Arterial stiffness in a muscular artery in women with longstanding rheumatoid arthritis compared with healthy controls and patients with traditional cardiovascular risk factors.

Pulse wave velocity (PWV), a marker of arterial stiffness, reflects vascular dysfunction and is associated with cardiovascular risk. Rheumatoid arthritis (RA) is associated with profound changes in vascular function and premature death, mainly caused by cardiovascular diseases. The aim of this study was to investigate arterial stiffness in the brachial artery (a muscular type of artery) as measured by PWV in women with longstanding RA and to compare the results with healthy controls and to patients with traditional cardiovascular risk factors without RA. A total of 80 female participants underwent non-invasive measurement of PWV. Participants were allocated to one of three groups: patients with longstanding RA (disease duration >5 years) without traditional cardiovascular risk factors (n = 30), patients with traditional cardiovascular risk factors (n = 20) and healthy controls (n = 30). Patients and controls were matched for age. PWV was significantly higher in RA patients (8.6 +/- 0.9 m/s) as compared with healthy controls (8.1 +/- 0.7 m/s; P = 0.02). PWV was virtually the same in RA patients and patients who had traditional cardiovascular risk factors (8.6 +/- 1.5 m/s; NS). PWV was also higher in this group as compared with healthy controls, but this difference did not reach statistical significance (NS). RA is associated with a higher PWV as compared with healthy controls and is comparable to patients with known traditional risk factors. This reflects vascular dysfunction in patients with RA.

The place of methotrexate perioperatively in elective orthopedic surgeries in patients with rheumatoid arthritis.

No clear consensus exists on whether methotrexate (MTX) should be continued or whether this therapy should be discontinued for a few weeks in patients with rheumatoid arthritis (RA) undergoing surgery. Continued MTX therapy may impair wound healing, but discontinuation of the therapy may increase the risk of flares. In this article we review published data on the perioperative management of MTX in patients with RA undergoing elective orthopedic surgery. Eight papers on this topic could be identified. These studies compare continued vs. discontinued MTX therapy or MTX therapy vs. therapies other than MTX. Summing up the published data, continued MTX therapy appears to be safe perioperatively and seems also to be associated with a reduced risk of flares. None of the examined papers addresses the issue of safety in connection with comorbidities, age or high doses of MTX.

Patients with rheumatoid arthritis undergoing surgery: how should we deal with antirheumatic treatment?

OBJECTIVES: To review published data on the perioperative management of antirheumatic treatment and perioperative outcome in patients with rheumatoid arthritis (RA). METHODS: The review is based on a MEDLINE (PubMed) search of the English-language literature from 1965 to 2005, using the index keywords "rheumatoid arthritis" and "surgery". As co-indexing terms the different disease-modifying antirheumatic drugs (DMARDs) as well as nonsteroidal anti-inflammatory drugs (NSAIDs) and "glucocorticoids" were used. In addition, citations from retrieved articles were scanned for additional references. Furthermore, because the number of published articles is so limited, relevant abstracts presented at congresses were included in the analysis. RESULTS: Continuation of methotrexate (MTX) appears to be safe in the perioperative period. Only a limited number of studies address the use of leflunomide and the results are conflicting. Because of the very long drug half-life, its discontinuation would need to be of long duration and is probably not necessary. Data on hydroxychloroquine do not show increased risks of infection. Regarding sulfasalazine, there are no studies from which definite answers could be drawn on whether it should be withheld perioperatively. Preliminary data show that the risk of infections during treatment with TNF-blocking agents may be lower than initially expected. The only available recommendation (Club Rhumatismes et Inflammation, CRI) suggests discontinuing the drugs before surgery for several weeks, depending on the risk of infection and the drug used. They should not be restarted until wound healing is complete. To avoid the antiplatelet effect during surgery, NSAIDs other than aspirin should be withheld for a duration of 4 to 5 times the drug half-life. Patients with chronic glucocorticoid therapy and suppressed hypothalamic-pituitary-adrenal (HPA) axis need perioperative supplementation. CONCLUSIONS: While continuation of MTX likely is safe, data on other DMARDs are sparse. In particular, more data on the perioperative use of the biologic agents are needed.

Administration of infliximab in general practitioners' offices is safe.

Infliximab is used in the treatment of various diseases, such as rheumatoid arthritis (RA), psoriasis, psoriatic arthritis (PA), Crohn's disease (CD) and ankylosing spondylitis (AS). In most countries, infliximab is given in hospitals or infusion centers, which are experienced in the management of infusion reactions. Because of this side effect, general practitioners (GPs) might refuse to administer infliximab in their offices. The aim of this study was to investigate the safety of infliximab administration in GPs' offices. Health system in the provincial state of Upper Austria (Austria) provides reimbursement of biological treatment only in outpatient care. Infliximab is due to cost effectiveness usually administered by GPs after a specific training and initialisation of treatment by specialists in the hospital. We sent out a form to 42 cooperating GPs, containing 20 questions concerning the administration of infliximab. Thirty-four forms were returned and evaluated. Altogether, 69 patients (2 patients per doctor mean) were treated with infliximab (1-42 months; 21 months mean). The overall observation period was 697 patients-months. During this period, 487 infusions (14.5 infusions per doctor mean) were administered. From five doctors, seven adverse events (AE) in six patients were reported. In all seven cases, infusion was discontinued; two had allergic reactions and five had nausea or cardiac symptoms, not definitely of allergic origin. Severe adverse events (SAE), defined as shock, emergency treatment or hospitalisation during or after infliximab administration were reported by two doctors. In contrast, SAE during the infusion of other drugs (e.g. analgetics, vitamins) were previously seen by 16 doctors, showing the overall possibility of infusion reactions with commonly prescribed drugs. Almost all (31/34) confirmed the overall safety of infliximab administration in GP's patient care. The administration of infliximab by specially trained general practitioners with background guidance through rheumatologist or gastroenterologist centers seems to be a safe and acceptable way to provide long-term treatment with infliximab to patients in need of biological treatment.

Augmentation index in patients with rheumatoid arthritis and ankylosing spondylitis treated with infliximab.

Premature atherosclerosis is linked to inflammation. Arterial stiffness is a marker of vascular dysfunction. We tested the hypothesis that treatment with infliximab, which is effective in reducing inflammation in rheumatoid arthritis (RA) and ankylosing spondylitis (AS), also lowers the augmentation index (AIx) in patients with active disease. We also analyzed the subendocardial viability ratio (SEVR), which is a measure of myocardial perfusion relative to cardiac workload. Included in the study were 30 patients (17 RA, 13 AS). Conventional treatment failed in all patients. The AIx and SEVR were determined by radial applanation tonometry before and after treatment with infliximab, at baseline and at week 7. After treatment with infliximab, Disease Activity Score for 28 joints (RA patients), Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index (AS patients), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) improved significantly (p < 0.001). The AIx for all patients increased from 22.0 +/- 14.0% to 24.6 +/- 13.0% (p = 0.03). The increase in the RA sub-group (p = 0.01) was also significant. The SEVR decreased from 148.6 +/- 23.7% to 141.2 +/- 23.7% (p = 0.04). Infliximab did not reduce the AIx in patients with RA and AS, although there were clinical improvements and CRP and ESR decreased. Instead, the AIx increased. This could negatively influence cardiac workload.

The use of tumour necrosis factor alpha-blockers in daily routine. An Austrian consensus project.

To define relevant disease parameters and their respective limits indicating the initiation of TNF-alpha-blockers in individual patients. Subsequently, to analyze retrospectively patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) or ankylosing spondylitis (AS), who started TNF-alpha inhibition in 2006. Points to consider, regarded relevant for individual treatment decisions as well as their assessment methods, were ascertained by experts' consensus applying the Delphi technique. Subsequently, these parameters' thresholds with respect to the initiation of a TNF-alpha-blocker were identified. Thereafter, the rheumatologists representing 12 centres all over Austria agreed to retrospectively analyze their patients started on a TNF-alpha-blocker in 2006. Experts' opinion regarding disease parameters relevant to initiate TNF-alpha-blockers in RA patients only slightly differed from those applied in clinical trials, but the parameters' threshold values were considerably lower. For PsA patients, some differences and for AS patients, considerable differences between experts' opinion and clinical studies appeared, which held also true for decisive parameters' means and thresholds. Six hundred and fifty patients, started on TNF-blockers in 2006, could be analyzed retrospectively, 408 RA patients (53.3 years mean, 340 females), 93 PsA patients (48.9 years mean, 59 males) and 149 AS patients AS (42.2 years mean, 108 males), representing approximately 25% of all Austrian patients initiated on a TNF-blocker in this respective year. Far more individualized, patient-oriented treatment approaches, at least in part, are applied in daily routine compared with those derived from clinical trials or recommendations from investigative rheumatologists.

Augmentation index and large-artery remodeling in patients with longstanding rheumatoid arthritis compared with healthy controls.

OBJECTIVE: There is growing evidence of premature atherosclerosis in patients with rheumatoid arthritis (RA), leading to a higher rate of cardiovascular events than in the general population. The augmentation index (AIx), a marker of arterial stiffness, is an indicator of vascular function. The aim of the study was as follows: (1) to investigate whether AIx is increased in RA patients without traditional cardiovascular risk factors and (2) to evaluate whether there is an interrelationship with large artery remodeling as ascertained by carotid ultrasound. METHODS: Thirty-six RA patients (age, 46.4 +/- 7.7 years; 31 female) were recruited. Patients were eligible for analysis if they had no traditional cardiovascular risk factors. AIx was assessed noninvasively during pulse wave analyses. For large artery remodeling the intima-media thickness (IMT) was measured in both common carotid arteries with ultrasound. Results were compared with 36 age- and sex-matched controls. RESULTS: AIx was statistically significantly higher in RA patients as compared with controls (27.4 +/- 9.4% versus 18.4 +/- 9.0%; P < 0.001). In addition, IMT was significantly higher in RA patients (0.73 +/- 0.16 mm versus 0.65 +/- 0.12 mm; P = 0.01). In RA patients there was a positive correlation between IMT and AIx (r[IMT; AIx] = 0.45; P = 0.008). CONCLUSION: AIx, a marker of arterial stiffness, as well as IMT, a marker of large-artery remodeling, are increased in RA patients without traditional cardiovascular risk factors. Measuring AIx might assist in better assessing the increased cardiovascular risk in RA patients.

The public neglect of rheumatic diseases: insights from analyses of attendees in a musculoskeletal disease awareness activity.

OBJECTIVES: To obtain data on the care received by individuals counselled during a public health awareness campaign on painful musculoskeletal conditions (MSC). METHODS: Easy non-formal access to rheumatologists/pain specialists was offered using a mobile unit (Rheuma-Bus) at widely accessible sites. Clients were asked to assess their severity of pain using a 100 mm visual analogue scale (VAS). Age, gender, disease duration, diagnosis if known, current and previous treatment as well as tentative diagnoses assigned and recommendations given to each individual by the counselling physicians were recorded. RESULTS: Average (SD) VAS pain rating was 59 (20.6) mm. Approximately 40% of clients had never consulted a physician for their condition before, but had lower pain scores than those who had seen a physician. Patients with inflammatory MSC had higher pain scores than those with non-inflammatory conditions. More than 2% of the clients had a newly detected inflammatory rheumatic disease. CONCLUSIONS: Many individuals having painful MSC seek medical help only when a very high threshold of pain is reached. Even while under treatment, the high mean pain scores suggest neglect of MSC that are not adequately recognised as important contributors to disability and decreased quality of life.

Spontaneous remission of therapy-resistant minimal change nephritis in an adult woman 12 years after onset of the disease.

A 23-year old woman was admitted to our hospital because of severe edema due to steroid resistant minimal change nephritis (MCN). The diagnosis was proven by renal biopsy nine years ago. At that time, steroid therapy led to a complete remission. Seven years later, patient was 22 years old, a relapse with severe nephrotic syndrome occurred. The diagnosis MCN was confirmed by a second renal biopsy. A combined therapy with prednisolone and cyclosporine A (CSA) led only to a partial reduction of protein excretion, the edema did not disappear. After 3 months, patient declined further therapy with CSA. On admission to our hospital, one year later in December 2000, the woman showed a severe nephrotic syndrome with edema and fluid lung, despite high doses of furosemide. Urinary protein excretion was 12.5 g/day, serum creatinine was increased to 1.4 mg/dl, the serum protein was reduced to 47 g/l. A repeated renal biopsy confirmed again the diagnosis MCN. Once again, a steroid bolus monotherapy over 4 weeks and an immunosuppressive therapy with CSA over 6 weeks had no effect on proteinuria. Further therapy regimes with mofetil mycophenolat, azathioprine, chlorambucil and cyclophosphamide over a period of 6-12 weeks of each regime was not well tolerated, proteinuria remained high with > 10 g/day. Moreover the patient suffered from severe edema despite furosemide infusions. Therefore, an additional mechanical ultrafiltration was performed 2-4 times monthly. Three months after the last immunosuppressive therapy the edema disappeared spontaneously, the diuretic therapy could be stopped. Serum creatinine was 0.8 mg/dl, protein in urine was still high with 9.8 g/day but serum protein for the first time was normal with 65 g/l. Three months later, the protein excretion was reduced to 0.48 g/l, and all other laboratory data were normal. Meanwhile, the woman has now enjoyed a complete second spontaneous remission for a period of three years.