Buerger Disease (Thromboangiitis Obliterans)

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Buerger Disease (Thromboangiitis Obliterans)

Synonyms and related keywords: Buerger's disease, TAO, endarteritis, endophlebitis, vasoocclusive disease, presenile spontaneous gangrene, corkscrew collaterals, bidi, cigarette smoking, tobacco use, secondhand smoke, smoking cessation, distal ischemic rest pain, ischemic ulcerations, amputation      


INTRODUCTION  
Background:
Buerger disease, a nonatherosclerotic vascular disease also known as thromboangiitis obliterans (TAO), is characterized by the absence or minimal presence of atheromas, segmental vascular inflammation, vasoocclusive phenomenon, and involvement of small- and medium-sized arteries and veins of the upper and lower extremities. The condition is strongly associated with heavy tobacco use, and progression of the disease is closely linked to continued use. The typical presentations are rest pain, unremitting ischemic ulcerations, and gangrene of the digits of hands and feet, and as the disease evolves, the patients may require several surgical amputations. The first reported case of thromboangiitis obliterans was described in Germany by von Winiwarter in an 1879 article titled "A strange form of endarteritis and endophlebitis with gangrene of the feet." A little more than a quarter of a century later, in Brookline, NY, Leo Buerger published a detailed description of the disease in which he referred to the clinical presentation of thromboangiitis obliterans as "presenile spontaneous gangrene." The paper discussed the pathological findings in 11 limbs amputated from Jewish patients with the disease.  

Pathophysiology:
While the etiology of Buerger disease is unknown, exposure to tobacco is essential for both initiation and progression of the disease. The notion that the condition is linked to tobacco exposure is supported by the fact that the disease is more common in countries with heavy use of tobacco and is perhaps most common among natives of Bangladesh who smoke a specific type of cigarettes, homemade from raw tobacco, called "bidi." While the overwhelming majority of patients with Buerger disease smoke, a few cases have been reported in nonsmokers that have been attributed to the use of chewing tobacco. The disease mechanism underlying Buerger disease remains unclear, but a few observations have led investigators to implicate an immunologic phenomenon that leads to vasodysfunction and inflammatory thrombi. Patients with the disease show hypersensitivity to intradermally injected tobacco extracts, have increased cellular sensitivity to types I and III collagen, have elevated serum anti–endothelial cell antibody titers, and have impaired peripheral vasculature endothelium-dependent vasorelaxation. Increased prevalence of HLA-A9, HLA-A54, and HLA-B5 is observed in these patients, which suggests a genetic component to the disease.  

Frequency:

• In the US: The prevalence of Buerger disease has decreased over the past half-decade, partly because the prevalence of smoking has decreased, but also because the diagnostic criteria have become more stringent. In 1947, the prevalence of the disease in the United States was 104 cases per 100,000 population. More recently, prevalence has been estimated at 12.6-20 cases per 100,000 population.

Mortality/Morbidity:
Death from Buerger disease is rare, but in patients with the disease who continue to smoke, 43% require 1 or more amputations in 7.6 years. Most recently, in a December 2004 CDC publication, the 2002 deaths report in the United States divided by cause of death, month, race, and sex (based on the International Classification of Diseases, Tenth Revision, 1992), reported a total of 9 deaths related to TAO, depicting male to female gender ratio of 2:1 and white to black ethnicity ratio of 8:1.  
Race:
Buerger disease is relatively less common in people of northern European descent. Natives of India, Korea, and Japan, and Israeli Jews of Ashkenazi descent, have the highest incidence of the disease.  
Sex:
Though Buerger disease is more common in males (male-to-female ratio, 3:1), incidence is believed to be increasing among women, and this trend is postulated to be due to the increased prevalence of smoking among women.  
Age:
Most patients with Buerger disease are aged 20-45 years.  

CLINICAL History:

• Because a firm diagnosis of Buerger disease is difficult to establish, a number of different diagnostic criteria have been proposed. Olin asserts that the following criteria must be met for the diagnosis to be made with reasonable certainty:

• Age younger than 45 years

• Current (or recent) history of tobacco use

• Presence of distal extremity ischemia (indicated by claudication, pain at rest, ischemic ulcers, or gangrene) documented by noninvasive vascular testing

• Exclusion of autoimmune diseases, hypercoagulable states, and diabetes mellitus by laboratory tests

• Exclusion of a proximal source of emboli by echocardiography and arteriography

• Consistent arteriographic findings in the clinically involved and noninvolved limbs

• Most patients (70-80%) with Buerger disease present with distal ischemic rest pain and/or ischemic ulcerations on the toes, feet, or fingers.

• Progression of the disease may lead to involvement of more proximal arteries, but involvement of large arteries is unusual.

• Patients may also present with claudication of the feet, legs, hands, or arms and often describe the Raynaud phenomenon of sensitivity of the hands and fingers to cold.

• Foot or arch claudication may be erroneously attributed to an orthopedic problem.

• Patients who seek medical attention late in the course of their disease may present with foot infections and, occasionally, with florid sepsis.

• Although classic Buerger disease affects the vessels of the extremities, a few cases of aortic, cerebral, coronary, iliac, mesenteric, pulmonary, and renal thromboangiitis obliterans have been reported.

Physical:

• Patients with Buerger disease develop painful ulcerations and/or frank gangrene of the digits.

• The hands and feet of patients with the disease are usually cool and mildly edematous.

• Superficial thrombophlebitis (often migratory) occurs in almost half of patients with Buerger disease.

• Paresthesias (numbness, tingling, burning, hypoesthesia) of the feet and hands and impaired distal pulses in the presence of normal proximal pulses are usually found in patients with the disease.

• More than 80% percent of patients present with involvement of 3-4 limbs.

• More recently a point-scoring system has been proposed by Papa to support or contest the diagnosis of TAO using the following criteria.

• Distal extremity (feet, toes, hands, fingers) involvement
• Onset before age 45
• Tobacco use
• Exclusion of atherosclerosis or proximal source of emboli
• Lack of hypercoagulable state
• Lack of definable arteritis (ie, progressive systemic sclerosis, giant cell arteritis)
• Classic arteriographic findings
• Involvement of digital arteries of finger or toes
• Segmental involvement (ie, "skip areas")
• Corkscrew collaterals
• No atherosclerotic changes
• Classic histopathologic findings
• Inflammatory cellular infiltrate within thrombus
• Intact internal elastic lamina
• Involvement of surrounding venous tissues

• Table 1. Scoring system for the diagnosis of thromboangiitis obliterans (x)

Positive points
Age at onset	Less than 30 (+2)/30-40 years (+1)
Foot intermittent claudication	Present (+2)/ by history (+1)
Upper extremity	Symptomatic (+2)/ asymptomatic (+1)
Migrating superficial vein thrombosis	Present (+2)/ by history only (+1)
Raynaud	Present (+2)/ by history only (+1)
Angiography; biopsy	If typical both (+2)/ either(+1)
Negative points
Age at onset	45-50 (-1)/more than 50 years (-2)
Sex, smoking	Female (-1)/ nonsmoker (-2)
Location	Single limb (-1)/no LE involved (-2)
Absent pulses	Brachial (-1)/femoral (-2)
Arteriosclerosis, diabetes, hypertension, hyperlipidemia	Discovered after diagnosis 5.1-10 years (-1)/2.1- 5 years later (-2)

• Table 2. Sum of points defines the probability of the diagnosis of thromboangiitis obliterans

Number of points	Probability of diagnosis
0-1	Diagnostic excluded
2-3	Suspected, low probability
4-5	Probable, medium probability
6 or more	Definite, high probability

Causes: Propagating agents include cigarettes, chewing tobacco, nicotine patches, and secondhand tobacco smoke (the latter two have been implicated as propagating agents of the disease only in former smokers).  

DIFFERENTIALS
Antiphospholipid Antibody Syndrome and Pregnancy Atherosclerosis Diabetes Mellitus, Type 1 Diabetes Mellitus, Type 2 Frostbite Giant Cell Arteritis Gout Infrainguinal Occlusive Disease Peripheral Arterial Occlusive Disease Polyarteritis Nodosa Raynaud Phenomenon Reflex Sympathetic Dystrophy Scleroderma Systemic Lupus Erythematosus Takayasu Arteritis Thoracic Outlet Obstruction

 Other Problems to be Considered:

• Acrocyanosis
• Carpal tunnel syndrome
• Cervical rib
• Ergotism
• Juvenile temporal arteritis with eosinophilia
• Livedo reticularis
• Metatarsalgia
• Neuropathy, peripheral
• Neurotrophic ulcers
• Orthopedic problem of the foot or arch
• Trauma
• Vasculitis, other causes
• Calcinosis cutis, Raynaud phenomenon, esophageal motility disorder, sclerodactyly, and telangiectasia (CREST) syndrome
• Systemic lupus erythematosus
• Rheumatoid vasculitis
• Mixed connective-tissue disease
• Antiphospholipid-antibody syndrome
• Diabetes mellitus
• Embolic occlusion of small or medium arteries
• Hyperhomocysteinemia with atherosclerosis
• Popliteal artery entrapment syndrome
• Repetitive vibratory equipment use
• Hypothenar hammer syndrome

WORKUP Lab Studies:

• No specific laboratory tests confirm or exclude the diagnosis of Buerger disease. The primary goal of a laboratory workup in patients thought to have the disease is to exclude other disease processes in the differential diagnosis. Tests often used as markers for the diagnosis of systemic vasculitis, such as the acute-phase reactants, are negative in TAO. A complete serologic profile must be obtained.

• CBC count with differential

• Liver function tests

• Renal function tests

• Urinalysis

• Glucose (fasting)

• Erythrocyte sedimentation rate

• C-reactive protein

• Antinuclear antibody

• Rheumatoid factor

• Complement

• Anticentromere antibody

• Scl-70 antibody

• Antiphospholipid antibodies

Imaging Studies:

• Angiography/arteriography

• Arteriographic abnormalities consistent with Buerger disease are sometimes seen in limbs that are not yet clinically involved; therefore, arteriography of all 4 limbs may be required.

• The hallmark angiographic findings in patients with Buerger disease are nonatherosclerotic, segmental occlusive lesions of the small- and medium-sized vessels (eg, digital, palmar, plantar, tibial, peroneal, radial, and ulnar arteries) with formation of distinctive small-vessel collaterals around areas of occlusion known as "corkscrew collaterals". Such arteriographic findings suggest Buerger disease but are not pathognomonic because similar lesions can be observed in patients with scleroderma, CREST syndrome, systemic lupus erythematosus, rheumatoid vasculitis, mixed connective-tissue disease, antiphospholipid-antibody syndrome, and even diabetes mellitus.

• Echocardiography: Always perform echocardiography in patients thought to have Buerger disease in order to exclude a proximal source of emboli as the cause of distal vessel occlusion.

Other Tests:

• An abnormal Allen test result indicating distal arterial disease and establishing involvement of the upper extremities in addition to the lower extremities helps differentiate thromboangiitis obliterans from atherosclerotic disease.

• To perform the Allen test, the patient is instructed to make a fist, which exsanguinates the hand and fingers. The examiner's thumbs are then used to occlude the radial and ulnar arteries. The patient then opens the hand, after which the examiner releases the pressure on the ulnar artery while the radial artery remains compressed.

• Prompt return of color to the hand indicates patency of the ulnar artery (ie, a normal or negative test result). The patency of the radial artery can then be tested by repeating the maneuver but with the pressure on the radial artery released while the ulnar artery remains compressed.

• Failure of the hand to promptly refill with blood indicates occlusion of the respective artery distal to the wrist (ie, an abnormal or positive test result). While an abnormal result can be present in other types of small-vessel occlusive disease of the hands, a positive Allen test finding in a young smoker with leg ulcerations is highly suggestive of Buerger disease.

Histologic Findings:
Olin contends that a biopsy is rarely needed unless the patient presents with unusual characteristics, such as large-artery involvement, or age older than 45 years.

• In its acute phase, Buerger disease is characterized by highly cellular, segmental, occlusive, inflammatory thrombi, with minimal inflammation in the walls of affected blood vessels. Secondary spread from the affected small- and medium-sized arteries to contiguous veins and nerves is often observed. Microscopically, the polymorphonuclear leukocyte–predominant inflammatory cellular aggregate may form microabscesses and multinucleated giant cells.
• In the subacute phase, intraluminal thrombosis progressively organizes, but it may defer to vascular recanalization.
• The end-stage phase of the disease is characterized by mature thrombus and vascular fibrosis.
• In all 3 stages, the integrity of the normal structure of the vessel wall, including the internal elastic lamina, is maintained. This distinguishes thromboangiitis obliterans from arteriosclerosis and from other types of systemic vasculitis, in which disruption of the internal elastic lamina and the media can be extensive.

TREATMENT  
Medical Care:
Absolute discontinuation of tobacco use is the only strategy proven to prevent the progression of Buerger disease. Smoking as few as 1 or 2 cigarettes daily, using chewing tobacco, or even using nicotine replacements may keep the disease active. Except for absolute tobacco avoidance, no forms of therapy are definitive. Treatment with intravenous iloprost (a prostaglandin analogue), an expensive therapy unavailable in the United States, has been shown to be somewhat effective in improving symptoms, accelerating resolution of distal extremity trophic changes, and reducing the amputation rate among patients with Buerger disease. Intravenous iloprost use is probably of greatest value in slowing progressive tissue loss and reducing the need for amputation in patients with critical limb ischemia during the period when they first discontinue cigarette smoking. The use of thrombolytic therapy in the treatment of Buerger disease has been proposed, but the data for this treatment remain inconclusive and the treatment is thus considered experimental. Recently, Isner and colleagues reported improved healing of ischemic ulcers and relief of rest pain in a small series of patients with Buerger disease using intramuscular gene transfer of vascular endothelial growth factor. The following strategies are important in prevention of complications from Buerger disease:

• Use of well-fitting protective footwear to prevent foot trauma and thermal or chemical injury

• Early and aggressive treatment of extremity injuries to protect against infections

• Avoidance of cold environments

• Avoidance of drugs that lead to vasoconstriction

Surgical Care:
Given the diffuse segmental nature of thromboangiitis obliterans and the fact that the disease primarily affects small- and medium-sized arteries, surgical revascularization for Buerger disease is usually not feasible and is extremely rare in the United States. However, make every effort to improve distal arterial flow in patients with Buerger disease, and consider autologous vein bypass of coexistent large-vessel atherosclerotic stenoses in patients with severe ischemia who have an acceptable distal target vessel.

• Other proposed surgical treatments for Buerger disease are as follows:

• Omental transfer

• Sympathectomy

• Spinal cord stimulator implantation

• Ultimate surgical therapy for refractory Buerger disease (in patients who continue smoking) is distal limb amputation for nonhealing ulcers, gangrene, or intractable pain. Avoid amputation when possible, but, if it is necessary, perform the operation in a way that preserves as much of the limb as possible.

Consultations:

• Rheumatologists

• Vascular surgeons

• Smoking cessation counselors

Diet: No dietary restrictions are needed. Diet has not been shown to affect the course of the disease. Activity: Encourage cardiovascular exercise. Activity should be restricted by symptoms only.  

MEDICATION
Other than the experimental use of iloprost and thrombolytics (as discussed previously), the use of antibiotics to treat infected ulcers, and palliative treatment of ischemic pain with nonsteroidal and narcotic analgesics, all other forms of pharmacologic treatment have been generally ineffective in the treatment of Buerger disease, including steroids, calcium channel blockers, reserpine, pentoxifylline, vasodilators, antiplatelet drugs, and anticoagulants.  

FOLLOW-UP Further Inpatient Care:

• Indications for admission of patients with Buerger disease include the following:

• Surgery

• Parenteral pharmacological treatment of infection or pain that is refractory to oral medical therapy

• Intensive behavioral modification therapy for patients unable to achieve smoking cessation at home

Further Outpatient Care:

• Outpatient management is generally appropriate for patients with Buerger disease and should include frequent follow-up examination by a physician or wound-care specialist.

In/Out Patient Meds:

• Oral nonsteroidal and narcotic analgesics can be administered to palliate ischemic pain, and appropriate oral antibiotics can be used to treat mild distal extremity ulcers.

Transfer:

• Other than in the rare Buerger patient with ascending limb infection and associated sepsis, transfer is generally safe.

Deterrence/Prevention:

• Patients must be counseled to never smoke.

Complications:

• Ulcerations

• Gangrene
• Infection

• Need for amputation

• Rare occlusion of coronary, renal, splenic, or mesenteric arteries

Prognosis:

• A striking dichotomy is observed with regard to the prognosis of patients with Buerger disease, which is dependent upon whether absolute avoidance of tobacco is achieved. Among patients with who quit smoking, 94% avoid amputation; among patients who quit smoking before gangrene develops, the amputation rate is near 0%. This is in stark contrast to patients who continue smoking, for whom there is a 43% chance that an amputation will be required sometime during a 7- to 8-year period. It is not uncommon for patients with Buerger disease who continue to smoke to require multiple amputations, and reports have even been made of patients who have required bilateral above-knee and above-elbow amputations. While smoking cessation generally removes the need for limb amputation, patients may continue to have claudication or Raynaud phenomenon even after complete discontinuation of tobacco use.

Patient Education:

• Patients with Buerger disease must be repeatedly implored to quit smoking and can be reassured that if they are able to discontinue tobacco use, the disease will remit and amputation will be avoided.

• Physicians should counsel patients that the level of tobacco avoidance required to achieve resolution of their disease often necessitates that they even rigorously limit their exposure to secondhand smoke. This can be extremely difficult for patients who live with another smoker, and it is therefore not unreasonable to consider referring such patients (and their loved ones) to multidisciplinary smoking cessation programs.

• Patients with Buerger disease who are bedridden should be educated about the importance of protective heel pads or foam boots.

MISCELLANEOUS Medical/Legal Pitfalls:

• Failure to recognize Buerger disease and to counsel patients about the necessity for smoking cessation to prevent limb loss can lead to medical/legal vulnerability.

Special Concerns:

• Buerger disease does not occur in pediatric or elderly patients. In the rare event that a pregnant woman presents with Buerger disease, the treatment would remain recommendation of absolute smoking cessation.

• The opinions or assertions contained herein are those of the authors and should not be construed as official or reflecting the views of the Department of Defense, the United States Air Force, or any other government agency.

Source : emedicine.com