Thromboangiitis Obliterans (Buerger’s Disease)

Epidemiology and Etiology

Epidemiology

• Thromboangiitis obliterans (TAO) is most prevalent in regions and countries with heavy tobacco use:
  • Mediterranean 
  • Middle East 
  • Asia
• Decreasing rates in North America and Western Europe are due to the decline in cigarette smoking:
  • Current rate of 12.6‒20 cases per 100,000 
  • Unclear how vaping will affect TAO cases
• Men > women (3:1)
• The majority of patients present before the age of 45.

Etiology

• Tobacco use is seen in all patients with TAO: 
  • Heavy cigarette smokers (most common)
  • Cigar smokers
  • Marijuana users (cannabis arteritis) 
  • Smokeless tobacco users (chewing tobacco and snuff)
• Potential genetic predisposition: 
  • HLA-A9 
  • HLA-B5
  • HLA-A54

Pathophysiology

• General pathophysiology is not well known:
  • An inflammatory and immunologic pathogenesis is postulated.
  • Tobacco use could be a toxic trigger, or cause a delayed hypersensitivity reaction.
• 3 pathologic phases:
  • Acute phase: 
    • Occlusive, inflammatory thrombi develop in arteries and veins of distal extremities.
    • Microabscesses and inflammatory cells are present.
    • Internal elastic lamina is intact.
    • External elastic lamina may be disrupted.
  • Intermediate (subacute) phase: 
    • Progressive organization of the inflammatory thrombus 
    • Vascular fibrosis is seen.
  • Chronic phase: 
    • Inflammation is no longer present.
    • Organized thrombus and vascular fibrosis remain.
    • Indistinguishable from other types of occlusive arterial disease in the chronic phase
• Other possible contributors: 
  • Endothelial dysfunction
  • ↑ Cytokine production
  • Prothrombotic factors

Clinical Presentation

Clinical presentation

• Young smoker (< 45 years of age)
• ≥ 2 extremities are usually involved (many times all 4 are involved)
• Symptoms:
  • Intermittent claudication of the feet, legs, hands, or arms
  • Progresses to pain of the digits at rest
  • Ulcerations on the fingers, toes, or feet
  • Paresthesias
  • Color changes of digits
  • Episodic arthralgias or arthritis (usually wrists and knees)

Physical exam

• Superficial thrombophlebitis (approximately 50% of cases):
  • An early manifestation
  • Often migratory
  • Tender nodules and cords
  • Follows a venous distribution
• Raynaud’s phenomenon (vasospasm of the digits in response to cold or emotional stress):
  • Another early manifestation
  • Reversible pallor, cyanosis, or erythema of the digits
  • May be asymmetric
• Digital ischemia (most common presentation):
  • Rubor or cyanosis of the digit (“Buerger’s color”)
  • Sensory abnormalities
  • Cool extremities
  • Diminished distal pulses
  • Ischemic ulcerations
  • Gangrene

Diagnosis

Clinical criteria

The diagnosis can be established without biopsy if the following criteria are met:

• Age less than 45 years
• Current or recent tobacco use
• Distal extremity ischemia on objective vascular testing:
  • Allen test: With simultaneous compression of the radial and ulnar arteries, the hand remains pale after alternately releasing.
  • Ankle-brachial index (ABI) 
  • Wrist-brachial index (WBI)
  • Typical arteriographic findings of TAO 
• Exclusion of other potential causes

Workup

• Biopsy: 
  • Rarely needed, but is the only modality that will give definitive diagnosis
  • May biopsy subcutaneous nodules or superficial thrombophlebitis
  • Findings: 
    • Inflammatory intraluminal thrombus, which is highly cellular 
    • Sparing of the vessel wall
  • Biopsy non-healing ulcers or lesions to rule out cancer.
• Laboratory tests: 
  • Used to rule out other causes of vascular disease
  • The following should all be normal:
    • Complete blood count (CBC) with differential
    • Complete metabolic panel
    • Urinalysis
    • Antinuclear antibody, rheumatoid factor, complement, anti-centromere antibody, anti-scleroderma 70 antibody → rule out vasculitis
    • Antiphospholipid antibody, partial thromboplastin time (PTT), prothrombin time (PT), factor V Leiden, antithrombin III, protein C and S, prothrombin gene mutation → rule out hypercoagulable disorders 
    • Toxicology panel → evaluate for cannabis arteritis
• Imaging:
  • Angiography:
    • Evaluates the extent of the disease
    • Non-atherosclerotic, segmental, occlusive lesions in small- to medium-sized vessels
    • Formation of small collateral vessels around the occlusion (“corkscrew collaterals”)
    • Similar findings can be seen in other autoimmune disorders
  • Computed tomography with angiography (CTA) and magnetic resonance with angiography (MRA): can be used, but may not provide adequate detail
  • Echocardiogram: used to rule out a cardioembolic source

Management, Complications, and Prognosis

Management

• Tobacco cessation:
  • Most effective way to “treat” TAO, and decreases the risk of amputation
  • Counseling on complete abstinence of tobacco and cannabis is required.
  • Medications: 
    • Only non-nicotine products are used (bupropion, varenicline).
    • Avoid nicotine patches and gum due to a concern that they may continue the disease.
  • Failure of tobacco cessation will lead to disease progression.
• Intermittent pneumatic compression: 
  • Limited data
  • Useful in small vessel occlusive disease of other etiologies
  • Can be used for painful ulcerations, but improvement is slow
• Vasodilators: 
  • Alleviate symptoms only
  • Medication options:
    • Prostacyclin analogues (iloprost)
    • Phosphodiesterase (PDE) inhibitors (cilostazol, pentoxifylline)
    • Alpha-adrenergic receptor antagonists
    • Nitrates
    • Calcium channel blockers (frequently used for Raynaud’s phenomenon)
• Revascularization:
  • May not be feasible due to distal disease
  • Arterial bypass surgery:
    • Reserved for severe ischemia
    • Requires a suitable target
  • Thrombolytic therapy and angioplasty are rarely used.

Complications

• Infection
• Ulcerations
• Gangrene
• Amputation
• Occlusion of coronary, renal, splenic, or mesenteric arteries causing organ ischemia

Prognosis

• 94% of patients who stop smoking will avoid amputation.
• 43% of patients who continue using tobacco will require amputation within 8 years.

Differential Diagnosis

• Peripheral artery disease (PAD): atherosclerotic arterial narrowing resulting in ischemia to the distal limbs. Risk factors include hypertension, hyperlipidemia, diabetes, tobacco use, and increased age. Patients will have intermittent claudication, cyanosis, ischemic ulcers, and gangrene. The clinical picture, along with abnormal ABIs, will establish the diagnosis and differentiate PAD from TAO. Management includes risk factor modification, antiplatelet agents, PDE inhibitors, and revascularization.

• Thromboembolic disease: vascular occlusion due to a dislodged thrombus from a more proximal source. The presentation depends on the source, size, and location of the embolism, but includes acute limb ischemia and blue toe syndrome. The clinical history, hypercoagulable workup, and imaging aid in the diagnosis, and a source will typically be suspected or found on workup, which differentiates thromboembolic disease from TAO. Management includes anticoagulation and revascularization. 

• Vasculitis: a vascular inflammatory disease, often resulting in ischemia, necrosis, and organ damage. Any vessel can be involved, which differentiates vasculitis from TAO. Etiologies include autoimmune disorders, drugs, and infections. Patients present with fever, arthralgias, arthritis, as well as potential end-organ damage. Diagnosis involves inflammatory markers, autoimmune serology, infectious workup, and biopsy. Management depends on the underlying cause.

• Popliteal artery entrapment syndrome: an uncommon condition in which an abnormally positioned, or enlarged, calf muscle compresses the popliteal artery. The compression leads to obstruction of blood flow to the lower extremity, and resembles the distal extremity ischemia, ulceration, or necrosis of TAO. The diagnosis is made with imaging, which will differentiate popliteal artery entrapment syndrome from TAO. Management includes avoiding any inciting exercise and vascular surgery evaluation.

• Frostbite: injury due to freezing of the tissues that can be associated with vascular thrombosis. Frostbite commonly affects the fingers, toes, nose, ears, cheeks, and chin. A severe cold exposure history is present, and findings include numbness, white or cyanotic discoloration of the skin, bullae, eschar, or tissue necrosis. The diagnosis is clinical, and management involves rewarming and wound care. Severe injuries receive thrombolysis and prostacyclin therapy.

• Raynaud’s syndrome: arterial vasospasm that causes episodes of reduced blood flow to the fingers and toes, typically due to cold exposure or stress. The affected digits may be transiently pale, cyanotic, or hyperemic, and accompanied by numbness or pain. Findings are generally symmetric. Secondary Raynaud’s syndrome can be seen with TAO, which will show asymmetric findings. Diagnosis is clinical, and management includes cold exposure avoidance and vasodilators.