CTA-defined LVV occurs in two-thirds of patients with GCA at the time of diagnosis and aortic dilation is already present in 15%. Previous corticosteroid treatment may decrease CTA-detected LVV.

GCA patients with a strong systemic inflammatory response, who have been previously shown to be more resistant to corticosteroid therapy, have elevated tissue expression of proinflammatory cytokines IL-1beta, TNFalpha and IL-6. High production of TNFalpha is associated with longer corticosteroid requirements.

Objective. Giant cell arteritis (GCA) may involve the aorta. Retrospective studies have demonstrated a higher prevalence of aortic aneurysm among patients with GCA compared with the general population. We investigated the prevalence of aortic aneurysm in a cohort of patients with biopsy-proven GCA using a defined protocol and assessed whether persisting low-grade disease activity is associated with higher risk of developing aortic aneurysm. Methods. Fifty-four patients with GCA (14 men and 40 women) were cross-sectionally evaluated after a median followup of 5.4 years (range 4.0 -10.5 years). The screening protocol included a chest radiograph, abdominal ultrasonography scan, and computed tomography scan when aortic aneurysm was suspected or changes with respect to the baseline chest radiograph were observed. Clinical and laboratory data, corticosteroid requirements, and relapses were prospectively recorded. Results. Twelve patients (22.2%) had significant aortic structural damage (aneurysm/dilatation), 5 of them candidates for surgical repair. Aortic aneurysm/dilatation was more frequent among men (50%) than women (12.5%; relative risk 3.5, 95% confidence interval 1.53-8.01, P ‫؍‬ 0.007). At the time of screening, patients with aneurysm/dilatation had lower serum acute-phase reactants, lower relapse rate, and needed shorter periods to withdraw prednisone than patients without aortic structural damage. Conclusion. There is a substantial risk of developing aortic aneurysm/dilatation among patients with GCA. Our data do not support that aneurysm formation mainly results from persistent detectable disease activity. Additional factors including characteristics of the initial injury or the target tissue may also determine susceptibility to aortic aneurysm/ dilatation.

Background— Patients with giant-cell arteritis (GCA) who develop a strong acute-phase response are at low risk of disease-related ischemic events. Methods and Results— To assess the potential protective role of proinflammatory cytokines in the development of ischemic events in GCA, we measured tissue expression (66 individuals) and/or circulating levels (80 individuals) of interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), and IL-6 in patients with biopsy-proven GCA. Tissue expression was determined by quantitative real-time polymerase chain reaction and immunohistochemistry. Circulating cytokines were determined by enzyme-linked immunoassay. We found that patients with disease-related ischemic events had lower IL-6 mRNA levels (5.9±2.1 versus 27.6±7.8 relative units, P =0.013), lower IL-6 immunohistochemical expression scores (1.5±0.9 versus 2.7±1, P =0.001), and lower circulating levels of IL-6 (13.6±2.1 versus 24±2.4 pg/mL, P =0.002) than patients without ischemic complications. No significant differences were found for either IL-1β or TNF-α. We subsequently investigated direct effects of IL-6 on vessel wall components. We found that IL-6 stimulates endothelial cell proliferation and differentiation into capillary-like structures and induces full angiogenic activity in both ex vivo (aortic ring) and in vivo (chick chorioallantoic membrane) assays. Conclusions— GCA patients with ischemic complications have lower tissue expression and circulating levels of IL-6 than patients with no ischemic events. IL-6 has relevant direct effects on vascular wall components that might be protective: IL-6 activates a functional program related to angiogenesis that may compensate for ischemia in patients with GCA.