Buerger Disease (Thromboangiitis Obliterans)

Article Author:
Erion Qaja
Article Editor:
Mark Fortune
Updated:
3/26/2018 1:28:51 PM
PubMed Link:
Buerger Disease (Thromboangiitis Obliterans)

Introduction

Buerger disease, also know thromboangiitis obliterans (TAO) is a progressive, nonatherosclerotic, segmental, inflammatory disease that most often affects small and medium arteries of the upper and lower extremities. The typical age range for occurrence is 20 to 50 years, and the disorder is more frequently found in males who smoke. Migratory superficial phlebitis can be present in up to 16% of patients and indicates a systemic inflammatory response. 

Patients initially present with foot, leg, arm, or hand claudication which may be mistaken for joint or neuromuscular problems. Progression of the disease leads to calf claudication, and eventually, ischemic rest pain and ulcerations on the toes, feet, or fingers. This is also called Raynaud's.

The treatment of TAO revolves around strict smoking cessation. In patients who can abstain, disease remission is impressive, and amputation avoidance is increased. The role of surgical intervention is minimal in Buerger’s disease as there is often no acceptable target vessel for bypass. Furthermore, autogenous vein conduits are limited secondary to coexisting migratory thrombophlebitis.

Etiology

There is no definitive etiology of TAO, yet tobacco exposure is required for both disease initiation and progression. The mechanism of disease remains a mystery, but it may involve immunologic dysfunction and tobacco hypersensitivity that is associated with enhanced cellular sensitivity to type-I and type-III collagen, impaired endothelium-dependent vasorelaxation, and increased anti-endothelial cell antibody titers. A genetic link may exist as affected subjects have an increased prevalence of human leukocyte antigen (HLA)-A9, HLA-B5, and HLA-54.

Epidemiology

Initially described by von Winiwarter in 1879, although the eponym was given to Leo Buerger who published extensive pathologic findings from the amputated limbs of afflicted patients in 1908. 

Segmental, nonatherosclerotic inflammatory disease of the small and medium arteries, veins, and nerves most commonly affecting the hands and feet.

There are cases in which thromboangiitis obliterans (TAO) has also been associated with chewing tobacco. Prevalence has diminished over the past 5 years because of decreased smoking and adherence to more stringent diagnostic criteria. The highest incidence occurs in Israeli Jews of Ashkenazi descent and natives of Indian, Korean, and Japanese ancestry. It is less frequent in subjects of northern European descent. Death from TAO is unusual, but morbidity is substantial. When affected patients continue to smoke, 43% require 1 or more amputations in 7.6 years.

Pathophysiology

Pathologically, thrombosis occurs in small to medium arteries and veins with associated dense polymorphonuclear leukocyte aggregation, microabscesses, and multinucleated giant cells. The chronic phase of the disease shows a decrease in the hypercellularity and frequent recanalization of the vessel lumen. End-stage lesions demonstrate organized thrombus and blood vessel fibrosis. Although the disease is common in Asia, North American males do not appear to have any particular predisposition, as the diagnosis is made in less than 1% of patients with severe limb ischemia.

In contrast to atherosclerosis, which involves the intima and media, TAO is manifested by infiltration of round cells in all 3 layers of the arterial wall. Patients with Buerger disease may have specific cellular immunity against arterial antigens, specific humoral anti-arterial antibodies, and elevated circulatory, immune complexes, but a precise diagnosis can be made only by tissue histology.

History and Physical

Patients with TAO typically present with ischemic signs and symptoms in the distribution of the distal arteries of the upper or lower extremities. Manifestations may include claudication in the arch of the foot as well as the calf. This is also called Raynaud's phenomenon or livedo reticularis that presents as pain in hands, feet, and digits at rest. TAO commonly begin in the distal extremities, but as the disease progresses, it will affect the proximal vessels. The Allen test is done to test the extent of initial disease. Superficial thrombophlebitis complicates almost half of all cases of TAO. Due to associated neurologic involvement, paresthesias of the acral portions of the upper and lower extremities are often described.

Evaluation

Laboratory Studies

No specific laboratory tests are available that confirm the diagnosis of TAO. Comprehensive serology should be completed to rule out other causes for ischemic digits including thrombophilic states, diabetes, and autoimmune diseases. Some studies show that the level of anticardiolipin antibody may be a predictor of age of onset of disease as well as a risk of amputation.

Radiographic Studies

Classic arteriographic findings include nonatherosclerotic segmental occlusions of the small- and medium-d arteries (e.g., tibioperoneal, radioulnar, palmoplantar, and digital arteries). Arteriography may show the characteristic "pig-tailing" or "corkscrewing" of the arteries representing small collateral arteries around associated occlusions. However, corkscrew arteries are not specific for TAO. Echocardiography should be obtained to exclude a proximal source of emboli.

Histology

Acute Phase: Initial inflammatory response leads to neutrophil infiltration and granulomatous formation resulting in vessel occlusion by inflammatory thrombus with relative sparing of the vessel wall.

Subacute Phase: After the initial inflammation the thrombus organizes with continuing platelet adherence.

Chronic Phase: Inflammatory mediators are no longer present, and organized thrombus and vascular fibrosis occlude the vessel. The chronic phase may resemble atherosclerotic disease as well as other vasculitides; however, TAO may be distinguished through the maintenance of the internal elastic lamina.

Treatment / Management

Although there is no cure for TAO, the cornerstone of management is smoking cessation. Even smoking 1 or 2 cigarettes per day can perpetuate the disease. Symptomatic management with calcium channel blockers or other vasodilators can be implemented, especially if there is concurrent Raynaud's phenomenon. Prostaglandin analogs such as intravenous iloprost can be used to treat the pain and ischemic complications. Intramuscular vascular endothelial growth factor (VEGF) has been used experimentally. Lumbar and/or cervical sympathectomy or spinal cord stimulators have been sporadically utilized.

Pearls and Other Issues

Death from TAO is rare. Between 1999 and 2007, according to data from the US Centers for Disease Control and Prevention (CDC), TAO (code I73.1 in the International Classification of Diseases, Tenth Revision [ICD-10]) was the underlying cause of 117 deaths in the United States. A striking dichotomy is observed in the prognosis of patients with TAO, which is dependent on whether absolute avoidance of tobacco is achieved. Among patients who stop using tobacco, 94% avoid amputation; among patients who stop using tobacco before progression to critical limb ischemia, the amputation rate is near 0%. In stark contrast, among patients who continue using tobacco, there is an 8-year amputation rate of 43%.

Experimental Therapies

Therapeutic angiogenesis has been evaluated for the treatment of peripheral artery disease, and this therapy may improve the ischemic manifestations of thromboangiitis obliterans. Short-term results of therapeutic angiogenesis using growth factors or autologous bone marrow have been promising, but longer-term studies are needed.

Immunoabsorption therapy was tested in a pilot study of 10 patients. The treatment was tolerated without side effects. Pain intensity decreased rapidly from a mean of 7.7/10.0 before treatment to 2.0/10.0 at the second day of five consecutive days of therapy. One month after immunoabsorption, all patients were without pain, an effect that persisted over the follow-up period of 6 months.

Bosentan, which is an endothelin receptor antagonist, was used to treat 12 patients with thromboangiitis obliterans and ischemic ulceration or rest pain. An increase in distal flow was observed in 10 out of the 12 patients on magnetic resonance, and digital subtraction arteriography and clinical improvement were observed in 12 of the 13 extremities; however, 2 extremities subsequently required amputation.

Cilostazol is a phosphodiesterase inhibitor that suppresses platelet aggregation and is a direct arterial vasodilator. It is often used in the treatment of peripheral artery disease. In one small study, flow improvements measured in response to reactive hyperemia were significantly increased after 2 weeks of cilostazol therapy. Case reports treating patients with digital ischemia with cilostazol have reported improvements in digit pain and ulceration.

Surgical revascularization is usually not indicated due to the distal nature of the occlusive disease and because most patients do well with smoking cessation. It is accepted that surgery is rarely needed if the patient can stop smoking. 

Bypass surgery may be considered in select patients with severe ischemia and suitable distal target vessels.