Thrombo-occlusive vasculitis (TAO), also known as Buerger’s disease, is a chronic progressive occlusive disease characterized by segmental, nonsuppurative inflammation of small and medium-sized arteries and veins and intra-arterial thrombosis. TAO affects mainly the extremities, especially the small and medium-sized arteries and veins of the lower extremities, leading to ischemic lesions in the distal extremities of the affected limbs. TAO occurs in young and middle-aged men, most of whom have a history of smoking, and is more common in the Middle, Southeast and Far East of Asia and Eastern Europe.
1.Diagnosis of TAO
The diagnostic criteria proposed by Olin in 2000 considered that TAO can be diagnosed if the following conditions are met.
(1) Age less than 45 years.
(2) Current or recent history of smoking.
(3) Distal limb ischemia (manifested by claudication, resting pain, ischemic ulcers or gangrene).
(4) Exclusion of autoimmune diseases, hypercoagulable states and diabetes mellitus.
(5) Exclusion of thrombus of proximal origin by echocardiography or arteriography.
(6) Consistency with angiographic findings in clinically involved or uninvolved limbs. A typical angiogram shows small and medium-sized vessel involvement distal to the knee or elbow, with jumping damage to the affected artery and multiple, segmental obstructions; spiraling collateral vessels appear, directly connected to the thrombosed vessel. Histopathological examination is the last means to confirm the diagnosis.
2.Differential diagnosis of TAO
TAO is often confused with other diseases that cause reduced blood flow to the extremities such as atherosclerosis, endocarditis, other types of vasculitis, severe Raynaud’s syndrome, and connective tissue diseases (lupus or scleroderma), so a clear differential diagnosis must be made because TAO and the above diseases are treated differently and there is no clear effective treatment.
(1) Arteriosclerotic occlusive disease:
(i) It is mostly seen in middle-aged and elderly people, and can develop in both sexes.
(2) The lesions mainly involve large and medium-sized arteries. Especially the lower abdominal aorta and the iliofemoral artery are the most common.
(iii) It is often combined with hypertension, hyperlipidemia, diabetes mellitus and visceral atherosclerotic ischemia.
(iv) Mostly without wandering superficial thrombophlebitis.
(⑤) Thoracic and abdominal plain radiographs may show prominent aortic arch and arterial calcification shadow, arteriography shows irregular filling defect of arterial lumen with worm-like changes, and arteries distal to occlusion may be visualized via collateral vessels.
(6) Pathological examination shows degeneration of both the middle layer and intima of the artery, while the veins are not involved.
(2) Multiple aortitis.
(1) Most often seen in young women.
The lesions often involve multiple large arteries at the same time, mainly invading branches of the aortic arch and/or the aorta and its visceral branches. Vascular murmurs can be heard and tremors can be detected in the lesion.
③There are often clinical manifestations of chronic ischemia of the limbs, but ischemic ulceration and gangrene of the limbs are usually not present.
(4) Arteriography shows stenosis or occlusion at the opening of the main branches of the aorta.
(3) Idiopathic arterial thrombosis: It is rare.
(1) Most often seen in patients with connective tissue disease, hematologic disease and metastatic cancer.
(2) The onset of the disease is acute, mainly manifesting as sudden occlusion of the iliofemoral artery, which may cause extensive necrosis of the limb.
(3) It may be accompanied by iliofemoral vein thrombosis.
(4) Periarteritis nodosa: mainly involves middle and small arteries, and may present with limb ischemic symptoms similar to those of TAO, but with the following characteristics.
(1) Mostly accompanied by systemic symptoms such as fever, malaise and joint pain.
②The lesions are widespread, often involving the kidney, heart, liver, intestine and other visceral arteries, with clinical manifestations of corresponding visceral ischemia.
③Subcutaneous nodules arranged along the arterial line often appear.
④Laboratory tests show hyperglobulinemia and increased sedimentation.
(⑤ Biopsy can clarify the diagnosis.
(5) Diabetic gangrene.
(① Clinical manifestations of three polydipsia and one hypodynamia, i.e., polyhydrosis, polyuria, polyphagia and weight loss.
② Laboratory tests show elevated blood glucose or positive urine glucose.
3.Treatment of TAO
The treatment principle of TAO is to prevent the development of lesions, improve the blood supply of the affected limb, reduce the pain of the affected limb and promote the healing of ulcers. Specific methods are as follows.
(1) General treatment
The prognosis of this disease is largely determined by whether the patient insists on quitting smoking. Smoking cessation is the fundamental way to control the progression of TAO and prevent amputation, but it cannot stop the progression of the disease. Avoiding cold, moisture, trauma and proper warmth of the affected limb can help prevent further aggravation and complications. Exercises for the affected limb (Buerger exercise) can help promote the establishment of lateral branch circulation and increase blood supply to the affected limb.
(2) Drug therapy
(1) Vasodilators have the effect of relieving arterial spasm and dilating blood vessels, and are suitable for the first and second stage patients. Commonly used drugs include: benztropine (tolazoline), nicotinic acid, poppy bases, etc. The use of intra-arterial injection of tolazoline, 654-2, procaine and other drugs can improve the efficacy, but repeated puncture of the artery is required, which can cause arterial injury or spasm, and the clinical application is limited.
② Prostaglandins have the effect of vasodilatation and platelet inhibition, and have achieved good results in the treatment of TAO. Prostacyclin (PGI2) has stronger vasodilating and platelet inhibiting effects, but its half-life is short and its performance is unstable, so its clinical efficacy is not certain.
③Hexketone cocaine (Pentoxifylline) can reduce blood viscosity and increase the deformability of red blood cells, enabling them to pass through narrow blood vessels, thus increasing tissue perfusion.
④Eastern Lindif (Batroxobin) is a single-component thrombin-like enzyme, a type of serine protease, which has the effect of reducing fibrinogen.
⑤ Agatroban is a thrombin inhibitor that reversibly binds to the active site of thrombin and exerts its anticoagulant effects by inhibiting reactions catalyzed or induced by thrombin, including inhibition of fibrin formation, activation of coagulation factors V, VIII and XIII, activation of proteinase C, and inhibition of platelet aggregation. It is used to improve symptoms such as ulceration of the extremities, resting pain and cold sensation in patients with TAO.
(6) Hormone Hormone treatment is not uniform, and some people believe that hormone can control the development of the disease and relieve the pain of the affected limbs.
(3) Surgical treatment
① Sympathectomy can release vasospasm, promote the establishment of collateral circulation and improve blood supply to the affected limb, and is suitable for the first and second stage patients. Depending on whether the lesion involves the upper or lower extremity artery, ipsilateral thoracic or lumbar 2nd, 3rd, 4th sympathetic ganglion and its nerve chain should be removed. Since sympathectomy mainly improves the blood supply to the skin, it often results in increased skin temperature and healing of skin ulcers, but does not relieve the symptoms of interstitial claudication.
② Arterial thrombectomy is a surgical procedure to remove the thrombotic endothelium of the diseased artery, thereby reestablishing blood flow in the artery of the affected limb. It is suitable for patients with stage II or III occlusion of the femoral and N arteries, while at least one of the branches of the N artery is patent. Because of the low clinical suitability and poor long-term efficacy of endarterectomy for TAO, it is now less commonly used.
(iii) Arterial bypass grafting is performed at the proximal or distal end of the occluded artery, with the same indications as endarterectomy. Most of the arterial graft materials are autologous saphenous veins, and artificial vessels can be used above the knee. Since TAO lesions mainly involve small and medium-sized arteries, the condition of the output tract is often poor, so arterial bypass grafting is rarely available.
④ The greater omentum graft is performed by freeing the greater omentum, anastomosing the right artery and vein of the gastric omentum with the femoral artery, saphenous vein or N artery and vein, and then transplanting the clipped or unclipped greater omentum to the medial side of the affected limb. The near-term outcome is satisfactory, but the long-term outcome is uncertain.
⑤ Arterialization of the vein is an anastomosis of the occluded proximal artery with the vein, so that the arterial blood of the occluded proximal end is diverted to the venous system of the affected limb, thus improving the blood supply of the affected limb. The method is to form an arteriovenous fistula by anastomosing the femoral and N arteries with the superficial femoral vein, the tibiofibular trunk vein or the saphenous vein, depending on the level of arterial occlusion in the affected limb, so that arterial blood can both continuously impact the venous valve distal to the fistula and return to the heart from the vein proximal to the fistula. After a period of time (2 months), the valves in the distal veins of the fistula become incomplete due to the long-term impact of the reverse arterial blood flow and the expansion of the venous segments. At this point, the vein proximal to the fistula is then ligated, allowing unidirectional perfusion of arterial blood through the vein to the distal end of the affected limb.
(6) In recent years, balloon dilation and stenting have been widely used in the interventional treatment of peripheral arterial stenosis or occlusive lesions, and good results and application prospects have been obtained for segmental arterial stenosis and occlusion, but most patients with vasculitis have complete occlusion from the N artery downward, and the entire vessel wall is inflamed and the lesion segment is long.
(7) In cases where revascularization is ineffective and the limb (toe) has become necrotic, amputation of the limb (toe) may be considered.
TAO is a chronic progressive disease and patients are not at immediate risk of death, but their life expectancy will be shorter than normal and the risk of amputation is twice as high as that of a smoker who has quit smoking. Abstaining from smoking, avoiding dampness and cold, protecting the feet, avoiding trauma, and preventing vasospasm of the limbs are effective measures to prevent TAO from becoming disabling.