Showing papers in "Modern Rheumatology in 2017"
TL;DR: The current optimal approach for the diagnosis of IgG4-RD is described, based on both comprehensive and organ-specific diagnostic criteria, in patients with diseases such as IgG 4-related pancreatitis (AIP), sclerosing cholangitis, and renal, lung and orbital diseases.
Abstract: IgG4-related disease (IgG4-RD) is a fascinating clinical entity proposed by Japanese investigators, and includes a wide variety of diseases, formerly diagnosed as Mikulicz's disease (MD), autoimmune pancreatitis (AIP), interstitial nephritis, prostatitis, retroperitoneal fibrosis, etc. Although all clinicians in every field of medicine may encounter this new disease, a unifying diagnostic criterion has not been established. In 2011, the Japanese IgG4 team, organized by the Ministry of Health, Labor and Welfare (MHLW) of Japan, published comprehensive diagnostic criteria for IgG4-RD. Several problems with these criteria have arisen in clinical practice, however, including the difficulty obtaining biopsy samples from some patients, and the sensitivity and the specificity of techniques used to measure serum IgG4 concentrations. Although serum IgG4 concentration is an important clinical marker for IgG4-RD, its diagnostic utility in differentiating IgG4-RD from other diseases, called IgG4-RD mimickers, remains unclear. This review describes the current optimal approach for the diagnosis of IgG4-RD, based on both comprehensive and organ-specific diagnostic criteria, in patients with diseases such as IgG4-related pancreatitis (AIP), sclerosing cholangitis, and renal, lung and orbital diseases.
161 citations
TL;DR: Logistic regression analysis showed that hypertension, impaired glucose tolerance, and mild cognitive impairment increase the risk of KOA, and excess weight was inversely associated with the occurrence of femoral neck osteoporosis.
Abstract: Although locomotive organ disorders are major causes of disability and require support, little information is available regarding their epidemiology. Prevalence and co-existence of locomotive organ disorders including knee osteoarthritis (KOA), lumbar spondylosis (LS), hip osteoarthritis, and osteoporosis have been determined from baseline results of the Research on Osteoarthritis/Osteoporosis Against Disability (ROAD) study. KOA, LS, and hip osteoarthritis overlap in the population, while KOA and LS co-exist in 42.0% of people. Mutual associations between locomotive organ disorders, metabolic syndrome components, and mild cognitive impairment were found using baseline and 3-year follow-up data from the ROAD study. Logistic regression analysis showed that hypertension, impaired glucose tolerance, and mild cognitive impairment increase the risk of KOA. Osteoporosis at L2-4 was significantly influenced by the presence of femoral neck osteoporosis, and vice versa. In turn, excess weight was inversely...
95 citations
TL;DR: Shoulder complaint, neuropathic pain, nociceptive pain, shoulder complaints, and QOL differed significantly among all three groups and worsened with decline in mobility on the LS risk test.
Abstract: Objectives: A locomotive syndrome (LS) risk test for evaluation of physical ability is recently proposed. The objective of this study is to evaluate the utility of this test by examining physical ability, neuropathic pain, nociceptive pain, shoulder complaints, and quality of life (QOL).Methods: A prospective cohort study was conducted in 523 subjects (240 males, 283 females; mean age: 63.3 years) at a health checkup. Data collected using visual analog scales (VAS) for shoulder pain, low back pain, sciatica, and knee pain, neuropathic pain, shoulder complaint, body mass index (BMI), osteoporosis, and SF-36 were compared among three LS risk stages.Results: Subjects in LS risk stage 1 (24%) had significantly more osteoporosis, slower gait speed, weaker muscle strength and higher VAS, with no difference in age and BMI compared to those with no LS risk (50%). Subjects in stage 2 (26%) had significantly poorer results for all items. Shoulder complaint, neuropathic pain and QOL differed significantly am...
63 citations
TL;DR: Four factors associated with OMAAV were found to be related to an unfavorable clinical course threatening the patient's hearing and/or lives, namely facial palsy, hypertrophic pachymeningitis, both ANCAs-negative phenotype, and disease relapse.
Abstract: Objective: We aimed to analyze clinical features and treatment outcomes of otitis media caused by antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), i.e. otitis media with AAV (OMAAV).Methods: This survey was performed between December 2013 and February 2014. The study began with a preliminary survey to 123 otolaryngology institutions in Japan to inquire about their experiences with OMAAV patients during the past 10 years, and was followed by a questionnaire survey to investigate clinical and laboratory findings. OMAAV was defined using the criteria described in the text.Results: Two hundred and thirty-five patients classified as OMAAV were enrolled in this study. They were characterized as follows: (1) disease onset with initial signs/symptoms due to intractable otitis media with effusion or granulation, which did not respond to ordinary treatments such as antibiotics and insertion of tympanic ventilation tubes, followed by progressive hearing loss; (2) predominantly female (73%) and...
61 citations
TL;DR: CT-P13 was well tolerated in patients who maintained the treatment after 54 weeks and in patients in the switch group who switched to CT-P 13 after 54 Weeks of IFX treatment, and the study demonstrated a stable clinical efficacy of CT- P13 in RA patients.
Abstract: Objectives: This study aimed to evaluate the safety of CT-P13 in patients with rheumatoid arthritis (RA) during long-term treatment or after switching from innovator infliximab (IFX).Methods: Patients who completed 54 weeks of treatment in a phase I/II study (PI/II) received CT-P13 at an initial dose of 3 mg/kg at Week 62, with dose increases permitted up to 10 mg/kg. The primary endpoint was adverse event (AE) incidence.Results: Thirty-four of 38 patients in the maintenance group and 29 of 33 in the switch group reported at least one AE. Safety profiles in both groups were similar to those in PI/II. Eleven of 28 patients who were positive for anti-drug antibodies (ADA) at Week 62 discontinued the study before Week 110. Forty-one of 43 ADA-negative patients remained negative, and 10 of 28 ADA-positive patients became negative during the study. The mean DAS28 (ESR) at Week 134 was 3.166 in the maintenance group and 3.955 in the switch group.Conclusions: CT-P13 was well tolerated in patients who mai...
57 citations
Kanazawa Medical University1, University of Toyama2, University of Tsukuba3, University of Occupational and Environmental Health Japan4, Kagawa University5, Kanazawa University6, RMIT University7, Niigata University8, University of Fukui9, Shimane University10, Okayama University11, Nagoya University12, Dokkyo University13
TL;DR: Glucocorticoid treatment is usually effective for patients with IgG4-RD, and the possibility of other disorders when a patient is glucocortioid refractory should be examined.
Abstract: Objective: Although glucocorticoids are effective for patients with IgG4-related disease, the treatment has not yet been standardized. Therefore, the treatment strategy should be established.Patients and methods: Patients who fulfilled the comprehensive diagnostic criteria for definite IgG4-related disease were started on prednisolone (0.6 mg/kg body weight) with the dose reduced every two weeks. The subsequent maintenance dose and need for prednisolone were determined for individual patients. The primary endpoint was the complete remission (CR) rate at one year. Secondary endpoints included overall response rate (ORR), the maintenance dose, the relapse rate, and adverse events.Results: This study enrolled 61 patients. After clinicopathological review, three patients were excluded, and one, 13, and 44 patients were diagnosed with probable, possible, and definite IgG4-related disease, respectively. Of the 44 patients with definite IgG4-RD, 29 (65.9%) achieved CR, and the ORR was 93.2%. No patient w...
56 citations
TL;DR: This review article focuses on the recent advances in the field of AS research, including HLA and non-HLA susceptibility genes identified in genome-wide association studies (GWAS), and aberrant epigenetic modifications of gene loci associated with AS.
Abstract: Ankylosing spondylitis (AS) is a chronic inflammatory autoimmune disease, characterized by typically an axial arthritis. AS is the prototype of a group of disorders called spondyloarthropathies, which is believed to have common clinical manifestations and genetic predisposition. To date, the exact etiology of AS remains unclear. Over the past few years, however, the role of genetic susceptibility and epigenetic modifications caused through environmental factors have been extensively surveyed with respect to the pathogenesis of AS, resulted in important advances. This review article focuses on the recent advances in the field of AS research, including HLA and non-HLA susceptibility genes identified in genome-wide association studies (GWAS), and aberrant epigenetic modifications of gene loci associated with AS. HLA genes most significantly linked with AS susceptibility include HLA-B27 and its subtypes. Numerous non-HLA genes such as those in ubiquitination, aminopeptidases and MHC class I presentation molecules like ERAP-1 were also reported. Moreover, epigenetic modifications occurred in AS has been summarized. Taken together, the findings presented in this review attempt to explain the circumstance by which both genetic variations and epigenetic modifications are involved in triggering and development of AS. Nonetheless, several unanswered dark sides continue to clog our exhaustive understanding of AS. Future researches in the field of epigenetics should be carried out to extend our vision of AS etiopathogenesis.
52 citations
TL;DR: The multiple roles of fractalkine in the pathogenesis of RA and its potential as a therapeutic target for this disease are reviewed.
Abstract: Fractalkine is a CX3C chemokine that exists in both membrane-bound and soluble forms. Interaction between fractalkine and its unique receptor (CX3CR1) induces cell adhesion, chemotaxis, crawling, "accessory cell" activity, and survival. The serum level of fractalkine is elevated in patients with rheumatoid arthritis (RA) and is correlated with disease activity. Peripheral blood CD16+ monocytes and a subset of T cells express CX3CR1, while fractalkine is expressed on fibroblast-like synoviocytes and endothelial cells in the synovial tissue of patients with RA. Fractalkine expression is enhanced by tumor necrosis factor-α and interferon-γ, and it promotes the migration of monocytes, T cells, and osteoclast precursors into RA synovial tissue. Fractalkine also induces the production of inflammatory mediators by macrophages, T cells, and fibroblast-like synoviocytes. Moreover, fractalkine promotes angiogenesis and osteoclastogenesis. In an animal model of RA, arthritis was improved by the abrogation of fractalkine. Recently, a clinical trial of an anti-fractalkine monoclonal antibody for the treatment of RA commenced in Japan. We review the multiple roles of fractalkine in the pathogenesis of RA and its potential as a therapeutic target for this disease.
50 citations
TL;DR: Gene ontology analysis indicated transcript alternative splicing and protein modification mediated by DNA methylation might play an important role in the pathogenesis of RA.
Abstract: Introduction: Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic inflammation of the joints. Recent evidence indicated the epigenetic changes may contribute to the pathogenesis of RA.Method: To understand the extent and nature of dysregulated DNA methylation in RA CD4T cells, we performed a genome-wide DNA methylation study in CD4 + T cells in 12 RA patients compared to 12 matched normal healthy controls. Cytosine methylation status was quantified with Illumina methylation 450K microarray.Result: The DNA methylation profiling showed 383 hyper- and 785 hypo-methylated genes in the CD4 + T cells of the RA patients (p < 3.4 × 10−7). Gene ontology analysis indicated transcript alternative splicing and protein modification mediated by DNA methylation might play an important role in the pathogenesis of RA. In addition, the result showed that human leukocyte antigen (HLA) region including HLA-DRB6, HLA-DQA1 and HLA-E was frequently hypomethylated, but HLA-DQB1 hypermethylated in CpG i...
44 citations
TL;DR: It is suggested that rituximab has the potential to offer an effective agent for the treatment of anti-MDA5-positive RP-ILD of CADM, although there was no significant effect due to standard immunosuppressive treatment.
Abstract: Rapidly progressive interstitial lung disease (RP-ILD) in patients with clinically amyopathic dermatomyositis (CADM) associated with antibodies to melanoma differentiation-associated gene5 (MDA5) results in a high mortality rate. We experienced a case of anti-MDA5-positive RP-ILD of CADM which showed a response to rituximab, although there was no significant effect due to standard immunosuppressive treatment. This case suggests that rituximab has the potential to offer an effective agent for the treatment of anti-MDA5-positive RP-ILD of CADM.
42 citations
TL;DR: Recent pieces of evidence suggested that bone-resorbing osteoclasts are highly responsive to RA-related autoantibodies, providing a novel link between autoimmunity and bone, allowing unraveling the underlying mechanisms, which are responsible for the well-known clinical observation that RA- related autoant ibodies are associated with a more severe disease course.
Abstract: Bone loss is a central feature of rheumatoid arthritis (RA). It is considered to represent a sign of irreversible structural damage triggered by chronic inflammation. Recent evidence, however, suggests that autoantibodies are an important and earlier driver for bone damage in RA. This article summarizes current evidence for the role of RA-related autoantibodies in mediating bone loss. Rheumatoid factor and antibodies recognizing modified (citrullinated) proteins are the central features of autoimmunity in RA patients. Despite being used as diagnostic markers for many years, ascertaining the differentiation of RA from other forms of inflammatory arthritides, the role of these antibodies as pathogenic players has long been unrecognized. Recently, several pieces of evidence suggested that bone-resorbing osteoclasts are highly responsive to RA-related autoantibodies, providing a novel link between autoimmunity and bone. These developments have allowed unraveling the underlying mechanisms, which are responsible for the well-known clinical observation that RA-related autoantibodies are associated with a more severe disease course. At present, rheumatoid factor and antibodies recognizing citrullinated proteins are considered as potent osteoclast inducers and triggers for bone loss in arthritis.
TL;DR: Men with PsA are more likely to have higher PASI scores and longer duration to develop arthritis after the onset of psoriasis, while women are morelikely to haveHigher disease activity and report more fatigue and physical activity limitations.
Abstract: Objectives: To assess gender related differences in a cohort of patients with psoriatic arthritis (PsA).Methods: Consecutively recruited patients were included and underwent clinical, radiological and laboratory evaluation by using standardized protocol and case report forms.Results: Women (n = 115) with PsA had higher symptom duration and body mass index (BMI), tender and swollen joint counts, disease activity score-28 joints (DAS28), Erythrocyte sedimentation rate (ESR) and poorer physical activity and fatigue than men (n = 72) with PsA. Psoriasis area and severity index (PASI) were higher in male patients. However quality of life (SF36 physical and mental component scores), articular pattern, extra-articular features (including uveitis, iritis) and family history for psoriasis, spondyloarthritis (SpA) (PsA and ankylosing spondylitis [AS]) were quite similar between men and women.Conclusions: Some of the clinical and laboratory variables tend to be different between men and women with PsA. The e...
TL;DR: It is suggested that despite an improvement of clinical manifestations has been observed in more than half of the patients, it is not possible to draw firm conclusions about the effectiveness of CZP in BD and further studies with larger cohorts of patients are warranted.
Abstract: Objectives: The purpose of the present study was to describe our experience with the recombinant Fab’ antibody fragment against TNF-α Certolizumab Pegol (CZP) in patients with Behcet’s disease (BD) refractory to standardized therapies and previous biologic agents.Methods: Retrieved data including demographic characteristics, clinical manifestations, and previous treatments were collected in three different specialized Rheumatologic Units in Italy. In order to evaluate disease activity, the BD current activity form (BDCAF) has been used before starting CZP therapy and at each visit during treatment.Results: Thirteen BD patients (mean age 42.6 ± 8.8 years) with a disease duration of 8.80 ± 6.9 years, underwent CZP treatment for 6.92 ± 3.52 months. Six patients (46.15%) experienced a worsening of symptoms after 4.16 ± 1.21 months, whereas a satisfactory response was achieved in seven patients (53.84%) who were still on CZP therapy at the last follow-up visit (after 9.28 ± 3.03 months of treatment). T...
TL;DR: The SUA level and HUA prevalence showed U-shaped or J-shaped associations with age, and Multivariate logistic regression revealed age, waist circumference, total cholesterol, triglyceride, hypertension and non-alcoholic fatty liver disease history, prolonged sitting, alcohol consumption, and oral diuretics were independent risk factors of HUA, while long sleep duration was protective against HUA.
Abstract: Objective: The objective of this study is to determine the serum uric acid (SUA) level and the prevalence of hyperuricemia (HUA) in Chinese population.Methods: We conducted a cross-sectional study among 100,226 employees (79.9% male) of the Kailuan Group using physical examination data in 2006–2007. HUA was defined as SUA >356.9 μmol/L (6.0 mg/dL) for women and SUA >416.4 μmol/L (7.0 mg/dL) for men. We investigated crude and age adjusted HUA prevalence and compared characteristics of subjects with and without HUA in men and women using multivariate logistic regression.Results: SUA levels were 244.9 ± 71.5 μmol/L in women and 302.0 ± 83.5 μmol/L in men. About 8290 (8.27%) subjects were diagnosed with HUA. Age-adjusted prevalence of HUA was 8.02% in the total sample (6.87% in women and 8.57% in men). The SUA level and HUA prevalence showed U-shaped or J-shaped associations with age. Multivariate logistic regression revealed age, waist circumference, total cholesterol, triglyceride, hypertension and ...
TL;DR: Two cases of TAFRO syndrome are found and another eighteen previously reported cases are reviewed, finding historical findings of the lymph nodes and levels of interleukin 6 (IL-6) and vascular endothelial growth factor in both serum/plasma and effusions are important characteristics for diagnosing this syndrome.
Abstract: Recently, more than ten cases of thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly (TAFRO) syndrome or Castleman-Kojima disease exhibiting such symptoms as thrombocytopenia, anasarca, fever, reticulin fibrosis and organomegaly have been reported in Japan. We have found two cases of TAFRO syndrome and have reviewed another eighteen previously reported cases. Histological findings of the lymph nodes and levels of interleukin 6 (IL-6) and vascular endothelial growth factor in both serum/plasma and effusions are important characteristics for diagnosing this syndrome.
TL;DR: The oxidative stress markers in blood for patients with SSC were aberrant, indicating the imbalanced states of oxidation and antioxidation in SSC.
Abstract: Objectives: The purpose of this study is to clarify the relationship between systemic sclerosis (SSC) and oxidative stress markers in blood.Methods: We conducted a systematic literature search of databases, including PubMed and Embase, for studies reporting circulating oxidative stress markers in patients with SSC and controls published from 1980 to December 2015. Standardized mean differences (SMDs) and 95% confidence intervals (95%CI) were calculated.Results: Of the 1076 articles initially retrieved, 47 were included in our meta-analysis including 12 oxidative stress markers. The concentrations of nitric oxide (SMD = 0.77; 95%CI: 0.18, 1.36; p = 0.01), malondialdehyde (SMD =1.63; 95%CI: 1.03, 2.24; p = 0.000), asymmetric dimethylarginine (SMD = 0.51; 95%CI: 0.12, 0.91; p = 0.011), and ROOH (SMD = 3.37; 95%CI: 0.28, 6.46; p = 0.033) in the blood of patients with SSC were higher than those of the control group, whereas the concentrations of superoxide dismutase (SMD = −1.11; 95%CI: −1.57, −0.65; p...
TL;DR: For severe cases with low respiratory function, intensive therapy, including cyclophosphamide, has a potential to improve the prognosis and is effective for exacerbations of rheumatoid arthritis-associated interstitial lung disease.
Abstract: Objectives: Acute or subacute exacerbations are recognized as a severe complication of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Nevertheless, the role of intensive immunosuppression in RA-ILD remains elusive. We attempted to evaluate the clinical characteristics and efficacy of immunosuppressive treatment in exacerbated RA-ILD.Methods: Clinical data, including respiratory function, imaging, treatment, and prognosis, were retrospectively collected for 17 patients with RA-ILD who required hospitalization at the University of Tokyo Hospital due to an acute exacerbation (12 patients) or subacute exacerbation (5 patients).Results: Patients with RA-ILD demonstrated a significantly higher titers of anticyclic citrullinated peptide antibodies compared with RA patients in Japanese Ninja registry, suggesting the role of adaptive immunity. Immunosuppressive treatment suppressed the deterioration of pulmonary functions with improved ground grass opacity and consolidation. In particu...
TL;DR: Serum IL-17 was significantly associated with cartilage defects and BMLs in patients with an increased inflammatory status, suggesting that metabolic and inflammatory mechanisms may have a role to play in knee OA.
Abstract: Objectives: To investigate cross-sectional associations between serum levels of resistin and interleukin-17 (IL-17) and cartilage defects and bone marrow lesions (BMLs) in patients with knee symptomatic osteoarthritis (OA).Methods: One hundred and ninety-four consecutively-selected patients with knee symptomatic OA (mean 55.4 years, range 34–74, 87% females) were included in Anhui Osteoarthritis (AHOA) Study. Knee cartilage defects and BMLs were determined at different sites using T2-weighted fat-suppressed fast spin echo MRI. Serum resistin, IL-17, and high-sensitivity C-reactive protein (hs-CRP) levels were measured using ELISA.Results: In multivariable analyses, serum resistin was positively associated with cartilage defects at lateral femoral, lateral tibial, and medial tibial (all p 2.45 pg/ml), IL-17 was...
TL;DR: Modified metatarsal shortening offset osteotomy was recommended for RA forefoot disorders as one of the joint preservation surgeries in short- to mid-term follow-up, however, some modifications to avoid limitation of ROM in the MTP joint are required.
Abstract: Objectives: Advances in drug therapy for rheumatoid arthritis (RA) have been encouraging us to preserve the metatarsopharangeal (MTP) joint in correction of forefoot deformities, and original metatarsal shortening offset osteotomy was recommended as one of the conventional surgical options for forefoot deformities in RA cases. The objective of this study was to evaluate short- to mid-term outcomes of modified metatarsal shortening offset osteotomy.Methods: A retrospective observational study was completed for 80 RA cases (mean follow-up period: 3.2 years) who underwent modified metatarsal shortening offset osteotomy. Both lesser toe scales and RA foot ankle scales were administered using the Japanese Society for Surgery of the Foot (JSSF) standard rating system, and a postoperative self-administered foot evaluation questionnaire (SAFE-Q) at final follow-up was also checked to evaluate clinical outcomes.Results: This procedure significantly improved clinical scores of both the JSSF [lesser toes and...
TL;DR: IBD is significantly associated with AS and RA in the large-scaled population-based study, which suggests that etiopathogenesis of IBD might be shared withAS and RA.
Abstract: Objectives: Tantalizing connections between autoimmune rheumatic diseases (ARDs) and inflammatory bowel disease (IBD) have become evident with regard to their genetic and immunologic background. However, the association between these two disease entities remains unclear. The aim of this study is to investigate the association between each ARD and IBD.Methods: A nationwide population-based cross-sectional study was performed using the Korean National Health Insurance Claims database. The data of patients with IBD and age- and sex-matched controls between 2009 and 2013 were collected from the database. The prevalence of ARDs, including systemic lupus erythematosus (SLE), inflammatory myositis (polymyositis and dermatomyositis), systemic sclerosis (SSc), Sjogren’s syndrome (SjS), ankylosing spondylitis (AS), and rheumatoid arthritis (RA), was determined. The associations between each ARD and IBD were analyzed using multivariate logistic regression models.Results: A total of 40,843 IBD patients (28,19...
TL;DR: Histological examination of bioptic samples from the sinonasal area and oral cavity represents the mainstay for the diagnosis of IgG4-RD involvement of the midline structures.
Abstract: Objective: A series of destructive and tumefactive lesions of the midline structures have been recently added to the spectrum of IgG4-related disease (IgG4-RD). We examined the clinical, serological, endoscopic, radiological, and histological features that might be of utility in distinguishing IgG4-RD from other forms of inflammatory conditions with the potential to involve the sinonasal area and the oral cavity.Methods: We studied 11 consecutive patients with erosive and/or tumefactive lesions of the midline structures referred to our tertiary care center. All patients underwent serum IgG4 measurement, flow cytometry for circulating plasmablast counts, nasal endoscopy, radiological studies, and histological evaluation of tissue specimens. The histological studies included immunostaining studies to assess the number of IgG4 + plasma cells/HPF for calculation of the IgG4+/IgG + plasma cell ratio.Results: Five patients with granulomatosis with polyangiitis (GPA), three with cocaine-induced midline d...
TL;DR: The abnormal increase of LDGs may exacerbate abnormal NET regulation and further contribute to the pathogenesis of ILD in DM patients by abnormally forming NETs.
Abstract: Objective: We previously found that neutrophil extracellular traps (NETs) were associated with interstitial lung disease (ILD) in dermatomyositis (DM) patients. However, it is unclear whether low-density granulocytes (LDGs), endowed with enhanced NET formation capabilities, contribute to the pathogenesis of ILD. This study aims to elucidate the relationship between LDGs and DM-associated ILD.Methods: We recruited 48 DM patients (28 with ILD) as well as 19 healthy volunteers for this study. The percentage of LDGs in peripheral blood mononuclear cells (PBMCs) was ascertained by flow cytometry. Plasma cfDNA was measured by using the Quant-iT PicoGreen dsDNA Kit and plasma LL-37 was tested by using the LL-37 ELISA kit.Results: The percentage of LDGs was 7.1 times higher in DM patients than in healthy controls. LDG percentage was 2.7 times higher in DM patients with ILD than in DM patients without ILD. Additionally, LDG percentage positively correlated with MYOACT lung disease activity scores, and NET/...
TL;DR: Although a safety concern was identified with concomitant use of IGU and warfarin, this real-world study showed no other new safety concerns and similar effectiveness to clinical trials.
Abstract: Objective: To determine the real-world safety and effectiveness of iguratimod (IGU) for rheumatoid arthritis (RA), a 52-week, Japanese, post-marketing surveillance study was conducted. An interim analysis at week 24 was performed.Methods: This study included all RA patients who received IGU following its introduction to the market. All adverse events (AEs) and adverse drug reactions (ADRs) were collected. Effectiveness was evaluated by the change in Disease Activity Score 28-C-reactive protein (DAS28-CRP) from baseline to week 24.Results: Safety was analyzed in 2679 patients. The overall incidences of AEs, ADRs, and serious ADRs were 38.41, 31.65, and 3.21%, respectively; the most commonly reported serious ADRs were pneumonia/bacterial pneumonia, interstitial lung disease, and Pneumocystis jiroveci pneumonia. Concomitant glucocorticoid use and comorbid conditions associated with respiratory disease were identified as risk factors for serious infections. Pulmonary alveolar hemorrhage and increased ...
TL;DR: The data suggest that UPR activation occurs in M-CSF-derived macrophages of AS patients and is accompanied by overexpression of HLA-B27, which appears to be associated with overproduction of IL-23 in AS macrophage markers.
Abstract: Objective: Interleukin (IL)-23/IL-17 pathway involves in the pathogenesis of ankylosing spondylitis (AS). The exact mechanism implicated in overexpression of IL-23 and activation of the IL-23/IL-17 axis is not clear. The aim of the study was to clarify whether macrophages of AS patients undergo unfolded protein response (UPR) and secret increased IL-23.Methods: Peripheral blood monocyte isolated from 10 HLA-B27+ patients and five HLA-B27+ normal subjects were differentiated to macrophages by macrophage-colony stimulating factor (M-CSF) for seven days. Flow cytometry was used to detect monocyte purity and expression of macrophage markers. Analysis of mRNA expression for HLA-B and B27, UPR-associated proteins (BiP, CHOP, MDG1, and XBP1) and IL-23 was performed by RT-qPCR.Results: RT-qPCR data showed a significant overexpression of HLA-B27, UPR genes (BiP, CHOP, and XBP1), and IL-23 in M-CSF-derived macrophages from AS patients compared to healthy controls. Increased expression of MDG1 was not signif...
TL;DR: The serum MK level could be a marker of disease activity in RA and an indicator of a poor prognosis, and may have a role in the pathogenesis of RA via induction of inflammatory mediators.
Abstract: Objectives: Midkine (MK) is involved in cell proliferation, differentiation, migration, and survival. In this study, we measured serum MK levels in rheumatoid arthritis (RA) and investigated the correlation of serum MK with RA disease activity. Expression and effect of MK in RA synovial tissue were also examined.Methods: Serum MK and production of inflammatory mediators by rheumatoid synovial fibroblasts (RSFs) were measured by enzyme-linked immunosorbent assay. MK expression in synovial tissue was examined by immunohistochemistry. MK receptor expression was analyzed by RT-PCR and Western blotting.Results: RA patients had a significantly higher serum MK level than healthy controls. In RA patients, the MK level was correlated with DAS28-ESR, disability index of the Health Assessment Questionnaire, and rheumatoid factor level. The serum MK level tended to be decreased by anti-TNF therapy. MK was expressed by synovial lining cells in RA synovial tissues and it enhanced the production of IL-6, IL-8, a...
TL;DR: PSS has a negative impact on smell, taste, sexual function and quality of life in women, and its influence on quality ofLife in women.
Abstract: Objectives: The aim of this study is to assess the impact of dryness caused by primary Sjogren’s Syndrome (pSS) on smell, taste and sexual function in female patients, and its influence on quality of life.Methods: Electronic databases including MEDLINE via Ovid, Web of Science, SCOUPUS, EMBASE and COCHRANE LIBRARY were searched until April 2016. Studies that assessed the function of smell, taste and sexuality in pSS patients, defined by the American European Consensus Group (AECG) criteria. Standardized mean differences (SMD) for individual studies using random-effects meta-analysis were feasible.Results: Five studies incorporated 378 participants were included in the quantitative synthesis. The impact of pSS vs. healthy controls was: smell SMD −0.78 (95% CI −1.29 to −0.27); taste SMD −1.01 (95% CI −1.54 to −0.49); total sexual function SMD −0.93 (95% CI −1.22 to −0.64); physical and mental component of the quality of life SMD −1.28 (95% CI −1.65 to −0.90) and SMD −0.83 (95% CI −1.27 to −0.40) res...
TL;DR: A significant prevalence of anti-gAChR antibodies in patients with AID is demonstrated, which is independent of the production of other autoantibodies in Patients with autoimmune diseases.
Abstract: Objectives: Autonomic dysfunction is closely associated with autoimmune diseases (AID) including primary biliary cirrhosis (PBC). The objective of this study was to determine the prevalence of anti-ganglionic (nicotinic) acetylcholine receptor (gAChR) antibodies in patients with AID.Methods: We determined the presence of gAChR antibodies in serum samples from 146 patients (systemic lupus erythematosus [SLE] = 32; rheumatoid arthritis [RA] = 43; systemic sclerosis [SSc] = 38; PBC= 33) without information regarding autonomic symptoms, as well as 34 patients with other neurological diseases [OND], and 73 healthy controls [HC]. We specifically analyzed sera for anti-gAChRα3 and -β4 antibodies using the luciferase immunoprecipitation system (LIPS) assay.Results: LIPS assay detected anti-gAChRα3 and -β4 antibodies in the sera from patients with SLE (12.5%, 4/32), RA (18.6%, 8/43), SSc (13.2%, 5/38), PBC (9.1%, 3/33), OND (2.9%, 1/34), and HC (0.0%, 1/73). There were no significant correlations between t...
TL;DR: The IgG4-related IPTs diagnosed on biopsies with requisite features showed prompt response to steroids indicating specificity of histopathological findings in predicting treatment response.
Abstract: Objectives: There is marked inconsistency in reporting the key features of IgG4-related inflammatory pseudotumor (IPT) cases. We aimed to analyze the various aspects of IgG4-related IPTs and to test the performance of the consensus criteria for their diagnosis.Methods: PubMed database was searched for IgG4-related IPT cases. The data regarding patient demographics, clinical presentation, laboratory findings, histopathological features, and treatment response are extracted and are presented here in a descriptive manner.Results: The study included 40 papers describing the clinicopathological features of 83 IPTs in 80 patients. Seventeen cases were diagnosed on biopsies; while remaining were diagnosed on excision specimens. Among these, 50 cases were categorized as highly suggestive and 24 cases as probable for IgG4RD; while nine cases had insufficient histopathological evidence of IgG4RD. Two cases diagnosed on biopsies having insufficient evidence of IgG4RD showed partial or no response to steroids...
TL;DR: These data validate the importance of TCZ treatment in the early stages of RA in biologic-naive patients to achieve increased effectiveness and validate the safety profile ofTCZ, which may allow discontinuation of concomitant MTX and GCs without affecting remission.
Abstract: Objective: To evaluate effectiveness and safety of tocilizumab (TCZ) in biologic-naive Japanese patients with rheumatoid arthritis (RA) in real-world settings, and to analyze the relationship between disease duration and clinical outcomes.Methods: The FIRST Bio study was a postmarketing surveillance study of intravenous TCZ in biologics-naive patients who had a prior inadequate response or were intolerant to ≥1 conventional synthetic disease-modifying antirheumatic drug (csDMARD). Effectiveness, safety, and concomitant csDMARD administration were assessed.Results: Of the 839 patients analyzed, 72.3% completed 52 weeks of treatment. The Clinical Disease Activity Index (CDAI) remission rate at week 52 was 36.8%. Contributing factors for CDAI remission were younger age, early disease stage, and no comorbidities. Health Assessment Questionnaire Disability Index ≤0.5 was achieved in 65.1% of patients, and was significantly associated with disease duration. Discontinuation of concomitant methotrexate (M...
TL;DR: Anti-IL-1 agents are rational treatment modalities in patients resistant or intolerant to colchicine and they have a promising role in the treatment of FMF.
Abstract: Objective: To investigate the effect of anti-interleukin-1 (anti-IL-1) treatment on the frequency and severity of attacks and other disease-related clinical parameters and to evaluate the adverse effects associated with anti-IL-1 treatment in 26 patients with refractory familial mediterranean fever (FMF).Methods: The study included 26 FMF patients followed up in our centre using colchicine for 4 months to 30 years. The treatment was switched to anti-IL-1 treatment for various reasons; 20 cases were resistant to colchicine, 8 were intolerant to colchicine, and 3 had prolonged arthritis under colchicine. Clinical response was monitored through the number of attacks, and laboratory inflammation was monitored through erythrocyte sedimentation rate, C-reactive protein, and serum amyloid A concentrations. Colchicine resistance was defined as at least two attacks/month together with C-reactive protein and serum amyloid A levels above the normal range between attacks. The colchicine dose was increased to ...