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Ngian G.-S.,University of Melbourne | Sahhar J.,Rheumatology Unit | Proudman S.M.,University of Adelaide | Stevens W.,St Vincents Hospital | And 2 more authors.
Annals of the Rheumatic Diseases | Year: 2012

Objectives: To determine the prevalence of coronary heart disease (CHD) and cardiovascular risk factors in a well-characterised cohort of systemic sclerosis (SSc) patients, and to compare this with the general population. Methods: A cross-sectional study of the prevalence of CHD and cardiovascular risk factors in participants in the Australian Scleroderma Cohort Study was performed. Controls were drawn from the 2007-8 National Health Survey (NHS) and the Australian Diabetes, Obesity and Lifestyle Study (AusDiab). OR and 95% CI were calculated to determine the prevalence of CHD and cardiovascular risk factors in SSc patients compared with controls. Results: Data were available for 850 SSc patients (86% female), 15 787 NHS participants (53% female) and 8802 AusDiab participants (56% female). Adjusted for age and gender, the OR of CHD in SSc patients was 1.9 (95% CI 1.4 to 2.4) compared with controls from AusDiab and 2.0 (95% CI 1.5 to 2.5) compared with controls from the NHS. The OR of CHD increased to 3.2 (95% CI 2.3 to 4.5) for SSc patients compared with controls from AusDiab after further adjustment for cardiovascular risk factors. Hypercholesterolaemia, diabetes mellitus and obesity were significantly less prevalent in the SSc cohort than in AusDiab. Within the SSc cohort, the presence of pulmonary arterial hypertension was associated with CHD. Conclusions: This is the first report of an increased prevalence of CHD in SSc patients. Further studies are required to determine the relative contribution of scleroderma-specific factors such as microvascular disease to the development of CHD.


Salvarani C.,Unit of Rheumatology | Salvarani C.,Rheumatology Unit | Hunder G.G.,Rochester College
Current Opinion in Rheumatology | Year: 2012

Our better understanding of the PCNSV spectrum and its subsets will facilitate early recognition. This may facilitate earlier treatment and may prevent irreversible or even lethal outcomes. Copyright © Lippincott Williams & Wilkins.


To update the 2006 Italian Society for Rheumatology recommendations for the use of biologic (TNF-α blocking) agents in the treatment of psoriatic arthritis (PsA). A panel of experts performed a literature search and identified the items that required updating on the basis of new published data. A draft of the updated recommendations was circulated to a group of Italian Rheumatologists with a specific expertise in PsA and in therapy with biologic agents, and their suggestions were incorporated in the final version. A consensus was achieved regarding the initiation and the monitoring of anti-TNF-α agents in PsA. Inclusion and exclusion criteria were defined and specific recommendations were made for patients with psoriatic peripheral synovitis, spondylitis, enthesitis, and dactylitis, respectively. We also specified criteria for assessment of response to treatment and for withholding and withdrawal of therapy. These recommendations may be used for guidance in deciding which patients with PsA should receive biologic therapy. Further updates of these recommendations may be published on the basis of the results of new clinical studies and of data from post-marketing surveillance.


Andersson U.,Karolinska University Hospital | Harris H.E.,Rheumatology Unit
Biochimica et Biophysica Acta - Gene Regulatory Mechanisms | Year: 2010

HMGB1 is a ubiquitous nuclear protein that can be released by any damaged cell or by activated macrophages and certain other cell types. HMGB1 has been successfully therapeutically targeted in multiple preclinical models of infectious and sterile diseases including arthritis. Extracellular HMGB1 mediates inflammation via induction of cytokine and metalloproteinase production and recruitment and activation of dendritic cells needed for priming of naïve T helper type 1 lymphocytes. HMGB1 can bind endogenous molecules such as IL-1β and nucleosomes and exogenous agents like endotoxin and microbial DNA. These complexes synergistically increase the capacity for activation of adaptive and innate immunity. HMGB1-nucleosome complexes induce autoantibody formation against double-stranded DNA and nucleosomes, which does not occur if HMGB1 is absent. These antibodies are central in the pathogenesis of systemic lupus erythematosus and patients with active disease have both increased HMGB1 and HMGB1-nucleosome levels in circulation. Furthermore, HMGB1 is strongly bipolar charged, enabling cell membrane passage and intracellular transport of complexed molecules including DNA. Rheumatoid arthritis patients have excessive extracellular HMGB1 levels in joints and serum. The HMGB1 release is caused by cytokines, activated complement and hypoxia. The most prominent HMGB1 protein and mRNA expression arthritis is present in pannus regions, where synovial tissue invades articular cartilage and bone. HMGB1 promotes the activity of proteolytic enzymes, and osteoclasts need HMGB1 for functional maturation. Neutralizing HMGB1 therapy in preclinical models of arthritis confers striking protection against structural damage. This review summarizes selected aspects of HMGB1 biology relevant for induction and propagation of some autoimmune conditions. © 2009 Elsevier B.V. All rights reserved.


Unizony S.,Rheumatology Unit | Stone J.H.,Rheumatology Unit | Stone J.R.,Harvard University
Current Opinion in Rheumatology | Year: 2013

Purpose of Review: Recent advancements in the understanding of the pathogenesis of large-vessel vasculitis may broaden our currently limited therapeutic possibilities. This review summarizes the available evidence for new treatment strategies in this spectrum of diseases. Recent Findings: Interleukin (IL) 6 appears to be an important mediator of the pathology in large-vessel vasculitis. IL-6 is upregulated in inflamed arteries of patients with giant cell arteritis and Takayasu arteritis, and serum levels of this cytokine mirror disease activity. Encouraging preliminary results have been obtained with the IL-6 receptor (IL-6R) antagonist tocilizumab for the treatment of large-vessel vasculitides, including both giant cell arteritis and Takayasu arteritis, and the aortitis of Cogan syndrome and relapsing polychondritis. A small number of patients with Takayasu arteritis and IgG4-related aortitis have also been successfully treated with the B-cell depleting agent rituximab, and some patients with refractory Takayasu arteritis have responded to the immunomodulator leflunomide. Summary: The possibility of biologic therapy in large vessel vasculitis has emerged. At this time, better delineation of the immunopathogenic mechanisms of this spectrum of diseases and prospective randomized clinical trials are required to move the field forward and decrease the cumulative glucocorticoid toxicity seen in these disorders. Copyright © 2012 Lippincott Williams & Wilkins.


Lidar M.,Rheumatology Unit | Langevitz P.,Rheumatology Unit
Autoimmunity Reviews | Year: 2012

Systemic sclerosis is a systemic, inflammatory, autoimmune disease affecting the skin and viscera, manifesting pathologically with microvascular lesions, perivascular infiltration by mononuclear cells and increased deposition of extracellular collagen. The rarity of the disease as well as its propensity to appear in the early 1940s, explain the low frequency of concurrent scleroderma and pregnancy. However, the marked female excess, as well as the trend for increasing maternal age due to social change and assisted reproductive technologies, renders heightened significance to issues of fertility, pregnancy course and pregnancy outcomes.In the past, scleroderma patients were thought to be at high risk for poor fetal and maternal outcome, but more current retrospective studies show that despite an increased frequency of prematurity and small for gestational age infants, overall maternal and neonatal survival is good. Hence, at present, with close monitoring and appropriate therapy most scleroderma patients can sustain a successful pregnancy. Therapy with hydroxychloroquine and low dose steroids as well as judicious use of intravenous immunoglobulins is permitted. Renal crisis remains the most dreaded complication of a scleroderma pregnancy and necessitates prompt institution of ACE inhibitor therapy despite its potential teratogenicity. In order minimize the risk for renal crisis, pregnancies should be avoided in rapidly progressive diffuse disease as such patients are at a greater risk for developing serious cardiopulmonary and renal problems early in the disease. This review shall focus on the bi-directional effects of scleroderma on fertility and pregnancy as well as on the management of pregnancy and delivery in the scleroderma patient. © 2011 Elsevier B.V.


Carruthers M.N.,Rheumatology Unit | Stone J.H.,Massachusetts General Hospital | Khosroshahi A.,Rheumatology Unit
Current Opinion in Rheumatology | Year: 2012

The diagnosis of IgG4 related disease continues to be challenging. Increasing recognition of IgG4 related disease has led to a large body of literature on organ sites of involvement. Understanding how the disease manifests itself is critical to diagnosis and ultimately treatment. Copyright © Lippincott Williams & Wilkins.


Seidel M.F.,Rheumatology Unit | Muller W.,University of Basel
Expert Opinion on Pharmacotherapy | Year: 2011

Introduction: The fibromyalgia syndrome (FMS) has a prevalence of about 2% and is characterized by generalized musculoskeletal pain, reduced pain threshold and autonomic and functional symptoms. It is a multifactorial syndrome with four different subgroups exhibiting pathophysiological and psychiatric findings. No precise treatment strategy is currently available for the different FMS subgroups. Areas covered: This article reviews the evidence for treatment options for the different FMS subgroups. Expert opinion: Therapy for the first subgroup of primary FMS, with high levels of pain but no psychopathological alterations, is targeted at nociceptors expressing serotonin (5-hydroxytryptamine-3; 5-HT3) receptors with 5-HT3 receptor antagonists. The second and third subgroups are characterized by depressive syndromes with a major indication for antidepressants. The fourth subgroup with psychosomatic syndromes requires psychotherapeutic treatment. Secondary FMS is similar to the primary syndromes but is triggered by a variety of other diseases and frequently responds to 5-HT3 receptor antagonist treatment. Different classes of drug, such as pregabalin, must be tested for efficacy and tolerance. FMS treatment strategies should be tailored after the identification of individual FMS subgroups. Although several groups of drug have been studied extensively, 5-HT3 receptor antagonists are most effective in patients without psychopathological alterations. © 2011 Informa UK, Ltd.


Reitblat T.,Rheumatology Unit | Reitblat O.,Rheumatology Unit
American Journal of Case Reports | Year: 2013

Background: Tumor necrosis factor-alpha inhibitors treatment is accosiated with several side effects. The most common are injection side reactions, headache, nausea and infections. The more rare are development of systemic autoimmune diseases. Case Report: We describe two patients, who developed ANCA associated vasculitis during Tumor necrosis factor alpha inhibitors treatment. The diagnosis was confirmed by appropriate tissue picture, CT scan and laboratory findings. Conclusions: Our case series are unique, because vasculitis appeared after many years of the treatment and during complete patient's remission of there main illness. © Am J Case Rep.


Abou-Raya A.,Rheumatology Unit | Abou-Raya S.,Geriatric Unit | Khadrawi T.,Alexandria University | Helmii M.,Medical Research Institute
Journal of Rheumatology | Year: 2014

Objective. To investigate the efficacy of 6 weeks of daily low-dose oral prednisolone in improving pain, mobility, and systemic low-grade inflammation in the short term and whether the effect would be sustained at 12 weeks in older adults with moderate to severe knee osteoarthritis (OA). Methods.A total of 125 patients with primary knee OA were randomized 1:1; 63 received 7.5 mg/day of prednisolone and 62 received placebo for 6 weeks. Outcome measures included pain reduction and improvement in function scores and systemic inflammation markers. Pain was assessed using the visual analog pain scale (0-100 mm). Secondary outcome measures included the Western Ontario and McMaster Universities Osteoarthritis Index scores, patient global assessment (PGA) of the severity of knee OA, and 6-min walk distance (6MWD). Serum levels of interleukin 1 (IL-1), IL-6, tumor necrosis factor (TNF)-α, and high-sensitivity C-reactive protein (hsCRP) were measured. Results. There was a clinically relevant reduction in the intervention group compared to the placebo group for knee pain, physical function, PGA, and 6MWD at 6 weeks. The mean difference between treatment arms (95% CI) was 10.9 (4.8-18.0), p < 0.001; 9.5 (3.7-15.4), p < 0.05; 15.7 (5.3-26.1), p < 0.001; and 86.9 (29.8-144.1), p < 0.05, respectively. Further, there was a clinically relevant reduction in the serum levels of IL-1, IL-6, TNF-α, and hsCRP at 6 weeks in the intervention group when compared to the placebo group. These differences remained significant at 12 weeks. The Outcome Measures in Rheumatology Clinical Trials- Osteoarthritis Research Society International responder rate was 65% in the intervention group and 34% in the placebo group (p < 0.05). Conclusion. Low-dose oral prednisolone had both a short-term and a longer sustained effect resulting in less knee pain, better physical function, and attenuation of systemic inflammation in older patients with knee OA (Clinical Trials.gov identifier NCT01619163). The Journal of Rheumatology Copyright © 2014. All rights reserved.

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