Interrelated modulation of endothelial function in Behcet's disease by clinical activity and corticosteroid treatment

Corticosteroids are commonly used in empirical treatment of Behcet's disease (BD), a systemic inflammatory condition associated with reversible endothelial dysfunction. In the present study we aimed to dissect the effects of clinical disease activity and chronic or short-term corticosteroid treatment on endothelial function in patients with BD. In a case-control, cross-sectional study, we assessed endothelial function by endothelium dependent flow mediated dilatation (FMD) at the brachial artery of 87 patients, who either were or were not receiving chronic corticosteroid treatment, and exhibiting variable clinical disease activity. Healthy individuals matched for age and sex served as controls. Endothelial function was also assessed in a prospective study of 11 patients before and after 7 days of treatment with prednisolone given at disease relapse (20 mg/day). In the cross-sectional component of the study, FMD was lower in patients than in control individuals (mean ± standard error: 4.1 ± 0.4% versus 5.7 ± 0.2%, P = 0.003), whereas there was a significant interaction between the effects of corticosteroids and disease activity on endothelial function (P = 0.014, two-factor analysis of variance). Among patients with inactive BD, those who were not treated with corticosteroids (n = 33) had FMD comparable to that in healthy control individuals, whereas those treated with corticosteroids (n = 15) had impaired endothelial function (P = 0.023 versus the respective control subgroup). In contrast, among patients with active BD, those who were not treated with corticosteroids (n = 20) had lower FMD than control individuals (P = 0.007), but in those who were receiving corticosteroids (n = 19) the FMD values were comparable to those in control individuals. Moreover, FMD was significantly improved after 7 days of prednisolone administration (3.7 ± 0.9% versus 7.6 ± 1.4%, P = 0.027). Taken together, these results imply that although corticosteroid treatment may impair endothelial function per se during the remission phase of the inflammatory process, it restores endothelial dysfunction during active BD by counteracting the harmful effects of relapsing inflammation.