Thromboangiitis obliterans (TAO) is a nonatherosclerotic, segmental inflammatory disease that most commonly affects the small and medium-sized arteries and veins in the upper and lower extremities. Cigarette smoking has been implicated as the main etiology of the disease. In eastern parts of the world TAO forms 40–60% of peripheral vascular diseases. Clinical features and angiographic finding are the basis of early diagnosis of TAO. Abstinence from smoking is the only definitive treatment to prevent disease progression. Medical management in form of aspirin, pentoxyfylline, cilostazol, and verapamil increase pain-free walking distance in intermittent claudication, but long term usage fails to prevent disease progression in patients who continue to smoke. Surgical treatment in form of revascularization, lumbar sympathectomy, omentopexy, and Ilizarov techniques help reduce pain and promote healing of trophic changes. Newer treatment modalities like spinal cord stimulation, prostacyclin, bosentan, VEGF, and stem cell therapy have shown promising results. Latest treatment options include peripheral mononuclear stem cell, and adipose tissue derived mononuclear stem cells have been shown to be effective in preventing disease progression, decrease major amputation rates, and improving quality of life. 1. Introduction Thromboangiitis obliterans (TAO) is a nonatherosclerotic, segmental inflammatory disease that most commonly affects the small and medium-sized arteries and veins in the upper and lower extremities. In the characteristic acute-phase lesion, in association with occlusive cellular thrombosis, the acute inflammation involving all layers of the vessel wall led TAO to be classified as a vasculitis. TAO can be distinguished from other types of vasculitis based on its tendency to occur in young male subjects, its close association with tobacco consumption, the rarity of systemic signs and symptoms, a highly cellular thrombus with relative sparing of the blood vessel wall, and the absence of elevated acute-phase reactants and of immunological markers. Thromboangiitis obliterans (TAO) was first described in 1879, when Felix von Winiwarter, an Austrian surgeon who was an associate of Theodor Billroth, reported in the German Archives of Clinical Surgery a single case of what he described as presenile spontaneous gangrene [1]. Buerger related the cellular nature of arterial thrombosis, as had von Winiwarter, and described the absence of large vessel involvement. It was Buerger who named the disorder “thromboangiitis obliterans”, and only briefly mentioned its
References
[1]
J. T. Lie, R. J. Mann, and J. Ludwig, “The brothers von Winiwarter, Alexander (1848–1917) and Felix (1852–1931), and thromboangiitis obliterans,” Mayo Clinic Proceedings, vol. 54, no. 12, pp. 802–807, 1979.
[2]
L. Buerger, The Circulatory Disturbances of the Extremities, WB Saunders, Philadelphia, Pa, USA, 1924.
[3]
M. Cachovan, “Epidemiologic und geographisches Verteilungsmuster der Thromboangiitis obliterans,” in Thromboangiitis Obliterans Morbus Winiwarter-Buerger, H. H. Stuttgart, Ed., pp. 31–36, Germany Georg Thieme, 1988.
[4]
J. L. Mills, L. M. Taylor Jr., and J. M. Porter, “Buerger's disease in the modern era,” American Journal of Surgery, vol. 154, no. 1, pp. 123–129, 1987.
[5]
R. Adar, M. Z. Papa, and Z. Halpern, “Cellular sensitivity to collagen in thromboangiitis obliterans,” The New England Journal of Medicine, vol. 308, no. 19, pp. 1113–1116, 1983.
[6]
M. Papa, A. Bass, R. Adar et al., “Autoimmune mechanisms in thromboangiitis obliterans (Buerger's disease): the role of tobacco antigen and the major histocompatibility complex,” Surgery, vol. 111, no. 5, pp. 527–531, 1992.
[7]
M. Matsushita, S. Shionoya, and T. Matsumoto, “Urinary cotinine measurement in patients with Buerger's disease—effects of active and passive smoking on the disease process,” Journal of Vascular Surgery, vol. 14, no. 1, pp. 53–58, 1991.
[8]
N. A. Choudhury, M. H. Pietraszek, T. Hachiya et al., “Plasminogen activators and plasminogen activator inhibitor 1 before and after venous occlusion of the upper limb in thromboangiitis obliterans (Buerger's disease),” Thrombosis Research, vol. 66, no. 4, pp. 321–329, 1992.
[9]
M. H. Pietraszek, N. A. Choudhury, K. Koyano et al., “Enhanced platelet response to serotonin in Buerger's disease,” Thrombosis Research, vol. 60, no. 3, pp. 241–246, 1990.
[10]
P. Caramaschi, D. Biasi, A. Carletto et al., “Three cases of Buerger's disease associated with hyperhomocysteinemia,” Clinical and Experimental Rheumatology, vol. 18, no. 2, pp. 264–265, 2000.
[11]
J. W. Olin, M. B. Childs, J. R. Bartholomew, et al., “Anticardiolipin antibodies and homocysteine levels in patients with thromboangiitis obliterans,” Arthritis & Rheumatism, vol. 39, supplement 9, p. 47, 1996.
[12]
J. W. Olin, “Are anticardiolipin antibodies really important in thromboangiitis obliterans (Buerger's disease)?” Vascular Medicine, vol. 7, no. 4, pp. 257–258, 2002.
[13]
J. Eichhorn, D. Sima, G. Lindschau et al., “Antiendothelial cell antibodies in thromboangiitis obliterans,” American Journal of the Medical Sciences, vol. 315, no. 1, pp. 17–23, 1998.
[14]
S. Makita, M. Nakamura, H. Murakami, K. Komoda, K. Kawazoe, and K. Hiramori, “Impaired endothelium-dependent vasorelaxation in peripheral vasculature of patients with thromboangiitis obliterans (Buerger's disease),” Circulation, vol. 94, no. 9, pp. II211–II215, 1996.
[15]
L. Buerger, “Is thromboangiitis an infection disease?” The Journal of Surgery, Gynecology and Obstetrics, vol. 19, pp. 582–588, 1914.
[16]
E. V. Allen and G. E. Brown, “Thromboangiitis obliterans. A clinical study of 200 cases,” Annals of Internal Medicine, vol. 1, pp. 535–549, 1928.
[17]
T. Iwai, Y. Inoue, M. Umeda et al., “Oral bacteria in the occluded arteries of patients with Buerger disease,” Journal of Vascular Surgery, vol. 42, no. 1, pp. 107–115, 2005.
[18]
T. Iwai, S. Sato, H. Kume, et al., “Clinical study of phlebitis migrans and incompetence of the leg's superficial vein in Buerger disease,” Annals of Vascular Surgery, vol. 5, no. 1, pp. 45–51, 2012.
[19]
X. Li, T. Iwai, H. Nakamura et al., “An ultrastructural study of Porphyromonas gingivalis-induced platelet aggregation,” Thrombosis Research, vol. 122, no. 6, pp. 810–819, 2008.
[20]
T. Iwai, Buerger Disease: New Evidence, Vascular and endovascular surgery highlights, Health Press, Oxford, UK, 2009, Edited by: Davies A.H., Mitchell AWM.
[21]
Z. Chen, M. Takahashi, T. Naruse et al., “Synergistic contribution of CD14 and HLA loci in the susceptibility to Buerger disease,” Human Genetics, vol. 122, no. 3-4, pp. 367–372, 2007.
[22]
R. Roncon de Albuquerque, L. Delgado, P. Correia, J. Fleming Torrinha, D. Serrao, and A. Braga, “Circulating immune complexes in Buerger's disease. Endarteritis obliterans in young men,” Journal of Cardiovascular Surgery, vol. 30, no. 5, pp. 821–825, 1989.
[23]
L. Maslowski, R. McBane, P. Alexewicz, and W. E. Wysokinski, “Antiphospholipid antibodies in thromboangiitis obliterans,” Vascular Medicine, vol. 7, no. 4, pp. 259–264, 2002.
[24]
Y.-W. Chen, T. Iwai, M. Umeda et al., “Elevated IgG titers to periodontal pathogens related to Buerger disease,” International Journal of Cardiology, vol. 122, no. 1, pp. 79–81, 2007.
[25]
K. Halacheva, M. V. Gulubova, I. Manolova, and D. Petkov, “Expression of ICAM-1, VCAM-1, E-selectin and TNF-α on the endothelium of femoral and iliac arteries in thromboangiitis obliterans,” Acta Histochemica, vol. 104, no. 2, pp. 177–184, 2002.
[26]
S. Sasaki, M. Sakuma, T. Kunihara, and K. Yasuda, “Distribution of arterial involvement in thromboangiitis obliterans (Buerger's disease): results of a study conducted by the intractable vascalitis syndromes research group in Japan,” Surgery Today, vol. 30, no. 7, pp. 600–605, 2000.
[27]
S. Shionoya, “Buerger's disease (thromboangiitis obliterans),” in Vascular Surgery, R. B. Rutherford, Ed., pp. 207–217, WB Saunders, Philadelphia, Pa, USA, 3rd edition, 1989.
[28]
S. Barlas, T. Elmaci, E. Dayio?lu et al., “Has the clinical definition of thromboangiitis obliterans changed indeed?” International Journal of Angiology, vol. 6, no. 1, pp. 49–55, 1997.
[29]
J. W. Olin, J. R. Young, R. A. Graor, W. F. Ruschhaupt, and J. R. Bartholomew, “The changing clinical spectrum of thromboangiitis obliterans (Buerger's disease),” Circulation, vol. 82, no. 5, pp. V-3–V-8, 1990.
[30]
M. Hirai and S. Shionoya, “Arterial obstruction of the upper limb in Buerger's disease: its incidence and primary lesion,” British Journal of Surgery, vol. 66, no. 2, pp. 124–128, 1979.
[31]
J. L. Juergens, “Thromboangiitis obliterans, (Buerger's disease, TAO),” in Peripheral Vascular Diseases, J. L. Juergens, J. A. Spittel, and J. F. Fairbairn, Eds., pp. 469–491, WB Saunders, Philadelphia, Pa, USA, 1980.
[32]
M. Kobayashi, K. Kurose, T. Kobata, K. Hida, S. Sakamoto, and J. Matsubara, “Ischemic intestinal involvement in a patient with Buerger disease: case report and literature review,” Journal of Vascular Surgery, vol. 38, no. 1, pp. 170–174, 2003.
[33]
F. Sauvaget, M. Debray, J.-P. H. De Sigalony et al., “Colonic ischemia reveals thromboangiitis obliterans (Buerger's disease),” Gastroenterology, vol. 110, no. 3, pp. 900–903, 1996.
[34]
Y. J. No, E. M. Lee, D. H. Lee, and J. S. Kim, “Cerebral angiographic findings in thromboangiitis obliterans,” Neuroradiology, vol. 47, no. 12, pp. 912–915, 2005.
[35]
T. E. Hong and D. P. Faxon, “Coronary artery disease in patients with Buerger's disease,” Reviews in Cardiovascular Medicine, vol. 6, pp. 222–226, 2005.
[36]
H. Ohno, Y. Matsuda, and K. Takashiba, “Acute myocardial infarction in Buerger's disease,” American Journal of Cardiology, vol. 57, no. 8, pp. 690–691, 1986.
[37]
O. Lambotte, P. Chazerain, C. Vinciguerra, O. Meyer, and J.-M. Ziza, “Thromboangiitis obliterans with inaugural rheumatic manifestations. A report of three cases,” Revue du Rhumatisme, vol. 64, no. 5, pp. 334–338, 1997.
[38]
X. Puéchal, J.-N. Fiessinger, A. Kahan, and C. J. Menkès, “Rheumatic manifestations in patients with thromboangiitis obliterans (Buerger's disease),” Journal of Rheumatology, vol. 26, no. 8, pp. 1764–1768, 1999.
[39]
S. T. Boyd and B. A. Fremming, “Rimonabant—a selective CB1 antagonist,” Annals of Pharmacotherapy, vol. 39, no. 4, pp. 684–690, 2005.
[40]
J. A. Dormandy and R. B. Rutherford, “Management of peripheralarterial disease (PAD). TASC Working Group. TransAtlantic Inter-Society Concensus (TASC),” Journal of Vascular Surgery, vol. 31, pp. S1–S296, 2000.
[41]
S. Novo, G. Coppola, and G. Milio, “Critical limb ischemia: definition and natural history,” Current Drug Targets, vol. 4, no. 3, pp. 219–225, 2004.
[42]
J. P. Bagger, P. Helligsoe, F. Randsbaek, H. H. Kimose, and B. S. Jensen, “Effect of verapamil in intermittent claudication: a randomized, double- blind, placebo-controlled, cross-over study after individual dose-response assessment,” Circulation, vol. 95, no. 2, pp. 411–414, 1997.
[43]
M. K. Lazarides, G. S. Georgiadis, T. T. Papas, and E. S. Nikolopoulos, “Diagnostic criteria and treatment of Buerger's disease: a review,” International Journal of Lower Extremity Wounds, vol. 5, no. 2, pp. 89–95, 2006.
[44]
S. Shionoya, “Diagnostic criteria of Buerger's disease,” International Journal of Cardiology, vol. 66, no. 1, pp. S243–S245, 1998.
[45]
J. W. Olin, “Thromboangiitis obliterans (Buerger's disease),” The New England Journal of Medicine, vol. 343, no. 12, pp. 864–869, 2000.
[46]
T. Sasajima, Y. Kubo, M. Inaba, K. Goh, and N. Azuma, “Role of infrainguinal bypass in Buerger's disease: an eighteen-year experience,” European Journal of Vascular and Endovascular Surgery, vol. 13, no. 2, pp. 186–192, 1997.
[47]
A. K. Bozkurt, K. Besirli, C. Koksal, et al., “Surgical treatment of Buerger's disease,” Vascular, vol. 12, pp. 192–197, 2004.
[48]
J. Chander, L. Singh, P. Lal, A. Jain, P. Lal, and V. K. Ramteke, “Retroperitoneoscopic lumbar sympathectomy for buerger's disease: a novel technique,” Journal of the Society of Laparoendoscopic Surgeons, vol. 8, no. 3, pp. 291–296, 2004.
[49]
P. N. Nesargikar, M. K. Ajit, P. S. Eyers, B. J. Nichols, and J. F. Chester, “Lumbar chemical sympathectomy in peripheral vascular disease: does it still have a role?” International Journal of Surgery, vol. 7, no. 2, pp. 145–149, 2009.
[50]
S. Hoshino, K. Nakayama, T. Igari, and K. Honda, “Long-term results of omental transplantation for chronic occlusive arterial diseases,” International Surgery, vol. 68, no. 1, pp. 47–50, 1983.
[51]
M. Chaudhary, P. Chaudhary, and M. R. Chaudhary, “Buerger's disease—its management by bone widening technique of Ilizarov,” Recent Advances in Surgery, Roshan Lal Gupta, Jaypee Brothers, New Delhi, vol. 8, pp. 259–271, 2006.
[52]
J. J. Patwa and A. Krishnan, “Buerger's disease (thromboangiitis obliterans)—management by ilizarov's technique of horizontal distraction. A retrospective study of 60 cases,” Indian Journal of Surgery, vol. 73, no. 1, pp. 40–47, 2011.
[53]
M. Stanton-Hicks and J. Salamon, “Stimulation of the central and peripheral nervous system for the control of pain,” Journal of Clinical Neurophysiology, vol. 14, no. 1, pp. 46–62, 1997.
[54]
K. P. Donas, S. Schulte, K. Ktenidis, and S. Horsch, “The role of epidural spinal cord stimulation in the treatment of Buerger's disease,” Journal of Vascular Surgery, vol. 41, no. 5, pp. 830–836, 2005.
[55]
G. Fabregat, V. L. Villanueva, J. M. Asensio, J. De Andrés, and D. López, “Spinal cord stimulation for the treatment of buerger disease: a report on 3 cases,” Clinical Journal of Pain, vol. 27, no. 9, pp. 819–823, 2011.
[56]
J. N. Fiessinger and M. Sch?fer, “Trial of iloprost versus aspirin treatment for critical limb ischaemia of thromboangiitis obliterans,” The Lancet, vol. 335, no. 8689, pp. 555–557, 1990.
[57]
M. Verstraete, “Oral iloprost in the treatment of thromboangiitis obliterans (Buerger's disease): a double-blind, randomised, placebo-controlled trial,” European Journal of Vascular and Endovascular Surgery, vol. 15, no. 4, pp. 300–307, 1998.
[58]
E. R. Mohler III, W. R. Hiatt, J. W. Olin, M. Wade, R. Jeffs, and A. T. Hirsch, “Treatment of intermittent claudication with beraprost sodium, an orally active prostaglandin I2 analogue: double-blinded, randomized, controlled trial,” Journal of the American College of Cardiology, vol. 41, no. 10, pp. 1679–1686, 2003.
[59]
A. K. Bozkurt, K. Cengiz, C. Arslan, et al., “A Stable prostacyclin analogue (iloprost) in the treatment of Buerger's disease: a prospective analysis of 150 patients,” Annals of Thoracic and Cardiovascular Surgery, vol. 19, no. 2, pp. 120–150, 2013.
[60]
M. Czarnacki, M. Gacka, and R. Adamiec, “A role of endothelin 1 in the pathogenesis of thromboangiitis obliterans (initital news),” Przeglad Lekarski, vol. 61, no. 12, pp. 1346–1350, 2004.
[61]
J. De Haro, F. Acin, S. Bleda, C. Varela, and L. Esparza, “Treatment of thromboangiitis obliterans (Buerger's disease) with bosentan,” BMC Cardiovascular Disorders, vol. 12, article 5, 2012.
[62]
J. M. Isner, I. Baumgartner, G. Rauh et al., “Treatment of thromboangiitis obliterans (Buerger's disease) by intramuscular gene transfer of vascular endothelial growth factor: preliminary clinical results,” Journal of Vascular Surgery, vol. 28, no. 6, pp. 964–975, 1998.
[63]
H. J. Kim, S. Y. Jang, J. I. Park, et al., “Vascular endothelial growth factor-induced angiogenic gene therapy in patients with peripheral arterydisease,” Experimental & Molecular Medicine, vol. 36, pp. 336–344, 2004.
[64]
E. B. Friedrich, K. Walenta, J. Scharlau, G. Nickenig, and N. Werner, “CD34-/CD133+/VEGFR-2+ endothelial progenitor cell subpopulation with potent vasoregenerative capacities,” Circulation Research, vol. 98, no. 3, pp. e20–e25, 2006.
[65]
E. Tateishi-Yuyama, H. Matsubara, T. Murohara et al., “Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: a pilot study and a randomised controlled trial,” The Lancet, vol. 360, no. 9331, pp. 427–435, 2002.
[66]
J. Moriya, T. Minamino, K. Tateno et al., “Long-term outcome of therapeutic neovascularization using peripheral blood mononuclear cells for limb ischemia,” Circulation, vol. 2, no. 3, pp. 245–254, 2009.
[67]
A. Kawamoto, M. Katayama, N. Handa et al., “Intramuscular transplantation of G-CSF-mobilized CD34+ cells in patients with critical limb ischemia: a phase I/IIa, multicenter, single-blinded, dose-escalation clinical trial,” Stem Cells, vol. 27, no. 11, pp. 2857–2864, 2009.
[68]
R. H. Lee, B. Kim, I. Choi et al., “Characterization and expression analysis of mesenchymal stem cells from human bone marrow and adipose tissue,” Cellular Physiology and Biochemistry, vol. 14, no. 4-6, pp. 311–324, 2004.
[69]
H. C. Lee, S. G. An, J. S. Park, et al., “Safety and effect of adipose tissue-derived stem cell implantation in patients with critical limb ischemia,” Circulation Journal, vol. 76, no. 7, pp. 1750–1760, 2012.