Clinical features and diagnosis of lower extremity peripheral artery disease

Authors: David G Neschis, MDMichael A Golden, MDSection Editors: John F Eidt, MDJoseph L Mills, Sr, MDDenis L
Clement, MD, PhDDeputy Editor: Kathryn A Collins, MD, PhD, FACS

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Mar 2019. | This topic last updated: Jun 11, 2018.

INTRODUCTION

Peripheral artery disease (PAD), specifically atherosclerotic disease leading to peripheral artery obstruction, may be
silent or present with a variety of symptoms and signs indicative of extremity ischemia. The clinical manifestations of
arterial insufficiency (regardless of etiology) are due to a lack of blood flow to the musculature relative to its
metabolism, which results in pain in the affected muscle groups. The presence of an extremity ulcer is one of the more
obvious clinical signs that can be due to ischemia, but other manifestations, such as claudication and rest pain, should be
actively sought out and differentiated from nonatherosclerotic and nonvascular conditions to ensure timely referral to a
vascular specialist, when indicated. Ideally, a multidisciplinary approach involving the primary care provider, medical
specialists, podiatrist, vascular specialist (interventionalist and/or surgeon), and plastic surgery provides optimal medical
and surgical care. PAD is a treatable condition. When recognized early and appropriately managed, complications that
can lead to limb loss can be minimized.

The clinical features and diagnosis of lower extremity PAD are reviewed here. The epidemiology, risk factors, and natural
history of PAD, as well as the medical and surgical treatment of PAD, are discussed elsewhere. (See "Epidemiology, risk
factors, and natural history of peripheral artery disease" and "Surgical management of claudication" and "Percutaneous
interventional procedures in the patient with lower extremity claudication".)

The majority of patients with PAD have atherosclerotic disease of the lower extremity. Atherosclerotic PAD of the upper
extremity is much less common and is discussed elsewhere. (See "Overview of upper extremity peripheral artery
disease".)

PERIPHERAL ARTERY DISEASE

Many pathologic processes can cause arterial obstruction leading to symptoms of arterial insufficiency because of
reduced blood flow. In this topic, we focus on atherosclerosis as a cause of progressive narrowing of the lower extremity
arteries, or as a source of atheroembolization.

Variable terminology has been used to refer to arterial disease that is due to atherosclerosis. Older terms include
arteriosclerotic disease and peripheral artery occlusive disease. In many resources, the term peripheral artery disease
(PAD) is regarded as a general term encompassing a range of noncoronary arterial syndromes caused by the altered
structure and function of the aorta and peripheral arteries due to numerous pathophysiological processes [1-3]. We
regard the term PAD as denoting arterial disease affecting the peripheral (noncoronary) vasculature due to
atherosclerosis, distinguishing PAD from other processes, which are given below and discussed in separate topic
reviews. (See 'Other causes of arterial obstruction' below.)
Epidemiology and risk factors — Risk factors for PAD are similar to those that promote the development of coronary
atherosclerosis. (See "Overview of established risk factors for cardiovascular disease" and "Overview of possible risk
factors for cardiovascular disease".)

The American College of Cardiology/American Heart Association (ACC/AHA) guidelines on PAD identified the following
groups with a higher prevalence of PAD [1]:

●Age ≥70 years

●Age 50 to 69 years with a history of smoking or diabetes

●Age 40 to 49 with diabetes and at least one other risk factor for atherosclerosis

●Leg symptoms suggestive of claudication with exertion, or ischemic pain at rest

●Abnormal lower extremity pulse examination

●Known atherosclerosis at other sites (eg, coronary, carotid, renal artery disease)

Other risk factors include male gender, black ethnicity, a family history of atherosclerosis, smoking, hypertension,
hyperlipidemia, and homocysteinemia. These risk factors and those listed above are discussed in detail elsewhere. (See
"Epidemiology, risk factors, and natural history of peripheral artery disease".)

CLINICAL PRESENTATIONS

Patients with PAD often have no complaints. However, if the supply of blood fails to satisfy ongoing metabolic
requirements as a consequence of arterial narrowing, symptoms will occur, the severity of which depends upon the
degree of arterial narrowing, number of arteries affected, and the activity level of the patients. PAD can present with
pain of one or more lower extremity muscle groups related to activity (ie, intermittent claudication), atypical pain, pain
at rest, or with nonhealing wounds, ulceration, or gangrene. (See 'Symptoms' below.)

The 2005 American College of Cardiology/American Heart Association (ACC/AHA) guidelines on PAD suggested the
following distribution of clinical presentation of PAD in patients ≥50 years of age [1,3]:

●Asymptomatic – 20 to 50 percent

●Atypical leg pain – 40 to 50 percent

●Classic claudication – 10 to 35 percent

●Threatened limb – 1 to 2 percent

Asymptomatic patients screened for PAD — Patients with peripheral artery disease may be diagnosed based upon
screening (algorithm 1). Recommendations for screening are discussed elsewhere. (See "Screening for lower extremity
peripheral artery disease".)
Screening identifies PAD by lower extremity examination and/or measurement of the ankle-brachial index (ABI). (See
'Diagnosis of lower extremity PAD' below.)

Detection of asymptomatic PAD has value because it identifies patients at increased risk of atherosclerosis at other sites.
Patients with asymptomatic PAD identified on screening also benefit from medical therapies (eg, aspirin, lipid lowering,
blood pressure control, smoking cessation) that reduce their risk for myocardial infarction (MI), stroke, and death. (See
"Overview of the prevention of cardiovascular disease events in those with established disease (secondary prevention)
or at high risk".)

Intermittent claudication and atypical lower extremity pain — most symptomatic patients with PAD present with lower
extremity pain, either as classic intermittent claudication or atypical leg pain. Intermittent claudication (derived from the
Latin word for limp) is defined as a reproducible discomfort of a defined group of muscles that is induced by exercise and
relieved with rest. Although the supply of blood may be adequate to meet the demands of inactive muscle, a mismatch
develops between the supply of blood and increased demand induced by activity. This mismatch may also lead to
atypical lower extremity pain. (See 'Claudication' below and 'Atypical extremity pain' below.)

Atypical symptoms may be more common than classic claudication due to comorbidities, physical inactivity, and
alterations in pain perception [4-6]. A low rate of classic claudication was noted in the report from the PARTNERS
program, in which 6417 patients were at risk for PAD (either age ≥70 or age 50 to 69 with a history of diabetes or more
than 10 pack-years of cigarette smoking) in a primary care setting [4]. PAD, identified by the ABI or by history, was
present in 29 percent:

●Among the patients with a new diagnosis of PAD, approximately 47 percent had no history of leg symptoms, 47
percent had atypical leg symptoms, and only 6 percent had classic claudication.

●Among the patients with known prior PAD, approximately 25 percent had no leg symptoms, 61 percent had atypical leg
symptoms, and 14 percent had classic claudication.

Threatened limb — Patients with PAD can present initially with a threatened limb (critical limb ischemia). It has been
estimated that 1 to 2 percent of patients with PAD who are 50 years of age or older present in this manner [1, 3]. Limb
threat is part of a broad disease spectrum, of which perfusion is one determinant of outcome. Other important factors
include the extent and severity of any wounds, and the presence and severity of infection. (See 'Ulceration' below and
'Gangrene' below.)

Ischemia sufficient to threaten a limb occurs when arterial blood flow is insufficient to meet the metabolic demands of
resting muscle or tissue. Patients may present with varying degrees of tissue loss or frankly gangrenous digits, forefoot,
or hindfoot.

According to the 2007 Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II), limb
ischemia that manifests as a sudden decrease in limb perfusion presenting within two weeks of the inciting event is
defined as acute [7]. Patients with similar manifestations who present more than two weeks later are considered to
have chronic ischemia.

Although acute limb ischemia sufficient to threaten the lower extremity is more commonly due to thromboembolism
(eg, atrial fibrillation), it can be due to a sudden thrombotic occlusion of a narrowed arterial segment, occlusion from
atheroembolic debris shed from a more proximal location, or occlusion due to arterial dissection. In patients who have
undergone prior intervention for PAD, acute limb ischemia may be due to stent or bypass graft thrombosis. Acute limb
ischemia can be stratified by symptoms (eg, pain, paresthesias) and physical findings (eg, severely diminished or absent
pulses, coolness), which help to determine treatment (table 1). The clinical manifestations, diagnosis, and treatment of
acute limb ischemia are discussed in detail elsewhere. (See "Clinical features and diagnosis of acute lower extremity
ischemia".)

Chronic ischemia sufficient to threaten the limb is often the result of arterial stenoses or occlusions that affect more
than one level of the arterial tree; however, isolated tibial vessel disease frequently threatens the viability of the lower
extremity in patients with diabetes, and in the elderly. This most often involves the aortoiliac and femoropopliteal
segments, or femoropopliteal and tibial segments [3]. Multiple levels of disease promote severe ischemia by reducing
the effectiveness of collateral flow and by lowering distal systolic pressures that drive tissue perfusion. The major
manifestations of chronic ischemia are rest pain, ischemic ulceration, and gangrene. (See 'Ischemic rest pain' below and
'Ulceration' below and 'Gangrene' below.)

CLINICAL FEATURES

History — the prevalence of PAD increases progressively with age, beginning after age 40. As a result, PAD is growing as
a clinical problem due to the aging population in the United States and other developed countries. As such, a standard
review during the examination of older patients should always include questions related to a history of walking
impairment, extremity pain that might be due to ischemia, and the presence of nonhealing wounds [1].

Specific questions include:

●Does the patient have any pain with ambulation? If so, how far can the patient walk before the pain occurs? Does the
pain cause the patient to stop walking? If so, after how much time is the patient able to resume walking? Does the pain
recur after a similar walking distance? Has the patient's ability to walk diminished over time or altered the patient's
lifestyle in any way?

●Does the patient experience any pain in the extremity that wakens them from sleep? If so, where is the pain located? Is
the pain relieved once the foot is hung over the side of the bed? Does pain cause the patient to sleep sitting in a chair?

●Has the patient noticed any nonhealing wounds or ulcers on the toes? If so, how long have the wounds or ulcers been
present? If wounds have occurred in the past, what measures were used to promote healing?

●Is the patient known to have PAD? If so, has the patient undergone any prior interventions to manage PAD, or other
arterial disease?
Patients with risk factors for PAD who report no or few symptoms should be asked about functional capacity and decline
in activity over time. Several questionnaires estimating walking ability, functional capacity, and the psychosocial effects
of PAD are available [8-16]. Although useful for quantifying data and following patients participating in clinical studies,
these have limited use in routine clinical practice.

Symptoms

Lower extremity pain — Lower extremity pain is the predominant symptom in patients with PAD and is due to varying
degrees of ischemia. Patients with PAD may complain of pain in the calf, thigh, or buttock brought on with activity and
relieved with rest (ie, intermittent claudication), atypical leg pain, or constant pain in the forefoot aggravated by
elevation and relieved by dependency (ie, rest pain). Less commonly, patients may present with diffuse, severe lower
extremity pain as a manifestation of acute extremity ischemia.

Claudication — Pain within a defined group of muscles that is induced by exercise and relieved with rest defines classic
intermittent claudication (derived from the Latin word for limp). The severity of claudication symptoms reported by the
patient depends upon the degree of stenosis, the effectiveness of collateral vascular channels, and the vigor of exercise.
The perception of claudication can range from a bothersome discomfort of little consequence to a severe, debilitating
pain that becomes lifestyle limiting [17]. A classification of PAD disease severity is presented elsewhere. (See
"Classification of acute and chronic lower extremity ischemia", section on 'Symptom classification'.)

Classic symptoms of claudication manifest as exertional leg pain that begins after a certain walking distance, causes the
patient to stop walking, and resolves within 10 minutes of rest, allowing the patient to resume walking again, typically
for the same distance after which the pain recurs. Claudication can present unilaterally or bilaterally, as buttock and hip,
thigh, calf, or foot pain, singly or in combination. The usual relationships between pain location and corresponding
anatomic site of PAD are as follows:

●Buttock and hip claudication – Patients with aortoiliac disease may complain of buttock, hip, and, in some cases, thigh
claudication. The pain is often described as aching in nature and may be associated with weakness of the hip or thigh
with walking. Pulses in one or both groins are diminished. Bilateral aortoiliac PAD that is severe enough to cause lower
extremity symptoms almost always causes erectile dysfunction in men. Leriche syndrome is the triad of claudication,
absent or diminished femoral pulses, and erectile dysfunction [18,19].

●Thigh claudication – Atherosclerotic occlusion of the common femoral artery may induce claudication in the thigh, calf,
or both. Patients with disease isolated to the superficial femoral or popliteal arteries have normal groin pulses but
decreased pulses distally.

●Calf claudication – Calf claudication is the most common complaint. It is usually described as escalating pain that is
consistently reproduced with exercise and relieved with rest. Pain in the upper two-thirds of the calf is usually due to
superficial femoral artery stenosis, whereas pain in the lower third of the calf is due to popliteal disease.

●Foot claudication – Claudication of the foot is usually accompanied by occlusive disease of the tibial and peroneal
vessels. Isolated foot claudication is uncommon with PAD.
Atypical extremity pain — Among patients diagnosed with PAD, reports of atypical symptoms may be more common
than classic claudication given comorbidities, physical inactivity, and alterations in pain perception [4-6]. In patients with
multiple medical comorbidities, it is sometimes difficult to separate the contributions to extremity pain by arthritis,
neuropathy, spinal stenosis, fibromyalgia, statin-induced myalgia, and other entities from those of PAD. Extremity pain
due to PAD has its genesis in the muscles and typical or atypical should follow an exercise-induced and rest-relieving
pattern of onset and resolution with a repeatable cycle. Nevertheless, before attributing atypical symptoms to PAD,
other lower extremity disorders must be considered [4,5,7]. (See 'Nonarterial etiologies for limb pain' below.)

Ischemic rest pain — A severe decrease in limb perfusion can result in ischemic rest pain due to diffuse pedal ischemia.
Ischemic rest pain is typically localized in the forefoot and toes and is not readily controlled by analgesics. Ischemic rest
pain is brought on, or made worse by, elevation of the lower extremity, and is often worse when the patient reclines
[20]. The pain can also be felt more proximally, but when this occurs, the pain usually does not spare the foot. Pain can
be more localized in patients who develop an ischemic ulcer or gangrenous digits. (See 'Nonhealing wound/ulcer' below
and 'Skin discoloration/gangrene' below.)

Affected patients frequently find that the pain is relieved by hanging their feet over the edge of the bed, or,
paradoxically (in contrast to claudication), by walking around the room because of the gravitational effect of
dependence on extremity perfusion.

Chronic reductions in extremity blood flow can also lead to a superimposed ischemic neuropathic pain that is frequently
described as throbbing or burning, and/or severe shooting pains in the limb. In patients with diabetes, differentiating
diabetic neuropathy from combined diabetic ischemic neuropathy can be difficult. (See "Evaluation of the diabetic
foot".)

Severe diffuse pain — Diffuse acute limb ischemia is characterized by the sudden onset of extremity pain progressing to
numbness and finally paralysis of the extremity, accompanied by pallor, paresthesias, coolness, and absence of palpable
pulses. In patients with PAD, diffuse ischemia can be due to atheroembolism, thrombotic occlusion of a stenotic artery,
or thrombosis of a vascular prior stent or vascular reconstruction [21].

Nonhealing wound/ulcer — Ischemic ulcers often begin as minor traumatic wounds and then fail to heal because the
blood supply is insufficient to meet the increased demands of the healing tissue (picture 1) [21]. Ischemic ulcers, which
most often involve the foot, can become infected and may lead to osteomyelitis. In patients who are bedbound, lower
extremity pressure ulcers can develop, and fail to heal with standard therapies. In patients with diabetes, nonhealing
ulcers can develop over points of bony pressure. The general assessment of wounds and special considerations for
pressure ulcers and diabetic ulcers are discussed in detail elsewhere. (See "Clinical assessment of chronic wounds" and
"Epidemiology, pathogenesis, and risk assessment of pressure-induced skin and soft tissue injury" and "Evaluation of the
diabetic foot".)

Skin discoloration/gangrene — Extremity ischemia alters the appearance of the skin. Patients may notice focal areas of
discoloration or skin color changes when their foot is elevated (pale or white) or lowered (redness). If the blood supply
falls below what is necessary to meet minimal metabolic requirements, focal areas of ischemia that begin as skin
discoloration can progress to full-thickness skin necrosis, which can progress into the deeper tissues (picture 2) [21].

The blue toe syndrome (picture 3), usually due to embolic occlusion of digital arteries with atheroembolic material from
a proximal arterial source, may progress to a nonhealing ulcer or focal areas of gangrene if severe PAD is present. (See
"Embolism from atherosclerotic plaque: Atheroembolism (cholesterol crystal embolism)".)

Physical examination — Individuals with risk factors and those with symptoms suspicious for PAD (eg, claudication, rest
pain, ulcer, gangrene) should undergo cardiovascular assessment. (See 'Epidemiology and risk factors' above.)

The patient's vital signs should be recorded and abnormalities noted. The patient's temperature and blood pressure in
each upper extremity should be documented and the higher of the two noted for ankle-brachial index calculation. Fever
may indicate the presence of an infected ulcer, and the presence of tachycardia and tachypnea may support the
diagnosis of a deep space infection of the foot that may not be readily apparent on physical examination.

The vascular examination is best performed with the patient supine on the examination table and should be performed
only after the patient has rested for at least 15 minutes and has warmed up if coming indoors from cold weather.
Patients with advanced ischemia who do not tolerate having their feet elevated can be briefly placed supine to examine
the abdomen and femoral vessels and thereafter seated upright to perform the remainder of the examination. The
examination should include inspection of the skin of the extremities, examination of the abdomen, palpation of all
peripheral pulses, auscultation for bruits, and extremity neurologic examination.

The vascular examination in patients with PAD commonly reveals diminished or absent pulses below the level of arterial
stenosis with occasional bruits over stenotic lesions and evidence of poor wound healing in the area of diminished
perfusion [22,23]. Other physical findings may include an abnormal body habitus, skin color and nail changes, and
abnormal venous filling time [22]. These physical signs help determine the extent and distribution of vascular disease.

Extremity appearance — Changes in extremity appearance depend on the duration and severity of PAD. With
significantly diminished blood flow, the skin becomes thin with functional loss of the dermal appendages, which is
evident as dry, shiny, and hairless skin. However, one study found that a lack of lower extremity hair is not a predictor of
PAD [24]. The nails may become brittle, hypertrophic, and ridged. Comparison of color and trophic changes between
extremities can give a good indication of the severity of PAD unless bilateral disease is present, in which case the
appearance of the extremities may approximate each other, and experience of the examiner is required to judge the
severity.

Skin temperature and color — The color of the skin is produced by blood in the subpapillary layer and varies with
temperature of the skin, position of the extremity, and degree of blood oxygenation (reduced hemoglobin appears
blue).
Skin temperature is an indicator of the blood flow rate in the dermal vessels, though flow is governed primarily by
constriction or dilation of the arterioles to maintain a constant core temperature. The temperature of the skin as a
marker of perfusion is useful and can be assessed by lightly palpating the skin with the back of the hand and comparing
similar sites from one extremity to the other. An ischemic limb is cool, and demarcation of temperature gives a rough
indication of the level of the occlusion. Assessment of temperature differences is confounded when both extremities are
affected.

The Buerger test involves first elevating the foot with the patient in the supine position and waiting until the veins have
completely drained, and then placing the foot in a dependent position [25]. Elevation of the extremity above the level of
the central venous pressure (rarely greater than 25 cm) permits the pooled venous blood to drain, allowing an accurate
assessment of the degree of arterial flow [26]. The time of return of blood to the dependent extremity is a useful marker
of the severity of disease (normally <20 seconds).

●The normal extremity will remain pink with elevation.

●Patients with significant PAD will have foot pallor with elevation, and, in the dependent position, a dusky flush will
occur spreading proximally from the toes. The color can be rubrous or cyanotic depending on skin temperature.

●In patients with chronic arterial occlusion, the arterioles are maximally dilated as a compensatory response to the
chronic ischemia, which intensifies skin color changes.

●It is important to differentiate the rubor associated with arterial insufficiency from cellulitis accompanying an infective
process. A red, cellulitic appearance will persist despite extremity elevation.

●In patients with acute arterial occlusion, the venules empty, leading to a chalky white skin appearance regardless of
extremity position.

Ulceration — Extremity ulcerations have a characteristic appearance depending upon their origin (table 2). Ulcerations
caused by ischemia are typically located at the termination of arterial branches. They are commonly found on the tips of
the toes and between the digits. Ischemic ulcers also form at sites of increased focal pressure, such as the lateral
malleolus and metatarsal heads. The lesions often appear dry and punched out and are painful, but exhibit little
bleeding. Ischemic ulcers are usually associated with the other clinical features of chronic ischemia, including pallor, hair
loss, and nail changes, as discussed above.

Some patients have combined arterial and venous disease and manifest signs of both arterial and venous insufficiency,
including ulcers with a mixed etiology. Similarly, patients with diabetes can have arterial disease and peripheral
neuropathy, each of which can contribute to ulcer formation. (See 'Nonarterial etiologies for ulceration' below.)

Gangrene — In addition to ulcers, patients can have a frankly gangrenous digit(s), forefoot, or hindfoot. Gangrene can be
described as either dry or wet. Dry gangrene is characterized by a hard, dry texture, usually occurring in the distal
aspects of toes and fingers, often with a clear demarcation between viable and black, necrotic tissue. This form of
gangrene is common in patients with PAD. Wet gangrene is characterized by its moist appearance, gross swelling, and
blistering [27]. Wet gangrene represents a surgical emergency, and appropriate consultation should be made when
identified.
Pulses — The assessment of pulses of the patient with suspected PAD should include palpation of the brachial, radial,
femoral, popliteal, dorsalis pedis, and posterior tibial arteries. The normal popliteal artery is often unable to be easily
palpated but can usually be identified with Doppler. Assessment for bruits with a stethoscope should also be undertaken
over the iliac arteries. The inability to easily palpate a given vessel should lead to interrogation with a handheld
continuous wave Doppler ultrasound. (See "Noninvasive diagnosis of arterial disease", section on 'Continuous wave
Doppler'.)

Bedside ABI — The resting ankle-brachial systolic pressure index (ABI) is a simple test that can be performed at the
bedside and should be measured in patients with one or more findings consistent with PAD on the review of symptoms
or other findings on physical exam. The ABI is the ratio of the ankle systolic blood pressure divided by the brachial
systolic pressure detected with a Doppler probe. In patients with no or mild to moderate symptoms, an ABI of <0.90 has
a high degree of sensitivity and specificity for PAD, using arteriography as the reference standard [7]. Techniques for
performing the ABI are discussed separately. (See "Noninvasive diagnosis of arterial disease", section on 'Ankle-brachial
index'.)

An attempt can be made to obtain an ABI in patients with more severe ischemia at the bedside; however, the patient
may not tolerate inflation of the blood pressure cuff on the affected extremity, and Doppler signals in the pedal vessels
may be too weak to accurately gauge cut-off pressures. (See 'Site and severity of PAD' below.)

Neurologic assessment — Lower extremity neurologic examination is important and should include motor and sensory
testing. In the patient with acute limb ischemia, sensory loss and progressive lower extremity motor loss are ominous
signs indicating the need for prompt intervention. Patients with acute arterial or graft thrombosis superimposed upon
chronic ischemia may be more tolerant depending on the effectiveness of collateral vessels.

Chronic ischemia can cause varying patterns of sensory loss, progressing from distal to proximal as the severity of
ischemia worsens. Diabetic patients may have a superimposed sensory neuropathy, which is typically in a glove-and-
stocking distribution and reduced vibration sense and two-point discrimination. The use of monofilament gauges
(Semmel-Weinstein) is a good objective way to assess for diabetic neuropathy. (See "Evaluation of the diabetic foot",
section on 'Screening tests for peripheral neuropathy'.)

Laboratory studies — There is no specific biomarker for PAD. Routine laboratory studies include complete blood count
with differential, metabolic panel, lipid profile, and, possibly, homocysteine, lipoprotein A, and C-reactive protein. (See
"Overview of established risk factors for cardiovascular disease", section on 'Inflammatory markers' and "Overview of
possible risk factors for cardiovascular disease", section on 'Circulating serum or plasma markers'.)

Plain radiographs — Plain films of the lower extremity may demonstrate arterial calcification in locations consistent with
PAD, such as at arterial branch points (image 1), or along the mid to distal thigh along the course of the superficial
femoral artery (image 2A-B), or distally in the distribution of the tibial vessels.

DIAGNOSIS OF LOWER EXTREMITY PAD

For many patients, a history of risk factors or symptoms of PAD, in combination with physical examination findings, is
sufficient to establish a diagnosis of PAD. For patients with atypical symptoms, or a pulse examination that is equivocal,
the ankle-brachial index (with or without exercise) is diagnostic for PAD if ≤0.9. (See 'Abnormal ankle-brachial index'
below.)
Abnormal arterial examination/tissue loss — For patients with risk factors for PAD and without a history of symptoms to
suggest an alternative vascular process (eg, abdominal or back pain as with aortic dissection), the presence of obvious
abnormalities in the pulse examination, rest pain, or tissue loss strongly suggests the presence of PAD (algorithm 2). A
systematic review comparing clinical signs of PAD with ankle-brachial systolic pressure index (ABI), duplex ultrasound, or
arteriography found that the presence of any bruit or pulse abnormality significantly increased the likelihood of PAD
[23].

Abnormal ankle-brachial index — Although the history, symptoms, physical examination, and bedside ABI can strongly
suggest a diagnosis of PAD, these are frequently not specific or sensitive enough to accurately localize the site(s) or
judge the severity of disease. Depending upon the clinical presentation, formal ABI testing or additional studies may be
indicated (algorithm 2). These may include other physiologic tests in a vascular laboratory (treadmill exercise testing,
segmental pressures, or pulse volume recordings) or vascular imaging. (See 'Site and severity of PAD' below.)

●For patients with risk factors for PAD and exertional leg symptoms (claudication, atypical pain), we suggest formal
vascular laboratory testing to confirm the diagnosis. Some of these patients may benefit from exercise testing,
particularly if the diagnosis is uncertain.

●For patients with risk factors for PAD and exertional leg symptoms (claudication, atypical pain), but with a normal
examination or bedside ABI (or ABI not performed), we suggest exercise testing to provide diagnostic data useful in
differentiating arterial claudication from non-arterial claudication ("pseudoclaudication").

●The need for testing in patients with tissue loss should be individualized. For most patients, we suggest formal vascular
laboratory studies, whenever possible, prior to vascular intervention. Although the patient may not tolerate ankle-
brachial or segmental pressure testing, perfusion assessment can usually be performed, provided the patient does not
require immediate intervention or surgery.

●The indications for screening patients with risk factors but no symptoms for PAD are discussed in detail elsewhere.
Patients who are diagnosed with PAD on the basis of a screening ABI should undergo formal testing to confirm severity
and level of disease. (See "Screening for lower extremity peripheral artery disease".)

An abnormal ankle-brachial index (ABI <0.9) has an excellent overall accuracy for detecting arterial stenosis ≥50 percent
using arteriography as the standard. For most patients with exertional extremity pain (classic claudication, atypical
symptoms), an ABI <0.9 is diagnostic for PAD, particularly in the context of the appropriate history. However, other
nonatherosclerotic disease processes can also lead to arterial occlusion and an abnormal ABI (eg, thrombosed popliteal
aneurysm), and these need to be distinguished from atherosclerosis. (See 'Differential diagnosis of PAD' below.)

There is a general, but not absolute, correlation between symptoms and the site and severity of PAD, with severity being
estimated from the ankle-brachial index [28-30]. (See "Noninvasive diagnosis of arterial disease", section on 'Ankle-
brachial index'.)

●Claudication: 0.4 and 0.9

●Rest pain: 0.2 to 0.4

●Tissue loss (ulcer, gangrene): 0 to 0.4

In a study using a claudication questionnaire for exertional leg pain in 3658 subjects, 24 percent of whom had PAD
(defined as an ABI <0.9) in one or both legs, the following findings were noted [31]:

●At ABIs of 1.00 to 1.09 (normal), 0.80 to 0.89 (just abnormal), and 0.40 to 0.49 (markedly reduced), the proportion of
legs with any leg pain increased progressively from 18 to 61 to 83 percent. Pain was also more common in legs with ABIs
≥1.40, a presumed marker of vascular stiffness due to arterial wall calcification.
●At ABIs of 1.00 to 1.09 (normal), 0.80 to 0.89 (just abnormal), and 0.40 to 0.49 (markedly reduced), the proportion of
legs with classic claudication increased progressively from 2 to 22 to 46 percent. In contrast, atypical pain and non-calf
pain did not show much correlation with the ABI.

●Discordance was noted in some patients between the site of PAD and the site of pain. Patients with unilateral PAD
were more likely to report bilateral rather than unilateral pain (42 versus 29 percent).

Not surprisingly, since PAD is a manifestation of systemic atherosclerosis, a low ABI is also predictive of an increased risk
of all-cause and cardiovascular mortality [32-34], and the development of coronary artery calcification [35]. A high ABI is
also associated with increased cardiovascular risk. (See "Screening for lower extremity peripheral artery disease" and
"Noninvasive diagnosis of arterial disease", section on 'High ABI'.)

Site and severity of PAD

Segmental pressure and pulse volume recordings — Segmental pressures and pulse volume recordings, which are
physiologic studies performed in the vascular laboratory, are useful for confirming a diagnosis of suspected lower
extremity PAD based upon history and physical examination and determining the site and severity of disease. These
studies include formal ankle-brachial index testing and are performed in both legs. Toe pressure/toe-brachial index
measurement is an alternative to the ABI to establish a diagnosis of PAD in patients with noncompressible vessels
(usually patients with long-standing diabetes or advanced age). The performance of these studies and their
interpretation is discussed in detail elsewhere. (See "Noninvasive diagnosis of arterial disease", section on 'Physiologic
testing'.)

Exercise testing — some patients with PAD who have a classic history of claudication, and others with atypical extremity
pain, have a normal resting ABI (0.91 to 1.30). For these patients, exercise testing is indicated. Abnormal exercise ABIs
support a diagnosis of PAD as the etiology of their symptoms (algorithm 2).

The study should be performed in a vascular laboratory using a standardized exercise protocol (fixed or graded) and a
motorized treadmill to ensure reproducibility of measurements of pain-free walking distance and maximal walking
distance. (See "Noninvasive diagnosis of arterial disease", section on 'Exercise testing'.)

Exercise treadmill tests are useful for providing the most objective evidence of the magnitude of the functional
limitation in patients with claudication and can also be used to guide the response to treatment [1].

Vascular imaging — Vascular imaging is not generally necessary for establishing a diagnosis of PAD; however, it may be
indicated to differentiate PAD from other vascular etiologies as a source of arterial obstruction, if PAD as the primary
etiology for the symptoms is in question (eg, arterial aneurysm or thromboembolism is suspected). However, vascular
imaging is necessary to identify appropriate targets for intervention, and for ongoing surveillance following intervention.
Contrast arteriography remains the gold standard for the evaluation of the threatened limb. A complete, bilateral study
of the aorta, iliac, femoral, popliteal, and run-off vessels should be performed in patients who are expected to undergo
revascularization, provided there are no contraindications. (See "Noninvasive diagnosis of arterial disease", section on
'Advanced imaging' and "Noninvasive diagnosis of arterial disease", section on 'Duplex imaging'.)

DIFFERENTIAL DIAGNOSIS OF PAD

Other causes of arterial obstruction — Any vascular disease that results in arterial stenosis or occlusion can cause
symptoms of extremity pain or tissue loss. These include arterial thrombosis due to aneurysm, arterial injury, arterial
dissection, or thromboembolism. Other causes are listed in the table (table 3). Lower extremity arterial imaging
differentiates many of these etiologies from each other.

●Arterial aneurysm – The popliteal artery is the most common site of a peripheral artery aneurysm that causes
symptoms of lower extremity ischemia, which is due to aneurysm thrombosis [36]. The presence of a peripheral
aneurysm should prompt evaluation for other aneurysms [37]. The clinical evaluation of aneurysmal disease is discussed
in detail elsewhere. (See "Popliteal artery aneurysm" and "Iliac artery aneurysm" and "Clinical features and diagnosis of
abdominal aortic aneurysm".)

●Arterial dissection – Arterial dissection can lead to lower extremity ischemia; however, acute dissection is typically
accompanied by sudden, focal pain overlying the affected artery. For aortic dissection, the pain often begins in the chest,
traveling to the abdomen or pelvis as the dissection progresses. Following instrumentation, focal areas of dissection can
occur in the region of arterial access. The history of preceding pain or a prior interventional procedure distinguishes
these from PAD; however, PAD may be superimposed. (See "Clinical features and diagnosis of acute aortic dissection".)

●Embolism – Debris from proximal sources can embolize distally to the toes or more proximally, causing acute limb
ischemia. The more acute time course of symptoms generally distinguishes these patients from patients with PAD. (See
"Embolism from aortic plaque: Thromboembolism" and "Embolism from atherosclerotic plaque: Atheroembolism
(cholesterol crystal embolism)" and "Clinical features and diagnosis of acute lower extremity ischemia".)

●Popliteal entrapment syndrome – Popliteal entrapment syndrome can also present with intermittent claudication and
should be suspected in the young patient who presents with claudication but lacks atherosclerotic risk factors. Popliteal
entrapment syndrome, which is due to anomalous musculoskeletal attachments or an abnormal course of the popliteal
artery, leads to compression of the popliteal artery with activity.

●Adventitial cystic disease – Adventitial cystic disease is a rare entity that can lead to arterial obstruction related to
mucoid degeneration of the artery. When it occurs in the femoral or popliteal artery, claudication symptoms are
indistinguishable from atherosclerotic popliteal disease [38,39]. Patients tend to be younger, and typical risk factors for
cardiovascular disease are often absent [40].

●Thromboangiitis obliterans (Buerger's disease) – Thromboangiitis obliterans, also called Buerger's disease, is a
nonatherosclerotic, segmental, inflammatory disease that most commonly affects the small to medium-sized arteries
and veins of the extremities. Patients are younger than the typical patients with atherosclerotic vascular disease and are
heavy smokers. Digit ischemia is the most common presentation, and although larger artery involvement is uncommon,
claudication can occur but is nearly always associated with signs of distal ischemia. (See "Thromboangiitis obliterans
(Buerger's disease)".)

●Other vascular disorders – Other vascular etiologies that can lead to lower extremity ischemia include limb trauma,
radiation arteritis, vasculitis, or ergot use for migraines. In endurance athletes, especially cyclists, an even more unusual
cause of claudication is due to repeated trauma (stretching or kinking) of the external iliac artery, which can result in
endofibrosis of the vessel [41]. (See "Severe extremity injury in the adult patient".)

Nonarterial etiologies for limb pain — The etiology of extremity pain can be divided into categories that include vascular
(arterial or venous), neurogenic, and musculoskeletal causes. Arterial causes are discussed in the preceding section.
Nonarterial pathologic conditions should also be considered in the differential diagnosis of limb pain. The major clinical
features that distinguish these disorders from arterial claudication are given in the table (table 4).

●Neurologic pain is predominantly due to neurospinal (eg, disc disease, spinal stenosis, tumor) or neuropathic causes
(eg, diabetes, alcohol abuse). Neurogenic claudication, also called "spinal claudication" or "pseudoclaudication,"
describes a pain syndrome due to lumbar neurospinal canal compression, which is usually due to osteophytic narrowing
of the neurospinal canal. The clinical presentation often helps to distinguish vasculogenic (ie, true) claudication from
pseudoclaudication. Unlike true claudication, which occurs with walking and is relieved by stopping, pseudoclaudication
causes pain with erect posture (lumbar lordosis) and is relieved by sitting or lying down. Symptoms in patients with
pseudoclaudication may also be relieved by leaning forward and straightening the spine (usually done with pushing a
shopping cart or leaning against a wall). (See "Lumbar spinal stenosis: Pathophysiology, clinical features, and diagnosis".)

●Musculoskeletal pain derives from the bones, joints, ligaments, tendons, and fascial elements of the lower extremity.

•Osteoarthritis of the hip or knee joints can be distinguished clinically from aortoiliac disease because osteoarthritic pain
may not disappear promptly after exercise, may be associated with weather changes, and may vary in intensity from day
to day (usually worse in the morning or upon wakening).

•Nocturnal leg cramps occur among older and infirmed patients and, unlike claudication, are not associated with
exercise. This complaint is thought to be neuromuscular rather than vascular in origin. (See "Nocturnal leg cramps".)

•Calf pressure and tightness is a complaint primarily seen in athletes and is usually associated with chronic exercise. It is
thought to be due to increased compartment pressure and may persist even after rest. (See "Chronic exertional
compartment syndrome".)

●Chronic venous disease can cause "venous claudication" but is usually easily distinguished from arterial claudication by
a variable degree of limb swelling, or varicosities, and increased discomfort with limb dependency. (See "Clinical
manifestations of lower extremity chronic venous disease".)

Nonarterial etiologies for ulceration — Ischemic ulcers need to be distinguished from ulcers associated with venous
insufficiency and peripheral neuropathy, which are the other major causes of foot and leg ulcers (table 2). The
differentiation of these etiologies is important since their pathophysiology, and thus management, differs. The
differentiation of ischemic ulcers from venous ulcers, pressure ulcers, neuropathic ulcers, malignant ulcers, and
hypertensive ulcers is presented elsewhere. (See "Clinical assessment of chronic wounds", section on 'Differentiation of
chronic ulcers'.)
CLASSIFICATION OF DISEASE

Classification of chronic lower extremity PAD is based upon the severity of symptoms and markers for severe, chronic
disease, such as ulceration and gangrene. The various classifications including the Rutherford, Fontaine (table 5), and
WIfI systems are discussed in detail elsewhere [7,42]. (See "Classification of acute and chronic lower extremity
ischemia", section on 'Rutherford' and "Classification of acute and chronic lower extremity ischemia", section on
'Fontaine' and "Classification of acute and chronic lower extremity ischemia", section on 'WIfI (Wound, Ischemia, foot
Infection)'.)

SUMMARY AND RECOMMENDATIONS

●The prevalence of peripheral artery disease (PAD) increases progressively with age, beginning after age 40. As a result,
PAD is growing as a clinical problem due to the aging population in the United States and other developed countries.
Risk factors for PAD are similar to those that promote the development of coronary atherosclerosis (ie, hyperlipidemia,
smoking, hypertension, diabetes). (See 'Epidemiology and risk factors' above.)

●A standard review during the examination of older patients should always include questions related to a history of
walking impairment, extremity pain that might be due to ischemia, and the presence of nonhealing wounds. Patients
with risk factors for PAD who report no or few symptoms should be asked about functional capacity and decline in
activity over time. (See 'History' above.)

●Patients with compromised blood flow to the extremities as a consequence of arterial stenosis due to PAD may present
with pain of one or more muscle groups, atypical pain, or no symptoms. Intermittent claudication (derived from the
Latin word for limp) is defined as a reproducible discomfort of a defined group of muscles that is induced by exercise and
relieved with rest. This disorder results from an imbalance between supply and demand of blood flow that fails to satisfy
ongoing metabolic requirements. (See 'Clinical presentations' above.)

●Classic claudication is characterized by leg pain that is consistently reproduced with exercise and relieved with rest. The
degree of symptoms of claudication depends upon the severity of stenosis, the collateral circulation, and the vigor of
exercise. Patients with claudication can present with buttock, hip, thigh, calf, or foot pain, alone or in combination. The
usual relationships between pain location and corresponding anatomic site of arterial occlusive disease can be
summarized as follows (see 'Claudication' above):

•Buttock and hip: Aortoiliac disease

•Thigh: Aortoiliac or common femoral artery

•Upper two-thirds of the calf: Superficial femoral artery

•Lower one-third of the calf: Popliteal artery

•Foot claudication: Tibial or peroneal artery

●Severe decreases in limb perfusion can result in ischemic rest pain that involves the digits and forefoot and typically
occurs at night. The pain may be more localized in patients who develop an ischemic ulcer or gangrenous toe. The pain
may be relieved by dependent positioning of the foot. (See 'Ischemic rest pain' above.)

●Some patients with PAD have atypical symptoms as a result of comorbidities, physical inactivity, and alterations in pain
perception. Compared with patients with classic claudication, those with leg pain on exertion and at rest are more likely
to have diabetes, neuropathy, or spinal stenosis in addition to PAD. (See 'Atypical extremity pain' above.)

●To confirm the diagnosis of arterial stenosis or occlusion, which is most commonly due to PAD, the resting ankle-
brachial systolic pressure index (ABI) should be performed in patients with lower extremity exertional symptoms and in
those patients with risk factors for PAD. An ABI of ≤0.90 has a high degree of sensitivity and specificity for a diagnosis of
PAD. (See 'Diagnosis of lower extremity PAD' above.)

●Any process that leads to arterial stenosis or occlusion can cause symptoms of lower extremity ischemia (table 3).
These include arterial aneurysm, arterial dissection, and arterial embolism, among others. Nonarterial pathologic
conditions should also be considered, including neurologic disorders, musculoskeletal disorders, and acute and chronic
venous disease such as deep vein thrombosis and post-thrombotic syndrome. The presenting clinical features should
help distinguish atypical symptoms of PAD from other causes of extremity pain (table 4). (See 'Differential diagnosis of
PAD' above.)

REFERENCES

1. Norgren L, Hiatt WR, Dormandy JA, et al. Inter-Society Consensus for the Management of Peripheral Arterial
Disease (TASC II). J Vasc Surg 2007; 45 Suppl S:S5.

2. Creager MA, Kaufman JA, Conte MS. Clinical practice. Acute limb ischemia. N Engl J Med 2012; 366:2198.

3. Rutherford RB, Baker JD, Ernst C, et al. Recommended standards for reports dealing with lower extremity
ischemia: revised version. J Vasc Surg 1997; 26:517.

4. Gerhard-Herman MD, Gornik HL, Barrett C, et al. 2016 AHA/ACC Guideline on the Management of Patients With
Lower Extremity Peripheral Artery Disease: A Report of the American College of Cardiology/American Heart
Association Task Force on Clinical Practice Guidelines. Circulation 2017; 135:e726.

5. Writing Committee to Develop Clinical Data Standards for Peripheral Atherosclerotic Vascular Disease, Creager
MA, Belkin M, et al. 2012 ACCF/AHA/ACR/SCAI/SIR/STS/SVM/SVN/SVS key data elements and definitions for
peripheral atherosclerotic vascular disease: a report of the American College of Cardiology
Foundation/American Heart Association Task Force on Clinical Data Standards (Writing Committee to Develop
Clinical Data Standards for Peripheral Atherosclerotic Vascular Disease). Circulation 2012; 125:395.

6. Yeager RA, Moneta GL, Taylor LM Jr, et al. Surgical management of severe acute lower extremity ischemia. J
Vasc Surg 1992; 15:385.

7. Kashyap VS, Gilani R, Bena JF, et al. Endovascular therapy for acute limb ischemia. J Vasc Surg 2011; 53:340.

8. Hynes BG, Margey RJ, Ruggiero N 2nd, et al. Endovascular management of acute limb ischemia. Ann Vasc Surg
2012; 26:110.

9. Baril DT, Patel VI, Judelson DR, et al. Outcomes of lower extremity bypass performed for acute limb ischemia. J
Vasc Surg 2013; 58:949.

10. Callum K, Bradbury A. ABC of arterial and venous disease: Acute limb ischaemia. BMJ 2000; 320:764.

11. Crawford JD, Perrone KH, Wong VW, et al. A modern series of acute aortic occlusion. J Vasc Surg 2014; 59:1044.
12. Nasser TK, Mohler ER 3rd, Wilensky RL, Hathaway DR. Peripheral vascular complications following coronary
interventional procedures. Clin Cardiol 1995; 18:609.

13. Messina LM, Brothers TE, Wakefield TW, et al. Clinical characteristics and surgical management of vascular
complications in patients undergoing cardiac catheterization: interventional versus diagnostic procedures. J Vasc
Surg 1991; 13:593.

14. Clagett GP, Sobel M, Jackson MR, et al. Antithrombotic therapy in peripheral arterial occlusive disease: the
Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126:609S.

15. Abbott WM, Maloney RD, McCabe CC, et al. Arterial embolism: a 44 year perspective. Am J Surg 1982; 143:460.

16. Karmody AM, Powers SR, Monaco VJ, Leather RP. "Blue toe" syndrome. An indication for limb salvage surgery.
Arch Surg 1976; 111:1263.

17. Miller S, Causey MW, Schachter D, et al. A case of limb ischemia secondary to paradoxical embolism. Vasc
Endovascular Surg 2010; 44:604.

18. Dao CN, Tobis JM. PFO and paradoxical embolism producing events other than stroke. Catheter Cardiovasc
Interv 2011; 77:903.

19. Hugl B, Klein-Weigel P, Posch L, et al. Peripheral ischemia caused by paradoxical embolization: an
underestimated problem? Mt Sinai J Med 2005; 72:200.

20. Travis JA, Fuller SB, Ligush J Jr, et al. Diagnosis and treatment of paradoxical embolus. J Vasc Surg 2001; 34:860.

21. Herity NA, Dalzell GW. Venous thrombosis causing arterial embolization to the same limb through a patent
foramen ovale. Clin Cardiol 1997; 20:893.

22. Paes EH, Greven T, Heredia D. Paradoxical embolism and aortic occlusion: a case report. Int Angiol 1997; 16:72.

23. AbuRahma AF, Downham L. The role of paradoxical arterial emboli of the extremities. Am J Surg 1996; 172:214.

24. Katzen BT. Clinical diagnosis and prognosis of acute limb ischemia. Rev Cardiovasc Med 2002; 3 Suppl 2:S2.

25. Hirsch AT, Haskal ZJ, Hertzer NR, et al. ACC/AHA 2005 Practice Guidelines for the management of patients with
peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report
from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular
Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology,
and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the
Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of
Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular
Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation. Circulation 2006; 113:e463.