Harrison's Cardiovascular Medicine 2 ed.

CHAPTER 39. VASCULAR DISEASES OF THE EXTREMITIES

Mark A. Creager image Joseph Loscalzo

ARTERIAL DISORDERS

PERIPHERAL ARTERY DISEASE

Peripheral artery disease (PAD) is defined as a clinical disorder in which there is a stenosis or occlusion in the aorta or the arteries of the limbs. Atherosclerosis is the leading cause of PAD in patients >40 years old. Other causes include thrombosis, embolism, vasculitis, fibromuscular dysplasia, entrapment, cystic adventitial disease, and trauma. The highest prevalence of atherosclerotic PAD occurs in the sixth and seventh decades of life. As in patients with atherosclerosis of the coronary and cerebral vasculature, there is an increased risk of developing PAD in cigarette smokers and in persons with diabetes mellitus, hypercholesterolemia, hypertension, or hyperhomocysteinemia.

Pathology

(See also Chap. 30) Segmental lesions that cause stenosis or occlusion are usually localized to large and medium-size vessels. The pathology of the lesions includes atherosclerotic plaques with calcium deposition, thinning of the media, patchy destruction of muscle and elastic fibers, fragmentation of the internal elastic lamina, and thrombi composed of platelets and fibrin. The primary sites of involvement are the abdominal aorta and iliac arteries (30% of symptomatic patients), the femoral and popliteal arteries (80–90% of patients), and the more distal vessels, including the tibial and peroneal arteries (40–50% of patients). Atherosclerotic lesions occur preferentially at arterial branch points, which are sites of increased turbulence, altered shear stress, and intimal injury. Involvement of the distal vasculature is most common in elderly individuals and patients with diabetes mellitus.

Clinical evaluation

Fewer than 50% of patients with PAD are symptomatic, although many have a slow or impaired gait. The most common symptom is intermittent claudication, which is defined as a pain, ache, cramp, numbness, or a sense of fatigue in the muscles; it occurs during exercise and is relieved by rest. The site of claudication is distal to the location of the occlusive lesion. For example, buttock, hip, and thigh discomfort occurs in patients with aortoiliac disease, whereas calf claudication develops in patients with femoral-popliteal disease. Symptoms are far more common in the lower than in the upper extremities because of the higher incidence of obstructive lesions in the former region. In patients with severe arterial occlusive disease in whom resting blood flow cannot accommodate basal nutritional needs of the tissues, critical limb ischemia may develop. Patients complain of rest pain or a feeling of cold or numbness in the foot and toes. Frequently, these symptoms occur at night when the legs are horizontal and improve when the legs are in a dependent position. With severe ischemia, rest pain may be persistent.

Important physical findings of PAD include decreased or absent pulses distal to the obstruction, the presence of bruits over the narrowed artery, and muscle atrophy. With more severe disease, hair loss, thickened nails, smooth and shiny skin, reduced skin temperature, and pallor or cyanosis are common physical signs. In patients with critical limb ischemia, ulcers or gangrene may occur. Elevation of the legs and repeated flexing of the calf muscles produce pallor of the soles of the feet, whereas rubor, secondary to reactive hyperemia, may develop when the legs are dependent. The time required for rubor to develop or for the veins in the foot to fill when the patient’s legs are transferred from an elevated to a dependent position is related to the severity of the ischemia and the presence of collateral vessels. Patients with severe ischemia may develop peripheral edema because they keep their legs in a dependent position much of the time. Ischemic neuropathy can result in numbness and hyporeflexia.

Noninvasive testing

The history and physical examination are often sufficient to establish the diagnosis of PAD. An objective assessment of the presence and severity of disease is obtained by noninvasive techniques. Arterial pressure can be recorded noninvasively in the legs by placement of sphygmomanometric cuffs at the ankles and the use of a Doppler device to auscultate or record blood flow from the dorsalis pedis and posterior tibial arteries. Normally, systolic blood pressure in the legs and arms is similar. Indeed, ankle pressure may be slightly higher than arm pressure due to pulse-wave amplification. In the presence of hemodynamically significant stenoses, the systolic blood pressure in the leg is decreased. Thus, the ratio of the ankle and brachial artery pressures (termed the ankle:brachial index, or ABI) is ≥1.0 in normal individuals and <1.0 in patients with PAD; a ratio of <0.5 is consistent with severe ischemia.

Other noninvasive tests include segmental pressure measurements, segmental pulse volume recordings, duplex ultrasonography (which combines B-mode imaging and Doppler flow velocity waveform analysis examination), transcutaneous oximetry, and stress testing (usually using a treadmill). Placement of pneumatic cuffs enables assessment of systolic pressure along the legs. The presence of pressure gradients between sequential cuffs provides evidence of the presence and location of hemodynamically significant stenoses. In addition, the amplitude of the pulse volume contour becomes blunted in the presence of significant PAD. Duplex ultrasonography is used to image and detect stenotic lesions in native arteries and bypass grafts.

Treadmill testing allows the physician to assess functional limitations objectively. Decline of the ABI immediately after exercise provides further support for the diagnosis of PAD in patients with equivocal symptoms and findings on examination.

Magnetic resonance angiography (MRA), computed tomographic angiography (CTA), and conventional contrast angiography should not be used for routine diagnostic testing but are performed before potential revascularization (Fig. 39-1). Each test is useful in defining the anatomy to assist planning for catheter-based and surgical revascularization procedures.

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FIGURE 39-1

Magnetic resonance angiography
 of a patient with intermittent claudication, showing stenoses of the distal abdominal aorta and right iliac common iliac artery (A) and stenoses of the right and left superficial femoral arteries (B). (Courtesy of Dr. Edwin Gravereaux; with permission.)

Prognosis

The natural history of patients with PAD is influenced primarily by the extent of coexisting coronary artery and cerebrovascular disease. Approximately one-third to one-half of patients with symptomatic PAD have evidence of coronary artery disease (CAD) based on clinical presentation and electrocardiogram, and over one-half have significant CAD by coronary angiography. Patients with PAD have a 15–30% 5-year mortality rate and a two- to sixfold increased risk of death from coronary heart disease. Mortality rates are highest in those with the most severe PAD. Measurement of ABI is useful for detecting PAD and identifying persons at risk for future atherothrombotic events. The likelihood of symptomatic progression of PAD is lower than the chance of succumbing to CAD. Approximately 75–80% of nondiabetic patients who present with mild to moderate claudication remain symptomatically stable. Deterioration is likely to occur in the remainder, with approximately 1–2% of the group ultimately developing critical limb ischemia each year. Approximately 25–30% of patients with critical limb ischemia undergo amputation within 1 year. The prognosis is worse in patients who continue to smoke cigarettes or have diabetes mellitus.


TREATMENT Peripheral Artery Disease

Patients with PAD should receive therapies to reduce the risk of associated cardiovascular events, such as myocardial infarction and death, and to improve limb symptoms, prevent progression to critical limb ischemia, and preserve limb viability. Risk factor modification and antiplatelet therapy should be initiated to improve cardiovascular outcomes. The importance of discontinuing cigarette smoking cannot be overemphasized. The physician must assume a major role in this lifestyle modification. Counseling and adjunctive drug therapy with the nicotine patch, bupropion, or varenicline increase smoking cessation rates and reduce recidivism. It is important to control blood pressure in hypertensive patients. Angiotensin converting-enzyme inhibitors may reduce the risk of cardiovascular events in patients with symptomatic PAD. β-adrenergic blockers do not worsen claudication and may be used to treat hypertension, especially in patients with coexistent CAD. Treatment of hypercholesterolemia with statins is advocated to reduce the risk of myocardial infarction, stroke, and death. The National Cholesterol Education Program Adult Treatment Panel considers PAD a coronary heart disease equivalent and recommends treatment to reduce low-density lipoprotein (LDL) cholesterol to <100 mg/dL. Platelet inhibitors, including aspirin and clopidogrel, reduce the risk of adverse cardiovascular events in patients with atherosclerosis and are recommended for patients with PAD. Dual antiplatelet therapy with both aspirin and clopidogrel is not more effective than aspirin alone in reducing cardiovascular morbidity and mortality rates in patients with PAD. The anticoagulant warfarin is as effective as antiplatelet therapy in preventing adverse cardiovascular events but causes more major bleeding; therefore, it is not indicated to improve outcomes in patients with chronic PAD.

Therapies for intermittent claudication and critical limb ischemia include supportive measures, medications, nonoperative interventions, and surgery. Supportive measures include meticulous care of the feet, which should be kept clean and protected against excessive drying with moisturizing creams. Well-fitting and protective shoes are advised to reduce trauma. Elastic support hose should be avoided, as it reduces blood flow to the skin. In patients with critical limb ischemia, shock blocks under the head of the bed together with a canopy over the feet may improve perfusion pressure and ameliorate some of the rest pain.

Patients with claudication should be encouraged to exercise regularly and at progressively more strenuous levels. Supervised exercise training programs for 30- to 45-min sessions, three to five times per week for at least 12 weeks, prolong walking distance. Patients also should be advised to walk until nearly maximum claudication discomfort occurs and then rest until the symptoms resolve before resuming ambulation. Pharmacologic treatment of PAD has not been as successful as the medical treatment of CAD (Chap. 33). In particular, vasodilators as a class have not proved to be beneficial. During exercise, peripheral vasodilation occurs distal to sites of significant arterial stenoses. As a result, perfusion pressure falls, often to levels lower than that generated in the interstitial tissue by the exercising muscle. Drugs such as α-adrenergic blocking agents, calcium channel antagonists, papaverine, and other vasodilators have not been shown to be effective in patients with PAD.

Cilostazol, a phosphodiesterase inhibitor with vasodilator and antiplatelet properties, increases claudication distance by 40–60% and improves measures of quality of life. The mechanism of action accounting for its beneficial effects is not known. Pentoxifylline, a substituted xanthine derivative, increases blood flow to the microcirculation and enhances tissue oxygenation. Although several placebo-controlled studies have found that pentoxifylline increases the duration of exercise in patients with claudication, its efficacy has not been confirmed in all clinical trials. Statins appeared promising for treatment of intermittent claudication in initial clinical trials, but more studies are needed to confirm their efficacy. There is no definitive medical therapy for critical limb ischemia, although several studies have suggested that long-term parenteral administration of vasodilator prostaglandins decreases pain and facilitates healing of ulcers. Clinical trials of angiogenic growth factors are proceeding. Intramuscular gene transfer of DNA encoding vascular endothelial growth factor, fibroblast growth factor, hepatocyte growth factor, or hypoxia-inducible factor 1α, as well as administration of endothelial progenitor cells, may promote collateral blood vessel growth in patients with critical limb ischemia. Some trial results have been negative, and others encouraging. The outcome of ongoing studies will further elucidate the potential role of therapeutic angiogenesis for PAD.

REVASCULARIZATION Revascularization procedures, including catheter-based and surgical interventions, are usually indicated for patients with disabling, progressive, or severe symptoms of intermittent claudication despite medical therapy and for those with critical limb ischemia. MRA, CTA, or conventional contrast angiography should be performed to assess vascular anatomy in patients who are being considered for revascularization. Nonoperative interventions include percutaneous transluminal angiography (PTA), stent placement, and atherectomy (Chap. 36). PTA and stenting of the iliac artery are associated with higher success rates than are PTA and stenting of the femoral and popliteal arteries. Approximately 90–95% of iliac PTAs are initially successful, and the 3-year patency rate is >75%. Patency rates may be higher if a stent is placed in the iliac artery. The initial success rates for femoral-popliteal PTA and stenting are approximately 80%, with 60% 3-year patency rates. Patency rates are influenced by the severity of pretreatment stenoses; the prognosis of occlusive lesions is worse than that of nonocclusive stenotic lesions. The role of drug-eluting stents in PAD is under investigation.

Several operative procedures are available for treating patients with aortoiliac and femoral-popliteal artery disease. The preferred operative procedure depends on the location and extent of the obstruction(s) and the general medical condition of the patient. Operative procedures for aortoiliac disease include aortobifemoral bypass, axillofemoral bypass, femoro-femoral bypass, and aortoiliac endarterectomy. The most frequently used procedure is the aortobifemoral bypass using knitted Dacron grafts. Immediate graft patency approaches 99%, and 5- and 10-year graft patency in survivors is >90% and 80%, respectively. Operative complications include myocardial infarction and stroke, infection of the graft, peripheral embolization, and sexual dysfunction from interruption of autonomic nerves in the pelvis. The operative mortality rate ranges from 1–3%, mostly due to ischemic heart disease.

Operative therapy for femoral-popliteal artery disease includes in situ and reverse autogenous saphenous vein bypass grafts, placement of polytetrafluoroethylene (PTFE) or other synthetic grafts, and thromboendarterectomy. The operative mortality rate ranges from 1–3%. The long-term patency rate depends on the type of graft used, the location of the distal anastomosis, and the patency of runoff vessels beyond the anastomosis. Patency rates of femoral-popliteal saphenous vein bypass grafts approach 90% at 1 year and 70–80% at 5 years. Five-year patency rates of infrapopliteal saphenous vein bypass grafts are 60–70%. In contrast, 5-year patency rates of infrapopliteal PTFE grafts are <30%. Lumbar sympathectomy alone or as an adjunct to aortofemoral reconstruction has fallen into disfavor.

Preoperative cardiac risk assessment may identify individuals who are especially likely to experience an adverse cardiac event during the perioperative period. Patients with angina, prior myocardial infarction, ventricular ectopy, heart failure, or diabetes are among those at increased risk. Stress testing with treadmill exercise (if feasible), radionuclide myocardial perfusion imaging, or echocardiography permits further stratification of patient risk (Chap. 36). Patients with abnormal test results require close supervision and adjunctive management with anti-ischemic medications. β-adrenergic blockers and statins reduce the risk of postoperative cardiovascular complications. Coronary angiography and coronary artery revascularization compared with optimal medical therapy do not improve outcomes in most patients undergoing peripheral vascular surgery, but cardiac catheterization should be considered in patients with unstable angina and angina refractory to medical therapy as well as those suspected of having left main or three-vessel CAD.


FIBROMUSCULAR DYSPLASIA

Fibromuscular dysplasia is a hyperplastic disorder that affects medium-size and small arteries. It occurs predominantly in females and usually involves the renal and carotid arteries but can affect extremity vessels such as the iliac and subclavian arteries. The histologic classification includes intimal fibroplasia, medial dysplasia, and adventitial hyperplasia. Medial dysplasia is subdivided into medial fibroplasia, perimedial fibroplasia, and medial hyperplasia. Medial fibroplasia is the most common type and is characterized by alternating areas of thinned media and fibromuscular ridges. The internal elastic lamina usually is preserved. The iliac arteries are the limb arteries most likely to be affected by fibromuscular dysplasia. It is identified angiographically by a “string of beads” appearance caused by thickened fibromuscular ridges contiguous with thin, less-involved portions of the arterial wall. When limb vessels are involved, clinical manifestations are similar to those for atherosclerosis, including claudication and rest pain. PTA and surgical reconstruction have been beneficial in patients with debilitating symptoms or threatened limbs.

THROMBOANGIITIS OBLITERANS

Thromboangiitis obliterans (Buerger’s disease) is an inflammatory occlusive vascular disorder involving small and medium-size arteries and veins in the distal upper and lower extremities. Cerebral, visceral, and coronary vessels may be affected rarely. This disorder develops most frequently in men <40 years of age. The prevalence is higher in Asians and individuals of Eastern European descent. Although the cause of thromboangiitis obliterans is not known, there is a definite relationship to cigarette smoking in patients with this disorder.

In the initial stages of thromboangiitis obliterans, polymorphonuclear leukocytes infiltrate the walls of the small and medium-size arteries and veins. The internal elastic lamina is preserved, and a cellular, inflammatory thrombus develops in the vascular lumen. As the disease progresses, mononuclear cells, fibroblasts, and giant cells replace the neutrophils. Later stages are characterized by perivascular fibrosis, organized thrombus, and recanalization.

The clinical features of thromboangiitis obliterans often include a triad of claudication of the affected extremity, Raynaud’s phenomenon, and migratory superficial vein thrombophlebitis. Claudication usually is confined to the calves and feet or the forearms and hands because this disorder primarily affects distal vessels. In the presence of severe digital ischemia, trophic nail changes, painful ulcerations, and gangrene may develop at the tips of the fingers or toes. The physical examination shows normal brachial and popliteal pulses but reduced or absent radial, ulnar, and/or tibial pulses. Arteriography is helpful in making the diagnosis. Smooth, tapering segmental lesions in the distal vessels are characteristic, as are collateral vessels at sites of vascular occlusion. Proximal atherosclerotic disease is usually absent. The diagnosis can be confirmed by excisional biopsy and pathologic examination of an involved vessel.

There is no specific treatment except abstention from tobacco. The prognosis is worse in individuals who continue to smoke, but results are discouraging even in those who stop smoking. Arterial bypass of the larger vessels may be used in selected instances, as well as local debridement, depending on the symptoms and severity of ischemia. Antibiotics may be useful; anticoagulants and glucocorticoids are not helpful. If these measures fail, amputation may be required.

VASCULITIS

Other vasculitides may affect the arteries that supply the upper and lower extremities.

ACUTE ARTERIAL OCCLUSION

Acute arterial occlusion results in the sudden cessation of blood flow to an extremity. The severity of ischemia and the viability of the extremity depend on the location and extent of the occlusion and the presence and subsequent development of collateral blood vessels. There are two principal causes of acute arterial occlusion: embolism and thrombus in situ.

The most common sources of arterial emboli are the heart, aorta, and large arteries. Cardiac disorders that cause thromboembolism include atrial fibrillation, both chronic and paroxysmal; acute myocardial infarction; ventricular aneurysm; cardiomyopathy; infectious and marantic endocarditis; thrombi associated with prosthetic heart valves; and atrial myxoma. Emboli to the distal vessels may also originate from proximal sites of atherosclerosis and aneurysms of the aorta and large vessels. Less frequently, an arterial occlusion results paradoxically from a venous thrombus that has entered the systemic circulation via a patent foramen ovale or another septal defect. Arterial emboli tend to lodge at vessel bifurcations because the vessel caliber decreases at those sites; in the lower extremities, emboli lodge most frequently in the femoral artery, followed by the iliac artery, aorta, and popliteal and tibioperoneal arteries.

Acute arterial thrombosis in situ occurs most frequently in atherosclerotic vessels at the site of an atherosclerotic plaque or aneurysm and in arterial bypass grafts. Trauma to an artery may also result in the formation of an acute arterial thrombus. Arterial occlusion may complicate arterial punctures and placement of catheters; it also may result from arterial dissection if the intimal flap obstructs the artery. Less common causes include thoracic outlet compression syndrome, which causes subclavian artery occlusion, and entrapment of the popliteal artery by abnormal placement of the medial head of the gastrocnemius muscle. Polycythemia and hypercoagulable disorders are also associated with acute arterial thrombosis.

Clinical features

The symptoms of an acute arterial occlusion depend on the location, duration, and severity of the obstruction. Often, severe pain, paresthesia, numbness, and coldness develop in the involved extremity within 1 h. Paralysis may occur with severe and persistent ischemia. Physical findings include loss of pulses distal to the occlusion, cyanosis or pallor, mottling, decreased skin temperature, muscle stiffening, loss of sensation, weakness, and/or absent deep tendon reflexes. If acute arterial occlusion occurs in the presence of an adequate collateral circulation, as is often the case in acute graft occlusion, the symptoms and findings may be less impressive. In this situation, the patient complains about an abrupt decrease in the distance walked before claudication occurs or of modest pain and paresthesia. Pallor and coolness are evident, but sensory and motor functions generally are preserved. The diagnosis of acute arterial occlusion is usually apparent from the clinical presentation. In most circumstances, MRA, CTA, or catheter-based arteriography is used to confirm the diagnosis and demonstrate the location and extent of occlusion.


TREATMENT Acute Arterial Occlusion

Once the diagnosis is made, the patient should be anticoagulated with intravenous heparin to prevent propagation of the clot. In cases of severe ischemia of recent onset, particularly when limb viability is jeopardized, immediate intervention to ensure reperfusion is indicated. Endovascular or surgical thromboembolectomy or arterial bypass procedures are used to restore blood flow to the ischemic extremity promptly, particularly when a large proximal vessel is occluded.

Intraarterial thrombolytic therapy with recombinant tissue plasminogen activator, reteplase, or tenecteplase is often effective when acute arterial occlusion is caused by a thrombus in an atherosclerotic vessel or arterial bypass graft. Thrombolytic therapy may also be indicated when the patient’s overall condition contra-indicates surgical intervention or when smaller distal vessels are occluded, thus preventing surgical access. Meticulous observation for hemorrhagic complications is required during intraarterial thrombolytic therapy. Another endovascular approach to thrombus removal is percutaneous mechanical thrombectomy using devices that employ hydrodynamic forces or rotating baskets to fragment and remove the clot. These treatments may be used alone but usually are used in conjunction with pharmacologic thrombolysis. Amputation is performed when the limb is not viable, as characterized by loss of sensation, paralysis, and the absence of Doppler-detected blood flow in both arteries and veins.

If the limb is not in jeopardy, a more conservative approach that includes observation and administration of anticoagulants may be taken. Anticoagulation prevents recurrent embolism and reduces the likelihood of thrombus propagation; it can be initiated with intravenous heparin and followed by oral warfarin. Recommended doses are the same as those used for deep vein thrombosis. Emboli resulting from infective endocarditis, the presence of prosthetic heart valves, or atrial myxoma often require surgical intervention to remove the cause.


ATHEROEMBOLISM

Atheroembolism constitutes a subset of acute arterial occlusion. In this condition, multiple small deposits of fibrin, platelets, and cholesterol debris embolize from proximal atherosclerotic lesions or aneurysmal sites. Large protruding aortic atheromas are a source of emboli that may lead to stroke and renal insufficiency as well as limb ischemia. Atheroembolism may occur after intraarterial procedures. Since the emboli tend to lodge in the small vessels of the muscle and skin and may not occlude the large vessels, distal pulses usually remain palpable. Patients complain of acute pain and tenderness at the site of embolization. Digital vascular occlusion may result in ischemia and the “blue toe” syndrome; digital necrosis and gangrene may develop (Fig. 39-2). Localized areas of tenderness, pallor, and livedo reticularis (see later) occur at sites of emboli. Skin or muscle biopsy may demonstrate cholesterol crystals.

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FIGURE 39-2

Atheroembolism
 causing cyanotic discoloration and impending necrosis of the toes (“blue toe” syndrome).

Ischemia resulting from atheroemboli is notoriously difficult to treat. Usually, neither surgical revascularization procedures nor thrombolytic therapy is helpful because of the multiplicity, composition, and distal location of the emboli. Some evidence suggests that platelet inhibitors prevent atheroembolism. Surgical intervention to remove or bypass the atherosclerotic vessel or aneurysm that causes the recurrent atheroemboli may be necessary.

THORACIC OUTLET COMPRESSION SYNDROME

This is a symptom complex resulting from compression of the neurovascular bundle (artery, vein, or nerves) at the thoracic outlet as it courses through the neck and shoulder. Cervical ribs, abnormalities of the scalenus anticus muscle, proximity of the clavicle to the first rib, or abnormal insertion of the pectoralis minor muscle may compress the subclavian artery, subclavian vein, and brachial plexus as these structures pass from the thorax to the arm. Depending on the structures affected, thoracic outlet compression syndrome is divided into arterial, venous, and neurogenic forms. Patients with neurogenic thoracic outlet compression may develop shoulder and arm pain, weakness, and paresthesias. Patients with arterial compression may experience claudication, Raynaud’s phenomenon, and even ischemic tissue loss and gangrene. Venous compression may cause thrombosis of the subclavian and axillary veins; this is often associated with effort and is referred to as Paget-Schroetter syndrome.


APPROACH TO THE PATIENT Thoracic Outlet Compression Syndrome

Examination of a patient with thoracic outlet compression syndrome is often normal unless provocative maneuvers are performed. Occasionally, distal pulses are decreased or absent and digital cyanosis and ischemia may be evident. Tenderness may be present in the supraclavicular fossa. In patients with axillo-subclavian venous thrombosis, the affected extremity typically is swollen. Dilated collateral veins may be apparent around the shoulder and upper arm.

Several maneuvers that support the diagnosis of thoracic outlet compression syndrome may be used to precipitate symptoms, cause a subclavian artery bruit, and diminish arm pulses. These maneuvers include the abduction and external rotation test, in which the affected arm is abducted by 90° and the shoulder is externally rotated; the scalene maneuver (extension of the neck and rotation of the head to the side of the symptoms); the costoclavicular maneuver (posterior rotation of shoulders); and the hyperabduction maneuver (raising the arm 180°). A chest x-ray will indicate the presence of cervical ribs. Duplex ultrasonography, MRA, and contrast angiography can be performed during provocative maneuvers to demonstrate thoracic outlet compression of the subclavian artery. Duplex ultrasography, magnetic resonance venography, or contrast venography can be used to diagnose axillo-subclavian vein thrombosis. Neurophysiologic tests such as the electromyogram, nerve conduction studies, and somatosensory evoked potentials may be abnormal if the brachial plexus is involved, but the diagnosis of neurogenic thoracic outlet syndrome is not necessarily excluded if these tests are normal owing to their low sensitivity.

Most patients can be managed conservatively. They should be advised to avoid the positions that cause symptoms. Many patients benefit from shoulder girdle exercises. Surgical procedures such as removal of the first rib and resection of the scalenus anticus muscle are necessary occasionally for relief of symptoms or treatment of ischemia.


POPLITEAL ARTERY ENTRAPMENT

Popliteal artery entrapment typically affects young athletic men and women when the gastrocnemius or popliteus muscle compresses the popliteal artery and causes intermittent claudication. Thrombosis, embolism, or popliteal artery aneurysm may occur. The pulse examination may be normal unless provocative maneuvers such as ankle dorsiflexion and plantar flexion are performed. The diagnosis is confirmed by duplex ultrasound, CTA, MRA, or conventional angiography. Treatment involves surgical release of the popliteal artery or vascular reconstruction.

POPLITEAL ARTERY ANEURYSM

Popliteal artery aneurysms are the most common peripheral artery aneurysms. Approximately 50% are bilateral. Patients with popliteal artery aneurysms often have aneurysms of other arteries, especially the aorta. The most common clinical presentation is limb ischemia secondary to thrombosis or embolism. Rupture occurs less frequently. Other complications include compression of the adjacent popliteal vein or peroneal nerve. Popliteal artery aneurysm can be detected by palpation and confirmed by duplex ultrasonography. Repair is indicated for symptomatic aneurysms or when the diameter exceeds 2–3 cm, owing to the risk of thrombosis, embolism, or rupture.

ARTERIOVENOUS FISTULA

Abnormal communications between an artery and a vein, bypassing the capillary bed, may be congenital or acquired. Congenital arteriovenous fistulas are a result of persistent embryonic vessels that fail to differentiate into arteries and veins; they may be associated with birthmarks, can be located in almost any organ of the body, and frequently occur in the extremities. Acquired arteriovenous fistulas either are created to provide vascular access for hemodialysis or occur as a result of a penetrating injury such as a gunshot or knife wound or as complications of arterial catheterization or surgical dissection. An uncommon cause of arteriovenous fistula is rupture of an arterial aneurysm into a vein.

The clinical features depend on the location and size of the fistula. Frequently, a pulsatile mass is palpable, and a thrill and a bruit lasting throughout systole and diastole are present over the fistula. With long-standing fistulas, clinical manifestations of chronic venous insufficiency, including peripheral edema; large, tortuous varicose veins; and stasis pigmentation become apparent because of the high venous pressure. Evidence of ischemia may occur in the distal portion of the extremity. Skin temperature is higher over the arteriovenous fistula. Large arteriovenous fistulas may result in an increased cardiac output with consequent cardiomegaly and high-output heart failure (Chap. 17).

The diagnosis is often evident from the physical examination. Compression of a large arteriovenous fistula may cause reflex slowing of the heart rate (Nicoladoni-Branham sign). Duplex ultrasonography may detect an arteriovenous fistula, especially one that affects the femoral artery and vein at the site of catheter access. Computed tomographic and conventional angiography can confirm the diagnosis and are useful in demonstrating the site and size of the arteriovenous fistula.

Management of arteriovenous fistulas may involve surgery, radiotherapy, or embolization. Congenital arteriovenous fistulas are often difficult to treat because the communications may be numerous and extensive, and new communications frequently develop after ligation of the most obvious ones. Many of these lesions are best treated conservatively using elastic support hose to reduce the consequences of venous hypertension. Occasionally, embolization with autologous material, such as fat or muscle, or with hemostatic agents, such as gelatin sponges or silicon spheres, is used to obliterate the fistula. Acquired arteriovenous fistulas are usually amenable to surgical treatment that involves division or excision of the fistula. Occasionally, autogenous or synthetic grafting is necessary to reestablish continuity of the artery and vein.

RAYNAUD’S PHENOMENON

Raynaud’s phenomenon is characterized by episodic digital ischemia, manifested clinically by the sequential development of digital blanching, cyanosis, and rubor of the fingers or toes after cold exposure and subsequent rewarming. Emotional stress may also precipitate Raynaud’s phenomenon. The color changes are usually well demarcated and are confined to the fingers or toes. Typically, one or more digits will appear white when the patient is exposed to a cold environment or touches a cold object. The blanching, or pallor, represents the ischemic phase of the phenomenon and results from vasospasm of digital arteries. During the ischemic phase, capillaries and venules dilate, and cyanosis results from the deoxygenated blood that is present in these vessels. A sensation of cold or numbness or paresthesia of the digits often accompanies the phases of pallor and cyanosis.

With rewarming, the digital vasospasm resolves, and blood flow into the dilated arterioles and capillaries increases dramatically. This “reactive hyperemia” imparts a bright red color to the digits. In addition to rubor and warmth, patients often experience a throbbing, painful sensation during the hyperemic phase. Although the triphasic color response is typical of Raynaud’s phenomenon, some patients may develop only pallor and cyanosis; others may experience only cyanosis.

Raynaud’s phenomenon is broadly separated into two categories: the idiopathic variety, termed Raynaud’s disease, and the secondary variety, which is associated with other disease states or known causes of vasospasm (Table 39-1).

TABLE 39-1

CLASSIFICATION OF RAYNAUD’S PHENOMENON

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Raynaud’s disease

This appellation is applied when the secondary causes of Raynaud’s phenomenon have been excluded. Over 50% of patients with Raynaud’s phenomenon have Raynaud’s disease. Women are affected about five times more often than men, and the age of presentation is usually between 20 and 40 years. The fingers are involved more frequently than the toes. Initial episodes may involve only one or two fingertips, but subsequent attacks may involve the entire finger and may include all the fingers. The toes are affected in 40% of patients. Although vasospasm of the toes usually occurs in patients with symptoms in the fingers, it may happen alone. Rarely, the earlobes, the tip of the nose, and the penis are involved. Raynaud’s phenomenon occurs frequently in patients who also have migraine headaches or variant angina. These associations suggest that there may be a common predisposing cause for the vasospasm.

Results of physical examination are often entirely normal; the radial, ulnar, and pedal pulses are normal. The fingers and toes may be cool between attacks and may perspire excessively. Thickening and tightening of the digital subcutaneous tissue (sclerodactyly) develop in 10% of patients. Angiography of the digits for diagnostic purposes is not indicated.

In general, patients with Raynaud’s disease have milder forms of Raynaud’s phenomenon. Fewer than 1% of these patients lose a part of a digit. After the diagnosis is made, the disease improves spontaneously in approximately 15% of patients and progresses in about 30%.

Secondary causes of Raynaud’s phenomenon

Raynaud’s phenomenon occurs in 80–90% of patients with systemic sclerosis (scleroderma) and is the presenting symptom in 30%. It may be the only symptom of scleroderma for many years. Abnormalities of the digital vessels may contribute to the development of Raynaud’s phenomenon in this disorder. Ischemic fingertip ulcers may develop and progress to gangrene and autoamputation. About 20% of patients with systemic lupus erythematosus (SLE) have Raynaud’s phenomenon. Occasionally, persistent digital ischemia develops and may result in ulcers or gangrene. In most severe cases, the small vessels are occluded by a proliferative endarteritis. Raynaud’s phenomenon occurs in about 30% of patients with dermatomyositis or polymyositis. It frequently develops in patients with rheumatoid arthritis and may be related to the intimal proliferation that occurs in the digital arteries.

Atherosclerosis of the extremities is a common cause of Raynaud’s phenomenon in men >50 years. Thromboangiitis obliterans is an uncommon cause of Raynaud’s phenomenon but should be considered in young men, particularly those who are cigarette smokers. The development of cold-induced pallor in these disorders may be confined to one or two digits of the involved extremity. Occasionally, Raynaud’s phenomenon may follow acute occlusion of large and medium-size arteries by a thrombus or embolus. Embolization of atheroembolic debris may cause digital ischemia. The latter situation often involves one or two digits and should not be confused with Raynaud’s phenomenon. In patients with thoracic outlet compression syndrome, Raynaud’s phenomenon may result from diminished intravascular pressure, stimulation of sympathetic fibers in the brachial plexus, or a combination of both. Raynaud’s phenomenon occurs in patients with primary pulmonary hypertension (Chap. 40); this is more than coincidental and may reflect a neurohumoral abnormality that affects both the pulmonary and digital circulations.

A variety of blood dyscrasias may be associated with Raynaud’s phenomenon. Cold-induced precipitation of plasma proteins, hyperviscosity, and aggregation of red cells and platelets may occur in patients with cold agglutinins, cryoglobulinemia, or cryofibrinogenemia. Hyperviscosity syndromes that accompany myeloproliferative disorders and Waldenström macroglobulinemia should also be considered in the initial evaluation of patients with Raynaud’s phenomenon.

Raynaud’s phenomenon occurs often in patients whose vocations require the use of vibrating hand tools, such as chain saws or jackhammers. The frequency of Raynaud’s phenomenon also seems to be increased in pianists and keyboard operators. Electric shock injury to the hands or frostbite may lead to the later development of Raynaud’s phenomenon.

Several drugs have been causally implicated in Raynaud’s phenomenon. They include ergot preparations, methysergide, β-adrenergic receptor antagonists, and the chemotherapeutic agents bleomycin, vinblastine, and cisplatin.


TREATMENT Raynaud’s Phenomenon

Most patients with Raynaud’s phenomenon experience only mild and infrequent episodes. These patients need reassurance and should be instructed to dress warmly and avoid unnecessary cold exposure. In addition to gloves and mittens, patients should protect the trunk, head, and feet with warm clothing to prevent cold-induced reflex vasoconstriction. Tobacco use is contraindicated.

Drug treatment should be reserved for severe cases. Dihydropyridine calcium channel antagonists such as nifedipine, isradipine, felodipine, and amlodipine decrease the frequency and severity of Raynaud’s phenomenon. Diltiazem may be considered but is less effective. The postsynaptic α1-adrenergic antagonist prazosin has been used with favorable responses; doxazosin and terazosin may also be effective. Topical glyceryl trinitrate may be useful in some patients. Digital sympathectomy is helpful in some patients who are unresponsive to medical therapy.


ACROCYANOSIS

In this condition, there is arterial vasoconstriction and secondary dilation of the capillaries and venules with resulting persistent cyanosis of the hands and, less frequently, the feet. Cyanosis may be intensified by exposure to a cold environment. Acrocyanosis may be categorized as primary or secondary to an underlying condition. In primary acrocyanosis, women are affected much more frequently than men, and the age of onset is usually <30 years. Generally, patients are asymptomatic but seek medical attention because of the discoloration. The prognosis is favorable, and pain, ulcers, and gangrene do not occur. Examination reveals normal pulses, peripheral cyanosis, and moist palms. Trophic skin changes and ulcerations do not occur. The disorder can be distinguished from Raynaud’s phenomenon because it is persistent and not episodic, the discoloration extends proximally from the digits, and blanching does not occur. Ischemia secondary to arterial occlusive disease can usually be excluded by the presence of normal pulses. Central cyanosis and decreased arterial oxygen saturation are not present. Patients should be reassured and advised to dress warmly and avoid cold exposure. Pharmacologic intervention is not indicated.

Secondary acrocyanosis may result from hypoxemia, connective tissue diseases, atheroembolism, antiphospholipid antibodies, cold agglutinins, or cryoglobulins and is associated with anorexia nervosa and orthostatic tachycardia syndrome. Treatment should be directed at the underlying disorder.

LIVEDO RETICULARIS

In this condition, localized areas of the extremities develop a mottled or rete (netlike) appearance of reddish to blue discoloration. The mottled appearance may be more prominent after cold exposure. There are primary and secondary forms of livedo reticularis. The primary, or idiopathic, form of this disorder may be benign or associated with ulcerations. The benign form occurs more frequently in women than in men, and the most common age of onset is the third decade. Patients with the benign form are usually asymptomatic and seek attention for cosmetic reasons. These patients should be reassured and advised to avoid cold environments. No drug treatment is indicated. Primary livedo reticularis with ulceration is also called atrophie blanche en plaque. The ulcers are painful and may take months to heal. Secondary livedo reticularis can occur with atheroembolism (see earlier), SLE and other vasculitides, anticardiolipin antibodies, hyper-viscosity, cryoglobulinemia, and Sneddon’s syndrome (ischemic stroke and livedo reticularis). Rarely, skin ulcerations develop.

PERNIO (CHILBLAINS)

Pernio is a vasculitic disorder associated with exposure to cold; acute forms have been described. Raised erythematous lesions develop on the lower part of the legs and feet in cold weather. They are associated with pruritus and a burning sensation, and they may blister and ulcerate. Pathologic examination demonstrates angiitis characterized by intimal proliferation and perivascular infiltration of mononuclear and polymorphonuclear leukocytes. Giant cells may be present in the subcutaneous tissue. Patients should avoid exposure to cold, and ulcers should be kept clean and protected with sterile dressings. Sympatholytic drugs and dihydropyridine calcium channel antagonists may be effective in some patients.

ERYTHROMELALGIA

This disorder is characterized by burning pain and erythema of the extremities. The feet are involved more frequently than the hands, and males are affected more frequently than females. Erythromelalgia may occur at any age but is most common in middle age. It may be primary (also termed erythermalgia) or secondary. The most common causes of secondary erythromelalgia are myeloproliferative disorders such as polycythemia vera and essential thrombocytosis. Less common causes include drugs, such as calcium channel blockers, bromocriptine, and pergolide; neuropathies; connective tissue diseases such as SLE; and paraneoplastic syndromes. Patients complain of burning in the extremities that is precipitated by exposure to a warm environment and aggravated by a dependent position. The symptoms are relieved by exposing the affected area to cool air or water or by elevation. Erythromelalgia can be distinguished from ischemia secondary to peripheral arterial disorders and peripheral neuropathy because the peripheral pulses are present and the neurologic examination is normal. There is no specific treatment; aspirin may produce relief in patients with erythromelalgia secondary to myeloproliferative disease. Treatment of associated disorders in secondary erythromelalgia may be helpful.

FROSTBITE

In this condition, tissue damage results from severe environmental cold exposure or from direct contact with a very cold object. Tissue injury results from both freezing and vasoconstriction. Frostbite usually affects the distal aspects of the extremities or exposed parts of the face, such as the ears, nose, chin, and cheeks. Superficial frostbite involves the skin and subcutaneous tissue. Patients experience pain or paresthesia, and the skin appears white and waxy. After rewarming, there is cyanosis and erythema, wheal-and-flare formation, edema, and superficial blisters. Deep frostbite involves muscle, nerves, and deeper blood vessels. It may result in edema of the hand or foot, vesicles and bullae, tissue necrosis, and gangrene.

Initial treatment is rewarming, performed in an environment where reexposure to freezing conditions will not occur. Rewarming is accomplished by immersion of the affected part in a water bath at temperatures of 40°–44°C (104°–111°F). Massage, application of ice water, and extreme heat are contraindicated. The injured area should be cleansed with soap or antiseptic, and sterile dressings should be applied. Analgesics are often required during rewarming. Antibiotics are used if there is evidence of infection. The efficacy of sympathetic blocking drugs is not established. After recovery, the affected extremity may exhibit increased sensitivity to cold.

DISORDERS OF THE VEINS AND LYMPHATICS

VENOUS DISORDERS

Veins in the extremities can be broadly classified as either superficial or deep. In the lower extremity, the superficial venous system includes the greater and lesser saphenous veins and their tributaries. The deep veins of the leg accompany the major arteries. Perforating veins connect the superficial and deep systems at multiple locations. Bicuspid valves are present throughout the venous system to direct the flow of venous blood centrally.

Venous thrombosis

The presence of thrombus within a superficial or deep vein, along with the accompanying inflammatory response in the vessel wall, is termed venous thrombosis or thrombophlebitis. Initially the thrombus is composed principally of platelets and fibrin. Red cells become interspersed with fibrin, and the thrombus tends to propagate in the direction of blood flow. The inflammatory response in the vessel wall may be minimal or characterized by granulocyte infiltration, loss of endothelium, and edema.

The factors that predispose to venous thrombosis were initially described by Virchow in 1856 and include stasis, vascular damage, and hypercoagulability. Accordingly, a variety of clinical situations are associated with increased risk of venous thrombosis (Table 39-2). Venous thrombosis may occur in >50% of patients having orthopedic surgical procedures, particularly those involving the hip or knee, and in 10–40% of patients who undergo abdominal or thoracic operations. The prevalence of venous thrombosis is particularly high in patients with cancer of the pancreas, lungs, genitourinary tract, stomach, and breast. Approximately 10–20% of patients with idiopathic deep vein thrombosis have or develop clinically overt cancer; there is no consensus on whether these individuals should be subjected to intensive diagnostic workup to search for occult malignancy.

TABLE 39-2

CONDITIONS ASSOCIATED WITH AN INCREASED RISK FOR DEVELOPMENT OF VENOUS THROMBOSIS

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The risk of thrombosis is increased after trauma such as fractures of the spine, pelvis, femur, and tibia. Immobilization, regardless of the underlying disease, is a major predisposing cause of venous thrombosis. This may account for the relatively high incidence in patients with acute myocardial infarction or congestive heart failure. The incidence of venous thrombosis is increased during pregnancy, particularly in the third trimester, and in the first month postpartum, as well as in individuals who use oral contraceptives, postmenopausal hormone replacement therapy, or selective estrogen receptor modulators. A variety of inherited and acquired disorders that produce systemic hypercoagulability, including resistance to activated protein C (factor V Leiden); prothrombin G20210A gene mutation; antithrombin III, protein C, and protein S deficiencies; antiphospholipid syndrome; hyperhomocysteinemia; SLE; myeloproliferative diseases; dysfibrinogenemia; heparin-induced thrombocytopenia; and disseminated intravascular coagulation, are associated with venous thrombosis. Venulitis occurring in thromboangiitis obliterans, Behçet’s syndrome, and homocystinuria may also cause venous thrombosis.

Superficial vein thrombosis

Thrombosis of the greater or lesser saphenous veins or their tributaries (i.e., superficial vein thrombosis) does not result in pulmonary embolism. It is associated with intravenous catheters and infusions, occurs in varicose veins, and may develop in association with deep venous thrombosis (DVT). Migrating superficial vein thrombosis is often a marker for a carcinoma and may also occur in patients with vasculitides, such as thromboangiitis obliterans. The clinical features of superficial vein thrombosis are easily distinguished from those of DVT. Patients complain of pain localized to the site of the thrombus. Examination reveals a reddened, warm, and tender cord extending along a superficial vein. The surrounding area may be red and edematous.


TREATMENT Superficial Vein Thrombosis

Treatment is primarily supportive. Initially, patients can be placed at bed rest with leg elevation and application of warm compresses. Nonsteroidal anti-inflammatory drugs may provide analgesia but may also obscure clinical evidence of thrombus propagation. If a thrombosis of the greater saphenous vein develops in the thigh and extends toward the saphenofemoral vein junction, it is reasonable to consider anticoagulant therapy to prevent extension of the thrombus into the deep system and a possible pulmonary embolism.


Varicose veins

Varicose veins are dilated, tortuous superficial veins that result from defective structure and function of the valves of the saphenous veins, intrinsic weakness of the vein wall, high intraluminal pressure, or, rarely, arteriovenous fistulas. Varicose veins can be categorized as primary or secondary. Primary varicose veins originate in the superficial system and occur two to three times as frequently in women as in men. Approximately one-half of these patients have a family history of varicose veins. Secondary varicose veins result from deep venous insufficiency and incompetent perforating veins or from deep venous occlusion that causes enlargement of superficial veins that are serving as collaterals.

Patients with venous varicosities are often concerned about the cosmetic appearance of their legs. Symptoms consist of a dull ache or pressure sensation in the legs after prolonged standing; this is relieved with leg elevation. The legs feel heavy, and mild ankle edema develops occasionally. Extensive venous varicosities may cause skin ulcerations near the ankle. Superficial venous thrombosis may be a recurring problem, and, rarely, a varicosity ruptures and bleeds. Visual inspection of the legs in the dependent position usually confirms the presence of varicose veins.

Varicose veins usually can be treated with conservative measures. Symptoms often decrease when the legs are elevated periodically, prolonged standing is avoided, and elastic support hose are worn. External compression stockings provide a counterbalance to the hydrostatic pressure in the veins. Ablative procedures, including sclerotherapy, endovenous radio frequency or laser ablation, and surgery, may be considered to treat varicose veins in selected patients who have persistent symptoms, have recurrent superficial vein thrombosis, and/or develop skin ulceration. Ablative therapy may also be indicated for cosmetic reasons. Small, symptomatic varicose veins can be treated with sclerotherapy, in which a sclerosing solution is injected into the involved varicose vein and a compression bandage is applied. Percutaneous, endovenous delivery of radio frequency or laser energy can be used to treat incompetent great saphenous veins. Surgical therapy usually involves ligation and stripping of the great and small saphenous veins.

Chronic venous insufficiency

Chronic venous insufficiency may result from DVT and/or valvular incompetence. After DVT, the delicate valve leaflets become thickened and contracted so that they cannot prevent retrograde flow of blood; the vein becomes rigid and thick walled. Although most veins recanalize after an episode of thrombosis, the large proximal veins may remain occluded. Secondary incompetence develops in distal valves because high pressures distend the vein and separate the leaflets. Primary deep venous valvular dysfunction may also occur without previous thrombosis. Patients with venous insufficiency often complain of a dull ache in the leg that worsens with prolonged standing and resolves with leg elevation. Examination demonstrates increased leg circumference, edema, and superficial varicose veins. Erythema, dermatitis, and hyperpigmentation develop along the distal aspect of the leg, and skin ulceration may occur near the medial and lateral malleoli (Fig. 39-3). Cellulitis may be a recurring problem. The CEAP (clinical, etiologic, anatomic, pathophysiologic) classification schema incorporates the range of symptoms and signs of chronic venous insufficiency to characterize its severity (Table 39-3).

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FIGURE 39-3

Venous insufficiency with active venous ulcer
 near the medial malleolus. (Courtesy of Dr. Steven Dean, with permission.)

TABLE 39-3

CEAP (CLINICAL, ETIOLOGIC, ANATOMIC, PATHOPHYSIOLOGIC) CLASSIFICATION

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Patients should be advised to avoid prolonged standing or sitting; frequent leg elevation is helpful. Graduated compression stockings should be worn during the day.

These efforts should be intensified if skin ulcers develop. Ulcers should be treated with applications of wet to dry dressings or occlusive hydrocolloid dressings. Commercially available compressive dressings that consist of paste with zinc oxide, calamine, glycerin, and gelatin may be applied and should be changed weekly until healing occurs. Recurrent ulceration and severe edema may be treated by surgical interruption of incompetent communicating veins. Subfascial endoscopic perforator surgery (SEPS) is a minimally invasive technique to interrupt incompetent communicating veins. Rarely, surgical valvuloplasty and bypass of venous occlusions are employed.

LYMPHATIC DISORDERS

Lymphatic capillaries are blind-ended tubes formed by a single layer of endothelial cells. The absent or widely fenestrated basement membrane of lymphatic capillaries allows access to interstitial proteins and particles. Lymphatic capillaries merge to form larger vessels that contain smooth muscle and are capable of vasomotion. Small- and medium-size lymphatic vessels empty into progressively larger channels, most of which drain into the thoracic duct. The lymphatic circulation is involved in the absorption of interstitial fluid and in the response to infection.

Lymphedema

Lymphedema may be categorized as primary or secondary (Table 39-4). The prevalence of primary lymph-edema is approximately 1 per 10,000 individuals. Primary lymphedema may be secondary to agenesis, hypoplasia, or obstruction of the lymphatic vessels. It may be associated with Turner’s syndrome, Klinefelter’s syndrome, Noonan’s syndrome, yellow nail syndrome, intestinal lymphangiectasia syndrome, and lymphangiomyomatosis. Women are affected more frequently than are men. There are three clinical subtypes: congenital lymphedema, which appears shortly after birth; lymphedema praecox, which has its onset at the time of puberty; and lymph-edema tarda, which usually begins after age 35. Familial forms of congenital lymphedema (Milroy’s disease) and lymphedema praecox (Meige’s disease) may be inherited in an autosomal dominant manner with variable penetrance; autosomal or sex-linked recessive forms are less common.

TABLE 39-4

CAUSES OF LYMPHEDEMA

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Secondary lymphedema is an acquired condition that results from damage to or obstruction of previously normal lymphatic channels (Table 39-4). Recurrent episodes of bacterial lymphangitis, usually caused by streptococci, are a very common cause of lymphedema. The most common cause of secondary lymphedema worldwide is filariasis. Tumors, such as prostate cancer and lymphoma, can also obstruct lymphatic vessels. Both surgery and radiation therapy for breast carcinoma may cause lymphedema of the upper extremity. Less common causes include tuberculosis, contact dermatitis, lymphogranuloma venereum, rheumatoid arthritis, pregnancy, and self-induced or factitious lymphedema after application of tourniquets.

Lymphedema is generally a painless condition, but patients may experience a chronic dull, heavy sensation in the leg, and most often they are concerned about the appearance of the leg. Lymphedema of the lower extremity, initially involving the foot, gradually progresses up the leg so that the entire limb becomes edematous. In the early stages, the edema is soft and pits easily with pressure. In the chronic stages, the limb has a woody texture, and the tissues become indurated and fibrotic. At this point the edema may no longer be pitting. The limb loses its normal contour, and the toes appear square. Lymphedema should be distinguished from other disorders that cause unilateral leg swelling, such as DVT and chronic venous insufficiency. In the latter condition, the edema is softer, and there is often evidence of a stasis dermatitis, hyperpigmentation, and superficial venous varicosities. Other causes of leg swelling that resemble lymphedema are pretibial myxedema and lipedema. Pretibial myxedema occurs in patients with hyperthyroidism, especially Graves’ disease, and is caused by deposition of hyaluronic acid-rich protein in the dermis. Lipedema usually occurs in women and is caused by accumulation of adipose tissue in the leg from the thigh to the ankle with sparing of the feet. The evaluation of patients with lymphedema should include diagnostic studies to clarify the cause. Abdominal and pelvic ultrasound and CT can be used to detect obstructing lesions such as neoplasms. MRI may reveal edema in the epifascial compartment and identify lymph nodes and enlarged lymphatic channels. Lymphoscintigraphy and lymphangiography are rarely indicated, but either can be used to confirm the diagnosis or differentiate primary from secondary lymphedema. Lymphoscintigraphy involves the injection of radioactively labeled technetium-containing colloid into the distal subcutaneous tissue of the affected extremity. In lymphangiography, contrast material is injected into a distal lymphatic vessel that has been isolated and cannulated. In primary lymphedema, lymphatic channels are absent, hypoplastic, or ectatic. In secondary lymphedema, lymphatic channels are usually dilated, and it may be possible to determine the level of obstruction.


TREATMENT Lymphedema

Patients with lymphedema of the lower extremities must be instructed to take meticulous care of their feet to prevent recurrent lymphangitis. Skin hygiene is important, and emollients can be used to prevent drying. Prophylactic antibiotics are often helpful, and fungal infection should be treated aggressively. Patients should be encouraged to participate in physical activity; frequent leg elevation can reduce the amount of edema. Physical therapy, including massage to facilitate lymphatic drainage, may be helpful. Patients can be fitted with graduated compression hose to reduce the amount of lymphedema that develops with upright posture. Occasionally, intermittent pneumatic compression devices can be applied at home to facilitate reduction of the edema. Diuretics are contraindicated and may cause depletion of intravascular volume and metabolic abnormalities. Microsurgical lymphaticovenous anastomotic procedures have been performed to rechannel lymph flow from obstructed lymphatic vessels into the venous system.