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

ID PMID Title PublicationDate abstract
16734120 Thyroid disorders and autoantibodies in systemic lupus erythematosus and rheumatoid arthri 2004 To determine the patterns of thyroid dysfunction and autoantibodies associated with SLE and RA patients, twenty patients with SLE and another group of twenty with RA were studied. The results were compared with those of twenty apparently healthy age- and sex- matched controls. All patients were subjected to complete history taking, thorough clinical examination and joint examination. All patients and controls were subjected to the following investigations: T3, T4, TSH, antithyroglobulin antibodies (ATGAb) and thyroid peroxidase antibodies (TPOAb). Also, complete blood picture, ESR, RF, ANA, CRP and LE cells were done. This study revealed that thyroid disorders were significantly increased in SLE patients (50%) when compared to RA (15%) (P<0.05). In SLE group, 20% had euthyroid sick syndrome, 20% had hypothyroidism (10% subclinical and 10% biochemical), and 10% had hyperthyroidism (5% subclinical and 5% biochemical). However, in RA, 10% had hypothyroidism (subclinical) and 5% had subclinical hyperthyroidism. TPOAb was found in 15% of SLE and 5% of RA patients and 10% of controls, but the titres were higher in SLE and RA patients. Also, ATGAb was found in 5% of SLE, 30% of RA patients and 10% of controls, but the titres were higher in SLE and RA patients. It is concluded that thyroid abnormalities are more implicated with euthyroid sick syndrome and hypothyroidism (subclinical and overt) than hyperthyroidism in SLE patients. SLE and RA were associated with antithyroid antibodies (TPOAb in SLE and ATGAb in RA). Performance of thyroid function tests in patients with SLE, in particular and RA as a part of the biochemical and immunological profiles, may help in early detection of associated thyroid disorders.
15172045 Adalimumab therapy in rheumatoid arthritis. 2004 May Adalimumab is a recombinant human immunoglobulin G1 monoclonal antibody that is specific for human tumor necrosis factor. Based on the data presented in this article, adalimumab administered alone or in patients partially responsive to methotrexate exhibits a rapid onset of action, provides a substantial reduction in signs and symptoms, and results in an improvement in physical function and health-related quality of life. Adalimumab has been demonstrated to inhibit progression of structural joint damage in patients who have long-standing rheumatoid arthritis. Taken together, the data support adalimumab as a new therapeutic option for patients with moderate to severe rheumatoid arthritis.
12087908 [Synchronous programmed intensive therapy of patients with severe rheumatoid arthritis]. 2002 AIM: To evaluate efficiency and safety of intensive treatment program (synchroneous plasmapheresis, large-dose methotrexate and methypred) for patients with severe rheumatoid arthritis (RA). MATERIAL AND METHODS: 45 patients with highly active and progressive RA, systemic symptoms, corticosteroid dependence who had intolerance to standard therapy or had not responded to it were divided into 2 comparable groups. 25 patients of group 1 for a month got 6 plasmapheresis procedures with synchroneous intravenous injection of 40 mg of methotrexate and 250 mg of methypred. 20 patients of group 2 received pulse therapy with methypred (3 g) and methotrexate (200 mg). The intensive therapy was followed in all the patients with methotrexate in a dose 10-20 mg/week. RESULTS: One, six and twelve months after treatment patients of group 1 demonstrated a decrease in RA clinical activity and inflammation. In a year remission by ACR criteria was achieved in one-third of the patients. CONCLUSION: The sychroneous program of intensive therapy is highly effective in RA patients with vasculitis, ineffective standard therapy and corticosteroid dependence.
15338487 Connective tissue metabolism in patients with unclassified polyarthritis and early rheumat 2004 Sep OBJECTIVE: To assess the applicability of serum concentrations of markers of synovial inflammation, cartilage, and bone metabolism in relation to conventional markers of disease activity, bone mineral density (BMD) of the hand, and radiographic outcome. METHODS: Biochemical markers of collagen tissue metabolism were measured in 72 patients with symmetrically swollen and tender second and third metacarpophalangeal or proximal interphalangeal joints for at least 4 weeks and less than 2 years. At 2 years, 51 patients fulfilled the American College Rheumatology criteria for rheumatoid arthritis (RA) and 21 patients had unclassified polyarthritis. Patients with RA were divided into groups according to the mean disease activity and to magnetic resonance imaging and radiographically detected bone erosions in the hands. RESULTS: Patients with RA had significantly higher serum concentrations of matrix metalloproteinase-3 (MMP-3) at baseline and higher mean concentrations of serum MMP-3 and pyridinoline (Pyd) during the first 6 and 12 months than patients with unclassified polyarthritis. RA patients with persistent disease activity and erosive disease had significantly higher concentrations of serum MMP-3 and Pyd than patients with no disease activity or nonerosive disease. Significant mutual correlations between serum MMP-3 and Pyd and C-reactive protein and erythrocyte sedimentation rate were observed. The mean values of MMP-3 and Pyd correlated significantly to the alpha coefficient of the digital x-ray radiogrammetry (DXR-BMD). CONCLUSION: Serum MMP-3 and Pyd varied according to disease activity, periarticular osteoporosis measured by DXR, and radiographic outcome, and thus appear to supplement the conventional markers of disease activity for monitoring patients with RA.
15170905 Lefunomide in combination therapy. 2004 Jun In most studies of disease modifying antirheumatic drug therapy, in combination with either leflunomide or biological agents, patients are given an additional agent after they have failed treatment with methotrexate (MTX). This review of clinical studies shows that leflunomide is clinically efficacious and well tolerated when added to either sulfasalazine or MTX, as both an initial and ongoing treatment for rheumatoid arthritis (RA). Experience in combining leflunomide with biological agents is limited to a small number of open-label studies with infliximab. According to the opinion obtained at an International Expert Panel Meeting held in Paris in May 2003, leflunomide can be used in combination therapy: 61% of the Expert Panel would use leflunomide with MTX, 71% with sulfasalazine, 43% with infliximab, 33% with adalimumab, 19% with etanercept, and 38% with anakinra. The Expert Panel stated that the combination of leflunomide and infliximab warrants a prospective, randomized, controlled trial in patients with incomplete clinical responses to leflunomide monotherapy, provided leflunomide is started first, without a loading dose, and infliximab is added after good tolerability to leflunomide has been established. The Expert Panel concluded that combination therapy with leflunomide has a place in the treatment of RA. Caution is advised, however, when using combination treatments and, therefore, the patient's safety should be carefully monitored.
12404030 [Early electroretinografic changes in elderly RA patients treated with hydroxychloroquine] 2002 Jul OBJECTIVE: To evaluate the effectiveness of fundoscopy, electrooculography, electroretinogram and visually evoked potentials in early detection of hydroxychloroquine retinal toxicity in RA patients and to evaluate the influence of patients' age, drug dosage, concomitant therapy (prednisone and methotrexate) and serum creatinine levels in the development of this side effect. METHODS: From september to december 1999, we have enrolled 32 RA patients (13 males, 19 females) starting hydroxychloroquine treatment. The patients underwent regular ophthalmological examination (fundoscopy, electro-oculography, electroretinogram and visually evoked potentials) every 4 months. Disease activity was evaluated every two months by clinical and routine serological examination. RESULTS: No patients developed retinopathy during 1 year's follow-up; fundoscopy, electrooculography, and visually evoked potentials did not vary from the baseline. On the other hand, electroretinogram showed early alterations of scotopic and photopic response; moreover a significant statistical correlation between patients' age (more than 65 years) and b1 photopic wave increase (p < 0,05) was observed. No correlation was found between the development of electro-retinographic alterations and hydroxychloroquine dosage, concomitant therapy and serum creatinine levels CONCLUSION: Our data show the inefficacy of fundoscopy, electrooculography and visually evoked potentials in early detection of hydroxychloroquine retinopathy. On the other hand electroretinogram allows early detection of retinal alterations during hydroxychloroquine treatment, in patients older than 65 years.
12495637 Chemokines and chemokine receptors in rheumatoid arthritis. 2003 Feb Chemokines are chemotactic cytokines involved in a number of pathological processes, including inflammatory conditions. Chemokines play a role in the pathogenesis of various inflammatory diseases. Based on a burgeoning body of literature, RA was chosen as a prototype to discuss this issue. In this review, the authors give a detailed introduction to the classification and function of chemokines and their receptors. This is followed by a discussion of the role of chemokines and chemokine receptors in RA. Chemokines interact with other inflammatory mediators, such as cytokines. Thus, the regulation of chemokine production and the place of chemokines in the network of inflammatory mediators present in the rheumatoid synovium are also reviewed. Finally, potential strategies using anti-chemokine or anti-chemokine receptor biologicals in anti-rheumatic therapy are discussed.
12209034 Efficacy and safety of valdecoxib in treating the signs and symptoms of rheumatoid arthrit 2002 Sep OBJECTIVE: To compare the efficacy of the COX-2 specific inhibitor valdecoxib with the conventional NSAID naproxen and placebo in treating rheumatoid arthritis (RA). METHODS: This multi-centre, randomized, double-blind, placebo-controlled trial compared the efficacy and safety of valdecoxib 10 mg (n=209), 20 mg (n=212) or 40 mg once daily (q.d.) (n=221) with naproxen 500 mg b.i.d. (n=226) or placebo (n=222), in treating the signs and symptoms of RA. Efficacy was assessed by the number of patients responding to treatment according to the American College of Rheumatology-Responder Index (ACR-20). RESULTS: ACR-20 response was recorded for all randomized patients who received a single dose of study medication (above). Valdecoxib, at all administered doses, produced significant improvements in the ACR-20 Responder Index at weeks 2, 6 and 12 compared with placebo (P
12754727 Relationship of social role quality to psychological well-being in women with rheumatoid a 2003 Jun The purpose of this study was to examine the mediating and moderating effects of women's social role quality on the psychological well-being of women with rheumatoid arthritis (RA). One hundred and fifty-six women with a diagnosis of RA (M age = 59, SD = 11) completed self-report measures of arthritis history, physical health, psychological well-being, and role quality. Hierarchical multiple regression analyses indicated that role quality mediated the effects of physical health on depression and purpose in life, moderated the effects of health on depression, and moderated the effects of pain on purpose in life. Women in poor health with high role quality were significantly less depressed than women in poor health with poor role quality. Women with high levels of pain and high role quality had more purpose in life than women with high levels of pain and low role quality. Despite difficulties with their physical health, women who had high role quality had higher levels of psychological well-being. Findings from this study may aid in the development of meaningful interventions to help women with RA manage their daily lives to optimize well-being.
12096230 The prevalence of rheumatoid arthritis in the United Kingdom: new estimates for a new cent 2002 Jul BACKGROUND: It is 40 yr since the last age- and sex-specific estimates of the prevalence of rheumatoid arthritis (RA) for the UK were published. Since then the classification criteria for RA have been revised and there has been evidence of a fall in the incidence of RA, especially in women. OBJECTIVES: To estimate the age- and sex-specific point prevalence of RA (defined as fulfilment of a modification of the 1987 ACR classification criteria for RA on the day of assessment). The estimate was made in the primary care setting in Norfolk, UK. METHODS: A stratified random sample was drawn from seven age and gender bands. The 7050 individuals selected were mailed a screening questionnaire. Positive responders were invited to attend for a clinical examination. The sample was matched against the names in the Norfolk Arthritis Register (NOAR), a register of incident cases of inflammatory polyarthritis which has been in existence since 1990. RESULTS: The overall response rate was 82%. Sixty-six cases of RA were identified. Extrapolated to the population of the UK, the overall minimum prevalence of RA is 1.16% in women and 0.44% in men. A number of incident cases of RA previously notified to NOAR were not identified as cases in the survey because they had entered into treatment-induced remission. In addition, some cases who failed to attend for examination had significant disability. These prevalence figures are therefore an underestimate. CONCLUSIONS: The prevalence of RA in women, but not in men, in the UK may have fallen since the 1950s.
15026584 Long-term treatment with etanercept significantly reduces the number of proinflammatory cy 2004 Aug OBJECTIVES: To determine the influence of etanercept treatment on the number of peripheral blood mononuclear cells (PBMC) secreting immunoregulatory key cytokines and the correlation of these cell counts with treatment response in patients with rheumatoid arthritis (RA). METHODS: Nineteen patients with RA were treated with etanercept as monotherapy. Frequencies of PBMC secreting cytokines were determined by ELISPOT analysis before and after 9 months of therapy and compared with values for healthy controls (HC). The clinical outcome was assessed as defined by the ACR criteria. RESULTS: Fifteen patients fulfilled the ACR20, seven patients the ACR50 and two patients the ACR70 criteria. Initially elevated numbers of tumour necrosis factor-alpha- and interleukin (IL)-1beta-secreting PBMC were reduced to HC levels, and normal or low numbers of IL-6- and interferon-gamma (IFN-gamma)-secreting PBMC were reduced below HC levels. The number of IL-10-secreting PBMC did not differ from that in HC and did not change significantly over time. The pretreatment IFN-gamma:IL-10 ratio correlated to reduction in the tender and swollen joint counts. CONCLUSIONS: Long-term treatment with etanercept in patients with RA significantly reduces the numbers of proinflammatory cytokine-secreting PBMC, while the number of IL-10-secreting cells is unaffected. Although the changes described did not affect the safety or efficacy of etanercept therapy, these alterations may account for the long-term systemic effects. The pretreatment IFN-gamma:IL-10 ratio may be of prognostic value in predicting the improvement in joint symptoms.
12913921 Search for correlation of CD8 T cell response to Epstein-Barr virus with clinical status i 2003 Aug OBJECTIVE: To assess in a longitudinal 15 month followup study the CD8 T cell response to immunodominant Epstein-Barr virus (EBV) antigens of 17 patients with rheumatoid arthritis (RA); and to seek an association between these responses and both clinical activity/severity of RA and a qualitative PCR for EBV in peripheral blood. METHODS: At each patient's visit every 3 months: (1) RA activity was assessed for Disease Activity Score (DAS-28); (2) a qualitative PCR for EBV was performed; (3) CD8 T cell response to EBV epitopes was screened in peripheral blood, using an autopresentation assay of 13 EBV peptides previously identified as immunodominant targets in RA synovia. Activation of anti-EBV CD8 T cells was evaluated by measuring the release of tumor necrosis factor-a. RESULTS: The semiquantitative CD8 T cell response to EBV roughly paralleled RA clinical activity in only 4/17 patients. No clear association could be found between positive PCR for EBV (performed at least once in 10/17 patients) and RA activity/severity or fatigue. Reactivity was not qualitatively broader in samples where PCR for EBV proved positive, and most often focused on one or 2 EBV antigens. However, these antigens differed between patients, as did the magnitude of CD8 T cell response to immunodominant antigens at different timepoints for the same patient. CONCLUSION: The CD8 T cell response to EBV paralleled clinical activity in only 4/17 patients. Our pilot study does not support the hypothesis that this CD8 response contributes to RA activity/flares, although the quantitative variations in the pattern of this reactivity over time confirmed that control of EBV manifestations was difficult in most patients with RA.
12375311 Anti-Sa sera from patients with rheumatoid arthritis contain at least 2 different subpopul 2002 Oct OBJECTIVE: Anti-Sa antibodies have been described to be a highly specific marker for rheumatoid arthritis (RA). We demonstrate the existence of 2 different subsets of anti-Sa antibodies, only one of which is specific for RA. Our objective was to purify the Sa antigen, and to achieve partial characterization of these proteins. METHODS: Saline extract and mitochondrial extract from human placenta were used as antigenic sources. Antigens were purified by immunoaffinity chromatography and studied by ELISA and immunoblotting. RESULTS: Three antigenically active bands of 68, 50, and 46 kDa were purified from the saline extract by immunoaffinity chromatography. Two other bands of 29 and 10 kDa that do not react with anti-Sa antibodies were obtained as well. The 68 kDa band was purified from a mitochondrial extract. These bands are not the same as other known mitochondrial autoantigens such as M2, M4, or M9. The amino terminal sequence of the 68 kDa Sa band is DEPKXEVP. The sequence of the 68 kDa Sa band is not compiled in the databases we searched, as either aminoterminal or internal sequence. Antibodies to 50/46 kDa anti-Sa bands detected by immunoblotting were highly specific for RA, while the 68 kDa antigen reacted in ELISA with sera from patients with RA and systemic lupus erythematosus, the latter showing a marked increase in features of RA. Antibodies directed against the 68 and 50/46 kDa Sa bands fluctuated with time, the 50/46 kDa anti-Sa antibodies present during the active period of the disease, and the 68 kDa anti-Sa antibodies during the remission period. CONCLUSION: At least 2 subsets of autoantibodies are present in anti-Sa sera, one directed against a 68 kDa Sa protein and another to the typical 50/46 bands of the Sa system.
14673966 Validation of a rheumatoid arthritis health-related quality of life instrument, the CSHQ-R 2003 Dec 15 OBJECTIVE: To test the validity and reliability of a newly developed disease-specific multidimensional quality of life instrument: the Cedars-Sinai Health-Related Quality of Life Instrument (CSHQ-RA). METHODS: A total of 350 rheumatoid arthritis (RA) patients were asked to complete the CSHQ-RA at 2 time points (4 weeks apart). Patients also completed the Medical Outcomes Study Short Form 36 (SF-36) and the Stanford Health Assessment Questionnaire (HAQ) Disability Index (DI) at the second time point. Construct validity was tested, using Pearson's correlations, by comparing subscale scores on the CSHQ-RA to those obtained from the mental component summary (MCS) and physical component summary (PCS) of the SF-36. HAQ DI scores were used to assess the discriminant validity of the CSHQ-RA. Intraclass correlation coefficients (ICCs) were used to assess test-retest reliability. RESULTS: Response rates for the first and second survey were 83% (291) and 93% (276), respectively; 84% of respondents were women, and mean age was 57 years. Mean scores +/- SDs on instruments were: HAQ 0.73 +/- 0.69; MCS 49 +/- 12; and PCS 33 +/- 11. Pearson's correlations between the CSHQ-RA subscale scores and the SF-36 scores ranged from 0.55 to 0.76 (P < 0.001). Analysis of variance indicate that scores on the CSHQ-RA discriminated between levels of physical disability as measured by the HAQ (P < 0.001). Test-retest reliability was demonstrated in the instrument's subscale scores (ICC 0.70-0.90). CONCLUSION: These results support the construct validity, discriminant validity, and reliability of the CSHQ-RA as a measure that captures the impact of RA on patients' health-related quality of life.
12922953 Scintigraphic detection of tumour necrosis factor in patients with rheumatoid arthritis. 2003 Sep OBJECTIVES: To investigate the biodistribution and specific targeting for tumour necrosis factor (TNF) of a fully human, radiolabelled anti-TNF monoclonal antibody (anti-TNF mAb) in patients with active rheumatoid arthritis (RA). To assess whether this agent is suitable for visualisation of synovitis. METHODS: Ten patients with RA underwent whole body scintigraphy after administration of a tracer-subtherapeutic dose of 100 microg (99m)Tc human anti-TNF mAb. After two weeks, the procedure was repeated to assess the specificity of the radiolabelled antibody for TNF and its sensitivity for changes in inflammation. Therefore, a competition study was performed in five patients, who received excess unlabelled anti-TNF mAb before the tracer dose of (99m)Tc-anti-TNF. Another five patients received 120 mg methylprednisolone two days before the second scintigraphy. RESULTS: Radiolabelled anti-TNF mAb allowed clear visualisation of inflamed joints in patients with active RA with a high specificity. Concomitant administration of excess unlabelled anti-TNF reduced the joint uptake of (99m)Tc-anti-TNF mAb by a median of 25% as a percentage of the injected dose after 24 hours, whereas uptake in liver and spleen remained unchanged. Systemic corticosteroids reduced the disease activity, which was mirrored by a decreased joint uptake of the tracer. The anti-TNF mAb retained its high affinity for TNF alpha after labelling and was cleared from the circulation with an elimination half life of 48 hours. The procedure was well tolerated. CONCLUSIONS: Radiolabelled human anti-TNF mAb allows visualisation of synovitis in patients with RA. Joint accumulation of this agent is partly due to specific TNF targeting and is highly predictive for inflammation.
12114300 Decreased catecholamine-induced cell death in B lymphocytes from patients with rheumatoid 2002 Jun The expression of beta2-adrenergic receptors (beta2-R) on B lymphocytes and agonist-induced cAMP production is reduced in patients with rheumatoid arthritis (RA). To further study functional consequences of the diminished beta2-R density on B lymphocytes in RA patients, agonist-induced cell death was evaluated and compared to healthy controls. B lymphocytes from patients with RA and healthy controls were activated with anti-IgM-antibody. Coincubation was carried out with isoprenaline (iso, 0.001-10 microM). Apoptotic and necrotic cells were determined using Annexin-V and propidium-iodide staining. beta2-R-induced cell death in B cells from healthy volunteers was stimulated after 24 h (medium, 21.2 +/- 1.6%; iso, 34.6 +/- 4.4%; increase 59.3 +/- 10.1%). However, in RA patients the increase in cell death following beta2-R stimulation (21.8 +/- 8.9%) was significantly impaired (p = 0.02). Our data demonstrate that catecholamine-induced cell death after stimulation of beta2-R on B lymphocytes is decreased in RA patients, possibly contributing to the pathogenesis of the disease.
12011369 Anti-tumour necrosis factor (TNF)-alpha therapy (etanercept) down-regulates serum matrix m 2002 May OBJECTIVES: Matrix metalloproteinases (MMPs) are cytokine-modulated enzymes that play an important role in the pathogenesis of rheumatoid arthritis (RA) by inducing bone resorption and cartilage destruction. This study evaluated the modulation of serum and synovial MMPs and their inhibitor, tissue inhibitor of matrix metalloproteinases (TIMP)-1, by therapy with soluble tumour necrosis factor (TNF) alpha receptor (etanercept). METHODS: Serum samples were collected from 60 RA patients at baseline and after 8 or 12 weeks of treatment. Paired synovial biopsies were obtained from 11 patients at two time points, before and after 8 weeks of treatment. We measured serum levels of MMP-1, MMP-3 and TIMP-1 by ELISA. Immunohistological analysis of synovial tissue was performed using monoclonal antibodies specific for MMP-1, MMP-3 and TIMP-1. RESULTS: Etanercept therapy significantly down-regulated serum levels of MMP-3 and MMP-1 in parallel with the reduction in inflammatory parameters (C-reactive protein concentration and erythrocyte sedimentation rate) in RA patients. Baseline pretreatment serum levels of MMP-3 correlated with changes in clinical disease activity during therapy. No consistent changes in serum level of TIMP-1 were observed, while ratios of MMP-1 and MMP-3 to TIMP-1 were down-regulated following etanercept treatment. Immunohistochemical analyses revealed great interindividual variability, with generally a high level of expression of MMP and low expression of TIMP. No significant change in the pattern or number of positive cells occurred during therapy. CONCLUSIONS: In RA patients, etanercept therapy down-regulates serum levels of MMP-3 and MMP-1 and the ratio between MMPs and TIMP-1. This may be an important mechanism for the prevention of future development of joint damage.
11782015 The genetic control of sialadenitis versus arthritis in a NOD.QxB10.Q F2 cross. 2002 Jan The non-obese diabetic (NOD) mouse spontaneously develops diabetes and sialadenitis. The sialadenitis is characterized by histopathological changes in salivary glands and functional deficit similar to Sjögren's syndrome. In humans, Sjögren's syndrome could be associated with other connective tissue disorders, such as rheumatoid arthritis. In the present study the genetic control of sialadenitis in mice was compared to that of arthritis. We have previously reported a NOD locus, identified in an F2 cross with the H2(q) congenic NOD (NOD.Q) and C57BL/10.Q (B10.Q) strains, that promoted susceptibility to collagen-induced arthritis. The sialadenitis in NOD.Q showed a similar histological phenotype as in NOD, whereas no submandibular gland infiltration was found in B10.Q. The development of sialadenitis was independent of immunization with type II collagen and established arthritis. To identify the genetic control of sialadenitis, a gene segregation experiment was performed on an (NOD.QxB10.Q)F2 cross and genetic mapping of 353 F2 mice revealed one significant locus associated with sialadenitis on chromosome 4, LOD score 4.7. The NOD.Q allele-mediated susceptibility under a recessive inheritance pattern. The genetic control of sialadenitis seemed to be unique in comparison to diabetes and arthritis, as no loci associated with these diseases have been identified at the same location.
15163108 Improvement of refractory rheumatoid arthritis after depletion of B cells. 2004 OBJECTIVE: B cells are involved in the pathogenesis of rheumatoid arthritis (RA). To evaluate the effect of therapeutic B-cell depletion for treatment of RA, an open label study has been performed using the B-cell depleting anti-CD20 antibody rituximab. METHODS: Five patients with refractory RA were treated weekly with four infusions of rituximab (375 mg/m2) alone, or in combination with ongoing methotrexate (MTX). Patients were followed for at least 44 weeks and monitored for safety and tolerability of treatment. RESULTS: Treatment could be performed without serious side effects and resulted in peripheral B-cell depletion lasting between 36 weeks up to > 1 year. The follow-up revealed no significant treatment-associated side effects. At 22 weeks, 4/5 patients showed a significant improvement (> 1.2) of the Disease Activity Score (DAS28). The mean DAS28 of all patients declined from 6.2 to 4.1. At 44 weeks there was one drop-out, another patient still had a sustained response, and three patients showed slowly increasing disease activity (mean DAS28 of the remaining four patients: Week 0: 6.0; Week 22: 3.85; Week 44: 5.6). Despite relatively constant immunoglobulin levels, rheumatoid factor levels decreased parallel to disease activity. CONCLUSION: In patients with refractory RA, B-cell depletion with rituximab is safe and well tolerated. A reduction of disease activity could be observed, which eventually deteriorated after B-cell repopulation. The findings give more evidence for B-cell targeted therapies in RA.
12666389 [Oral symptoms of immunologic disorders. Part I. Systemic autoimmune diseases]. 2003 Feb Polysystemic autoimmune diseases often cause orofacial and stomatognathic symptoms. Inflammation of the temporomandibular joint only rarely and slightly reduces the range of mouth opening (rheumatoid arthritis), which is much more restricted in systemic sclerosis due to fibrosis of perioral soft tissues. Weakness of masticatory and pharyngeal muscles in idiopathic inflammatory myopathies results in dysphagia and dystonia. Ulcerations, petechiae, teleangiectasia, and lichenoid lesions are the characteristic symptoms of oral mucosal involvement, but drugs used in systemic treatment can also cause very similar side effects. Salivary gland hypofunction (Sjögren's syndrome) is common, and in addition to the subjective complaints, leads to objective pathologic alterations such as oral mycotic infections, purulent sialadenitis, and increased caries prevalence. The side effects of steroid administration should be taken into account also during dental treatments. Regular dental follow-up and treatment is a basic part of the complex care of these patients in order to diagnose and cure oral abnormalities and salivary gland hypofunction in time. Impairment of hand functions (rheumatoid arthritis, scleroderma) reduces the oral hygienic activity and therefore special devices, local antiseptics and local fluoride preparations are necessary.