Skip to search form Skip to main content You are currently offline. Some features of the site may not work correctly. DOI: Thromboangiitis obliterans TAO is a segmental, inflammatory, vasoocclusive disease that predominantly affects the small and medium-sized arteries and veins of the extremi- ties. It most often occurs in young male smokers, especially those from Mediterranean and Asian countries.
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Thromboangiitis obliterans TAO is a segmental inflammatory occlusive disorder that affects small- and medium-sized arteries, and arm and leg veins of young smokers. Several different diagnostic criteria have been offered for the diagnosis of TAO. Clinically, it manifests as migratory thrombophlebitis or signs of arterial insufficiency in the extremities.
It is characterized by highly cellular and inflammatory occlusive thrombi, primarily of the distal extremities. Thromboses are often occlusive and sometimes display moderate, nonspecific inflammatory infiltrate, consisting mostly of polymorphonuclear leukocytes, mononuclear cells and rare multinuclear giant cells. The immune system appears to play a critical role in the etiology of TAO.
However, knowledge about immunological aspects involved in the progression of vascular tissue inflammation, and consequently, the evolution of this disease, is still limited.
There are several studies that suggest the involvement of genetic factors and results have shown increasing levels of antiendothelial cell antibodies in patients with active disease. Vasodilation is impaired in patients with TAO.
TAO disorder may actually be an autoimmune disorder, probably initiated by an unknown antigen in the vascular endothelium, possibly a component of nicotine.
There are various therapies available for treatment of TAO, but the major and indispensable measure is smoking cessation. Except for discontinuation of tobacco use, no forms of therapy are definitive. Sympathectomy, cilostazol and prostaglandin analogues prostacyclin or prostaglandin E have been used in specific conditions. Recently, therapeutic angiogenesis with autologous transplantation of bone marrow mononuclear cells has been studied in patients with critical limb ischemia.
Thromboangiitis obliterans TAO was first described in , 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. In , Buerger reported that tobacco use was probably a predisposing factor 3. It is characterized by chronic inflammation and acute thrombosis of medium- and small-calibre arteries in the arms and legs, particularly the tibial and radial arteries, with occasional extension to veins and nerves of the extremities 5 — 7.
The precise cause of TAO is still unknown and different hypotheses are suggested. A reaction to the constituents of cigarettes is recognized as a factor of initiation, progression and prognosis of this disease. Possibly, genetic modifications or autoimmune disorders are implicated 8 — Thus, the strong relationship with smoking seems to involve direct toxicity to the endothelium by certain tobacco products nicotine or an idiosyncratic immune response to some agents. Most patients with TAO have hypersensitivity to extracts of tobacco.
Peripheral endothelium-dependent vasodilation is impaired in the nondiseased limbs of patients with TAO, and this type of vascular dysfunction may contribute to such characteristics as segmental proliferative lesions or thrombus formation in the peripheral vessels The incidence of TAO has decreased in men, despite the relative increase in the number of female cases due to the increasing number of female smokers The number of women presenting to the clinic with TAO was almost equal to that of men.
The only difference was the higher incidence of female nonsmokers at the first consultation, but this did not influence the response to treatment or outcome Cigarette smoking is regarded as the only strong contributing factor to TAO.
When patients stopped smoking at the initial stage, the disease did not progress. Thus, it was suggested that TAO is a process of self-aggression triggered by substances in tobacco. The initial injuries are immune reactions associated with activation of lymphocytes, macrophages and dendritic cells in the arterial wall, followed by deposition of antiendothelial cell antibodies 16 — Genetic influences are suggested by different prevalences in certain ethnic groups TAO occurs frequently in Israelis, some Indian groups, the Japanese, Southeast Asians and Middle Eastern groups, and rarely in African-Americans and an association with major histocompatibility complex haplotypes 21 — Mutations in prothrombin G-A have also been the object of research 24 , Moreover, Barlas et al 26 described a study in a group of patients with TAO total; At the time of admission, The study was divided into early to and late to periods.
In the late period, an increase in the upper extremity involvement rate In addition, sympathectomy, amputation, revascularization and medical therapy were proven to be mostly ineffective in these patients. Of the patients who stopped smoking, 5. Clinically, TAO manifests as migratory thrombophlebitis or signs of arterial insufficiency in the extremities. Vascular insufficiency caused by TAO tends to be accompanied by intense pain, even at rest, possibly related to nerve involvement and inflammatory mediators.
The patients remain in generally good condition, without any manifestation of systemic disease. Later, with the worsening of symptoms, gradual evolution of ischemia results in gangrene of the extremities 27 , Studies have shown a possible relationship of TAO with hypercoagulable states, although its details are presently unknown.
There are cases associated with protein S and protein C deficiencies 29 , 30 , antiphospholipid antibodies 31 and hyperhomocysteinemia 32 , A recently published study showed that high concentrations of anticardiolipin antibodies were correlated with an early and more severe form of disease, including higher rates of amputation 15 , In other publications, high concentrations of plasma catecholamines were found in TAO patients, likely because there is a possible change of relaxation due to endothelial dysfunction, which could be attributed to the adrenergic effect of tobacco Regarding possible peripheral adrenergic system involvement, some authors have proposed that cocaine abuse may be the underlying cause in many cases of TAO Other studies have not confirmed the relationship between the sympathetic system and TAO, suggesting that a local vascular disruption is the responsible mechanism The physiological function of the immune system to provide defenses against infectious organisms, as well as noninfectious foreign substances, can trigger an immune response.
Moreover, the mechanisms that normally protect people from infection and remove foreign substances are capable of causing tissue damage and diseases in some situations. Different molecules, glycoproteins, cells and lymphoid tissues directly act together to guarantee the body defense system.
Moreover, the spectrum of events observed during inflammation varies according to the tissue and the type of injury involved. The most important characteristics are the changes in diameter and permeability of blood vessels, and the local expression of molecules on the endothelial surface of these vessels. However, a response may also involve influx of specific types of white blood cells, occurrence of fever, activation of the clotting system, release of immune and complementary kinins, and many other phenomena 38 , The immune system seems to play a critical role in the etiology of TAO.
However, knowledge about immunological aspects involved in the progression of vascular tissue inflammation, and consequently the evolution of this disease, is still limited. Results have shown increased levels of antiendothelial cell antibodies in patients with active disease. TAO may actually be an autoimmune disorder, likely initiated by an unknown antigen in the vascular endothelium, possibly a component of nicotine.
Accordingly, the formation of immune complexes, activation of cell-mediated phagocytosis and the release of toxins stimulated by nicotine are the main agents responsible for vascular damage.
Another factor of vascular injury is changes in the balance of prostacyclin I2 and thromboxane A2, which can further accelerate platelet aggregation causing spasms of the arterioles 15 , Maslowski et al 16 suggested that anticardiolipin antibodies are important for the pathogenesis of TAO.
However, patients with generalized periodontitis had significantly greater titres of IgG or IgM anticardiolipin antibodies, and these levels were significantly higher in smokers than in nonsmokers In addition, elevated titres of IgG against periodontal pathogens are related to development of TAO Slavov et al 18 reported that in TAO patients with persistent immune inflammation, production of culture supernatant and serum interleukin IL -6, IL and IL was altered, and apoptosis in cultures of polymorphonuclear leukocytes was increased.
An increase in plasma levels of endothelin-1 was associated with clinical exacerbation of symptoms of TAO Some molecules, such as the P-, E- and L-selectins, play an important role in the vascular endothelium and have increased expression in these patients. Prostaglandin E1 could be an alternate treatment for repair of the vascular wall endothelium. Simultaneously, it can produce an improvement in tissue perfusion, thus promoting a reduction in expression of selectins, which hamper the inflammatory response and leukocyte aggregation in the vascular endothelium 42 , 46 , Halacheva et al 50 showed that endothelial cells were activated in TAO.
Vascular lesions may trigger the secretion of TNF-alpha by inflammatory cells and express intercellular adhesion molecule 1-, vascular cell adhesion molecule and E-selectin-favouring leukocyte adherence.
The presence of lymphocytes T and B and macrophages was observed in biopsies of muscle fibres affected by TAO, suggesting that immunogenic factors can be found along these elastic fibres 51 — Recently, a case of TAO involving multiple large vessels was described These findings indicate inflammation and immunological processes in TAO with multiorgan involvement.
Brodmann et al 55 reported that nitric oxide is synthesized by nitric oxide synthase NOS , and plays a key role in the adaptation of endothelial function, such as vasodilation and reduction of free radicals caused by smoking. In smokers, a genetic defect of endothelial NOS could result in impairment of endothelial function. A biopsy is rarely needed to make the diagnosis unless the patient presents with an unusual characteristic, such as large artery involvement or age older than 45 years.
The acute lesion is considered diagnostic The artery or vein is modestly swollen, and there is a moderate infiltrate of the adventitia and media. The lumen is occluded by a highly cellular, unique thrombus, with characteristic microabscesses. Lymphocytes exceed neutrophils, and occasional giant cells, and some eosinophils may be seen.
In the subacute phase, cellularity of the vessel wall and thrombus decreases, microabscesses disappear and recanalization begins. Several misconceptions in the past led to either overdiagnosis of TAO or refusal to accept its existence as a specific disorder 60 , Sometimes this pathology may be presented in asymptomatic patients as occlusive lesions, and has been demonstrated in angiograms in the small arteries of the foot or hand and may remain unnoticed until the involvement of arteries in the calf or forearm.
Surprisingly, gangrene precedes claudication, which is not frequent, and when present, is usually confined to the foot There are two important distinctions between TAO and other arteritides — the absence of positive serological markers of inflammation and the nonexistence of autoantibodies.
Preservation of the internal elastic lamina distinguishes it from the true necrotizing forms of arteritis. Because there are no specific laboratory tests for TAO, a definite diagnosis should be based on clinical data and the investigation should exclude other disorders that may mimic the disease, as described in Table 1 7. Adapted from reference 7.
The angiographic findings in patients with TAO, although considered by some investigators to be pathognomonic, are not adequate to make a diagnosis, and their sensitivity and specificity are not high enough to be considered the gold standard. Cocaine and cannabis abuse can also mimic TAO arteriographic findings 64 — Furthermore, angiography alone or in combination with biopsy or a revascularization procedure in patients undergoing amputation of limbs can also provide important findings.
Angiographic findings are considered relevant in patients older than 40 years of age, and young female or male passive or active smokers. The absence of gangrenous limbs or end-stage ischemic ulcers, and previous sympathectomy chest, bilateral lumbar, thoracic and lumbar, lumbar and unilateral may also be important in the clinical diagnosis of TAO The differential diagnosis of TAO is usually not difficult in the presence of a typical clinicopathological picture.
The most important diseases to exclude are atherosclerosis, emboli and autoimmune diseases. There are situations in which diagnosis can be difficult, such as early onset arteriosclerosis in young male smokers, and collagen and autoimmune diseases in young people associated with digital cyanosis, pain and gangrene.
The literature has demonstrated that ischemia induced by cocaine and cannabis ingestion can mimic TAO 66 , Occlusive disease of the digits is a frequent vascular manifestation of hematological disorders.
Síndrome de Leo Buerger (Tromboangeitis Obliterante). A Propósito de un Caso.
Thromboangiitis obliterans TAO is a segmental inflammatory occlusive disorder that affects small- and medium-sized arteries, and arm and leg veins of young smokers. Several different diagnostic criteria have been offered for the diagnosis of TAO. Clinically, it manifests as migratory thrombophlebitis or signs of arterial insufficiency in the extremities. It is characterized by highly cellular and inflammatory occlusive thrombi, primarily of the distal extremities. Thromboses are often occlusive and sometimes display moderate, nonspecific inflammatory infiltrate, consisting mostly of polymorphonuclear leukocytes, mononuclear cells and rare multinuclear giant cells.
Enfermedad de Buerger (tromboangeítis obliterante)
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