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ID PMID Title PublicationDate abstract
23465990 Diagnosis of early-stage rheumatoid arthritis: usefulness of unenhanced and gadolinium-enh 2013 Mar Forty-one consecutive unclassified arthritis patients with polyarthralgia including wrist joint were evaluated with 3-T MRI as possible early-stage rheumatoid arthritis (RA). After prospective follow-up, 21 of 41 patients fulfilled the American College of Rheumatology (ACR) criteria. Synovitis was detected in all 21 RA patients (sensitivity=100%) with postcontrast MRI and in 14 patients (67%) with unenhanced MRI when none of them fulfilled ACR diagnostic criteria. Fat-suppressed intermediate-weighted fast spin-echo (FSE) image showed high detection rate of synovitis and bone erosion, whereas FIESTA image clearly delineated joint fluid and bone trabeculae. MRI at 3 T is a potentially powerful tool for discriminating and managing early-stage RA patients.
21710217 [Endoprostheses of the hip joint]. 2011 Jul In many cases rheumatoid arthritis leads to functional disturbances and deformities of the hip joint despite intensive conservative treatment. Joint replacement becomes necessary to preserve mobility and independence. The choice of implant and fixation system depends on the results of clinical and radiological examinations and the individual patient situation (e.g. age, bone quality, deformities of adjacent joints). The procedure, pre-operative and postoperative treatment, all require special expertise. If possible surgical procedures should be carried out in specialized surgical institutions by surgeons experienced in rheumatology and orthopedics.
21935726 Morning stiffness of the joints is the sole predictor of short-term response to glucocorti 2012 Dec Several studies show that the application of oral glucocorticoids in patients with active RA leads to fast resolution of disease activity. Treatment strategies that include the initial application of glucocorticoids seem to have a favourable outcome in terms of long-term control of disease activity. Moreover, when tapered down to low doses, glucocorticoids show disease-modifying actions such as the inhibition of progression of structural damage to the inflamed joints. The goal of this study was to examine the predictors of short-term response to intermediate-dose glucocorticoids in patients with active RA.
22941456 [Inflammatory rheumatic diseases in the elderly: rheumatoid arthritis and polymyalgia rheu 2012 Sep Inflammatory rheumatic diseases with first onset in advanced age have some specific clinical features. Late-onset rheumatoid arthritis and polymyalgia rheumatica/giant cell arteriitis are the most relevant rheumatic diseases among older patients. They are characterized by acute onset, early functional impairment, and difficult differential diagnosis. First-line therapy usually consists of glucocorticoids. During long-term therapy, a spectrum of immunosuppressive agents and biologicals can also be used in elderly patients.
22417670 TNFα modulates protein degradation pathways in rheumatoid arthritis synovial fibroblasts. 2012 Mar 14 INTRODUCTION: Rheumatoid arthritis (RA) is a chronic inflammatory and destructive disease of the joint. The synovial lining consists of two main types of cells: synovial fibroblasts and macrophages. The macrophage-derived cytokine TNFα stimulates RA synovial fibroblasts to proliferate and produce growth factors, chemokines, proteinases and adhesion molecules, making them key players in the RA disease process. If proteins are not correctly folded, cellular stress occurs that can be relieved in part by increased degradation of the aberrant proteins by the proteasome or autophagy. We hypothesized that the activity of the protein degradation pathways would be increased in response to TNFα stimulation in RA synovial fibroblasts compared with control fibroblasts. METHODS: Endoplasmic reticulum (ER) stress markers were examined in synovial fibroblasts by immunoblotting and PCR. Use of the autophagy and proteasome protein degradation pathways in response to TNFα stimulation was determined using a combination of experiments involving chemical inhibition of the autophagy or proteasome pathways followed by immunoblotting for the autophagy marker LC3, measurement of proteasome activity and long-lived protein degradation, and determination of cellular viability. RESULTS: RA synovial fibroblasts are under acute ER stress, and the stress is increased in the presence of TNFα. Autophagy is the main pathway used to relieve the ER stress in unstimulated fibroblasts, and both autophagy and the proteasome are more active in RA synovial fibroblasts compared with control fibroblasts. In response to TNFα, the autophagy pathway but not the proteasome is consistently stimulated, yet there is an increased dependence on the proteasome for cell viability. If autophagy is blocked in the presence of TNFα, an increase in proteasome activity occurs in RA synovial fibroblasts but not in control cells. CONCLUSIONS: TNFα stimulation of synovial fibroblasts results in increased expression of ER stress markers. Survival of synovial fibroblasts is dependent on continuous removal of proteins by both the lysosome/autophagy and ubiquitin/proteasome protein degradation pathways. Both pathways are more active in RA synovial fibroblasts compared with control fibroblasts. These results may provide a better understanding of the mechanism of TNFα on prolonging the survival of synovial fibroblasts in RA tissue.
23052555 [Postoperative treatment strategies after rheumatic orthopedic operations of the shoulder. 2012 Oct Although surgical treatment of rheumatoid patients is quite common for disorders of the shoulder, less is known about the efficacy of the postoperative regimens. Clear therapeutic standards are still missing; however, without systematic and intensive postoperative physical therapy, a good postoperative outcome cannot be achieved. This article shows our postoperative treatment regimens and describes our preferred techniques in physical therapy.
20685609 Estrogens in rheumatoid arthritis; the immune system and bone. 2011 Mar 15 Rheumatoid arthritis (RA) is an autoimmune disease that is more common in women than in men. The peak incidence in females coincides with menopause when the ovarian production of sex hormones drops markedly. RA is characterized by skeletal manifestations where production of pro-inflammatory mediators, connected to the inflammation in the joint, leads to bone loss. Animal studies have revealed distinct beneficial effects of estrogens on arthritis, and a positive effect of hormone replacement therapy has been reported in women with postmenopausal RA. This review will focus on the influence of female sex hormones in the pathogenesis and progression of RA.
23200066 Aging mechanisms in arthritic disease. 2012 Nov Arthritic disease is one of the most common age-related pathologies worldwide. The erosion of cartilaginous tissues from articular surfaces within the joint and the failure to efficiently repair and regenerate this region with age lead to debilitating joint destruction, severe pain, and a crippling loss of function. In addition to the accumulative damage brought about by years of mechanical forces acting upon this region of tissue, there are also defects in underlying biological mechanisms which predispose the older population to excessive joint erosion. This occurs as aberrations in normal chondrocyte biology lead to a reduction in crucial matrix proteins and inhibitory molecules, and elevated production of destructive enzymes. The end result is an accelerated loss of articular cartilage and increased erosion of the joint. As a significant global link exists between aging and the onset of arthritis, this review will consider whether factors known to affect lifespan may also play a role in arthritic disease.
21914216 Improved responsiveness and reduced sample size requirements of PROMIS physical function s 2011 INTRODUCTION: The Health Assessment Questionnaire Disability Index (HAQ) and the SF-36 PF-10, among other instruments, yield sensitive and valid Disability (Physical Function) endpoints. Modern techniques, such as Item Response Theory (IRT), now enable development of more precise instruments using improved items. The NIH Patient Reported Outcomes Measurement Information System (PROMIS) is charged with developing improved IRT-based tools. We compared the ability to detect change in physical function using original (Legacy) instruments with Item-Improved and PROMIS IRT-based instruments. METHODS: We studied two Legacy (original) Physical Function/Disability instruments (HAQ, PF-10), their item-improved derivatives (Item-Improved HAQ and PF-10), and the IRT-based PROMIS Physical Function 10- (PROMIS PF 10) and 20-item (PROMIS PF 20) instruments. We compared sensitivity to detect 12-month changes in physical function in 451 rheumatoid arthritis (RA) patients and assessed relative responsiveness using P-values, effect sizes (ES), and sample size requirements. RESULTS: The study sample was 81% female, 87% Caucasian, 65 years of age, had 14 years of education, and had moderate baseline disability. All instruments were sensitive to detecting change (< 0.05) in physical function over one year. The most responsive instruments in these patients were the Item-Improved HAQ and the PROMIS PF 20. IRT-improved instruments could detect a 1.2% difference with 80% power, while reference instruments could detect only a 2.3% difference (P < 0.01). The best IRT-based instruments required only one-quarter of the sample sizes of the Legacy (PF-10) comparator (95 versus 427). The HAQ outperformed the PF-10 in more impaired populations; the reverse was true in more normal populations. Considering especially the range of severity measured, the PROMIS PF 20 appears the most responsive instrument. CONCLUSIONS: Physical Function scales using item improved or IRT-based items can result in greater responsiveness and precision across a broader range of physical function. This can reduce sample size requirements and thus study costs.
22438290 Association between socioeconomic status, learned helplessness, and disease outcome in pat 2012 Aug OBJECTIVE: Independent investigations have shown that socioeconomic status (SES) and learned helplessness (LH) are associated with poor disease outcome in patients with rheumatoid arthritis (RA). Our aim was to investigate the cross-sectional relationship between SES, LH, and disease outcome in patients with recent-onset inflammatory polyarthritis (IP), the broader group of conditions of which RA is the major constituent. METHODS: SES was measured using the Index of Multiple Deprivation 2007 for 553 patients consecutively recruited to the Norfolk Arthritis Register. Patients also completed the Rheumatology Attitudes Index, a measure of LH. SES and LH were investigated as predictors of disease outcome (functional disability [Health Assessment Questionnaire (HAQ)] and disease activity [Disease Activity Score in 28 joints]) in a regression analysis, adjusted for age, sex, and symptom duration. The role of LH in the relationship between SES and disease outcome was then investigated. RESULTS: Compared to patients of the highest SES, those of the lowest SES had a significantly worse outcome (median difference in HAQ score 0.42; 95% confidence interval [95% CI] 0.08, 0.75). Compared to patients with normal LH, patients with low LH had a significantly better outcome and patients with high LH had a significantly worse outcome (median difference in HAQ score 1.12; 95% CI 0.82, 1.41). There was a significant likelihood that LH mediated the association between SES and disease outcome (P = 0.04). CONCLUSION: LH is robustly associated with cross-sectional disease outcome in patients with IP, and appears to mediate the relationship between SES and disease outcome. As LH is potentially modifiable, these findings have potential clinical implications.
21706387 Recurrent infections in a rheumatoid arthritis patient with a primary immunodeficiency, tr 2012 Apr A 64-year-old woman with longstanding rheumatoid arthritis suffered from recurrent severe infections after treatment with both synthetic and biologic disease-modifying anti-rheumatic drugs (DMARDs). She was found to have mannose-binding lectin (MBL) deficiency. MBL deficiency is associated with increased risk of infections, in particular in individuals treated with immunomodulating drugs. Patients with a history of recurrent infections in childhood, and severe infections after treatment with synthetic or biologic DMARDs, should be tested for MBL deficiency.
22882220 Current treatments of rheumatoid arthritis: from the 'NinJa' registry. 2012 Jul In this review, recent changes in both treatments and outcomes of rheumatoid arthritis (RA) in Japan were analyzed by viewing the National Database of Rheumatic Diseases by iR-net, one of the largest clinical databases for RA patients in Japan. Regarding drug therapy, the use of methotrexate has been continuously increasing and has established a place as an anchor drug in the treatment of RA among other nonbiologic disease-modifying antirheumatic drugs; however, the dosage used is still significantly less compared with that of western countries. In addition to methotrexate, the use of tacrolimus has increased gradually. The most prominent observed change is a rapid increase in the use of biologics, which rose to stardom in the treatment of RA in Japan and western countries. These changes in drug therapy could allow us to control RA disease activity more tightly. In line with this, the outcomes of patients with RA in Japan have been improving continuously, both clinically and functionally. Subsequently, the use of both NSAIDs and corticosteroids has decreased. In addition, overall rates of joint operations related to RA have also decreased; in particular, a significant decrease was noticed in the incidence of joint replacement and synovectomy. Overall, the trends in treatments and subsequent outcomes for RA in Japan have exactly followed those seen in western countries.
22709490 A study of the prevalence of sicca symptoms and secondary Sjögren's syndrome in patients 2012 Jun AIM: To examine the prevalence of sicca symptoms and secondary Sjögren's syndrome (sSS) in rheumatoid arthritis (RA) patients, and the impact of sSS on disease activity and treatment profile in RA patients. METHODS: Three hundred and seven RA patients responding positive to at least one of the questions in a questionnaire about sicca symptoms, were examined by Schirmer I test for tear production, and unstimulated whole saliva collection (USWC). Secondary Sjögren's syndrome was defined by at least one subjective sicca symptom, in addition to a positive Schirmer I test and positive USWC. RESULTS: Among the 307 RA patients, 86 (28%) responded positive to at least one question about sicca symptoms, and 11 patients were positive for both Schirmer I and USWC tests, giving a minimum prevalence of sSS at 3.6%. There were no differences in RA patients with and without sSS regarding age, sex, disease duration, disease activity score (DAS-28) and seropositivity for anti-cyclic citrullinated protein. RA patients with sSS had a tendency for higher numbers of tender and swollen joints and pain. None of the RA patients treated with tumor necrosis factor (TNF) inhibitors had sSS, compared to 22% of the rest of the RA population studied. The treatment of the RA patients with and without sSS was not different. CONCLUSION: Among the 307 RA patients, 28% had at least one sicca symptom. The estimated minimum of prevalence of sSS in 307 RA patients was 3.6%. Secondary Sjögren's syndrome was not found in RA patients treated with biologics such as TNF blockers.
21539939 Cardiovascular safety of anti-TNF-alpha therapies: facts and unsettled issues. 2011 Aug Tumor necrosis factor alpha (TNFa) plays a central role in the pathogenesis of both rheumatoid arthritis (RA) and heart failure (HF). Over the last years RA could benefit from TNFa inhibitors that mitigated disease activity, decreased structural damage, and prevented cardiovascular events. Contraindications to clinical use of TNFa inhibitors may include infections, autoimmune disorders, demyelinating disease, cancer, and heart failure. Overall, these pathological conditions do not appear to increase significantly during treatment with TNFa antagonists compared to placebo. Clinical trials probed these drugs in non RA HF patients produced disappointing results and formed the basis to contraindicate TNFa inhibitors in patients with moderate-severe HF. Although National Registries provide apparently encouraging data about HF safety of anti-TNFa therapies, they cannot adequately assess the actual risk, as these drugs are administered to patients with no cardiac dysfunction. These findings introduced a "rheumatological dilemma" in the clinical management of RA with anti-TNFa. Probably, in RA patients anti-TNFa agents would intercept TNFa and prevent its toxic effects on heart function, while in patients with advanced heart damage (NYHA class III-IV HF), anti-TNFa agents would interfere with the beneficial preconditioning effects of TNFa.
21557184 [Obesity has a protective effect on radiographic joint damage in rheumatoid arthritis]. 2011 May BACKGROUND: Obesity is a state of chronic low-grade inflammation that predisposes people to several diseases and that is increasingly prevalent. Rheumatoid arthritis (RA) is marked by the presence of proinflammatory cytokines and, in general, the presence of high levels of inflammatory markers is associated with a severe disease course and joint damage. AIM: To assess the impact of obesity on disease activity, quality of life and articular damage in patients with established RA. METHODS: Between July 2009 to December 2009, 119 RA patients were included and divided in two groups according to the body mass index (obeses and controls). RA activity was assessed by the Disease Activity Score (DAS) 28, quality of life by the Health Assessment Questionnaire (HAQ) and radiographic joint damage by the modified Sharp score. RESULTS: Obesity was not correlated with worsen RA activity (p=0.71) nor quality of life impairment (p=0.51). The obese group had a lower modified Sharp score than the control group (64.97versus113.64; p < 0.032) and this association remained significant after adjustment for age, sex, disease activity, extraarticular manifestations, comorbidities, presence of rheumatoid factor, and disease duration. CONCLUSION: Obesity does not have an impact on disease activity nor changes in quality of life, but it has a protective effect on the amount of joint destruction in established rheumatoid arthritis.
21890617 Rheumatoid arthritis and pregnancy: evolution of disease activity and pathophysiological c 2011 Nov It has long been known that pregnancy and childbirth have a profound effect on the disease activity of rheumatic diseases. For clinicians, the management of patients with RA wishing to become pregnant involves the challenge of keeping disease activity under control and adequately adapting drug therapy during pregnancy and post-partum. This article aims to summarize the current evidence on the evolution of RA disease activity during and after pregnancy and the use of anti-rheumatic drugs around this period. Of recent interest is the potential use of anti-TNF compounds in the preconception period and during pregnancy. Accumulating experience with anti-TNF therapy in other immune-mediated inflammatory diseases, such as Crohn's disease, provides useful insights for the use of TNF blockade in pregnant women with RA, or RA patients wishing to become pregnant.
23023405 Atypical continuous keratitis in a case of rheumatoid arthritis accompanying severe scleri 2012 Dec PURPOSE: Rheumatoid arthritis (RA) often presents with ocular complications: typically dry eye, peripheral corneal ulcer, and scleritis. We report for the first time a case of severe scleritis with RA, accompanying atypical continuous keratitis, which apparently differs from typical peripheral ulcerative keratitis (PUK). METHODS: Observational case report. RESULTS: A 68-year-old woman with RA presented at our hospital complaining of worsening arthritis accompanying ocular injection and discharge. On examination, nodular scleritis and peripheral corneal infiltration were noted. In addition to administering topical steroid and antibiotics, cyclosporine and an oral steroid were added because of the patient's worsening scleritis. Despite gradual improvement of the scleritis, the efficacy of the additional treatments was limited. Four months after initial treatment, the patient presented with uveitis, thought to be caused by a herpetic virus. Antivirus treatment was effective for the uveitis, but atypical continuous keratitis suddenly appeared. The keratitis was located from 4-o'clock to 10-o'clock positions continuously in the midperipheral cornea and apparently differed from herpetic keratitis or PUK as typically seen in RA cases. Immune reaction was suspected, and the keratitis improved within 2 weeks. After that, the introduction of an anti-tumor necrosis factor α drug (infliximab) completely resolved the severe scleritis and there was no recurrence of ocular inflammation. CONCLUSION: As is shown in this case, RA can present with atypical continuous keratitis, thought to be a manifestation of an immunologic reaction other than PUK. In addition, although immunosuppressants are often used for the treatment of RA with scleritis, the efficacy is limited. Infliximab may be a useful treatment for treatment-resistant scleritis.
21807794 Patient perspective on remission in rheumatoid arthritis. 2011 Aug Absence of disease activity, or remission, is the most important treatment goal for patients with rheumatoid arthritis (RA). Since a new preliminary definition of remission in RA for clinical trials has been proposed, we investigated what determinants of disease activity patients associate with a state of remission and whether dimensions of impact of disease on daily life are involved. Our report summarizes progress of a workshop at OMERACT 10 on the patient perspective on remission in RA, including the results of a short pre-conference survey among patients, the discussions among the participants and a research agenda resulting from these discussions. This initial OMERACT workshop on remission from the patient perspective showed that there is a great interest among patients, physicians, and researchers to study the concept of remission, taking into account measures that patients indicate as important, but that there is a lack of data on appropriate measures, resulting in a considerable research agenda.
22574709 Metabolic responses to change in disease activity during tumor necrosis factor inhibition 2012 Jul 6 Assessment of disease activity in patients with rheumatoid arthritis (RA) is of importance in the evaluation of treatment. The most important measure of disease activity is the Disease Activity Score counted in 28 joints (DAS28). In this study, we evaluated whether metabolic profiling could complement current measures of disease activity. Fifty-six patients, in two separate studies, were followed for two years after commencing anti-TNF therapy. DAS28 was assessed, and metabolic profiles were recorded at defined time points. Correlations between metabolic profile and DAS28 scores were analyzed using multivariate statistics. The metabolic responses to lowering DAS28 scores varied in different patients but could predict DAS28 scores at the individual and subgroup level models. The erythrocyte sedimentation rate (ESR) component in DAS28 was most correlated to the metabolite data, pointing to inflammation as the primary effect driving metabolic profile changes. Patients with RA had differing metabolic response to changes in DAS28 following anti-TNF therapy. This suggests that discovery of new metabolic biomarkers for disease activity will derive from studies at the individual and subgroup level. Increased inflammation, measured as ESR, was the main common effect seen in metabolic profiles from periods associated with high DAS28.
22333866 Total joint arthroplasty in patients with rheumatoid arthritis: a United States experience 2012 Jun To determine whether total joint arthroplasty (TJA) for patients with rheumatoid arthritis (RA) is decreasing, we collected Nationwide Inpatient Sample database information (1992 through 2005) on (1) the number of primary TJAs for all patient diagnoses, (2) the number of primary TJAs for patients with RA, and (3) distribution of age and sex in both groups. To account for population growth, a given year's arthroplasty estimate was normalized against its population. The trends over time were analyzed using a multivariable Poisson regression model (significance, P < .05). We found that the number of primary TJA procedures increased in the general and RA populations but that, after adjusting for population growth, age, and sex, the rate was significantly lower in patients with RA.