Vascular Diseases of the Extremities
Peripheral Arterial Disease
Atherosclerosis (arteriosclerosis obliterans) is the leading cause of occlusive arterial disease of the extremities in patients over 40 years old; the highest incidence occurs in the sixth and seventh decades of life. As in patients with atherosclerosis of the coronary and cerebral vasculature, there is an increased prevalence of peripheral atherosclerotic disease in individuals with diabetes mellitus, hypercholesterolemia, hypertension, or hyperhomocysteinemia and in cigarette smokers.
Segmental lesions causing stenosis or occlusion are usually localized in large and medium-sized 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 to 90% of patients), and the more distal vessels, including the tibial and peroneal arteries (40 to 50% of patients). Atherosclerotic lesions occur preferentially at arterial branch points, 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.
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 (Leriche syndrome), 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, critical limb ischemia may develop. Patients will 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 peripheral arterial disease 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 frequent physical signs. In addition, 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 neuritis can result in numbness and hyporeflexia.
The history and physical examination are usually sufficient to establish the diagnosis of peripheral arterial disease. An objective assessment of the severity of disease is obtained by noninvasive techniques. These include digital pulse volume recordings, Doppler flow velocity waveform analysis, duplex ultrasonography (which combines B-mode imaging and pulse-wave Doppler examination), segmental pressure measurements, transcutaneous oximetry, stress testing (usually using a treadmill), and tests of reactive hyperemia. In the presence of significant peripheral arterial disease, the volume displacement in the leg is decreased with each pulse, and the Doppler velocity contour becomes progressively flatter. Duplex ultrasonography is often useful in detecting stenotic lesions in native arteries and bypass grafts.
Arterial pressure can be recorded noninvasively along the legs by serial placement of sphygmomanometric cuffs and use of a Doppler device to auscultate or record blood flow. 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 reflection. In the presence of hemodynamically significant stenoses, the systolic blood pressure in the leg is decreased. Thus, if one were to obtain a ratio of the ankle and brachial artery pressures, it would be 1.0 in normal individuals and <1.0 in patients with peripheral arterial disease. A ratio of <0.5 is consistent with severe ischemia.
Treadmill testing allows the physician to assess functional limitations objectively. Decline of the ankle-brachial systolic pressure ratio immediately after exercise may provide further support for the diagnosis of peripheral arterial disease in patients with equivocal symptoms and findings on examination. Exercise testing also allows simultaneous evaluation for the presence of coronary artery disease.
Contrast angiography should not be used for routine diagnostic testing but is performed prior to potential revascularization. It is useful in defining the anatomy to assist operative planning and is also indicated if nonsurgical interventions are being considered, such as percutaneous transluminal angioplasty (PTA) or thrombolysis. Recent studies have suggested that magnetic resonance angiography has diagnostic accuracy comparable to that of contrast angiography.
The natural history of patients with peripheral arterial disease is influenced primarily by the extent of coexisting coronary artery and cerebral vascular disease. Studies using coronary angiography have estimated that approximately one-half of patients with symptomatic peripheral arterial disease also have significant coronary artery disease. Life-table analysis has indicated that patients with claudication have a 70% 5-year and a 50% 10-year survival rate. Most deaths are either sudden or secondary to myocardial infarction. The likelihood of symptomatic progression of peripheral arterial disease appears less than the chance of succumbing to coronary artery disease. Approximately 75% of nondiabetic patients who present with mild to moderate claudication remain symptomatically stable or improve. Deterioration is likely to occur in the remainder, with approximately 5% of the group ultimately undergoing amputation. The prognosis is worse in patients who continue to smoke cigarettes or who have diabetes mellitus.
Therapeutic options include supportive measures, pharmacologic treatment, 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. Sandals and shoes made of synthetic materials that do not "breathe" should be avoided. Elastic support hose should be avoided, as they reduce blood flow to the skin. In patients with ischemia at rest, 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.
Treatment of associated factors that contribute to the development of atherosclerosis should be initiated. The importance of discontinuing cigarette smoking cannot be overemphasized. The physician must assume a major role in this life-style modification. It is important to control blood pressure in hypertensive patients but to avoid hypotensive levels. Treatment of hypercholesterolemia is advocated, although reduction in cholesterol levels has not been shown unequivocally to reverse peripheral atherosclerotic lesions. However, it has been shown to prevent or to slow progression of the disease and to improve survival in patients with coronary atherosclerosis. Patients with claudication should also be encouraged to exercise regularly and at progressively more strenuous levels. Supervised exercise training programs may improve muscle efficiency and prolong walking distance. Patients also should be advised to walk for 30 to 45 min daily, stopping at the onset of claudication and resting until the symptoms resolve before resuming ambulation.
This form of treatment of patients with peripheral arterial disease has not been as successful as the medical treatment of coronary artery disease (Chap. 244). 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 less than that generated in the interstitial tissue by the exercising muscle. Drugs such as -adrenergic blocking agents, calcium channel antagonists, papaverine, and other vasodilators have not been shown to be effective in patients with peripheral arterial disease. Pentoxifylline, a substituted xanthine derivative, has been reported to decrease blood viscosity and to increase red cell flexibility, thereby increasing blood flow to the microcirculation and enhancing tissue oxygenation. Several placebo-controlled studies have reported that pentoxifylline increased the duration of exercise in patients with claudication, but its efficacy has not been confirmed in all clinical trials. Cilostazol, a phosphodiesterase inhibitor with vasodilator and antiplatelet properties, has been reported to increase claudication distance and recently received an indication for treatment of peripheral arterial disease by the U.S. Food and Drug Administration. Other drugs are being studied that potentially may improve claudication, such as L-arginine, which is the precursor of the endothelium-dependent vasodilator, nitric oxide, and vasodilator prostaglandins. Several studies have suggested that long-term parenteral administration of vasodilator prostaglandins decreases pain and facilitates healing of ulcers in patients with severe limb ischemia. Clinical trials with angiogenic growth factors such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are proceeding. A preliminary report suggested that intramuscular gene transfer of DNA encoding VEGF may promote collateral blood vessel growth in patients with critical limb ischemia.
Platelet inhibitors, particularly aspirin, reduce the risk of adverse cardiovascular events in patients with peripheral atherosclerosis. Clopidogril, a drug that inhibits platelet aggregation via its effect on ADP-dependent platelet-fibrinogen binding, appears to be more effective than aspirin in reducing cardiovascular morbidity and mortality in patients with peripheral arterial disease. The anticoagulants heparin and warfarin have not been shown to be effective in patients with chronic peripheral arterial disease but may be useful in acute arterial obstruction secondary to thrombosis or systemic embolism. Similarly, thrombolytic intervention using drugs such as streptokinase, urokinase, or recombinant tissue plasminogen activator (tPA) may have a role in the treatment of acute thrombotic arterial occlusion but is not effective in patients with chronic arterial occlusion secondary to atherosclerosis.
Revascularization procedures, including nonoperative as well as operative interventions, are usually reserved for patients with progressive, severe, or disabling symptoms and ischemia at rest, as well as for individuals who must be symptom-free because of their occupation. Angiography should be performed mainly in patients who are being considered for a revascularization procedure. Nonoperative interventions include PTA, stent placement, and atherectomy (Chap. 245). PTA of the iliac artery is associated with a higher success rate than PTA of the femoral and popliteal arteries. Approximately 90 to 95% of iliac PTAs are initially successful, and the 3-year patency rate is in excess of 75%. Patency rates may be higher if a stent is placed in the iliac artery. The initial success rate for femoral-popliteal PTA is approximately 80%, with a 60% 3-year patency rate. Patency rates are influenced by the severity of pretreatment stenoses; the prognosis of total occlusive lesions is worse than that of nonocclusive stenotic lesions.
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 general medical condition of the patient. Operative procedures for aortoiliac disease include aortobifemoral bypass, axillofemoral bypass, femoral-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 in excess of 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. Operative mortality ranges from 1 to 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. Operative mortality ranges from 1 to 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 at 1 year approach 90% and at 5 years, 70 to 80%. Five-year patency rates of infrapopliteal saphenous vein bypass grafts are 60 to 70%. In contrast, 5-year patency rates of infrapopliteal PTFE grafts are less than 30%. Lumbar sympathectomy alone or as an adjunct to aortofemoral reconstruction has fallen into disfavor.
Preoperative cardiac risk assessment may identify individuals 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. Noninvasive tests, such as treadmill testing (if feasible), dipyridamole thallium or sestamibi scintigraphy, dobutamine echocardiography, and ambulatory ischemia monitoring permit further stratification of patient risk (Chap. 245). Patients with abnormal test results require close supervision and adjunctive management with antianginal medications. It is not known whether coronary angiography and coronary arterial revascularization reduce overall perioperative mortality in high-risk patients undergoing peripheral vascular surgery, but cardiac catheterization should be considered in patients suspected of having left main or three-vessel coronary artery disease.
This is a hyperplastic disorder affecting medium-sized and small arteries. It occurs predominantly in females and usually involves renal and carotid arteries but can affect extremity vessels such as the iliac and subclavian arteries. The histologic classification includes intimal, medial, and periadventitial dysplasia. Medial dysplasia is the most common type and is characterized by hyperplasia of the media with or without fibrosis of the elastic membrane. 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 (Buerger's disease) is an inflammatory occlusive vascular disorder involving small and medium-sized arteries and veins in the distal upper and lower extremities. Cerebral, visceral, and coronary vessels may also be affected. This disorder develops most frequently in men under age 40. The prevalence is higher in Asians and individuals of eastern European descent. While 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-sized arteries and veins. The internal elastic lamina is preserved, and thrombus may develop in the vascular lumen. As the disease progresses, mononuclear cells, fibroblasts, and giant cells replace the neutrophils. Later stages are characterized by perivascular fibrosis and recanalization.
The clinical features of thromboangiitis obliterans often include a triad of claudication of the affected extremity, Raynaud's phenomenon (p. 1438), and migratory superficial vein thrombophlebitis. Claudication is usually 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. 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 do 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.
Other vasculitides may affect the arteries supplying the upper and lower extremities. Takayasu's arteritis and giant cell (temporal) arteritis are discussed in Chap. 317.
Acute Arterial Occlusion
This 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; 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 other septal defect. Arterial emboli tend to lodge at vessel bifurcations because the vessel caliber decreases at these 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 a stenosis 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. Less frequent causes include the 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 (Chaps. 110 and 118) are also associated with acute arterial thrombosis.
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 are generally preserved. The diagnosis of acute arterial occlusion is usually apparent from the clinical presentation. Arteriography is useful for confirming the diagnosis and demonstrating the location and extent of 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, and particularly when limb viability is jeopardized, immediate intervention to ensure reperfusion is indicated. 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 is 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 contraindicates surgical intervention or when smaller distal vessels are occluded, thus preventing surgical access. One approach for administering intraarterial urokinase is to give 240,000 IU/h for 4 h, followed by 120,000 IU/h for a maximum of 48 h. Intraarterial recombinant tPA may be administered at infusion rates of 1 mg/h or 0.05 mg/kg per hour. Meticulous observation for hemorrhagic complications is required during intraarterial thrombolytic therapy.
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 dosages are the same as those used for deep vein thrombosis (see below). Emboli resulting from infectious endocarditis, the presence of prosthetic heart valves, or atrial myxoma often require surgical intervention to remove the cause.
Atheroembolism constitutes a subset of acute arterial occlusion. In this condition, multiple small deposits of fibrin, platelet, and cholesterol debris embolize from proximal atherosclerotic lesions or aneurysmal sites. 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. Localized areas of tenderness, pallor, and livedo reticularis (see below) occur at sites of emboli. Skin or muscle biopsy may demonstrate cholesterol crystals.
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 and brachial plexus as these structures pass from the thorax to the arm. Patients may develop shoulder and arm pain, weakness, paresthesia, claudication, Raynaud's phenomenon, and even ischemic tissue loss and gangrene. Examination 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. Abducting the affected arm by 90° and externally rotating the shoulder may precipitate symptoms. Several additional maneuvers are used to confirm the diagnosis of vascular compression and to suggest the location of the abnormality. These include 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°), which may cause subclavian bruits and loss of pulses in the arm. A chest x-ray will indicate the presence of cervical ribs. The electromyogram will be abnormal if the brachial plexus is involved.
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 or resection of the scalenus anticus muscle are necessary occasionally for relief of symptoms or treatment of ischemia.
Abnormal communications between an artery and a vein, bypassing the capillary bed, may be congenital or acquired. Congenital arteriovenous fistulas are the 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 are either 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 infrequent 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 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. 232).
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). Arteriography can confirm the diagnosis and is 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 ones 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 is characterized by episodic digital ischemia, manifested clinically by the sequential development of digital blanching, cyanosis, and rubor of the fingers or toes following 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 originally proposed that cold-induced episodic digital ischemia was secondary to exaggerated reflex sympathetic vasoconstriction. This theory is supported by the fact that -adrenergic blocking drugs as well as sympathectomy decrease the frequency and severity of Raynaud's phenomenon in some patients. An alternative hypothesis is that the digital vascular responsiveness to cold or to normal sympathetic stimuli is enhanced. It is also possible that normal reflex sympathetic vasoconstriction is superimposed on local digital vascular disease or that there is enhanced adrenergic neuroeffector activity.
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 248-1).
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 and the tip of the nose 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 often are 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 appear to have the 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 to 90% of patients with systemic sclerosis (scleroderma) and is the presenting symptom in 30% (Chap. 313). 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 (Chap. 311). 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 (Chap. 382). 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 frequent cause of Raynaud's phenomenon in men over age 50. Thromboangiitis obliterans is an uncommon cause of Raynaud's phenomenon but should be considered in young men, particularly in 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-sized 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 the thoracic outlet 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. 260); 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's 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 typists. 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. These include ergot preparations, methysergide, -adrenergic receptor antagonists, and the chemotherapeutic agents bleomycin, vinblastine, and cisplatin.
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 the severe cases. The calcium channel antagonists, especially nifedipine and diltiazem, decrease the frequency and severity of Raynaud's phenomenon. Adrenergic blocking agents, such as reserpine, have been shown to increase nutritional blood flow to the fingers. Some, but not all, patients achieve satisfactory results with long-term reserpine therapy. Moreover, systemic use of this drug is limited by side effects of hypotension, nasal stuffiness, lethargy, and depression. The postsynaptic 1-adrenergic antagonist prazosin has been used with favorable responses. Doxazosin and terazosin may also be effective. Other sympatholytic agents, such as methyldopa, guanethidine, and phenoxybenzamine, may be useful in some patients. Surgical sympathectomy is helpful in some patients who are unresponsive to medical therapy, but benefit is often transient.
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. Women are affected much more frequently than men, and the age of onset is usually less than 30 years. Generally, patients are asymptomatic but seek medical attention because of the discoloration. 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.
In this condition, localized areas of the extremities develop a mottled or netlike appearance of reddish to blue discoloration. The mottled appearance may be more prominent following cold exposure. The idiopathic form of this disorder occurs equally in men and women, and the most common age of onset is in the third decade. Patients with the idiopathic form are usually asymptomatic and seek attention for cosmetic reasons. Livedo reticularis can also occur following atheroembolism (see above). Rarely, skin ulcerations develop. Patients should be reassured and advised to avoid cold environments. No drug treatment is indicated.
This 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. These 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 may be effective in some patients.
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 or secondary to myeloproliferative disorders such as polycythemia vera and essential thrombocytosis, or it may occur as an adverse effect of drugs such as nifedipine or bromocriptine. 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.
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 to 44°C (104 to 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 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. Following recovery, the affected extremity may exhibit increased sensitivity to cold.
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.
The presence of thrombus within a superficial or deep vein and 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 248-2). Venous thrombosis may occur in more than 50% of patients having orthopedic surgical procedures, particularly those involving the hip or knee, and in 10 to 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 to 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. Risk of thrombosis is increased following 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 fact 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, and in individuals who use oral contraceptives or receive postmenopausal hormone replacement therapy. A variety of clinical disorders that produce systemic hypercoagulability, including resistance to activated protein C (factor V Leiden); antithrombin III, protein C, and protein S deficiencies; antiphospholipid syndrome; SLE; myeloproliferative diseases; dysfibrinogenemia; and disseminated intravascular coagulation, are associated with venous thrombosis. Venulitis occurring in thromboangiitis obliterans, Behçet's disease, and homocysteinuria may also cause venous thrombosis.
Deep Venous Thrombosis
The most important consequences of this disorder are pulmonary embolism (Chap. 261) and the syndrome of chronic venous insufficiency. Deep venous thrombosis of the iliac, femoral, or popliteal veins is suggested by unilateral leg swelling, warmth, and erythema. Tenderness may be present along the course of the involved veins, and a cord may be palpable. There may be increased tissue turgor, distention of superficial veins, and the appearance of prominent venous collaterals. In some patients, deoxygenated hemoglobin in stagnant veins imparts a cyanotic hue to the limb, a condition called phlegmasia cerulea dolens. In markedly edematous legs, the interstitial tissue pressure may exceed the capillary perfusion pressure, causing pallor, a condition designated phlegmasia alba dolens.
The diagnosis of deep venous thrombosis of the calf is often difficult to make at the bedside. This is so because only one of multiple veins may be involved, allowing adequate venous return through the remaining patent vessels. The most common complaint is calf pain. Examination may reveal posterior calf tenderness, warmth, increased tissue turgor or modest swelling, and, rarely, a cord. Increased resistance or pain during dorsiflexion of the foot (Homans' sign) is an unreliable diagnostic sign.
Deep venous thrombosis occurs less frequently in the upper extremity than in the lower extremity, but the incidence is increasing because of greater utilization of indwelling central venous catheters. The clinical features and complications are similar to those described for the leg.
The noninvasive test used most often to diagnose deep venous thrombosis is duplex venous ultrasonography (B-mode, i.e., two-dimensional, imaging, and pulse-wave Doppler interrogation). By imaging the deep veins, thrombus can be detected either by direct visualization or by inference when the vein does not collapse on compressive maneuvers. The Doppler ultrasound measures the velocity of blood flow in veins. This velocity is normally affected by respiration and by manual compression of the foot or calf. Flow abnormalities occur when deep venous obstruction is present. The positive predictive value of duplex venous ultrasonography approaches 95% for proximal deep vein thrombosis. In the calf, because calf veins are more difficult to visualize than proximal veins, the sensitivity of this technique is only 50 to 75%, although its specificity is 95%.
Impedance plethysmography measures changes in venous capacitance during physiologic maneuvers. Venous obstruction blunts the normal changes in venous capacitance that occur following inflation and deflation of a thigh cuff. The predictive value of this test for detecting occlusive thrombi in proximal veins is approximately 90%. However, it is much less sensitive for diagnosing deep venous thrombosis of the calves.
Magnetic resonance imaging (MRI) is another noninvasive means to detect deep vein thrombosis. Its diagnostic accuracy for assessing proximal deep vein thrombosis is similar to that of duplex ultrasonography. It is useful in patients with suspected thrombosis of the superior and inferior venae cavae or pelvic veins.
Deep venous thrombosis can also be diagnosed by venography. Contrast medium is injected into a superficial vein of the foot and directed to the deep system by the application of tourniquets. The presence of a filling defect or absence of filling of the deep veins is required to make the diagnosis.
Deep vein thrombosis must be differentiated from a variety of disorders that cause unilateral leg pain or swelling, including muscle rupture, trauma, or hemorrhage; a ruptured popliteal cyst; and lymphedema. It may be difficult to distinguish swelling caused by the postphlebitic syndrome from that due to acute recurrent deep venous thrombosis. Leg pain may also result from nerve compression, arthritis, tendinitis, fractures, and arterial occlusive disorders. A careful history and physical examination can usually determine the cause of these symptoms.
Prevention of pulmonary embolism is the most important reason for treating patients with deep vein thrombosis, since in the early stages the thrombus may be loose and poorly adherent to the vessel wall. Patients should be placed in bed, and the affected extremity should be elevated above the level of the heart until the edema and tenderness subside. Anticoagulants prevent thrombus propagation and allow the endogenous lytic system to operate. Initial therapy should include either unfractionated heparin or low-molecular-weight heparin. Unfractionated heparin should be administered intravenously as an initial bolus of 7500 to 10,000 IU, followed by a continuous infusion of 1000 to 1500 IU/h. The rate of the heparin infusion should be adjusted so that the activated partial thromboplastin time (aPTT) is approximately twice the control value. Subcutaneous injection of heparin has been used as an alternative form of therapy. In fewer than 5% of patients, heparin therapy may cause thrombocytopenia. Infrequently, these patients develop arterial thrombosis and ischemia. Low-molecular-weight (4000 to 6000 Da) heparins are reported to be as effective as or better than conventional, unfractionated heparin in preventing extension or recurrence of venous thrombosis. Depending on the specific preparation, low-molecular-weight heparin is administered subcutaneously, in fixed doses, once or twice daily; for example, the dose of enoxaparin is 1 mg/kg subcutaneously bid. The incidence of thrombocytopenia is less with low-molecular-weight heparin than with conventional preparations. Hirudin, a direct thrombin inhibitor, may be used as initial anticoagulant therapy for patients in whom heparin is contraindicated because of heparin-induced thrombocytopenia. Warfarin is administered during the first week of treatment with heparin and may be started as early as the first day of heparin treatment if the aPTT is therapeutic. It is important to overlap heparin treatment with oral anticoagulant therapy for at least 4 to 5 days because the full anticoagulant effect of warfarin is delayed. The dose of warfarin should be adjusted to maintain the prothrombin time at an international normalized ratio (INR) of 2.0 to 3.0.
Anticoagulant treatment is indicated for patients with proximal deep vein thrombosis, since pulmonary embolism may occur in approximately 50% of untreated individuals. The use of anticoagulants for isolated deep vein thrombosis of the calf is controversial. However, approximately 20 to 30% of calf thrombi propagate to the thigh, thereby increasing the risk of pulmonary embolism. The overall incidence of pulmonary embolism in patients presenting initially with deep calf vein thrombosis is 5 to 20%. Also, isolated calf vein thrombosis has been identified as a cause of embolic stroke via a patent foramen ovale. Therefore, patients with calf vein thrombosis should either receive anticoagulants or be followed with serial noninvasive tests to determine whether proximal propagation has occurred. Anticoagulant treatment should be continued for at least 3 to 6 months for patients with acute idiopathic deep vein thrombosis and for those with a temporary risk factor for venous thrombosis to decrease the chance of recurrence. The duration of treatment is indefinite for patients with recurrent deep vein thrombosis and for those in whom associated causes, such as malignancy or hypercoagulability, have not been eliminated. If treatment with anticoagulants is contraindicated because of a bleeding diathesis or risk of hemorrhage, protection from pulmonary embolism can be achieved by mechanically interrupting the flow of blood through the inferior vena cava. Inferior vena cava plication generally has been replaced by percutaneous insertion of a filter.
Thrombolytic drugs such as streptokinase, urokinase, and tPA may also be used, but there is no evidence that thrombolytic therapy is more effective than anticoagulants in preventing pulmonary embolism. However, early administration of thrombolytic drugs may accelerate clot lysis, preserve venous valves, and decrease the potential for developing postphlebitic syndrome.
Prophylaxis should be considered in clinical situations where the risk of deep vein thrombosis is high. Low-dose unfractionated heparin (5000 units 2 h prior to surgery and then 5000 units every 8 to 12 h postoperatively), warfarin, and external pneumatic compression are all useful. Low-dose heparin reduces the risk of deep vein thrombosis associated with thoracic and abdominal surgery and with prolonged bed rest. Low-molecular-weight heparins have been shown to prevent deep vein thrombosis in patients undergoing general or orthopedic surgery and in acutely ill medical patients. They are said to be more effective than conventional heparin and to cause an equal or lower incidence of bleeding. Danaparoid, a low-molecular-weight heparinoid, may be used for prophylaxis in patients undergoing hip surgery. Warfarin in a dose that yields a prothrombin time equivalent to an INR of 2.0 to 3.0 is effective in preventing deep vein thrombosis associated with bone fractures and orthopedic surgery. Warfarin is started the night before surgery and continued throughout the convalescent period. External pneumatic compression devices applied to the legs are used to prevent deep vein thrombosis when even low doses of heparin or warfarin might cause serious bleeding, as during neurosurgery or transurethral resection of the prostate.
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 vein thrombosis. 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 deep vein thrombosis. 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 is primarily supportive. Initially, patients can be placed at bed rest with leg elevation and application of warm compresses. Nonsteroidal antiinflammatory 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 are dilated, tortuous superficial veins that result from defective structure and function of the valves of the saphenous veins, from intrinsic weakness of the vein wall, from high intraluminal pressure, or, rarely, from 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 half of 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 causing 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; it 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 can usually be treated with conservative measures. Symptoms often decrease when the legs are elevated periodically, when prolonged standing is avoided, and when elastic support hose are worn. External compression stockings provide a counterbalance to the hydrostatic pressure in the veins. 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. Surgical therapy usually involves extensive ligation and stripping of the greater and lesser saphenous veins and should be reserved for patients who are very symptomatic, suffer recurrent superficial vein thrombosis, and/or develop skin ulceration. Surgical therapy may also be indicated for cosmetic reasons.
Chronic Venous Insufficiency
Chronic venous insufficiency may result from deep vein thrombosis and/or valvular incompetence. Following deep vein thrombosis, 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. Cellulitis may be a recurring problem. 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 and, occasionally, dilute topical antibiotic solutions. Commercially available dressings comprising antiseptic solutions and compressive bandages 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. Rarely, surgical valvuloplasty and bypass of venous occlusions are employed.
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 which contain smooth muscle and are capable of vasomotion. Small and medium-sized 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 may be categorized as primary or secondary (Table 248-3). The prevalence of primary lymphedema 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 syndrome, Klinefelter syndrome, Noonan syndrome, the yellow nail syndrome, the intestinal lymphangiectasia syndrome, and lymphangiomyomatosis. Women are affected more frequently than 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 lymphedema 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.
Secondary lymphedema is an acquired condition resulting from damage to or obstruction of previously normal lymphatic channels (Table 248-3). 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 (Chap. 221). 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 following 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 deep vein thrombosis 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.
The evaluation of patients with lymphedema should include diagnostic studies to clarify the cause. Abdominal and pelvic ultrasound and computed tomography 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 to 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.
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. Recently, microsurgical lymphatico-venous anastomotic procedures have been performed to rechannel lymph flow from obstructed lymphatic vessels into the venous system.