Smoking, the oral contraceptive pill, and Crohn's disease

Abstract

Both cigarette smoking and the oral contraceptive pill have been implicated as aggravating factors in Crohn's disease. Based upon the recent demonstration of multifocal gastrointestinal infarction in Crohn's disease, a possible pathogenic mechanism for this condition, we propose how smoking and the oral contraceptive pill may potentiate a tendency for focal thrombosis and hence exacerbate the activity of Crohn's disease.

PIP: Both cigarette smoking and oral contraceptives (OCs) have been shown to exacerbate Crohn's disease. The pathogenic mechanism for Crohn's disease proposed by the authors--multifocal gastrointestinal infarction, mediated by a chronic mesenteric vasculitis--provides a framework for understanding these effects. Smoking induces morphologic injury to endothelial cells, inhibits aortic endothelial prostacyclin synthesis, and leads to elevated levels of plasma fibrinogen and decreased levels of plasminogen and tissue plasminogen activator activity. OCs that contain more than 50 mcg of ethinyl estradiol increase levels of procoagulant substrates and produce decreases in both anticoagulant and fibrinolytic activity. Enhanced expression of both monocyte and vascular endothelial cell procoagulant activity is the initiating event in the fibrin formation that initially characterizes Crohn's disease. Although microvascular changes have been observed in Crohn's disease patients who neither smoke nor use OCs, it appears likely that when further prothrombic stimuli such as OCs and nicotine are superimposed on Crohn's disease, the result is an exacerbation of disease activity.