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ID PMID Title PublicationDate abstract
15457442 The influence of genetic variation in the HLA-DRB1 and LTA-TNF regions on the response to 2004 Sep OBJECTIVE: To examine the roles of specific genetic polymorphisms as predictors of response to treatment of early rheumatoid arthritis (RA). METHODS: Subjects included 457 patients with early RA (duration of < or =3 years) who participated in a randomized controlled trial comparing weekly methotrexate and 2 dosages of etanercept (10 mg twice weekly and 25 mg twice weekly). Our primary outcome measure was achievement of 50% improvement in disease activity according to the criteria of the American College of Rheumatology (ACR50 response) after 12 months of treatment. Subjects were genotyped for HLA-DRB1 alleles and polymorphisms in the following genes: TNF, LTA, TNFRSF1A, TNFRSF1B, FCGR2A, FCGR3A, and FCGR3B. Univariate and multivariate analyses were performed to define the impact of specific polymorphisms and haplotypes on response to treatment. Covariates for the multivariate analyses included sex, ethnicity, age, disease duration, and baseline values for rheumatoid factor and the tender and swollen joint counts. RESULTS: The presence of 2 HLA-DRB1 alleles encoding the shared epitope (SE) (compared with 1 or 0 copies) was associated with response to treatment with standard-dose etanercept (odds ratio [OR] 4.3, 95% confidence interval [95% CI] 1.8-10.3). Among Caucasian patients, 2 extended haplotypes that included the HLA-DRB1 alleles *0404 and *0101 (both of which encode the SE) and 6 single-nucleotide polymorphisms in the LTA-TNF region were associated with response to treatment. In a multivariate model that included treatment received and the aforementioned covariates, the ORs for the association of these haplotypes with achievement of an ACR50 response at 12 months were 2.5 (95% CI 0.8-7.3) and 4.9 (95% CI 1.5-16.1) for the *0404- and *0101-containing haplotypes, respectively. CONCLUSION: Genetic variation in the HLA-DRB1 and the LTA-TNF regions is significantly associated with response to treatment of early RA. These findings may have clinical application through the identification of patients who are most likely to benefit from treatment with methotrexate or etanercept.
11953970 Local production of complement proteins in rheumatoid arthritis synovium. 2002 Apr OBJECTIVE: Complement has been repeatedly implicated in the pathogenesis of rheumatoid arthritis (RA) based on studies showing reduced levels of native complement components and increased levels of complement metabolites in plasma, synovial fluid (SF), and synovial tissue (ST) of RA patients. However, there is limited information on local production and activation of key factors of the complement cascade in RA synovium and their potential modulation by novel anticytokine therapies. This study was undertaken to characterize the expression of complement proteins and receptors in RA SF and ST. METHODS: Using in situ hybridization, immunohistochemistry, and Western blot techniques, we assessed the presence of complement proteins C3, factor B (FB), and C5b-9, as well as the expression of complement receptors C3aR and C5aR in rheumatoid synovium. C3 and FB levels in SF were determined by enzyme-linked immunosorbent assay. Functional assessment was performed by examining the effects of soluble tumor necrosis factor receptor (sTNFR) p55 gene transfer in the SCID mouse model of RA. RESULTS: Complement proteins and receptors could be localized in all RA synovial specimens, whereas in osteoarthritis (OA) synovium, only a few, single cells expressed complement proteins and receptors. No differences were noted in the concentration of C3 between RA and OA in SF; however, FB levels were markedly reduced in RA versus OA SF. In RA synovium, in contrast to OA synovium, local expression of complement factor and complement receptor messenger RNA was found throughout the various ST compartments, suggesting that activation of the complement cascade occurs in all parts of the rheumatoid synovium. Moreover, C5aR expression was up-regulated following overexpression of sTNFR p55 by adenovirus-based gene transfer. CONCLUSION: In summary, local complement production and activation may play an important role in RA, and specific modulation and inhibition of local complement production could be an attractive therapeutic target for RA.
12832705 Attitude of rheumatoid arthritis patients to treatment with oral corticosteroids. 2003 Oct OBJECTIVE: To assess the attitudes of rheumatoid arthritis (RA) patients to oral corticosteroid treatment, factors influencing these views and their likely clinical impact. METHODS: A cross-sectional survey of 158 consecutive RA out-patients was carried out at two centres over 2 weeks. Demography, disease duration, function [Health Assessment Questionnaire (HAQ)], erythrocyte sedimentation rate (ESR), years of formal education and social deprivation index were noted. Prospective recruitment into the multicentre West of Scotland Early Rheumatoid Arthritis Corticosteroid Trial (WOSERACT) was monitored and reasons for refusal to participate (when available) were noted at three of the centres. RESULTS: Forty-eight (32%) patients were willing to be treated with oral corticosteroid and 100 (68%) were not. The former were older (P = 0.002), had a higher ESR (P = 0.007), poorer function (P = 0.001) and greater previous exposure to disease-modifying anti-rheumatic drugs (P = 0.013). Ninety patients refused to participate in WOSERACT, in 46 cases (40 female, 6 male) the reason being concerns about corticosteroids. CONCLUSIONS: This study shows a high level of concern about and refusal of corticosteroid treatment in RA, due mainly to patient concerns about adverse effects. Rheumatologists need to be aware of these attitudes as they are likely to affect prescribing.
12866040 Association of aspirin and other non-steroidal anti-inflammatory drug use with incidence o 2003 Sep 20 Non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, seem to have chemopreventive properties against several types of cancer, particularly colon cancer. Persons with rheumatoid arthritis, an autoimmune disease for which NSAIDs are used commonly, have been reported to be at lower risk of colon cancer but at elevated risk of non-Hodgkin lymphoma (NHL), raising the possibility that NSAIDs may be a risk factor for NHL. We evaluated the association of use of NSAIDs, arthritis history, and risk of NHL in a prospective cohort of 27,290 postmenopausal women from the state of Iowa. The frequency of use of aspirin and of other NSAIDs excluding aspirin (e.g., ibuprofen), as well as a physician diagnosis of rheumatoid arthritis (RA) or osteoarthritis (OA), were self-reported on a questionnaire mailed in 1992. The incidence of NHL was ascertained through annual linkages to the Iowa SEER Cancer Registry. Relative risks (RR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards regression. Through 7 years of follow-up, 131 cases of NHL were identified. Compared to women who did not use either aspirin or other non-aspirin NSAIDs, women using aspirin exclusively (RR = 1.71; 95% CI = 0.94-3.13), non-aspirin NSAIDs exclusively (RR = 2.39; 95% CI = 1.18-4.83), or both types of drugs (RR = 1.97; 95% CI = 1.06-3.68) were at increased risk of NHL. A diagnosis of RA (RR = 1.75; 95% CI = 1.09-2.79), but not OA (RR = 1.06; 95% CI = 0.67-1.68), was associated with risk of NHL, but the positive association of use of aspirin and other NSAIDs with NHL was independent of RA history. Multivariate adjustment for other NHL risk factors only attenuated slightly these associations, whereas exclusion of cases occurring during the first 2 years of follow-up strengthened the associations. These data suggest that use of NSAIDs, either aspirin or other non-aspirin NSAIDs, are associated positively with risk of NHL, and that this association is independent of RA history.
15122064 Renal disease as a predictor of increased mortality among patients with rheumatoid arthrit 2004 AIMS AND METHODS: Mortality among RA patients and controls was analyzed with special attention to renal disease in population-based material (originally screened in 1988) of 604 patients with RA (470 females, 134 males) and 457 age- and sex-matched controls (352 females, 105 males). In the original RA population, isolated hematuria (HU) was observed in 54, isolated proteinuria (PU) in 27, combined hematuria and proteinuria (HUPU) in 7, chronic renal failure (CRFtot) in 36 and isolated chronic renal failure without HU or PU (CRFisol) in 15 patients. Among the controls, HU was observed in 39, PU in 11, CRFtot in 32 and CRFisol in 16 subjects. HUPU was not observed in any of the controls. Microalbuminuria (20-200 microg/min) was observed in 34 RA patients and in 27 controls. Histologically confirmed amyloidosis was found in 13 RA patients and mesangial glomerulonephritis (MesGN) in 17 patients. The mortality was evaluated in 1999 from data of the Statistical Office of Finland. Statistical analysis was performed by Cox regression analysis. RESULTS: Mortality was significantly increased in the RA population as compared to controls: hazard ratio (HR) 1.78 (95% CI 1.34-2.31) for all RA patients; HR 2.12 (1.52-2.94) for females; HR 1.15 (0.75-1.77) for males. In the RA material, increased mortality was detected in patients with HUPU (HR 4.45; 1.54-12.84), PU (HR 3.54; 1.88-6.65), CRFtot (HR 3.74; 2.55-5.56) or microalbuminuria (HR 2.77; 1.64-4.69) when compared to those with normal clinical renal findings, whereas HU (HR 1.49; 0.88-2.52), CRFisol (HR 1.71; 0.82-3.54), bacteriuria (HR 0.96; 0.35-2.59) or pyuria (HR 0.65; 0.09-4.65) did not predict mortality. Renal amyloidosis was associated with an over twofold mortality rate (HR 2.31; 1.03-5.15), whereas mortality was within expected limits in RA patients with MesGN (HR 1.61; 0.49-5.24). CONCLUSION: Our results show that nephropathy presenting with combined hematuria and proteinuria, proteinuria, microalbuminuria or histologically confirmed amyloidosis is associated with increased mortality in RA patients, whereas mortality is within expected limits in those with isolated hematuria or mesangial glomerulonephritis.
12695154 Autoantibodies can be prognostic markers of an erosive disease in early rheumatoid arthrit 2003 May OBJECTIVE: To evaluate a contribution of selected laboratory parameters for a prediction of progressive and erosive development in patients with early rheumatoid arthritis (RA). METHODS: In a prospective study baseline levels of antibodies to cyclic citrullinated peptide (anti-CCP), IgM, IgA, and IgG rheumatoid factors (RFs) were measured by enzyme linked immunosorbent assay (ELISA) in 104 patients with RA with disease duration <2 years. Antikeratin antibodies (AKA) and antiperinuclear factor (APF) were detected by indirect immunofluorescence. Patients were divided into two groups based either on the presence or absence of erosions or according to progression of Larsen score at the end of the 24 months' follow up. RESULTS: Sixty seven (64%) patients developed radiographic erosions, 49 (47%) had progression in Larsen score, and 36 (35%) progressed by more than 10 Larsen units. Significant differences in erosions and progression between the two groups were detected for anti-CCP, AKA, APF, IgM RF, IgA RF, and IgG RF. Baseline Larsen score correlated significantly with anti-CCP, IgM RF, and IgA RF levels, and all measured antibodies correlated with the progression >10 units. The combination of anti-CCP and IgM RF increased the ability to predict erosive and progressive disease. CONCLUSION: The data confirmed that measurement of anti-CCP, AKA, APF, and individual isotypes of RFs was useful for prediction of structural damage early in the disease course. Combined analysis of anti-CCP and IgM RF provides the most accurate prediction.
15287272 Functional ability, social support, and depression in rheumatoid arthritis. 2004 Aug OBJECTIVE: First, to investigate the patterns of functional ability, depressive feelings, and social support in early stage rheumatoid arthritis (RA) patients. Second, to demonstrate the stress buffering effect of social support. Social support is thought to reduce the impact of chronic stress on psychological well-being; for patients without social support the impact of functional ability on depressive feelings will be stronger. METHODS: In 4 waves with an intervening period of 1 year, longitudinal data was collected of 264 Dutch RA patients, of which 65% was female. At T1, the mean age of these patients was 53 years, while their mean disease duration was 22 months. In an interview at the patients' homes, data was collected on functional ability, social support en psychological well-being. The buffering effect of social support was examined by testing the significance of the (computed) stressor by social support interaction term in a regression analysis on depressive feelings. RESULTS: Although large differences between subjects existed, the mean scores on functional ability, social support, and depressive feelings barely changed from year to year. Patients who deteriorated in functional ability during one year had the best chances to improve next year, and visa versa. Furthermore, the stress by support interaction terms had no significant effect on depressive feelings in a regression analysis. CONCLUSIONS: This study demonstrated clearly the fluctuating pattern of RA in the first years after onset. The patients' level of depressive feelings was linearly related to the level of functional ability. Like many other studies, also this study could not provide evidence for the stress buffering effect of social support.
14760789 Patient questionnaires and formal education level as prospective predictors of mortality o 2004 Feb OBJECTIVE: To prospectively analyze patient questionnaire scores concerning functional disability as well as formal education level as potential predictors of premature mortality over 10 years in 1416 patients with rheumatoid arthritis (RA) from 15 private practice rheumatology settings in 11 diverse cities in the United States. METHODS: At baseline in 1985 and periodically over 10 years, patients completed mailed self-report multidimensional health assessment questionnaires (MDHAQ) that included functional disability scores, formal education level, and other demographic and clinical data. Vital status was determined 10 years after baseline. Potential predictors of 10 year mortality were analyzed using descriptive statistics and Cox proportional hazards models. RESULTS: Vital status was accounted for in 1378 patients, 97.3% of the cohort. The standard mortality ratio was 1.6, similar to most reported series of patients with RA, as 401 patients died versus 251 expected over 10 years. Evidence of "dose-response" relations was seen for age, formal education level, functional disability scores, and helplessness scores as predictors of mortality. In Cox proportional hazards models, age, sex, formal education level, functional disability, and helplessness scores remained significant independent predictors of 10 year mortality. CONCLUSION: Functional disability and low formal education level are significant predictors of premature mortality in people with RA under care in US private practice settings, as in most reported cohorts of patients with RA. This study shows that it is possible to account for more than 95% of patients over 10 years using mailed questionnaires to monitor patient status.
11858354 Second-line drugs used in recent-onset rheumatoid arthritis in Brittany (France). 2002 Jan OBJECTIVE: The management of recent-onset rheumatoid arthritis (RA) is not well standardized. We conducted a survey of drugs prescribed to RA patients in Brittany at presentation and during the first 1 to 3 years of follow-up. METHODS: A cohort of 270 patients with recent-onset inflammatory joint disease was recruited between 1995 and 1997. The evaluation at presentation included a medical history, a thorough physical examination, and a standard battery of investigations. Follow-up at 6-month intervals was offered. At the last visit, between June and December 1999, a panel of five rheumatologists established that 98 patients had RA. RESULTS: At presentation, hydroxychloroquine and injectable gold were the most widely used second-line drugs, and only two patients were offered a combination of second-line drugs. At the last visit, the most commonly used drugs were methotrexate, injectable gold, and hydroxychloroquine (23, 23, and 21 patients, respectively); only three patients were on more than one second-line drug and 38 (38/98, 39%) patients were on glucocorticoid therapy. CONCLUSION: Rheumatologists in Brittany prefer monotherapy with hydroxychloroquine or injectable gold as the initial treatment. Later, they rely mainly on methotrexate, injectable gold, and hydroxychloroquine, often in combination with glucocorticoid therapy.
11879250 Development of cellulose-DNA immunoadsorbent. 2002 Feb The aim of this study was to prepare a DNA immunoadsorbent for the specific, extracorporeal removal of anti-DNA antibodies from the blood of patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Two kinds of cellulose beads were applied as a carrier. Calf thymus DNA was covalently coupled to the carrier using the epichlorohydrin method. Efforts were focused on optimization of conditions for activation and coupling, trying to couple as much DNA as possible to a certain amount of carrier. It was found that the activation level increased with the increase of NaOH concentration and the amount of epichlorohydrin used. The mole of epichlorohydrin must be in excess of that of NaOH because excess NaOH could react further with the epoxy groups in the beads resulting in a decrease of activation level. High activation level could be obtained in a medium of 3.0 M NaOH. The DNA coupling was found to be mainly temperature and pH dependent. Using 0.1 M Tris-HCl buffer, pH 8 at a temperature of 50-90 degrees C, more than 3 mg of DNA could be coupled to 1 ml of wet beads. Prolonging the coupling reaction under 50 degrees C to 72 h resulted in the same coupling capacity as that obtained under 90 degrees C. To evaluate the adsorption ability for anti-DNA of this immunoadsorbent, batch and circulation tests were applied using SLE patient plasma. The immunoadsorbents showed excellent adsorption capacity, especially the cellulose with smaller size (200-300 microm). The incubation of 20 ml of patient's plasma with 1 ml of adsorbent resulted in an 80% decline in the anti-DNA antibody level. In the circulation tests, 30 ml of plasma was circulated through a column containing 3 ml of adsorbent. The maximum decline in anti-DNA level, 80%, was obtained after 60 min. Such high adsorption capacity and high adsorption rate suggest this immunoadsorbent may be used for treatment. For comparison, 1,4-butanediol diglycidyl ether activation method and other DNA sources were tested with the same protocol.
12772099 Longitudinal radiographic analysis of rheumatoid arthritis in the hand and wrist. 2003 May PURPOSE: To assess the longitudinal radiographic osseous changes of the wrist and hand other than interphalangeal joints in rheumatoid disease. METHODS: Serial wrist and hand x-rays in 96 patients with long-standing rheumatoid disease were reviewed. The average number of years between initial and most recent x-rays was 15.1. The Larsen scoring system was used to assess the degree and severity of joint involvement. We identified patterns of involvement in the wrist, thumb, and finger metacarpophalangeal (MCP) joints. RESULTS: The radioscaphoid and radiolunate joints had the earliest and most severe progression of all joints studied. Scaphoid erosions often were seen early (27%) and their presence was a predictor of progressive involvement. Ulnar styloid erosions commonly were seen as early isolated findings (25%). The distal radioulnar joint showed a rapid increase in Larsen score and was involved in 78% of patients on late x-rays. The thumb showed considerable late MCP joint disease that often led to boutonniere deformity and the trapeziometacarpal joint had the least rate of progression of all joints studied. The most severely and frequently involved MCP joints were the radial (index and middle), which also had the greatest increase in score over the span of the study. Finger MCP joint disease was observed to progress temporally in a predictable pattern: first radial MCP joints of the dominant hand, followed by the nondominant radial MCP joints, and last the ulnar MCP joints of the nondominant hand with small finger involvement preceding that of the ring finger. Of all MCP joints, the ring finger was least affected. CONCLUSIONS: This study clarified the longitudinal osseous radiographic changes of the wrist and hand (excluding interphalangeal joint) in rheumatoid disease.
12923291 A survey of British rheumatologists' DMARD preferences for rheumatoid arthritis. 2004 Feb OBJECTIVE: To determine the current disease-modifying anti-rheumatic drug (DMARD) preferences of UK consultant rheumatologists. METHODS: A questionnaire was sent in May 2002. We asked which DMARD(s) was most frequently preferred first and sought the most typical sequence of DMARDs, including DMARD combinations. Also we determined the extent to which prognostic and other factors influenced treatment choices. Comments were invited, written responses abstracted and key themes identified. RESULTS: After two mailings, 331 (of 460; 72%) suitable questionnaires were returned. Ninety-five per cent (315/331) preferred methotrexate (154, 46.5%) or sulphasalazine (144, 43.5%) or either of these two (17, 5%) as first-choice agent. Of those who chose methotrexate first, 80% (123/154) ranked sulphasalazine second, 45% (55/123) combined sulphasalazine and methotrexate and 49% (27/55) then added hydroxychloroquine to this combination, in active disease. Of those who chose sulphasalazine first, 95% (137/144) ranked methotrexate second, 75% (113/150) preferring methotrexate monotherapy and 12% (18/150) the combination with sulphasalazine. Rheumatologists who preferred sulphasalazine first more commonly used subsequent DMARDs singly than those who started with methotrexate (P < 0.0001). Leflunomide was more commonly preferred than intramuscular gold as third choice (52/145 vs 29/145; P < 0.003). The most popular sequence of DMARDs was methotrexate or sulphasalazine, singly or in combination, leflunomide, intramuscular gold and anti-tumour necrosis factor therapy. Poor prognostic factors influenced DMARD choice, but patient occupation and drug costs did not. CONCLUSION: Methotrexate has displaced other DMARDs, especially sulphasalazine, as agent of first choice and newer agents have displaced older DMARDs. Whether the expressed preference for particular DMARDs accurately reflects actual use, and is optimal in rheumatoid arthritis, remains to be determined.
12105679 [The role of interleukin-12 in immune-mediated rheumatic diseases]. 2002 Apr OBJECTIVE: IL-12 is a proinflammatory cytokine produced by different antigen presenting cells. It has been shown to exert a critical role in inducing Th1 phenotype, thus initiating cell-mediated immune responses, but the significance of IL-12 in rheumatic diseases is not clear. Aim of the study was to determine IL-12 serum levels in immune rheumatic diseases and to analyse the relationship of this cytokine with main clinical and laboratory parameters. METHODS: We analysed, by ELISA, serum IL-12 levels in 114 patients with SLE, 47 with SS, 32 with SSc, 84 with RA, 138 with PA and in 17 healthy controls. We also examined main clinical and laboratory parameters, including autoantibody profile and clinical indices of disease activity. RESULTS: IL-12 serum levels were significantly higher in SLE and SS patients respect to controls. IL-12 serum levels were significantly higher in SLE patients compared to those affected by RA, PA and SSc. When we evaluated disease activity in SLE patients, we found significantly higher IL-12 serum levels in subjects with fever or in those without renal involvement, while no correlation was found in the other rheumatic immune diseases. CONCLUSIONS: These findings suggest that IL-12, modulating cell and humoral immune responses, is involved in the pathogenesis of immune rheumatic diseases, such as SLE and SS.
11974902 [Two fatal cases of methotrexate-induced interstitial pneumonitis]. 2002 Mar We report two cases of methotrexate-induced pneumonitis. Both patients died despite steroid pulse therapy. Postmortem lung tissue revealed diffuse alveolar damage, and focal lung fibrosis. Physicians should be aware of the possibility of MTX-induced interstitial pneumonitis in diagnosing RA patients with MTX when diffuse pulmonary infiltration is present.
12868241 [The role of the conventional drugs in the treatment of rheumatoid arthritis]. 2003 Jul Rheumatoid arthritis (RA), the most frequent systemic connective tissue disease, is characterized by polyarticular symmetric chronic synovitis. It is generally a progressive disease with radiographic evidence of joint damage, functional status decline and premature mortality. Pharmacologic therapy for RA often consists of combination of non steroidal antiinflammatory drugs (NSAIDs), glucocorticoids and disease modifying antirheumatic drugs (DMARDs). Although NSAIDs and glucocorticoids may alleviate symptoms, joint damage may continue to occur and to progress. DMARDs should have the potential to reduce or prevent joint damage, preserve joint function and achieve remission. Many efforts have been taken in the past years to standardize the assessment of RA aiming at making study results comparable. Response criteria have been developed by the American College of Rheumatology and the European League against Rheumatism. These criteria have permitted the evaluation of the efficacy of the old and new therapies. The first one have been illustrated in this review. The second one will be treated in a next article.
15319533 Synovial fibroblasts from rheumatoid arthritis patients differ in their regulation of IL-1 2004 BACKGROUND: In rheumatoid arthritis (RA), synovial fibroblast-like cells (SF) contribute significantly to articular inflammation. They express distinct patterns of genes associated with cell proliferation and differentiation and elevated levels of cytokines and chemoattractant factors, including IL-16. Here we investigated pathways regulating IL-16 expression in fibroblasts from RA patients in comparison to fibroblasts from osteoarthritis (OA) patients. METHODS: Fibroblasts were isolated from dermal and articular biopsies, expanded and pathways of IL-16 induction were investigated by real time quantitative RT/PCR, immuno blot and ELISA. RESULTS: Stimulation of cAMP dependent signal transduction by forskolin induced prominent IL-16 RT/PCR signals in OA-DF and OA-SF. In contrast, in RA-DF and RA-SF staurosporine significantly augmented IL-16 RT/PCR signals, but forskolin induced less IL-16 transcript amounts. Activation of protein kinase C by PMA induced a significant IL-16 response only in RA-SF. Addition of IL-1beta or TNF-alpha did not upregulate IL-16 mRNA but secretion of the mature IL-16 cytokine was activated in serum starved cells in presence of IL-1beta. CONCLUSION: Our results suggest that RA fibroblasts differ from OA fibroblasts with respect to their sensitivities to kinase/phospatase signal transduction pathways. The enhanced expression of IL-16 in the synovial membrane early in RA vs OA may be associated in part with these distinct signaling responses.
12421102 Diagnosis and management of psoriatic arthritis. 2002 Psoriatic arthritis (PsA) is considered to be one of the spondyloarthritides, and as such has both spinal and peripheral joint involvement. In 80% of patients, psoriasis usually precedes the development of arthritis. Although there are no widely accepted diagnostic criteria, a number of distinct clinical features allow it to be distinguished from other forms of inflammatory arthritis. It affects both sexes equally, and the pattern of joint involvement is characteristic with distal interphalangeal joint involvement, asymmetry, dactylitis, flail or ankylotic deformities of digits, and the frequent presence of enthesitis and spinal involvement. It may have a pattern of joint involvement similar to rheumatoid arthritis (RA) but in these patients rheumatoid factor and the other systemic features of RA are usually absent. Radiographs frequently reveal evidence of asymmetric sacroiliitis and spinal disease, and peripheral joints, as well as showing erosions, may also demonstrate profuse new bone formation and ankylosis. Profound osteolysis producing the pencil-in-cup deformity can also occur in the same individual. It is now recognised that PsA can be a destructive arthritis with an increased morbidity and mortality. Studies of standard disease-modifying therapies have been small and frequently inconclusive because of a high placebo response rate. This may be as a result of heterogeneity in patient selection, poor assessment tools, or the difference in underlying pathogenesis and subsequent response to therapy. In meta-analyses, sulfasalazine and methotrexate have been shown to be effective. Treating the skin alone seems to have little impact on joint disease, and the relationship between skin and joints is still unclear. However, recent studies with anti-tumour necrosis factor agents, such as etanercept and infliximab, have shown considerable significant clinical benefit and provided the hope that we will at last have effective therapies for this disease.
15476220 Histone deacetylase inhibitor suppression of autoantibody-mediated arthritis in mice via r 2004 Oct OBJECTIVE: To examine whether depsipeptide (FK228), a histone deacetylase (HDA) inhibitor, has inhibitory effects on the proliferation of synovial fibroblasts from rheumatoid arthritis (RA) patients, and to examine the effects of systemic administration of FK228 in an animal model of arthritis. METHODS: Autoantibody-mediated arthritis (AMA) was induced in 19 male DBA/1 mice (6-7 weeks old); 10 of them were treated by intravenous administration of FK228 (2.5 mg/kg), and 9 were used as controls. The effects of FK228 were examined by radiographic, histologic, and immunohistochemical analyses and arthritis scores. RA synovial fibroblasts (RASFs) were obtained at the time of joint replacement surgery. In vitro effects of FK228 on cell proliferation were assessed by MTT assay. Cell morphology was examined by light and transmission electron microscopy. The effects on the expression of the cell cycle regulators p16INK4a and p21(WAF1/Cip1) were examined by real-time polymerase chain reaction and Western blot analysis. The acetylation status of the promoter regions of p16INK4a and p21(WAF1/Cip1) were determined by chromatin immunoprecipitation assay. RESULTS: A single intravenous injection of FK228 (2.5 mg/ml) successfully inhibited joint swelling, synovial inflammation, and subsequent bone and cartilage destruction in mice with AMA. FK228 treatment induced histone hyperacetylation in the synovial cells and decreased the levels of tumor necrosis factor alpha and interleukin-1beta in the synovial tissues of mice with AMA. FK228 inhibited the in vitro proliferation of RASFs in a dose-dependent manner. Treatment of cells with FK228 induced the expression of p16INK4a and up-regulated the expression of p21(WAF1/Cip1). These effects of FK228 on p16INK4a and p21(WAF1/Cip1) were related to the acetylation of the promoter region of the genes. CONCLUSION: Our findings strongly suggest that systemic administration of HDA inhibitors may represent a novel therapeutic target in RA by means of cell cycle arrest in RASFs via induction of p16INK4a expression and increase in p21(WAF1/Cip1) expression.
15020337 Increased levels of antibodies to cytokeratin 18 in patients with rheumatoid arthritis and 2004 Apr OBJECTIVE: To determine whether raised levels of antibodies to CK18 in patients with RA are associated with ischaemic heart disease (IHD). METHODS: IgA, IgG, and IgM antibodies to CK18 were measured by enzyme linked immunosorbent assay (ELISA) in patients with RA with (n = 34) or without (n = 28) IHD. The relationship between CK18 antibody levels and markers of inflammatory and/or cardiovascular disease was examined. RESULTS: Initial analysis showed that IgG antibody levels to CK18 were higher in patients with RA with IHD than in those without (50.1 v 34.5 AU, p = 0.047), although significance was lost after correction for multiple comparisons. Further analysis showed a significant difference (p = 0.015) between patients with IHD and a positive family history, and patients without IHD and a negative family history (53.7 v 29.0 AU, Kruskal-Wallis multiple comparison Z value test). There was also a significant trend of increasing 10 year cardiovascular risk with increasing CK18 IgG antibody levels (p = 0.01). No association was found between CK18 antibody levels and conventional markers of inflammation or cardiovascular disease, but an association was found between levels of CK18 IgG and IgG antibodies to cytomegalovirus (CMV) (Spearman's r(s) = 0.379, p(corr) = 0.04). No evidence for cross reactivity of CK18 antibodies with CMV antigens was found. CONCLUSION: Levels of IgG antibodies to CK18 are raised in patients with RA with IHD, particularly if they also have a positive family history. This may reflect damage to CK18 containing cells in the cardiac vasculature and/or in atherosclerotic plaques, and may be a useful additional marker for the identification of patients with, or likely to develop, IHD.
11994687 [New nonsteroidal antiinflammatory drugs in rheumatoid arthritis]. 2002 Feb Cyclooxygenase functions Fundamental aspects of coxibs Efficacy of coxibs in rheumatoid arthritis Tolerance to coxibs Conclusion