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ID PMID Title PublicationDate abstract
27053636 Etanercept improves endothelial function via pleiotropic effects in rat adjuvant-induced a 2016 Jul OBJECTIVES: To determine the effect of etanercept on endothelial dysfunction and on traditional cardiovascular (CV) risk factors in the adjuvant-induced arthritis (AIA) rat model. METHODS: At the first signs of arthritis, etanercept (10 mg/kg/3 days, s.c.) or saline was administered for 3 weeks in AIA rats. Body weights and arthritis scores were monitored daily. Endothelial function was studied in aortic rings relaxed with acetylcholine (Ach) with or without inhibitors of nitric oxide synthase (NOS), cyclo-oxygenase (COX-2), arginase, endothelium-derived hyperpolarizing factor and superoxide anions (O2 (-)°) production. Aortic expression of endothelial nitic oxide synthase (eNOS), Ser1177-phospho-eNOS, COX-2, arginase-2, p22(phox) and p47(phox) was evaluated by western blotting analysis. Blood pressure, heart rate and blood levels of triglycerides, cholesterol and glucose were measured. RESULTS: Etanercept significantly reduced arthritis score (P < 0.001). It improved Ach-induced relaxation (P < 0.05) as a result of increased NOS activity, decreased COX-2/arginase activities and decreased O2 (-)° production. These functional effects relied on increased eNOS expression and phosphorylation, and decreased COX-2, arginase-2 and p22(phox) expressions. No correlation was found between arthritis score and Ach-induced relaxation. The treatment did not change triglycerides, cholesterol and glucose levels, but significantly increased systolic blood pressure and heart rate (P < 0.05). CONCLUSION: Our data demonstrated that efficient dosage of etanercept on inflammatory symptoms improved endothelial function in AIA. This beneficial effect on endothelial function is disconnected from its impact on CV risk factors and relates to pleiotropic effects of etanercept on endothelial pathways. These results suggest that etanercept could be a good choice for patients with rheumatoid arthritis at high risk of CV events.
26968113 Serotonin Is Involved in Autoimmune Arthritis through Th17 Immunity and Bone Resorption. 2016 Apr Rheumatoid arthritis is a chronic disease that results in a disabling and painful condition as it progresses to destruction of the articular cartilage and ankylosis of the joints. Although the cause of the disease is still unknown, evidence argues that autoimmunity plays an important part. There are increasing but contradictory views regarding serotonin being associated with activation of immunoinflammatory pathways and the onset of autoimmune reactions. We studied serotonin's involvement during collagen-induced arthritis in wild-type and Tph1(-/-) mice, which have markedly reduced peripheral serotonin levels. In wild-type mice, induction of arthritis triggered a robust increase in serotonin content in the paws combined with less inflammation. In Tph1(-/-) mice with arthritis, a marked increase in the clinical and pathologic arthritis scores was noticed. Specifically, in Tph1(-/-) mice with arthritis, a significant increase in osteoclast differentiation and bone resorption was observed with an increase in IL-17 levels in the paws and in Th17 lymphocytes in the draining lymph nodes, whereas T-regulatory cells were dampened. Ex vivo serotonin and agonists of the 5-HT2A and 5-HT2B receptors restored IL-17 secretion from splenocytes and Th17 cell differentiation in Tph1(-/-) mice. These findings indicate that serotonin plays a fundamental role in arthritis through the regulation of the Th17/T-regulatory cell balance and osteoclastogenesis.
26631920 Gout on CT of the feet: A symmetric arthropathy. 2016 Feb INTRODUCTION: The aim of this study was to assess the distribution of bone erosions in the feet of patients with gout using CT and thereby to test the hypothesis that gout is an asymmetric arthropathy. METHODS: CT scans of both feet were obtained from 25 patients with chronic gout. CT scans were scored for bone erosion using a semi-quantitative method based on the rheumatoid arthritis MRI scoring system (RAMRIS). CT bone erosion was assessed at 22 bones in each foot (total 1,100 bones) by two independent radiologists. Symmetry was assessed by two methods: (i) comparing right and left foot scores for each patient; and (ii) calculating the proportion of paired joints with or without erosions. RESULTS: Observer agreement was excellent (intra-class correlation coefficient 0.92). In the group overall, the difference in scores between the feet was not significant (Student's t-test P = 0.8). In 17 of 25 patients, the difference in erosion scores between the two feet was less than the inter-observer difference. In 24 of 25 patients, the proportion of paired joints was greater than 0.5, indicating symmetric disease. CONCLUSIONS: Erosive disease from gout is, in fact, a symmetric process in our patient group. This finding is contrary to the established view of gout as an asymmetric arthritis and lends new insight into the behaviour of this common disease.
26436101 The Clinical Relevance of IL-17-Producing CD4+CD161+ Cell and Its Subpopulations in Primar 2015 OBJECTIVE: Th17 cells have been demonstrated to play an important role in the onset and development of primary Sjögren's syndrome (pSS). In this study, we evaluated the expansion and clinical significance of circulating CD4+CD161+ T cell and its "effector" (CD4+CD25-CD161+ T cell) and "regulatory" (CD4+CD25+CD161+ T cell) subpopulations. METHODS: Fifty-eight pSS patients and 16 healthy controls (HCs) were recruited in our study. The cell populations and intracellular IL-17 expression were analyzed by flow cytometry. The disease activity was evaluated by the EULAR-SS Disease Activity Index (ESSDAI). Autoantibodies were measured by ELISA or indirect immunofluorescence assay. RESULTS: The CD161+ T cell fractions showed higher proportions of IL-17-producing cells. The frequencies of the overall CD4+CD161+ T cell population and its effector subset were positively correlated with disease activity parameters and more severe disease manifestations. A significant elevation of the CD4+CD25+CD161+ T cell subpopulation was observed in the peripheral blood of pSS patients compared to HCs and this subset showed decreased regulatory functions compared with the CD4+CD25+CD161- population. CONCLUSION: Circulating CD4+CD161+ T cell populations associated with pSS disease activity and severity. These cells might be involved in the development of pSS and could be potential therapeutic targets in the treatment of pSS.
25933458 Recurrent Hypokalemic Periodic Paralysis Unmasks Sjogren Syndrome without Sicca Symptoms. 2015 Apr Hypokalemic Periodic Paralysis (HPP) may occur as a rare complication of Sjogren Syndrome (SS) and Renal Tubular Acidosis (RTA). A 64-year male patient came with HPP, and was later diagnosed with distal RTA. The patient, who had no xerostomia and xerophthalmia, was diagnosed with primary SS from serologic and histologic findings of minor salivary gland biopsy. The patient recovered after potassium replacement therapy. Renal biopsy was also performed and revealed evidence of tubulointerstitial nephritis. Corticosteroids were administered and there was no recurrence of HPP during a 4-year follow-up period. The case highlights the significance of acute hypokalemia management in emergency department as it can unmask SS even if the SS is not associated with sicca symptoms. Hypokalemic paralysis associated with normal anion gap metabolic acidosis should prompt toward the diagnosis of SS.
25915936 Sjögren's Syndrome Antigen B Acts as an Endogenous Danger Molecule to Induce Interleukin- 2015 BACKGROUND: Sjögren's syndrome antigen B is expressed in the nucleus and surface membrane of human polymorphonuclear neutrophils and is released after cell death. However, its biological role is not clear. This study is aimed to investigate the effect of Sjögren's syndrome antigen B on human polymorphonuclear neutrophils. METHODS: Human recombinant Sjögren's syndrome antigen B (rSSB) purified from E. coli was incubated with human polymorphonuclear neutrophils as well as retinoid acid-induced granulocytic differentiated HL-60 cells, HL-60 (RA). Interleukin (IL)-8 protein production and mRNA expressions were measured by enzyme-linked immunosorbent assay and quantitative-polymerase chain reaction, respectively. Uptake of fluorescein isothiocyanate (FITC)-rSSB was assessed by flow cytometry and fluorescence microscopy. Moreover, mitogen-activated protein kinase (MAPK) pathways and nuclear factor-kappaB activation were investigated. RESULTS: Human rSSB stimulated IL-8 production from normal human neutrophils and HL-60 (RA) cells in a time- and dose-dependent manner. This IL-8-stimulated activity was blocked by chloroquine and NH4Cl, indicating that endosomal acidification is important for this effect. We found rSSB activated both MAPK pathway and nuclear factor-kappaB signaling to transcribe the IL-8 gene expression of cells. Furthermore, tumor necrosis factor-α exerted an additive effect and rSSB-anti-SSB immune complex exhibited a synergistic effect on rSSB-induced IL-8 production. CONCLUSIONS: Sjögren's syndrome antigen B might act as an endogenous danger molecule to enhance IL-8 gene expression in human polymorphonuclear neutrophils.
25470448 Loss of SH3 domain-binding protein 2 function suppresses bone destruction in tumor necrosi 2015 Mar OBJECTIVE: SH3 domain-binding protein 2 (SH3BP2) is a signaling adapter protein that regulates the immune and skeletal systems. The present study was undertaken to investigate the role of SH3BP2 in arthritis using 2 experimental mouse models, i.e., human tumor necrosis factor α-transgenic (hTNF-Tg) mice and mice with collagen-induced arthritis (CIA). METHODS: First, Sh3bp2(-/-) and wild-type (Sh3bp2(+/+) ) mice were crossed with hTNF-Tg mice. Inflammation and bone loss were examined by clinical inspection and histologic and micro-computed tomography analysis, and osteoclastogenesis was evaluated using primary bone marrow-derived macrophage colony-stimulating factor-dependent macrophages (BMMs). Second, CIA was induced in Sh3bp2(-/-) and Sh3bp2(+/+) mice, and the incidence and severity of arthritis were evaluated. Anti-mouse type II collagen (CII) antibody levels were measured by enzyme-linked immunosorbent assay, and lymph node cell responses to CII were determined. RESULTS: SH3BP2 deficiency did not alter the severity of joint swelling but did suppress bone erosion in the hTNF-Tg mouse model. Bone loss at the talus and tibia was prevented in Sh3bp2(-/-) /hTNF-Tg mice compared to Sh3bp2(+/+) /hTNF-Tg mice. RANKL- and TNFα-induced osteoclastogenesis was suppressed in Sh3bp2(-/-) mouse BMM cultures. NF-ATc1 nuclear localization in response to TNFα was decreased in Sh3bp2(-/-) mouse BMMs compared to Sh3bp2(+/+) mouse BMMs. In the CIA model, SH3BP2 deficiency suppressed the incidence of arthritis and this was associated with decreased anti-CII antibody production, while antigen-specific T cell responses in lymph nodes were not significantly different between Sh3bp2(+/+) and Sh3bp2(-/-) mice. CONCLUSION: SH3BP2 deficiency prevents loss of bone via impaired osteoclastogenesis in the hTNF-Tg mouse model and suppresses the induction of arthritis via decreased autoantibody production in the CIA model. Therefore, SH3BP2 could potentially be a therapeutic target in rheumatoid arthritis.
25648515 Internet-based implementation of non-pharmacological interventions of the "people getting 2015 Feb 3 BACKGROUND: Rheumatoid arthritis (RA) affects 2.1% of the Australian population (1.5% males; 2.6% females), with the highest prevalence from ages 55 to over 75 years (4.4-6.1%). In Canada, RA affects approximately 0.9% of adults, and within 30 years that is expected to increase to 1.3%. With an aging population and a greater number of individuals with modifiable risk factors for chronic diseases, such as arthritis, there is an urgent need for co-care management of arthritic conditions. The increasing trend and present shifts in the health services and policy sectors suggest that digital information delivery is becoming more prominent. Therefore, it is necessary to further investigate the use of online resources for RA information delivery. OBJECTIVE: The objective is to examine the effect of implementing an online program provided to patients with RA, the People Getting a Grip on Arthritis for RA (PGrip-RA) program, using information communication technologies (ie, Facebook and emails) in combination with arthritis health care professional support and electronic educational pamphlets. We believe this can serve as a useful and economical method of knowledge translation (KT). METHODS: This KT randomized controlled trial will use a prospective randomized open-label blinded-endpoint design to compare four different intervention approaches of the PGrip-RA program to a control group receiving general electronic educational pamphlets self-management in RA via email. Depending on group allocation, links to the Arthritis Society PGrip-RA material will be provided either through Facebook or by email. One group will receive feedback online from trained health care professionals. The intervention period is 6 weeks. Participants will have access to the Internet-based material after the completion of the baseline questionnaires until the final follow-up questionnaire at 6 months. We will invite 396 patients from Canadian and Australian Arthritis Consumers' Associations to participate using online recruitment. RESULTS: This study will build on a pilot study using Facebook, which revealed promising effects of knowledge acquisition/integration of the evidence-based self-management PGrip educational program. CONCLUSIONS: The use of online techniques to disseminate knowledge provides an opportunity to reduce health care costs by facilitating self-management of people with arthritis. Study design strengths include the incorporation of randomization and allocation concealment to ensure internal validity. To avoid intergroup contamination, the Facebook group page security settings will be set to "closed", thus allowing only invited participants to access it. Study limitations include the lack of participant blinding due to the characteristics of this KT randomized controlled trial and a potential bias of recruiting patients only online, though this was proven effective in the previous pilot study. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12614000397617; http://www.anzctr.org.au/TrialSearch.aspx (Archived by WebCite at http://www.webcitation.org/6PrP0kQf8).
25957440 Development of the Sjögren's Syndrome Responder Index, a data-driven composite endpoint f 2015 Sep OBJECTIVES: To determine which outcome measures detected rituximab efficacy in the Tolerance and Efficacy of Rituximab in Sjögren's Disease (TEARS) trial and to create a composite endpoint for future trials in primary SS (pSS). METHODS: Post hoc analysis of the multicentre randomized placebo-controlled double-blind TEARS trial. The results were validated using data from two other randomized controlled trials in pSS, assessing rituximab (single-centre trial in the Netherlands) and infliximab, respectively. RESULTS: Five outcome measures were improved by rituximab in the TEARS trial: patient-assessed visual analogue scale scores for fatigue, oral dryness and ocular dryness, unstimulated whole salivary flow and ESR. We combined these measures into a composite endpoint, the SS Responder Index (SSRI), and we defined an SSRI-30 response as a ≥30% improvement in at least two of five outcome measures. In TEARS, the proportions of patients with an SSRI-30 response in the rituximab and placebo groups at 6, 16 and 24 weeks were 47% vs 21%, 50% vs 7% and 55% vs 20%, respectively (P < 0.01 for all comparisons). SSRI-30 response rates after 12 and 24 weeks in the single-centre rituximab trial were 68% (13/19) vs 40% (4/10) and 74% (14/19) vs 40% (4/10), respectively. No significant differences in SSRI-30 response rates were found between infliximab and placebo at any of the time points in the infliximab trial. CONCLUSION: A core set of outcome measures used in combination suggests that rituximab could be effective and infliximab ineffective in pSS. The SSRI might prove useful as the primary outcome measure for future therapeutic trials in pSS.
26473450 IgG4-related Disease from Head to Toe. 2015 Nov Immunoglobulin G4 (IgG4)-related disease is a relatively recently proposed clinical-pathologic entity that is characterized by fibro-inflammatory lesions rich in IgG4-positive plasma cells and, often but not always, elevated serum IgG4 concentrations. IgG4-related disease was recognized as a systemic disease in 2003, when extrapancreatic manifestations were identified in patients with autoimmune pancreatitis. Since then, the disease has been reported as affecting virtually every organ system and has been identified in the biliary tree, salivary and lacrimal glands, periorbital tissues, lungs, lymph nodes, thyroid gland, kidneys, prostate gland, testicles, breasts, and pituitary gland. Its pathogenesis is poorly understood, but findings are consistent with both an autoimmune and an allergic disorder. Although definitive diagnosis requires histopathologic analysis, imaging plays an important role in demonstrating infiltration and enlargement of involved organs. Because of the systemic nature of the disease, imaging workup of IgG4-related disease should always include whole-body examinations to detect multiorgan involvement. Patients often present with subacute development of a mass in or diffuse enlargement of the affected organ, sometimes mimicking a neoplastic process. In every anatomic location, several inflammatory and neoplastic entities must be considered in the differential diagnosis. Because IgG4-related disease usually shows a marked response to corticosteroid therapy, radiologists should be familiar with its clinical and imaging manifestations to avoid a delay in diagnosis and unnecessary surgical interventions.
24252015 Primary Sjögren's syndrome with chronic tubulointerstitial nephritis and lymphadenopathy 2015 Jul We describe a 62-year-old woman with Sjögren's syndrome (SS) presenting with tubulointerstitial nephritis (TIN) and lymphadenopathy mimicking IgG4-related disease (IgG4-RD). Computed tomography revealed multiple swollen lymph nodes. Biopsy of the largest lymph node showed reactive lymphadenopathy with dense IgG4 positive plasma cell (IgG4 + PC) infiltration. Renal biopsy showed chronic plasma cell-rich TIN with IgG4 + PC infiltration. This case suggests that Immunoglobulin G4 immunostaining does not always support the diagnosis of IgG4-RD in the differential diagnosis between SS and IgG4-RD.
27263804 Cytokine profile in adult-onset Still's disease: Comparison with systemic juvenile idiopat 2016 Aug To compare pro-inflammatory cytokine profiles and kinetics in patients with adult-onset Still's disease (AOSD) to those in patients with systemic juvenile idiopathic arthritis (s-JIA), we analyzed serum cytokine concentrations in 33 patients with AOSD and 77 patients with s-JIA and compared them with clinical features. Patients with AOSD and s-JIA shared a common cytokine profile pattern of a significant increase in IL-18. Patients with AOSD were classified into two subgroups based on serum IL-6 and IL-18 levels. The number of patients with arthritis was significantly higher in the IL-6-dominant subgroup. The cytokine patterns associated with s-JIA and AOSD share common features, such as a significant and predominant increase in IL-18. Distinct IL-6- and IL-18-based cytokine profiles might be responsible for distinct clinical manifestations. The presence of two distinct subgroups in patients with both diseases further supports the view that s-JIA and AOSD share a disease category.
25634183 Reactive hemophagocytic syndrome in adult-onset Still disease: clinical features, predicti 2015 Jan Hemophagocytic syndrome (HPS) is a potentially life-threatening complication of systemic inflammatory disorders. Adult-onset Still disease (AOSD) is one of the systemic autoimmune diseases associated with reactive hemophagocytic syndrome (RHS). This study aimed to evaluate the characteristic findings, predictive factors, and prognosis of RHS in patients with AOSD. We retrospectively evaluated 109 patients diagnosed with AOSD and reviewed their clinical data and laboratory findings, including the biopsy results of 21 AOSD patients with RHS. Moreover, data from 17 hemophagocytic lymphohistiocytosis (HLH) patients evaluated during the same period were compared with those from the RHS patients. Twenty-one patients (19.3%) developed RHS during the course of AOSD, and only 7 patients (6.4%) were confirmed by bone marrow, liver, or lymph node biopsy. AOSD patients with RHS showed significantly higher frequencies of splenomegaly, hepatomegaly, and lymphadenopathy than did those without RHS. Moreover, patients with RHS showed significantly higher relapse rates than those without RHS (61.9% vs 18.2%, P < 0.001). Possible triggering factors inducing hemophagocytosis were detected in 16 of 21 RHS patients (76.2%): disease flare in 12 patients (75%), infection in 3 patients (18.8%), and drug use in 1 patient (6.3%). AOSD patients with RHS showed higher frequencies of leukopenia, anemia, thrombocytopenia, hypoalbuminemia, hypofibrinogenemia, hypertriglyceridemia, hyperferritinemia, and elevated lactate dehydrogenase levels than did those without RHS. Multivariate logistic regression with forward selection procedure showed that low platelet count (<121,000/mm³), anemia, and hepatomegaly were independent predictors of RHS. Patients with definite RHS and those with probable RHS showed comparable results. Although RHS is a life-threatening complication of AOSD, long-term prognosis was observed to be similar in patients with and those without RHS. Compared to RHS patients, HLH patients had poor prognosis, such as higher death rates (52.9% vs 9.5%, P = 0.005). RHS can be considered when an AOSD patient shows at least 2 of the following 3 findings: low platelet count, anemia, and hepatomegaly. Diagnostic confirmation by biopsy may not be essential if typical clinical findings of RHS are present. Moreover, prognosis of RHS was better than that of HLH diagnosed by the presence of trilineage cytopenia at admission.
27803141 Development, Sensibility, and Validity of a Systemic Autoimmune Rheumatic Disease Case Asc 2017 Jan OBJECTIVE: Case ascertainment through self-report is a convenient but often inaccurate method to collect information. The purposes of this study were to develop, assess the sensibility, and validate a tool to identify cases of systemic autoimmune rheumatic diseases (SARD) in the outpatient setting. METHODS: The SARD tool was administered to subjects sampled from specialty clinics. Determinants of sensibility - comprehensibility, feasibility, validity, and acceptability - were evaluated using a numeric rating scale from 1-7. Comprehensibility was evaluated using the Flesch Reading Ease and the Flesch-Kincaid Grade Level. Self-reported diagnoses were validated against medical records using Cohen's κ statistic. RESULTS: There were 141 participants [systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis, Sjögren syndrome (SS), inflammatory myositis (polymyositis/dermatomyositis; PM/DM), and controls] who completed the questionnaire. The Flesch Reading Ease score was 77.1 and the Flesch-Kincaid Grade Level was 4.4. Respondents endorsed (mean ± SD) comprehensibility (6.12 ± 0.92), feasibility (5.94 ± 0.81), validity (5.35 ± 1.10), and acceptability (3.10 ± 2.03). The SARD tool had a sensitivity of 0.91 (95% CI 0.88-0.94) and a specificity of 0.99 (95% CI 0.96-1.00). The agreement between the SARD tool and medical record was κ = 0.82 (95% CI 0.77-0.88). Subgroup analysis by SARD found κ coefficients for SLE to be κ = 0.88 (95% CI 0.79-0.97), SSc κ = 1.0 (95% CI 1.0-1.0), PM/DM κ = 0.72 (95% CI 0.49-0.95), and SS κ = 0.85 (95% CI 0.71-0.99). The screening questions had sensitivity ranging from 0.96 to 1.0 and specificity ranging from 0.88 to 1.0. CONCLUSION: This SARD case ascertainment tool has demonstrable sensibility and validity. The use of both screening and confirmatory questions confers added accuracy.
26211509 Exacerbation of collagen antibody-induced arthritis in transgenic mice overexpressing pero 2015 Nov OBJECTIVE: Peroxiredoxin 6 plays important and complex roles in the process of inflammation, but its role in the development of rheumatoid arthritis (RA) remains unclear. We undertook this study to investigate the roles and mechanisms of peroxiredoxin 6 in the development of collagen antibody-induced arthritis (CAIA) and antigen-induced arthritis (AIA) in peroxiredoxin 6-overexpressing transgenic mice, in peroxiredoxin 6-transfected RAW 264.7 cells, in macrophages isolated from peroxiredoxin 6-overexpressing transgenic mice, and in synoviocytes from arthritis patients. METHODS: CAIA and AIA were induced using standard methods. Peroxiredoxin 6-transfected RAW 264.7 cells, macrophages isolated from peroxiredoxin 6-overexpressing transgenic mice, and synoviocytes from arthritis patients were used to study proinflammatory responses and mechanisms. Clinical scores and histopathologic changes were determined in peroxiredoxin 6-overexpressing transgenic mice and wild-type (WT) mice with CAIA or AIA. Generation of nitric oxide (NO), expression of inducible NO synthase and cyclooxygenase 2, and activity of NF-κB and activator protein 1 (AP-1) were determined in cultured macrophages and synoviocytes as well as in joint tissue from mice by Western blotting, electrophoretic mobility shift assay, and immunohistochemical analysis. RESULTS: Development of CAIA and AIA and proinflammatory responses were more exacerbated in peroxiredoxin 6-overexpressing transgenic mice than in WT mice. Overexpression of peroxiredoxin 6 increased lipopolysaccharide-induced inflammatory responses in RAW 264.7 cells, in macrophages isolated from peroxiredoxin 6-overexpressing transgenic mice, and in synoviocytes from arthritis patients, and this was accompanied by up-regulation of the JNK pathway. Moreover, a JNK inhibitor completely blocked RA development and proinflammatory responses. CONCLUSION: Our findings suggest that overexpression of peroxiredoxin 6 might promote development of RA through NF-κB and AP-1 activity via the JNK pathway.
25045858 Rapidly Fatal Internal Carotid Artery Mycotic Aneurysm Rupture in a Rheumatoid Patient Tak 2015 May OBJECT: Tumor necrosis factor (TNF)-α inhibitors are effective at treating certain inflammatory and autoimmune disorders. They are generally safe; potential adverse events include infections (bacterial, fungal, and viral), congestive heart failure exacerbations, and the potential for demyelinating diseases and possibly certain malignancies. We present the first documented case of fungal internal carotid artery (ICA) mycotic aneurysm in a patient being treated with a TNF-α inhibitor. We also review the literature on infections with TNF-α inhibition and the management of previously reported fungal ICA mycotic aneurysm cases. CASE DESCRIPTION: A 76-year-old woman with rheumatoid arthritis, treated with etanercept and methotrexate, presented with a 2-week history of left temporal headaches. She was treated empirically for giant cell arteritis (GCA) with oral prednisone, which provided no symptom relief. She was subsequently hospitalized for a superficial temporal artery biopsy, which was negative for GCA. She returned 2 weeks later after experiencing a left thromboembolic ischemic stroke. She had an acute neurologic decline, and a head computed tomography scan showed diffuse subarachnoid hemorrhage from a ruptured left fusiform paraclinoid ICA aneurysm. She was taken emergently for a craniotomy for clip-wrapping of the aneurysm, but intraoperative ultrasound revealed poor flow in the left anterior cerebral circulation and a complete infarct of the left-sided anterior circulation. The family withdrew care and the patient died. Postmortem analysis demonstrated fungi consistent with Aspergillus invading the necrotic left ICA. CONCLUSIONS: Although fungal mycotic aneurysms of the ICA are rare, their incidence may increase with the expanded use of immunosuppressive medications. Patients with rheumatoid arthritis who take potent immunosuppression regimens may be prime candidates for mycotic aneurysms because they often have two favoring conditions: atherosclerosis and immunosuppression. These ICA aneurysms carry a high mortality rate, so early diagnosis and aggressive therapy, potentially by endovascular trapping/vessel occlusion coupled with long-term antifungal therapy, is essential.
27607572 A national survey on the management of psoriatic arthritis using the Delphi method. 2017 Mar OBJECTIVES: Accurate diagnosis and appropriate management of psoriatic arthritis (PsA) is essential to avoid unnecessary morbidity. Our aim in this study was to evaluate the current approach to the management of PsA among rheumatologists. METHODS: A 16-item online questionnaire, produced using the Delphi method, was submitted to a panel of rheumatologists who anonymously expressed their opinions on a scale from 1 (maximum disagreement) to 5 (maximum agreement). Positive consensus was defined by ≥66% of the respondents scoring an item 3, 4 or 5. Negative consensus was defined by ≥66% of the respondents scoring an item 1 or 2. RESULTS: The surveyed rheumatologists agreed that in its early stage, PsA is characterised by the involvement of few joints and/or entheses and that psoriasis, although possibly absent, will be present in a patient's past personal or family history. There was no consensus among the rheumatologists regarding normalisation of C-reactive protein levels and erythrocyte sedimentation rates defining remission. The specialists believed that clinical remission was achieved more frequently and for longer among patients with PsA than rheumatoid arthritis. The participants believed that neutralising antibodies altered the efficacy of anti-tumour necrosis factor agents and that monoclonal antibodies induced greater production of neutralising antibodies than receptor proteins. However, knowledge was somewhat lacking in relation to the prophylaxis of latent tuberculosis. CONCLUSIONS: The data collected showed that the surveyed rheumatologists had a good knowledge of the diagnosis of early-stage PsA and a good understanding of its management in relation to its clinical phenotype, with the exception of the form having predominantly axial involvement.
27934678 Incidence of hepatitis B virus reactivation in patients with resolved infection on immunos 2017 Jun BACKGROUND: Although the reactivation of hepatitis B virus (HBV) is recognised as a serious complication in patients with rheumatic disease (RD) receiving immunosuppressive drugs (ISDs), the incidence and risk factors for reactivation remain controversial. OBJECTIVES: To investigate the incidence and risk factors for HBV reactivation in patients with RD. METHODS: We performed a multicentre, observational, prospective study over 2 years in patients with resolved HBV infection. Patients with RD treated with a dose of ≥5 mg/day prednisolone and/or synthetic or biological ISDs with negative HB virus surface antigen and positive anti-HB virus surface antibody (HBsAb) and/or anti-HB virus core antibody (HBcAb) were enrolled. Quantitative HBV DNA results and related data were regularly recorded. RESULTS: Among 1042 patients, including 959 with rheumatoid arthritis, HBV DNA was detected in 35 (1.93/100 person-years), with >2.1 log copies/mL observed in 10 patients (0.55/100 person-years). None of the reactivated patients, including seven treated with a nucleic acid analogue, showed overt hepatitis. Low HBsAb titres and advanced age seemed to be risk factors for HBV reactivation; however, reactivation was observed in three patients with positive HBsAb and negative HBcAb test results. The risk of reactivation was lower with methotrexate but higher with prednisolone among the different types of ISDs. The intervals from the start of ISD to reactivation were relatively long (3-182 months; median, 66 months). CONCLUSIONS: The incidence of HBV reactivation with ISD use was 1.93/100 person-years in patients with RD with resolved HBV infection. No overt hepatitis was observed in the reactivated patients.
27037381 Viral arthritis. 2016 Apr Acute-onset arthritis is a common clinical problem facing both the general clinician and the rheumatologist. A viral aetiology is though to be responsible for approximately 1% of all cases of acute arthritis with a wide range of causal agents recognised. The epidemiology of acute viral arthritis continues to evolve, with some aetiologies, such as rubella, becoming less common due to vaccination, while some vector-borne viruses have become more widespread. A travel history therefore forms an important part of the assessment of patients presenting with an acute arthritis. Worldwide, parvovirus B19, hepatitis B and C, HIV and the alphaviruses are among the most important causes of virally mediated arthritis. Targeted serological testing may be of value in establishing a diagnosis, and clinicians must also be aware that low-titre autoantibodies, such as rheumatoid factor and antinuclear antibody, can occur in the context of acute viral arthritis. A careful consideration of epidemiological, clinical and serological features is therefore required to guide clinicians in making diagnostic and treatment decisions. While most virally mediated arthritides are self-limiting some warrant the initiation of specific antiviral therapy.
25925313 Reduced levels of circulating progenitor cells in juvenile idiopathic arthritis are counte 2015 Apr 30 BACKGROUND: Endothelial progenitor cells (EPC) promote angiogenesis and vascular repair. Though reduced EPC levels have been shown in rheumatoid arthritis, no study has so far evaluated EPCs in children with juvenile idiopathic arthritis (JIA). We aimed to study circulating EPCs in children with JIA, their relation to disease activity, and effects of anti TNF-α treatment. METHODS: Circulating EPCs were quantified by flow cytometry based on CD34, CD133 and KDR expression in peripheral blood of 22 patients with oligoarticular JIA and 29 age-matched controls. EPCs were re-assessed in children with methotrexate-resistant oligo-extended JIA before and up to 12 month after initiation of anti-TNF-alpha therapy. Plasma concentrations of inflammatory and EPC-regulating factors were measured using a multiplex array. Confocal immunofluorescence was used to demonstrate EPCs in synovial tissues. RESULTS: Children with active JIA showed a significant reduction of relative and absolute counts of circulating progenitor cells and EPCs compared to age-matched healthy controls. CD34(+) cell levels were modestly and inversely correlated to disease activity. A strong inverse correlation was found between serum TNF-α and EPC levels. In 8 patients treated with anti TNF-α agents, the number of EPCs rose to values similar to healthy controls. CD34(+)KDR(+) EPCs were found in the synovial tissue of JIA children, but not in control. CONCLUSIONS: Children with JIA have reduced levels of the vasculoprotective and proangiogenic EPCs. While EPCs may contribute to synovial tissue remodelling, EPC pauperization may indicate an excess cardiovascular risk if projected later in life.