Buergers disease

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Hadeel Maksoud M.D.[2]

Buerger’s disease is an acute inflammation and thrombosis of the arteries and veins of the hands and feet. It is strongly associated with use of tobacco products, primarily from smoking, but also from smokeless tobacco. It is more often seen in men. There may be an autoimmune element as well. Raynaud’s phenomenon, ulcers and pain are typically seen. Immediate termination of smoking is essential.

Buerger’s disease was first discovered by Felix Von Winiwater, a German physician, in 1879. It was described in detail by Leo Buerger in 1908 in New York, who called it presenile spontaneous gangrene after studying amputations in 11 patients.

Buerger’s disease may be classified according to the type and size of corkscrew collaterals present into 4 subtypes: type I, artery diameter >2 mm, large helical sign; type II, diameter >1.5 mm and ≤2 mm, medium helical sign; type III, diameter ≥1 mm and ≤1.5 mm, small helical sign; and type IV, diameter <1 mm, tiny helical sign.

Buerger’s disease or thromboangiitis obliterans is a segmental vascular disease that causes occlusion and inflammation of the small and medium-sized vessels. Buerger’s disease vasculitis is unique in having features of hypercellularity with intraluminal thrombi in the vessel wall, but sparing the elastic internal laminae of the vessel wall. The details of pathogenesis is still largely unknown.

Buerger’s disease may be caused by tobacco smoking, Rickettsial infection, or autoimmune phenomena.

Buerger’s disease must be differentiated from other diseases that cause ischemic vasculitis such as atherosclerosis, raynaud phenomenon, thromboembolic disease, repeated trauma, vasculitides, frostbite, scleroderma, and systemic lupus erythematosus.

Buerger disease is more common in Israel, Japan and India along the “old silk route” than in the United States and Europe. The disease is most common among South Asians, who often smoke cigarettes made of raw tobacco (bidis). Buerger’s disease affects more males than females at a ratio of 3:1. The prevalence in the United States has decreased from 140 per 100,000 in 1947 to 8 – 12 per 100,000 as the prevalence of smoking has declined.

The most potent risk factor in the development of Buerger’s disease is tobacco smoking. Other risk factors include male sex, rickettsial infection, South Asian or Middle Eastern descent, age between 20-45 years and a medical history of Raynaud’s disease or autoimmune disease.

There is insufficient evidence to recommend routine screening for Buerger disease.

If left untreated, 75% of patients with Buerger’s disease may have a relapsing and remitting course, whilst 20% may progress and 5% may have a benign course of Buerger’s disease. Common complications of Buerger disease include amputation, gangrene and loss of circulation beyond the affected hand or foot. Smoking cessation leads to an 8-fold decrease in the risk for amputation. Amputation is common and more severe in patients who continue to use tobacco, which often leads to vascular insufficiency. Buerger’s disease is rarely immediately fatal, but rather a life shortening disease. Prognosis of Buerger’s disease varies from person to person, depending on the patient’s life-style and the severity of the damaged vessels.

Although clinical examination is sufficient for diagnosis, in cases where diagnosis is not definitive, a catheter-based arteriogram is the gold standard test for the diagnosis of Buerger disease. The following result of catheter-based arteriogram is confirmatory of Buerger disease and includes, absence of atherosclerosis, no cause for thromboembolism, small and medium-sized vessels involved, namely tibial, popliteal, and radial arteries, segmental affection of vessels between normal appearing segments and corkscrew collaterals described as collateralizations around an occlusion area but are not pathognomonic.

The hallmark of Buerger’s disease is pain and/or ischemia of the digits. A positive history of history of tobacco smoking is suggestive of Buerger’s disease. The most common symptoms of Buerger’s disease include pain and pallor of the extremities with weakness and swelling of the affected limb. Less common symptoms of Buerger’s disease include migratory phlebitis and claudication.

Common physical examination findings of Buerger’s disease include pallor, edema, swelling, ulceration and gangrene of the distal extremities.

There are no diagnostic laboratory findings associated with Buerger’s disease. Lab testing is done to exclude other vasculitides, such as lupus, scleroderma and mixed connective tissue disease.

There are no ECG findings associated with Buerger’s disease. ECG may detect atrial fibrillation, which may possibly be a source of thromboembolism and therefore, exclude Buerger’s disease.

There are no x-ray findings associated with Buerger’s disease.

Color duplex ultrasound may be helpful in the diagnosis of Buerger’s disease. Findings on an ultrasound suggestive of Buerger’s disease include corkscrew collaterals. Echocardiography may be helpful in detecting the source of thromboembolism and therefore, exclude Buerger’s disease.

Multidetector computed tomographic angiography (MCTA) may be helpful in the diagnosis of Buerger’s disease, as it is able to visualize vessels. However, MCTA lacks spatial resolution in visualizing the vessels of the hands and feets, where pathology is commonly found in Buerger’s disease.

Gadolinium-enhanced magnetic resonance angiography (MRA) may be helpful in the diagnosis of Buerger’s disease, as it is able to visualize vessels. However, MRA lacks spatial resolution in visualizing the vessels of the hands and feets, where pathology is commonly found in Buerger’s disease.

Buerger’s disease is diagnosed mostly clinically, however, in cases where diagnosis is indefinite and the extent of disease is unknown, a catheter-based arteriogram may be helpful in the diagnosis of Buerger’s disease. Findings on a catheter-based arteriogram suggestive of Buerger’s disease include the absence of atherosclerosis, lack of a source for thromboembolism, small and medium-sized vessel involvement, segmental affection of vessels between normal appearing segments, and corkscrew collaterals described as collateralizations around an occlusion area, however, this finding is not pathognomonic.

Biopsy is not routinely performed, however, may be carried out in patients older than 45 years presenting with nodules subcutaneously or migratory thrombophlebitis, with uncharacteristic large artery involvement and/or the presence of higher than normal anticardiolipin antibodies. Biopsy may therefore be helpful in the diagnosis of Buerger’s disease. Findings on a biopsy suggestive of Buerger’s disease include small and medium vessel involvement, hypercellularity with leukocytic infiltration, segmental affection, occlusion with inflammatory thrombi (may or may not be organized depending on stage of disease), sparing of the internal elastic laminae, formation of microabscesses, and multinucleated giant cells.

There is no treatment for Buerger’s disease. In order to prevent progression and control symptoms smoking cessation is crucial. Smoking cessation does not reverse damage already caused. Pharmacologic medical therapies for Buerger’s disease include smoking cessation, palliative treatments, prostaglandin analogs and phosphodiesterase inhibitors, calcium channel blockers, endothelin receptor antagonists, compression therapy and some experimental therapies. It should be noted, however, that these therapies are purely palliative and do not reverse previous damage caused. Analgesics including NSAIDs and acetaminophen may be used to provide pain relief.

Surgery is usually not feasible in Buerger’s disease since the integrity of the distal vessels usually does not allow for revascularization, nevertheless, surgical intervention may be considered in order to maintain peripheral blood flow as much possible. Surgical intervention may also be carried out in order to provide pain relief, heal ulcers and decrease the chances of future amputations, such as sympathectomy.

An effective measure for the primary prevention of Buerger’s disease includes smoking cessation. This should include complete abstinence without the use of nicotine-containing anti-smoking aids, such as transdermal patches and gum. However, the use of bupropion and varenicline as a means of preventing cravings is permissible.

Effective measures for the secondary prevention of the complications of Buerger’s disease include debridement and dressing of ulcers, wearing protective footwear to avoid injury and lack of healing thereafter, early detection and treatment of injuries in the extremities including the use of prophylactic antibiotics, wearing thick gloves and avoidance of cold weather, and finally, the use of vasoconstricting drugs must be avoided.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Hadeel Maksoud M.D.[2]

Buerger’s disease was first discovered by Felix Von Winiwater, a German physician, in 1879. It was described in detail by Leo Buerger in 1908 in New York,who called it presenile spontaneous gangrene after studying amputations in 11 patients.

• Buerger’s disease was first discovered by Felix Von Winiwater, a German physician, in 1879.^[1]
• It was described in detail by Leo Buerger in 1908 in New York, who at the time coined the term “presenile spontaneous gangrene” after studying amputations in 11 patients.^[2]

• King George VI (father of the current Queen of England) was diagnosed with Buerger’s disease on 12 November 1948.
• On 12 March 1949, the King underwent a successful lumbar sympathectomy, however, continued to smoke.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Hadeel Maksoud M.D.[2]

Buerger’s disease or thromboangiitis obliterans is a segmental vascular disease that causes occlusion and inflammation of the small and medium-sized vessels. Buerger’s disease vasculitis is unique in having features of hypercellularity with intraluminal thrombi in the vessel wall, but sparing the elastic internal laminae of the vessel wall. The details of pathogenesis are still largely unknown.

Buerger’s disease or thromboangiitis obliterans is a segmental vascular disease that causes occlusion and inflammation of the small and medium-sized vessels. Buerger’s disease vasculitis is unique in having hypercellularity with intraluminal thrombi within the vessel wall that spares the elastic internal laminae of the vessel wall. The details of pathogenesis are still largely unknown.^{[1][2][3][4][5][6][7][8][9][10][11][12]}

• In the acute phase the following occurs:
  • The external lamina of the vessels of the distal extremities are usually affected first by inflammatory thrombi.
  • The thrombi cause vessel occlusion whilst leukocytes and giant cells infiltrate the vessel margins.
  • Fibrinoid necrosis is not a feature of Buerger’s disease, however, microabscesses may be present.
  • Superficial veins in particular may show evidence of thrombophlebitis, and this is characteristic and diagnostic of the acute phase.
• The subacute or intermediate phase is characterized by progressive organization of thrombi with the vessel.
• The chronic phase is characterized by the continued presence of organized thrombi with fibrosis, ending with the resolution of inflammation.
  • In the chronic phase, the diseased vessels are not distinct from other vascular diseases.
• Obliteration of the supplying vessels of the extremities suffer severe ischemia and this may lead to gangrene and superimposed infection, mostly of the digits and toes.
• Tibial, popliteal and radial arteries are most often involved.
• The development of Buerger’s disease may be the result of an immunologic phenomenon that leads to vascular dysfunction and the development of inflammatory thrombi.
  • Patients with Buerger’s disease have been identified to have a hypersensitivity against tobacco extracts that are injected intradermally.
  • Evidence has demonstrated that upon exposure to tobacco there is an increased cellular response against collagen type I and III with increased levels of circulating anti-endothelial cell antibody.
  • This increased cellular sensitivity leads to an impaired relaxation mechanism of the peripheral vessels.
  • Cytokines are also thought to be produced in large quantities and may lead to the activation of inflammatory signals.
  • The presence of elevated anti-cardiolipin antibodies is thought to be indicative of prognosis and severity.
• Rickettsial infection has been proposed to be involved in the pathogenesis of Buerger’s disease.^[13]

• Genes that have been identified to be associated with tobacco hypersensitivity in patients with Buerger’s disease include DRBl*0405, DQAl *03, DQBl*0401, DPBl*0501, HLA-A54, HLA-A9,and HLA-B54.^[14]

• Smoking tobacco is critical to the initiation, progression and recurrence of Buerger’s disease. ^[4][5][6]
• It is not understood how smoking leads to the development of thromboangiitis, however, it has been hypothesized that chemical compounds within the tobacco smoke leads to a delayed hypersensitivity and may directly cause a toxic angiitis.

• On gross pathology, ischemia, cyanosis, rubor, ulceration, or dry or wet gangrene with or without autoamputation are characteristic findings of Buerger’s disease.^[11]

• On microscopic histopathological analysis, an occluding thrombus, microabscesses, leukocytes and giant cells are characteristic findings of Buerger’s disease.^[12]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Hadeel Maksoud M.D.[2]

Buerger’s disease may be caused by tobacco smoking, rickettsial infection, or autoimmune phenomena.

Buerger’s disease may be caused by:

• Tobacco smoking
• Rickettsiae
• Autoimmune phenomenon

• Buerger disease may be caused by a mutation in DRBl*0405, DQAl *03, DQBl*0401, DPBl*0501, HLA-A54, HLA-A9,and HLA-B54 genes.

Cardiovascular	No underlying causes
Chemical/Poisoning	No underlying causes
Dental	No underlying causes
Dermatologic	No underlying causes
Drug Side Effect	No underlying causes
Ear Nose Throat	No underlying causes
Endocrine	No underlying causes
Environmental	Smoking
Gastroenterologic	No underlying causes
Genetic	DRBl*0405, DQAl *03, DQBl*0401, DPBl*0501, HLA-A54, HLA-A9,and HLA-B54
Hematologic	No underlying causes
Iatrogenic	No underlying causes
Infectious Disease	Rickettsial infection
Musculoskeletal/Orthopedic	No underlying causes
Neurologic	No underlying causes
Nutritional/Metabolic	No underlying causes
Obstetric/Gynecologic	No underlying causes
Oncologic	No underlying causes
Ophthalmologic	No underlying causes
Overdose/Toxicity	No underlying causes
Psychiatric	No underlying causes
Pulmonary	No underlying causes
Renal/Electrolyte	No underlying causes
Rheumatology/Immunology/Allergy	Autoimmune with presence of anti-endothelial cell antibody and anti-cardiolipin antibodies
Sexual	No underlying causes
Trauma	No underlying causes
Urologic	No underlying causes
Miscellaneous	No underlying causes

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Hadeel Maksoud M.D.[2]

Buerger’s disease must be differentiated from other diseases that cause ischemic vasculitis such as atherosclerosis, raynaud phenomenon, thromboembolic disease, repeated trauma, vasculitides, frostbite, scleroderma and systemic lupus erythematosus.

Buerger’s disease must be differentiated from other diseases that cause ischemic vasculitis such as atherosclerosis, raynaud phenomenon, thromboembolic disease, repeated trauma, vasculitides, frostbite, scleroderma and systemic lupus erythematosus.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Hadeel Maksoud M.D.[2]

Buerger disease is more common in Israel, Japan and India along the “old silk route” than in the United States and Europe. The disease is most common among South Asians, who often smoke cigarettes made of raw tobacco (bidis). Buerger’s disease affects more males than females at a ratio of 3:1. The prevalence in the United States has decreased from 140 per 100,000 in 1947 to 8 – 12 per 100,000 as the prevalence of smoking has declined.

The exact incidence of Buerger’s disease is not known, since the prevalence of smoking has dropped and diagnostic criteria have become more strict.^[1][2]

• The prevalence of Buerger’s disease is approximately 8-12 per 100,000 individuals in the USA.^[3]
• In 1947, the prevalence of Buerger’s disease was estimated to be 140 cases per 100,000 individuals.

• Buerger disease commonly affects male individuals between 20-45 years old who have a history of heavy smoking or chewing tobacco, with a median age for onset at 35.^[4]
• Buerger disease does not affect the very young or elderly. However, an autoimmune disease in children may lead to Buerger disease.

• Buerger disease usually affects individuals of the Jewish race, in particular Ashkenazi Jews. European individuals are less likely to develop Buerger disease.^[5]
• Buerger disease is also prevalent among Mediterranean, South Asian, East Asian and Middle Eastern individuals.

• Buerger’s disease is more common among men than women.^[6]
• Women and older adults are affected less often, however there is an increasing prevalence among women with the rising trend in smoking among them.
• Male to female ratio is 3:1.

The majority of Buerger disease cases are reported in countries such as Iran, Bangladesh, India, Japan, Korea and Israel.^[7][8]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Hadeel Maksoud M.D.[2]

The most potent risk factor in the development of Buerger’s disease is tobacco smoking. Other risk factors include male sex, rickettsial infection, South Asian or Middle Eastern descent, age between 20 – 45 years and a medical history of Raynaud’s disease or autoimmune disease.

The most potent risk factor in the development of Buerger’s disease is tobacco smoking. Other risk factors include:^[1][2][3]

• Male sex
• Rickettsial infection
• South Asian or Middle Eastern descent
• Age between 20 – 45 years
• Medical history of Raynaud’s disease or autoimmune disease

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Hadeel Maksoud M.D.[2]

If left untreated, 75% of patients with Buerger’s disease may have a relapsing and remitting course, whilst 20% may progress and 5% may have a benign course of Buerger’s disease. Common complications of Buerger disease include amputation, gangrene and loss of circulation beyond the affected hand or foot. Smoking cessation leads to an 8-fold decrease in the risk for amputation. Amputation is common and more severe in patients who continue to use tobacco, which often leads to vascular insufficiency. Buerger’s disease is rarely immediately fatal, but rather a life shortening disease. Prognosis of Buerger’s disease varies from person to person, depending on the patient’s life-style and the severity of the damaged vessels.

• The symptoms of Buerger disease usually develop in the third to forth decade of life, and start with symptoms such as pallor and ischemia of the extremities.^[1][2]
• If left untreated, approximately 75% of patients with Buerger’s disease may have a relapsing and remitting course, whilst 20% may progress and 5% may have a benign course of Buerger’s disease.

• Common complications of Buerger disease include:^[1][2]
  • Amputation
  • Gangrene
  • Loss of circulation beyond the affected hand or foot

• Smoking cessation leads to an 8-fold decrease in the risk for amputation.^[1][2]
• Amputation is common and more severe in patients who continue to use tobacco, which often leads to vascular insufficiency.
• Buerger’s disease is rarely immediately fatal, but rather a life shortening disease.
• Prognosis of Buerger’s disease varies from person to person, depending on:
  • The patient’s life-style
  • The severity of the damaged vessels

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