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

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

Epidemiology

• The incidence is falling. In the USA it has fallen from around 100 per 100,000 people to fewer than 20 per 100,000.²
• 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.
• it is worldwide but people from India, Korea, and Japan, and Israeli Jews of Ashkenazi descent, have the highest incidence of the disease.² It is also more common in those from elsewhere in Southeast Asia and the Middle East. It is less common in those of African origin and in people of northern European descent. Part of this difference in disease incidence may be due to variability in diagnostic criteria.³
• 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.⁴ However, cardiovascular risk factors other than smoking may also be important, especially glucose intolerance.⁵

Presentation

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

Assessment should also include consideration of other associated cardiovascular disease and other smoking-related health problems.

Differential diagnosis

• In the early stages other causes of Raynaud's phenomenon must be considered, including systemic lupus erythematosus (SLE) and scleroderma.
• Compared with other causes of peripheral vascular disease, tends to be aggressive with early onset of gangrene and ulceration.
• Exclude autoimmune diseases, hypercoagulable states and diabetes mellitus.
• A proximal source of embolism may be sought by echocardiography and arteriography.

Diagnostic criteria

Diagnosis based on a system of scoring points has been suggested:⁶

More recently, easier-to-use diagnostic criteria have been suggested:^1,7

• 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 five 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.

Investigations

There is no specific diagnostic test.⁷

• Serological - there are no specific serological markers to diagnose Buerger's disease. Recommended tests to rule out other causes of vasculitis include FBC, LFTs, renal function tests, fasting glucose, ESR, CRP, autoantibodies and screening for hypercoagulability.
• Imaging:
  • Angiography - certain angiographic features are typical (but not pathognomonic) of Buerger's disease.⁷ 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 disease.
  • 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.⁸
  • 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.

Management

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.⁹ Supportive measures include:

• Gentle massage and warmth to increase circulation.
• Avoiding conditions that reduce peripheral circulation, like cold temperatures.
• Avoiding sitting or standing in one position for long periods.
• Not walking barefoot, to avoid injury.
• Avoiding 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.⁷

Drug treatment

• Although low-dose aspirin has been used, the drug iloprost (a prostacyclin analogue) has been shown to be superior.^10,11
• 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 nicotine replacement therapy (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.¹²
• 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; however, this is still at the research stage.¹³

Surgical

• Lumbar sympathectomy may provide temporary relief but outcome is variable.¹⁴
• Bypass surgery has not yielded good results in these patients.⁷
• Distal limb amputation: areas with gangrene must be removed surgically; patients who continue to smoke are likely to require amputation of fingers and toes.¹²

Complications

Ulceration, infection and gangrene must be treated energetically.

Prognosis

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.

Document references

1. Arkkila PE; Thromboangiitis obliterans (Buerger's disease). Orphanet J Rare Dis. 2006 Apr 27;1:14. [abstract]
2. Hanly EJ et al; Buerger Disease (Thromboangiitis Obliterans), Medscape, May 2009
3. Olin JW; Thromboangiitis obliterans (Buerger's disease), N Engl J Med 2000 Sep 21;343(12):864-9
4. Papa M, Bass A, Adar R, et al; Autoimmune mechanisms in thromboangiitis obliterans (Buerger's disease): the role of tobacco antigen and the major histocompatibility complex.; Surgery. 1992 May;111(5):527-31. [abstract]
5. Malecki R, Zdrojowy K, Adamiec R; Thromboangiitis obliterans in the 21st century--a new face of disease. Atherosclerosis. 2009 Oct;206(2):328-34. Epub 2009 Feb 12. [abstract]
6. Papa MZ, Rabi I, Adar R; A point scoring system for the clinical diagnosis of Buerger's disease.; Eur J Vasc Endovasc Surg. 1996 Apr;11(3):335-9. [abstract]
7. Lazarides MK, Georgiadis GS, Papas TT, et al; Diagnostic criteria and treatment of Buerger's disease: a review. Int J Low Extrem Wounds. 2006 Jun;5(2):89-95. [abstract]
8. Schmidt WA, Krause A, Schicke B, et al; Color Doppler ultrasonography of hand and finger arteries to differentiate primary from secondary forms of Raynaud's phenomenon. J Rheumatol. 2008 Aug;35(8):1591-8. Epub 2008 Jul 15. [abstract]
9. Paraskevas KI; Treatment-of-choice for Buerger's disease (thromboangiitis obliterans): still an unresolved issue. Clin Rheumatol. 2008 Apr;27(4):547. Epub 2008 Feb 2.
10. Fiessinger JN, Schafer M; Trial of iloprost versus aspirin treatment for critical limb ischaemia of thromboangiitis obliterans. The TAO Study.; Lancet. 1990 Mar 10;335(8689):555-7. [abstract]
11. No authors listed; Oral iloprost in the treatment of thromboangiitis obliterans (Buerger's disease): a double-blind, randomised, placebo-controlled trial. The European TAO Study Group.; Eur J Vasc Endovasc Surg. 1998 Apr;15(4):300-7. [abstract]
12. Lawrence PF, Lund OI, Jimenez JC, et al; Substitution of smokeless tobacco for cigarettes in Buerger's disease does not prevent limb loss. J Vasc Surg. 2008 Jul;48(1):210-2. [abstract]
13. Al Mheid I, Quyyumi AA; Cell Therapy in Peripheral Arterial Disease. Angiology. 2008 Sep 25. [abstract]
14. Bozkurt AK, Besirli K, Koksal C, et al; Surgical treatment of Buerger's disease.; Vascular. 2004 May-Jun;12(3):192-7. [abstract]

Acknowledgements