Obliterative diseases of the lower extremities: causes, symptoms, diagnosis, treatment

This group of diseases is based on atherosclerosis of the arteries of the lower extremities, causing ischemia. Moderate disease may be asymptomatic or cause intermittent claudication.

In severe cases, rest pain may occur with skin atrophy, hair loss, cyanosis, ischemic ulcers, and gangrene. Diagnosis is by history, physical examination, and measurement of the ankle-brachial index. Treatment of moderate disease includes risk factor elimination, exercise, antiplatelet agents, and cilostazol or pentoxifylline depending on symptoms. Severe AAD usually requires angioplasty or bypass surgery and sometimes amputation. Prognosis is generally good with treatment, although mortality is relatively high because the disorder is often associated with coronary or cerebrovascular disease.

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What causes occlusive disease of the lower extremities?

Obliterating diseases of the lower extremities (OLED) affect approximately 12% of people in the United States, with men being affected more often. Risk factors are the same as those for atherosclerosis: hypertension, dyslipidemia [high low-density lipoprotein (LDL) cholesterol, low high-density lipoprotein (HDL) cholesterol], smoking (including passive smoking), diabetes, and a family history of atherosclerosis. Obesity, male gender, and high homocysteine levels are also risk factors. Atherosclerosis is a systemic disease. 50-75% of patients with OLED also have clinically significant coronary artery disease or cerebrovascular disease. However, OLED may be undetectable because patients with OLED cannot tolerate the physical activity that causes an attack of angina.

Symptoms of obliterating diseases of the lower extremities

Typically, occlusive disease of the lower extremities causes intermittent claudication: a nagging, painful, cramping, uncomfortable, or tired feeling in the legs that occurs during walking and is relieved by rest. Claudication symptoms usually occur in the shins, but may also occur in the thighs, buttocks, or (rarely) arms. Intermittent claudication is a manifestation of exercise-induced reversible ischemia, similar to angina. As occlusive disease progresses, the distance a patient can walk without developing symptoms may decrease, and patients with severe disease may experience pain at rest, indicating irreversible ischemia. Rest pain typically occurs distally, on raising the leg (often at night), and is relieved when the leg is lowered below the level of the heart. The pain may be felt as a burning sensation, although this is uncommon. Approximately 20% of patients with occlusive disease of the lower extremities have no clinical symptoms, sometimes because they are not active enough to cause leg ischemia. Some patients have atypical symptoms (eg, nonspecific decreased exercise tolerance, hip or other joint pain).

Mild disease often causes no clinical manifestations. Moderate and severe disease usually results in a decrease or disappearance of the peripheral (popliteal, dorsal foot, and posterior shin) pulse. If the pulse cannot be detected by palpation, Doppler ultrasonography is used.

When the limb is below cardiac level, a deep red discoloration of the skin (called dependent blush) may occur. In some patients, elevating the leg causes the limb to turn pale and worsen ischemic pain. When the leg is lowered, venous filling time is prolonged (> 15 sec). Edema does not usually occur unless the patient keeps the leg still and in a forced position to relieve pain. Patients with chronic obliterating disease of the lower extremities may have thin, pale skin with decreased or lost hair. The distal legs may feel cold. The affected leg may sweat excessively and become cyanotic, probably due to increased sympathetic nervous system activity.

As ischemia progresses, ulcers may develop (usually on the toes or heel, sometimes on the shin, thigh, or foot), especially after local trauma. The ulcers are often surrounded by black necrotic tissue (dry gangrene). They are usually painful, but may not be felt by patients with peripheral neuropathy due to diabetes or chronic alcoholism. Infection of ischemic ulcers (wet gangrene) is common and leads to rapidly progressive panniculitis.

The level of arterial occlusion affects the symptoms. Occlusive disease of the lower extremities involving the aorta and iliac arteries may cause intermittent sensations in the buttocks, thighs, or calves, thigh pain, and erectile dysfunction in men (Leriche syndrome). In femoropopliteal occlusion, claudication typically affects the calves, and the pulse below the femoral artery is weak or absent. In occlusion of most distal arteries, the femoropopliteal pulse may be palpated, but it is absent in the feet.

Diagnosis of obliterating diseases of the lower extremities

Obliterating diseases of the lower extremities may be suspected clinically, but are often unrecognized because many patients have atypical symptoms or are not active enough to cause clinical manifestations. Radicular syndrome may also cause leg pain during walking, but it differs in that the pain (called pseudoclaudication) requires sitting rather than just stopping movement to relieve it, and the distal pulse is preserved.

The diagnosis is confirmed by noninvasive studies. Blood pressure is measured in both arms and both legs. Since the pulse in the legs can be difficult to palpate, the Doppler probe is placed over the a. dorsalis pedis or posterior tibial artery. Doppler ultrasonography is often used, since pressure gradients and the shape of the pulse wave can help differentiate the isolated form of ALI with localization in the area of the aortic bifurcation from the femoropopliteal and the variant with localization of changes in vessels located below the knee level.

A low (0.90) ankle-brachial index (ratio of ankle to arm BP) indicates a variant of the disease that can be classified as mild (0.71-0.90), moderate (0.41-0.70), or severe (0.40). If the index is normal (0.91-1.30), but OD is still suspected, the index is determined after exercise. A high index (> 1.30) may indicate decreased elasticity of the leg vessel wall (eg, in Mönckeberg's arteriosclerosis with arterial wall calcification). If the index is > 1.30, but OD is still suspected, additional tests are performed (eg, Doppler ultrasonography, BP measurement on the first toe using a toe cuff) to identify possible arterial stenosis or occlusion. Ischemic lesions usually do not heal when systolic BP is < 55 mmHg (< 70 mmHg in patients with diabetes); wounds following below-knee amputations usually heal if BP is > 70 mmHg.

Vasography provides detailed clarification of the location and extent of arterial stenosis or occlusion. The data from this study determine the indications for surgical correction or percutaneous intravascular angioplasty (PVA). Vasography does not replace noninvasive studies, since it does not provide any additional information about the functional state of pathological areas. Vasography with MRI and vasography with CT are atraumatic studies that may eventually replace contrast vasography.

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Treatment of obliterating diseases of the lower extremities

All patients require active elimination or modification of risk factors, including smoking cessation and control of diabetes mellitus, dyslipidemia, hypertension, and hyperhomocysteinemia. β-Adrenergic blockers are safe if the severity of the disease is moderate.

Physical activity, such as 35–50 min of treadmill or exercise-rest-exercise treadmill walking 3–4 times per week, is an important but uncommon treatment. It may increase symptom-free walking distance and improve quality of life. Mechanisms likely include increased collateral circulation, improved endothelial function due to capillary vasodilation, decreased blood viscosity, improved red blood cell membrane flexibility, decreased ischemic inflammation, and improved tissue oxygenation.

Patients are advised to keep their legs below the level of the heart. To reduce night pain, the head of the bed can be raised 4-6 inches (10-15 cm) to improve blood flow to the legs.

It is also recommended to avoid cold and drugs that cause vasoconstriction (such as pseudoephedrine, found in many headache and cold medications).

Preventive foot care should be extremely thorough, similar to the special care given to patients with diabetes:

• daily inspection of the feet for damage and lesions;
• treatment of corns and calluses under the guidance of an orthopedist;
• daily washing of feet in warm water with mild soap, followed by light but thorough blotting and complete drying;
• prevention of thermal, chemical and mechanical injury, especially due to uncomfortable footwear.

Antiplatelet drugs may reduce symptoms somewhat and increase the asymptomatic walking distance. More importantly, these drugs modify atherogenesis and help prevent coronary heart disease attacks and transient ischemic attacks. Possible treatment options include 81 mg of acetylsalicylic acid once daily, 25 mg of acetylsalicylic acid with 200 mg of dipyridamole once daily, 75 mg of clopidogrel orally once daily, or 250 mg of ticlopidine orally with or without acetylsalicylic acid. Acetylsalicylic acid is usually used as a monotherapy as the first drug, then may be added or replaced with other drugs if the obliterating disease of the lower extremities progresses.

Pentoxifylline orally 400 mg 3 times daily with meals or cilostazol orally 100 mg may be given to reduce intermittent claudication, improve blood flow, and increase tissue oxygenation in damaged areas; however, these drugs are not a substitute for risk factor elimination and exercise. Taking this drug for 2 months or more may be safe because adverse effects, although varied, are rare and mild. The most common adverse effects of cilostazol are headache and diarrhea. Cilostazol is contraindicated in severe heart failure.

Other drugs that may reduce claudication are under study. They include L-arginine (a precursor of an endothelium-dependent vasodilator), nitric oxide, vasodilatory prostaglandins, and angiogenic growth factors (eg, vascular endothelial growth factor, basic fibroblast growth factor). Gene therapy for occlusive disease of the lower extremities is also being studied. In patients with severe limb ischemia, long-term parenteral use of vasodilatory prostaglandins may reduce pain and facilitate ulcer healing, and intramuscular injection of genetically engineered DNA containing vascular endothelial growth factor may induce the growth of collateral blood vessels.

Percutaneous endovascular angioplasty

Percutaneous angioplasty with or without stenting is the mainstay of nonsurgical techniques for dilating vascular occlusions. Percutaneous angioplasty with stenting can maintain arterial dilation better than balloon dilation alone, with a lower rate of reocclusion. Stents are more effective in large, high-flow arteries (iliac and renal), and less effective in smaller arteries and in long occlusions.

Indications for percutaneous angioplasty are similar to those for surgical treatment: intermittent claudication that reduces physical activity, pain at rest, and gangrene. Curable lesions are flow-limiting short iliac stenoses (less than 3 cm in length) and short single or multiple stenoses of the superficial femoropopliteal segment. Complete occlusions (up to 10-12 cm in length) of the superficial femoral artery can be successfully dilated, but the results are better for occlusions 5 cm or less in length. Percutaneous angioplasty is also effective for limited iliac stenosis located proximal to the femoropopliteal artery bypass graft.

Percutaneous intravascular angioplasty is less effective in diffuse lesions, long occlusions and eccentric calcified plaques. This pathology most often develops in diabetes mellitus, mainly affecting small arteries.

Complications of percutaneous intravascular angioplasty include thrombosis at the dilation site, distal embolization, intimal dissection with flap occlusion, and complications associated with the use of sodium heparin.

With proper patient selection (based on complete and well-performed angiography), the initial success rate approaches 85-95% for iliac arteries and 50-70% for leg and femoral arteries. Recurrence rates are relatively high (25-35% within 3 years), and repeat percutaneous intravascular angioplasty may be successful.

Surgical treatment of obliterating diseases of the lower extremities

Surgical treatment is indicated for patients who can safely undergo major vascular intervention and whose severe symptoms do not respond to non-invasive treatments. The goal is to relieve symptoms, heal the ulcer, and prevent amputation. Since many patients have concomitant coronary artery disease, they are considered high-risk for surgery in light of the risk of acute coronary syndrome, so the patient's cardiac function is usually assessed prior to surgery.

Thromboendarterectomy (surgical removal of the occluding object) is performed for short, limited lesions in the aorta, iliac, common femoral, or deep femoral arteries.

Revascularization (eg, femoropopliteal anastomosis) using synthetic or natural (often the saphenous vein or other vein) materials is used to bypass occluded segments. Revascularization helps prevent limb amputation and reduces lameness.

In patients unable to tolerate extensive surgery, sympathectomy may be effective when distal occlusion causes severe ischemic pain. Chemical sympathetic blockade is similar in effectiveness to surgical sympathectomy, so the latter is rarely performed.

Amputation is a last resort, indicated for intractable infection, intractable pain at rest, and progressive gangrene. Amputation should be as distal as possible, preserving the knee to allow optimal use of the prosthesis.

External compression therapy

External pneumatic compression of the lower limb to increase distal blood flow is the method of choice for limb salvage in patients with severe disease who are unable to tolerate surgery. Theoretically, it reduces edema and improves arterial blood flow, venous return, and tissue oxygenation, but there is insufficient research to support its use. Pneumatic cuffs or stockings are placed on the lower leg and inflated rhythmically during diastole, systole, or part of both for 1 to 2 hours several times a week.

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