Etiology
Buerger disease was initially described by Leo Buerger in 1908 as "a strange endarteritis and endophlebitis with gangrene of the feet;" its exact etiology remains unknown.[8] It is likely to be related to tobacco constituents with a genetic predisposition, associated with immunologic, endothelial, and coagulation responses. An increased risk of Buerger disease has been seen in Bangladeshi patients who smoke >20 "bidis" a day (a home-made cigarette consisting of low-quality tobacco and smoked without filters).[9] Cannabis arteritis closely resembles Buerger disease and has been reported in people who smoke cannabis.[10]
An infectious agent has been suggested as the cause of Buerger disease, although no pathogen has been identified. One early study reported that 75% of people with Buerger disease had periodontal infections, and an association with periodontal bacteria, in particular Porphyromonas gingivalis, has been made.[11][12][13] It is postulated that a platelet thrombus containing oral bacteria does not adhere to the vessel wall and lodges distally as an embolus.
A genetic predisposition has been suggested due to the higher incidence of Buerger disease in Ashkenazi than in non-Ashkenazi Jews in Israel.[14] The gene myeloid differentiation primary-response protein 88 (MyD88) has been identified as potentially offering resistance to Buerger disease in Japanese people.[15]
The multifactorial etiology of Buerger disease involves interactions between hereditary susceptibility, tobacco exposure, and immune and coagulable responses.
Pathophysiology
Buerger disease is a vasculitis affecting crural and brachial arteries. Advanced disease may include subclavian and axillary artery involvement. It has been known to affect cerebral, coronary, renal, gonadal, and mesenteric vessels to a much lesser degree.
In the acute pathologic phase, active inflammation of all 3 vessel layers is seen. In the chronic pathologic phase, the thrombus is organized with revascularization of the medial and adventitial layers. A hypercellular thrombus rich in lymphocytes, fibroblasts, and giant cells fills the vessel lumen. The internal elastic lamina remains intact with no vessel wall necrosis, calcification, or atheromatous plaques. Upon limb or digit amputation of chronically diseased tissue, the lumen is often found to be narrowed or occluded with fibrous thickening of the tunica intima. The vasculitis may be triggered by a hypersensitivity to tobacco constituents. Impaired endothelium-dependent vasodilation has been identified in patients with thromboangiitis obliterans, which may encourage thrombus formation.[16]
A cell-mediated immune response to artery collagen components has been suggested. The histocompatibility leukocyte antigen (HLA)-DRA was more frequently found and HLA-DRW6 less frequently found in patients with Buerger disease compared with smokers without Buerger disease and nonsmokers.[17]
Plasma levels of kallikreins and kininase II (components of the kinin system of blood proteins) are higher in patients with Buerger disease who are active smokers compared with non-Buerger disease patients, whether or not they smoke. These protein levels were significantly greater in patients with Buerger disease who were active smokers than in those who were ex-smokers. This may indicate that vasodilatation occurs in response to the vascular changes taking place, supporting a theory of immune complex deposition due to nicotine stimulation.[18]
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