Thromboangiitis obliterans (Buerger's disease)
- Emile R Mohler III, MD
Emile R Mohler III, MD
- Section Editor — Vascular Medicine
- Professor of Medicine
- University of Pennsylvania School of Medicine
- Jeffrey W Olin, DO
Jeffrey W Olin, DO
- Professor of Medicine (Cardiology)
- Icahn School of Medicine at Mount Sinai
- Section Editors
- Gene G Hunder, MD
Gene G Hunder, MD
- Section Editor — Vasculitis
- Emeritus Consultant
- Professor Emeritus
- Mayo Clinic College of Medicine
- John F Eidt, MD
John F Eidt, MD
- Section Editor — Vascular Surgery
- Professor of Surgery
- University of South Carolina School of Medicine Greenville
- Joseph L Mills, Sr, MD
Joseph L Mills, Sr, MD
- Section Editor — Vascular Surgery
- Professor of Surgery
- University of Arizona Health Sciences Center
Thromboangiitis obliterans, also called Buerger's disease, is a nonatherosclerotic, segmental, inflammatory disease that most commonly affects the small to medium-sized arteries and veins of the extremities [1-3]. Thromboangiitis obliterans is characterized by highly cellular and inflammatory occlusive thrombus with relative sparing of the blood vessel wall . Patients are young smokers who present with distal extremity ischemia, ischemic digit ulcers or digit gangrene . The disease is strongly associated with the use of tobacco products and smoking cessation is important to decrease the risk for amputation. The epidemiology, clinical manifestations, diagnosis, and treatment of thromboangiitis obliterans are reviewed here.
Thromboangiitis obliterans is more common in countries where tobacco is heavily used, especially among people who make homemade cigarettes from raw tobacco . As such, thromboangiitis obliterans is most prevalent in the Mediterranean, Middle East and Asia [7,8]. In North America, the prevalence of thromboangiitis obliterans has declined in the past 30 years due to a decline in smoking [8,9]. In other parts of the world, the prevalence of this disease among patients with arterial occlusive disease varies widely, ranging from 0.5 to 5.6 percent in Western Europe to as high as 45 to 63 percent in India. .
Men are more commonly affected than women and the typical age of onset is 40 to 45 years. Of patients diagnosed with thromboangiitis obliterans, 70 to 91 percent are male and 11 to 30 percent are female . However, there are reports of increasing prevalence of disease in women, possibly due to the increasing use of cigarettes among women [5,9,11-17].
The use of tobacco is essential for the initiation and progression of thromboangiitis obliterans [18-20]. Most patients are heavy cigarette smokers. In one study, patients diagnosed with thromboangiitis obliterans smoked an average of 23 years . Thromboangiitis obliterans has also been reported in cigar smokers, marijuana users and those who use smokeless tobacco such as chewing tobacco and snuff [4,5,21-24].
Chronic anaerobic periodontal infection may also play a role in the development of thromboangiitis obliterans [25,26]. Nearly two-thirds of patients with thromboangiitis obliterans have severe periodontal disease. In one study, DNA fragments associated with anaerobic bacteria were found within both the arterial lesions and oral cavities of patients with thromboangiitis obliterans . However, the prevalence of periodontal disease in smokers without thromboangiitis obliterans is similarly high and thus the association may be confounded.
- Buerger L. Landmark publication from the American Journal of the Medical Sciences, 'Thrombo-angiitis obliterans: a study of the vascular lesions leading to presenile spontaneous gangrene'. 1908. Am J Med Sci 2009; 337:274.
- Piazza G, Creager MA. Thromboangiitis obliterans. Circulation 2010; 121:1858.
- Dargon PT, Landry GJ. Buerger's disease. Ann Vasc Surg 2012; 26:871.
- Olin JW. Thromboangiitis obliterans (Buerger's disease). N Engl J Med 2000; 343:864.
- Mills JL, Porter JM. Buerger's disease: a review and update. Semin Vasc Surg 1993; 6:14.
- Grove WJ, Stansby GP. Buerger's disease and cigarette smoking in Bangladesh. Ann R Coll Surg Engl 1992; 74:115.
- Dilege S, Aksoy M, Kayabali M, et al. Vascular reconstruction in Buerger's disease: is it feasible? Surg Today 2002; 32:1042.
- Lie JT. The rise and fall and resurgence of thromboangiitis obliterans (Buerger's disease). Acta Pathol Jpn 1989; 39:153.
- Lie JT. Thromboangiitis obliterans (Buerger's disease) in women. Medicine (Baltimore) 1987; 66:65.
- Arkkila PE. Thromboangiitis obliterans (Buerger's disease). Orphanet J Rare Dis 2006; 1:14.
- Mills JL, Taylor LM Jr, Porter JM. Buerger's disease in the modern era. Am J Surg 1987; 154:123.
- Olin JW, Young JR, Graor RA, et al. The changing clinical spectrum of thromboangiitis obliterans (Buerger's disease). Circulation 1990; 82:IV3.
- Cooper LT, Tse TS, Mikhail MA, et al. Long-term survival and amputation risk in thromboangiitis obliterans (Buerger's disease). J Am Coll Cardiol 2004; 44:2410.
- Ehrenfeld M, Adar R. Rheumatic manifestations in patients with thromboangiitis obliterans (Buerger's disease). J Rheumatol 2000; 27:1818.
- Lau H, Cheng SW. Buerger's disease in Hong Kong: a review of 89 cases. Aust N Z J Surg 1997; 67:264.
- Shionoya S, Ban I, Nakata Y, et al. Involvement of the iliac artery in Buerger's disease (pathogenesis and arterial reconstruction). J Cardiovasc Surg (Torino) 1978; 19:69.
- Sasaki S, Sakuma M, Yasuda K. Current status of thromboangiitis obliterans (Buerger's disease) in Japan. Int J Cardiol 2000; 75 Suppl 1:S175.
- Mills JL, Porter JM. Buerger's disease (thromboangiitis obliterans). Ann Vasc Surg 1991; 5:570.
- Papa M, Bass A, Adar R, et al. Autoimmune mechanisms in thromboangiitis obliterans (Buerger's disease): the role of tobacco antigen and the major histocompatibility complex. Surgery 1992; 111:527.
- Tavakoli H, Rezaii J, Esfandiari K, et al. Buerger's disease: a 10-year experience in Tehran, Iran. Clin Rheumatol 2008; 27:369.
- Lie JT. Thromboangiitis obliterans (Buerger's disease) and smokeless tobacco. Arthritis Rheum 1988; 31:812.
- Combemale P, Consort T, Denis-Thelis L, et al. Cannabis arteritis. Br J Dermatol 2005; 152:166.
- Disdier P, Granel B, Serratrice J, et al. Cannabis arteritis revisited--ten new case reports. Angiology 2001; 52:1.
- Cottencin O, Karila L, Lambert M, et al. Cannabis arteritis: review of the literature. J Addict Med 2010; 4:191.
- Iwai T, Inoue Y, Umeda M, et al. Oral bacteria in the occluded arteries of patients with Buerger disease. J Vasc Surg 2005; 42:107.
- Chen YW, Nagasawa T, Wara-Aswapati N, et al. Association between periodontitis and anti-cardiolipin antibodies in Buerger disease. J Clin Periodontol 2009; 36:830.
- Lie JT. Diagnostic histopathology of major systemic and pulmonary vasculitic syndromes. Rheum Dis Clin North Am 1990; 16:269.
- Małecki R, Zdrojowy K, Adamiec R. Thromboangiitis obliterans in the 21st century--a new face of disease. Atherosclerosis 2009; 206:328.
- Leu HJ. Early inflammatory changes in thromboangiitis obliterans. Pathol Microbiol (Basel) 1975; 43:151.
- Lie JT. Thromboangiitis obliterans (Buerger's disease) revisited. Pathol Annu 1988; 23 Pt 2:257.
- Adar R, Papa MZ, Halpern Z, et al. Cellular sensitivity to collagen in thromboangiitis obliterans. N Engl J Med 1983; 308:1113.
- Lee T, Seo JW, Sumpio BE, Kim SJ. Immunobiologic analysis of arterial tissue in Buerger's disease. Eur J Vasc Endovasc Surg 2003; 25:451.
- Kobayashi M, Ito M, Nakagawa A, et al. Immunohistochemical analysis of arterial wall cellular infiltration in Buerger's disease (endarteritis obliterans). J Vasc Surg 1999; 29:451.
- Guzel E, Topal E, Yildirim A, et al. Targeting novel antigens in the arterial wall in thromboangiitis obliterans. Folia Histochem Cytobiol 2010; 48:134.
- Edo N, Miyai K, Ogata S, et al. Thromboangiitis obliterans with multiple large vessel involvement: case report and analysis of immunophenotypes. Cardiovasc Pathol 2010; 19:59.
- Dellalibera-Joviliano R, Joviliano EE, Silva JS, Evora PR. Activation of cytokines corroborate with development of inflammation and autoimmunity in thromboangiitis obliterans patients. Clin Exp Immunol 2012; 170:28.
- Tamai H, Kobayashi M, Takeshita K, et al. Possible involvement of Notch signaling in the pathogenesis of Buerger's disease. Surg Today 2014; 44:307.
- Eichhorn J, Sima D, Lindschau C, et al. Antiendothelial cell antibodies in thromboangiitis obliterans. Am J Med Sci 1998; 315:17.
- Azizi M, Boutouyrie P, Bura-Rivière A, et al. Thromboangiitis obliterans and endothelial function. Eur J Clin Invest 2010; 40:518.
- Joras M, Poredos P, Fras Z. Endothelial dysfunction in Buerger's disease and its relation to markers of inflammation. Eur J Clin Invest 2006; 36:376.
- 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:II211.
- Avcu F, Akar E, Demirkiliç U, et al. The role of prothrombotic mutations in patients with Buerger's disease. Thromb Res 2000; 100:143.
- Maslowski L, McBane R, Alexewicz P, Wysokinski WE. Antiphospholipid antibodies in thromboangiitis obliterans. Vasc Med 2002; 7:259.
- Hus I, Sokolowska B, Walter-Croneck A, et al. Assessment of plasma prothrombotic factors in patients with Buerger's disease. Blood Coagul Fibrinolysis 2013; 24:133.
- Puéchal X, Fiessinger JN. Thromboangiitis obliterans or Buerger's disease: challenges for the rheumatologist. Rheumatology (Oxford) 2007; 46:192.
- Olin JW, Shih A. Thromboangiitis obliterans (Buerger's disease). Curr Opin Rheumatol 2006; 18:18.
- Hartmann P, Mohokum M, Schlattmann P. The association of Raynaud syndrome with thromboangiitis obliterans--a meta-analysis. Angiology 2012; 63:315.
- Donatelli F, Triggiani M, Nascimbene S, et al. Thromboangiitis obliterans of coronary and internal thoracic arteries in a young woman. J Thorac Cardiovasc Surg 1997; 113:800.
- Lie JT. Visceral intestinal Buerger's disease. Int J Cardiol 1998; 66 Suppl 1:S249.
- Kurata A, Nonaka T, Arimura Y, et al. Multiple ulcers with perforation of the small intestine in buerger's disease: a case report. Gastroenterology 2003; 125:911.
- Cakmak A, Gyedu A, Akyol C, et al. Occlusion of the celiac trunk, the inferior mesenteric artery and stenosis of the superior mesenteric artery in peripheral thrombangiitis obliterans. Vasa 2009; 38:394.
- Michail PO, Filis KA, Delladetsima JK, et al. Thromboangiitis obliterans (Buerger's disease) in visceral vessels confirmed by angiographic and histological findings. Eur J Vasc Endovasc Surg 1998; 16:445.
- Fujii Y, Soga J, Hidaka T, et al. Color doppler flows of corkscrew collaterals in Thromboangiitis obliterans (Buerger's disease) using color duplex ultrasonography. J Am Coll Cardiol 2011; 57:2539.
- Pereira de Godoy JM, Braile DM. Buerger's disease and anticardiolipin antibodies. J Cardiovasc Med (Hagerstown) 2009; 10:792.
- Shionoya S. Diagnostic criteria of Buerger's disease. Int J Cardiol 1998; 66 Suppl 1:S243.
- Shionoya S. What is Buerger's disease? World J Surg 1983; 7:544.
- Dimmick SJ, Goh AC, Cauzza E, et al. Imaging appearances of Buerger's disease complications in the upper and lower limbs. Clin Radiol 2012; 67:1207.
- Lambeth JT, Yong NK. Arteriographic findings in thromboangiitis obliterans with emphasis on femoropopliteal involvement. Am J Roentgenol Radium Ther Nucl Med 1970; 109:553.
- Yoshimuta T, Akutsu K, Okajima T, et al. Corkscrew collaterals in Buerger's disease. Can J Cardiol 2009; 25:365.
- Marder VJ, Mellinghoff IK. Cocaine and Buerger disease: is there a pathogenetic association? Arch Intern Med 2000; 160:2057.
- Noël B. Cocaine and arsenic-induced Raynaud's phenomenon. Clin Rheumatol 2002; 21:343.
- Papa MZ, Rabi I, Adar R. A point scoring system for the clinical diagnosis of Buerger's disease. Eur J Vasc Endovasc Surg 1996; 11:335.
- Canter HI, Isci E, Erk Y. Vacuum-assisted wound closure for the management of a foot ulcer due to Buerger's disease. J Plast Reconstr Aesthet Surg 2009; 62:250.
- Hurt RD, Hays JT. Urinary tobacco alkaloid measurement in patients having thromboangiitis obliterans. Mayo Clin Proc 2008; 83:1187.
- Ohta T, Ishioashi H, Hosaka M, Sugimoto I. Clinical and social consequences of Buerger disease. J Vasc Surg 2004; 39:176.
- Hooten WM, Bruns HK, Hays JT. Inpatient treatment of severe nicotine dependence in a patient with thromboangiitis obliterans (Buerger's disease). Mayo Clin Proc 1998; 73:529.
- Oral iloprost in the treatment of thromboangiitis obliterans (Buerger's disease): a double-blind, randomised, placebo-controlled trial. The European TAO Study Group. Eur J Vasc Endovasc Surg 1998; 15:300.
- Fiessinger JN, Schäfer M. Trial of iloprost versus aspirin treatment for critical limb ischaemia of thromboangiitis obliterans. The TAO Study. Lancet 1990; 335:555.
- Bozkurt AK, Köksal C, Demirbas MY, et al. A randomized trial of intravenous iloprost (a stable prostacyclin analogue) versus lumbar sympathectomy in the management of Buerger's disease. Int Angiol 2006; 25:162.
- Bozkurt AK, Cengiz K, Arslan C, et al. A stable prostacyclin analogue (iloprost) in the treatment of Buerger's disease: a prospective analysis of 150 patients. Ann Thorac Cardiovasc Surg 2013; 19:120.
- Labropoulos N, Watson WC, Mansour MA, et al. Acute effects of intermittent pneumatic compression on popliteal artery blood flow. Arch Surg 1998; 133:1072.
- Montori VM, Kavros SJ, Walsh EE, Rooke TW. Intermittent compression pump for nonhealing wounds in patients with limb ischemia. The Mayo Clinic experience (1998-2000). Int Angiol 2002; 21:360.
- Isner JM, Baumgartner I, Rauh G, et al. Treatment of thromboangiitis obliterans (Buerger's disease) by intramuscular gene transfer of vascular endothelial growth factor: preliminary clinical results. J Vasc Surg 1998; 28:964.
- Kim HJ, Jang SY, Park JI, et al. Vascular endothelial growth factor-induced angiogenic gene therapy in patients with peripheral artery disease. Exp Mol Med 2004; 36:336.
- Idei N, Soga J, Hata T, et al. Autologous bone-marrow mononuclear cell implantation reduces long-term major amputation risk in patients with critical limb ischemia: a comparison of atherosclerotic peripheral arterial disease and Buerger disease. Circ Cardiovasc Interv 2011; 4:15.
- Fadini GP, Agostini C, Avogaro A. Autologous stem cell therapy for peripheral arterial disease meta-analysis and systematic review of the literature. Atherosclerosis 2010; 209:10.
- Matoba S, Tatsumi T, Murohara T, et al. Long-term clinical outcome after intramuscular implantation of bone marrow mononuclear cells (Therapeutic Angiogenesis by Cell Transplantation [TACT] trial) in patients with chronic limb ischemia. Am Heart J 2008; 156:1010.
- Motukuru V, Suresh KR, Vivekanand V, et al. Therapeutic angiogenesis in Buerger's disease (thromboangiitis obliterans) patients with critical limb ischemia by autologous transplantation of bone marrow mononuclear cells. J Vasc Surg 2008; 48:53S.
- Saito S, Nishikawa K, Obata H, Goto F. Autologous bone marrow transplantation and hyperbaric oxygen therapy for patients with thromboangiitis obliterans. Angiology 2007; 58:429.
- Durdu S, Akar AR, Arat M, et al. Autologous bone-marrow mononuclear cell implantation for patients with Rutherford grade II-III thromboangiitis obliterans. J Vasc Surg 2006; 44:732.
- Boda Z, Udvardy M, Rázsó K, et al. Stem cell therapy: a promising and prospective approach in the treatment of patients with severe Buerger's disease. Clin Appl Thromb Hemost 2009; 15:552.
- Baumann G, Stangl V, Klein-Weigel P, et al. Successful treatment of thromboangiitis obliterans (Buerger's disease) with immunoadsorption: results of a pilot study. Clin Res Cardiol 2011; 100:683.
- Inan M, Alat I, Kutlu R, et al. Successful treatment of Buerger's Disease with intramedullary K-wire: the results of the first 11 extremities. Eur J Vasc Endovasc Surg 2005; 29:277.
- Miyamoto K, Nishigami K, Nagaya N, et al. Unblinded pilot study of autologous transplantation of bone marrow mononuclear cells in patients with thromboangiitis obliterans. Circulation 2006; 114:2679.
- De Haro J, Acin F, Bleda S, et al. Treatment of thromboangiitis obliterans (Buerger's disease) with bosentan. BMC Cardiovasc Disord 2012; 12:5.
- Reilly MP, Mohler ER 3rd. Cilostazol: treatment of intermittent claudication. Ann Pharmacother 2001; 35:48.
- Yasuda K, Sakuma M, Tanabe T. Hemodynamic effect of cilostazol on increasing peripheral blood flow in arteriosclerosis obliterans. Arzneimittelforschung 1985; 35:1198.
- Dean SM, Satiani B. Three cases of digital ischemia successfully treated with cilostazol. Vasc Med 2001; 6:245.
- Lee T, Ra HD, Park YJ, et al. New routing alternative for proximal anterior tibial artery bypass in patients with Buerger disease. J Vasc Surg 2011; 54:1839.
- Sayin A, Bozkurt AK, Tüzün H, et al. Surgical treatment of Buerger's disease: experience with 216 patients. Cardiovasc Surg 1993; 1:377.
- Sasajima T, Kubo Y, Inaba M, et al. Role of infrainguinal bypass in Buerger's disease: an eighteen-year experience. Eur J Vasc Endovasc Surg 1997; 13:186.
- Singh I, Ramteke VK. The role of omental transfer in Buerger's disease: New Delhi's experience. Aust N Z J Surg 1996; 66:372.
- Agarwal VK. Long-term results of omental transplantation in chronic occlusive arterial disease (Buerger's disease) and retinal avascular diseases (retinitis pigmentosa). Int Surg 2007; 92:174.
- Nishikimi N. Fate of limbs with failed vascular reconstruction in Buerger's disease patients. Int J Cardiol 2000; 75 Suppl 1:S183.
- Graziani L, Morelli L, Parini F, et al. Clinical outcome after extended endovascular recanalization in Buerger's disease in 20 consecutive cases. Ann Vasc Surg 2012; 26:387.
- Ates A, Yekeler I, Ceviz M, et al. One of the most frequent vascular diseases in northeastern of Turkey: Thromboangiitis obliterans or Buerger's disease (experience with 344 cases). Int J Cardiol 2006; 111:147.
- Chander J, Singh L, Lal P, et al. Retroperitoneoscopic lumbar sympathectomy for buerger's disease: a novel technique. JSLS 2004; 8:291.
- Watarida S, Shiraishi S, Fujimura M, et al. Laparoscopic lumbar sympathectomy for lower-limb disease. Surg Endosc 2002; 16:500.
- De Giacomo T, Rendina EA, Venuta F, et al. Thoracoscopic sympathectomy for symptomatic arterial obstruction of the upper extremities. Ann Thorac Surg 2002; 74:885.
- Swigris JJ, Olin JW, Mekhail NA. Implantable spinal cord stimulator to treat the ischemic manifestations of thromboangiitis obliterans (Buerger's disease). J Vasc Surg 1999; 29:928.
- Chierichetti F, Mambrini S, Bagliani A, Odero A. Treatment of Buerger's disease with electrical spinal cord stimulation--review of three cases. Angiology 2002; 53:341.
- Pace AV, Saratzis N, Karokis D, et al. Spinal cord stimulation in Buerger's disease. Ann Rheum Dis 2002; 61:1114.
- Donas KP, Schulte S, Ktenidis K, Horsch S. The role of epidural spinal cord stimulation in the treatment of Buerger's disease. J Vasc Surg 2005; 41:830.
- Hussein EA, el Dorri A. Intra-arterial streptokinase as adjuvant therapy for complicated Buerger's disease: early trials. Int Surg 1993; 78:54.
- RISK FACTORS
- CLINICAL PRESENTATION
- CLINICAL AND LABORATORY EVALUATION
- Vascular evaluation
- Laboratory tests
- Imaging studies
- Clinical criteria
- MEDICAL MANAGEMENT
- Smoking cessation
- Calcium channel blockers
- Intermittent pneumatic compression
- Experimental therapies
- Other interventions
- SUMMARY AND RECOMMENDATIONS