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

ID PMID Title PublicationDate abstract
23904975 "Remotion" total wrist arthroplasty: preliminary results of a prospective international mu 2012 Aug This study reports the current results of an international multicenter study of one last generation total wrist arthroplasty (TWA) ("ReMotion," Small Bone Innovation, Morristown, PA). The two first authors (G.H. and M.B.) built a Web-based prospective database including clinical and radiological preoperative and postoperative reports of "ReMotion" TWA at regular intervals. The cases of 7 centers with more than 15 inclusions were considered for this article. A total of 215 wrists were included. In the rheumatoid arthritis (RA; 129 wrists) and nonrheumatoid arthritis (non-RA; 86 wrists) groups, there were respectively 5 and 6% complications requiring implant revision with a survival rate of 96 and 92%, respectively, at an average follow-up of 4 years. Within the whole series, only one dislocation was observed in one non-RA wrist. A total of 112 wrists (75 rheumatoid and 37 nonrheumatoid) had more than 2 years of follow-up (minimum: 2 years, maximum: 8 years). In rheumatoid and non-RA group, visual analog scale (VAS) pain score improved by 48 and 54 points, respectively, and QuickDASH score improved by 20 and 21 points, respectively, with no statistical differences. Average postoperative arc of wrist flexion-extension was 58 degrees in rheumatoid wrists (loss of 1 degree) compared with 63 degrees in non-RA wrists (loss of 9 degrees) with no statistical differences. Grip strength improved respectively by 40 and 19% in rheumatoid and non-RA groups (p = 0.033). Implant loosening was observed in 4% of the rheumatoid wrists and 3% of the non-RA wrists with no statistical differences. A Web-based TWA international registry was presented. Our results suggest that the use of the "ReMotion" TWA is feasible in the midterm both for rheumatoid and non-RA patients. This is a significant improvement compared with the previous generation TWA. The level of evidence for this study is IV.
21364050 Diagnostic and prognostic value of history-taking and physical examination in undifferenti 2011 Mar OBJECTIVE: To review the diagnostic and prognostic value of history/physical examination among patients with undifferentiated peripheral inflammatory arthritis (UPIA). METHODS: We conducted a systematic review evaluating the association between history/physical examination features and a diagnostic or prognostic outcome. RESULTS: Nineteen publications were included. Advanced age, female sex, and morning stiffness were predictive of a diagnosis of rheumatoid arthritis (RA) from UPIA. A higher number of tender and swollen joints, small/large joint involvement in the upper/lower extremities, and symmetrical involvement were associated with progression to RA. Similar features were associated with persistent disease and erosions, while disability at baseline and extraarticular features were predictive of future disability. CONCLUSION: History/physical examination features are heterogeneously reported. Several features predict progression from UPIA to RA or a poor prognosis. Continued measurements in the UPIA population are needed to determine if these features are valid and reliable predictors of outcomes, especially as new definitions for RA and disease states emerge.
22517208 Rituximab for noninfectious uveitis. 2012 Rituximab (RTX) is a monoclonal antibody directed against the CD20 antigen expressed on B cells. This drug has been successfully employed in the treatment of non-Hodgkin's lymphoma and different systemic autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, granulomatosis with polyangiitis (Wegener's) and anti-neutrophil cytoplasmic antibody-associated vasculitis. At present, RTX may be used in patients with rheumatoid arthritis who qualify for treatment with tumor necrosis factor blockers and have had an inadequate response or intolerance to one or more of these agents. In ophthalmology, there is a growing amount of literature which suggests that RTX may be useful for inflammatory ocular diseases. Only few cases have been reported on treatment of ocular inflammatory disease mostly refractory scleritis, peripheral ulcerative keratitis, uveitis in adulthood and in children with juvenile idiopathic arthritis. RTX has also been employed in ocular surface diseases such as ocular cicatricial pemphigoid and conjunctival lymphoma. The tolerability and safety of RTX is good with the most common adverse events encountered being infusion reactions. RTX may be effective in the treatment of ocular inflammatory diseases, in particular the most aggressive, recalcitrant and sight-threatening forms of inflammation and uveitis. Although further studies are needed to assess the efficacy of RTX and the exact dosing regimen, RTX may be considered as a treatment alternative in patients with the most aggressive forms of inflammatory ocular diseases who fail to respond to conventional and other biologic agents.
21295331 Imaging of synovitis in osteoarthritis: current status and outlook. 2011 Oct OBJECTIVES: This review article provides an overview of the current state of imaging of synovitis in osteoarthritis (OA), looking at recent advances and controversies and focusing particularly on the application of ultrasound and magnetic resonance imaging (MRI) in the assessment of the hand and knee joint. Computed tomography and nuclear medicine including positron emission tomography are also briefly discussed. METHODS: PubMed and MEDLINE search for articles published up to 2010, using the keywords synovitis, osteoarthritis, rheumatoid arthritis, pathogenesis, imaging, radiography, computed tomography, nuclear medicine, magnetic resonance imaging, ultrasound, and pain. RESULTS: Synovitis is defined as inflammation of the synovial membrane. Modern imaging techniques have demonstrated that synovial pathology is common in the early and late stages of OA and may be associated with pain. The current standard for OA imaging in clinical practice is conventional radiography but it does not allow direct visualization of synovitis. MRI without contrast administration, although widely used in clinical studies, cannot assess synovitis directly. Contrast-enhanced MRI and ultrasound, however, both allow direct visualization of synovitis including early inflammatory changes. They are regularly used to image synovitis in rheumatoid arthritis and increasingly in OA. CONCLUSIONS: Synovitis is increasingly recognized as an important feature of the pathophysiology of OA, although there is conflicting evidence with respect to its association with disease severity and clinical parameters. Contrast-enhanced MRI and ultrasound are the most important methods for assessing synovitis associated with OA.
21526507 Identification of dendritic cells in the blood and synovial fluid of children with Juvenil 2011 Childhood chronic arthritis of unknown etiology is known collectively as juvenile idiopathic arthritis (JIA) and consists of heterogeneous subtypes with unique clinical patterns of disease. JIA is the commonest rheumatic disease in children and may still result in significant disability, with joint deformity, growth impairment, and persistence of active arthritis into adulthood. Basic research is rather focused on rheumatoid arthritis, and this lead to small number of publications considering JIA. In this study we examine, by flow cytometry, the expression of dendritic cells (DCs) in the peripheral blood and synovial fluid of children with active JIA in a group of 220 patients. We reveal a significant decrease in the percentage of immature DCs in the blood of patients compared to control children. Surprisingly, we found higher percentages of mature circulating dendritic cells. Both populations of DCs, immature and mature, were accumulated in patients' synovial fluid. We also confirmed the presence of CD206+/CD209+ in JIA samples, which can represent a population of macrophages with dendritic cells morphology. Our results support the thesis that dendritic cells are crucial in the induction and maintenance of autoimmune response and local inflammation during juvenile idiopathic arthritis.
34633781 Upadacitinib. 2012 Upadacitinib is an oral selective inhibitor of Janus associated kinase 1 (JAK-1) that is used in the therapy of moderate-to-severe rheumatoid arthritis. Upadacitinib has been associated with a low rate of serum enzyme elevations during therapy, but has not been linked to cases of clinically apparent acute liver injury although it may pose a risk for reactivation of hepatitis B in susceptible patients.
31643344 Baricitinib. 2012 Baricitinib is an orally available small molecule inhibitor of Janus kinases that is used to treat moderate-to-severe rheumatoid arthritis and in late 2020 was given emergency use authorization as therapy in combination with remdesivir for severe COVID-19. Baricitinib is associated with transient and usually mild elevations in serum aminotransferase levels during therapy but has yet to be linked to cases of clinically apparent acute liver injury.
22004905 Regulatory T cells protect from autoimmune arthritis during pregnancy. 2012 May Pregnancy frequently has a beneficial effect on the autoimmune disease Rheumatoid Arthritis, ranging from improvement in clinical symptoms to complete remission. Despite decades of study, a mechanistic explanation remains elusive. Here, we demonstrate that an analogous pregnancy-induced remission can be observed in a mouse model of arthritis. We demonstrate that during pregnancy mice are protected from collagen-induced arthritis, but are still capable of launching normal immune responses to influenza infections. We examine the role of regulatory T (T(R)) cells in this beneficial effect. T(R) cells are essential for many aspects of immune tolerance, including the suppression of autoimmune responses. Remarkably, transfer of regulatory T cells from pregnant 'protected' mice was sufficient to confer protection to non-pregnant mice. These results suggest that regulatory T cells are responsible for the pregnancy-induced amelioration of arthritis.
21302166 Wear analysis in anatomical and reversed shoulder prostheses. 2011 Oct This paper describes the development of a computational model to calculate wear rates in total shoulder prostheses, for a 5-150 degrees arm abduction. Anatomical keeled and pegged prosthesis as well as reversed prosthesis were the studied implants. The bone models were built based on computed tomography (CT) images and using a computer aided design-based modelling pipeline. The finite element method was used to solve the contact problem between the surface of the polyethylene (PE) components and the corresponding articular component. The aim of this work was to determine linear and volumetric PE wear, for several radial mismatches, in conditions of pathological (rheumatoid arthritis) and non-pathological bone. Results showed that contact pressures and linear wear developed in anatomical prosthesis were higher than those visualised in reversed prosthesis. However, anatomical prosthesis exhibited a better volumetric wear performance. Moreover, our findings indicated higher values of volumetric wear in higher congruent models and on pathological bone conditions.
31643544 Methotrexate. 2012 Methotrexate is an antineoplastic and immunosuppressive agent widely used in the therapy of leukemia, lymphoma, solid tumors, psoriasis and rheumatoid arthritis. When given in high intravenous doses, methotrexate can cause acute elevations in serum enzymes, and long term methotrexate therapy has been associated with frequent but mild elevations in serum liver enzymes and, more importantly, with development of chronic liver injury, progressive fibrosis, cirrhosis and portal hypertension.
31643528 Infliximab. 2012 Infliximab is a monoclonal antibody to human tumor necrosis factor alpha (TNFα) which has potent antiinflammatory activity and is used in the therapy of severe inflammatory bowel disease and rheumatoid arthritis. Infliximab has been linked to many instances of idiosyncratic acute liver injury and is a well known cause of reactivation of hepatitis B.
23124734 The co-occurrence of Hashimoto thyroiditis in primary Sjogren's syndrome defines a subset 2013 May To evaluate in a cohort of 100 consecutive patients affected by primary Sjogren's syndrome (pSS) the incidence of Hashimoto thyroiditis (HT) and to compare the clinical features and the laboratory parameters of patients affected by pSS with and without concomitant HT. In 100 consecutive patients affected by pSS, the occurrence of other autoimmune diseases was recorded and a full examination of thyroid function obtained. HT was associated with pSS in 27 cases. The comparison between pSS cases with and without HT showed that only patients with isolated pSS had low C4 level [p = 0.032, OR (IC 95 %) 230 (13.13-4,046)]. In addition, only patients affected by pSS without HT had evidence of cryoglobulins, cutaneous vasculitis with palpable purpura, peripheral neuropathy, and development of lymphoma, although all these manifestations were observed in a 4.1-8.2 % of the cases, without reaching statistical significance. The association of HT in patients suffering from pSS defines a subset of patients with milder disease and normal C4 levels.
21960213 Small-molecule protein and lipid kinase inhibitors in inflammation and specific models for 2012 The inflammatory response requires complex and coordinated cooperation of different signaling pathways and cell types. Therefore, more than 40 different protein or lipid kinases can be regarded as potential small-molecule inhibitor targets to approach a therapy of acute inflammation, such as septic syndrome, and especially chronic inflammation, such as rheumatoid arthritis or inflammatory bowel disease. Besides the general considerations about selectivity and potency of small-molecule kinase inhibitors, in this chapter special emphasis is put on the inflammation-specific methods and assays available for testing potential small-molecule inhibitors for their anti-inflammatory activity. Examples for human cell-based assays for characterization of the effect of inhibitors on contribution of various cell types, such as monocytes, neutrophils, mast cells, T-cells, and synovial fibroblasts, to the inflammatory scenario are given. It is further demonstrated how these assays are complemented by rodent models for septic syndrome, rheumatoid arthritis, ulcerative colitis, Crohn's disease, and systemic lupus erythematosus. Finally, it is discussed how the results obtained by these methods can be further validated and which future strategies for the treatment of chronic inflammation will exist.
21810731 Autoimmune disease and subsequent digestive tract cancer by histology. 2012 Apr BACKGROUND: Dysregulation of the immune function in autoimmune diseases could potentially lead to cancer development and there is definite evidence linking some autoimmune mechanisms with cancer. We analyzed systematically the occurrence of histology-specific digestive tract cancers in patients diagnosed with 33 different autoimmune diseases in order to address the question of shared susceptibility. PATIENTS AND METHODS: Standardized incidence ratios (SIRs) were calculated for subsequent digestive tract cancers up to the year 2008 and in patients hospitalized for autoimmune disease after the year 1964. RESULTS: Myasthenia gravis associated with five different cancers with SIRs ranging from 1.35 to 2.78. Pernicious anemia, Crohn disease, ulcerative colitis, systemic lupus erythematosis and psoriasis were also associated with cancers at multiple sites. Rheumatoid arthritis associated with no cancer and the standardized incidence ratio was decreased for colon adenocarcinoma, also in ankylosing spondylitis patients. CONCLUSIONS: Increased risks of cancer were observed in patients with several autoimmune diseases. Myasthenia gravis and pernicious anemia were associated with many cancers; this is possibly related to immunosuppressant medication in myasthenia gravis. The decreased risks in colon and rectal adenocarcinomas in rheumatoid arthritis and ankylosing spondylitis suggest underlying inflammatory mechanisms as the risks may have been suppressed by the use of anti-inflammatory medication.
21426373 Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized t 2011 Nov Effective therapeutic options for patients living with chronic pain are limited. The pain relieving effect of cannabinoids remains unclear. A systematic review of randomized controlled trials (RCTs) examining cannabinoids in the treatment of chronic non-cancer pain was conducted according to the PRISMA statement update on the QUORUM guidelines for reporting systematic reviews that evaluate health care interventions. Cannabinoids studied included smoked cannabis, oromucosal extracts of cannabis based medicine, nabilone, dronabinol and a novel THC analogue. Chronic non-cancer pain conditions included neuropathic pain, fibromyalgia, rheumatoid arthritis, and mixed chronic pain. Overall the quality of trials was excellent. Fifteen of the eighteen trials that met the inclusion criteria demonstrated a significant analgesic effect of cannabinoid as compared with placebo and several reported significant improvements in sleep. There were no serious adverse effects. Adverse effects most commonly reported were generally well tolerated, mild to moderate in severity and led to withdrawal from the studies in only a few cases. Overall there is evidence that cannabinoids are safe and modestly effective in neuropathic pain with preliminary evidence of efficacy in fibromyalgia and rheumatoid arthritis. The context of the need for additional treatments for chronic pain is reviewed. Further large studies of longer duration examining specific cannabinoids in homogeneous populations are required.
22390563 Treatment of interstitial lung diseases associated with connective tissue diseases. 2012 Mar A variety of interstitial lung diseases (ILDs) have been reported in association with connective tissue diseases (CTDs). ILD is commonly associated with multiple CTDs and accounts for significant morbidity and mortality in these conditions. In rheumatoid arthritis and systemic sclerosis, ILD commonly occurs in the course of these disorders (incidence: 20-44%). The pathological findings of ILDs are similar to those of idiopathic interstitial pneumonia. A wide variety of histopathologic features, such as various types of interstitial pneumonia and airway involvement, have been observed that are specific for ILDs in rheumatoid arthritis, and this high variety makes its pathology complicated. The diagnosis of ILD is generally based on clinical presentation, bronchioalveolar lavage fluid and high-resolution computed tomography, among others. The most important differential diagnosis is infection, especially pneumocystis pneumonia, and treatment-related toxic damage. The immunosuppressive agents most widely used for the treatment of ILDs are cyclophosphamide, azathioprine, mycophenolate mofetil and calcineurin inhibitors. Other therapeutic strategies are currently being extensively studied, such as antifibrotic agents, endothelin-1 receptor antagonists, tyrosine kinase inhibitors and newer biological agents. In this article, we describe novel therapies for ILDs associated with CTDs.
23835885 Bridging Clinical Outcomes of Canakinumab Treatment in Patients With Rheumatoid Arthritis 2012 Sep 26 Canakinumab, an anti-interleukin-1β (IL-1β) monoclonal antibody, is approved for cryopyrin-associated periodic syndromes and is under investigation for the management of other inflammatory disorders. In this study, population-based pharmacokinetic-pharmacodynamic models were developed to understand responses to canakinumab in patients with rheumatoid arthritis (RA). Total canakinumab and total IL-1β concentrations were obtained from four clinical trials (n = 472). In contrast to traditional models, free IL-1β concentrations were calculated and used to link canakinumab to changes in C-reactive protein (CRP) concentrations and American College of Rheumatology (ACR) scores of 20, 50, and 70% improvement. Temporal patterns of total canakinumab, total IL-1β, CRP, and ACR scores were all well described. Simulations confirmed that 150 mg every 4 weeks improved ACR scores in patients with RA, but no additional benefit was provided by higher doses or more frequent administration. Integrating predicted endogenous free ligand concentrations with biomarkers and clinical outcomes could be extended to new therapies of anti-inflammatory diseases.CPT: Pharmacometrics & Systems Pharmacology (2012) 1, e5; doi:10.1038/psp.2012.6; advance online publication 26 September 2012.
21258795 Interstitial cystitis: a rare manifestation of primary Sjögren's syndrome, successfully t 2012 May Chronic interstitial cystitis (IC), mostly affecting middle-aged women, is a very rare manifestation of primary Sjögren's syndrome (pSS). Hereby, we report a 42-year-old woman with pSS, presenting with dysuria, urinary frequency, and suprapubic pain. She was diagnosed to have chronic IC, based upon the cystoscopic biopsy finding of chronic inflammation in the bladder wall. Systemic corticosteroid and azathioprine treatments together with local intravesical therapies were not effective. Therefore, cyclosporine (CSA) therapy was initiated. Initial low dose of CSA (1.5 mg/kg/d) improved the symptoms of the patient, with no requirement for dose increment. After 4 months of therapy, control cystoscopic biopsy showed that bladder inflammation regressed and IC improved. This case suggests that even low doses of CSA may be beneficial for treating chronic IC associated with pSS syndrome.
24029100 Spinal gout: a great mimicker. A case report and literature review. 2012 Nov Spinal gout is not as rare as was previously thought and mimics heterogeneous spinal conditions such as rheumatoid, septic, seronegative arthropathies and primary or secondary neoplasms. Imaging findings are nonspecific and usually manifest late. In clinical settings, suspicious for spinal gout, needle biopsy may help for further characterization. A 57-year-old man with no significant past medical history presented in the emergency department with severe non radiating low back pain of one week duration. His laboratory tests were significant for uric acid of 642 μmol/L, erythrocyte sedimentation rate 93 mm/hour, and C-reactive protein 8.3 mg/dl. The lumbar spine MRI showed nonspecific acute inflammatory extensive lumbar facet arthropathy and soft tissue enhancement. The radiological and clinical information was insufficient to differentiate among septic arthritis, rheumatoid arthritis, seronegative arthropathy or gout. A lumbar facet fluoroscopy-fluoroscopic CT-guided needle biopsy was performed. The biopsy demonstrated negative birefringent crystals consistent with gout. Although the spinal gout is not rare, few case reports describe the role of needle biopsy and mimics. We present a comparative review of limited reports addressing the role of needle biopsy in mimics of spinal gout.
22397245 Differential diagnostic performance of Rose Bengal Score Test in Sjøgren's syndrome patie 2011 Dec Aim of the study was to evaluate the diagnostic performance of the Rose Bengal score test for Sjøgren's syndrome (SS), and to explore differences between other tests and examinations. All participants were examined, including (but not limited to) unstimulated (UWS) and stimulated (SWS) whole saliva, labial gland biopsy (LGB or focus score), ophthalmologic questionnaire (ocular surface disease index OSDI) and objective tests: Schirmer test 1 (Sch. 1), Schirmer test 2 (Sch.2), Tear Break-up Time (TBUT) test and Rose Bengal score (RBS). Data were analyzed using Mann Whitney U-test, Receiver Operating Characteristic analysis, with specificity and sensitivity calculations and Spearman's correlation test. ROC curves showed a poor diagnostic performance of TBUT and OSDI. Sch. 1, Sch.2 and LGB all exhibited a high diagnostic performance. RBS exhibited the best performance (sensitivity 100,00; specificity 100,00; AUC 1,000). Study reveals the scarce reliability of TBUT, OSDI and Sch.1, and emphasizes RBS as the test of choice in the SS diagnosis.