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ID PMID Title PublicationDate abstract
18512003 Total knee arthroplasty for rheumatoid knee with bilateral, severe flexion contracture: re 2008 The treatment of patients with severe flexion contracture of the rheumatoid knee, deprived of ambulation for long periods of time, is challenging. Based on three cases, we indicate the potential risks of posterior dislocation of the knee after total knee arthroplasty. In this pathological condition, surgeons must carefully select the type of implant in order to avoid this serious complication. We also emphasize the importance of working on disuse muscle atrophy of trunk (back, abdominal) and lower limbs, both of which play an integral role in ambulation. The personality of each rheumatoid patient should be carefully considered when considering surgical and rehabilitation options.
17888224 Quantification of the synovial perfusion in rheumatoid arthritis using Doppler ultrasonogr 2007 Jul In the past decade, Power Doppler ultrasound (PDUS) has been established as a new imaging modality for the evaluation of synovial perfusion in the inflamed joints of patients with rheumatic diseases. Various studies have been dealing with the problem of a reproducible quantification method in PDUS as this still appears to be one of the main disadvantages in comparison with magnetic resonance imaging and also with contrast-enhanced ultrasound technique. The main studies addressing this problem are presented and compared to the recently described three-dimensional power Doppler ultrasound by outlining the advantages and the remaining difficulties in quantifying synovial vascularity with PDUS.
16832852 Magnetic resonance imaging of the hand for the diagnosis of rheumatoid arthritis in the ab 2006 Sep OBJECTIVE: To assess the practical usefulness of magnetic resonance imaging (MRI) in establishing a positive diagnosis of rheumatoid arthritis (RA) in a cohort of patients with early inflammatory polyarthralgia, in the absence of anti-cyclic citrullinated peptide (anti-CCP) antibodies. METHODS: We prospectively followed 30 outpatients with inflammatory polyarthralgia and/or synovitis of at least one joint. Patients were disease modifying antirheumatic drug-naive and received no corticosteroids. At the initial visit a clinical examination, radiographs of hands, wrists and feet, and MRI of hands were performed. Rheumatoid factor and anti-CCP antibodies were assessed. The MRI procedure was T1 fat saturation with gadolinium injection [scores were established on the basis of the axial view of the carpal and metacarpal joints, using the RA MRI scoring system (RAMRIS) defined in the OMERACT study]. In all patients, radiographs at baseline were normal and anti-CCP antibodies were negative. RESULTS: At one-year followup, the final diagnosis was: 16 RA; the non-RA group was composed of 4 cases of spondyloarthropathy, 2 cases of fibromyalgia, 4 cases of undifferentiated arthritis (3 of which were self-limiting), 1 sicca syndrome, 1 hemochromatosis, 1 polymyositis, and 1 paraneoplastic syndrome. No statistical difference was found between patients with and without RA for carpal erosion, synovitis, and tenosynovitis. However, a statistical difference was observed between the RA and non-RA group where metacarpophalangeal (MCP) erosion scores were concerned (p = 0.024). This difference persisted when we compared erosions of the second and third MCP in the 2 groups (p = 0.044). ROC curve analysis revealed a positive MCP score at 15, with a specificity of 70% and a sensitivity of 64%. CONCLUSION: In our population of 30 anti-CPP negative patients with normal radiographs, MRI of hands, showing MCP erosions, can be helpful for the diagnosis of RA.
17003175 Rates and predictors of herpes zoster in patients with rheumatoid arthritis and non-inflam 2006 Nov OBJECTIVES: Herpes zoster (HZ) is a common disorder that causes substantial pain and morbidity. We examined its rate and predictors in rheumatoid arthritis (RA) and non-inflammatory musculoskeletal (MSK) disorders to determine if HZ was increased in RA and whether treatment contributed to the risk of HZ. METHODS: After excluding patients witzh prior HZ, we assessed 10 614 RA and 1721 MSK patients by semi-annual questionnaires during 33 825 patient-years of follow-up. Predictors of HZ were determined by Cox regression and expressed as hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: The annualized incidence rate per 1000 patient-years was 13.2 (95% CI 11.9-14.5) in RA and 14.6 (95% CI 11.2-18.1) in MSK, and did not differ significantly after adjustment for age and sex. HZ was predicted by impaired functional status, as measured by the Health Assessment Questionnaire (HAQ), [HR 1.3 (95% CI 1.1-1.5)] and by the use of COX-2-specific non-steroidal anti-inflammatory drugs (NSAIDs) [HR 1.3 (95% CI 1.1-1.6)] in RA and MSK. In multivariable analyses in patients with RA, cyclophosphamide HR 4.2 (95% CI 1.6-11.5), azathioprine HR 2.0 (1.2-3.3), prednisone HR 1.5 (1.2-1.8), leflunomide HR 1.4 (1.1-1.8) and COX-2 NSAIDs HR 1.3 (95% CI 1.1-1.6) were significant predictors of HZ. CONCLUSION: The incidence of HZ is increased in RA and MSK compared with population-based rates. However, the rate of HZ in RA is not increased compared with MSK. After adjustment for severity, various treatments, but not methotrexate or biologics, were risk factors for HZ.
17207378 Association of tumour necrosis factor a, b and c microsatellite polymorphisms with clinica 2006 Nov OBJECTIVE: To study the associations of tumor necrosis factor (TNF) a, b and c microsatellite markers with 1) the clinical disease activity and 2) the induction of remissions in patients with early rheumatoid arthritis (RA) treated with two treatment strategies. METHODS: In the FIN-RACo (FINnish Rheumatoid Arthritis Combination therapy) trial of two years, 195 patients with recent-onset RA were randomly assigned to receive either a combination (COMBI) (sulphasalazine, methotrexate, hydroxychloroquine, and prednisolone) or a single (SINGLE) (initially sulphasalazine with or without prednisolone) disease modifying antirheumatic drug (DMARD) therapy. TNF a, b and c microsatellite and HLA-DRB1 typings were carried out in 165 (79 COMBI; 86 SINGLE) study completers. RESULTS: At baseline the 28 joint disease activity scores (DAS28) of the patients positive for TNFa2, a13 or b1 microsatellite markers were significantly higher than in the other patients. In the SINGLE patients the DAS28 improved comparably in patients with (n = 31) or without (n = 53) the TNFb1 marker (NS), while the DAS28 of the TNFb1-positive COMBI patients (n = 22) improved significantly more than that of the TNFb1-negative cases (n = 57) (p = 0.014). Respective 31.8% (7/22) and 28.1% (16/57) of the COMBI patients with or without TNFb1 allele achieved remission at one year. The corresponding figure in SINGLE patients were 0% (0/31) and 20.8% (11/53) (p = 0.006). At two years the remission frequencies in the TNFb1+/TNFb1- patients in the COMBI and SINGLE were 50.0%/38.6% and 9.7%/22.6%, respectively. CONCLUSION: Early TNFb1+ RA patients have more active disease but respond more favourably to COMBI treatment than the patients without this microsatellite allele. The finding may be of clinical relevance for the choice of DMARDs in early RA.
16550015 Atlantoaxial osteoarthritis in rheumatoid arthritis: FDG PET/CT findings. 2006 Apr The cervical spine is a common focus of destruction in patients with rheumatoid arthritis, and the resultant instability and neural compression represent severe complications in these patients. Evaluation of disease activity at the level of the atlantoaxial joint is important in such cases. Here, we report a 47-year-old man with a 3-year history of rheumatoid arthritis. FDG PET/CT clearly demonstrated a hot spot in the atlantoaxial area, suggesting high metabolic activity of synovitis.
17093901 Emerging and future therapies for the treatment of bone loss associated with chronic infla 2006 Dec Currently there are many emerging therapies for the treatment of chronic osteoporosis. This is a major problem world wide and particularly of concern in post-menopausal women. This has offered a large expanding market for the pharmaceutical industry and consequently large amounts of money and resources have been used to develop new treatments. These new and emerging treatments have largely targeted the mechanisms of bone loss associated with post-menopausal osteoporosis. However, there are many other important bone loss disorders and it is possible that some of these new therapies may be useful in treating bone loss associated with other diseases. This review identifies several of these pharmacologic treatments of osteoporosis and discusses the possibility of using these drugs for the treatment of bone loss associated with inflammatory diseases. In addition, other approaches, such as regulating apoptosis and intracellular signalling, may be developed in the future and may better target bone loss associated with chronic inflammation are identified.
16460133 Sociodemographic differences in quality of life in rheumatoid arthritis. 2006 Assessment of health-related quality of life (HR-QOL) in people with rheumatoid arthritis (RA) has become important in health research and can inform clinical care. Many studies have found sociodemographic differences in the HR-QOL of people with RA, and interpreting these differences can be challenging. Biological, health disparity, reporting and assessment instrument differences are a few of the possible explanations that should be considered when interpreting results. Our review of the evidence of sociodemographic differences in HR-QOL in people with RA produced 34 articles describing 49 studies.Typically, patients with RA who were older, female, less educated, non-employed and/or less affluent tended to have significantly lower HR-QOL than other groups. Some evidence also indicated that people with RA who are non-White or who live in rural settings may also tend to have lower HR-QOL scores, but the number of studies supporting these findings was sparse. Researchers and clinicians can optimise their assessment of HR-QOL by finding well validated instruments for the context they are working in. Additional research is needed to identify the exact causes of HR-QOL differences so that quality treatment can be provided to those in need.
17934080 Optimal use of methotrexate: the advantages of tight control. 2007 Nov The CAMERA study shows that using methotrexate in a tight control setting might lead to considerable improvement in disease activity in early rheumatoid arthritis See linked article p 1443.
18351533 [Epitheliotrophic capacity of serum eye drops from healthy donors versus serum from immuno 2008 Mar BACKGROUND: Autologous serum has been advocated for the treatment of persistent corneal epithelial defects and other ocular surface disorders which may be a local manifestation of a systemic disease. Many of these underlying disorders are cytokine-mediated and require immunosuppressive therapy. The systemic disease and medication could potentially influence the epitheliotrophic capacity of serum eye drops. We compared the effect of serum from healthy and immunosuppressed donors in a human corneal epithelial cell culture model. METHODS: Serum was prepared under standardised conditions from full blood samples of 10 healthy donors and 10 patients suffering from rheumatoid arthritis. All patients were treated with prednisolone and methotrexate, one also with azathioprine. In these serum samples EGF, FGF, HGF, PDGF-AB, TGF-beta1, fibronectin, vitamin A and E as well as IL-6 were quantified by means of routine ELISA or HPLC technology. SV-40 immortalised human corneal keratinocytes were cultured in 96-well plates at 37 degrees C, 5 % CO (2) with a fully defined culture medium. At 30 % confluency the culture medium was substituted by one of the test preparations. Proliferation of cell cultures was quantified by means of a luminescence-based ATP assay in dose-response experiments. A colony dispersion assay was used to examine the effect on cell migration and differentiation was assessed by means of scanning electron microscopy. RESULTS: Serum from healthy donors differed from serum of immunosuppressed individuals suffering from rheumatoid arthritis only in that it contained significantly higher amounts of fibronectin and TGF-beta1. Support of proliferation, migration and differentiation of corneal epithelial cells was dose-dependent, but no significant difference was observed between the serum of the two different groups of donors. At a dilution of 25 % serum of healthy donors showed a significantly higher stimulation of migration than serum of immunosuppressed patients. CONCLUSION: The effect of serum on migration but not proliferation is affected by systemic diseases requiring immunosuppression. If an epithelial defect of a patient with rheumatoid arthritis does not respond to treatment with diluted autologous serum, undiluted serum should be tried since the positive effect of serum on cell migration is positively correlated with dose.
18349742 The safety of anti-tumour necrosis factor therapy in rheumatoid arthritis. 2008 Mar PURPOSE OF REVIEW: Anti-tumour necrosis factor therapy has proven effective as treatment against a series of autoimmune inflammatory diseases, and has displayed a rapidly increasing market penetration. The safety profile of these drugs is, however, both uncertain and debated, in particular with respect to infections and malignancy. Lack of uniform definitions and methods of analysis makes it difficult to directly compare data from randomized controlled trials, meta-analyses of trials, open-label extensions, data from spontaneous reporting, and particularly, observational cohort studies. RECENT FINDINGS: In this review, we provide a summary of currently published data on infection, malignancy, cardiovascular disease, interstitial lung disease, and death in relation to treatment of rheumatoid arthritis with anti-tumour necrosis factor agents. SUMMARY: Superficially contradictory data on infection display a more or less coherent pattern of an increased risk shortly after treatment starts. Available data on malignancy, cardiovascular disease, interstitial lung disease, and death do not exclude clinically important increased risks, nor do they refute beneficial effects. Harmonized methods of reporting safety data would greatly improve the interpretation and comparison of class and drug-specific risks.
18496698 A case of AA amyloidosis associated with rheumatoid arthritis effectively treated with Inf 2008 Sep We report the case of a 55-year-old Japanese woman with reactive AA amyloidosis associated with rheumatoid arthritis, in which inflammatory disease was completely suppressed with infliximab. Nephrotic syndrome was observed and renal biopsy specimens revealed amyloidosis deposits. Treatment with infliximab normalized the serum amyloid A (SAA) protein level, and subsequently nephritic syndrome disappeared and her creatinine clearance improved. Serial gastrointestinal biopsy specimens showed marked lasting regression of amyloid deposits. Thus treatment with infliximab represents an important therapeutic strategy for AA amyloidosis associated with RA.
17006638 Galactosylation of IgG from rheumatoid arthritis (RA) patients--changes during therapy. 2006 Nov It is well documented that serum IgG from rheumatoid arthritis (RA) patients exhibits decreased galactosylation of its conservative N-glycans (Asn-297) in CH2 domains of the heavy chains; it has been shown that this agalactosylation is proportional to disease severity. In the present investigation we analyzed galactosylation of IgG derived from the patients using a modified ELISA-plate test, biosensor BIAcore and total sugar analysis (GC-MS). For ELISA and BIAcore the binding of IgG preparations, purified from the patients' sera, to two lectins: Ricinus communis (RCA-I) and Griffonia simplicifolia (GSL-II) was applied. Based on ELISA-plate test an agalactosylation factor (AF, a relative ratio of GSL-II/RCA-I binding) was calculated, which was proportional to actual disease severity. Repeated testing of several patients before and after treatment with methotrexate (MTX) alone or in combination with Remicade (a chimeric antibody anti-TNF-alpha) supplied results indicating an increase of IgG galactosylation during the treatment. This introductory observation suggests that IgG galactosylation may be an additional indicator of the RA patients' improvement.
18805724 Leflunomide-induced toxic epidermal necrolysis in a patient with rheumatoid arthritis. 2008 Oct INTRODUCTION: Leflunomide is an immunomodulating agent with proven efficacy in rheumatoid arthritis. Although its overall safety profile is good, a few cases of toxic epidermal necrolysis have been reported. CASE REPORT: This 36-year-old woman had rheumatoid arthritis that proved refractory to sulfasalazine and methotrexate, which were used successively in combination with symptomatic drugs. Leflunomide was started. A maculopapular rash and a fever developed 2 weeks later. The skin lesions spread rapidly to most of the body, and ulcers of the ocular and oral mucosa appeared. Leflunomide was stopped. Cholestyramine washout and prednisolone (60 mg/day) were given. The skin lesions healed over the next month. Punctate keratitis with keratinization of the cornea led to complete loss of vision. DISCUSSION: The main adverse effects of leflunomide consist of diarrhea, nausea, liver enzyme elevation, hypertension, alopecia, and allergic skin reactions. A few cases of severe skin reactions such as toxic epidermal necrolysis have been reported. They require immediate discontinuation of the drug and a washout procedure to hasten drug elimination from the body. CONCLUSION: Close monitoring for severe skin reactions is in order when using leflunomide.
18713784 Effects of infliximab therapy on biological markers of synovium activity and cartilage bre 2009 Jul BACKGROUND: Defining the remission criteria of rheumatoid arthritis (RA) remains a critical issue. Markers of synovium activity, urinary glucosyl-galactosyl-pyridinoline (Glc-Gal-PYD) and of cartilage destruction, urinary C-terminal crosslinking telopeptide of type II collagen (CTX-II) have been shown to reflect disease activity and joint damage progression in RA. METHODS: The prospective study cohort comprised 66 RA patients treated with infliximab and methotrexate and 76 healthy controls. Measurements of urinary Glc-Gal-PYD and CTX-II were performed at baseline and at 1 year of infliximab therapy. RESULTS: At baseline, urinary Glc-Gal-PYD and CTX-II levels were increased in patients with RA and correlated with modified Sharp scores and progression of joint damage. Patients with more progressive joint destruction had higher Glc-Gly-PYD and CTX-II baseline levels. CONCLUSION: These markers reflected bone erosion evolution and might be useful for treatment monitoring and evaluation of RA. Markers remained high even in clinical responders after infliximab, suggesting persistence of synovitis.
17096694 Investigation of the clinical effect of large volume leukocytapheresis on methotrexate-res 2006 Oct Leukocytapheresis (LCAP) is already being used in a clinical setting for the treatment of autoimmune diseases such as inflammatory bowel disease and rheumatoid arthritis, and it has been reported to be effective. However, it is totally or partially ineffective in some patients, which has forced clinicians to rethink therapeutic strategies and concurrent treatment. With the aim of enhancing the therapeutic effect, we carried out large volume leukocytapheresis, with a throughput of 5000 mL instead of the 3000-mL throughput of conventional leukocytapheresis in nine patients with rheumatoid arthritis resistant to methotrexate treatment. Using Cellsorba, the column filled with the unwoven fabric made of the polyethylene phthalate, a leukocyte removal filter, large volume leukocytapheresis was carried out once a week for a total of five sessions. The observation period was the 12-week period following completion of treatment. The American College of Rheumatology (ACR) core set was used for assessment of efficacy. Eight weeks after completion of treatment, a 20% improvement in ACR was observed in 77.8% (7/9) of subjects, a 50% improvement in ACR was seen in 55.6% (5/9) of subjects, and a 70% improvement in ACR was observed in 22.2% (2/9) of subjects. C-reactive protein decreased gradually as treatment progressed, and a significant decrease was observed 4 weeks after completion of treatment. The fact that some subjects had an ACR70 response, few reports of which are observed in the case of conventional leukocytapheresis, and the fact that the effect continued up to 12 weeks after completion of treatment suggests that the degree and duration of the effect of large volume leukocytapheresis might be longer than those of conventional leukocytapheresis.
18578961 Amyloidosis as a cause of death in patients with rheumatoid arthritis. 2008 May OBJECTIVE: To study amyloidosis as a cause of death along with associated factors and frequency of pre-mortem diagnosis in patients with rheumatoid arthritis (RA) autopsied between 1952 and 1991. METHODS: We studied causes of death in 369 consecutively autopsied RA and 370 autopsied non-RA patients of the same sex, age at death, and year of autopsy. In those RA patients who died from 1973 onwards, we were also able to analyse clinical data: pre-mortem diagnosis of amyloidosis, clinical features of RA, and treatment. RESULTS: Based on autopsy, amyloidosis was determined as a cause of death in 9.5% of RA and in none of the non-RA patients (p<0.001). In our RA patients, we detected no trend in deaths from amyloidosis between 1952 and 1991. The RA patients dying of amyloidosis died younger than those dying of other causes (p=0.001). During the course of the disease, the RA patients with amyloidosis had: higher erythrocyte sedimentation rate (p=0.002), lower haemoglobin (p<0.001), more frequently proteinuria (p<0.001) and renal failure (p<0.001) than did the rest of the RA patients. Pre-mortem, amyloidosis was diagnosed by biopsy in 65% of the RA patients with amyloidosis as their cause of death. CONCLUSION: Amyloidosis may be undetected during the course of RA. Thus, it should be actively searched for in the patients with long-lasting and active disease, especially, if they have proteinuria or renal failure.
17022047 Multiple myeloma presented as acute interstitial nephritis and rheumatoid arthritis-like p 2007 Apr Acute interstitial nephritis and rheumatoid arthritis (RA) or RA-like polyarthritis are among the very rare paraneoplastic manifestations of multiple myeloma (MM). A 47-year-old man with acute renal failure due to interstitial nephritis was admitted to our university hospital and successfully treated with corticosteroid. He later developed a symmetric distal polyarthritis with morning stiffness mimicking RA. On follow-up, the patient had a rise in serum creatinine, hypercalcemia, anemia, and a monoclonal spike (Bence Jones protein) on the urine protein electrophoresis. Bone marrow biopsy demonstrated a diffuse neoplastic plasma cell infiltration. Diagnosis of MM was made and the patient received chemotherapy. After four-course chemotherapy, the patient's articular manifestations resolved, urine monoclonal spike disappeared, and serum creatinine returned to a near normal level. We hypothesize that in this case, immunologic hypersensitivity reactions to the light-chain molecules or other tumoral antigens deposited within the kidney or joint spaces, in the context of MM cytokine milieu may have resulted in this unusual presentation. Ultimately, clinicians and pathologists should consider MM in the differential diagnosis of the acute interstitial nephritis and RA-like polyarthritis.
18457979 Severe atherosclerosis in rheumatoid arthritis and hyperhomocysteinemia: is there a link? 2008 Jul Rheumatoid arthritis (RA) is a chronic inflammatory joint disease whose main complication is accelerated atheroma responsible for high rates of cardiovascular morbidity and mortality. Hyperhomocysteinemia is among the factors incriminated in RA-associated atheroma. We managed a 46-year-old patient with RA who required admission to evaluate severe arterial and venous disease with involvement of the coronary, renal, and peripheral arteries. She had no laboratory evidence of rheumatoid vasculitis or conventional cardiovascular risk factors (diabetes and hypercholesterolemia) and had never smoked. Her serum homocysteine level was elevated to 20.9 micromol/L as a result of a homozygous C667T mutation in the methylenetetrahydrofolate (MTHFR) gene. Folate and vitamin B12 levels were normal. A circulating anticoagulant was identified. Hyperhomocysteinemia, which is defined as a homocysteine level greater than 15 micromol/L, is a risk factor for arterial and venous disease. Hyperhomocysteinemia is found in 20%-42% of patients with RA. Methotrexate therapy is the most common causative factor. Other causes include MTHFR deficiency, vitamin B12 deficiency, renal failure, old age, and smoking. Whatever the underlying cause, folic acid supplementation returns the homocysteine level to normal.
16869001 A randomized controlled trial with an anti-CCL2 (anti-monocyte chemotactic protein 1) mono 2006 Aug OBJECTIVE: Chemokines such as CCL2/monocyte chemotactic protein 1 (MCP-1) play a key role in leukocyte migration and are potential targets in the treatment of chronic inflammatory disorders. The objective of this study was to evaluate the effects of human anti-CCL2/MCP-1 monoclonal antibody (ABN912) treatment in patients with rheumatoid arthritis (RA). METHODS: Patients with active RA were enrolled in a randomized, placebo-controlled, dose-escalation study of ABN912. Infusions were administered on day 1 and day 15. In the dose-escalation phase, 4 cohorts of 8 patients each underwent serial arthroscopic biopsy of synovial tissue. Immunohistochemistry and digital image analysis were used to characterize biomarkers in synovial tissue. Laboratory evaluation included pharmacokinetic analysis and immunotypic studies of peripheral blood mononuclear cells. To assess the clinical effects of treatment with ABN912, an additional 21 patients were treated with the highest dose tolerated. RESULTS: The total study population comprised 45 patients: 33 patients received ABN912, and 12 patients received placebo. ABN912 treatment was well tolerated. Unexpectedly, there was a dose-related increase in ABN912-complexed total CCL2/MCP-1 levels in peripheral blood, up to 2,000-fold. There was no detectable clinical benefit of ABN912 compared with placebo, nor did treatment with the study drug result in a significant change in the levels of biomarkers in synovial tissue and peripheral blood. CONCLUSION: ABN912 treatment did not result in clinical or immunohistologic improvement and may have been associated with worsening of RA in patients treated with the highest dose. The results might be related to the greatly increased level of total CCL2/MCP-1 in serum that was observed following treatment with ABN912. This observation may be relevant for a variety of antibody-based therapies.