TAO is a rare disease with differing worldwide prevalence. Reportedly, annual prevalence is 12.6 per 100,000, representing only 0.5 % of all PVD [6]. It is more frequent in East Europe, the Middle East and Asia with a high prevalence as 80 % among the Ashkenazi Jew population. Genetic influences are suggested by different prevalence in certain ethnic groups like in Israelis, some Indian groups, the Japanese, Southeast Asians and Middle Eastern groups and rarely in African-Americans. Buerger’s disease is now increasing in prevalence among women owing to changing patterns in smoking with an incidence between 11 and 23 % in the most recent studies [6–8].

The precise cause of TAO is still unknown and different hypotheses are suggested but the most important is tobacco smoking. Because 95 % of the patients are smokers, it is suggested that the factor of initiation, progression and prognosis of this disease is a reaction to the constituents of cigarettes. TAO is probably a process of self-aggression triggered by nicotine or an idiosyncratic immune response to some agents present in tobacco such as arsenic. Other addictions such as cannabis and cocaine may be co-responsible for Buerger’s disease, accelerating its clinical presentation and aggravating its extension. Since 1960, several case reports or case series, mainly from French authors, have reported distal arteritis mimicking TAO in cannabis users, suggesting a link with cannabis use [9–17]. Some authors suggest even the existence of a ‘cannabis arteritis’ [18], while others need more convincing scientific evidence [19]. However, if cannabis-associated arteritis is a distinct clinical entity, a subtype of TAO or a fortuitous association between a widely used drug and a rare disease, it remains controversial. Recurrent periodontal infections could play a role as well: polymerase chain reaction analysis demonstrated DNA fragments from anaerobic bacteria in both arterial lesions and oral cavities of patients with thromboangiitis obliterans but not in arterial samples from healthy controls [20]. Possibly, genetic modifications or autoimmune disorders are implicated [21]. Peripheral endothelium-dependent vasodilation is impaired in the no diseased limbs of patients with TAO, and this type of vascular dysfunction may contribute to such characteristics as segmental proliferative lesions or thrombus formation in the peripheral vessels [22]. Genetic influences are suggested by different prevalences in certain ethnic groups. In fact, TAO occurs frequently in Israelis, some Indian groups, the Japanese, Southeast Asians and Middle Eastern groups and rarely in African-Americans [23, 24]. Mutations in prothrombin 20210 G-A have also been the object of research [25, 26]. Studies have shown a possible relationship of TAO with hypercoagulable states, although its details are presently unknown. There are cases associated with protein S and protein C deficiencies [27, 28], antiphospholipid antibodies [29] and hyperhomocysteinemia [30, 31]. A recently published study showed that high concentrations of anticardiolipin antibodies were correlated with an early and more severe form of disease, including higher rates of amputation [32, 33].

Although TAO is a type of vasculitis, it is distinct from other vasculitis. There are two important distinctions: the absence of positive serological markers of inflammation and the nonexistence of autoantibodies. Acute-phase reactants such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), circulating immune complexes and autoantibodies such as antinuclear antibody, rheumatoid factor and complement levels are usually normal or negative.

Histologically, in the acute phase, preservation of the internal elastic lamina distinguishes it from the true necrotizing forms of arteritis. The artery or vein is modestly swollen, and there is a moderate infiltrate of the adventitia and media. The initial injuries are immune reactions associated with activation of lymphocytes, macrophages and dendritic cells in the arterial wall, followed by deposition of antiendothelial cell antibodies [4, 22, 23]. Pathologically, the thrombus in TAO is highly cellular, with much less intense cellular activity in the wall of the blood vessel. Lymphocytes exceed neutrophils, and occasional giant cells, and some eosinophils may be seen. In the chronic phase, cellularity of the vessel wall and thrombus decreases, microabscesses disappear and recanalization may begin .

Buerger’s disease is a clinical diagnosis that requires a compatible history, supportive physical findings and diagnostic vascular abnormalities on imaging studies [34–37]. Several different diagnostic criteria have been offered for the diagnosis of TAO (Table 23.1). The traditional diagnosis of TAO is based on the five criteria of Shionoya [34, 35], which are smoking history, onset before 50 years of age, infrapopliteal arterial occlusive disease, either upper limb involvement or phlebitis migrans and absence of atherosclerotic risk factors other than smoking, or based on the Olin criteria [6, 36], which are onset before 45 years of age; current tobacco use; distal extremity ischemia (infrapopliteal and/or infrabrachial) such as claudication, rest pain, ischemic ulcers or gangrene documented with noninvasive testing; laboratory tests to exclude autoimmune or connective tissue diseases and diabetes mellitus; exclusion of a proximal source of emboli with echocardiography and arteriography; and demonstration of consistent arteriographic findings in the involved and clinically noninvolved limbs.

Clinical manifestations of TAO may include painful digital ischemia, distal digital ulcerations, superficial thrombophlebitis and extremity claudication (Fig. 23.1). Raynaud’s phenomenon is present in greater than 40 % of patients with TAO and may be asymmetric. As BD progresses, it may lead to gangrene and amputation. Commonly, two extremities are involved. Beacuse the disease affects the distal vessels, gangrene usually precedes claudication, which is not frequent and, whenever present, is confined to the foot. Sometimes, this pathology may be presented in asymptomatic patients as occlusive lesions and demonstrated in angiograms in the small arteries of the foot or hand. It may remain unnoticed until the involvement of arteries in the calf or forearm. Although most common in the extremities, TAO may also involve the cerebral, coronary, renal, mesenteric and pulmonary arteries.

The differential diagnosis of TAO is quite simple in the presence of a typical clinic pathological picture. There are situations in which diagnosis can be difficult, such as early onset arteriosclerosis in young male smokers and collagen and autoimmune diseases in young people associated with digital cyanosis, pain and gangrene. The literature has demonstrated that ischemia induced by cocaine and cannabis consumption can mimic BD [9–19, 38]. Superficial thrombophlebitis differentiates TAO from other vasculitides and atherosclerosis, though it may also be observed in Behçet’s disease. In fact, patients may describe a migratory pattern of tender nodules that follow a venous distribution. Differential diagnosis must be done also with other arteritis such as Takayasu’s arteritis, in which larger elastic arteries such as the aorta and its branches are affected and where most of the patients are female in their second and third decade. With giant cell arteritis (temporal arteritis) which is a granulomatous vasculitis affecting large- and medium-sized arteries, cranial vessels are mostly affected. Polyarteritis nodosa is a necrotising vasculitis affecting small- and medium-sized artery vessels. Gastrointestinal and renal involvement is common, and males are mostly affected in middle age. Connective tissue disorders have to be kept in mind in patients with digital ulceration without typical findings of atherosclerosis. Differential diagnosis includes atherosclerosis, thromboembolism, CREST syndrome, systemic lupus erythematosus, rheumatoid arthritis, connective tissue disease and antiphospholipid antibody syndrome [39]. Drugs induced such as sulphonamide, cocaine and penicillins must be kept in mind. In the presence of lower extremity involvement, the possibility of popliteal artery entrapment syndrome or cystic adventitial disease should be considered, both of which should be readily apparent on arteriography, computed tomography or magnetic resonance imaging. If there is isolated involvement of the upper extremity, thoracic outlet syndrome and occupational hazards such as use of vibratory tools and hypothenar hammer syndrome should be considered as well .

Physical examination must include a thorough vascular examination with particular attention to pulses, bruits and assessment of the ankle brachial index. An Allen test should be performed to demonstrate arterial involvement of the upper extremities even if asymptomatic. Laboratory testing in patients with suspected BD is used to exclude alternative diagnoses. Initial laboratory studies should include a complete blood count, metabolic panel, liver function tests, fasting blood glucose, inflammatory markers such as erythrocyte sedimentation rate and C-reactive protein, cold agglutinins and cryoglobulins. In addition, serological markers of autoimmune disease including antinuclear antibody (ANA), anticentromere antibody and anti-SCL-70 antibody should be obtained and are typically negative in thromboangiitis obliterans. Lupus anticoagulant and anticardiolipin antibodies are detected in some patients with thromboangiitis obliterans but may also indicate an isolated thrombophilia. Echocardiography may be indicated in certain cases when acute arterial occlusion due to thromboembolism is suspected, in order to detect a cardiac source of embolism. Computed tomography (Fig. 23.2), magnetic resonance or invasive contrast angiography may be performed to exclude a proximal arterial source of embolism and to define the anatomy and extent of disease. Although advances in computed tomographic and magnetic resonance angiography show promise for imaging distal vessels, most patients require invasive contrast angiography to provide the spatial resolution necessary to detect the distal arteriopathy (Fig. 23.3). The most important arteriographic features of the disease include segmental occlusive lesions of small- or medium-sized vessels (tibial, peroneal, plantar, palmar or digital arteries) interspersed with healthy-appearing segments; abundant collaterals described as ‘corkscrew’, ‘spider legs’ or ‘tree roots’; and normal proximal arteries free of atherosclerosis or aneurysms [37]. Biopsy is rarely indicated, but is most likely to be diagnostic in a vein with superficial thrombophlebitis during the acute phase of the disease.