Thromboangiitis Obliterans (Buerger's Disease)

Synonyms: endangitis obliterans von Winiwarter-Buerger, Winiwarter-Buerger syndrome, Winiwarter-Manteuffel-Buerger syndrome and Billroth-von Winiwarter disease.

This is a chronic disease characterised by segmental inflammation and thrombosis of the small and medium size arteries and veins of both the peripheral upper and lower limbs. The thrombus leads to arterial ischaemia in the distal extremities and superficial thrombophlebitis.¹ This may progress to gangrene and ulceration. The aetiology is unknown but the use of tobacco is a key factor in the development and progression of the disease.¹

• The incidence is falling as the association with tobacco is recognised. In the USA it has fallen from around 100 per 100,000 people to less than 20 per 100,000.
• It mostly affects men but women, who used to represent about 5% of cases, now account for about a third of cases. This reflects changes in smoking habits.
• It usually occurs between the ages of 20 and 45 but recently it has been seen more in people over the age of 50.
• Rarely it affects children with auto-immune phenomena and a significant degree of underlying inflammation.
• Although it is a worldwide problem, there are considerable geographical and racial differences. It is more common in those of oriental race, including those from South-east Asia, India and the Middle East but it is less common in those of African origin. It is also less common in people of northern European descent. Natives of India, Korea, Japan and especially Israeli Jews of Ashkenazi descent, have the highest incidence of the disease. Part of this difference in disease incidence may be due to variability in diagnostic criteria.²
• The association of Buerger's disease with tobacco use, particularly cigarette smoking, cannot be overemphasised. Most patients with Buerger's disease are heavy smokers but some cases occur in patients who smoke "moderately". It has been postulated that Buerger's disease is an "autoimmune" reaction triggered by some constituent of tobacco.³

The early symptoms of Buerger's disease include claudication in the feet and/or hands or pain in these areas at rest (about 20% of cases). The pain typically begins in the extremities but may radiate to more central parts of the body. It may be very intense. As the disease progresses, the resting pain can be severe enough to cause insomnia. Other signs and symptoms may include:

• Two or more limbs being affected
• Discoloration of the affected limb
• Pain may increase with activity such as walking and decrease with rest
• Symptoms may worsen with exposure to cold or with emotional stress
• Numbness and tingling in the limbs
• Raynaud's phenomenon
• Skin ulcerations and gangrene of the digits are common
• Pulses may be decreased or absent in the affected extremity
• Later symptoms include enlarged, red, tender cord-like veins

• In the early stages other causes of Raynaud's phenomenon must be considered including SLE and scleroderma but the aggressive nature of Buerger's disease shows the true diagnosis as gangrene and ulceration set in.
• Exclude autoimmune diseases, hypercoagulable states and diabetes mellitus.
• A proximal source of embolism may be sought by echocardiography and arteriography.

Diagnosis based on a system of scoring points has been suggested:⁴

• Age under 45 years
• Current or recent history of tobacco use
• Presence of infrapopliteal arterial occlusive disease indicated by claudication, pain at rest, ischaemic ulcers or gangrenes and documented by non-invasive vascular testing
• Either upper limb involvement or phlebitis migrans
• Absence of atherosclerotic risk factors other than smoking i.e. exclusion of:
  • Autoimmune diseases
  • Hypercoagulable states
  • Diabetes mellitus
  • A proximal source of emboli by echocardiography or arteriography

There must also be consistent arteriographic findings in the clinically involved and non-involved limbs. Confident clinical diagnosis of Buerger's disease requires all 5 features. Strict clinical diagnostic criteria are essential for any study of a disease to ensure the homogeneity of the selected patient population for valid comparisons.

There is no specific diagnostic test.⁵

• Serological - there are no specific serological markers to diagnose Buerger's disease. Recommended tests to rule out other causes of vasculitis include FBC, LFTs, creatinine, fasting glucose, ESR or PV, antinuclear antibody, rheumatoid factor, serologic markers for CREST syndrome and scleroderma and screening for hypercoagulability.
• Imaging
  • Angiography - certain angiographic features are typical (but not pathognomonic) of Buerger's disease.⁵ These include a "corkscrew" appearance of arteries that results from vascular damage, particularly the arteries in the region of the wrists and ankles. Angiograms may also show occlusions or stenoses in multiple areas of both the arms and legs. It is sometimes necessary to perform angiograms of other parts of the body regions, like a mesenteric angiogram to exclude other forms of vasculitis that involve vascular regions atypical for Buerger's.
  • Doppler ultrasound may be helpful - lately colour doppler has been used to distinguish Buerger's disease and other causes of secondary Raynaud's phenomenon from primary disease.⁶
  • Echocardiography may be required to exclude a source of recurrent emboli.
• Other - skin biopsies of affected extremities are rarely performed because of fear that a biopsy site in an ischaemic area will not heal.

General points

Patients with Buerger's disease must be advised to stop smoking immediately and completely. This is the only treatment known to be effective. Otherwise, there is not yet an agreed consensus on the treatment of choice.⁷ Supportive measures include:

• Gentle massage and warmth to increase circulation
• Avoid conditions that reduce peripheral circulation, like cold temperatures
• Avoid sitting or standing in one position for long periods
• Do not walk barefoot to avoid injury
• Avoid tight or restrictive clothing
• Aggressive treatment of any injuries (such as ulcers)

Patients who have claudication but not critical ischaemia should be encouraged to walk whereas those with critical ischaemia should be admitted for bed rest.⁵

Drug treatment

• Although low-dose aspirin has been used, the drug iloprost (a prostacyclin analogue) has been shown to be superior.^8,9
• Other proposed treatments have included carperitide (atrial natriuretic peptide), limaprost and a number of other prostaglandin analogues.
• Calcium channel blockers, steroids, anticoagulants and other antiplatelet drugs are ineffective.
• Some have suggested that if the disease is due to sensitivity to a component of tobacco other than nicotine then NRT may be used. However, recent findings suggest that there is an association of smokeless tobacco with progressive limb ischaemia and therefore all tobacco products should be stopped.¹⁰
• Vasoconstricting drugs should be avoided.

There is work being done in the field of stem cell therapy to treat intractable symptoms related to ischaemia where conventional therapy has failed but this is still at the research stage.¹¹

Surgical

Lumbar sympathectomy may provide temporary relief but outcome is variable.¹² Bypass surgery has not yielded good results in these patients.⁵ Areas with gangrene must be removed surgically; patients who continue to smoke are likely to require amputation of fingers and toes.¹⁰

Ulcers, infection and gangrene must be treated energetically.

The disease is progressive in patients who do not stop smoking. The only way to prevent the progression of the disease is to abstain from all tobacco products.

The first reported case was by von Winiwarter from Germany in1879 in an article entitled "A strange form of endarteritis and endophlebitis with gangrene of the feet." In 1908, Leo Buerger published a detailed description of the disease¹³ in which he referred to "presenile spontaneous gangrene." The paper discussed the pathological findings in 11 limbs amputated from Jewish patients in New York.

Leo Buerger was born in Vienna in 1879 but his parents emigrated to New York the following year. He studied at the College of Physicians and Surgeons, Columbia University, where he graduated in 1901. He studied at the Breslau Surgical Clinic in Germany for a time and then returned to private practice in New York where from 1905 he had an attachment to the Mount Sinai Hospital as professor of urological surgery.