To determine whether concomitant treatment with angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) is associated with changes in the outcome of patients with giant cell arteritis (GCA).
A study cohort of 106 patients with biopsy-proven GCA was longitudinally followed for 7.8 ± 3.3 years. Patients were stratified according to their treatment with ACEI, ARB, or no ACEI/ARB. Time to first relapse, number of flares, time to achieve a stable prednisone dose <10 mg/day and <5 mg/day with no relapses, time required to completely discontinue prednisone, cumulative dose of prednisone received during the first year and concentrations of acute-phase reactants at pre-defined time points (baseline, 6, 12, 18 and 24 months) were compared among the 3 groups. Cox proportional hazards models were performed to adjust for potential confounders.
Patients receiving ARB presented a significantly longer relapse-free survival than patients treated with ACEI or patients not receiving ACEI/ARB (p=0.02). The adjusted hazard ratio for relapses in patients treated with ARB was 0.32 (95% CI 0.12-0.81, p=o.017). In addition, patients who received ARB achieved a prednisone maintenance dose <10 mg/day faster than all other patients (p=0.0002). No significant differences were observed among groups in acute-phase reactant levels during follow-up. However, patients not receiving ACEI/ARB had significantly higher C-reactive protein and haptoglobin concentrations than those receiving ACEI or ARB at various time-points.
Addition of ARB to glucocorticoids is associated with lower relapse rate and more prolonged disease-free survival in patients with GCA.
[Show abstract][Hide abstract] ABSTRACT: To explore whether the insertion (I) and deletion (D) polymorphism of angiotensin-converting enzyme (ACE) confers susceptibility to vasculitis.
A meta-analysis was conducted on the associations between the ACE I/D polymorphism and vasculitis.
Twelve studies, including four on Behçet's disease (BD), four on Henoch-Schenlein purpura (HSP), three on Kawasaki disease (KD), and one on Wegener's granulomatosis, were available for the meta-analysis. Meta-analysis showed that the DD + ID genotype was associated with susceptibility to vasculitis (odds ratio [OR] 1.468, 95% confidence interval [CI] 1.214-1.468, p = 7.4 × 10(-5)). The overall OR for the D allele was significantly increased in BD (OR 1.313, 95% CI 1.017-1.695). Meta-analysis of the DD+ID genotype, the DD genotype and the DD vs. II genotype showed marginal associations with BD, but meta-analysis of the D allele, and the DD+ID genotype showed significant associations with HSP (OR 1.446, 95% CI 1.021-2.049, p = 0.038; OR 1.881, 95% CI 1.385-2.595, p = 6.6 × 10(-5)). On the other hand, meta-analysis showed no association between KD and the ACE I/D polymorphism.
This meta-analysis shows that the ACE I/D polymorphism is associated with vasculitis susceptibility, especially in BD and HSP.
Journal of Renin-Angiotensin-Aldosterone System 03/2012; 13(1):196-201. DOI:10.1177/1470320311434240 · 2.40 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The balance between different immunological stimuli is essential in the progression and stabilization of atherosclerotic plaques. Immune regulation has been suggested as potential target for the treatment of atherosclerotic disease. We sought to determine whether treatment with pentoxifylline, a phosphodiesterase inhibitor with immunomodulating properties, could reduce the pro-inflammatory response observed in patients with acute coronary syndromes (ACS) and increase anti-inflammatory activity. In a double-blind, prospective, placebo-controlled study, 64 patients with ACS were randomized to receive pentoxifylline 400mg TID or placebo for 6 months. Analysis of the pro-inflammatory markers, C-reactive protein (CRP), interleukin (IL)-6, IL-12, interferon-gamma and tumor necrosis factor (TNF)-alpha and the anti-inflammatory cytokines, transforming growth factor (TGF)-beta1 and IL-10 were done at baseline, 1 and 6 months. Pentoxifylline treatment significantly reduced the adjusted levels of CRP and TNF-alpha compared to placebo after 6 months (P=0.04 and P<0.01, respectively). IL-12 increase was significantly less pronounced with pentoxifylline (P=0.04). The levels of the anti-inflammatory cytokine, IL-10, also declined significantly less in the pentoxifylline group compared to placebo (P<0.01) with a trend towards a higher increase of TGF-beta1 in the former group (P=0.16). Pentoxifylline reduces pro-inflammatory and increases anti-inflammatory response in patients with ACS and may have beneficial clinical effects on cardiovascular events.
[Show abstract][Hide abstract] ABSTRACT: Background Interleukin 17A (IL-17A) exerts pivotal proinflammatory functions in chronic inflammatory and autoimmune diseases.
Objective To investigate IL-17A expression in temporal artery lesions from patients with giant-cell arteritis (GCA), and its relationship with disease outcome.
Methods Fifty-seven patients with biopsy-proven GCA were prospectively evaluated, treated and followed for 4.5 years (52–464 weeks). Relapses, time (weeks) required to achieve a maintenance prednisone dose <10 mg/day, and time (weeks) to complete prednisone withdrawal were prospectively recorded. IL-17A mRNA was measured by real-time quantitative RT-PCR in temporal arteries from all patients and 19 controls. IL-17 protein expression was assessed by immunohistochemistry/immunofluorescence.
Results IL-17A expression was significantly increased in temporal artery samples from GCA patients compared with controls (6.22±8.61 vs 2.50±3.9 relative units, p=0.016). Surprisingly, patients with strong IL-17A expression tended to experience less relapses, and required significantly shorter treatment periods (median 25 vs 44 weeks to achieve <10 mg prednisone/day, p=0.0079). There was no correlation between IL-17A and RORc or RORα expression suggesting that these transcription factors may not exclusively reflect Th17 differentiation, and that cells other than Th17 cells might contribute to IL-17 expression in active patients. Accordingly, FoxP3+IL-17A+ cells were identified in lesions by confocal microscopy and were dramatically reduced in specimens from treated patients.
Conclusions IL-17A expression is increased in GCA lesions, and is a predictor of response to glucocorticoid treatment. The contribution of FoxP3+ cells to IL-17A production in untreated patients suggests that induced-Tregs may facilitate disease remission when proinflammatory cytokine production is downregulated by glucocorticosteroids.
Annals of the Rheumatic Diseases 09/2012; DOI:10.1136/annrheumdis-2012-201836 · 10.38 Impact Factor
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