Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003873 (rheumatoid arthritis)
 53,068 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our objective was to study the demographic characteristics of patients referred from general practitioners to a rheumatology outpatient clinic and to analyse the content and quality of the referral letters. During a 12-month period 346 randomly chosen referral letters of new patients from GPs to a rheumatology outpatient clinic were evaluated. The mean age of the 346 referred patients (73.1% females and 26.9% males) was 45.5 years and 17.8% were 60 or older. Mean disease duration at the time of referral was 50.9 months (1-432 months). Only about 10% of the patients referred had a disease duration of 1 month or less. The current clinical problem was appropriately presented in 95% of the referral letters. In only 0.9% of referrals had there been a prior phone consultation. Altogether, 95.1% of the referrals were as a result of diagnosis or treatment, and in nearly half the cases a diagnosis of inflammatory rheumatic disease was suggested. In 23% of the letters the result of clinical examinations were missing. Laboratory tests such as serum rheumatoid factor, antinuclear antibodies and HLA-B27 were used by GPs to screen for rheumatic disease in general. A lack of correlation between clinical manifestations and subsequently requested laboratory examinations was frequently found in the referral letters, exemplified by the use of HLA-B27 in rheumatoid arthritis and serum rheumatoid factors in ankylosing spondylitis. These results show that among GPs the threshold for referring patients to a rheumatology outpatient clinic appears rather high, and that patients are subjected to long observation periods before referral. A more frequent use of phone consultations and an improvement in the diagnostic skills of GPs may positively influence the selection of patients for referral and shorten the long waiting lists in rheumatology. This need for improvement was further strengthened by GPs' inappropriate use of laboratory tests.
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PMID:Referrals from general practice to an outpatient rheumatology clinic: disease spectrum and analysis of referral letters. 1114 54

Knowledge of the genetic background of patients with inflammatory arthritis may be useful for disease management. The main markers are the HLA-DR-associated Shared Epitope (SE) for Rheumatoid Arthritis (RA) and HLA-B27 for ankylosing spondylitis. We have developed a simple molecular biology-based test to provide this essential information. HLA targets are amplified by polymerase chain reaction (PCR), then simultaneously analyzed using 16 individual hybridization reactions in two 8-well ELISA strips with colorimetric detection. Concordance was evaluated using a cohort of RA patients with known genotype. Using this new assay, 100% concordance was observed with conventional genotyping in RA patients both for HLA-DR SE and B27 genotypes. Seventy-three percent of the patients with destructive RA had at least one susceptible allele within SE, compared to 38% of those patients with non-destructive disease. This new assay, which requires minute amount of blood, could be used to determine the genetic background of inflammatory arthritis, particularly in non-specialized settings and for large-scale clinical trials.
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PMID:A routine assay for the direct analysis of HLA-DR-related shared epitope and B27 alleles in chronic inflammatory arthritis. 1151 54

Experimental models of arthritis and their human counterparts fall into three distinct classes: (a) responses of T cells to disseminated microbial antigens (Ags) as such; (b) responses of T cells to cartilage autoAgs; and (c) responses of T cells to major histocompatibility complex (HLA-B27, DRB1) or other membrane components (LFA-1) expressed on bone marrow-derived cells. The primary immune response is driven, in naturally occurring disease, by microbial infection, e.g. with streptococci, enteric gram-negative rods or spirochetes, or is experimentally induced with mycobacterial and other adjuvants. The response to cartilage components, such as collagen type-II and various proteoglycans, may be driven by cross-reactive microbial Ags, heat shock proteins (HSPs) in particular, or the adjuvant effect of intense primary joint inflammation, as in rheumatoid arthritis and the spondyloarthropathies. Adjuvant disease appears to be purely T-cell-mediated, whereas both T cells and antibody play a role in collagen and many other forms of arthritis. Experimental evidence suggests a pathogenetic role for T-cell receptor gammadelta T cells in some lesions. Arthritis may be regulated by microbial and tissue HSPs, when these are administered by a nonimmunizing route or as altered peptide ligands, by anti-idiotypic responses that block the action of effector T cells, and by competing Ags. Immune regulation involving natural killer (NK), NK T and certain subsets of gammadelta and alphabeta T cells, which may affect the occurrence, localization and character of this group of diseases, presents a challenge for further investigation.
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PMID:Immune regulation in adjuvant disease and other arthritis models: relevance to pathogenesis of chronic arthritis. 1210 Apr 68

The aim of the study was to investigate the long-term outcome of non-specific seronegative oligoarthritis in adults. The study included 64 adult patients with recent (<6 months) seronegative oligoarthritis (rheumatoid factor negative, number of swollen joints 1-4 during the first 6 months). Follow-up examinations were carried out at onset and at 1, 3 and 8 years from entry. A total of 47 patients attended the 23-year follow-up. The endpoint outcome was good. Seven had mild erosions in the hands or feet. Only one patient with HLA-B27 developed bilateral sacroiliitis. Three patients had retired from work because of joint disease. The functional outcome of the patients analysed by HAQ was very good after 23 years: 0 in 33 and 0.1-0.9 in 12 of the 47 patients. Reclassification revealed a certain heterogeneity: one case each of rheumatoid arthritis, SLE and ankylosing spondylitis, two cases of post-traumatic arthritis, four of osteoarthrosis, and six of possible reactive arthritis. Out of the remaining 49 patients 15 were HLA-B27 positive and 16 had at least one of the psoriasis-related HLA antigens (HLA-B13, 17, w16). In conclusion, our 23-year prospective follow-up study of patients with seronegative oligoarthritis confirms their favourable outcome. The reason is that the endpoint diagnoses seemed to be similar to those of mild spondylarthropathies.
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PMID:Seronegative oligoarthritis: a 23-year follow-up study. 1222 80

Previous work suggested that expanded CD8+ T-cell clones in the synovial fluid (SF) of HLA-B27+ patients with reactive arthritis (ReA) preferentially use the T-cell receptor variable region (TCRBV) 1, similar CDR3 sequences, and joining region (BJ) 2S3. To determine the range of conservation and disease-specificity of CDR3-sequences, we analyzed the TCRBV1-J2S3 repertoire from 33 healthy HLA-B27+ individuals, patients with various types of spondyloarthropathies (SpA), and with rheumatoid arthritis (RA) by CDR3-spectratyping. After collection and database submission of all available TCRB-CDR3 from HLA-B27-restricted or SpA-derived T cells, we systematically screened the entire human sequence database for sequences similar to the B27/SpA-related CDR3. Spectratyping revealed expanded T cell clones using conserved TCRBV1J2S3 in the SF from 5/6 of the patients with acute ReA but not among the controls. In database searches, 50 HLA-B27 or SpA-related CDR3-sequences generated similar clusters of matched sequences, and matched reciprocally. Identical or closely related sequences were identified in 15 different individuals and a canonical ReA-associated TCRB was defined [BV1-CASSVG(V/I/L)(Y/F)STDTQYF-J2S3]. All but one patient-derived conserved sequences originated from acute stage ReA-patients, and were not present among approximately 3800 other human TCRB sequences in the database. Five of the conserved sequences originated from T cell clones that recognized uninfected cells in an HLA-B27-restricted fashion, implying a role of HLA-B27-restricted CD8+ T cells specific for a ubiquitous self- or cross-reactive microbial determinant in the early phase of ReA. Related sequences were independently identified in four different laboratories. The consensus TCRB motif could be a helpful diagnostic marker in HLA-B27-associated 'undifferentiated arthritis'.
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PMID:Conserved TCR beta chain usage in reactive arthritis; evidence for selection by a putative HLA-B27-associated autoantigen. 1247 59

Spondyloarthritis (SpA) represents a group of related arthritides characterized by their association with HLA-B27 and the development of sacroiliitis and enthesitis. Functional impairment, disability, and loss of quality of life may resemble that observed in rheumatoid arthritis. The SpA Research Consortium of Canada (SPARCC) is an informal association of rheumatologist members of the Canadian Rheumatology Association (CRA) with a special interest in therapeutics and outcomes research in SpA. Recent experience with anti-tumor necrosis factor-a (anti-TNF-a) directed therapies prompted a consensus-based evaluation of the evidence supporting their efficacy, safety, and appropriate use in SpA. We evaluated the clinical evidence in support of anti-TNF-a directed therapies in SpA. Medline was searched using appropriate keywords. Abstracts of the 1999-2002 annual meetings of the American College of Rheumatology and the European Congress of Rheumatology were extracted and admitted if sufficient detail was available to determine the level of evidence. Recommendations were based on randomized placebo-controlled trials (Level A evidence) and clinical studies without randomization (Level B evidence). Where the scientific literature was incomplete, recommendations reflected the consensus of SPARCC members (Level C evidence). Following development of an original draft document, consensus for revisions was achieved among members of SPARCC. The document was then posted on the CRA website prior to its final revision. The following recommendations have been endorsed by the Therapeutics Committee of the CRA: Infliximab and etanercept are indicated for reduction of signs and symptoms of moderate to severely active SpA in patients who have had an inadequate response to maximal doses of > or = 2 nonsteroidal antiinflammatory drugs (NSAID) over a 3-month period of observation; and either sulfasalazine or methotrexate is indicated in those with predominantly active peripheral arthritis. Current evidence supports their use as monotherapy (level of evidence A) for at least one year. NSAID and/or second line therapy with either sulfasalazine or methotrexate can be continued concomitantly. There is no evidence addressing potential advantages or disadvantages of combining methotrexate with anti-TNF therapy for SpA. Recommended doses for adults are: infliximab 5 mg/kg at 0, 2, and 6 weeks and every 8 weeks thereafter; etanercept 25 mg subcutaneously twice weekly. No therapy has been shown to slow progression of axial disease in SpA, and prognostic factors for determining response to therapy remain to be determined. It is the position of the CRA that all therapeutic options should be equally available according to the best judgments of the treating physician and the informed decision of the patient.
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PMID:Canadian Rheumatology Association Consensus on the use of anti-tumor necrosis factor-alpha directed therapies in the treatment of spondyloarthritis. 1512 34

Spondylo-arthropathies are a broad group of inflammatory diseases that primarily involve the axial skeleton and the sacro-iliac joints. The pattern of peripheral joint involvement in spondylo-arthropathies differs from rheumatoid arthritis. Spondylo-arthropathies are known to include several conditions like ankylosing spondylitis, reactive arthritis (including Reiter's syndrome), arthritis associated with psoriasis and inflammatory bowel disease, juvenile and also undifferentiated spondylo-arthropathies. The characteristic features of spondylo-arthropathies are absence of rheumatoid factor, inflammatory low backache, sacro-iliitis, peripheral arthritis, enthesopathy, tendency to familial aggregation and association with HLA-B27. ESR may be elevated and patients may exhibit anaemia of chronic inflammation. HLA-B27 is a useful adjunctive test. The radiologic interpretation is very important. Non-steroidal anti-inflammatory drugs and spinal exercises are the cornerstone of therapy. Intra-articular corticosteroids are helpful. Patients may be benefited from, sulfasalazine, methotrexate or azathioprine.
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PMID:Spondylo-arthropathies. 1516 85

Ankylosing spondylitis (AS) is a member of the family of spondyloarthropathies, which are inflammatory arthritides largely involving the axial skeleton and commonly accompanied by peripheral arthritis. Genetic factors, particularly the presence of HLA-B27, are major contributors to the susceptibility for AS. Despite some therapeutic advances, the treatment options for patients with AS and related disorders have been limited. Several lines of evidence have led to the hypothesis that patients with AS might benefit from treatment with tumor necrosis factor (TNF). Specifically, TNF concentrations are known to be significantly elevated in the synovium of patients with rheumatoid arthritis (RA), in the inflamed gut of patients with inflammatory bowel disease, and in the inflamed sacroiliac joints of patients with AS. The anti-TNF agents have been shown to be of benefit in, and currently have indications for, RA (etanercept, infliximab, adalimumab), Crohn's disease (infliximab), and psoriatic arthritis (etanercept). Because the spondyloarthropathies share pathogenetic mechanisms with the above-specified disease states, studies have been conducted to evaluate the effectiveness of anti-TNF agents in several disorders, including AS. Data from clinical trials so far with infliximab and etanercept show that patients with AS and related disorders achieve significant improvement in clinical signs and symptoms based on validated outcomes measures. Computed tomography and magnetic resonance imaging (MRI) can facilitate the early diagnosis of AS. Studies with infliximab using MRI together with updated scoring methods demonstrated significant decreases in associated spinal inflammation. TNF antagonist therapy is well tolerated in patients with AS, with a side effect profile consistent with the prior experience of patients with RA.
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PMID:Expanding the armamentarium for the spondyloarthropathies. 1522 20

Recent breakthroughs in genetic methodology have greatly augmented our understanding of the contribution of genetics to susceptibility to the rheumatic diseases. Disorders in which familial aggregation has been best documented include rheumatoid arthritis (RA), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), and systemic sclerosis (SSc). Much of the genetic contribution to these diseases lies in the MHC, including HLA-DR4 (RA), HLA-B27 (AS), HLA-DRB1*0301, DRB1*1501/*1503, DRB1*08, and C4 null alleles (SLE), and HLA-DRB1*11 and DRB1*1502 (SSc). Genome-wide scans have provided inconsistent data in RA, although consistent regions have been observed in scans from different groups in AS and SLE. No consistent non-MHC candidate gene has been identified in RA. There is active investigation in AS in this area. In SLE the Fc gamma RIIa and Fc gamma IIIa genes have been most thoroughly described, and in SSc fibrillin and SPARC. Newer techniques being developed presently, such as high density single nucleotide polymorphism genome-wide scanning, show promise to bring these analyses to the next level, which will hopefully result not only in better screening of individuals at highest risk, but also in novel treatments.
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PMID:Genetic studies in the rheumatic diseases: present status and implications for the future. 1566 Apr 56

Inflammation is now recognized as a key component in a number of diseases such as atherosclerosis, rheumatoid arthritis, and inflammatory bowel disease. The transcription factor NF-kappaB has been shown to be involved in both the early and late stages of the inflammatory-proliferative process. In this report, we describe the identification of the pathway-selective estrogen receptor (ER) ligand, WAY-169916, that inhibits NF-kappaB transcriptional activity but is devoid of conventional estrogenic activity. This pathway-selective ligand does not promote the classic actions of estrogens such as stimulation of uterine proliferation or ER-mediated gene expression, but is a potent antiinflammatory agent, as demonstrated in the HLA-B27 transgenic rat model of inflammatory bowel disease. Our results indicate the potential utility of pathway-selective ER ligands such as WAY-169916 in the treatment of chronic inflammatory diseases.
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PMID:Identification of pathway-selective estrogen receptor ligands that inhibit NF-kappaB transcriptional activity. 1569 42


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