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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
12195635 Adult onset Still's disease as a cause of ARDS and acute respiratory failure. 2002 We report a case of a young woman with pyrexia and progressive lung disease who developed acute respiratory distress syndrome (ARDS) and required prolonged mechanical ventilator support. The patient had a markedly elevated serum ferritin concentration of 7880 micrograms/L, a specific finding for the adult onset Still's disease (AOSD). Treatment of the patient with supportive and immunosuppressive therapy, resulted in patient survival and cure. The early consideration of the diagnosis of AOSD in patients with fever of unknown origin and a compatible clinical course may modify its severe complications.
15040587 Elucidation of Lyme arthritis. 2004 Feb Before the first description of Lyme arthritis in 1976, patients with this disease were often thought to have juvenile or adult rheumatoid arthritis. It is now known that Lyme arthritis is caused by a tick-borne spirochete that disseminates to joints, where it induces marked pro-inflammatory responses. In most patients, the arthritis resolves with antibiotic treatment. However, in the United States, about 10% of patients with Lyme arthritis develop persistent synovitis, which lasts for months or even several years after the apparent eradication of the spirochete from the joint with antibiotic therapy. The elucidation of Lyme arthritis, from acute infection to chronic synovitis, might help in our understanding not only of this entity, but also of other forms of chronic inflammatory arthritis, including rheumatoid arthritis.
15278746 Lupus arthropathy: historical evolution from deforming arthritis to rhupus. 2004 Dec Systemic lupus erythematosus is an autoimmune and inflammatory disease with multiple clinical manifestations, including arthropathy. The clinical presentation of articular involvement is variable, ranging from arthralgia without erosions or deformity to an erosive arthropathy and severe functional disability. A subset of patients with this articular involvement have Jaccoud's arthropathy, and others have an arthropathy with clinical findings similar to rheumatoid arthritis that has been called "rhupus." In this paper we review the historical evolution of concepts of lupus arthropathy, from deforming arthritis to rhupus, and conclude that rhupus is not a combination of rheumatoid arthritis and lupus. Instead, rhupus arthropathy should be regarded as a variant of the arthropathy of systemic lupus erythematosus.
17043458 Successful therapy of rheumatoid arthritis with rituximab: renewed interest in the role of 2004 Feb Rheumatoid arthritis (RA) is often considered a T cell-mediated disease, yet recent studies describe benefit with rituximab, a monoclonal antibody directed against the B cell antigen CD20. We report our experience using rituximab for 5 patients with severe, disease-modifying antirheumatic drug (DMARD)-refractory RA. Five patients with seropositive, erosive RA received rituximab as 4 weekly doses of 375 mg/m. Four subjects experienced remission lasting 5 to 12 months after noting lack of efficacy with antitumor necrosis factor (TNF) therapy. All patients have relapsed, with signs and symptoms of RA returning a mean of 8 months after therapy. Rituximab appears to be a safe and potentially helpful treatment of refractory RA and, until U.S. Food and Drug Administration approval, could be considered for compassionate use in people who have failed multiple DMARDs. Individuals who do not respond to anti-TNF therapy could experience arthritis that is perpetuated by B cell more than T cell function; these patients could be most likely to respond to rituximab. Further studies are needed to clarify the optimal dose and frequency of rituximab therapy, and its role in combination therapy for individuals with RA.
11908582 Ultrasonography of the hip in the evaluation of children with seronegative juvenile rheuma 2002 Mar OBJECTIVE: To find an objective measure of hip joint effusion with ultrasound (US) in patients with juvenile rheumatoid arthritis (JRA). METHODS: The hip joints of 24 children with JRA were evaluated with US. All patients were negative for rheumatoid factor and antinuclear antibodies. Patients with unilateral or bilateral hip pain, swelling, or limitation of range of motion were included. In each hip, the distance from the femoral neck to joint capsule was measured. Values were compared to measurements in a control group of 24 children with no history of hip joint or rheumatic disease. Statistically significant differences between the 2 groups were analyzed by t test. Two standard deviations above the control group mean was used as the standard for an effusion. RESULTS: There was a statistically significant difference in US joint space between the children with JRA and the control subjects (p < 0.001). The mean in the control group was 0.43 cm and the mean in the JRA group was 0.60 cm. A distance of 0.59 cm from femoral neck to joint capsule was determined to be consistent with an effusion. Using this standard, 71% of the children with JRA had effusion in at least one hip, and 25% had effusion bilaterally. No control subjects had measurements above this level. CONCLUSION: Ultrasonography is effective in the evaluation of hip joint involvement in patients with JRA, and may be useful in facilitating the diagnosis, classification, and followup of this illness.
15775139 [Mechanism of cartilage destruction in rheumatoid arthritis]. 2003 Jun Destruction of cartilage in rheumatoid arthritis (RA) is mediated mainly by proteinases which can degrade cartilage matrix including type II collagen and aggrecan. Of these proteinases, matrix metalloproteinases (MMP) play significant roles in RA pathology, however recent studies show that a disintegrin and metalloproteinase (ADAM) families are another candidates. These proteinases are mainly produced from synovial cells and inflammatory cells, and concentrations of these proteinases in synovial fluid are significantly higher in RA than in OA. Several proteinases have been shown to express in chondorocytes of RA and these chondrocytic proteinases are thought to mediate cartilage destruction in RA. Apoptosis which is mediated by nitric oxide (NO) is another pathway of cartilage destruction in RA.
12463452 Disease-modifying antirheumatic drug therapy for psoriatic arthritis. 2002 Nov As erosive and deforming arthritis is present in 40% of patients with psoriatic arthritis (PsA), early and aggressive treatment with disease-modifying antirheumatic drugs (DMARDs) may be as effective in controlling the progression of the disease as it is for rheumatoid arthritis (RA). Methotrexate (MTX), sulfasalazine (SSZ), and cyclosporine (CsA) are the most widely used DMARDs in the treatment of PsA and are safe and effective in patients with active peripheral arthritis, although they do not appear to be effective on axial manifestations. No controlled study has evaluated the efficacy of these drugs on the progression of radiological damage. It has recently been demonstrated that leflunomide and anti-tumor necrosis factor (TNF) agents are effective in PsA and psoriasis. The symptomatic improvement has been important and sustained and side effects minimal. In particular, inhibitors of TNF appear to have excellent potential to treat PsA. These agents are able to slow joint damage in rheumatoid arthritis and they are effective on spinal symptoms in ankylosing spondylitis. Hopefully, these findings will prove true in PsA as well.
15775143 [Early diagnosis and treatment of the bone and cartilage lesions in rheumatoid arthritis]. 2003 Jun Rheumatoid arthritis (RA) is chronic destructive synovitis affecting the bone and joints. The early suppression of disease activity during the first several months in RA has been reported to be exclusively important to prevent joint destruction and functional decline. Effective treatment of active RA requires early diagnosis. Diagnostic criteria for early RA was proposed in Japan, and this criteria has still problems for accurate diagnosis. Some new diagnositic methods have been developed such as MRI evaluation of joints and nti-CCP antibodies.
12410801 Evidence of clonotypic pattern of T-cell repertoire in synovial fluid of children with juv 2002 Nov Rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA) are characterized by chronic inflammation, synovial cell proliferation and progressive joint damage. It has been speculated that T cells play an important role in the pathogenesis of RA and JRA in the early stage of the disease. Previous studies have demonstrated discrepant results regarding the significance of T-cell clonality in RA or JRA lesions. It can be postulated that the heterogeneity of these data may be linked to the stage of the disease, as the relative importance of selective immunological events is different during the time from onset to established disease. To avoid this problem, we conducted the present study in nine children affected by JRA at the onset of the disease and before treatment. We analysed the T-cell receptor beta chain variable (TCRBV) of CD4+ and CD8+ lymphocytes in peripheral blood (PBL) and synovial fluid (SFL), by a panel of monoclonal antibodies (MoAbs). Furthermore, to assess the clonotypic pattern of T-cell repertoire, the CDR3 length distribution was evaluated by spectratyping analysis. Our results showed no significant expansion of distinct TCRBV subset in either synovial or peripheral compartments. Conversely, when we studied the CDR3 length distribution, an oligoclonal pattern was found in the SFL of six patients, suggesting the presence of a clonotypic restriction of T cells in SFL, which is not detectable in PBL. These findings are consistent with an antigen driven T-cell expansion sequestered at the inflammatory site.
14674012 Antiidiotypic antibodies neutralize autoantibodies that inhibit cholinergic neurotransmiss 2003 Dec OBJECTIVE: Functional autoantibodies that inhibit M(3) muscarinic receptor (M3R)-mediated neurotransmission have been reported in patients with Sjögren's syndrome (SS) and in patients with scleroderma. Because of limited reports that intravenous immunoglobulin (IVIG) improves dysautonomia in primary SS, we investigated whether IVIG neutralizes the effect of anti-M3R antibodies on colon smooth muscle contractions, in an in vitro functional assay. METHODS: IgG obtained from patients with primary SS, patients with rheumatoid arthritis and secondary SS, and patients with scleroderma was tested, before and after coincubation with equimolar amounts of IVIG or its F(ab')(2) and Fc fractions, for the ability to inhibit carbachol-evoked colon smooth muscle contractions. In addition, patient IgG was passed through an IVIG F(ab')(2) column, and unretained IgG was tested for functional activity on colon smooth muscle strips. Purified IgG obtained from healthy adults was also examined for a neutralizing effect on anti-M3R antibody activity. RESULTS: Inhibition of colon contractions was mediated by the Fab fraction of patient IgG. Coincubation of IgG from the 3 patient groups with IVIG or its F(ab')(2) fragment neutralized anti-M3R antibody-mediated inhibition of cholinergic smooth muscle contractions. Preabsorption of patient IgG with Sepharose-bound IVIG F(ab')(2) removed the anti-M3R inhibitory activity. In addition, purified IgG from each of 4 healthy adults neutralized the functional autoantibodies. CONCLUSION: Anti-M3R antibody activity does not require receptor crosslinking. Antiidiotypic antibodies present in pooled IgG neutralize patient IgG-mediated inhibition of M3R cholinergic neurotransmission, providing a rationale for IVIG as a treatment of autonomic dysfunction in patients with SS and patients with scleroderma. Furthermore, antiidiotypic antibodies in healthy individuals may prevent the emergence of pathogenic anti-M3R autoantibodies.
15468377 Favorable outcome in patients with renal involvement complicating macrophage activation sy 2004 Oct Systemic-onset juvenile rheumatoid arthritis (SoJRA) constitutes about 10-20% of all JRA. However more than two-thirds of the mortality seen in JRA patients is accounted for by SoJRA. Macrophage activation syndrome (MAS), which can also be considered as a form of secondary hemophagocytic lymphohistiocytosis, is a major cause of morbidity and mortality in children with SoJRA. MAS is characterized by persistent high fever, pancytopenia, mild to serious derangements of liver cell function, encephalopathy, and disseminated intravascular coagulation. Renal involvement in MAS is a rarely recognized feature. In 2 recently reported case series of MAS in SoJRA, renal involvement appeared to be associated with poor prognosis. We describe 3 children with SoJRA who had renal involvement complicating MAS and had a favorable outcome.
17043497 Pathogenesis of rheumatoid arthritis. 2004 Jun Although widely diverse mechanisms have been held responsible for tissue damage in rheumatoid arthritis (RA), it is likely that immune complexes are the underlying cause. Self-aggregating complexes of 7s rheumatoid factors in synovial fluid are a distinguishing feature of RA, whilst circulating complexes of 19s rheumatoid factor directed against the hinge region of 7s immunoglobulins are perhaps less specific. Other autoimmune complexes, such as those containing antibodies directed against citrullinated peptides, have been identified and may be more specific for RA, although the antigens against which these antibodies are directed have not been fully characterized. Together with phagocytic cells such as neutrophils, immune complexes are critical to the pathogenesis of RA; their effects are mediated by a complex cascade involving complement activation and stimulation of phagocytes via C5a and Fc receptors. These mechanisms result in a release of mediators of inflammation and joint destruction: cytokines, metalloproteinases, and reactive oxygen intermediates. This article will review recent, and some not too recent, progress made towards working out the pathogenesis of RA.
14979924 Citrullination, a possible functional link between susceptibility genes and rheumatoid art 2004 Antibodies directed to citrullinated proteins (anti-cyclic citrullinated peptide) are highly specific for rheumatoid arthritis (RA). Recent data suggest that the antibodies may be involved in the disease process of RA and that several RA-associated genetic factors might be functionally linked to RA via modulation of the production of anti-cyclic citrullinated peptide antibodies or citrullinated antigens.
24387116 Evaluation of Kampo medicines used to treat rheumatoid arthritis in collagen-induced arthr 2003 Mar Abstract To evaluate the usefulness of Kampo medicines (traditional herbal medicines) used clinically for the treatment of rheumatoid arthritis (RA), we selected eight of them and examined their effects on collagen-induced arthritic and pX transgenic mice. Among these, Dai-bofu-to, Kanzo-bushi-to, and Makyo-yokkan-to significantly reduced the severity of arthritis in collagen-induced arthritis (CIA) mice. The onset of arthritis was delayed by three Kampo medicines, but only the effect of Makyo-yokkan-to was statistically significant. In addition, three Kampo medicines suppressed the arthropathy of pX transgenic mice, which had developed spontaneously. The onset of arthritis was delayed by 10.7, 8.3, and 15.4 days following treatment with Dai-bofu-to, Kanzo-bushi-to, and Makyo-yokkan-to, respectively. A study of the underlying mechanism showed that Kanzo-bushi-to decreased serum antitype II collagen antibody levels, suggesting that Kanzo-bushi-to possesses immunomodulating activity. This study shows that some Kampo medicines are effective in an induced or spontaneously developed arthritis animal model of human RA.
14962963 Polymorphisms in the tumour necrosis factor gene are not associated with severity of infla 2004 Mar BACKGROUND: Tumour necrosis factor alpha (TNFalpha) is a powerful inflammatory mediator in rheumatoid and other types of inflammatory arthritis. Polymorphisms within the TNFalpha gene have previously been investigated to determine their role in the aetiopathogenesis of rheumatoid arthritis (RA), but it is unclear whether reported associations are with susceptibility to, or severity of, disease. OBJECTIVE: To examine the association between both individual TNFalpha single nucleotide polymorphisms (SNPs) and haplotypes with the development and severity of erosions by 5 years in patients with inflammatory polyarthritis (IP). METHODS: 438 patients from the Norfolk Arthritis Register observational inception cohort of patients with IP were x rayed 5 years after disease onset. They were genotyped for nine SNPs mapping to the TNFalpha gene, using a SNaPshot primer extension assay. Haplotypes were constructed in patients with IP, who were compared for the presence and extent of erosions at 5 years. RESULTS: No association between individual TNFalpha SNPs or haplotypes in the patients who developed erosions at 5 years compared with those who remained non-erosive was found. Restricting analysis to patients who satisfied ACR criteria for RA by 5 years did not affect the conclusions. CONCLUSION: The TNFalpha gene does not seem to be associated with severity as assessed by erosive outcome at 5 years in patients with IP.
12443596 Treatment of rheumatoid tenosynovitis with cytokine inhibitors. 2002 Nov 16 Hand function depends on tendon integrity, but in rheumatoid arthritis tenosynovitis can result in tendon adhesions and rupture. Cytokine inhibitors have proved effective in rheumatoid joint disease; however, their effect on the tenosynovium is not well understood. We investigated the ability of inhibitors of tumour necrosis factor alpha and interleukin 1 to reduce production of collagenolytic matrix metalloproteinases 1 and 13 in tenosynovial tissue obtained from patients with rheumatoid arthritis. Our data show that cytokine blockade can reduce collagenase concentrations in tenosynovial tissue, suggesting cytokine inhibitors could be effective in reduction of tendon damage.
14689077 [44-year-old female patient with cutaneous rash, sore throat, fever and arthritis]. 2003 Nov We report on a 44 year old woman with fever, cutaneous rash, severe sore throat, arthritis, leukocytosis, splenomegaly and liver dysfunction. After exclusion of an infectious or malignant disease, adult onset Still's disease was diagnosed according to the Yamaguchi criteria. Reduction of the initial treatment with corticosteroids after 4 month caused a relapse of disease. Thus methotrexate treatment was started, which resulted in improvement of symptoms and inflammatory activity.
24383837 Atypical mycobacteriosis in two patients with rheumatoid arthritis. 2002 Mar Abstract We report two cases of rheumatoid arthritis (RA) with atypical mycobacteriosis. Opportunistic infections are critical complications for rheumatic diseases. The use of steroids or immunosuppressants may increase the risk of opportunistic infections. However, these reports are rare in that they demonstrate atypical mycobacterial infections as complications of RA, even though no immunosuppressive agents were used. We discuss the characteristics of atypical mycobacterial infections of the lung in RA.
12109538 Sjögren's syndrome: viewpoint on pathogenesis. One of the reasons I was never asked to wr 2002 OBJECTIVE: To critically consider the public opinion/consensus on SS formulated by opinion leaders and textbook chapters. RATIONALE: Although our clinical work is based on evidence-based medicine, it is obvious that we do not have evidence-based solutions to the etiology and pathogenesis of autoimmune rheumatic diseases. In spite of this, consensus if often taken as a truth, which may hamper the production, funding and/or publication of new and original ideas and views. METHODS: Comparison of the classic view with one of the many other possible views. RESULTS: The consensus view states that 1) SS is initiated and/or caused by an exogenous agent, probably some type of retrovirus, and 2) after initiation, a straightforward sequence of events follows: a) salivary gland epithelial cells are disrupted, b) T lymphocytes migrate to and are activated in the glands, c) B cells get the help they need and start to produce SS and RF autoantibodies, which processes lead to structural destruction and loss of acinar cells and, thus, to sicca symptoms (an example of the linear, step-by-step "computer" logic). The problems inherent to this view include: 1) why women? (gender aspect), 2) why at the age of 50? (chronobiologic aspect), 3) is the normal immune system in SS only responding to normal (formely sequestrated) autoantigens? Is the loss of exocrine gland function really caused by "autoimmune" destruction? - or do the SS-autoantibodies and lymphocyte infiltrates only represent markers in an appropriate HLA background? (autoimmune aspect), 4) are the retroviral diseases really similar to SS? (exogenous rs endogenous causes), 5) is our current view compatible with unexpected, future findings? Is the textbook interpretation the final truth (evolutionary aspect of our view on pathogenesis). CONCLUSION: The tubuloalveolar exocrine glands may be seen as 1) locus minoris resistentiae for normal oral microbial flora and immune-inflammatory attacks at the normal environment-host interface. Apoptotic and/or necrotic cells are released into the intraluminal space and pass in normal glands through normal, immunologically competent lymphocyte foci and/or ectopic lymphatic tissue. Acinar cell degeneration/death may increase upon 2) aging and acinar cell renewal and well-being may be hampered by age-dependent deficiencies in the trophic 3) neuro-endocrine support. In a proper immunogenetic setting, a) marker autoantibodies (e.g. RF, SS-A/Ro, SS-B/La), useful in the diagnosis, are produced. However, sicca symptoms/SS develop only if muscarinic receptor or other b) pathogenetic autoantibodies disrupting the normal neuronal-to acinar cell communication are also produced. c) Systemic symptoms could be produced on neuroendocrine, chronobiologic and autoimmune basis. Other professionals are invited to entertain their own views on the pathogenesis of SS - make your own one!
12184431 Current and potential treatments for primary Sjögren's syndrome. 2002 Jun A precise definition of primary Sjögren's syndrome resting on 'revised' or 'international' criteria has been accepted by most experts. This is important because the symptoms of primary Sjögren's syndrome, namely, dryness, fatigue, and pain, are common in the population at large and can occur in the absence of autoimmune disease as a result of medication use, anxiety and depression, or normal aging. This widely accepted definition is particularly valuable as a tool for obtaining homogenous patient populations for trials of new therapeutic agents. In this review article, before discussing treatments for complications and current hopes about second-line drugs, we present an update on available treatments forthe symptomatic triad (dryness, fatigue, and diffuse pain) seen in autoimmune Sjögren's syndrome and in some cases of isolated sicca syndrome. These very bothersome and permanent symptoms have a negative effect on quality of life. The most recent data show that systemic cholinergic agonists (pilocarpine and cevimiline) are effective in the symptomatic treatment of dryness, that cyclosporine eye drops may relieve ocular symptoms, and that TNFalpha inhibitors may find a new indication in Sjögren's syndrome.