Buerger's Disease: Causes, Pathophysiology, Risk Factors, Diagnosis, Management and Prevention

Buerger’s Disease (Thromboangiitis Obliterans): Causes, Symptoms, Diagnosis and Management

~Introduction

Buerger’s disease, medically known as Thromboangiitis Obliterans (TAO), is a rare, non-atherosclerotic, segmental inflammatory disease that affects the small and medium-sized arteries and veins, primarily in the arms and legs. It is strongly associated with tobacco use and usually occurs in young male smokers under the age of 45. The disease leads to reduced blood flow (ischemia) to the extremities, resulting in pain, ulcers, and even gangrene in severe cases.

The condition was first described in 1908 by Leo Buerger, who identified it as a distinct clinical entity from atherosclerosis. Despite advances in vascular medicine, Buerger’s disease remains a challenging disorder due to its uncertain etiology and the lack of curative treatment other than absolute smoking cessation.

~Definition

Buerger’s disease is defined as a segmental, inflammatory, thrombotic occlusive disease of the small and medium-sized arteries and veins of the extremities, leading to tissue ischemia and necrosis. Unlike atherosclerosis, which involves lipid deposition in arterial walls, Buerger’s disease is primarily an inflammatory and thrombotic process affecting both arteries and veins.

~Epidemiology

Buerger’s disease is relatively rare compared to other vascular disorders but is more prevalent in certain populations. The disease predominantly affects:

• Young men (20–45 years), although cases in women are increasing with rising smoking rates.

• Heavy tobacco users (smokers or users of smokeless tobacco).

• Geographic prevalence is higher in South and Southeast Asia, the Middle East, Eastern Europe, and the Mediterranean regions, where tobacco use starts early and is widespread.

In Western countries, improved awareness and reduction in smoking have led to a decline in incidence, but the disease continues to pose a major problem in developing regions.

~Etiology (Causes)

The exact cause of Buerger’s disease remains unclear. However, the use of tobacco in any form—smoking, chewing, or vaping—is universally recognized as the main trigger for disease onset and progression.

1. Tobacco Use

Tobacco toxins are believed to cause endothelial cell injury, leading to inflammation of the vessel wall and subsequent thrombus formation. Even small amounts of nicotine can trigger disease activity.

2. Autoimmune Mechanisms

Some studies suggest an autoimmune response to components of tobacco or endothelial cells, causing the immune system to attack the blood vessels.

3. Genetic Predisposition

There may be a genetic susceptibility, as certain HLA types (HLA-A9, HLA-B5, HLA-B54) have been found more frequently in affected individuals.

4. Hypersensitivity to Tobacco

Patients often exhibit increased cellular sensitivity to tobacco extracts and abnormal immune responses to collagen and elastin.

5. Endothelial Dysfunction

Chronic exposure to tobacco toxins leads to impaired nitric oxide production and endothelial injury, contributing to thrombus formation and vascular inflammation.

~Pathophysiology

Buerger’s disease involves an inflammatory process that affects the entire vessel wall (panarteritis and panphlebitis). The disease is segmental, meaning that healthy and diseased portions of vessels alternate. The main features include:

1. Acute Inflammation: Early lesions show inflammation of all three layers (intima, media, and adventitia) with polymorphonuclear leukocytes and microabscesses.

2. Thrombosis: Formation of occlusive thrombi with preserved internal elastic lamina, differentiating it from atherosclerosis.

3. Recanalization: Over time, the thrombus may partially organize and recanalize, but blood flow remains impaired.

4. Tissue Ischemia: Reduced perfusion causes pain, ulceration, and tissue necrosis.

Unlike atherosclerosis, lipid deposition is absent, and the inflammatory process primarily drives vessel occlusion.

~Risk Factors

The major risk factor is tobacco use in any form, but additional factors that may increase susceptibility include:

• Male gender (though female cases are rising)

• Age under 45 years

• Family history of Buerger’s disease

• Chronic exposure to cold (may exacerbate symptoms)

• Genetic predisposition (specific HLA types)

• Low socioeconomic status (linked to high smoking prevalence)

• Possible autoimmune factors

~Clinical Features

Buerger’s disease typically presents with symptoms of limb ischemia, progressing from mild claudication to rest pain and gangrene. The disease usually begins distally (in the hands or feet) and advances proximally.

1. Intermittent Claudication

• The earliest symptom is pain in the legs, feet, hands, or arms during activity, which is relieved by rest.

• Often described as cramping or burning pain due to reduced oxygen delivery.

2. Rest Pain

• As the disease progresses, pain occurs even at rest, particularly at night.

• Elevating the limb worsens pain; lowering it may bring temporary relief.

3. Ulceration and Gangrene

• Ischemic ulcers appear on fingers or toes, often painful and resistant to healing.

• Untreated cases may progress to dry or wet gangrene, requiring amputation.

4. Raynaud’s Phenomenon

• Episodic color changes (pallor, cyanosis, redness) in response to cold or stress due to vasospasm.

5. Superficial Thrombophlebitis

• Painful, inflamed veins under the skin, often migratory and recurrent.

6. Coldness and Numbness

• Affected extremities feel cold, with diminished sensation due to reduced blood flow.

7. Diminished Pulses

• Peripheral pulses (especially dorsalis pedis and posterior tibial) may be weak or absent.

8. Trophic Changes

• Skin becomes shiny, thin, and hairless.

• Nails may become brittle or thickened.

~Sites Commonly Affected

• Lower limbs are affected more often than upper limbs.

• Arteries commonly involved include:

  • Tibial and peroneal arteries

  • Radial and ulnar arteries

  • Digital arteries of hands and feet

• Occasionally, visceral or cerebral arteries may be involved in advanced cases.

~Complications

If not diagnosed and treated early, Buerger’s disease can lead to serious complications:

1. Ischemic Ulcers and Gangrene – May result in tissue loss and need for amputation.

2. Superimposed Infection – Necrotic tissue becomes prone to infection.

3. Amputation – In severe cases, due to irreversible ischemic damage.

4. Psychological Distress – Chronic pain and disability lead to depression and reduced quality of life.

~Diagnosis

Buerger’s disease is primarily a clinical diagnosis, supported by imaging studies. There is no specific laboratory test, but diagnostic criteria help exclude other vascular diseases.

1. Diagnostic Criteria (Shionoya’s Criteria)

To diagnose Buerger’s disease, the following are typically present:

• Onset before age 50

• History of tobacco use

• Infrapopliteal arterial occlusions

• Upper limb involvement or migratory phlebitis

• Absence of atherosclerotic risk factors (other than smoking)

2. Physical Examination

• Absent distal pulses (pedal, radial)

• Positive Allen’s test indicating ulnar or radial artery occlusion

• Ischemic ulcers or gangrene at finger or toe tips

3. Laboratory Investigations

• Normal lipid profile (helps differentiate from atherosclerosis)

• Normal autoimmune markers (ANA, rheumatoid factor, etc.)

• Exclusion of diabetes, hypercoagulable states, and autoimmune vasculitis

4. Imaging Studies

a. Doppler Ultrasound

• Shows segmental arterial occlusions with normal proximal flow.

b. Angiography (Gold Standard)

• Reveals characteristic “corkscrew collaterals”—tortuous collateral vessels near occluded segments.

• Segmental occlusions in small- and medium-sized arteries.

• Absence of atherosclerotic changes in major arteries.

c. MR Angiography / CT Angiography

• Non-invasive alternatives providing detailed vascular mapping.

~Differential Diagnosis

Conditions that mimic Buerger’s disease include:

• Atherosclerosis obliterans

• Thromboembolic disorders

• Systemic lupus erythematosus vasculitis

• Polyarteritis nodosa

• Scleroderma

• Diabetes-related peripheral artery disease

Distinguishing features include younger age of onset, strong tobacco association, and absence of lipid abnormalities in Buerger’s disease.

~Management

The cornerstone of management is complete cessation of tobacco use. No treatment is effective unless the patient completely stops all forms of tobacco, including nicotine patches and e-cigarettes.

1. Smoking Cessation (Primary Treatment)

• Most important and effective intervention.

• Even small amounts of tobacco can reactivate the disease.

• Counseling, behavioral therapy, and pharmacological aids (varenicline, bupropion, nicotine-free patches) can help.

• Absolute abstinence is essential to prevent progression.

2. Medical Management

a. Vasodilators

• Drugs like calcium channel blockers (nifedipine), pentoxifylline, or cilostazol improve blood flow and relieve ischemic pain.

b. Antiplatelet Agents

• Aspirin and clopidogrel reduce platelet aggregation and improve microcirculation.

c. Analgesics

• For pain management, including opioids in severe cases.

d. Iloprost (Prostacyclin Analog)

• Shown to improve ulcer healing and reduce rest pain in some patients.

e. Anticoagulants

• Limited role; used only in cases with thrombotic complications.

f. Antibiotics

• For secondary infection in ischemic ulcers.

3. Surgical and Interventional Management

a. Sympathectomy

• Surgical or chemical interruption of sympathetic nerves to reduce vasospasm and pain.

• Provides symptomatic relief but does not cure the disease.

b. Spinal Cord Stimulation

• Improves blood flow and reduces pain in selected cases.

c. Bypass Surgery

• Usually not feasible because distal vessels are diffusely affected.

d. Amputation

• Required in severe gangrene or uncontrollable infection to prevent sepsis.

4. Emerging Therapies

a. Stem Cell Therapy

• Promotes angiogenesis and improves perfusion in ischemic limbs.

b. Gene Therapy

• Delivery of vascular endothelial growth factor (VEGF) genes to stimulate new blood vessel growth.

c. Hyperbaric Oxygen Therapy

• Enhances oxygen delivery to ischemic tissues and promotes ulcer healing.

Though still experimental, these therapies offer hope for patients unresponsive to conventional treatment.

~Prognosis

The prognosis of Buerger’s disease depends almost entirely on smoking behavior.

• If smoking is stopped completely: Disease progression halts, pain subsides, and amputation can often be avoided.

• If smoking continues: Progressive ischemia and gangrene occur, often leading to multiple amputations and disability.

Long-term survival is usually good, as visceral arteries are rarely involved, but quality of life may be significantly affected by limb loss.

~Prevention

Since tobacco use is the primary trigger, prevention focuses on avoiding or quitting smoking.

Primary Prevention

• Public education on the dangers of tobacco.

• Smoking cessation programs and counseling.

• Early screening of young smokers with limb pain or ulcers.

Secondary Prevention

• Regular follow-up for those diagnosed.

• Avoidance of cold exposure and trauma to limbs.

• Proper foot care to prevent ulceration.

• Compliance with medications and lifestyle modifications.

~Recent Advances and Research

Ongoing studies aim to better understand the immunopathogenesis of Buerger’s disease and develop novel therapies:

• Endothelial progenitor cell therapy to restore vascular integrity.

• Immunomodulatory drugs targeting vascular inflammation.

• Molecular genetic studies exploring susceptibility genes.

• Advanced imaging techniques for early detection of microvascular changes.

While no cure exists, these innovations hold promise for improving management and quality of life.

~Conclusion

Buerger’s disease (Thromboangiitis Obliterans) remains one of the few vascular conditions directly linked to tobacco use, making it both preventable and reversible if recognized early. It primarily affects young adults, causing severe ischemic pain, ulcers, and gangrene of the extremities. The hallmark of management is absolute cessation of tobacco, as continued smoking invariably leads to progression and limb loss.

A multidisciplinary approach involving vascular specialists, surgeons, and smoking cessation experts can significantly improve outcomes. Future therapies focusing on stem cells and angiogenesis may further enhance treatment possibilities. Ultimately, prevention through tobacco control remains the most effective strategy in combating Buerger’s disease.