Abstract
Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare form of vasculitis associated with asthma and eosinophilia. Endothelial dysfunction has been well documented in other types of vasculitis but not in EGPA. Thirty patients (10 men and 20 women) diagnosed with EGPA and remaining in a remission, and 58 controls (24 men and 34 women) matched for age, sex, and body mass index, were enrolled in the study. We assessed each participants for typical risk factors of cardiovascular diseases and measured serum levels of vascular cell adhesion molecule-1 (VCAM-1), interleukin 6 (IL-6), and thrombomodulin. We also measured flow-mediated dilatation (FMD) of the brachial artery and intima-media thickness (IMT) of the common carotid artery using ultrasonography. Patients with EGPA had 20% higher serum level of VCAM-1 (p < 0.001) and 41.9% of thrombomodulin (p < 0.001). They also had 38.8% lower relative increase of FMD (FMD%) (p < 0.001), indicating endothelial dysfunction. These differences remained significant also after adjustment for potential confounders. Laboratory and ultrasonographic parameters of endothelial injury were correlated to the markers of inflammation and impaired kidney function. Determinants of lower FMD% in a simple regression model were pack-years of smoking (β = − 0.3 [95% confidence interval (CI) − 0.5 to − 0.1]), serum level of IL-6 (β = − 0.36 [95% CI − 0.62 to − 0.1]), and thrombomodulin (β = − 0.34 [95% CI − 0.6 to − 0.08]). EGPA patients are characterized by inflammatory endothelial injury that is likely related to the pathogenesis of the disease. Proper immunosuppressive treatment is the best method to prevent atherosclerosis and future cardiovascular events, the patients may also benefit from additional preventive interventions.
Highlights
Eosinophilic granulomatosis with polyangiitis (EGPA, formerly named Churg-Strauss syndrome) is a rare disease withClin Rheumatol (2019) 38:417–424EGPA is a systemic disease, clinical manifestation can be highly variable and patients with EGPA may present with gastrointestinal, neurological, and cardiovascular symptoms [7,8,9].In anti-neutrophil cytoplasmic antibody (ANCA)-positive associated vasculitis (AAV), vascular damage is caused by the stimulation of neutrophils by antibodies, their subsequent adhesion and migration to endothelium, release of proteolytic enzymes, and proinflammatory cytokines, leading to endothelial cell damage [3]
The inflammatory state was estimated by interleukin-6 (IL-6) serum level, while injury of endothelium was assessed by serum concentration of vascular cell adhesion molecule-1 (VCAM1) and thrombomodulin
We demonstrated that even when EGPA is in remission, increased levels of thrombomodulin and vascular cell adhesion molecule-1 (VCAM-1) are present in the blood, suggesting ongoing endothelial damage
Summary
In ANCA-positive AAV, vascular damage is caused by the stimulation of neutrophils by antibodies, their subsequent adhesion and migration to endothelium, release of proteolytic enzymes, and proinflammatory cytokines, leading to endothelial cell damage [3]. In the 60% of EGPA patients who are ANCA-negative, the exact pathology in unknown, but it is suspected to be related to impaired eosinophil function. A few studies have found endothelial damage and progression of atherosclerosis in AAV patients [10,11,12,13] but the significance of their results is limited by small sample size. Endothelial function was determined by ultrasound measurements of flow-mediated dilatation (FMD) of a brachial artery. This method enables estimation of the endothelium’s response to shear, releasing nitric oxide and dilatation. Progression of atherosclerosis was assessed by intima-media thickness (IMT) measurements of the common carotid arteries
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