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Thromboangiitis Obliterans

Buerger Disease

Thromboangiitis obliterans is an inflammatory vasculopathy of small and medium sized vessels. Primary features include thrombosed and recanalized arteries and veins of the extremities, with no atherosclerotic degeneration.


The clinical picture of TAO encompasses symptoms originating from arterial occlusion and superficial thrombophlebitis. Initially the symptoms are observed in the extremities, both hands and feet, and include:

  • Low temperature in the extremities
  • Paresthetic experiences, such as tingling, pricking and numbness
  • Raynaud's syndrome, which involves hands changing their color to white, blue and red when exposed to cold [12]
  • Claudication occurring most commonly in the feet or legs in a periodic manner. Severer symptoms lead to pain and cyanosis, as well as excessive sweating in the limb. In progressed stages, pain can also be experienced while resting
  • Ulcers due to ischemia. They occur in the initial phases of the disease but not during the acute phase
  • Weak pulse or absent pulse in wrist or foot arteries and pallor
  • Positive Allen test. A positive Allen test includes pallor in the hand, after compression of the ulnar and radial artery
  • Human disease Buerger's disease Presenile gangrene Presenile gangrene (disorder) Thromboangiitis obliterans (disorder) Thromboangiitis obliterans NOS (disorder) Thromboangiitis obliterans [Buerger's disease] Thromboangiitis obliterans BUERGER DISEASE[wikidata.org]
  • Selective low-dose intra-arterial streptokinase was used in 11 long standing, complicated cases of Buerger's disease of the lower limbs suffering from acute exacerbations or thrombotic episodes with resulting variable degrees of gangrene or pre-gangrene[ncbi.nlm.nih.gov]
  • This can cause the skin and tissue on the ends of your fingers and toes to die (gangrene). Signs and symptoms of gangrene include black or blue skin, a loss of feeling in the affected finger or toe, and a foul smell from the affected area.[mayoclinic.org]
Limb Pain
  • For the remaining 59 patients (75 affected limbs), pain and cold sensation of the affected limbs were improved with varying extent 3 months after transplantation; there were statistically significant differences in pain score and cold sensation score[ncbi.nlm.nih.gov]
  • Discolouration 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.[patient.info]
  • Indications of lumbar sympathetic block are vascular insufficiency, sympathetically mediated pain (reflex sympathetic dystrophy and causalgia), phantom limb pain, peripheral neuropathies, and postherpetic neuralgia.[karnatakaanaesthj.org]
Gangrene of the Toe
  • Affected patients are mostly young male smokers who develop ulcers and gangrene of the toes and fingers as a result of vascular ischaemia. We report a 47-year-old man with scrotal and penile necrosis.[ncbi.nlm.nih.gov]
  • Affected patients are mostly young male smokers who develop ulcers and gangrene of the toes and fingers as a result of vascular ischaemia. We report a 47‐year‐old man with scrotal and penile necrosis.[doi.org]
  • The initial symptom was limited gangrene of a toe (n 9) or a finger (n 2), foot claudication (n 6), calf claudication (n 3), rest pain (n 3), migratory superficial phlebitis (n 4), and Raynaud phenomenon (n 2).[ncbi.nlm.nih.gov]
Arm Pain
  • Our case exemplifies the most common presentation, diagnosis, and treatment in a 53-year-old male smoker who presents with arm pain and dusky cool fingers. A Buerger diagnosis requires exclusion of autoimmune, diabetic, and embolic causes.[ncbi.nlm.nih.gov]
Heavy Tobacco Use
  • Abstract We describe a 56-year-old patient with progressive cognitive decline in the context of heavy tobacco use and migraine, and imaging evidence of an occlusive terminal cerebral vasculopathy.[ncbi.nlm.nih.gov]
  • The condition is strongly associated with heavy tobacco use, and disease progression is closely linked to continued use. (See Pathophysiology and Etiology .)[emedicine.com]
  • Epidemiological reports have shown the disease to be more common in countries with heavy tobacco use. 4 Although TAO disease is most common with the smoked form of tobacco, a few cases have been reported in nonsmokers using chewing tobacco.[vasculardiseasemanagement.com]
Vascular Disease
  • We suggest that thromboangiitis obliterans probably is a generalized vascular disease.[ncbi.nlm.nih.gov]
  • Intestinal manifestations included stricture and perforation of the colon, and these preceded any symptoms of peripheral vascular disease.[ncbi.nlm.nih.gov]
  • Abstract Thromboangiitis obliterans (Buerger's disease) is an occlusive vascular disease that occurs almost exclusively in young male tobacco users.[ncbi.nlm.nih.gov]
  • Abstract Thromboangiitis obliterans (TAO) or Buerger's disease is a nonatherosclerotic vascular disease of unknown etiology that occurs almost exclusively in young male tobacco users.[ncbi.nlm.nih.gov]
  • The pulmonary arterial involvement in this patient may suggest that thromboangiitis obliterans is a generalized vascular disease.[ncbi.nlm.nih.gov]
  • The authors present the case of a 34-year-old male, with ulcers in the fingertips with progressive worsening: acrocyanosis, slow healing, necrosis and finally loss of substance. Dorsalis pedis and posterior tibial pulses were not palpable.[ncbi.nlm.nih.gov]
  • […] without gangrene I73.01 Raynaud's syndrome with gangrene I73.1 Thromboangiitis obliterans [Buerger's disease] I73.8 Other specified peripheral vascular diseases I73.81 Erythromelalgia I73.89 Other specified peripheral vascular diseases Inclusion term(s): Acrocyanosis[icd10coded.com]
Left Ventricular Dysfunction
  • Left ventricular dysfunction was detected by ventriculography. The patient had undergone bilateral sympathectomy of the lumbar branches for distal arterial occlusions due to thromboangiitis obliterans 12 years previously.[ncbi.nlm.nih.gov]
Fingertip Ulceration
  • Marked increase in finger blood flow was induced even after the first series, and complete disappearance of both fingertip ulcerations and ischemic rest pain was achieved. No side effects were observed.[ncbi.nlm.nih.gov]
  • Possible complications Fingertip ulcerations. Muscle atrophy. Gangrene in the foot or leg caused by a loss of blood supply. This may result in amputation.[nmihi.com]
Foot Ulcer
  • Symptoms and signs include claudication, nonhealing foot ulcers, rest pain, and gangrene. Diagnosis is by clinical findings, noninvasive vascular testing, angiography, and exclusion of other causes. Treatment is cessation of tobacco use.[merckmanuals.com]
  • Eg: Brain strokes can occur giving features of paralysis, paresthesia and cranial nerve palsy. In spinal cord, features of infarction like limb paralysis, paresthesia, bladder/ bowel dysfunction.[explainmedicine.com]
  • […] numbness or tingling may have autoamputation of digits Raynaud phenomenon Physical exam superficial thrombophlebitis often migratory distended veins with redness and tenderness darkened or discolored skin gangrene cool extremities limb ischemia pain, paresthesia[step2.medbullets.com]
  • Features of acute limb ischemia (eg, pain, paresthesia, palor, mottling, poikilothermia, paresis, and pulselessness) are common signs and symptoms encountered in the emergency setting. [1, 2, 3, 4] (See Presentation .)[emedicine.com]
Numbness of the Hand
  • Symptoms Buerger's disease symptoms include: Tingling or numbness in the hands or feet. Pale, reddish or blue-tinted hands or feet. Pain that may come and go in your legs and feet or in your arms and hands.[mayoclinic.org]
  • Indications of lumbar sympathetic block are vascular insufficiency, sympathetically mediated pain (reflex sympathetic dystrophy and causalgia), phantom limb pain, peripheral neuropathies, and postherpetic neuralgia.[karnatakaanaesthj.org]


There is no specific test, invasive or not, to definitively diagnose TAO in a patient. Test are carried out primarily to eliminate the possibility of another disease that could produce symptomatology similar to TAO's. 

A complete blood count, glucose tests, ESR and liver function tests are amongst the first to be performed. Additional laboratory examinations include a urinalysis, c-reactive protein, complement, scl-70, antinuclear and antiphospholipid antibodies and rheumatoid factor. These tests will help to exclude other conditions, such as systematic vasculitis. An echocardiographic evaluation or a computerized tomography angiography (CTA) will help to diagnose conditions that lead to the formation of emboli in the heart, which can cause an arterial blockage in smaller vessels if they are transferred [13].

Angiography can detect arterial occlusion in patients with TAO, that has no atherosclerotic components. Revascularization is also detected and is characteristic for the disease, since smaller vessels try to overcome the blockage and are a result of the vascular dilation in the site of occlusion. They are called corkscrew collaterals and contribute to the prevention of complete ischemia but have a typically increased resistance to blood flow. The aforementioned findings are typical of TAO but not exclusively: they can be observed in patients with a multitude of other conditions such as rheumatoid vasculitis,  systemic scleroderma, systemic lupus erythematous, diabetes mellitus etc.

Multiple Ulcerations
  • View Article PubMed Google Scholar Kurata A, Nonaka T, Arimura Y, Nunokawa M, Terado Y, Sudo K, Fujioka Y: Multiple ulcers with perforation of the small intestine in Buerger's disease: a case report.[ojrd.com]
  • Multiple ulcers with perforation of the small intestine in Buerger's disease: a case report. Gastroenterology. 2003; 125 :911–916. doi: 10.1016/S0016-5085(03)01065-5. [ PubMed ] [ CrossRef ] [ Google Scholar ] Shionoya S.[ncbi.nlm.nih.gov]
  • It occurs more commonly in people with HLA-A9 and HLA-B5 genotypes. Prevalence is highest in Asia and the Middle East.[merckmanuals.com]
  • Genetic factors implicated Autoimmune component which is not fully understood Chronic anaerobic periodontal infection Genetics Greater prevalence of HLA-A54, HLA-A9, and HLA-B5 HLA-B12 antigen may be associated resistance to disease.[unboundmedicine.com]
  • They also show a higher prevalence of human leukocyte antigen (HLA)–A9, HLA-A54, and HLA-B5, suggesting a genetic component to the disease.[emedicine.com]
  • It occurs more commonly in people with HLA-A9 and HLA-B5 genotypes. Prevalence is highest in Asia and the Middle East.[merckmanuals.com]
  • Genetic factors implicated Autoimmune component which is not fully understood Chronic anaerobic periodontal infection Genetics Greater prevalence of HLA-A54, HLA-A9, and HLA-B5 HLA-B12 antigen may be associated resistance to disease.[unboundmedicine.com]
  • They also show a higher prevalence of human leukocyte antigen (HLA)–A9, HLA-A54, and HLA-B5, suggesting a genetic component to the disease.[emedicine.com]


There is no definitive treatment for TAO except for the cessation of smoking. It has been proposed that the use of tobacco in any of its forms (cigarettes, chewed tobacco) can further deteriorate the clinical picture; therefore, patients are advised to refrain from the use of all tobacco products [14]. Adaptations to a person's dietary habits are not required and have not proven to be successful in controlling the disease.

TAO patients do not usually need to be hospitalized for the condition, since adequate follow up and wound care suffice. The indications for hospitalization include inability to stop smoking independently, active infection that does not respond to per os medication treatments and the need for surgery. 

Drug therapy has been applied with minimal response from the patients. It seems that IV administration of iloprost, which is an analogue of prostaglandin, ameliorates the symptomatology to an acceptable extent and leads to a decrease in the frequency of amputations. Thrombolysis and gene transfer of VEGF (vascular endothelial growth factor) have been performed but are not yet recommended therapeutic schemes [15].

Ischemic ulcers are treated with antimicrobial agents and patients may also be prescribed various painkillers and narcotic ones to alleviate the pain, although they are not expected to have very effective results.

Surgical therapy is usually not an option for TAO patients. Revascularization is a challenging procedure because the condition affects only small and medium sized vessels. It is, however attempted, if an appropriate distal site is found and a vein bypass can be performed. Hyperbaric oxygen therapy could be chosen for patients who cannot be operated on, although it is a rather experimental approach with scarce scientific data [16].


Thromboangiitis obliterans follows a deteriorating course, unless the patient strictly ceases the use of tobacco in any form. Individuals who smoked for more than 20 years exhibited a significantly higher risk of undergoing considerable amputation due to TAO [11]. The most frequently diagnosed disease type is the remitting/relapsing type, followed by the primary and secondary relapsing and the benign type.


The causes of TAO still remain unclear but the disease is generally considered as requiring the implication of multiple factors in order to develop. Substances contained in tobacco, immunological defects, coagulation irregularities and genetic factors are believed to contribute to its etiology.

Smoking, in particular, is a confirmed etiologic factor. Statistically relevant increase in the frequency of the disease has been observed amongst known smokers of non-filtered tobacco products, such as Bangladeshi patients who smoke homemade unfiltered "bidis", a type of cigarette, and cannabis users [3] [4].

Genetic factors are also believed to play a role. Japanese patients are believed to be significantly immune to TAO because of their MyD88 gene, which is responsible for the production of the myeloid differentiation primary-response protein 88 [5]. It has been also debated whether infection is a possible cause of TAO: patients often present with the vasculopathy accompanied by periodontal inflammation. Pseudomonas gingivalis is is thought to possibly contribute to the TAO disease, in the sense that thrombi containing the bacteria can be transferred from the oral cavity to non-adjacent vessels.


The condition is strongly associated with tobacco use, especially unprocessed tobacco that people in some regions of the world use to produce their own homemade cigarettes. Hence, TAO is frequently observed amongst populations in Asia, the Middle East and Mediterranean countries [6], while it has displayed a definite decrease in frequency in North America; this is thought to have occurred due to an alteration in smoking habits [7]. Individuals start to experience symptoms at the age of 40-45 years old and there is a predilection for male patients, since approximately 80% of the individuals diagnosed with the disease are males. A steady increase has been observed in the female population affected by TAO in some areas, which is attributed to more women opting for smoking [8].

Sex distribution
Age distribution


TAO is a pathophysiologically multi-factorial inflammatory vasculitis. Both arteries and veins are prone to occlusion and the most common sites of disturbance include small and medium sized vessels of the extremities, brain, kidneys, heart and genitalia. Late-stage disease may also encompass the axial artery and subclavian arteries.

It has been confirmed that all three vascular layers partake in the inflammatory process in its acute phase; when the condition lapses into a chronic type, inflammation is restricted within the adventitial and medial layers, accompanied by a revascularization process. The occlusion occurs as a result of thrombi formation, with the elastic lamina remaining normal

The accurate pathogenesis of thrombus formation is still unconfirmed, although various observation-based suggestions have been made. It is believed that the vasodilatory process in patients with TAO is distorted as a result of a dysfunctional endothelium [9]. Tobacco use is the only confirmed factor causing TAO, probably due to a certain hypersensitivity to substances contained within the product. Nicotine abuse has been found to increase the concentration of kallikreins and kininase II : patients who were not affected by the condition, regardless of their smoking habit, and TAO patients who ceased to smoke, exhibited significantly lower levels of these components when compared to TAO patients who continued to smoke [10].

Immunologic factors are also believed to partake in the pathogenesis of TAO. The HLA-DRA (histocompatibility leukocyte antigen) was more often detected in TAO patients compared to people who did not smoke and people who smoked but where not affected by TAO. The HLA-DRW6 component was respectively less often detected.


TAO can generally not be prevented, especially amongst smokers. Rapid deterioration, however, can be prevented with smoking cessation, early wound treatment, appropriate shoes that protect the feet from sustaining traumatization and avoiding medications that cause vasoconstriction.


Thromboangiitis obliterans affects the small and medium sized vessels of the extremities. It is characterized by profound inflammation and vascular occlusion due to the formation of localized thrombi. Its typical presentation includes significant claudication, which can follow a rapidly deteriorating course and lead to critically decreased perfusion of the affected areas and ischemic phenomena. Acute ischemia is an emergency condition and typically presents with pain in the affected body part, pallor, sensory impairment, temporary paralysis and localized low temperature [1] [2].

Thromboangiitis obliterans, abbreviated as TAO, is also known as Buerger's disease and is strongly linked to tobacco use. There has yet to be developed a successful therapeutic scheme involving the administration of medications, and smoking cessation is the only proven way to hinder the condition's progress.

Patient Information

Thromboangiitis obliterans (TAO) is a condition that affects small and medium sized vessels. Due to various causes, blood clots are formed in some parts of the arteries and veins and block the blood flow.

The only known cause of TAO is smoking. Cigarettes are believed to contain compounds to which some individuals are extremely sensitive. Dental infections have been proposed as a possible co-factor, while other researchers believe that the disease could also be autoimmune.

Symptoms of TAO include pain in the legs or feet during exercise or rest, cold and pale extremities, strange sensations such as numbness, tingling, or picking and ulcers. Raunaud's phenomenon can also be observed: the hands first become white, then blue and ultimately red when a person exposes them to a cold environment. This symptomatology is experienced almost exclusively in the hands and feet, as those are the sites where the vessels are most frequently affected by TAO.

TAO is diagnosed mainly after other diseases are excluded, which can cause similar symptomatology. Blood tests are performed in order to detect various antibodies or markers which would point to another condition. Angiography can reveal findings which are compatible with TAO, but they are not specific to this condition either.

Unfortunately, there is no particular treatment for TAO and it cannot be cured. The only known way to reduce symptoms and stop the rapid progression is to stop smoking. Painkillers are prescribed for the pain and wound care should be sought as well. Surgical procedures to improve the blood flow are possible, yet difficult to achieve, because of the small size of the affected vessels.



  1. von Winiwarter F. Ueber eine eigenthumliche Form von Endarteriitis und Endophlebitis mit Gangran des Fusses. Arch Klin Chir. 1879; 23:202-26.
  2. Buerger L. Thrombo-angiitis obliterans: a study of the vascular lesions leading to presenile spontaneous gangrene. Am J Med Sci. 1908; 136:567-80.
  3. Rahman M, Chowdhury AS, Fukui T, et al. Association of thromboangiitis obliterans with cigarette and bidi smoking in Bangladesh: a case-control study. Int J Epidemiol. 2000; 29:266-270.
  4. Disdier P, Granel B, Serratrice J, et al. Cannabis arteritis revisited - ten new case reports. Angiology. 2001; 52:1-5.
  5. Chen Z, Nakajima T, Inoue Y, et al. A single nucleotide polymorphism in the 3'-untranslated region of MyD88 gene is associated with Buerger disease but not with Takayasu arteritis in Japanese. J Hum Genet. 2011; 56:545-547.
  6. Dilege S, Aksoy M, Kayabali M, et al. Vascular reconstruction in Buerger's disease: is it feasible? Surg Today. 2002; 32(12):1042.
  7. Lie JT. The rise and fall and resurgence of thromboangiitis obliterans (Buerger's disease). Acta Pathol Jpn. 1989; 39(3):153.
  8. Mills JL, Porter JM. Semin Vasc Surg. Buerger's disease: a review and update. 1993; 6(1):14.
  9. Makita S, Nakamura M, Murakami H, et al. Impaired endothelium-dependent vasorelaxation in peripheral vasculature of patients with thromboangiitis obliterans (Buerger's disease). Circulation. 1996; 94(9 suppl):II211-II215.
  10. Dellalibera-Joviliano R, Joviliano EE, et al. Determination of kininogens levels and kallikrein/kininase II activities in patients with thromboangiitis obliterans. Scand J Immunol. 2010; 72:128-133.
  11. Fazeli B, Ravari H, Assadi R. Natural history definition and a suggested clinical approach to Buerger's disease: a case-control study with survival analysis. Vascular. 2012 Aug; 20(4):198-202.
  12. Hartmann P, Mohokum M, Schlattmann P. The association of Raynaud syndrome with thromboangiitis obliterans--a meta-analysis. Angiology. 2012; 63:315.
  13. Fujii Y, Soga J, Nakamura S, et al. Classification of corkscrew collaterals in thromboangiitis obliterans (Buerger's disease): relationship between corkscrew type and prevalence of ischemic ulcers. Circ J. 2010 Aug; 74(8):1684-8.
  14. 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.
  15. Tavakoli H, Salimi J, Rashidi A. Reply: "Treatment-of-choice for Buerger's disease (thromboangiitis obliterans): still an unresolved issue". Clin Rheumatol. 2008 Jun; 27(6):813.
  16. Saito S, Nishikawa K, Obata H, et al. Autologous bone marrow transplantation and hyperbaric oxygen therapy for patients with thromboangiitis obliterans. Angiology. 2007 Aug-Sep; 58(4):429-34.

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Last updated: 2018-06-21 20:47