Diseases of the Aorta

2103CHAPTER 280

ascending aorta may cause congestive heart failure as a consequence of

aortic regurgitation, and compression of the superior vena cava may

produce congestion of the head, neck, and upper extremities.

A chest x-ray may be the first test that suggests the diagnosis of

a thoracic aortic aneurysm (Fig. 280-1). Findings include widening

of the mediastinal shadow and displacement or compression of the

trachea or left main stem bronchus. Echocardiography, particularly

transesophageal echocardiography, can be used to assess the proximal

ascending aorta and descending thoracic aorta. Contrast-enhanced CT,

magnetic resonance imaging (MRI), and conventional invasive aortography are sensitive and specific tests for assessment of aneurysms

of the thoracic aorta and involvement of branch vessels (Fig. 280-2).

In asymptomatic patients whose aneurysms are too small to justify

surgery, noninvasive testing with either contrast-enhanced CT or MRI

should be performed at least every 6–12 months to monitor expansion.

FIGURE 280-1 A chest x-ray of a patient with a thoracic aortic aneurysm.

TREATMENT

Thoracic Aortic Aneurysms

β-Adrenergic blockers currently are recommended for patients

with thoracic aortic aneurysms, particularly those with Marfan’s

syndrome, who have evidence of aortic root dilatation to reduce

the rate of further expansion. Additional medical therapy should be

given as necessary to control hypertension. Angiotensin receptor

antagonists may reduce the rate of aortic dilation in patients with

Marfan’s syndrome by blocking TGF-β signaling. Clinical outcome

trials have found that the rate of aortic root enlargement in patients

with Marfan’s syndrome was similar with atenolol and losartan.

Operative repair with placement of a prosthetic graft is indicated

in patients with symptomatic ascending thoracic aortic aneurysms,

and for most asymptomatic aneurysms, including those associated

with bicuspid aortic valves when the aortic root or ascending aortic diameter is ≥5.5 cm, or when the growth rate is >0.5 cm per

year. Replacement of the ascending aorta >4.5 cm is reasonable in

patients with bicuspid aortic valves undergoing aortic valve replacement because of severe aortic stenosis or aortic regurgitation. In

patients with Marfan’s syndrome, ascending thoracic aortic aneurysms of 4–5 cm should be considered for surgery. Operative repair

is indicated for patients with degenerative descending thoracic aortic aneurysms when the diameter is >6 cm, and endovascular repair

should be considered if feasible when the diameter is >5.5 cm.

Repair is also recommended when the diameter of a descending

thoracic aortic aneurysm has increased >1 cm per year.

■ ABDOMINAL AORTIC ANEURYSMS

Abdominal aortic aneurysms occur more frequently in males than in

females, and the incidence increases with age. Cigarette smoking is a

potent modifiable risk factor. Abdominal aortic aneurysms ≥4.0 cm

may affect 1–2% men aged >50 years. At least 90% of all abdominal

aortic aneurysms >4.0 cm are related to atherosclerotic disease, and

most of these aneurysms are below the level of the renal arteries.

Prognosis is related to both the size of the aneurysm and the severity

of coexisting coronary artery and cerebrovascular disease. The risk

of rupture increases with the size of the aneurysm: the 5-year risk for

aneurysms <5 cm is 1–2%, whereas it is 20–40% for aneurysms >5 cm

in diameter. The formation of mural thrombi within aneurysms may

predispose to peripheral embolization.

An abdominal aortic aneurysm commonly produces no symptoms.

It usually is detected on routine examination as a palpable, pulsatile,

expansile, and nontender mass, or it is an incidental finding observed

on an abdominal imaging study performed for other reasons. As

abdominal aortic aneurysms expand, however, they may become

painful. Some patients complain of strong pulsations in the abdomen;

others experience pain in the chest, lower back, or scrotum. Aneurysmal pain is usually a harbinger of rupture and represents a medical

emergency. More often, acute rupture occurs without any prior warning, and this complication is always life-threatening. Rarely, there is

leakage of the aneurysm with severe pain and tenderness. Acute pain

and hypotension occur with rupture of the aneurysm, which requires

an emergency operation or endovascular repair.

Abdominal radiography may demonstrate the calcified outline

of the aneurysm; however, ~25% of aneurysms are not calcified and

cannot be visualized by x-ray imaging. An abdominal ultrasound can

delineate the transverse and longitudinal dimensions of an abdominal

aortic aneurysm and may detect mural thrombus. Abdominal ultrasound is useful for serial documentation of aneurysm size and can be

used to screen patients at risk for developing an aortic aneurysm. In

one large study, ultrasound screening of men aged 65–74 years was

associated with a risk reduction in aneurysm-related death of 42%.

In a meta-analysis of population-based randomized clinical trials,

ultrasound screening of men aged 65 years or older was associated

with a 35% risk reduction in aneurysm-related death over 12–15 years.

Screening by ultrasonography is recommended for men aged 65–75 years

who have ever smoked. The benefits of screening women aged

FIGURE 280-2 A magnetic resonance angiogram demonstrating a fusiform

aneurysm of the ascending thoracic aorta. (Courtesy of Dr. Michael Steigner,

Brigham and Women’s Hospital, Boston, MA, with permission.)

2104 PART 6 Disorders of the Cardiovascular System

65–75 years who have ever smoked is not established. In addition,

male and female siblings or offspring of persons with abdominal aortic

aneurysms, as well as individuals with thoracic aortic or peripheral

arterial aneurysms, should be considered for screening for abdominal

aortic aneurysms. CT with contrast and MRI are accurate noninvasive

tests to determine the location and size of abdominal aortic aneurysms

and to plan endovascular or open surgical repair (Fig. 280-3). Contrast

aortography may be used for the evaluation of patients with aneurysms, but the procedure carries a small risk of complications such as

bleeding, allergic reactions, and atheroembolism. Since the presence of

mural thrombi may reduce the luminal size, aortography may underestimate the diameter of an aneurysm.

TREATMENT

Abdominal Aortic Aneurysms

Statins are indicated to reduce the risk of cardiovascular events

related to atherosclerosis. Medical therapies, such as β-adrenergic

blockers and renin-angiotensin inhibitors, have not proven effective

in reducing the rate of aneurysm growth. Operative repair of the

aneurysm with insertion of a prosthetic graft or endovascular placement of an aortic stent graft (Fig. 274-3) is indicated for abdominal

aortic aneurysms of any size that are expanding rapidly or are associated with symptoms. For asymptomatic aneurysms, abdominal

aortic aneurysm repair is indicated if the diameter is ≥5.5 cm. In

randomized trials of patients with abdominal aortic aneurysms

<5.5 cm, there was no difference in the long-term (>8-year) mortality rate between those followed with ultrasound surveillance and

those undergoing elective endovascular or surgical repair. Thus,

serial noninvasive follow-up of smaller aneurysms (<5.5 cm) is an

alternative to immediate repair. The decision to perform an open

surgical operation or endovascular repair is based in part on the

vascular anatomy and comorbid conditions. Endovascular repair

of abdominal aortic aneurysms has a lower short-term morbidity

rate, but a comparable long-term mortality rate with open surgical

reconstruction. Long-term surveillance with CT or MR aortography is indicated after endovascular repair to detect leaks and possible aneurysm expansion.

In surgical candidates, careful preoperative cardiac and general

medical evaluations (followed by appropriate therapy for complicating conditions) are essential. Preexisting coronary artery disease,

congestive heart failure, pulmonary disease, diabetes mellitus, and

advanced age add to the risk of surgery. With careful preoperative

cardiac evaluation and postoperative care, the operative mortality

rate approximates 1–2%. After acute rupture, the mortality rate

of emergent operation is 45–50%. Endovascular repair with stent

placement is an alternative approach to treat ruptured aneurysms

and may be associated with a lower mortality rate.

ACUTE AORTIC SYNDROMES

The four major acute aortic syndromes are aortic rupture (discussed

earlier), aortic dissection, intramural hematoma, and penetrating

atherosclerotic ulcer. Aortic dissection is caused by a circumferential

or, less frequently, transverse tear of the intima. It often occurs along

the right lateral wall of the ascending aorta where the hydraulic shear

stress is high. Another common site is the descending thoracic aorta

just below the ligamentum arteriosum. The initiating event is either

a primary intimal tear with secondary dissection into the media or

a medial hemorrhage that dissects into and disrupts the intima. The

pulsatile aortic flow then dissects along the elastic lamellar plates of

the aorta and creates a false lumen. The dissection usually propagates

distally down the descending aorta and into its major branches, but

it may propagate proximally. Distal propagation may be limited by

atherosclerotic plaque. In some cases, a secondary distal intimal disruption occurs, resulting in the reentry of blood from the false to the

true lumen.

There are at least two important pathologic and radiologic variants

of aortic dissection: intramural hematoma without an intimal flap

and penetrating atherosclerotic ulcer. Acute intramural hematoma is

thought to result from rupture of the vasa vasorum with hemorrhage

into the wall of the aorta. Most of these hematomas occur in the

descending thoracic aorta. Acute intramural hematomas may progress

to dissection and rupture. Penetrating atherosclerotic ulcers are caused

by erosion of a plaque into the aortic media, are usually localized, and

are not associated with extensive propagation. They are found primarily in the middle and distal portions of the descending thoracic aorta

and are associated with extensive atherosclerotic disease. The ulcer can

FIGURE 280-3 A computed tomographic angiogram depicting a fusiform abdominal aortic aneurysm before (left) and after (right) treatment with a bifurcated stent graft.

(Courtesy of Drs. Elizabeth George and Frank Rybicki, Brigham and Women’s Hospital, Boston, MA, with permission.)

Diseases of the Aorta

2105CHAPTER 280

erode beyond the internal elastic lamina, leading to medial hematoma,

and may progress to false aneurysm formation or rupture.

Several classification schemes have been developed for thoracic

aortic dissections. DeBakey and colleagues initially classified aortic

dissections as type I, in which an intimal tear occurs in the ascending

aorta but the dissection may propagate to the aortic arch, the descending thoracic aorta, and even the abdominal aorta; type II, in which the

dissection is limited to the ascending aorta; and type III, in which the

intimal tear is located in the descending aorta with distal propagation

of the dissection (Fig. 280-4). Another classification (Stanford) is that

of type A, in which the dissection involves the ascending aorta (proximal dissection), and type B, in which it is limited to the arch and/or

descending aorta (distal dissection). From a management standpoint,

classification of aortic dissections and intramural hematomas into type

A or B is more practical and useful, since DeBakey types I and II are

managed in a similar manner.

The factors that predispose to aortic dissection include those associated with medial degeneration and others that increase aortic wall

stress (Table 280-1). Systemic hypertension is a coexisting condition in

70% of patients. Aortic dissection is the major cause of morbidity and

mortality in patients with Marfan’s syndrome (Chap. 413) or LoeysDietz syndrome, and similarly may affect patients with Ehlers-Danlos

syndrome. The incidence also is increased in patients with inflammatory aortitis (i.e., Takayasu’s arteritis, giant cell arteritis), congenital

aortic valve anomalies (e.g., bicuspid valve), coarctation of the aorta,

and a history of aortic trauma. In addition, the risk of dissection is

increased in otherwise normal women during the third trimester

of pregnancy. Aortic dissection also may occur as a consequence of

weight lifting, cocaine use, or deceleration injury.

■ CLINICAL MANIFESTATIONS

The peak incidence of aortic dissection is in the sixth and seventh

decades. Men are more affected than women by a ratio of 2:1. The

presentations of aortic dissection and its variants are the consequences

Type A

Type B

FIGURE 280-4 Classification of aortic dissections. Stanford classification: Type A

dissections (top) involve the ascending aorta independent of site of tear and distal

extension; type B dissections (bottom) involve transverse and/or descending

aorta without involvement of the ascending aorta. DeBakey classification: Type I

dissection involves ascending to descending aorta (top left); type II dissection is

limited to ascending or transverse aorta, without descending aorta (top center + top

right); type III dissection involves descending aorta only (bottom left). (Reproduced

with permission from DC Miller, in RM Doroghazi, EE Slater [eds]: Aortic Dissection.

New York, McGraw-Hill, 1983.)

of intimal tear, dissecting hematoma, occlusion of involved arteries,

and compression of adjacent tissues. Acute aortic dissection presents

with the sudden onset of pain (Chap. 14), which often is described as

very severe and tearing and is associated with diaphoresis. The pain

may be localized to the front or back of the chest, often the interscapular region, and typically migrates with propagation of the dissection.

Other symptoms include syncope, dyspnea, and weakness. Physical

findings may include hypertension or hypotension, loss of pulses, aortic regurgitation, pulmonary edema, and neurologic findings due to

carotid artery obstruction (hemiplegia, hemianesthesia) or spinal cord

ischemia (paraplegia). Bowel ischemia, hematuria, and myocardial

ischemia all may occur. These clinical manifestations reflect complications resulting from the dissection occluding the major arteries. Furthermore, clinical manifestations may result from the compression of

adjacent structures (e.g., superior cervical ganglia, superior vena cava,

bronchus, esophagus) by the expanding dissection causing aneurysmal

dilation and include Horner’s syndrome, superior vena cava syndrome,

hoarseness, dysphagia, and airway compromise. Hemopericardium

and cardiac tamponade may complicate a type A lesion with retrograde

dissection. Acute aortic regurgitation is an important and common

(>50%) complication of proximal dissection. It is the outcome of either

a circumferential tear that widens the aortic root or a disruption of the

annulus by a dissecting hematoma that tears a leaflet(s) or displaces

it, inferior to the line of closure. Signs of aortic regurgitation include

bounding pulses, a wide pulse pressure, a diastolic murmur often

radiating along the right sternal border, and evidence of congestive

heart failure. The clinical manifestations depend on the severity of the

regurgitation.

In dissections involving the ascending aorta, the chest x-ray often

reveals a widened superior mediastinum. A pleural effusion (usually

left-sided) also may be present. This effusion is typically serosanguineous and not indicative of rupture unless accompanied by hypotension

and falling hematocrit. In dissections of the descending thoracic aorta,

a widened mediastinum may be observed on chest x-ray. In addition,

the descending aorta may appear to be wider than the ascending

portion. An electrocardiogram that shows no evidence of myocardial

ischemia is helpful in distinguishing aortic dissection from myocardial

infarction among patients who present with chest pain. Rarely, the dissection involves the right or, less commonly, left coronary ostium and

causes acute myocardial infarction.

The diagnosis of aortic dissection can be established by noninvasive

techniques such as echocardiography, CT, and MRI. Aortography is

used less commonly because of the accuracy of these noninvasive techniques. Transthoracic echocardiography can be performed simply and

rapidly and has an overall sensitivity of 60–85% for aortic dissection.

For diagnosing proximal ascending aortic dissections, its sensitivity

exceeds 80%; it is less useful for detecting dissection of the arch and

descending thoracic aorta. Transesophageal echocardiography requires

greater skill and patient cooperation but is very accurate in identifying

dissections of the ascending and descending thoracic aorta but not the

arch, achieving 98% sensitivity and ~90% specificity. Echocardiography also provides important information regarding the presence and

severity of aortic regurgitation and pericardial effusion. CT and MRI

are both highly accurate in identifying the intimal flap and the extent

of the dissection and involvement of major arteries; each has a sensitivity and specificity >90%. They are useful in recognizing intramural

hemorrhage and penetrating ulcers. The relative utility of transesophageal echocardiography, CT, and MRI depends on the availability and

expertise in individual institutions as well as on the hemodynamic

stability of the patient, with CT and MRI obviously less suitable for

unstable patients.

TREATMENT

Aortic Dissection

Medical therapy should be initiated as soon as the diagnosis is considered. The patient should be admitted to an intensive care unit for

hemodynamic monitoring. Unless hypotension is present, therapy

2106 PART 6 Disorders of the Cardiovascular System

should be aimed at reducing cardiac contractility and systemic

arterial pressure, and thus shear stress. For acute dissection, unless

contraindicated, β-adrenergic blockers should be administered

parenterally, using intravenous propranolol, metoprolol, or the

short-acting esmolol to achieve a heart rate of ~60 beats/min. This

should be accompanied by sodium nitroprusside infusion to lower

systolic blood pressure to ≤120 mmHg. Labetalol (Chap. 277), a

drug with both β- and α-adrenergic blocking properties, also may

be used as a parenteral agent in acute therapy for dissection.

The calcium channel antagonists verapamil and diltiazem may be

used intravenously if nitroprusside or β-adrenergic blockers cannot

be employed. The addition of a parenteral angiotensin-converting

enzyme (ACE) inhibitor such as enalaprilat to a β-adrenergic

blocker also may be considered. Isolated use of a direct vasodilator

such as hydralazine is contraindicated because these agents can

increase hydraulic shear and may propagate the dissection.

Emergent or urgent surgical correction is the preferred treatment

for acute ascending aortic dissections and intramural hematomas

(type A). Surgery involves excision of the intimal flap, obliteration

of the false lumen, and placement of an interposition graft. Aortic

valve repair or a composite valve-graft conduit is used if the aortic valve is disrupted. The overall in-hospital mortality rate after

surgical treatment of patients with aortic dissection is reported

to be 15–25%. The major causes of perioperative mortality and

morbidity include myocardial infarction, paraplegia, renal failure,

tamponade, hemorrhage, and sepsis. Thoracic endovascular aortic

repair with an endoluminal stent graft is indicated for complicated

type B dissections, including those characterized by propagation,

compromise of major aortic branches, impending rupture, or continued pain. Other transcatheter techniques, such as fenestration of

the intimal flaps and stenting of narrowed branch vessels to increase

flow to compromised organs, are used in selected patients. Surgical

correction is indicated for complicated type B dissections, particularly if endovascular repair is not feasible. Hybrid procedures consisting of both surgery and endovascular repair may be used when

the dissection involves both the aortic arch and the descending

thoracic aorta. For uncomplicated and stable distal dissections and

intramural hematomas (type B), medical therapy is the preferred

treatment. The in-hospital mortality rate of medically treated patients

with type B dissection is ~12%. Long-term therapy for patients with

aortic dissection and intramural hematomas (with or without surgery)

consists of control of hypertension and reduction of cardiac contractility with the use of β-adrenergic blockers plus other antihypertensive agents, such as ACE inhibitors or calcium antagonists. Patients

with chronic type B dissection and intramural hematomas should be

followed on an outpatient basis every 6–12 months with contrastenhanced CT or MRI to detect propagation or expansion. Patients with

Marfan’s syndrome are at high risk for postdissection complications.

The long-term prognosis following hospital discharge for patients

with treated dissections is generally good with careful follow-up;

the 10-year survival rate is ~60%.

■ CHRONIC ATHEROSCLEROTIC

OCCLUSIVE DISEASE

Atherosclerosis may affect the thoracic and abdominal aorta. Occlusive

aortic disease caused by atherosclerosis usually is confined to the distal

abdominal aorta below the renal arteries. Frequently the disease extends

to the iliac arteries (Chap. 281). Claudication characteristically involves

the buttocks, thighs, and calves and may be associated with impotence

in males (Leriche’s syndrome). The severity of the symptoms depends

on the adequacy of collaterals. With sufficient collateral blood flow,

a complete occlusion of the abdominal aorta may occur without the

development of ischemic symptoms. The physical findings include the

absence of femoral and other distal pulses bilaterally and the detection

of an audible bruit over the abdomen (usually at or below the umbilicus) and the common femoral arteries. Atrophic skin, loss of hair, and

coolness of the lower extremities usually are observed. In advanced

ischemia, rubor on dependency and pallor on elevation can be seen.

The diagnosis usually is established by physical examination and

noninvasive testing, including leg pressure measurements, Doppler

velocity analysis, pulse volume recordings, and duplex ultrasonography. The anatomy may be defined by MR, CT, or conventional

contrast angiography, typically performed when one is considering

revascularization. Catheter-based endovascular or operative treatment

is indicated in patients with lifestyle-limiting or debilitating symptoms

of claudication and patients with critical limb ischemia.

■ ACUTE AORTIC OCCLUSION

Acute occlusion in the distal abdominal aorta constitutes a medical

emergency because it threatens the viability of the lower extremities; it

usually results from an occlusive (saddle) embolus that almost always

originates from the heart. Rarely, acute occlusion may occur as the

result of in situ thrombosis in a preexisting severely narrowed segment

of the aorta.

The clinical picture is one of acute ischemia of the lower extremities. Severe rest pain, coolness, and pallor of the lower extremities and

the absence of distal pulses bilaterally are the usual manifestations.

Diagnosis should be established rapidly by MRI, CT, or aortography.

Emergency thrombectomy or revascularization is indicated.

AORTITIS

Aortitis, a term referring to inflammatory disease of the aorta, may

be caused by large vessel vasculitides such as Takayasu’s arteritis and

giant cell arteritis, rheumatic and HLA-B27–associated spondyloarthropathies, Behçet’s syndrome, antineutrophil cytoplasmic antibody

(ANCA)–associated vasculitides, Cogan’s syndrome, Erdheim-Chester

disease, IgG4-related systemic disease, and infections such as syphilis,

tuberculosis, and Salmonella, or it may be associated with retroperitoneal fibrosis. Aortitis may result in aneurysmal dilation and aortic

regurgitation, occlusion of the aorta and its branch vessels, or acute

aortic syndromes.

■ TAKAYASU’S ARTERITIS

(See also Chap. 363) This inflammatory disease often affects the

ascending aorta and aortic arch, causing obstruction of the aorta and

its major arteries. Takayasu’s arteritis is also termed pulseless disease

because of the frequent occlusion of the large arteries originating from

the aorta. It also may involve the descending thoracic and abdominal

aorta and occlude large branches such as the renal arteries. Aortic

aneurysms also may occur. The pathology is a panarteritis characterized by mononuclear cells and occasionally giant cells, with marked

intimal hyperplasia, medial and adventitial thickening, and, in the

chronic form, fibrotic occlusion. The disease is most prevalent in

young females of Asian descent but does occur in women of other

geographic and ethnic origins and also in young men. During the acute

stage, fever, malaise, weight loss, and other systemic symptoms may be

evident. Elevations of the erythrocyte sedimentation rate and C-reactive

protein are common. The chronic stages of the disease, which is intermittently active, present with symptoms related to large artery occlusion, such as upper extremity claudication, cerebral ischemia, and

syncope. The process is progressive, and there is no definitive therapy.

Glucocorticoids are effective in most patients during the acute phase.

Other immunosuppressive agents, such as methotrexate, azathioprine,

leflunomide, or mycophenolate, are prescribed to some patients to

lower glucocorticoid requirements and treat relapses. Biologically targeted agents are also used, but efficacy has not been established in randomized clinical trials. Surgical bypass or endovascular intervention of

a critically stenotic artery may be necessary.

■ GIANT CELL ARTERITIS

(See also Chap. 363) This vasculitis occurs in older individuals and

affects women more often than men. Primarily large and mediumsize arteries are affected. The pathology is that of focal granulomatous

lesions involving the entire arterial wall; it frequently is associated with

polymyalgia rheumatica. Obstruction of medium-size arteries (e.g.,

temporal and ophthalmic arteries) and major branches of the aorta

Arterial Diseases of the Extremities

2107CHAPTER 281

and the development of aortitis and aortic regurgitation are important

complications of the disease. High-dose glucocorticoid therapy should

be administered early and then gradually tapered. Immunosuppressive

therapy with methotrexate may allow reduction in steroid dosage and

reduce the risk of relapse. Tocilizumab, an interleukin-6 antagonist,

demonstrated efficacy in several randomized trials. Other biologically

targeted therapies are under investigation.

■ RHEUMATIC AORTITIS

Rheumatoid arthritis (Chap. 358), ankylosing spondylitis (Chap. 362),

psoriatic arthritis (Chap. 362), reactive arthritis (formerly known as

Reiter’s syndrome) (Chap. 362), relapsing polychondritis, and inflammatory bowel disorders may all be associated with aortitis involving

the ascending aorta. The inflammatory lesions usually involve the

ascending aorta and may extend to the sinuses of Valsalva, the mitral

valve leaflets, and adjacent myocardium. The clinical manifestations

are aneurysm, aortic regurgitation, and involvement of the cardiac

conduction system.

■ IDIOPATHIC AORTITIS

Idiopathic abdominal aortitis is characterized by adventitial and

periaortic inflammation with thickening of the aortic wall. It is associated with abdominal aortic aneurysms and idiopathic retroperitoneal

fibrosis. Affected individuals may present with vague constitutional

symptoms, fever, and abdominal pain. Retroperitoneal fibrosis can

cause ureteral obstruction and hydronephrosis. Glucocorticoids and

immunosuppressive agents may reduce the inflammation.

■ INFECTIVE AORTITIS

Infective aortitis may result from direct invasion of the aortic wall by

bacterial pathogens such as Staphylococcus, Streptococcus, and Salmonella or by fungi. These bacteria cause aortitis by infecting the aorta at

sites of atherosclerotic plaque. Bacterial proteases lead to degradation

of collagen, and the ensuing destruction of the aortic wall leads to the

formation of a saccular aneurysm referred to as a mycotic aneurysm.

Mycotic aneurysms have a predilection for the suprarenal abdominal

aorta. The pathologic characteristics of the aortic wall include acute

and chronic inflammation, abscesses, hemorrhage, and necrosis.

Mycotic aneurysms typically affect the elderly and occur in men three

times more frequently than in women. Patients may present with fever,

sepsis, and chest, back, or abdominal pain; there may have been a preceding diarrheal illness. Blood cultures are positive in the majority of

patients. Both CT and MRI are useful to diagnose mycotic aneurysms.

Treatment includes antibiotic therapy and surgical removal of the

affected part of the aorta and revascularization of the lower extremities

with grafts placed in uninfected tissue.

Syphilitic aortitis is a late manifestation of luetic infection (Chap. 182)

that usually affects the proximal ascending aorta, particularly the aortic

root, resulting in aortic dilation and aneurysm formation. Syphilitic

aortitis occasionally may involve the aortic arch or the descending

aorta. The aneurysms may be saccular or fusiform and are usually

asymptomatic, but compression of and erosion into adjacent structures

may result in symptoms; rupture also may occur.

The initial lesion is an obliterative endarteritis of the vasa vasorum,

especially in the adventitia. This is an inflammatory response to the

invasion of the adventitia by the spirochetes. Destruction of the aortic

media occurs as the spirochetes spread into this layer, usually via the

lymphatics accompanying the vasa vasorum. Destruction of collagen

and elastic tissues leads to dilation of the aorta, scar formation, and

calcification. These changes account for the characteristic radiographic

appearance of linear calcification of the ascending aorta.

The disease typically presents as an incidental chest radiographic

finding 15–30 years after initial infection. Symptoms may result from

aortic regurgitation, narrowing of coronary ostia due to syphilitic aortitis, compression of adjacent structures (e.g., esophagus), or rupture.

Diagnosis is established by a positive serologic test, i.e., rapid plasmin

reagin (RPR) or fluorescent treponemal antibody. Treatment includes

penicillin and surgical excision and repair.

■ FURTHER READING

Chaikof EL et al: The Society for Vascular Surgery practice guidelines

on the care of patients with an abdominal aortic aneurysm. J Vasc

Surg 67:2, 2018.

Evangelista A et al: Insights from the international registry of acute

aortic dissection: A 20-year experience of collaborative clinical

research. Circulation 137:1846, 2018.

Guirguis-Blake JM et al: Primary care screening for abdominal aortic

aneurysm: Updated evidence report and systematic review for the US

Preventive Services Task Force. JAMA 322:2211, 2019.

Hiratzka LF et al: 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/

SIR/STS/SVM guidelines for the diagnosis and management of

patients with Thoracic Aortic Disease: A report of the American

College of Cardiology Foundation/American Heart Association Task

Force on Practice Guidelines, American Association for Thoracic

Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional

Radiology, Society of Thoracic Surgeons, and Society for Vascular

Medicine. Circulation 121:e266, 2010.

Hofmann Bowman MA et al: Update on clinical trials of losartan with

and without beta-blockers to block aneurysm growth in patients with

Marfan syndrome: A review. JAMA Cardiol 4:702, 2019.

Lederle FA et al: Open versus endovascular repair of abdominal aortic

aneurysm. N Engl J Med 380:2126, 2019.

Merkel PA, Cid MC: Large vessel vasculitis, in Vascular Medicine. A

Companion to Braunwald’s Heart Disease. 3rd ed. MA Creager MA et

al (eds). Philadelphia, Elsevier, 2020, pp 533-554.

Pinard A et al: Genetics of thoracic and abdominal aortic diseases.

Circ Res 124:588, 2019.

Tadros RO et al: Optimal treatment of uncomplicated type B aortic

dissection: JACC review topic of the week. J Am Coll Cardiol 74:1494,

2019.

■ 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 renal insufficiency.

Pathology 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.

281 Arterial Diseases of

the Extremities

Mark A. Creager, Joseph Loscalzo

2108 PART 6 Disorders of the Cardiovascular System

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

typical 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,

thigh, and calf 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

A B

FIGURE 281-1 Magnetic resonance angiography of a patient with intermittent claudication, showing stenoses of the distal abdominal aorta and right common iliac artery

(A) and stenoses of the right and left superficial femoral arteries (B). (Courtesy of Dr. Edwin Gravereaux, with permission.)

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 1.00–1.40

in normal individuals. ABI values of 0.91–0.99 are considered “borderline,” and those <0.90 are abnormal and diagnostic of PAD. ABIs >1.40

indicate noncompressible arteries secondary to vascular calcification.

Other noninvasive tests include segmental pressure measurements,

segmental pulse volume recordings, duplex ultrasonography (which

combines B-mode imaging and Doppler flow velocity waveform

analysis), 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 catheter-based angiography

should not be used for routine diagnostic testing, but are performed

before potential revascularization (Fig. 281-1). Each test is useful in

defining the anatomy to assist planning for endovascular and surgical

revascularization procedures.

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

15–25% 5-year mortality rate and a two- to fourfold increased risk of

death from cardiovascular disease. Measurement of ABI is useful for

detecting PAD and identifying persons at risk for adverse cardiovascular and limb events. Mortality rates are highest in those with the most

Arterial Diseases of the Extremities

2109CHAPTER 281

severe PAD. The ABI worsens in almost 40% of patients, and symptoms

progress in ~20–25% when assessed over a period of 5 years. Approximately 11% of patients with symptomatic PAD ultimately develop critical limb ischemia, and 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 antithrombotic 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 and angiotensin receptor blockers 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 and, if needed, adjunctive lipid-lowering agents such

as ezetimibe or a PCSK9 inhibitor, is advocated to reduce the risk

of myocardial infarction, stroke, and death. The 2018 American

Heart Association (AHA)/American College of Cardiology (ACC)

Guideline on the Management of Blood Cholesterol recommends

high-intensity statin treatment in patients with atherosclerotic disorders, including PAD, with the aim of achieving a 50% or greater

reduction in low-density lipoprotein cholesterol. Platelet inhibitors, including aspirin and the adenosine diphosphate (ADP)

antagonist clopidogrel, reduce the risk of adverse cardiovascular

events in patients with atherosclerosis and are recommended for

patients with symptomatic PAD, including those with intermittent

claudication or critical limb ischemia or prior lower extremity

revascularization. Outcomes with ticagrelor are similar to those

with clopidogrel. The benefit of dual antiplatelet therapy with both

aspirin and clopidogrel compared with aspirin alone in reducing

cardiovascular morbidity and mortality rates in patients with PAD

is uncertain. When added to other antiplatelet therapy, vorapaxar,

a protease activated receptor-1 antagonist that inhibits thrombinmediated platelet activation, decreases the risk of adverse cardiovascular events in patients with atherosclerosis, including PAD.

It also reduces the risk of acute limb ischemia and peripheral

revascularization; however, it is associated with an increased rate

of moderate bleeding. 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. The combination

of a low dose of the oral factor Xa inhibitor rivaroxaban and aspirin improves cardiovascular and limb outcomes in patients with

established atherosclerosis, including PAD, including those who

have undergone peripheral revascularization, but is associated with

increased risk of bleeding.

Therapies for intermittent claudication and critical limb ischemia include supportive measures, medications, exercise training,

endovascular 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, at least three

per week for 12 weeks, prolong walking distance. The beneficial

effect of supervised exercise training on walking performance in

patients with claudication often is similar to or greater than that

realized after a revascularization procedure. Structured home and

community-based exercise programs are also effective. Pharmacologic treatment of PAD has not been as successful as the medical

treatment of CAD (Chap. 273). 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 those

generated in the interstitial tissue by the exercising muscle. Drugs

such as α-adrenergic blocking agents, calcium channel antagonists,

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 modestly

increases the duration of exercise, its efficacy has not been confirmed in other clinical trials. Statins appeared effective for treatment of intermittent claudication in initial clinical trials, but more

studies are needed to confirm the efficacy of this class of drugs.

There is no definitive medical therapy for critical limb ischemia.

Vasodilator prostaglandins are not effective in relieving symptoms or preventing limb loss. Enthusiasm for therapy with angiogenic growth factors abated when clinical trials of intramuscular

gene transfer of DNA encoding vascular endothelial growth factor,

fibroblast growth factor, hepatocyte growth factor, or hypoxiainducible factor 1α failed to demonstrate improvement in symptoms or outcomes in patients with intermittent claudication or

critical limb ischemia. Most clinical trials of bone marrow–derived

vascular progenitor cells to promote angiogenesis and preserve

limb viability in patients with critical limb ischemia have failed to

demonstrate benefit, although a meta-analysis of these trials suggested a modest reduction in the risk of amputation.

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 in order to improve walking distance and

functional capacity. These are also indicated in patients with critical

limb ischemia to relieve pain and prevent limb loss. MRA, CTA, or

conventional angiography should be performed to assess vascular

anatomy in patients who are being considered for revascularization. Endovascular interventions include percutaneous transluminal balloon angioplasty (PTA) (including drug-coated balloons),

stent placement (including drug-eluting stents), stent grafts, and

atherectomy (Chap. 276). When endovascular intervention is performed in conjunction with a supervised exercise program, walking

distance improves more than with exercise training alone.

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

rate for femoral-popliteal PTA and stenting approximate 90% with

60% 3-year patency rates. Several clinical trials have found lower

femoral-popliteal restenosis rates with drug-coated balloons than

with PTA, and with drug-eluting stents compared with bare metal

stents. Recent meta-analyses have raised concerns about increased

mortality in patients treated with paclitaxel drug-coated balloons

and drug-eluting stents, but conclusive evidence of this adverse

2110 PART 6 Disorders of the Cardiovascular System

outcome from prospective randomized trials is lacking. Endovascular interventions of the infrapopliteal, tibial, and peroneal arteries,

often in conjunction with treatment of more proximal lesions, can

be undertaken to treat critical limb ischemia and prevent limb loss.

Several operative procedures are available for treating patients

with PAD. 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, femorofemoral 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 rates in survivors are >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 to 3%, mostly due to ischemic

heart disease.

Operative therapy for femoral-popliteal and tibioperoneal 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 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 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%.

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, heart failure, diabetes, or renal insufficiency

are among those at increased risk. Stress testing with treadmill

exercise (if feasible), radionuclide myocardial perfusion imaging,

or echocardiography permits further stratification of risk in these

patients, particularly those with poor or unknown functional

capacity (Chap. 276). Patients with abnormal test results require

close supervision and adjunctive management with anti-ischemic

medications. 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 typically affects

medium-size and small arteries, but it can also affect larger arteries. It

occurs predominantly in females and usually involves the renal and

carotid/vertebral arteries but can involve coronary and mesenteric

arteries, as well as extremity vessels such as the iliac and subclavian

arteries. Fibromuscular dysplasia may cause stenosis, dissection, aneurysm, or thrombosis in affected 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. A contemporary classification

based on the angiographic appearance divides fibromuscular dysplasia

into two types: multifocal (analogous to medial dysplasia) and focal

(intimal fibroplasia).

The iliac arteries are the limb arteries most likely to be affected by

fibromuscular dysplasia. It is identified angiographically by a “string

of beads” multifocal appearance caused by thickened fibromuscular

ridges contiguous with thin, less-involved portions of the arterial wall,

or less commonly, as a focal tubular stenosis. 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. MRA, CTA, and conventional arteriography are 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. Takayasu’s arteritis and giant cell (temporal)

arteritis are discussed in Chap. 363.

■ ACUTE LIMB ISCHEMIA

Acute limb ischemia occurs when 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. Principal causes of acute arterial occlusion include

embolism, thrombus in situ, arterial dissection, and trauma.

The most common sources of arterial emboli are the heart, aorta,

and large arteries. Cardiac disorders that cause thromboembolism

include atrial fibrillation; 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.

Arterial Diseases of the Extremities

2111CHAPTER 281

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 disrupt continuity

of blood flow and cause acute limb ischemia via formation of an acute

arterial thrombus or by disruption of an artery’s integrity and extravasation of blood. 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 (Chaps. 103 and 116) 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 severe. 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 clinical

evaluation includes Doppler assessment of peripheral blood flow. The

diagnosis of acute limb ischemia 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 arterial occlusion.

TREATMENT

Acute Limb Ischemia

Once the diagnosis is made, the patient should be anticoagulated

with intravenous heparin to prevent propagation of the clot and

recurrent embolism. In cases of severe ischemia of recent onset,

particularly when limb viability is jeopardized, immediate intervention to ensure reperfusion is indicated. Catheter-directed thrombolysis/thrombectomy, surgical thromboembolectomy, and 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 most effective when

acute arterial occlusion is recent (<2 weeks) and caused by a thrombus in an atherosclerotic vessel, arterial bypass graft, or occluded

stent. Thrombolytic therapy is also indicated when the patient’s

overall condition contraindicates surgical intervention or when

smaller distal vessels are occluded, thus preventing surgical access.

Meticulous observation for hemorrhagic complications is required

during intraarterial thrombolytic therapy. Ultrasound-emitting

catheters may accelerate reperfusion by improving thrombus permeability to thrombolytic agents. 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. Surgical revascularization is preferred when restoration of blood flow must occur within 24 h to prevent limb loss

or when symptoms of occlusion have been present for >2 weeks.

Amputation is performed when the limb is not viable, as characterized by loss of sensation, paralysis, and the absence of Dopplerdetected blood flow in both arteries and veins.

Long-term anticoagulation is indicated when acute limb ischemia is caused by cardiac thromboembolism. Emboli resulting from

FIGURE 281-2 Atheroembolism causing cyanotic discoloration and impending

necrosis of the toes (“blue toe” syndrome).

infective endocarditis, the presence of prosthetic heart valves, or

atrial myxoma often require surgical intervention to remove the

cause.

■ ATHEROEMBOLISM

Atheroembolism is another cause of limb ischemia. 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 limb ischemia, as well as stroke and renal insufficiency. Atheroembolism may occur after intraarterial procedures. Since atheroemboli

to limbs 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. 281-2). 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. Local foot care and occasionally amputation may be needed to

treat necrotic areas. Analgesics are indicated for pain relief. Usually

neither surgical revascularization procedures nor thrombolytic therapy

is helpful because of the multiplicity, composition, and distal location

of the emboli. Therapy with antiplatelet drugs and statins improves

cardiovascular outcome in patients with atherosclerosis, but it is not

established whether either class of drugs prevents recurrent atheroembolism. Similarly, it is not known whether anticoagulant therapy is

effective. Endovascular or surgical intervention to exclude 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

2112 PART 6 Disorders of the Cardiovascular System

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 arterial 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.

Several maneuvers that support the diagnosis of arterial 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. 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 longstanding 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. 257).

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. CTA 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 (Fig. 281-3A). 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:

idiopathic, termed primary Raynaud’s phenomenon, and secondary

Raynaud’s phenomenon, which is associated with other disease states

or known causes of vasospasm (Table 281-1).

Primary Raynaud’s Phenomenon This appellation is applied

when the secondary causes of Raynaud’s phenomenon have been

excluded. Over 50% of patients with Raynaud’s phenomenon have the

primary form. 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, tongue, nipple, or penis are

involved. Raynaud’s phenomenon occurs frequently in patients who

also have migraine headaches or variant angina. These associations

Arterial Diseases of the Extremities

2113CHAPTER 281

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. Nailfold capillaroscopy

reveals normal superficial capillaries, which appear as regularly spaced

hairpin loops. 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 primary Raynaud’s disease have milder

clinical manifestations. Fewer than 1% of these patients lose a part of a

digit. After the diagnosis is made, the disease improves spontaneously

in ~15% of patients and progresses in ~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% (Chap. 360).

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. 356). 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 ~30% of patients with dermatomyositis or

polymyositis (Chap. 365). 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 aged >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-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 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

A B C

D E F

FIGURE 281-3 Vascular diseases associated with temperature: A. Raynaud’s phenomenon; B. acrocyanosis; C. livedo reticularis; D. pernio; E. erythromelalgia; and

F. frostbite.

TABLE 281-1 Classification of Raynaud’s Phenomenon

Primary or idiopathic Raynaud’s phenomenon

Secondary Raynaud’s phenomenon

 Collagen vascular diseases: scleroderma, systemic lupus erythematosus,

rheumatoid arthritis, dermatomyositis, polymyositis, mixed connective tissue

disease, Sjögren’s syndrome

 Arterial occlusive diseases: atherosclerosis of the extremities, thromboangiitis

obliterans, acute arterial occlusion, thoracic outlet syndrome

Pulmonary hypertension

 Neurologic disorders: intervertebral disk disease, syringomyelia, spinal cord

tumors, stroke, poliomyelitis, carpal tunnel syndrome, complex regional pain

syndrome

 Blood dyscrasias: cold agglutinins, cryoglobulinemia, cryofibrinogenemia,

myeloproliferative disorders, lymphoplasmacytic lymphoma

 Trauma: vibration injury, hammer hand syndrome, electric shock, cold injury,

typing, piano playing

 Drugs and toxins: ergot derivatives, methysergide, β-adrenergic receptor

blockers, bleomycin, vinblastine, cisplatin, gemcitabine, vinyl chloride

2114 PART 6 Disorders of the Cardiovascular System

primary pulmonary hypertension (Chap. 283); 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

lymphoplasmacytic lymphoma (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 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, cisplatin, and gemcitabine.

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 coldinduced 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. Phosphodiesterase type 5 inhibitors such

as sildenafil, tadalafil, and vardenafil may improve symptoms in

patients with secondary Raynaud’s phenomenon, as occurs with

systemic sclerosis. There is also evidence that topical nitroglycerin

preparations are effective. Digital sympathectomy is helpful in

some patients who are unresponsive to medical therapy. Injection

of botulinum toxin into the perivascular tissue of the wrist or palm

improved ischemic manifestations of severe Raynaud’s phenomenon in case series, but controlled clinical trials are lacking.

■ 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 (Fig. 281-3B).

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, vasopressor medications, connective tissue diseases, atheroembolism,

antiphospholipid antibodies, cold agglutinins, or cryoglobulins and is

associated with anorexia nervosa and postural 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

(Fig. 281-3C). 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. The mottling typically is symmetric and uniform

and may be more prominent after cold exposure and improve with

warming. 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 above), SLE and other vasculitides, antiphospholipid antibodies,

hyperviscosity, cryoglobulinemia, and Sneddon’s syndrome (ischemic

stroke and livedo reticularis). Livedo racemosa is the term used to

characterize secondary livedo reticularis, when the mottling is irregular and disrupted, and does not improve with warming. 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 most

commonly on the toes or fingers in cold weather (Fig. 281-3D). 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 (Fig. 281-3E). 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.

Mutations in the SCN9A gene, which encodes the Nav1.7 voltagegated sodium channel expressed in sensory and sympathetic nerves,

have been described in inherited forms of erythromelalgia. 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 because the peripheral pulses are present.

There is no specific treatment; aspirin may produce relief in patients

with erythromelalgia secondary to myeloproliferative disease. Topical

anesthetics may be considered to relieve pain. 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