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ID PMID Title PublicationDate abstract
30101019 Lymphoproliferative disorder with pathological fracture of the femur in a patient with rhe 2018 Aug Methotrexate (MTX) is the key drug for the treatment of rheumatoid arthritis (RA). MTX-treated RA has been associated with the development of lymphoproliferative disorders (LPDs). Notably, the hyperimmune state of RA itself or the immunosuppressive state induced by MTX administration may contribute to development of LPD. Furthermore, Epstein-Barr virus (EBV) has been indicated to contribute to the development of MTX-LPD. MTX-associated LPD (MTX-LPD) may affect nodal or extranodal sites, including the gastrointestinal tract, skin, lungs, kidneys, and soft tissues, at an almost equal frequency. However, it is rare for MTX-LPD to manifest as multiple bone tumors with a pathological fracture. The present study reported the case of a 46-year-old Japanese woman with RA who had complications of EBV-positive MTX-LPD during an approximate 5-year course of MTX therapy. The present study indicated a rare case in which the LPD had spread to multiple bones in a patient with a pathologic fracture. Notably, the LPD was subclassified as diffuse large B-cell lymphoma (DLBCL).
30607397 Inflammation beyond the Joints: Rheumatoid Arthritis and Cardiovascular Disease. 2018 Rheumatoid Arthritis (RA), a chronic systemic inflammatory disease which affects approximately 1% of the population, is classically characterized by inflammation and synovitis that leads to cartilage damage and juxta-articular bone destruction. Accumulating evidence indicates that a major cause of death among RA patients is Cardio Vascular Disease (CVD), in excess of that in the general population. In this review, we discuss the epidemiology of CVD in RA populations, the underlying pathophysiologic mechanisms of CVD in RA including the role of chronic inflammation in driving accelerated atherosclerosis, the obesity paradox and altered metabolic pathways leading to pro-inflammatory HDL formation and insulin resistance. We also discuss the pitfalls in the evaluation of CVD utilizing traditional risk scores which tend to underestimate CVD risk in RA population and the efforts directed to find more accurate predictors for early CVD detection. Finally, we will present the latest developments in the evaluation and management of CVD in RA patients, given recent evidence on the role of inflammation and its impact on CVD.
30588174 Serum adiponectin as a predictor of laboratory response to anti-TNF-α therapy in rheumato 2018 INTRODUCTION: While adiponectin is typically viewed as an anti-inflammatory mediator, such an activity of adiponectin in rheumatoid arthritis (RA) is not so obvious. In the present study we examined whether serum levels of adiponectin reflect the clinical phenotype of RA patients and/or correlate with severity of the disease and the response to anti-TNF-α therapy. MATERIAL AND METHODS: Twenty-one female RA patients qualified to receive anti-TNF-α treatment were prospectively assessed before and after 12 weeks of therapy. Patients underwent full clinical and biochemical assessment. Disease activity was assessed by the Modified Disease Activity Scores (DAS28). Serum concentrations of adiponectin were measured with an immunoassay. The individuals were divided into two subgroups according to whether their baseline serum adiponectin was below or above the median value. The subgroups did not differ in basic demographic, anthropometric, and clinical parameters. RESULTS: Anti-TNF-α treatment resulted in a significant clinical (DAS28) improvement in patients from both subgroups, but no significant differences between basal and post-treatment serum adiponectin concentrations were observed. However, patients with higher baseline adiponectin experienced a significant and more pronounced improvement in laboratory parameters of inflammation (ESR, CRP, neutrophil count, neutrophil-to-lymphocyte ratio). CONCLUSIONS: It is possible that adiponectin exerts systemic anti-inflammatory effects independently of the local activity of RA.
30568425 Infliximab dose adjustment can improve the clinical and radiographic outcomes of rheumatoi 2018 PURPOSE: We evaluated the clinical responses and radiographic outcomes of 90 patients with rheumatoid arthritis (RA) undergoing continuous or dose-adjusted infliximab treatment over 104 weeks. PATIENTS AND METHODS: Patients received 3 mg/kg infliximab continuously (the contin group; n=50), or the dose escalation and de-escalation of infliximab (3, 6, and 10 mg/kg) from week 14 (the adjusted group; n=40) based on the patient's Disease Activity Score in 28 joints (DAS28). The retention rate, clinical response, and radiographic assessment were determined at week 104. RESULTS: The contin and adjusted groups' retention rates at week 104 were 56.8 and 66.7%, and the groups' low disease activity in the DAS28 was 39.1 and 66.7%, respectively. Remission based on the DAS28 and the American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) Boolean-based criteria was significantly increased in the adjusted group. In the radiographic assessment, there was also a significant reduction in the mean changes in total Sharp score. The cumulative rates of any adverse effects showed no significant difference between the groups. CONCLUSION: In an assessment of adequate DAS28 results, the RA patients who did not respond to the initial dose of infliximab showed improved clinical responses and radiographic assessment after a dose adjustment of infliximab, without an increased risk of serious adverse events.
29506437 Adult-onset Still's disease with prominent polyserositis. 2018 May Adult-onset Still's disease is a systemic autoinflammatory disease the presentation of which can often mimic infection. As a consequence, there is often a delay in diagnosis. Serositis is a recognised but less common clinical feature that can result in complications including cardiac tamponade and constrictive pericarditis. We describe a case of adult-onset Still's disease without the hallmark rash or significant arthritis, presenting with polyserositis that showed a good response to initial steroid treatment and sustained remission with anakinra. An elevated procalcitonin level was due to active adult-onset Still's disease, not bacterial infection.
29779214 Cyanidin-3-glucoside inhibits inflammatory activities in human fibroblast-like synoviocyte 2018 Oct Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint tissue inflammation. Cyanidin-3-glucoside (C3G) is a major component in the flavonoid family and has shown anti-inflammatory, anti-oxidant and anti-tumour activity. In this study, we investigated the effects of C3G on lipopolysaccharides (LPS)-induced inflammation on human rheumatoid fibroblast-like synoviocytes (FLS) and on collagen-induced arthritis (CIA) mice model. We treated FLS with C3G followed by LPS induction, the expressions of tumour necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β) and IL-6 and the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) signalling pathway were analyzed. CIA was induced in mice and the arthritic mice were treated with C3G for 3 weeks. The disease severity was compared between control and C3G treated mice. The serum levels of TNF-α, IL-1β and IL-6 were analyzed by ELISA. C3G inhibited LPS-induced TNF-α, IL-1β and IL-6 expression in FLS. Moreover, C3G inhibited LPS-induced p65 production and IκBa, p38, ERK and JNK phosphorylation. Administration of C3G significantly attenuated disease in mice with CIA and decreased the serum level of TNF-α, IL-1β and IL-6. C3G inhibited LPS-induced inflammation in human FLS by inhibiting activation of NF-κB and MAPK signalling pathway. C3G exhibited therapeutic effects in mice with CIA.
29900970 The Association of Anti-Aminoacyl-Transfer Ribonucleic Acid Synthetase Antibodies in Patie 2018 Mar OBJECTIVES: This study aims to analyze the distribution and clinicopathological characteristics of anti-aminoacyl-transfer ribonucleic acid (tRNA) synthetase (ARS) antibodies in rheumatoid arthritis patients. PATIENTS AND METHODS: We retrospectively studied the anti-ARS antibody levels in 228 RA patients' (44 males, 184 females; mean age 62.9±14.0 years; range 23 to 88 years) sera from their medical charts. We determined the association with anti-cyclic citrullinated peptide antibody levels, interstitial lung disease (ILD), rheumatoid factor, and methotrexate or biological disease modifying antirheumatic drug treatments. RESULTS: Anti-ARS antibodies were detected in 14 RA patients (6.1%). ILD complications were significantly higher among anti-ARS antibody-positive patients (57.1% vs 22.4%, p<0.05). Levels of anti-threonyl-tRNA-synthetase (anti-PL-7) and anti-alanyl-tRNA-synthetase (anti-PL-12), two anti-ARS antibodies, were higher in RA patients with concurrent ILD (both p<0.05). Myositis and ILD worsening were not observed in three anti-ARS antibody- positive patients despite biological disease modifying antirheumatic drug administration. There was no difference in anti-cyclic citrullinated peptide and rheumatoid factor specificities between patients with or without ARS antibodies. CONCLUSION: Anti-ARS antibodies were detected in RA patients, with higher prevalence in patients with concurrent ILD. RA patients, specifically those with ILD complications, should be tested for anti-ARS antibodies.
29027192 Hip resurfacing arthroplasty for patients with inflammatory arthritis: a systematic review 2018 Jan INTRODUCTION: Modern metal-on-metal hip resurfacing arthroplasty has led to decreased revision rates and high implant survival rates as compared to prior generations of resurfacing. Many of the series that report on resurfacing outcomes focus upon patients treated with a diagnosis of osteoarthritis. Patients with inflammatory arthritis such as rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are also treated in these series, however, their outcomes following resurfacing are underreported. The aim of this study was to determine complications that may occur following hip resurfacing in patients with inflammatory arthritis. A secondary aim was to determine functional outcomes following resurfacing. METHODS: A search was performed in MEDLINE (PubMed/OVID), Cochrane Library, and Google Scholar. 5 studies met eligibility criteria. This review includes 196 hips; 120 had a diagnosis of AS or seronegative spondyloarthropathy and 76 had a diagnosis of RA or juvenile RA. 8 revisions were reported at a mean time of 64.2 (8.67-275.58) weeks. RESULTS: Femoral neck fracture was the most common indication for revision, occurring in 3.06% of all hips at 34.5 weeks (16.0-52.0). 2 infections, 2 reports of acetabular radiolucency, and no dislocations were reported. The University of California at Los Angeles score, Harris Hip Score, and Range of Motion were the most common functional outcomes measured, which increased in the majority of studies following resurfacing. CONCLUSIONS: Femoral neck fracture was the most common reason for revision in patients with inflammatory arthritis following resurfacing and there were no dislocations reported. Following resurfacing, these patients have improved functional outcomes.
29599624 Histological Evaluation of Lumbar Spine Changes in Rats with Collagen-induced Arthritis. 2018 Mar BACKGROUND: To histologically evaluate lumbar involvement in rheumatoid arthritis (RA) by investigating rats with collagen-induced arthritis (CIA) and to assess the potential effects of RA on the discovertebral joints and facet joints. METHODS: Seven-month-old female Sprague-Dawley rats were divided into groups with CIA and without CIA (control). All rats were sacrificed at 8 weeks after initial sensitization and the lumbar spine (L5/6) was harvested. Then the lumbar spine block specimens were stained with Villaneuva bone stain and sectioned in the midsagittal plane. The left facet joints were also sectioned in the midaxial plane. Specimens were studied under a microscope and infiltration of inflammatory cells was investigated. RESULTS: In the CIA group, lumbar lesions were observed in 13/18 rats (76%). Lymphocytes infiltrated into the anterior rim of the vertebral bodies only in 2 rats, while lymphocytes infiltrated the facet joints only in 4 rats. Both sites were involved in 7 rats. In addition, osteoclasts invaded the anterior rim of the vertebral bodies and formed cavities that also contained lymphocytes. Formation of pannus was seen in the facet joints in 11/18 rats. CONCLUSION: In CIA rats, infiltration of inflammatory cells into the anterior rim of the vertebral bodies alone or into the facet joints alone was demonstrated in 2 rats and 4 rats, respectively, while both sites were involved in 7 rats. Therefore, lesions at the anterior rim of the vertebral body did not arise secondary to facet joint involvement, but were caused by CIA along with synovial lesions of the facet joints.
30013786 Use of autologous bone grafting from the calcaneus and interconnected porous hydroxyapatit 2018 Cancellous bone grafts from the calcaneus have been used for the foot and ankle as well as iliac bone graft; however, there is a sparse report for calcaneal bone transplantation in the field of rheumatoid foot surgery. In this study, safety and usefulness of calcaneal bone grafts, and combination with interconnected porous hydroxyapatite ceramic, was evaluated in rheumatoid arthritis foot surgeries. Of six rheumatoid arthritis cases, three (talo-navicular joint fusion) used a calcaneal bone graft alone, and the remaining three cases (subtalar joint and talo-navicular joint fusion) used a combination of calcaneal bone graft and interconnected porous hydroxyapatite ceramic augmented with dense calcium hydroxyapatite for subtalar bony defect (1.5-2.0 cm) after the correction. Pre- and postoperative Japanese Society for Surgery of the Foot rheumatoid arthritis foot ankle scale scores were obtained for the clinical assessment. As radiographic assessment, tibio-calcaneal angle, calcaneal pitch, talo-1st metatarsal angle, and pronated foot index were also evaluated. After starting weight-bearing or walking, there was no pain and skin trouble at the fusion and harvesting sites. All cases achieved bony fusion within 6-10 weeks. Japanese Society for Surgery of the Foot rheumatoid arthritis foot ankle score was improved in all six cases. Furthermore, tibio-calcaneal angle, talo-1st metatarsal angle, and pronated foot index were also improved at latest follow-up in all cases. In conclusion, autologous bone grafting from the calcaneus was safe and convenient even in rheumatoid foot surgeries. For larger bony defects (1.5-2.0 cm), combination use with interconnected porous hydroxyapatite ceramic augmented with dense calcium hydroxyapatite was also useful.
30143001 Suspected drug-induced liver injury associated with iguratimod: a case report and review o 2018 Aug 24 BACKGROUND: Iguratimod is a novel anti-rheumatic drug with the capability of anti-cytokines as report goes. It has been reported that iguratimod is effective and safe for rheumatoid arthritis and other rheumatisms. As side effects, iguratimod can cause gastrointestinal reactions, dizziness, headache and itchy. CASE PRESENTATION: In this case report, a 60-year-old female patient was admitted with suspected drug-induced liver injury (DILI) caused by iguratimod. The causality assessment was done by the updated RUCAM, and the possibility of the case in our paper diagnosed as highly probable for the score was 9 points. Iguratimod was discontinued immediately, and methylprednisolone was used for acute liver injury and Sjogren's syndrome. The data showed the patient has improved gradually, and she was discharged on day 27. The true incidence of iguratimod-related hepatotoxicity and its pathogenic mechanism are largely unknown. It is difficult to recognize and diagnose DILI, and there is no standard for diagnosis of DILI. At the same time, the DILI is still lack of specific treatment. CONCLUSIONS: Based on this rare case of severe liver injury, we recommend careful monitoring of liver function throughout iguratimod treatment for diseases.
29887906 Ultrasonographic findings of rheumatoid arthritis patients who are in clinical remission. 2018 BACKGROUND: The aim of this study was to recognize the findings of ultrasonography (US) in remitted rheumatic arthritis (RA) patients for detection subclinical arthritis. MATERIALS AND METHODS: This descriptive study was conducted during 2016 in a rheumatology center. A total of 70 patients with remitted RA were included in the study. Sonography was performed on all 70 patients who did not show any clinical arthritis in clinical examination to find synovitis and effusion were evaluated with gray scale and hyperemia with power Doppler US. RESULTS: Nearly 44.3% (n = 31) of our patients had positive sonography results including 20% synovitis, 21.4% hyperemia, and 18.6% (n = 13) effusion. A total of 1960 joints of 70 patients were evaluated, in which 3.2% (n = 63) of joints had positive sonography findings including 1.2% synovitis, 1.5% hyperemia, and 1.1 with effusion. CONCLUSION: US can diagnosis subclinical arthritis in patients with remitted RA who does not show any joint involvement in clinical examination.
30588173 Correlation of interleukin 6 and transforming growth factor β1 with peripheral blood regu 2018 INTRODUCTION: Proinflammatory cytokines and regulatory T cells (Tregs) are considered as important factors involved in autoimmunity development especially in rheumatoid arthritis (RA). AIM OF THE STUDY: To investigate the frequency of peripheral blood Tregs and related cytokines in RA patients and to determine the possible correlation between Treg percentage and interleukin 6 (IL-6) and transforming growth factor β1 (TGF-β1) as indicators in assessment of Treg function and mechanisms preceding autoimmunity in RA. MATERIAL AND METHODS: Thirty-seven Iranian RA patients with a moderate (3.2-5.1) disease activity score (DAS) and the same number of healthy age- and sex-matched individuals were enrolled. Frequency of peripheral blood Tregs (CD4(+)FoxP3(+)CD25(high)) was determined by flow cytometry. Serum levels of IL-6 and TGF-β1 and their expression levels in peripheral blood mononuclear cells (PBMCs) were evaluated by ELISA and Q-PCR, respectively. RESULTS: Rheumatoid arthritis patients showed significantly lower peripheral blood Treg frequencies compared to healthy individuals. Additionally, Treg (%) showed a significant inverse correlation between serum concentrations of IL-6 and mRNA expression of PBMCs, whereas there was no significant correlation between Treg (%) and TGF-β1 levels. CONCLUSIONS: The current study revealed that Treg numbers were reduced in peripheral blood of RA patients. This reduction inversely correlated with IL-6 levels, which may lead to persistent autoimmune and inflammatory conditions in RA patients.
28781105 Adult onset Still's disease occurring during pregnancy: Case-report and literature review. 2018 Feb INTRODUCTION: Adult onset Still's disease is a rare affection classified among non-hereditary autoinflammatory diseases. We here report a case of AOSD revealed during pregnancy with a life-threatening presentation along with a review of 19 cases from literature. CASE: A 38-years old woman was treated in our department for diffuse systemic sclerosis and associated Sjögren syndrome. She was pregnant and presented with acute fever and arthralgias. Laboratory data revealed mild liver cytolysis but a large screening for infectious and auto-immune diseases was negative and hepato-biliar imaging was normal. Ferritin levels were at 41 000 ng/mL with glycosylated ferritin less than 5%. The diagnosis of AOSD was stated and because of persistent fever and polyarthralgias, after exclusion of active infection, steroids were started (prednisone 1 mg/kg) associated with colchicine, which allowed clinical remission and C-reactive protein significant decrease. CONCLUSION: Pregnancy-revealed AOSD appears to be a specifical subset of the disease with a systemic course, flares on first and second trimester, obstetrical complications such as prematurity and IUGR sometimes leading to life-threatening situations requiring parenteral corticotherapy and intravenous immunoglobulins.
30508859 [Sjögren's Syndrome: Early diagnosis and effective treatment]. 2018 Dec Primary Sjögren's syndrome (pSS) is an autoimmune disease affecting the salivary and lachrymal glands. The patients complain of symptoms of dry eyes and dry mouth, but up to 50 % may additionally develop extraglandular manifestations such as arthritis, vasculitis, polyneuropathy, pulmonary fibrosis or interstitial nephritis. Most therapeutic studies on the glandular manifestations of pSS failed to meet their primary endpoints, possibly since many of the patients had already advanced and irreversible disease.In recent years several important advances have been made. The role of B and T lymphocytes in the pathogenesis of pSS has been identified. The disease activity scores ESSDAI and ESSPRI were developed and can now be used as endpoints in therapeutical studies. Since then, numerous promising new drugs, mostly affecting B and T lymphocytes, have been studied in clinical trials. New classification criteria have been proposed, which will be an important tool in making a diagnosis in an early disease stage, in which the glandular function may still be normal. It is very likely therefore, that we will soon have efficient therapies, which will be able to stop the disease progression in an early stage of pSS.
30469466 Defective T-Cell Apoptosis and T-Regulatory Cell Dysfunction in Rheumatoid Arthritis. 2018 Nov 22 Rheumatoid arthritis (RA) is a chronic, progressive, systemic autoimmune disease that mostly affects small and large synovial joints. At the molecular level, RA is characterized by a profoundly defective innate and adaptive immune response that results in a chronic state of inflammation. Two of the most significant alterations in T-lymphocyte (T-cell) dysfunction in RA is the perpetual activation of T-cells that result in an abnormal proliferation state which also stimulate the proliferation of fibroblasts within the joint synovial tissue. This event results in what we have termed "apoptosis resistance", which we believe is the leading cause of aberrant cell survival in RA. Finding therapies that will induce apoptosis under these conditions is one of the current goals of drug discovery. Over the past several years, a number of T-cell subsets have been identified. One of these T-cell subsets are the T-regulatory (T(reg)) cells. Under normal conditions T(reg) cells dictate the state of immune tolerance. However, in RA, the function of T(reg) cells become compromised resulting in T(reg) cell dysfunction. It has now been shown that several of the drugs employed in the medical therapy of RA can partially restore T(reg) cell function, which has also been associated with amelioration of the clinical symptoms of RA.
30487995 ACPA and RF as predictors of sustained clinical remission in patients with rheumatoid arth 2018 OBJECTIVES: This study evaluated the interaction of anticitrullinated protein antibody (ACPA) and rheumatoid factor (RF) in predicting sustained clinical response in an observational registry of patients with rheumatoid arthritis (RA) followed in routine practice. METHODS: Patients with RA enrolled in the Ontario Best Practices Research Initiative registry, with ≥1 swollen joint, autoantibody information and ≥1 follow-up assessment were included. Sustained clinical remission was defined as Clinical Disease Activity Index (CDAI) ≤2.8 in at least two sequential visits separated by 3-12 months. Time to sustained remission was assessed using cumulative incidence curves and multivariate cox regression. RESULTS: Among 3251 patients in the registry, 970 were included, of whom 262 (27%) were ACPA(neg)/RF(neg), 60 (6.2%) ACPA(pos) /RF(neg), 117 (12.1%) ACPA(neg)/RF(pos) and 531 (54.7%) ACPA(pos) /RF(pos) at baseline. Significant between group differences were observed in age (p=0.02), CDAI (p=0.03), tender joint count (p=0.02) and Health Assessment Questionnaire (p=0.002), with ACPA(pos) patients being youngest with lowest disease activity and disability. No difference in biologic use was found between groups (20.2% of patients).Over a mean follow-up of 3 years, sustained remission was achieved by 43.5% of ACPA(pos)/RF(pos) patients, 43.3% of ACPA(pos) /RF(neg) patients, 31.6 % of ACPA(neg)/RF(pos) patients and 32.4% of ACPA(neg)/RF(neg) patients (p=0.01). Significant differences were observed in CDAI improvement based on ACPA and RF status where ACPA(pos)/RF(pos) had a shorter time to achieving sustained remission (HR 1.30; 95% CI 1.01 to 1.67) and experienced significantly higher improvements compared with ACPA(neg)/RF(neg) patients. CONCLUSIONS: Combined ACPA and RF positivity were associated with improved and faster response to antirheumatic medications in patients with RA.
30244449 Human Xenograft Model. 2018 Human-SCID grafting is a commonly used technique for the long-term investigation of rheumatoid arthritis (RA) explants. To establish a chimeric immunological system in NOD/SCID mice, RA patient-derived pannus tissue from the synovial membrane, articular cartilage, and bone can be transplanted subcutaneously. The same patient-derived peripheral blood mononuclear cell chimerism can be successfully achieved by intraperitoneal engraftment. This xenograft model is able to be used for initial screening of human target-specified biologics.
29398958 Treatment Response Evaluation using Yttrium-90 in Patients with Rheumatoid Arthritis of Kn 2018 Jan For radiosynovectomy, we have measured the retention time of yttrium-90 ((90)Y) hydroxyapatite (particle size 1-10 μm) within the knee joint space and evaluated the treatment responses in knees with rheumatoid arthritis. Radioactive measurements in the region of knee after injection of (90)Y hydroxyapatite into the joint space were made with a single prove system designed to monitor radioactivity and showed retention of (90)Y in the knee ranged 76.6% ±5.4% after 4 days of injection. The clinical improvements in rheumatoid arthritis of knee joint with steinbroker Stages I and II were increased as time goes by, the improvement ratio is in 72% at 6(th) months and 76% at 12(th) months after injection of (90)Y 185 MBq (5 mCi) per joint.
28975544 The role of α9β1 integrin and its ligands in the development of autoimmune diseases. 2018 Mar Adhesion of cells to extracellular matrix proteins through integrins expressed on the cell surface is important for cell adhesion/motility, survival, and differentiation. Recently, α9β1 integrin was reported to be important for the development of autoimmune diseases including rheumatoid arthritis, multiple sclerosis, and their murine models. In addition, ligands for α9β1 integrin, such as osteopontin and tenascin-C, are well established as key regulators of autoimmune diseases. Therefore, this review focused on the role of interactions between α9β1 integrin and its ligands in the development of autoimmune diseases.