Rheumatoid Arthritis: Turiel M

Sitia S, Atzeni F, Sarzi-Puttini P, Di Bello V, Tomasoni L, Delfino L, Antonini-Canterin F, Di Salvo G, De Gennaro Colonna V, La Carrubba S, Carerj S, Turiel M. · IRCCS Orthopedic Galeazzi Institute, University of Milan, Department of Health Technologies, Cardiology Unit, Milan, Italy. · Autoimmun Rev. · Pubmed #18817899 No free full text.

Abstract: Autoimmune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), primary antiphospholipid syndrome (APS), systemic sclerosis and systemic vasculitis, affect a large number of people in whom one of the leading causes of morbidity and mortality is cardiovascular disease. Cardiovascular disease is associated with the development of accelerated atherosclerosis. It seems to occur at a younger age than in the general population, is often asymptomatic and, in addition to traditional risk factors, also involves specific risk factors as chronic inflammation, the duration and activity of the autoimmune disease, and immunosuppressive therapy. The early phases of cardiovascular involvement in patients with autoimmune diseases may be clinically silent, with only a microcirculation disorder present. There are various means of detecting morphological cardiac damage: coronary angiography remains the gold standard for diagnosing coronary stenosis, but new, non invasive and more reliable methods have been introduced into clinical practice in order to detect subclinical microcirculation abnormalities.

Atzeni F, Doria A, Carrabba M, Turiel M, Sarzi-Puttini P. · Rheumatology Unit, L. Sacco Hospital, University of Milan, Via GB Grassi 74, 20157 Milan, Italy. · Autoimmun Rev. · Pubmed #17854744 No free full text.

Abstract: Tumour necrosis factor-alpha (TNF-alpha) is a pro-inflammatory cytokine produced by many cell types (blood monocytes, macrophages, mast cells and endothelial cells), that play a key role in the pathogenesis of multiple autoimmune and nonautoimmune disorders. A number of large placebo-controlled trials have shown that infliximab, a chimeric monoclonal antibody against TNF-alpha, is effective and well tolerated in patients with Crohn's disease, rheumatoid arthritis and spondiloarthritides and has become a widely used treatment for these diseases. Preliminary data suggest that several forms of vasculitis appear responsive to TNF antagonists: Behçet's disease, Churg-Strauss vasculitis, polyarteritis nodosa, and giant cell arteritis, among others. Wegener's granulomatosis and sarcoidosis have been shown to improve with infliximab. Polymyositis/dermatomyositis may also be responsive to TNF blockade. TNF likely plays little role in Sjögren's syndrome as evidenced by the lack of efficacy of TNF antagonists. There is a rationale for using TNF blockade even in systemic lupus erythematosus, a prototype of autoantibody-mediated disease, and a pilot study seems to confirm this potential effective approach. A number of other more rare disorders also may be responsive to TNF blockade. We here review the current and prospective roles of infliximab in the treatment of autoimmune diseases and other conditions.

Sarzi-Puttini P, Atzeni F, Doria A, Iaccarino L, Turiel M. · Rheumatology Unit, L Sacco University Hospital, Milan, Italy. · Lupus. · Pubmed #16218487 No free full text.

Abstract: The increased risk of premature cardiovascular disease (CVD) in rheumatoid arthritis (RA) patients may depend on traditional risk factors but may also be attributable to RA-specific risk factors such as disease-related dyslipidemia, or cytokines such as tumor necrosis factor-alpha (TNF-alpha). TNF-alpha is a proinflammatory cytokine that can produce widespread deleterious effects when expressed in large amounts. It is produced in the heart by both cardiac myocytes and resident macrophages under conditions of cardiac stress, and is thought to be responsible for many of the untoward manifestations of cardiac disease. TNF-alpha may play a role in the triggering and perpetuation of atherosclerosis. Treatment with biologic agents directed against TNF-alpha has significant clinical benefits in inflammatory diseases such as RA and may be able to reduce cardiovascular risk. The disappointing results of the recent studies to antagonize TNF-alpha in CVD may have various explanations. However, the effects of TNF-alpha blockers on incident cases of congestive heart failure (CHF) in RA remains controversial. Due to the lack of evidence of a beneficial effect of anti-TNF-alpha agents in treatment of CHF, they should not be used to treat patients with New York Heart Association (NYHA) class III or IV heart failure.

Turiel M, Peretti R, Sarzi-Puttini P, Atzeni F, Doria A. · Department of Cardiology, Istituto Ortopedico Galeazzi, University of Milan, Milan, Italy. · Lupus. · Pubmed #16218476 No free full text.

Abstract: Systemic autoimmune disorders are frequently associated to cardiac involvement and to a high prevalence of ischemic coronary events, often occurring at a younger age than in the normal population. Large increase in mortality is related to premature atherosclerosis with coronary artery disease and stroke in patients with connective tissue diseases. Coronary heart disease is responsible for 40-50% of the deaths of patients with rheumatoid arthritis. Transesophageal or transthoracic echocardiography are the most useful and noninvasive techniques able to detect not only valvular abnormalities, embolic sources or pulmonary hypertension, but also left ventricular systolic or diastolic dysfunction. Furthermore, the introduction of new indexes, contrast agents and software increased the accuracy of this technique. It is possible now to evaluate coronary flow reserve by transthoracic echocardiography in patients with systemic autoimmune disease in order to detect microvasculature disorder. However, an ischemic response in a symptomatic patient requires, in most cases, further evaluation with cardiac catheterization. Coronary artery imaging allows confirmation of the presence, extent and position of atheromatous lesions. More recently, other imaging modalities including magnetic resonance and computerized tomography angiography have been developed to allow imaging of the coronary arteries.

Atzeni F, Turiel M, Capsoni F, Doria A, Meroni P, Sarzi-Puttini P. · Rheumatology Unit, Department of Rheumatology, University Hospital L Sacco, Via GB Grassi 74, 20157 Milan, Italy. · Ann N Y Acad Sci. · Pubmed #16126996 No free full text.

Abstract: Treatment of rheumatoid arthritis (RA) patients with anti-tumor necrosis factor-alpha (anti-TNF-alpha) biologic agents has been associated with a reduction in the levels of specific autoantibodies, such as rheumatoid factor (RF) and anticyclic citrullinated peptide (anti-CCP), and the induction of non- organ-specific autoantibodies (antinuclear antibodies [ANAs], anti-dsDNA, and antiphospholipid antibodies [aPLs]). The mechanisms by which the blockade of anti-TNF-alpha decreases the generation of specific autoantibodies, such as anti-CCP and RF, are not yet known. However, it has been shown that these agents can downregulate the production of several inflammatory cytokines and mediators and that these anti-inflammatory effects may account for reduced autoantibody generation, particularly in the synovial compartment. Infliximab treatment leads to the induction of ANAs in 63.8% of RA patients and 49.1% of Crohn's disease (CD) patients, and anti-dsDNA antibodies in 13% of RA patients and 21.5% of CD patients, respectively. The development of ANAs and anti-dsDNA antibodies has also been described after etanercept therapy in 11% and 15% of RA patients, respectively. In the controlled trials, increases in ANA and anti-dsDNA titers were observed in 5.3% and in 12.9% of adalimumab-treated RA patients. Only limited data on the induction of aPL antibodies during TNF-alpha blocking treatment are available.

Sarzi-Puttini P, Comi D, Boccassini L, Muzzupappa S, Turiel M, Panni B, Salvaggio A. · Department of Internal Medicine, University Hospital L. Sacco, Milan, Italy. · Scand J Rheumatol. · Pubmed #11093596 No free full text.

Abstract: OBJECTIVE: To evaluate the effects of a diet therapy in patients with rheumatoid arthritis (RA). METHODS: Fifty RA patients entered a 24-week double-blind, randomised, controlled-study of two different dietary regimens (an experimental diet high in unsaturated fats, low in saturated fats with hypoallergenic foods vs. a control well-balanced diet). The primary end points of the study were 20% and 50% improvement in disease activity according to composite symptoms (Paulus index) of arthritis. Other end points were the other measures of disease activity at 12 and 24 weeks of diet treatment. RESULTS: The 2 groups were comparable at inclusion. Diet treatment was well tolerated and the rate of drop-outs was low. Percentage of patients with global 20 or 50% response didn't differ between experimental and control group after the 24-week of diet treatment. The experimental diet group did better for all the variables considered but only four variables (Ritchie's index, tender and swollen joints, and ESR) reached a statistical difference by multivariate analysis. Adjusting these data for weight variations, the number of tender joints (p=0.014) and ESR (p=0.025) were still statistically significant. CONCLUSIONS: Dietary manipulation, either by modifying food supplements or by reducing weight, may give some clinical benefit although no significant improvement can be observed assessing the results with a composite index.

Turiel M, Atzeni F, Tomasoni L, de Portu S, Delfino L, Bodini BD, Longhi M, Sitia S, Bianchi M, Ferrario P, Doria A, De Gennaro Colonna V, Sarzi-Puttini P. · Department of Health Technologies, Cardiology Unit, IRCCS Orthopedic Galeazzi Institute, University of Milan, Milano, Italy. · Rheumatology (Oxford). · Pubmed #19465588 No free full text.

Abstract: OBJECTIVE: Plasma concentration of asymmetric dimethylarginine (ADMA), a major endogenous inhibitor of nitric oxide synthase, is considered a novel risk factor for endothelial dysfunction associated with enhanced atherosclerosis. Coronary microcirculation abnormalities have been demonstrated in patients with early rheumatoid arthritis (ERA) without any signs or symptoms of coronary artery disease (CAD). The aim of the study was to compare the ERA and control groups with ADMA, intima-media thickness (IMT) and coronary flow reserve (CFR) levels. It assessed whether ERA patients have more cardiovascular risk (endothelial dysfunction and coronary microvascular abnormalities), and evaluated whether any difference in IMT/CFR between ERA and controls can be explained by any difference in ADMA levels between the groups. METHODS: The study involved 25 ERA patients (female/male 21/4; mean age 52.04 +/- 14.05 years; disease duration <or=12 months) and 25 healthy volunteers with no history or current signs of CAD or other traditional risk factors. Dipyridamole trans-thoracic stress echocardiography was preformed to evaluate CFR, and carotid ultrasound to measure the IMT of the common carotid arteries. Blood samples were obtained in order to assess ADMA levels before the patients had received any biological or non-biological DMARDs, or steroid therapy. RESULTS: CFR was significantly reduced in the ERA patients (2.5 +/- 0.5 vs 3.5 +/- 0.8; P <0.01). In particular, 6/25 (24%) had a CFR of <2 consistent with potentially dangerous coronary flow impairment. Common carotid IMT was significantly greater in the ERA patients, although still within the normal range (0.68 +/- 0.1 vs 0.56 +/- 0.11 mm; P <0.01). There was a significant correlation between CFR and plasma ADMA levels in the ERA population (r = -0.53; P <0.01). IMT was negatively associated with CFR (P <0.05). CONCLUSIONS: Plasma ADMA levels were significantly higher in the ERA patients. A statistically significant negative effect of ADMA levels on CFR value was observed. The effect of ADMA levels on IMT is not significant.

Atzeni F, Doria A, Ghirardello A, Turiel M, Batticciotto A, Carrabba M, Sarzi-Puttini P. · Rheumatology Unit, L Sacco University Hospital, Milan, Italy. · Autoimmunity. · Pubmed #18176873 No free full text.

Abstract: OBJECTIVES: The aim of this study was to assess thyroid function as well as the prevalence and clinical value of anti-thyroid antibodies in patients with rheumatoid arthritis (RA). METHODS: Seventy patients with active RA (ACR criteria), 9 males and 61 females, mean age 47 years (range 15-77) were analyzed. Anti-thyroperoxidase (TPOAb) and anti-thyroglobulin antibodies (TgAb) were tested using radioimmunoassay. Free thyroxine (FT4) and free triiodothyronine (FT3) and thyroid-stimulating hormone (TSH) serum levels were measured using electro-immunochemiluminescence (ECLIA, Elecsys Roche). Clinical variables, including tender and swollen joint count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-cyclic citrullinated peptide antibody (anti-CCP) and antinuclear antibodies (ANA) were also evaluated. Statistics were performed by the SPSS statistical software for Windows. RESULTS: Twenty-six patients (37%) with RA were positive for TPOAb and 16 (23%) for TgAb. In 5 (7.1%) patients TSH level was slightly elevated, ranging between 4.52 and 15.65 UI/ml. The increase of TSH levels was associated with normal FT4 in 3 cases (4.2%) and with reduced FT4 in 2 cases (2.8%). One patient (1.5%) had low TSH serum value along with normal FT4. No differences in clinical and serological data between anti-thyroid positive and negative patients were observed. CONCLUSION: Our study shows an increased prevalence of anti-thyroid antibodies in RA patients with a low prevalence of hormonal alterations. However, anti-thyroid antibodies do not seem to identify any peculiar RA phenotype.

Magagnin V, Caiani EG, Delfino L, Champlon C, Cerutti S, Turiel M. · Biomedical Engineering Dept., Polytechnic of Milan, Italy. · Conf Proc IEEE Eng Med Biol Soc. · Pubmed #17946419 No free full text.

Abstract: Coronary flow velocity reserve (CFVR) is conventionally obtained by manual tracings of Doppler profiles, as ratio of stress vs baseline diastolic peak velocity. When <1.9, this parameter evidences reduced coronary flow and possible microcirculatory disease. Our goals were: 1) to develop a novel technique for semi-automated detection of Doppler flow velocity profile, allowing the automated computation of CFVR and other parameters; 2) to validate this technique in comparison with conventional measurements obtained by manual tracing; 3) to test for differences between normal (N) subjects and patients with rheumatoid arthritis (RA). Linear correlation and Bland-Altman analyses showed that the proposed method was highly accurate and repeatable compared to the manual measurements. Comparison between N and RA groups evidenced significant differences in some of the automated parameters.

Atzeni F, Sarzi-Puttini P, De Blasio G, Delfino L, Tomasoni L, Turiel M. · Rheumatology Unit, L. Sacco Hospital, University of Milan, Milan, Italy. · Ann N Y Acad Sci. · Pubmed #17894002 No free full text.

Abstract: Cardiovascular involvement in rheumatoid arthritis (RA) is common, although the true prevalence of cardiac abnormalities is difficult to measure, as much disease remains clinically silent. The pathogenesis of cardiac lesions in RA is related to the primary disorder of microcirculation with diffuse arteriolar and capillary lesions. Previous studies demonstrated that coronary flow reserve (CFR) is impaired in patients with connective tissue diseases (CTD). This review focuses on transthoracic Doppler echocardiography as a noninvasive method used to assess CFR in RA patients. CFR is early reduced in RA patients without clinical evidence of heart disease as a result of impaired microcirculation. CFR seems a useful technique able to follow-up and to assess effects of new drugs on RA patients.

Sarzi-Puttini P, Fiorini T, Panni B, Turiel M, Cazzola M, Atzeni F. · Rheumatology Unit, University Hospital L. Sacco, Milan, Italy. · BMC Musculoskelet Disord. · Pubmed #12133169 links to  free full text

Abstract: BACKGROUND: To analyse the relationship between subjective pain score and other measures of clinical, radiographic and functional status; in particular Larsen radiographic scores and Health Assessment Questionnaire (HAQ); in patients with severe rheumatoid arthritis (RA) with a disease duration of less than 3 years. METHODS: In this cross sectional study of 105 patients with RA (76 women, 29 men: mean age 50.93; mean disease duration 15.86 months; 71% rheumatoid factor positive) subjective pain was assessed according to the Visual Analog Scale (VAS). Correlation coefficients between pain score and disease activity measures (patients' global assessment of disease by VAS, number of tender and swollen joints, morning stiffness, erythrocyte sedimentation rate [ESR], C-reactive protein [CRP] and titre of rheumatoid factor, radiographic evaluations (Larsen-Dale scores for radiographic damage of the small joints of the hands, wrist and feet), disability measures (health assessment questionnaire [HAQ]), and demographic variables were calculated; hierarchical regression analysis was done with subjective pain score as the dependent variable. RESULTS: The Spearman's correlation coefficient comparing subjective pain and HAQ was 0.421 (p < 0.001), between subjective pain and global assessment of disease and morning stiffness was 0.573 (p < 0.001) and 0.427 (p < 0.001) respectively, and between pain and number of tender and swollen joints 0.037 and 0.050 respectively (p > 0.05). In regression analysis, global assessment of disease by patients explained 32.8% of the variation in pain intensity score, morning stiffness 10.7%, CRP 4.0%, HAQ 3.8% and Larsen-Dale scores explained 2.1%; other variables were not significant in the model. CONCLUSIONS: Pain scores of patients with early severe rheumatoid arthritis are correlated at higher levels with patients' global assessment of disease and with morning stiffness rather than with radiographic or other clinical variables such as number of tender and swollen joints.