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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
16980214 B cell depletion therapy in rheumatic disease. 2006 Oct B cell depletion therapy was introduced for auto-antibody associated rheumatic disease in 1998. Encouraging pilot studies in rheumatoid arthritis were followed by randomised controlled trials confirming major benefit. Licensing for use in patients unable to benefit from tumour necrosis factor alpha (TNFalpha) neutralising agents is envisaged shortly. Open studies in other disorders, in particular systemic lupus erythematosus (SLE), have also suggested benefit and its use in life-threatening situations is becoming widespread. Toxicity appears to compare favourably with other agents, but respiratory problems may be more common. Repeated therapy is effective, but may lead to hypogammaglobulinemia. Rituximab is currently the main agent used but other agents are in development. Optimal protocols are not well characterised and will probably be different for different conditions.
17086139 [Tuberculosis during treatment by TNFalpha-inhibitors]. 2006 Nov The clinical forms of tuberculosis that occur during anti-TNFalpha treatment are frequently extrapulmonary or even disseminated and life-threatening. The paradoxical reactions that can occur under appropriate treatment after stopping TNFalpha inhibitors raise the question of an immune restoration phenomenon. Adverse drug reaction reporting and epidemiologic studies, despite their methodological limitations, appear to show an excess risk of tuberculosis. Experimental studies reinforce these data. The French drug agency (Afssaps) has issued guidelines for the prevention and management of tuberculosis occurring under anti-TNFalpha treatment. Analogous guidelines in Spain led to a reduction in the incidence of these cases.
17960584 Basic fibroblast growth factor accelerates matrix degradation via a neuro-endocrine pathwa 2008 May Pain-related neuropeptides released from synovial fibroblasts, such as substance P, have been implicated in joint destruction. Substance P-induced inflammatory processes are mediated via signaling through a G-protein-coupled receptor, that is, neurokinin-1 tachykinin receptor (NK(1)-R). We determined the pathophysiological link between substance P and its receptor in human adult articular cartilage homeostasis. We further examined if catabolic growth factors such as basic fibroblast growth factor (bFGF or FGF-2) or IL-1beta accelerate matrix degradation via a neural pathway upregulation of substance P and NK(1)-R. We show here that substance P stimulates the production of cartilage-degrading enzymes, such as matrix metalloproteinase-13 (MMP-13), and suppresses proteoglycan deposition in human adult articular chondrocytes via NK(1)-R. Furthermore, we have demonstrated that substance P negates proteoglycan stimulation promoted by bone morphogenetic protein-7, suggesting the dual role of substance P as both a pro-catabolic and anti-anabolic mediator of cartilage homeostasis. We report that bFGF-mediated stimulation of substance P and its receptor NK(1)-R is, in part, through an IL-1beta-dependent pathway.
17986340 Mycophenolate sodium treatment in patients with primary Sjögren syndrome: a pilot trial. 2007 The aim of this study was to evaluate the efficacy and safety of mycophenolate sodium (MPS) in patients with primary Sjögren syndrome (pSS) refractory to other immunosuppressive agents. Eleven patients with pSS were treated with MPS up to 1,440 mg daily for an observation period of 6 months in this single-center, open-label pilot trial. At baseline, after 3 months, and after 6 months, we examined the clinical status, including glandular function tests, as well as different laboratory parameters associated with pSS. In addition, subjective parameters were determined on the basis of different questionnaires. Treatment with MPS was well tolerated in 8 of 11 patients. Due to vertigo or gastrointestinal discomfort, two patients did not complete the trial. One patient developed pneumonia 2 weeks after treatment and was withdrawn. In the remaining patients, MPS treatment resulted in subjective improvement of ocular dryness on a visual analogue scale and a reduced demand for artificial tear supplementations. However, no significant alterations of objective parameters for dryness of eyes and mouth were observed, although a substantial improvement of glandular functions occurred in two patients with short disease duration. In addition, treatment with MPS resulted in significant reduction of hypergammaglobulinemia and rheumatoid factors as well as an increase of complement levels and white blood cells. MPS promises to be an additional therapeutic option for patients with pSS, at least in those with shorter disease duration. Further investigations about the efficacy and safety of MPS in pSS have to be performed in larger numbers of patients.
19641497 BNIP3 subfamily BH3-only proteins: mitochondrial stress sensors in normal and pathological 2008 Dec The BNIP3 subfamily of BH3-only proteins consists of BNIP3 and BNIP3-like (BNIP3L) proteins. These proteins form stable homodimerization complexes that localize to the outer membrane of the mitochondria after cellular stress. This promotes either apoptotic or non-apoptotic cell death such as autophagic cell death. Although the mammalian cells contain both members of this subfamily, the genome of Caenorhabditis elegans codes for a single BNIP3 ortholog, ceBNIP3, which shares homology in the transmembrane (TM) domain and in a conserved region close to the BH3 domain of mammalian BNIP3 protein. The cell death activities of BNIP3 and BNIP3L are determined by either the BH3 domain or the C-terminal TM domain. The TM domain of BNIP3 is unique, as it is capable of autonomous stable dimerization and contributes to mitochondrial localization of BNIP3. In knockout mouse models, BNIP3L was shown to be essential for normal erythrocyte differentiation and hematopoietic homeostasis, whereas BNIP3 plays a role in cellular responses to ischemia/reperfusion injury in the heart. Both BNIP3 and BNIP3L play a role in cellular responses to stress. Under hypoxia, both BNIP3 and BNIP3L expression levels are elevated and contribute to hypoxia-induced cell death. In addition, these proteins play critical roles in disease states. In heart disease, both BNIP3 and BNIP3L play a critical role in cardiomyocyte cell death following ischemic and non-ischemic injuries. In cancer, expression of BNIP3 and BNIP3L is downregulated by promoter hypermethylation or by homozygous deletion of the gene locus in certain cancers, whereas their expression was increased in other cancers. In addition, BNIP3 expression has been correlated with poor prognosis in some cancers. The results reviewed here suggest that BNIP3 and BNIP3L may be novel therapeutic targets for intervention because of their pathological roles in regulating cell death in disease states.
16487455 Comparison of conference abstracts and presentations with full-text articles in the health 2006 Feb OBJECTIVES: To assess the extent of use of data from conference abstracts and presentations in health technology assessments (HTAs) provided as part of the National Institute for Health and Clinical Excellence (NICE) appraisal process. Also to assess the methodological quality of trials from conference abstracts and presentations, the consistency of reporting major outcomes between these sources and subsequent full-length publications, the effect of inclusion or exclusion of data from these sources on the meta-analysis pooled effect estimates, and the timeliness of availability of data from these sources and full articles in relation to the development of technology assessment reviews (TARs). DATA SOURCES: A survey of seven TAR groups. An audit of published TARs: included all NICE TARs published between January 2000 and October 2004. Case studies of selected TARs. REVIEW METHODS: Analyses of the results of the survey and audit were presented as a descriptive summary and in a tabular format. Sensitivity analyses were carried out to compare the effect of inclusion of data from abstracts and presentations on the meta-analysis pooled effect estimates by including data from both abstracts/presentations and full papers, and data from only full publications, included in the original TAR. These analyses were then compared with meta-analysis of data from trials that have subsequently been published in full. RESULTS: All seven TAR groups completed and returned the survey. Five out of seven groups reported a general policy that included searching for and including studies available as conference abstracts/presentations. Five groups responded that if they included data from these sources they would carry out methodological quality assessment of studies from these sources using the same assessment tools as for full publications, and manage the data from these sources in the same way as fully published reports. All groups reported that if relevant outcome data were reported in both an abstract/presentation and a full publication, they would only consider the data in the full publication. Conversely, if data were only available in conference abstract/presentation, all but two groups reported that they would extract and use the data from the abstract/presentation. In total, 63 HTA reports for NICE were identified. In 20 of 63 TARs (32%) explicit statements were made with regards to inclusion and assessment of data from abstracts/presentations. Thirty-eight (60%) identified at least one randomised controlled trial (RCT) available as a conference abstract or presentation. Of these, 26 (68%) included trials available as abstracts/presentations. About 80% (20/26) of the 26 TARs that included RCTs in abstract/presentation form carried out an assessment of the methodological quality of such trials. In 16 TARs full reports of these trials were used for quality assessment where both abstracts/presentations and subsequent full publications were available. Twenty-three of 63 TARs (37%) carried out a quantitative analysis of results. Of these, ten (43%) included trials that were available as abstracts/presentations in the review; however, only 60% (6/10) of these included data from abstracts/presentations in the data analysis of results. Thirteen TARs evaluated rapidly evolving technologies and only three of these identified and included trial data from conference abstracts/presentations and carried out a quantitative analysis where abstract/presentation data were used. These three TARs were used as case studies. In all three case studies the overall quality of reporting in abstracts/presentations was generally poor. In all case studies abstracts and presentations failed to describe the method of randomisation or allocation concealment. Overall, there was no mention of blinding in 66% (25/38) of the abstracts and in 26% (7/27) of the presentations included in case studies, and one presentation (4%) explicitly stated use of intention-to-treat analysis. Results from one case study demonstrated discrepancies in data made available in abstracts or online conference presentations. Not only were discrepancies evident between these sources, but also comparison of conference abstracts/presentations with subsequently published full-length articles demonstrates data discrepancies in reporting of results. Sensitivity analyses based on one case study indicated a change in significance of effect in two outcome measures when only full papers published to date were included. CONCLUSIONS: There are variations in policy and practice across TAR groups regarding searching for and inclusion of studies available as conference abstracts/presentations. There is also variation in the level of detail reported in TARs regarding the use of abstracts/presentations. Therefore, TAR teams should be encouraged to state explicitly their search strategies for identifying conference abstracts and presentations, their methods for assessing these for inclusion, and where appropriate how the data were used and their effect on the results. Comprehensive searching for trials available as conference abstracts/presentations is time consuming and may be of questionable value. However, there may be a case for searching for and including abstract/presentation data if, for example, other sources of data are limited. If conference abstracts/presentations are to be included, the TAR teams need to allocate additional time for searching and managing data from these sources. Incomplete reporting in conference abstracts and presentations limits the ability of reviewers to assess confidently the methodological quality of trials. Where conference abstracts and presentations are considered for inclusion in the review, the TAR teams should increase their efforts to obtain further study details by contacting trialists. Where abstract/presentation data are included, reviewers should discuss the effect of including data from these sources. Any data discrepancies identified across sources in TARs should be highlighted and their impact discussed in the review. In addition, there is a need to carry out, for example, a sensitivity analysis with and without abstract/presentation data in the analysis. There is a need for research into the development of search strategies specific to identification of studies available as conference abstracts and presentations in TARs. Such strategies may include guidance with regard to identification of relevant electronic databases and appropriate conference sites relevant to certain clinical areas. As there are limited case studies included in this report, analyses should be repeated as more TARs accrue, or include the work of other international HTA groups.
23105578 Lipid peroxidation and antioxidant status in blood of rheumatoid arthritis patients. 2006 Mar The main objective of the study was to assess the oxidative stress in plasma and erythrocytes of rheumatoid arthritis patients by measuring the levels of thiobarbituric acid reactive substances (TBARS), non-enzymatic antioxidants (vitamin E, C and reduced glutathione) and enzymatic antioxidants [superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSHPx)]. This study has been conducted on twenty-two adult female rheumatoid arthritis patients and an equal number of healthy subjects. Elevated lipid peroxidation and multidirectional changes in the antioxidant defence system were noticed in patients with rheumatoid arthritis. The enhanced lipid peroxidation accompanied by disturbance in antioxidant status indicates that rheumatoid arthritis patients are more prone to free radical mediated oxidative damage.
17086607 Autoimmune disease aggregation in families with primary Sjögren's syndrome. 2006 Nov OBJECTIVE: Diverse autoimmune diseases may coexist in the same individual and in families, implying a common etiology. We examined the aggregation of autoimmune diseases among first-degree relatives (FDR) of patients with primary Sjögren's syndrome (pSS). METHODS: This was a population-based case-control family study in which 101 families of women classified as having pSS according to the revised American-European criteria and 124 families of matched controls without autoimmune disease were enrolled to investigate the presence of autoimmune diseases. We performed a genetic analysis that included familial correlation and recurrent risk ratios. RESULTS: In family cases, 38% had at least one FDR with an autoimmune disease, versus 22% in control families [odds ratio (OR) 2.2, 95% confidence interval (CI) 1.2-3.9, p = 0.01]. An autoimmune disease was registered for 7.3% of 876 patients' FDR as compared with 3.85% of 857 controls' FDR (OR 1.97, 95% CI 1.28-3.03, p = 0.002). The most frequent autoimmune diseases registered among the pSS patients' FDR were autoimmune thyroid disease (AITD), systemic lupus erythematosus, and rheumatoid arthritis, which disclosed aggregation. The proband phenotype (i.e., pSS) was correlated with AITD, systemic sclerosis, and all autoimmune diseases when considered together as a trait. Maternal transmission of the autoimmunity trait was observed in cases but not in controls. CONCLUSION: Our results indicate that autoimmune diseases cluster within families of patients with pSS. This familial aggregation of autoimmune diseases adds further evidence that clinically different autoimmune phenotypes might share common susceptibility gene variants, which acting in epistatic pleitropy may represent risk factors for autoimmunity.
19088896 Incidence of Rheumatoid Arthritis in the Southern part of Denmark from 1995 to 2001. 2007 We estimated the incidence of rheumatoid arthritis in the southern part of Denmark from 1995 to 2001. At a rheumatology hospital serving a population of about 200 000 people over the age of 15, medical records were scrutinized. As case definition we used the tree and list format of 1987 American College of Rheumatology criteria for rheumatoid arthritis. The mean annual incidence rate per 100 000 person years was 40 in females, 21 in males, and 31 in females and males combined. The incidence of rheumatoid arthritis in Denmark is in accordance with recent studies from North America, the UK, and Northern European countries. The aetiology of rheumatoid arthritis is unknown but this study indicates that in these populations the exposure to non-genetic host and environmental aetiological factors is similar.
17266090 Characterization of B cell lymphoma in patients with Sjögren's syndrome and hepatitis C v 2007 Feb 15 OBJECTIVE: To characterize the clinical and immunologic patterns of expression, response to therapy, and outcome of patients with Sjögren's syndrome (SS) and associated hepatitis C virus (HCV) infection who developed B cell lymphoma. METHODS: Various international reference centers constituted a multicenter study group with the purpose of creating a registry of patients with SS-HCV who developed B cell lymphoma. A protocol form was used to record the main characteristics of SS, chronic HCV infection, and B cell lymphoma. RESULTS: Twenty-five patients with SS-HCV with B cell lymphoma were included in the registry. There were 22 (88%) women and 3 (12%) men (mean age 55, 58, and 61 years at SS, HCV infection, and lymphoma diagnosis, respectively). The main extraglandular SS manifestations were cutaneous vasculitis in 15 (60%) patients and peripheral neuropathy in 12 (48%); the main immunologic features were positive rheumatoid factor (RF) in 24 (96%) and type II cryoglobulins in 20 (80%). The main histologic subtypes were mucosa-associated lymphoid tissue (MALT) lymphoma in 11 (44%) patients, diffuse large B cell lymphoma in 6 (24%), and follicular center cell lymphoma in 6 (24%). Fifteen (60%) patients had an extranodal primary location, most frequently in the parotid gland (5 patients), liver (4 patients), and stomach (4 patients). Twelve (52%) of 23 patients died after a median followup from the time of lymphoma diagnosis of 4 years, with lymphoma progression being the most frequent cause of death. Survival differed significantly between the main types of B cell lymphoma. CONCLUSION: Patients with SS-HCV and B cell lymphoma are clinically characterized by a high frequency of parotid enlargement and vasculitis, an immunologic pattern overwhelmingly dominated by the presence of RF and mixed type II cryoglobulins, a predominance of MALT lymphomas, and an elevated frequency of primary extranodal involvement in organs in which HCV replicates (exocrine glands, liver, and stomach).
18466447 Linkage analysis of anti-CCP levels as dichotomized and quantitative traits using GAW15 si 2007 Rheumatoid arthritis is a clinically and genetically heterogeneous disease. Anti-cyclic citrullinated (anti-CCP) antibodies have a high specificity for rheumatoid arthritis and levels correlate with disease severity. The focus of this study was to examine whether analyzing anti-CCP levels could increase the power of linkage analysis by identifying a more homogeneous subset of rheumatoid arthritis patients. We also wanted to compare linkage signals when analyzing anti-CCP levels as dichotomized (CCP_binary), categorical (CCP_cat), and continuous traits, with and without transformation (log_CCP and CCP_cont). Illumina single-nucleotide polymorphism scans of the North American Rheumatoid Arthritis Consortium families were analyzed for four chromosomes (6, 7, 11, 22) using nonparametric linkage (NPL) (rheumatoid arthritis and CCP_binary), regress (CCP_cat and Log_CCP), and deviates (CCP_cont) analysis options as implemented in Merlin. Similar linkage results were obtained from analyses of rheumatoid arthritis, CCP_binary, and CCP_cont. The only exception was that we observed improved linkage signals and a narrower region for CCP_binary as compared to a clinical diagnosis of rheumatoid arthritis alone on chromosome 7, a region which previously showed variation in linkage results with rheumatoid arthritis according to anti-CCP levels. Analyses of CCP_cat and Log_CCP had little power to detect linkage. Our data suggested that linkage analyses of anti-CCP levels may facilitate identification of rheumatoid arthritis genes but quantitative analyses did not further improve power. Our study also highlighted that quantitative trait linkage results are highly sensitive to phenotype transformation and analytic approaches.
20477071 Infliximab for rheumatoid arthritis. 2006 Mar There is accumulating evidence that early and aggressive treatment of rheumatoid arthritis may lead to enhanced and sustained clinical outcomes. The goal of therapy in rheumatoid arthritis is remission. Tumor necrosis factor is a pivotal pro-inflammatory cytokine in rheumatoid arthritis. Infliximab, a chimeric murine human antitumor necrosis factor monoclonal antibody, was the first tumor necrosis factor blocking agent to be used in humans. Blockade of tumor necrosis factor occupies a central hierarchal role in the treatment of rheumatoid arthritis and now several other chronic inflammatory conditions. Although there are still many limitations and hurdles in the management of rheumatoid arthritis, the introduction of infliximab and related drugs into clinical practice represents a real therapeutic advance which has made remission an achievable goal for many more patients. This article describes the role of tumor necrosis factor and the impact of its blockade with infliximab in rheumatoid arthritis.
23105630 Oxidative stress and calcium-phosphorus levels in Rheumatoid arthritis. 2006 Sep Generation of reactive oxygen species is an important factor in the development and maintenance of rheumatoid arthritis (RA) in humans. This study was undertaken to investigate interplay among oxidants, antioxidants and pathogenesis of Rheumatoid arthritis. Serum levels of lipid peroxides, nitric oxide, vitamin E and ratio of calcium/phosphorus in RA patients were determined and compared with normal healthy controls. Significant increases in lipid peroxides (p<0.001) and nitric oxide (p<0.001) levels were found in patients presenting with RA as compared to controls. Whereas significant decrease in vitamin E (P<0.001) and calcium/phosphorus ratio (p<0.001) were found in Rheumatoid arthritis patients as compared to controls. Positive correlation was found between lipid peroxides and nitric oxide as well as between vitamin E and calcium. While lipid peroxides and nitric oxide were correlated negatively with vitamin E. whereas negative correlation was observed between MDA and Calcium/Phosphorus ratio in patients with rheumatoid arthritis. Our findings suggest that there is a close association between bone loss and oxidative threat in patients presenting with Rheumatoid arthritis.
20300340 Split skin grafting for leg ulcers complicating rheumatoid arthritis. 2008 Jan Leg ulcers as a complication of rheumatoid arthritis are difficult to heal. We present a case responding to treatment with cyclophosphamide and split skin grafting.
29783350 Identification of new susceptibility markers for rheumatoid arthritis and systemic lupus e 2008 Mar Evaluation of: Remmers EF, Plenge RM, Lee AT et al.: STAT4 and the risk of rheumatoid arthritis and systemic lupus erythematosus. N. Engl. J. Med. 6(10), 977-986 (2007). Rheumatoid arthritis is an autoimmune disease with a strong genetic component. The genetic component of rheumatoid arthritis is thought to be complex, with a wide number of predisposing alleles, each of them conferring a modest risk. The identification of the genetic component of complex diseases is of great interest, since a fuller understanding of disease etiology and pathogenesis is expected to lead to improved risk predictions for susceptibility, severity and outcome and, ultimately, may lead to the development of novel therapies. Until very recently, only two reproducible genetic associations were described. For 30 years, only HLA genes have been identified as sufficiently validated rheumatoid arthritis genetic risk factors. A second, more modest, association has been recently identified with the PTPN22 gene. In the study by Remmers et al., a new susceptibility marker for rheumatoid arthritis is identified, the STAT4 rs7574865 polymorphism. Interestingly, this SNP is also associated with systemic lupus erythematosus.
21348047 2007 Nov This report from the RTI-University of North Carolina Evidence-based Practice Center summarizes the evidence on the comparative efficacy, effectiveness, and harms of corticosteroids, synthetic DMARDs, and biologic DMARDs in the treatment of patients with either rheumatoid arthritis (RA) or psoriatic arthritis (PsA). The key questions (KQs) were developed through a public process in conjunction with the Scientific Resource Center at the Oregon Health and Science University. The KQs are as follows: KQ 1. For patients with rheumatoid arthritis or psoriatic arthritis, do drug therapies differ in their ability to reduce patient-reported symptoms, to slow or limit progression of radiographic joint damage, or to maintain remission? KQ 2. For patients with rheumatoid arthritis or psoriatic arthritis, do drug therapies differ in their ability to improve functional capacity or quality of life? KQ 3. For patients with rheumatoid arthritis or psoriatic arthritis, do drug therapies differ in harms, tolerability, adherence, or adverse effects? KQ 4. What are the comparative benefits and harms of drug therapies for rheumatoid arthritis and psoriatic arthritis in subgroups of patients based on stage of disease, history of prior therapy, demographics, concomitant therapies, or comorbidities?
18466445 Genome-wide single-nucleotide polymorphism linkage analyses of quantitative rheumatoid art 2007 We applied nonparametric quantitative trait linkage analysis to two rheumatoid arthritis quantitative phenotypes, IgM rheumatoid factor (RF) and anti-cyclic citrullinated peptide autoantibody titer measurements, using 5700 genome-wide Illumina single-nucleotide polymorphism genotypes on 658 Caucasian North American Rheumatoid Arthritis Consortium families. Peak LOD scores for both quantitative traits were located in the human leukocyte antigen region 6p21 (15.8 and 13.8 for RF and anti-cyclic citrullinated peptide, respectively) followed by 11p12 (3.2 and 3.6). In addition, there were LOD scores of 3.2 on 2q32 for RF and 3.6 on 4q24 for anti-cyclic citrullinated peptide. The resulting linkage signals for both phenotypes are very similar to previous results for rheumatoid arthritis as a qualitative variable, with rheumatoid factor measurements being most closely aligned. Interestingly, anti-cyclic citrullinated peptide exhibits a stronger linkage peak on 2p14 than rheumatoid factor and rheumatoid arthritis, and stronger linkage on 4q24. Finally, we used ordered subset analyses to determine if sub-ranges of these two traits increased rheumatoid arthritis linkage signals; however, our analyses did not reveal significant effects of the quantitative traits on rheumatoid arthritis linkage signals in this population.
19707351 Update on the use of etanercept across a spectrum of rheumatoid disorders. 2008 Jun Etanercept is a soluble TNF receptor p75 fusion protein which is approved for subcutaneous use (50 mg weekly) in the treatment of patients with active rheumatoid arthritis (RA), juvenile RA, ankylosing spondylitis, and psoriatic arthritis. Etanercept binds to both TNFalpha and lymphotoxin and has quite a short mean half-life (70 hours). Numerous randomized clinical trials have demonstrated its efficacy to improve signs and symptoms in early and established RA and other inflammatory arthritis. Furthermore, etanercept has shown its ability to prevent radiographic progression and to improve health-related quality of life in patients with RA and psoriatic arthritis. A combination of etanercept plus methotrexate was more efficacious than etanercept monotherapy in RA patients but there is currently no evidence that such rheumatic combination is better than monotherapy in other disorders. Etanercept was generally well tolerated both in controlled trials with withdrawal rates being similar to the comparator groups and in large observational studies. Infections and injection-site reactions were the most frequently reported events. Serious infections were slightly increased but the occurrence of tuberculosis seemed less frequent than with anti-TNF monoclonal antibodies (infliximab and adalimumab). The benefit-risk ratio of etanercept appeared to be very positive, and this drug has now emerged as a major therapy in patients with active inflammatory arthritis. Furthermore, it is more frequently considered as an emerging and valuable option in patients with early disease.
18460269 Total joint replacement in childhood arthritis. 2008 Apr Juvenile rheumatoid arthritis poses a distinct challenge to pediatric rheumatologists and orthopedic surgeons. Recent developments in the medical management of juvenile rheumatoid arthritis have decreased the need for surgical intervention in this subset of patients; however, those patients who need surgery are often the most challenging cases due to their relatively small bone size, the complex deformity caused by soft tissue contractures, and the tendency for multiple joint involvement. Nonetheless, technologic improvements in implant design and surgical techniques have led to successful outcomes in otherwise debilitating conditions. A careful and coordinated approach to the surgical management of juvenile rheumatoid arthritis can lead to improved function and significant pain relief for children with rheumatoid arthritis.
19105841 Limited Wegener's granulomatosis presenting as lung nodules in a patient with rheumatoid a 2008 Dec 23 BACKGROUND: Rheumatoid arthritis has varied pleuroparenchymal manifestations. Wegener's granulomatosis can develop in an established case of rheumatoid arthritis and this association although previously reported is very rare. CASE PRESENTATION: A 60-year-old lady had been diagnosed with rheumatoid arthritis on the basis of her clinical symptoms and serological tests which were positive RA factor and anti-CCP antibodies. Her rheumatoid arthritis activity had been mild and well controlled with hydroxychloroquine and low dose prednisone. She presented with a productive cough and right-sided pleuritic chest pain. CT scan of the chest showed three lung nodules with increased uptake on PET CT scan, raising concerns for an inflammatory or malignant process. The differential diagnosis included rheumatoid nodules, infections or malignancy. A CT-guided needle biopsy of the largest nodule was undertaken which showed vasculitis typical of Wegener's granulomatosis. Stains and cultures of the biopsy specimen were negative for bacteria, fungi and acid fast bacilli. A panel of serological tests for vasculitis were checked and showed elevated titers of cANCA and anti-proteinase 3 antibodies. Urine analysis and CT scan of paranasal sinuses was normal. Since the upper respiratory tract and the kidneys were spared a diagnosis of limited Wegener's granulomatosis affecting only the lungs was made. Due to the toxicity of cyclophosphamide, her relatively mild disease sparing the kidneys and the underlying rheumatoid arthritis, weekly methotrexate was started and low dose prednisone was continued. She had marked symptomatic improvement and complete resolution of the nodules was documented on subsequent imaging. CONCLUSION: Wegener's granulomatosis developing in a patient with rheumatoid arthritis is very rare but should be considered as it warrants a different and possibly more aggressive treatment approach.