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Fabiola Atzeni

Publications and source records attributed to Fabiola Atzeni.

At least 19 recordsLinked to original sources
PubMed2006

Long-term prognosis and causes of death in systemic lupus erythematosus.

PURPOSE: We studied survival rate, prognostic factors, and causes of death in patients with systemic lupus erythematosus (SLE), particularly focusing on the influence of disease severity. PATIENTS AND METHODS: A cohort of 207 consecutive Italian patients with SLE were prospectively studied. All prominent clinical and serologic parameters were evaluated and considered as prognostic risk factors. Causes of death were defined on the basis of clinical data and, when available, postmortem examination. Survival was calculated from the time of diagnosis by Kaplan-Meier method. RESULTS: A total of 17 of 207 patients died; causes of death were active disease manifestations in 35.3% of cases and complication of the disease or its treatment in 64.7% of cases. The survival rates at 5, 10, and 15 years after the diagnosis were 96%, 93% and 76%, respectively. By multivariate analysis of the risk factors, a predictive model consisting of male gender, positive lupus anticoagulant, and "severe" SLE was identified. The survival curve of the patients with severe disease was similar to that of patients with mild disease until 10 to 15 years from the diagnosis. Thereafter the two curves tended to diverge, showing a clear survival decline in patients with severe disease. CONCLUSIONS: Our study confirms the increase of short- and medium-term survival in patients with SLE, but long-term prognosis remains poor in patients with severe SLE manifestations.

Adolescent↗
PubMed2006

Calcium deposition and associated chronic diseases (atherosclerosis, diffuse idiopathic skeletal hyperostosis, and others).

Extracellular matrix mineralization or calcification occurs in many pathologic conditions, including atherosclerosis, medial wall calcification, diffuse idiopathic skeletal hyperostosis, and chondrocalcinosis. Vascular wall calcification is the most common and involves two mechanisms: passive calcification resulting from breakdown of the protection system and active calcification resulting from transdifferentiation of mesenchymal cells in the vascular wall to bone. Although reports are conflicting, several matrix proteins are identified as protective factors against dystrophic calcification in nonosseous tissues. Serum matrix Gla protein may be a marker of osteometabolic syndromes that cause hyperostosis and plays a role in Milwaukee shoulder syndrome.

Atherosclerosis↗
PubMed2006

Adalimumab clinical efficacy is associated with rheumatoid factor and anti-cyclic citrullinated peptide antibody titer reduction: a one-year prospective study.

Studies on autoantibody production in patients treated with tumor necrosis factor-alpha (TNF-alpha) inhibitors reported contradictory results. We investigated in a prospective study the efficacy of a treatment with human monoclonal anti-TNF-alpha antibody (adalimumab) in patients with rheumatoid arthritis (RA) and we evaluated the relationship between treatment efficacy and the incidence and titers of disease-associated and non-organ-specific autoantibodies. Fifty-seven patients with RA not responsive to methotrexate and treated with adalimumab were enrolled. Antinuclear, anti-double-stranded(ds)DNA, anti-extractable nuclear antigens, anti-cardiolipin (aCL), anti-beta2 glycoprotein I (anti-beta2GPI) autoantibodies, rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) autoantibodies were investigated at baseline and after 6 and 12 months of follow-up. Comparable parameters were evaluated in a further 55 patients treated with methotrexate only. Treatment with adalimumab induced a significant decrease in RF and anti-CCP serum levels, and the decrease in antibody titers correlated with the clinical response to the therapy. A significant induction of antinuclear autoantibodies (ANA) and IgG/IgM anti-dsDNA autoantibodies were also found in 28% and 14.6% patients, respectively, whereas aCL and anti-beta2GPI autoantibodies were not detected in significant quantities. No association between ANA, anti-dsDNA, aCL and anti-beta2GPI autoantibodies and clinical manifestations was found. Clinical efficacy of adalimumab is associated with the decrease in RF and anti-CCP serum levels that was detected after 24 weeks and remained stable until the 48th week of treatment. Antinuclear and anti-dsDNA autoantibodies, but not anti-phospholipid autoantibodies, can be induced by adalimumab but to a lower extent than in studies with other anti-TNF blocking agents.

Adalimumab↗
PubMed2006

Increased neural sympathetic activation in fibromyalgia syndrome.

Fibromyalgia (FM) is a syndrome characterized by widespread musculoskeletal pain, although the mechanisms underlying the pain have not been fully elucidated. FM patients describe a number of nonspecific symptoms, such as anxiety, depression, fatigue, unrefreshing sleep, and gastrointestinal complaints, which appear after a flu-like illness, or after physical or emotional trauma in half of the patients, and are often exacerbated by exertion, stress, lack of sleep, and weather changes. There may also be symptoms of orthostatic intolerance, which suggests underlying abnormalities in cardiovascular neural regulation. Research suggests that various components of the central nervous system are involved, including the hypothalamic-pituitary-adrenal (HPA) axis, pain-processing pathways, and the autonomic nervous system (ANS). This review discusses the general aspects of the altered HPA and ANS, sympathetic overactivity, and alterations in cardiovascular autonomic responses to gravitational stimuli.

Fibromyalgia↗
PubMed2005

Five-year follow-up by transesophageal echocardiographic studies in primary antiphospholipid syndrome.

This prospective study describes valvular abnormalities assessed by transesophageal echocardiography (TEE) in patients with primary antiphospholipid syndrome (APLS) over a 5-year follow-up. Of the 56 patients with APLS evaluated at baseline, 47 (84%) had repeat TEE examinations, including 3 patients who died before the end of the follow-up. The first TEE study showed cardiac involvement (thickening or vegetations and embolic sources) in 34 subjects (61%), with mitral valve thickening, the most common abnormality, present in 30 patients (54%). Embolic sources were found in 14 patients (25%; 9 severe spontaneous echocardiographic contrast, 5 Libman-Sacks endocarditis), associated with mitral valve thickening or stenosis in 10 patients. Over the 5-year follow-up, cardiac involvement was unchanged in 30 subjects (64%). New cardiac abnormalities were observed in 17 patients (36%), 15 (88%) with high immunoglobulin-G (IgG) anticardiolipin antibody (aCL) titers and 2 (12%) with low IgG aCL titers. In conclusion, this study showed that mitral valve thickening and embolic sources are frequently observed in patients with APLS. Anticoagulant and/or antiplatelet treatment was ineffective in terms of valvular lesion regression. New appearances of cardiac involvement are significantly related to high IgG aCL titers.

Adult↗
PubMed2005

Thrombotic risk factors in primary antiphospholipid syndrome: a 5-year prospective study.

BACKGROUND AND PURPOSE: Because thromboembolic events are frequently observed in primary antiphospholipid syndrome (PAPS), we assessed the risk factors for new thrombotic episodes. METHODS: Fifty-six PAPS patients (mean age, 37+/-10 years) were prospectively studied for 5 years. The preliminary Sapporo classification criteria for antiphospholipid syndrome (APS; a medium-high anticardiolipin antibody [aCL] titer and/or a positive lupus anticoagulant [LA] test in the presence of vascular thrombosis and/or pregnancy morbidity) were used to confirm the diagnosis. Thrombotic episodes or pregnancy losses before a diagnosis of PAPS were considered events, and any new disease manifestation other than thrombocytopenia was considered a recurrent event. Only patients with objectively verified thrombotic events were included in the study. RESULTS: Twenty-one new thrombotic events were observed in 15 subjects (26.8%), including 3 (5.4%) who died during the follow-up. The patients with IgG aCL levels of >40 IgG phospholipid unit (GPL-U) showed a higher incidence of new thrombotic events (43.3%) than those with levels of < or =40 GPL-U (7.7%). Univariate analysis identified a history of recurrent clinical events (P=0.004), a highly positive aCL titer (P=0.007), and the presence of cardiac abnormalities (P=0.036) as significant risk factors for new thrombotic events. A multivariate regression model confirmed that an IgG aCL titer of >40 GPL-U was an independent risk factor for thrombosis (odds ratio, 9.17; 95% confidence interval, 1.83 to 46.05). CONCLUSIONS: A high IgG aCL titer is the strongest predictor of new thrombotic events in PAPS patients.

Abortion, Spontaneous↗
PubMed2005

Effect of adalimumab on neutrophil function in patients with rheumatoid arthritis.

Neutrophils are known to be targets for the biological activity of tumour necrosis factor (TNF)-alpha in the pathogenesis of rheumatoid arthritis (RA). Therefore, these cells may be among the targets of anti-TNF-alpha therapy. In this study we evaluated the effect of therapy with adalimumab (a fully human anti-TNF-alpha mAb; dosage: 40 mg subcutaneously every other week) on certain phenotypic and functional aspects of neutrophils obtained from 10 selected patients with RA and 20 healthy control individuals. Peripheral blood neutrophils were obtained at baseline and during anti-TNF-alpha therapy (2, 6 and 12 weeks after the first administration of adalimumab). All patients had been receiving a stable regimen of hydroxychloroquine, methotrexate and prednisone for at least 3 months before and during the study. Baseline neutrophil chemotaxis was significantly decreased in RA patients when compared with control individuals (P < 0.001). Two weeks after the first administration of adalimumab, chemotactic activity was completely restored, with no differences noted between patients and control individuals; these normal values were confirmed 6 and 12 weeks after the start of anti-TNF-alpha therapy. Phagocytic activity and CD11b membrane expression on neutrophils were similar between RA patients and control individuals; no modifications were observed during TNF-alpha neutralization. The production of reactive oxygen species, both in resting and PMA (phorbol 12-myristate 13-acetate)-stimulated cells, was significantly higher in RA patients at baseline (P < 0.05) and was unmodified by anti-TNF-alpha mAb. Finally, we showed that the activation antigen CD69, which was absent on control neutrophils, was significantly expressed on neutrophils from RA patients at baseline (P < 0.001, versus control individuals); however, the molecule was barely detectable on cells obtained from RA patients during adalimumab therapy. Because CD69 potentially plays a role in the pathogenesis of arthritis, our findings suggest that neutrophils are among the targets of anti-TNF-alpha activity in RA and may provide an insight into a new and interesting mechanism of action of anti-TNF-alpha mAbs in the control of inflammatory arthritis.

Adalimumab↗
PubMed2005

Potential off-label use of infliximab in autoimmune and non-autoimmune diseases: a review.

TNF-alpha is a crucial cytokine in the establishment and maintenance of inflammation in multiple autoimmune and non-autoimmune 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 and rheumatoid arthritis (RA) and has become a widely used treatment for these diseases. More recent controlled trials have also shown the effectiveness of TNF-alpha blockers in psoriasis, psoriatic arthritis, and ankylosing spondylitis. The results of clinical trials, open-label studies, and case studies indicate that TNF inhibitors (alone or in combination with other protocols) look very promising for the treatment of a variety of other conditions, including uveitis, sarcoidosis, Sjögren's syndrome (SS), Behcet's syndrome, vasculitis, and graft versus host disease. 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. The neutralisation of TNF might therefore play a role in the treatment of many autoimmune and non-autoimmune disorders other than Crohn's disease or RA. We here review the current and prospective roles of infliximab in the treatment of autoimmune diseases and other conditions that do not currently have FDA or EMEA approval.

Animals↗
PubMed2005

The role of echocardiographic techniques in connective tissue diseases.

Connective tissue diseases (CTD) lead to a high prevalence of common cardiac manifestations (pericarditis and myocarditis) and of ischemic coronary events with a considerable increase in cardiac mortality related to premature atherosclerosis. Although there are several techniques able to detect cardiac involvement in CTD patients, the most useful and non-invasive technique is echocardiographic exam which is able to detect not only valvular abnormalities, pericardial diseases and pulmonary hypertension but also left ventricular (LV) systolic or diastolic (regional or global) wall motion dysfunction. It is also well known that transesophageal echocardiography (TEE) can better identify cardiac abnormalities, vegetations and embolic sources. Symptomatic patients with positive stress echocardiographic exam or dipyridamole thallium imaging test should be referred for possible cardiac catheterization, especially if a large ischemic territory is involved. Until now, the echocardiographic evaluation of coronary artery tree consisted of assessing regional and global left ventricular systolic and diastolic function at rest and during pharmacological stress test. Recently, a new echocardiographic noninvasive method that allows direct assessment of coronary flow velocity in the mid-distal portion of left anterior descending artery (LAD) has been developed and validated. Advanced ultrasound technology (high-frequency broadband transducer with second harmonic capability) has now made possible a direct arterial visualization and measurement of coronary artery flow in left anterior descending in CTD patients with the assessment of coronary flow reserve (CFR).

Adult↗
PubMed2005

TNF-alpha, rheumatoid arthritis, and heart failure: a rheumatological dilemma.

Cardiovascular disease (CVD) is responsible for 35-50% of rheumatoid arthritis (RA) deaths, whereas, in the general UK adult population, coronary heart disease is responsible for 1/4 deaths in males and 1/5 deaths in female. This increased risk may be attributable to RA-specific risk factors such as hyperhomocysteinemia, disease-related dyslipidemia or vascular inflammation, or to morbidity related to medications and high levels of tumor necrosis factor-alpha (TNF-alpha). The possible roles of TNF-alpha in the development of atherosclerosis include the recruitment of inflammatory cells to the site of injury or the promotion of adverse vascular smooth muscle cell remodelling. TNF-alpha may also act as a proinflammatory factor in plaque rupture. Anticytokine therapy could prove beneficial in the treatment of patients with heart failure. While early studies supported this hypothesis, anti-TNF strategies have not demonstrated salutary benefits in large multicenter randomized and placebo-controlled clinical trials in patients with symptomatic heart failure. There is a variety of possible explanations for the failure of anti-TNF therapy: (1) TNF antagonism has untoward effects in the setting of heart failure; (2) the biological agents used in the trials were intrinsically toxic; (3) sex and race may have important implications in the outcome after anticytokine therapy; (4) the TNF-alpha protein contains a polymorphism, and, in fact, genoma plays a role in modifying the pharmacologic response to anticytokines; (5) anti-TNF-alpha approaches could have had pharmacodynamic interactions with other heart failure medications; and (6) the patients in these trials may have been inappropriately selected. These disappointing results may determine controversial attitude in the long-term treatment with anti-TNF agents in RA or Crohn's disease. The effects of TNF-alpha blockers on incident cases of congestive heart failure (CHF) in RA are controversial. The available published data suggest the following: (a) RA patients with history of CHF and a concomitant indication for the use of TNF-alpha blockers do not need a baseline cardiac evaluation to screen for heart failure; (b) patients with well-compensated mild CHF New York Heart Association (NYHA) classes I and II and a concomitant indication for the use of TNF-alpha blockers should be evaluated at baseline and then be closely monitored for any clinical signs of worsening heart failure; and (c) patients with (NYHA) class III or IV heart failure should not be treated with TNF-alpha blockers in any case.

Adalimumab↗
PubMed2005

Osteoarthritis: an overview of the disease and its treatment strategies.

Osteoarthritis (OA) is currently defined by the American College of Rheumatology as a "heterogeneous group of conditions that leads to joint symptoms and signs which are associated with defective integrity of articular cartilage, in addition to related changes in the underlying bone at the joint margins." Its prevalence after the age of 65 years is about 60% in men and 70% in women. The etiology of OA is multifactorial, with inflammatory, metabolic, and mechanical causes. A number of environmental risk factors, such as obesity, occupation, and trauma, may initiate various pathological pathways. OA indicates the degeneration of articular cartilage together with changes in subchondral bone and mild intraarticular inflammation. The principal treatment objectives are to control pain adequately, improve function, and reduce disability. Acetaminophen is frequently used for symptomatic OA with mild to moderate pain. Nonsteroidal antiinflammatory drugs (NSAIDs) are more effective in the case of moderate-severe pain, but they have an increased risk of serious upper gastrointestinal adverse events. The newer cyclooxygenase COX-2 specific inhibitors (Coxibs) are as efficacious as traditional NSAIDs and have a better gastrointestinal safety profile. Other compounds (eg, chondroitin sulfate, diacerein, glucosamine sulfate) have a symptomatic effect that is slower and less than that of NSAIDs. The structure-modifying effects of drugs are currently being evaluated, and both glucosamine sulfate and diacerein have been shown in some trials to have a beneficial structural effect. Nonpharmacological interventions are frequently and widely used in the management of OA patients, but there is little evidence that they are effective: the best studied and most successful nonpharmacological interventions are patient education, self-management, and exercise. There is some evidence for the pain-relieving efficacy of thermotherapy and transcutaneous electrical nerve stimulation (TENS) but not of electrotherapy, acupuncture, homeopathy, or manual therapy. The value of interventions aimed at improving function and maximizing independence (occupational therapy, walking aids, workplace adaptation) is also unclear. The disease course and patient's requirements often change over time, thus requiring a periodic review and readjustment of therapy rather than the rigid continuation of a single treatment.

Aged↗
PubMed2005

Do physicians treat symptomatic osteoarthritis patients properly? Results of the AMICA experience.

OBJECTIVE: The main objective of the AMICA project was to photograph the Italian scenario of osteoarthritis (OA) and its treatment in general and specialty practice. The study was designed to evaluate their prescription modalities to determine whether they matched the recently proposed treatment guidelines for OA (ACR 2000; EULAR 2000; APS 2002). METHODS: The study involved 2764 general practitioners (GPs) and 316 specialists who enrolled a total of 25,589 patients with OA of the hand, knee, and hip. RESULTS: Pharmacological treatment alone was prescribed to 55% of the patients seen by GPs, 25% of those seen by rheumatologists, 8% of those seen by orthopedic surgeons, and 17% of those seen by physical medicine specialists (GPs versus specialists, P < 0.001). Specialists often prescribed a combined pharmacological and nonpharmacological approach (rheumatologists 51%, orthopedic surgeons 66%, physical medicine specialists 76%). Concomitant comorbidities and their treatment do not seem to influence OA prescription modalities except for peptic ulcer and anticoagulant therapy. The presence of peptic ulcer was associated with a reduction in NSAID prescriptions (OR 0.61, CI 0.53 to 0.69) and more frequent use of Coxibs (OR 1.15, CI 1.03 to 1.28) and simple analgesics (OR 1.42; CI 1.26 to 1.61), as well as physical therapy. NSAIDs and Coxibs also were less frequently prescribed if patients were receiving anticoagulant therapy (NSAIDs OR 0.86, CI 0.70 to 1.06; Coxibs: OR 0.77; CI 0.64 to 0.93). Gastroprotective therapy was more frequently used in patients treated with NSAIDs, Coxibs, and analgesics. There was no significant difference in therapies prescribed for patients with hypertension or cardiac disease (myocardial infarction and/or angina pectoris). CONCLUSIONS: The published guidelines appear to be properly used by most of the physicians in terms of the pharmacological approach; however, the increased use of Coxibs has not reduced the amount of prescribed gastroprotection. No specific precautions were observed in the treatment of patients with hypertension or cardiac problems. Nonpharmacological treatments are mainly used in conjunction with medications and did not take into account the findings of evidence-based medicine. Continuing education of GPs and specialists caring for OA patients is essential.

Combined Modality Therapy↗
PubMed2005

Environment and systemic lupus erythematosus: an overview.

Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown etiology that manifests as a pleomorphic systemic disease mainly affecting females. The variety of autoantibodies found in the serum of patients indicate that SLE is an autoimmune disease, but the mechanisms leading to the aberrant responses are not clearly understood although it is thought that a number of genetic and environmental factors may be involved. Environmental (or non-genetic) exposures could include infectious agents, chemicals or other compounds capable of modulating immune responses such as occupational/environmental pollutants or drugs, and behavioural factors such as smoking and diet. Environmental exposures may lead to the production of autoreactive T cells and autoantibodies, the stimulation of pro- and antiinflammatory cytokines, and target end-organ damage, but are not so convincing as agents causing SLE. Exposure to viruses increases antibody titres, but these may be the result of polyclonal B cell activation. The amount and timing of exposure to different environmental factors may play a significant and complex role in the pathogenesis of SLE and other autoimmune diseases. A better understanding of the etiopathogenetic mechanism of SLE is required in order to clarify the multiple interactions between environmental exposures and genetic factors.

Animals↗
PubMed2005

Drug-induced lupus erythematosus.

Drug-induced lupus is a syndrome which share symptoms and laboratory characteristics with idiopathic systemic lupus erythematosus (SLE). The terms drug-induced lupus (DIL) and drug-induced lupus erythematosus (DILE) are preferred, but other ones are also used-drug-related lupus, lupus-like syndrome and lupus erythematosus medicamentosus. The first case of DILE was reported in 1945 and associated with sulfadiazine. In 1953, it was reported that DILE was related to the use of hydralazine. More than 80 drugs have been associated with DILE. The average age of patients with DILE is nearly twice that of patients with idiopathic SLE. Approximately half the patients with drug-induced SLE are women, compared with 90% of patients with idiopathic SLE. Similarly to idiopathic lupus, DILE can be divided into systemic, sub-acute cutaneous and chronic cutaneous lupus. The syndrome is characterised by arthralgia, myalgia, pleurisy, rash and fever in association with antinuclear antibodies in the serum. The clinical and laboratory manifestations of drug-induced SLE are similar to those of idiopathic SLE, but central nervous system and renal involvement are rare in DILE. Recognition of DILE is important because it usually reverts within a few weeks after stopping the drug. This review discusses the general issues in DILE, such as pathogenic mechanisms, clinical forms and diagnostic criteria, and provides more detailed information for some of the most recent implicated drugs: minocycline, statins, anti-TNF-alpha agents.

Drug-Related Side Effects and Adverse Reactions↗
PubMed2005

Autoimmunity and anti-TNF-alpha agents.

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.

Adalimumab↗