Thromboangiitis Obliterans

Thromboangiitis obliterans (Buerger disease) is a segmental, non-atherosclerotic, inflammatory occlusive disease of small and medium-sized arteries and veins of the distal limbs. Tobacco exposure is nearly universal and is required for the diagnosis.

Epidemiology

• Onset before age 45 to 50. Traditionally a disease of young male smokers, but the proportion of women has risen to about 20 to 30% with increased smoking.
• Higher prevalence in the Middle East, South and East Asia, and Eastern Europe, accounting for under 1% of peripheral arterial disease in North America and Western Europe and a far higher share in endemic regions.
• Tobacco exposure includes cigarettes, bidis, chewing tobacco, snuff, water pipe and cannabis.

Pathophysiology

• An immune-mediated response to tobacco antigens (cellular and humoral reaction against collagen types I and III), endothelial dysfunction, and a hypercoagulable state. HLA-B5 and HLA-A9 associations and periodontal disease have been described.
• In the acute lesion, a highly cellular inflammatory thrombus fills the lumen, with neutrophil microabscesses and giant cells, while the vessel wall architecture and internal elastic lamina remain intact. This distinguishes it from atherosclerosis and vasculitis.
• Later phases show organising thrombus and fibrosis, with recanalisation and corkscrew collateral formation.

Diagnostic criteria (Shionoya)

• Smoking history.
• Onset before age 50.
• Infrapopliteal arterial occlusive disease.
• Either upper limb involvement or phlebitis migrans.
• Absence of atherosclerotic risk factors other than smoking.

Course is determined by smoking. Continued tobacco use leads to amputation in a substantial proportion, up to 40 to 50% over 5 to 10 years in persistent smokers, while complete cessation lowers it to under 10%.

Typical presentation

• Instep claudication (pain in the arch of the foot on walking) or hand claudication, progressing to ischaemic rest pain of toes and fingers.
• Painful digital ulcers and dry gangrene of the tips of fingers and toes, usually bilateral and multiple.
• Cold sensitivity and Raynaud phenomenon in 40 to 50% of patients.
• Superficial migratory thrombophlebitis in up to 40%, with tender red cords along superficial veins, often the first manifestation.

Signs

• Absent radial, ulnar, dorsalis pedis and posterior tibial pulses, with preserved brachial and popliteal pulses.
• Abnormal Allen test showing occlusion of the radial, ulnar or digital arteries.
• Cyanosis and pallor of digits, trophic nail changes, and paronychia.
• Involvement of upper limbs, or more than one limb, helps to differentiate from atherosclerosis.

Differential diagnosis

• Atherosclerosis, cardiac or aortic embolism, and thoracic outlet syndrome.
• Scleroderma, systemic lupus erythematosus, rheumatoid vasculitis, and mixed connective tissue disease.
• Antiphospholipid syndrome, hypercoagulable states and myeloproliferative disorders.
• Polyarteritis nodosa, cryoglobulinaemia, cannabis arteritis, ergotism, and frostbite.

Diagnosis is clinical, and supported by angiography after exclusion of other disease.

Laboratory exclusion screen

• CBC, glucose or HbA1c, lipid profile, renal and liver tests.
• ANA, anti-dsDNA, anti-centromere, anti-Scl-70, rheumatoid factor, anti-CCP, complement, ESR and CRP (usually normal or only mildly raised).
• Antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, anti beta-2 glycoprotein I), thrombophilia testing in selected cases, cryoglobulins and ANCA.
• Cotinine in urine or serum, or carboxyhaemoglobin, when smoking history is doubted.

Cardiac and proximal source evaluation

• Transthoracic and transoesophageal echocardiography, Holter monitoring, and CT or MR angiography of the aorta and proximal arteries, which are normal in Buerger disease.

Vascular studies

• Digital pressures with photoplethysmography, Doppler ankle pressures, and the Allen test.
• Angiography of upper and lower limbs, which shows segmental occlusions of distal small and medium arteries, normal proximal vessels, corkscrew and tree-root collaterals, and no atherosclerotic changes or aneurysms.
• Biopsy of a superficial vein is seldom required and shows the characteristic inflammatory thrombus.

Dental and periodontal assessment is recommended, since oral infection is associated with the condition.

Smoking and tobacco cessation (the only intervention proven to alter the course)

• Complete abstinence from all tobacco and cannabis products, including passive exposure, with behavioural counselling and relapse follow-up.
• Nicotine replacement is generally avoided, since nicotine itself may sustain the disease. Use varenicline (0.5 mg daily for 3 days, 0.5 mg twice daily for 4 days, then 1 mg twice daily for 12 weeks) or bupropion SR 150 mg daily then twice daily.
• Biochemical verification of abstinence with cotinine testing.

Medical therapy for ischaemia and pain

• Iloprost IV 0.5 to 2 nanograms/kg/min titrated, for 6 hours daily over 3 to 5 days (longer courses of up to 28 days are used) in rest pain and ulcers. It reduces pain, speeds ulcer healing, and decreases amputations. Oral iloprost and beraprost are alternatives.
• Calcium channel blockers (nifedipine ER 30 to 60 mg daily or amlodipine 5 to 10 mg daily) for Raynaud symptoms.
• Cilostazol 100 mg twice daily or pentoxifylline 400 mg three times daily may help perfusion.
• Bosentan 62.5 mg twice daily for 4 weeks, then 125 mg twice daily, has been used for digital ulcers with small supporting data, with liver function monitoring.
• Aspirin 75 to 100 mg daily is commonly given, though benefit is unproven. Anticoagulation is not indicated, except for symptomatic superficial thrombophlebitis where short-term treatment is used.
• Superficial thrombophlebitis: ibuprofen 400 mg three times daily or naproxen 500 mg twice daily for 1 to 2 weeks.
• Analgesia: paracetamol, gabapentin 300 mg at night titrated to 1800 mg/day, pregabalin 75 to 150 mg twice daily, amitriptyline 10 to 50 mg at night, and opioids for severe pain.
• Statins, when other atherosclerotic risk factors are present.

Interventional and surgical options

• Spinal cord stimulation relieves rest pain and promotes ulcer healing, with limb salvage in 60 to 80% of selected patients.
• Sympathectomy (lumbar by chemical neurolysis with phenol or surgical, or thoracoscopic for the upper limb) may help ulcers and pain, with temporary benefit.
• Revascularisation is rarely possible because of distal, diffuse disease, but bypass with autologous vein to the popliteal, tibial or pedal arteries is considered when a suitable distal target and vein exist.
• Cell therapy with autologous bone marrow mononuclear cells or mesenchymal stem cells is an evolving option for non-reconstructable chronic limb-threatening ischaemia.

Wound and local care

• Protect from cold and trauma, wear warm gloves and well fitted shoes, and avoid constrictive items.
• Debridement of infected tissue, topical dressings, and antibiotics for infection (flucloxacillin 500 mg to 1 g four times daily, or amoxicillin-clavulanate 875/125 mg twice daily), with parenteral therapy for deep infection.
• Allow dry gangrene to demarcate (autoamputation), and perform minimal level amputation after clear demarcation to preserve length. Early amputation is reserved for wet gangrene or uncontrolled sepsis.

Follow-up

Regular review of tobacco abstinence, ulcers, and perfusion. Relapse to smoking is the commonest cause of progression. Coordinate with dentistry, vascular surgery and pain services