithms featured 10 damaged amino acids in plasma, hydroxyproline and anti-CCP antibody status. Sensitivities/specificities were: (1) good skeletal health, 0.92/0.91; (2) early-stage OA, 0.92/0.90; early-stage RA, 0.80/0.78; and non-RA, 0.70/0.65 (training set). These were confirmed in independent test set validation. Damaged amino acids increased further in severe and advanced OA and RA. CONCLUSIONS: Oxidized, nitrated and glycated amino acids combined with hydroxyproline and anti-CCP antibody status provided a plasma-based biochemical test of relatively high sensitivity and specificity for early-stage diagnosis and typing of arthritic disease.
26195802 Spontaneous retrotransposon insertion into TNF 3'UTR causes heart valve disease and chroni 2015 Aug 4 Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are chronic inflammatory diseases that together affect 2-3% of the population. RA and AS predominantly involve joints, but heart disease is also a common feature in RA and AS patients. Here we have studied a new spontaneous mutation that causes severe polyarthritis in bone phenotype spontaneous mutation 1 (BPSM1) mice. In addition to joint destruction, mutant mice also develop aortic root aneurism and aorto-mitral valve disease that can be fatal depending on the genetic background. The cause of the disease is the spontaneous insertion of a retrotransposon into the 3' untranslated region (3'UTR) of the tumor necrosis factor (TNF), which triggers its strong overexpression in myeloid cells. We found that several members of a family of RNA-binding, CCCH-containing zinc-finger proteins control TNF expression through its 3'UTR, and we identified a previously unidentified regulatory element in the UTR. The disease in BPSM1 mice is independent of the adaptive immune system and does not appear to involve inflammatory cytokines other than TNF. To our knowledge, this is the first animal model showing both polyarthritis and heart disease as a direct result of TNF deregulation. These results emphasize the therapeutic potential of anti-TNF drugs for the treatment of heart valve disease and identify potential therapeutic targets to control TNF expression and inflammation.
26876387 Cannabinoids and autoimmune diseases: A systematic review. 2016 Jun Cannabinoids have shown to have a variety effects on body systems. Through CB1 and CB2 receptors, amongst other, they exert an effect by modulating neurotransmitter and cytokine release. Current research in the role of cannabinoids in the immune system shows that they possess immunosuppressive properties. They can inhibit proliferation of leucocytes, induce apoptosis of T cells and macrophages and reduce secretion of pro-inflammatory cytokines. In mice models, they are effective in reducing inflammation in arthritis, multiple sclerosis, have a positive effect on neuropathic pain and in type 1 diabetes mellitus. They are effective as treatment for fibromyalgia and have shown to have anti-fibrotic effect in scleroderma. Studies in human models are scarce and not conclusive and more research is required in this field. Cannabinoids can be therefore promising immunosuppressive and anti-fibrotic agents in the therapy of autoimmune disorders.
25901186 Perceived barriers to the management of foot health in patients with rheumatic conditions. 2015 BACKGROUND: Rheumatic conditions can have a significant impact on the feet and requires effective management. Podiatric involvement in the management of rheumatic conditions has previously been found to be inadequate in a hospital-setting and no study has examined current trends across New Zealand. The aim was to evaluate the perceived barriers of New Zealand podiatrists in the management of rheumatic conditions. METHODS: A cross-sectional observational design using a web-based survey. The self-administered survey, comprising of thirteen questions, was made available to podiatrists currently practicing in New Zealand. RESULTS: Fifty-six podiatrists responded and the results demonstrated poor integration of podiatrists into multidisciplinary teams caring for patients with arthritic conditions in New Zealand. Dedicated clinical sessions were seldom offered (16%) and few podiatrists reported being part of an established multidisciplinary team (16%). A poor uptake of clinical guidelines was reported (27%) with limited use of patient reported outcome measures (39%). The majority of podiatrists expressed an interest in professional development for the podiatric management of arthritic conditions (95%). All surveyed podiatrists (100%) agreed that there should be nationally developed clinical guidelines for foot care relating to arthritis. CONCLUSIONS: The results suggest that there are barriers in the involvement of podiatrists in the management of people with rheumatic conditions in New Zealand. Future studies may provide an in-depth exploration into these findings to identify and provide solutions to overcome potential barriers.
26202173 How complement activation influences the development of chronic synovitis in a mouse model 2016 Jan OBJECTIVES: Chronic synovitis is the main characteristic of rheumatoid arthritis (RA), defined by the proliferation of synovial lining cells, an important source of chemokines and cytokines associated with inflammation. The aim of this study was to examine the influence of complement functional activity on the development of chronic synovitis. METHOD: The experiments were conducted in zymosan-induced arthritis (ZIA) provoked by intra-articular injection of 180 μg zymosan. Mice were treated with 10 ng/g body weight (bw) cobra venom factor (CVF) on days -3 and -2 or with 10 ng/g bw CVF on days 7, 12, and 17 of ZIA. The percentage of neutrophils (CD11b+Ly6G+), macrophages (F4/80), and complement 5 anaphylatoxin receptor (C5aR)-positive cells in the synovial fluid (SF) were determined by flow cytometry and the expression of C5aR and C3aR in the synovium was detected immunohistochemically. RESULTS: The induction of ZIA in the absence of complement activity strongly inhibited the development of synovitis. By contrast, complement activation during ZIA exacerbated chronic synovitis through an increase in macrophage infiltration, C5aR and C3aR expression in the joints, and C5aR expression on SF cells. Levels of C5a and soluble receptor activator of nuclear factor kappa B ligand (sRANKL) in the SF were elevated whereas neutrophil infiltration and levels of tumour necrosis factor (TNF)-α and interleukin (IL)-6 in the SF were unchanged. CONCLUSIONS: Our findings indicate an important role for functional complement activity in the maintenance of chronic synovitis in a model of RA. Antagonizing complement activation represents new possibilities for the amelioration of synovitis symptoms.
27182427 Patient Preferences Regarding Rheumatoid Arthritis Therapies: A Conjoint Analysis. 2016 Apr BACKGROUND: Tofacitinib, an oral Janus kinase inhibitor approved for the treatment of rheumatoid arthritis (RA), provides patients with an alternative to subcutaneously or intravenously administered biologic disease-modifying antirheumatic drugs (DMARDs). Little is known about patient preference for novel RA treatments. OBJECTIVE: To investigate patient preferences for attributes associated with RA treatments. METHODS: A choice-based conjoint survey was mailed to 1400 randomly selected commercially insured patients (aged 21-80 years) diagnosed with RA, who were continuously enrolled from May 1, 2012, through April 30, 2013, and had ≥2 medical claims for International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code 714.0 and no previous biologic DMARD use. Treatment attributes included route of administration; monthly out-of-pocket cost; frequency of administration; ability to reduce daily joint pain and swelling; likelihood of serious adverse events; improvement in the ability to perform daily tasks; and medication burden. Mean attribute importance scores were calculated after adjusting for patient demographics (eg, age, sex, years since diagnosis) using a hierarchical Bayes model. Patient preferences for each treatment attribute were ranked by the importance score. Part-worth utilities (ie, preference scores) were used to perform a conjoint market simulation. RESULTS: A total of 380 patients (response rate, 27.1%) returned the survey. Their mean age (± standard deviation) was 54.9 (± 9.3) years. Nonrespondents were 2 years younger (mean, 52.9 years; P = .002) but did not differ significantly from respondents in known clinical characteristics. After adjustment for demographic characteristics, mean patients' ranking of treatment attribute importance, in decreasing order, was route of administration, 34.1 (± 15.5); frequency of administration, 16.4 (± 6.8); serious adverse events, 12.0 (± 9.3); cost, 10.1 (± 6.2); medication burden, 9.8 (± 8.2); joint pain reduction, 8.9 (± 3.8); and daily tasks improvement, 8.8 (± 4.7). For the route of administration attribute, the part-worth utility was highest for the oral route. Conjoint simulation results showed that 56.4% of respondents would prefer an oral route of administration. CONCLUSION: Based on this survey completed by 380 patients with RA, commercially insured patients with RA consider the route of administration to be the most important attribute of their RA treatment. In this study, the majority (56.4%) of patients preferred the oral route of administration over other routes. Understanding patient preferences may help to inform provider and payer decisions in treatment selection that may enhance patient adherence to therapy.
28243578 Net cholesterol efflux capacity of HDL enriched serum and coronary atherosclerosis in rheu 2016 Dec BACKGROUND/OBJECTIVES: Cardiovascular (CV) risk is increased in patients with rheumatoid arthritis (RA), but not fully explained by traditional risk factors such as LDL and HDL cholesterol concentrations. The cholesterol efflux capacity of HDL may be a better CV risk predictor than HDL concentrations. We hypothesized that HDL's cholesterol efflux capacity is impaired and inversely associated with coronary atherosclerosis in patients with RA. METHODS: We measured the net cholesterol efflux capacity of apolipoprotein B depleted serum and coronary artery calcium score in 134 patients with RA and 76 control subjects, frequency-matched for age, race and sex. The relationship between net cholesterol efflux capacity and coronary artery calcium score and other clinical variables of interest was assessed in patients with RA. RESULTS: Net cholesterol efflux capacity was similar among RA (median [IQR]: 34% removal [28, 41%]) and control subjects (35% removal [27%, 39%]) (P=0.73). In RA, increasing net cholesterol efflux capacity was not significantly associated with decreased coronary calcium score (OR=0.78 (95% CI 0.51-1.19), P=0.24, adjusted for age, race and sex, Framingham risk score and presence of diabetes). Net cholesterol efflux capacity was not significantly associated with RA disease activity score, C-reactive protein, urinary F(2)-isoprostanes, or degree of insulin resistance in RA. CONCLUSIONS: Net cholesterol efflux capacity is not significantly altered in patients with relatively well-controlled RA nor is it significantly associated with coronary artery calcium score.
27549026 The inflammatory role of phagocyte apoptotic pathways in rheumatic diseases. 2016 Aug 23 Rheumatoid arthritis affects nearly 1% of the world's population and is a debilitating autoimmune condition that can result in joint destruction. During the past decade, inflammatory functions have been described for signalling molecules classically involved in apoptotic and non-apoptotic death pathways, including, but not limited to, Toll-like receptor signalling, inflammasome activation, cytokine production, macrophage polarization and antigen citrullination. In light of these remarkable advances in the understanding of inflammatory mechanisms of the death machinery, this Review provides a snapshot of the available evidence implicating death pathways, especially within the phagocyte populations of the innate immune system, in the perpetuation of rheumatoid arthritis and other rheumatic diseases. Elevated levels of signalling mediators of both extrinsic and intrinsic apoptosis, as well as the autophagy, are observed in the joints of patients with rheumatoid arthritis. Furthermore, risk polymorphisms are present in signalling molecules of the extrinsic apoptotic and autophagy death pathways. Although research into the mechanisms underlying these pathways has made considerable progress, this Review highlights areas where further investigation is particularly needed. This exploration is critical, as new discoveries in this field could lead to the development of novel therapies for rheumatoid arthritis and other rheumatic diseases.
26535134 Efficacy and safety of tabalumab, an anti-BAFF monoclonal antibody, in patients with moder 2015 BACKGROUND: Tabalumab is a human monoclonal antibody that neutralises B-cell activating factor. OBJECTIVES: To evaluate tabalumab efficacy and safety in patients with rheumatoid arthritis (RA). METHODS: This phase 3, randomised, double-blind, placebo-controlled study evaluated 456 patients with active RA after 24-week treatment with subcutaneous tabalumab (120 mg every 4 weeks (120/Q4W) or 90 mg every 2 weeks (90/Q2W)) versus placebo, with loading doses (240 or 180 mg) at week 0. Patients were allowed background disease-modifying antirheumatic drugs and previously discontinued ≥1 tumour necrosis factor α inhibitors for lack of efficacy/intolerance. Primary end point was American College of Rheumatology 20% (ACR20) response at 24 weeks. This study was terminated early due to futility. RESULTS: Most patients had moderate-to-high baseline disease activity. There was no significant difference in week 24 ACR20 responses between 120/Q4W, 90/Q2W, and placebo (17.6%, 24.3%, 20%) per non-responder imputation analysis. Mean percent changes in CD20+ B-cell count (-10.8%, -9.6%, +10.9%) demonstrated expected pharmacodynamic effects. Treatment-emergent adverse events (AEs) were similar (59.5%, 51.7%, 52.6%), as were AE discontinuations (2.6%, 2.7%, 2.6%), serious AEs (4.6%, 4.1%, 3.9%), serious infectious events (1.3%, 0, 0) and events of interest: infections (23.5%, 25.9%, 24%), injection site reactions (13.1%, 25.8%, 11%) and allergy/hypersensitivity (3.9%, 4.1%, 3.9%) reports. Incidence of treatment-emergent antidrug antibodies was similar to placebo (3.9%, 4.8%, 3.9%). No deaths or new/unexpected safety findings were reported. CONCLUSIONS: Tabalumab did not demonstrate clinical efficacy in patients with RA in this phase 3 study, despite evidence of biological activity. There were no notable differences in safety parameters between tabalumab treatment groups and placebo. TRIAL REGISTRATION NUMBER: NCT01202773.
24666434 Rheumatoid factor in idiotypic regulation of autoimmunity. 2015 May AIM: Rheumatoid factor (RF) is known to be heterogeneous, and RFs detected by various methods exhibit different characteristics. In addition to interacting with the Fc region of immunoglobulin G (IgG), certain RFs are able to recognize idiotypes of antibodies. Given the important role of idiotypic interactions in regulating autoimmunity, we hypothesize that RF is involved in regulation of lymphocyte activity against autoimmune disease-inducing antigens via idiotype-anti-idiotype interactions with these lymphocytes. METHOD: RF level and the existence of idiotype-anti-idiotype interactions between RF and antibodies to autoimmunity-inducing antigens were studied in rats resistant and sensitive to collagen-induced arthritis, encephalomyelitis and atherosclerosis. RF was assayed by agglutination of tanned IgG-loaded erythrocytes. RESULTS: Rat resistance to autoimmune disease is associated with high RF production during the initiation of the immune response, and a low RF level during this period may be a preclinical marker of experimental autoimmune disease manifestation. RF-containing sera compete with an antigen if the RF-containing sera were obtained from rats immunized with that antigen, and they non-specifically inhibit binding of different antigen-antibody pairs. This suggests that RFs are anti-idiotypic antibodies that carry two kinds of paratopes: a particular paratope that recognizes the antigen-binding sites of antibodies, and a shared paratope that serves to recognize the recurrent idiotype on antibodies. Antigenic epitopes for the shared RF paratope can be created in the hinge region of Fc fragments of homologous IgG. CONCLUSION: RF detected by agglutination of tanned IgG-loaded erythrocytes is involved in negative idiotypic regulation of lymphocytes specific to autoimmunity-inducing antigens.
29744142 Interleukin-6 receptor inhibitor tocilizumab ameliorates periodontal inflammation in patie 2015 Dec Interleukin-6 (IL-6) may play a pathological role in rheumatoid arthritis (RA) and periodontitis. Although the efficacy of medication with IL-6 receptor inhibitor, tocilizumab (TCZ), has been demonstrated in the treatment of RA, very little is known about whether TCZ therapy affects periodontitis. The aim of the present study is to compare periodontal condition in patients with RA and periodontitis before and after TCZ therapy. The study participants consisted of 20 patients with RA and periodontitis who were treated with TCZ and 40 patients with RA and periodontitis who received medication with tumor necrosis factor inhibitor (TNFI). Clinical periodontal and rheumatologic assessments and serum biochemical measurements using enzyme-linked immunosorbent assays were performed at baseline and 3 and 6 months later. TCZ and TNFI therapies significantly reduced periodontal inflammation that was determined by gingival index, bleeding on probing, and probing depth (p < 0.017), although plaque levels were comparable before and after the therapies. Both therapies also significantly decreased disease activity score including 28 joints using C-reactive protein (CRP), number of tender and swollen joints, and serum levels of anti-cyclic citrullinated peptide antibodies, rheumatoid factor, CRP, and matrix metalloproteinase-3 (p < 0.017). Additionally, a significant decrease was observed in periodontal clinical attachment level after TCZ therapy (p < 0.017), but not after TNFI therapy. TCZ therapy significantly decreased serum levels of TNF-α, total immunoglobulin G, and serum amyloid A (p < 0.017), although serum levels of IL-6 and soluble IL-6R were significantly increased (p < 0.017). These results suggest a beneficial effect of TCZ therapy on levels of periodontal inflammation in patients with RA and periodontitis, which might be related to decrease in serum inflammatory mediators.
26241756 Prevalence of Arthritis in Africa: A Systematic Review and Meta-Analysis. 2015 OBJECTIVE: In this systematic review, we estimate the prevalence of six types of arthritis in Africa; namely rheumatoid arthritis, osteoarthritis, juvenile arthritis, psoriatic arthritis, gout, and ankylosing spondylitis. METHODS: We comprehensively searched literature on 31 August 2014 in MEDLINE, EMBASE, Web of Science and the Cochrane Library to identify eligible studies from 1975 up to 31 July 2014. Two review authors independently selected studies, extracted data, and appraised studies. We carried out random effects meta-analysis of prevalence of arthritis and assessed heterogeneity through subgroup analyses. We performed separate analyses for population- and hospital-based studies, as well as rural and urban settings. MAIN FINDINGS: We included 27 cross-sectional studies (20 population-based and 7 hospital-based) from Africa reporting on the prevalence of arthritis. The majority of the studies were from South Africa (44.4%, 12/27). Rheumatoid arthritis in urban settings ranged from 0.1% in Algeria, 0.6% in the DRC, to a meta-analysis overall prevalence of 2.5% in South Africa, and in rural settings ranged from a meta-analysis overall prevalence of 0.07% in South Africa, 0.3% in Egypt, to 0.4% in Lesotho. Osteoarthritis was the most prevalent form of arthritis and in urban settings it was 55.1% in South Africa and in rural settings, all in South Africa, ranged from 29.5%, 29.7%, up to 82.7% among adults aged over 65 years. Other results include highest prevalence of 33.1% for knee osteoarthritis in rural South Africa, 0.1% for ankylosing spondylitis in rural South Africa, 4.4% for psoriatic arthritis in urban South Africa, 0.7% for gout in urban South Africa, and 0.3% for juvenile idiopathic arthritis in urban Egypt. A third of the included studies had a low risk of bias (33.3%, 9/27), 40.8% (11/27) moderate risk, and 25.9% (7/27) had a high risk of bias. CONCLUSIONS: In this systematic review, we have identified the paucity of latest prevalence data on arthritis in Africa. More studies are needed to address the prevalence and the true burden of this disease in Africa.
27271273 Grape seed proanthocyanidin extract ameliorates murine autoimmune arthritis through regula 2018 May BACKGROUND/AIMS: Grape seed proanthocyanidin extract (GSPE) has been reported to have a beneficial effect on regulating inf lammation. However, the anti-inflammatory mechanism of GSPE remains unclear. The aim of this study was to verify the influence of GSPE on the Toll-like receptor 4 (TLR4)-mediated signaling pathway in the regulation of murine autoimmune arthritis. METHODS: Collagen-induced arthritis (CIA) was induced in dilute brown non-agouti (DBA)/1J mice. The mice were treated with GSPE (0 or 100 mg/kg) intraperitoneally. The severity of arthritis was assessed clinically, biochemically, and histologically. Immunostaining for TLR4 was performed. The expressions of TLR4 and downstream signaling molecules were analyzed by Western blot. The effect of GSPE on lipopolysaccharide (LPS)-induced TLR4 activation was also evaluated using RAW264.7 cells and fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis and from those with osteoarthritis. RESULTS: GSPE attenuated the clinical severity of arthritis and decreased histological damage. GSPE treatment reduced the number of TLR4-stained cells in the synovium of mice with CIA. GSPE also downregulated the expression of TLR4, myeloid differentiation factor 88 (MyD88) and phosphorylated IκBα synovial protein in CIA mice. Concurrently, GSPE inhibited the nuclear translocation of nuclear factor-κB (NF-κB) subunits (p65 and p50). LPS-induced TLR4 activation was suppressed by GSPE in human FLS as well as in murine macrophages in vitro. CONCLUSIONS: Our results demonstrated that GSPE ameliorated CIA by regulating the TLR4-MyD88-NF-κB signaling pathway.
27906058 Vascular endothelial growth factor levels and rheumatic diseases of the elderly. 2016 Dec 1 BACKGROUND: Increasing vascular endothelial growth factor (VEGF) has been reported in remitting symmetrical seronegative synovitis with pitting edema (RS3PE) syndrome, rheumatoid arthritis (RA), polymyalgia rheumatica (PMR) and giant cell arteritis (GCA). The aim of this study was to compare VEGF levels in patients over 60 years of age who have RS3PE, RA, PMR or GCA so as to determine whether elevated VEGF is specific for a rheumatic disease, the inflammation or edema that occurs with these pathological conditions. METHODS: In this retrospective, multicentric study we assessed serum and plasma levels of VEGF in patients over 60 years of age with rheumatic diseases that were either de novo or of recent onset according to the initial clinical presentation, and we compared these patients with a control group. RESULTS: Serum and plasma VEGF levels were determined in 80 patients (5 with RS3PE, 13 with RA, 44 with PMR, and 18 with GCA) and 37 controls. Edema occurred in five patients with RS3PE, four with RA, and one with PMR, but not patients with GCA. Serum VEGF levels were significantly higher in individuals with rheumatic diseases (849 (405.5-1235.5) pg/ml) relative to the controls (484 (302-555) pg/ml) (p < 0.001). There were no significant differences between patients with RS3PE, RA, PMR, or GCA in terms of the VEGF serum levels (p = 0.60) or plasma levels (p = 0.57). Similarly, the occurrence of edema did not correlate with VEGF levels. CONCLUSION: VEGF increases in rheumatic diseases compared to a control group. This was not associated with specific rheumatic diseases or with edematous rheumatic diseases.
24985362 Sjögren's syndrome: still not fully understood disease. 2015 Feb Primary Sjögren's syndrome is an autoimmune disorder with external exocrine glands dysfunction and multiorgan involvement. The pathogenesis of primary Sjogren's syndrome is still unclear; however, our knowledge of the involvement of different cells (e.g., B and T cells, macrophages and dendritic cells) and pathways (BAFF/APRIL and interferons) leading to the development of autoimmunity is continually expanding. For clinicians, the most frequent symptoms are dryness of eyes and mouth, but often the patients have musculoskeletal symptoms and systemic manifestations. However, the increased risk of lymphoproliferative disorders in this group of patients, most commonly B-cell marginal zone lymphoma, is particularly important. Recent separation of IgG4-related diseases and attempts to create further diagnostic criteria for pSS testify to the difficulties, and at the same time a large interest, in understanding the disease so as to allow the effective treatment. This article draws attention to the problems faced by the clinician wishing to securely identify pSS by using accurate laboratory biomarkers and useful imaging tools and predict the development of complications associated with this, still not fully understood, autoimmune disease.
24919594 Efficient diagnosis of Sjögren's syndrome to reduce the burden on patients. 2015 Jan OBJECTIVE: The purpose of this study was to investigate the procedures for efficiently diagnosing Sjögren's syndrome to reduce patient burden. METHODS: This study analyzed data from 254 Japanese patients diagnosed with Sjögren's syndrome out of 4967 who visited our clinic complaining of xerostomia. RESULTS: Of the 254 Sjögren's syndrome patients, 140 fulfilled the criteria proposed by the Committee on Sjögren's Syndrome of the Ministry of Health and Welfare of Japan, 228 fulfilled the criteria proposed by the American-European Consensus Group, and 69 fulfilled the criteria proposed by the American College of Rheumatology. Numbers of definitive cases varied with each set of criteria. Logistic regression analysis was used to analyze useful examination items for definitive diagnosis of Sjögren's syndrome, demonstrating that anti-Ro/SSA (odds ratio (OR), 7.165), lip biopsy (OR, 4.273), sialography (OR, 2.402), and ANA (OR, 0.678) correlated significantly with definitive diagnosis of Sjögren's syndrome. CONCLUSIONS: These results suggest that the following diagnostic procedure for Sjögren's syndrome would reduce burden on patients. When clinicians choose examination items for diagnosing Sjögren's syndrome, they should first select which criteria to use. Then, to minimize the number of examination items, examinations should be performed in order of anti-SSA antibody, lip biopsy, and parotid gland sialography.
27854095 Cerebral Venous Sinus Thrombosis in A Patient with Sjögren's Syndrome with Atypical Antib 2016 Jun 15 BACKGROUND: Although Sjögren's syndrome has been known to complicate with white matter lesions, encephalopathy, or stroke, reports of cerebral venous sinus thrombosis due to Sjögren's syndrome with atypical antibodies are rare. CASE REPORT: A 50-year-old woman was admitted to our neurological ward with nausea and vomiting following acute onset of severe headache in the left occipital region. Brain computed tomography revealed no abnormalities. The patient was fully conscious, with normal cognitive functioning, but exhibited unsteady tandem gait. Both magnetic resonance venography and computed tomography venography suggested left transverse sinus blockage. Intravenous enoxaparin, followed by oral warfarin, was initiated as treatment for cerebral venous sinus thrombosis. After investigation, Sjögren's syndrome was diagnosed and lupus anticoagulant antibody test was positive. The patient was treated with hydroxychloroquine, and appeared fully recovered at the 6-month follow-up, with no clinical or radiological signs of relapse. CONCLUSION: This case reports the relationship between cerebral venous sinus thrombosis and Sjögren's syndrome. It is necessary to screen autoimmune disorders in patients with cerebral venous sinus thrombosis that present with no common risk factors of venous thrombosis in order to prevent inappropriate management, and potentially adverse outcomes.
27136104 The Importance of Minor Salivary Gland Biopsy in Sjögren Syndrome Diagnosis and the Clini 2016 OBJECTIVE: Minor salivary gland biopsy is one of the objective tests used in the diagnosis of Sjögren syndrome. The aim of our study was to compare the clinical and laboratory data of primary and secondary Sjögren syndrome cases with a lymphocyte score 3 and 4 in the minor salivary gland biopsy. MATERIAL AND METHOD: Data from a total of 2346 consecutive minor salivary gland biopsies were retrospectively evaluated in this study. Clinical and autoantibody characteristics of 367 cases with lymphocyte score 3 or 4 and diagnosed with primary or secondary Sjögren syndrome were compared. RESULTS: There was no difference between lymphocyte score 3 and 4 primary Sjögren syndrome patients in terms of dry mouth, dry eye symptoms and Schirmer test results but Anti-Ro and Antinuclear Antibody positivity was statistically significantly higher in cases with lymphocyte score 4 (p= 0.025, p= 0.001). Anti-Ro test results were also found to be statistically significantly higher in secondary Sjögren syndrome patients with lymphocyte score 4 (p= 0.048). CONCLUSION: In this study, the high proportion of cases with negative autoantibody but positive lymphocyte score is significant in terms of showing the contribution of minor salivary gland biopsy to Sjögren syndrome diagnosis. Lymphocyte score 3 and 4 cases were found to have similar clinical findings but a difference regarding antibody positivity in primary Sjögren syndrome. We believe that cases with lymphocyte score 4 may be Sjögren syndrome cases whose clinical manifestations are relatively established and higher autoantibody levels are therefore found.
26759247 Elevated levels of faecal calprotectin in primary Sjögren's syndrome is common and associ 2016 Jan 12 BACKGROUND: Primary Sjögren's syndrome (pSS) is a systemic rheumatic disease in which gastrointestinal (GI) symptoms are common. Faecal calprotectin (FC) is a non-invasive biomarker that has been suggested to discriminate organic intestinal disease from functional disorders. The purpose of this study was to explore the usefulness of FC testing in patients with pSS. METHODS: In total, 56 consecutive patients with pSS and 29 healthy control subjects were included in this cross-sectional study. FC was measured with a commercially available enzyme-linked immunosorbent assay kit. GI symptoms were evaluated with the Rome III questionnaire and the Visual Analogue Scale for Irritable Bowel Syndrome. In patients with pSS, disease activity was estimated using the European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI), and patient-reported outcomes were evaluated with the EULAR Sjögren's Syndrome Patient-Reported Index. RESULTS: Patients with pSS had higher levels of FC than healthy control subjects (median 54 μg/g, interquartile range [IQR 20-128]; vs. 20 μg/g [20-43]; p = 0.002). Concomitant organic GI disease was found in 14 patients with pSS and included inflammatory bowel disease (n = 3), colonic adenoma (n = 2) and GI lymphoma (n = 1). Patients with organic GI disease had higher FC levels than the other patients with pSS (median 274 μg/g [IQR 61-363] vs. median 34 μg/g [IQR 20-76]; p < 0.001). Although patients with pSS reported abdominal discomfort more frequently than healthy control subjects did, such symptoms were not associated with organic GI disease or elevated FC levels. FC correlated moderately with ESSDAI. Excluding patients with organic GI disease, we did not identify any significant association between ESSDAI and FC levels. CONCLUSIONS: GI symptoms are frequent in pSS. Contrary to patient-reported outcomes, elevated FC levels in pSS indicate possible organic GI disease that warrants further investigation.
26231832 [Adult onset Still's disease with small vessel vasculitis]. 2015 Aug This article presents a particularly severe case of adult onset Still's disease aggravated by small vessel vasculitis. A satisfactory therapy was concluded 1.5 years after onset of the disease. The small vessel vasculitis was difficult to treat: methotrexate (MTX), cyclophosphamide and rituximab were not sufficiently effective. Tocilizumab in combination with intravenous immunoglobulin (IVIG) induced remission and maintenance therapy was carried out with tocilizumab.