Two classification systems have been developed to help identify and document chronic lower-extremity PAD: the Fontaine staging system and the Rutherford categorizing system. Both classification symptoms address the severity of symptoms and the presence of markers for severe chronic occlusive disease, such as ulceration and gangrene. Fontaine has four main stages, one of which is subdivided into two stages: Stage I (asymptomatic), Stage IIa (mild claudication), Stage IIb (moderate/severe claudication), Stage III (ischemic rest pain), and Stage IV (ulceration or gangrene). Rutherford established seven categories ranging from 0 to 6 (asymptomatic, mild claudication, moderate claudication, severe claudication, rest pain, minor tissue loss, and major tissue loss, respectively; Hirsch et al., 2006).

The physical examination involves inspecting the patient’s body for changes in appearance. Hair growth may be absent over the affected area. The nails may appear thick, yellow, and brittle. Motor function of the affected part may be impaired or absent. The muscles may also appear atrophied from severe nerve and skeletal muscle ischemia. Patients often complain of numbness and tingling in the extremity, as well as an inability to distinguish touch from pressure, pain, and temperature change.

The skin texture may also change with arterial insufficiency. The skin may appear shiny, taut, and thin; scaly and dry from ischemia; or progress to a deep red when the feet are in a dependent position. To assess the degree of arterial insufficiency, a reactive hyperemia test may be performed. This involves raising the legs above the level of the heart until the legs become a cadaveric pale color, followed by placing the patient in a seated position with the legs dependent. If pink coloration does not return within 15 seconds, the circulation is compromised. If the legs turn a deep red before reverting to their normal pink color, significant arterial occlusion is likely present. The skin temperature may vary. It is usually cool from vascular occlusion or vasoconstriction, hindering the blood supply. The best way to assess the temperature is to gently palpate the extremity with the dorsum of the hand.

A thorough patient history and physical assessment can help to distinguish ischemic ulcers caused by arterial disease from other types of ulcers (e.g., venous, pressure, trauma, and vasculitis). Breakdown of the skin may occur with severe ischemia, resulting in ulceration. These ulcers are often found over pressure points such as the heels, toes, bony prominences, the dorsum of the foot, or the metatarsal heads. Ulcers, which cause severe pain, are often symmetrical and without drainage. Mild edema may also be present. Patients experiencing pain at rest may have edema because they keep their legs in a dependent position for pain relief.

Palpating the patient’s pulses provides information about the condition of the arteries. With arterial obstruction, the pulses may be absent or weak. Pulses should be assessed bilaterally for equality and strength using a Doppler stethoscope, if necessary. The physical examination should also include auscultation and evaluation of the blood flow. Normally, no sound is heard over a vessel that is patent. When blood flow becomes turbulent through an obstructed vessel, a blowing sound, or bruit, can be heard. Although the presence of a bruit is not always hemodynamically significant, it often indicates the start of chronic arterial occlusive disease long before symptoms such as cramps and pain appear. It is important in this patient population to check pulses in all regions of the body where major vessels are located, including the carotid, abdominal aorta, iliac, femoral, popliteal, posterior tibial, and dorsalis pedis.

The clinical syndrome most difficult to distinguish from claudication is neurogenic claudication, more typically known as spinal stenosis. The pain characteristic of spinal stenosis is caused by a localized narrowing of the spinal canal from a structural abnormality that results in compression of the cauda equina. With spinal stenosis, the patient usually complains of pain in the lower back or buttock region as well as numbness and tingling in the feet with walking (Katz & Harris, 2008). Differentiation of claudication and spinal stenosis can be determined by the patient’s response to exercise. Symptoms of intermittent claudication are brought on by exercise and relieved with rest. Onset at a given distance of walking can be predicted fairly accurately. Spinal stenosis may also be precipitated by walking, but the distance walked before symptoms appear will vary. Standing may cause discomfort in patients with spinal stenosis, whereas standing relieves pain in intermittent claudication (Katz & Harris, 2008).

Nocturnal muscle cramps may be another symptom that can mimic claudication. However, these cramps are a common complaint and have a tendency to occur in older persons. The cramps are not related to exercise. Tightness and pain in the calf after exercise can affect athletes with chronic compartment syndrome (Twaddle & Amendola, 2008). This syndrome is usually found in young persons, presents after vigorous exercise, and does not quickly subside with rest. Osteoarthritis of the hip may mimic thigh and buttock claudication. However, osteoarthritic pain occurs with variable amounts of exercise. It is relieved after long periods of rest and changes in severity from day to day.

Another differential diagnosis to be considered is Raynaud’s disease, which is an interruption in arterial circulation to the extremities. In Raynaud’s disease, episodic vasospasm produces closure of the small arteries in the distal extremities. This may be elicited by exposure to cold, vibration, or emotional stimuli. About 5% of the U.S. population suffers from Raynaud’s disease. Although it is considered more of an inconvenience than a serious illness, in severe cases, gangrene may threaten tissues. If fingers or toes turn blue in response to even brief changes in temperature just below 60°F, followed by tingling, burning, or numbness, consultation with a primary care provider should be a priority. Diagnosis is difficult because there is no single test to confirm this diagnosis (James, Berger, & Elston, 2011).

The diagnosis of PAD is based on patient history, physical examination, and noninvasive testing. Examples of noninvasive tests that facilitate assessment of arterial disease include segmental limb pressures and the calculation of pressure index values (e.g., ABPI, wrist-brachial index), exercise testing, segmental volume plethysmography, transcutaneous oxygen measurements, and photoplethysmography. Doppler ultrasound, CT scans, and MRI are also valuable tools when assessing vascular disorders. CT scan and MRI are important alternative methods for vascular assessment, but their use for routine testing is limited by time and expense (Hirsch et al., 2006; Mohler & Mitchell, 2012; Rofsky & Adelman, 2000).

Doppler segmental pressures with an ABPI measurement provide information regarding the extent of the disease. Measurement of the ABPI is recommended in patients at high risk of PAD, defined as patients with exertional leg symptoms, nonhealing wounds, age >65 years, or age >50 years with a history of smoking or diabetes (Formosa, Gatt, & Chockalingam, 2012; Rooke et al., 2011). Further diagnostic testing is not recommended in asymptomatic patients.

Doppler segmental pressures are obtained by placing appropriately sized blood-pressure cuffs around the arm and at the proximal thigh, the distal thigh, the proximal calf, and the ankle of the affected leg. The ABPI is calculated by dividing the systolic blood pressure measured in the arterial conduits at the level of the ankle by the systolic blood pressure measured in the brachial artery (Al-Qaisi et al., 2009). The normal range of ABPI is 1.0 to 1.4 (Rooke et al., 2011). An ABPI >1.4 represents a noncompressible vessel. An ABPI of 0.91 to 0.99 is borderline abnormal. An ABPI <0.9 is abnormal, with 0.7 to 0.9 indicating mild disease, 0.41 to 0.69 indicating moderate disease, and a value <0.4 indicating severe disease. Ratios of <0.4 are typically seen in patients who present clinically with symptoms of critical ischemia, as would be associated with nonhealing wounds or pain at rest.

Occasionally, patients have normal ABPIs and segmental pressures at rest, but risk factors indicate an increased risk of PAD or their symptoms strongly suggest claudication. In these patients, segmental pressures and ABPIs should be obtained before and after exercise. For this diagnostic test, the patient may walk or lift the heels repeatedly to elicit a pain response. Exercise may reveal the arterial obstruction, resulting in a significant change from the Doppler segmental pressures and the ABPIs found at rest.

Pulse volume recordings (PVRs) can be obtained by plethysmography to evaluate limb perfusion. Arterial waveforms are recorded at different segments along the limb. The magnitude of the waveform correlates with blood flow; diminished waveforms indicate obstruction in the proximal limb segment. PVRs can be a useful screening tool in patients in whom ABPI shows noncompressible vessels.

Further diagnostic testing is not indicated in asymptomatic patients, and treatment focuses on risk factor reduction to slow disease progression. In patients with symptoms of claudication and abnormal ABPIs and/or PVRs, an imaging study is indicated to determine the location and severity of stenosis.

Contrast angiography is considered the gold standard diagnostic tool for evaluating arterial anatomy and is the test most widely performed prior to an intervention (Hirsch et al., 2006). It helps to reveal the exact location of the arterial obstruction and provides a road map for operative reconstruction. Contrast dye is used to visualize vessel anatomy and determine the degree of stenosis present. Contrast dye is associated with a low incidence of nephrotoxicity, especially in patients with baseline renal dysfunction, diabetes, or low output states. This risk, as well as other risks associated with any invasive procedure (e.g., bleeding, infection, vascular access complications), must be considered prior to ordering this test. Because of these risks, angiography is usually only performed when revascularization is being considered.

Significant advances have been made in duplex ultrasound, CT angiography, and MRI angiography, making these tests viable noninvasive alternatives. Doppler ultrasound is one of the most widely used noninvasive tools in the evaluation of PAD. It can be used to locate lesions, quantify disease severity, and follow the progression of disease. It is also recommended for periodic surveillance after bypass procedures. CT or MRI angiographies are other noninvasive imaging methods to evaluate for the location and severity of disease. An intravenous injection of iodinated contrast dye is given during CT angiography to fill vessels. However, contrast dye may be nephrotoxic in azotemic patients. The accuracy and effectiveness of CT angiography is not as well established as that of MRI angiography. MRI angiography with gadolinium enhancement can be used to visualize vessel anatomy through exposure to magnetic energy sources, without the use of radiation; but it is contraindicated in patients with pacemakers or other metallic implants.

Treatment Options, Expected Outcomes, and Comprehensive Management

The patient with claudication should be referred to a supervised exercise training program with sessions at least 3 days a week for 12 weeks (Hirsch et al., 2006). These exercise programs include an aggressive walking program for approximately 30 to 45 minutes at a pace that elicits claudication. When claudication occurs, the patient should be instructed to walk a little further, stop, wait for the discomfort to pass, and then continue walking. A successful walking program can increase the distance to onset of claudication and help to develop collateral circulation (Gardner, Ritti-Dias, Khurana, & Parker, 2010; Schmidt-Trucksäss, 2011).

Drug therapy for claudication enhances metabolic activity and increases blood flow to the affected muscles. Vasodilating agents have had little effect on patients with claudication. Anti platelet therapy (aspirin 75–325 mg daily) is indicated to reduce the risk of myocardial infarction, stroke, and vascular death in patients with symptomatic PAD or asymptomatic patients with an ABPI ≤0.90 (Rooke et al., 2011). Low-dose aspirin therapy has been correlated with protection from vascular events in patients with severe cardiovascular disease; however, the literature fails to support the same results for those who suffer with PAD or diabetes (Natarajan, Zaman, & Marshall, 2008). This failure is attributed to aspirin resistance in the PAD and diabetic patient population. Studies suggest that, in contrast to aspirin, clopidogrel, a thienopyridine derivative antiplatelet agent, seems to show promise in reduction of vascular events in patients with PAD and diabetes (Angiolillo, 2009). Clopidogrel (75 mg daily) could be considered as an alternative to aspirin for these patients.

Cilostazole, a phosphodiesterase type 3 inhibitor, given at 100 mg twice daily, has both vasodilator and platelet inhibitory properties. Its actual mechanism of action is unknown. It is a generally well-tolerated medication. It has been shown to improve claudication symptoms and increase walking distance by 40% to 60% after 12 to 24 weeks of therapy (Hirsch et al., 2006).

Pentoxifylline, a methylxanthine derivative, alters the structure of the red blood cell, decreases plasma viscosity, and decreases platelet aggregation to enhance blood flow through the obstructed artery. Pentoxifylline, given as 400 mg 3 times a day, may be considered as a second-line agent for patients with claudication (Hirsch et al., 2006). It is generally well tolerated and, when used in combination with lifestyle changes, has the potential for decreasing painful symptoms associated with walking in patients with intermittent claudication (Salhiyyah, Senanayake, Abdel-Hadi, Booth, & Michaels, 2012). It has been shown to increase walking distance by a modest degree but to a lesser extent than that seen with cilostazole.

Most patients with claudication respond to conservative therapy. Invasive procedures, including endovascular repair and surgical interventions, should only be performed on patients who have failed to respond to optimal therapy that includes risk factor modification, a supervised exercise program, and pharmacotherapy; on those who have symptoms so severe that quality of life is reduced; or on patients with progressive arterial occlusive disease that has clinical manifestation of critical limb ischemia (formerly known as limb-threatening ischemia) such as pain at rest, nonhealing wounds, or gangrene.

Local infusion of a thrombolytic agent or mechanical thrombectomy may be the next option before resorting to surgical revascularization in cases of acute limb-threatening ischemia of <14 days’ duration (Hirsch et al., 2006). Local lysis of acute arterial occlusions is safe and effective in restoring blood flow (Wissgott, Richter, Kamusella, & Steinkamp, 2007); however, before a decision is made to perform an invasive procedure, the risk of limb loss and the overall cardiovascular risk to the patient must be considered.

In vitro studies have suggested that recovery of the vascular network might be possible some day using mesenchymal stem cells (Guiducci et al., 2010). This might prove to be a promising therapeutic strategy for treating severe PAD.

Clinical practice guidelines from the American College of Cardiology and the American Heart Association (ACC/AHA) for the management of PAD (Hirsch et al., 2006; Rooke et al., 2011) are available here:

Anatomy, Physiology, and Pathology

Thromboangiitis obliterans, more commonly referred to as Buerger’s disease, is a recurring inflammatory occlusive process affecting the small- and medium-sized arteries and veins of the extremities.

Epidemiology

Buerger’s disease is a rare disease process with only a few patients affected annually. It is most prevalent in the Mideast and Asia. Its incidence has been on the decline corresponding to a decrease in smoking. The incidence in the United States is 12.6 per 100,000 persons (Olin, 2000). The incidence of Buerger’s disease is higher in males than females and occurs more commonly in patients younger than 45 years (Piazza & Creager, 2010). Risk factors include tobacco use and a family history (Olin & Shih, 2006).

Diagnostic Criteria

The diagnosis of Buerger’s disease is based on patient history and physical examination findings. Diagnosis is made predominantly on the basis of five criteria: smoking history; age <45 years; the presence of distal extremity ischemia confirmed by noninvasive vascular testing; angiographic findings; and the absence of autoimmune disease, thrombophilia, diabetes, or proximal embolic sources (Piazza & Creager, 2010). Biopsy can provide a definitive diagnosis but is rarely needed if the previously mentioned criteria are met.

History and Physical Examination

Patients most often present with ischemic symptoms from stenosis or occlusion of the small arteries and veins in the distal extremities. Symptoms often present as intermittent claudication of the arms, hands, legs, or feet. Patients may also experience numbness and tingling as well as color and temperature changes. Although symptoms may begin in one extremity, multiple extremities are usually involved. It may progress to ischemic ulcerations or gangrene of the fingers and toes. Raynaud’s phenomenon (sudden onset of cold digits associated with sharply demarcated color changes, skin pallor, or cyanosis) occurs in more than 40% of patients (Piazza & Creager, 2010).

Superficial thrombophlebitis, manifested as erythema, warmth, and swelling, often precipitates arterial signs and symptoms. Patients who develop ulceration have a greater chance of developing an infection, which may ultimately result in amputation of the affected body part.

The physical examination should include a full vascular examination with palpation of peripheral pulses, auscultation for bruits, and measurement of the ABPI (Piazza & Creager, 2010). Examine the extremities for superficial nodes and cords, in addition to signs of ischemia. Assessment reveals diminished or absent pulses and swelling is often noted in the feet.

The Allen test should be performed. To perform the Allen test, the patient is asked to make a tight fist to empty blood from the hand and fingers. The radial and ulnar arteries are then occluded by the examiner’s fingers. The patient opens the hand while the pressure over the ulnar artery is released, leaving the radial artery compressed. If the hand does not refill with blood, an occlusion of the ulnar artery is present. A hand that quickly refills with blood indicates patency of the ulnar artery; the test should be repeated with pressure on the radial artery released while the ulnar artery remains occluded to evaluate for occlusion of the radial artery.

Diagnostic Studies

An ankle or wrist brachial index should be performed to evaluate for occlusive disease; however, the measure is often normal if the disease is limited to distal vessels. Digital segmental pressures can be obtained to evaluate for distal occlusive disease.

Angiographic studies, whether by CT, MRI, or invasive contrast angiography, are done to look for features suggestive of thromboangiitis obliterans: no evidence of atherosclerosis, no embolic sources, involvement of small- or medium-sized vessels, segmental occlusion, and collateralization around areas of occlusion.

Laboratory tests are ordered to rule out other diagnoses (Piazza & Creager, 2010). A laboratory workup should include a complete blood count, chemistry profile, liver function tests, fasting blood glucose, and inflammatory markers such as erythrocyte sedimentation rate, C-reactive protein, cold agglutinins, and cryoglobulins. Serological testing for autoimmune disease should include an antinuclear antibody, rheumatoid factor, anticentromere antibody, and anti-SCL-70 antibody. In patients with thromboangiitis obliterans, these tests will be normal or negative.

Treatment Options, Expected Outcomes, and Comprehensive Management

Intravenous iloprost, a prostaglandin analog, may be used to aid in pain management in patients with critical limb ischemia while they get through the initial period of smoking cessation. Benefits in ulcer healing and reduced risk of amputation were also seen with the use of intravenous iloprost (Piazza & Creager, 2010). Although calcium channel blockers are frequently used to manage vasospasm, their use has not been validated in clinical trials.

Teaching and Self-Care

As smoking cessation remains the only definitive treatment option, teaching strategies should focus on the importance of ongoing cessation. Patients should be taught to protect their extremities from trauma. Hands and feet should be kept clean, dry, and moisturized. Circulation may be promoted by choosing exercises wisely; specifically, ankle rotations and leg lifts as are done during Buerger–Allen exercises. Pain can be controlled with analgesia or alternative therapies.

AORTIC ANEURYSMS

Anatomy, Physiology, and Pathology

An aneurysm is a defect in the anatomy of an artery resulting in weakness, stretching, and ballooning out of the arterial wall with at least a 50% increase in diameter compared to the normal diameter of the artery (Hiratzka et al., 2010). The most commonly affected artery is the aorta.

Risk factors for atherosclerosis (e.g., hypertension, hyperlipidemia, smoking) should be assessed, as atherosclerosis often coexists with aneurysmal disease. Atherosclerosis is associated with 80% of TAAs (Latessa, 2002). Most often aneurysms are asymptomatic and discovered incidentally during chest x-ray, ultrasound, CT scanning, or MRI. However, if a patient complains of symptoms such as sudden onset of severe chest, flank, or back pain, with any of the associated risk factors or a family history of aneurysm, an aortic aneurysm should be considered in the differential diagnoses. The patient should be sent for immediate imaging of the aorta.

Ascending TAAs may present with heart failure from associated aortic regurgitation. Symptoms of myocardial ischemia may occur from compression of the coronary arteries. Pain from an AAA is often associated with hypogastric or low back pain that is steady, with a gnawing quality, lasting for hours at a time, and unaffected by movement (Hirsch et al., 2006). Rupture of an AAA is often associated with acute onset abdominal and back pain with associated tenderness and a palpable, pulsatile abdominal mass on physical examination. Patients may be hypotensive from blood loss and may progress rapidly to hypovolemic shock. A ruptured TAA is often catastrophic, presenting with acute onset chest pain and progressing rapidly to shock.

An abdominal examination focusing on palpation and auscultation of the aorta should be performed in all patients with risk factors for or a known AAA. Assessment for perfusion differences in the limbs should be performed. If suspicion of aortic aneurysmal disease arises, the patient should be sent for an imaging study and be referred to a vascular surgeon for consultation. A thorough medical and family history should be obtained to identify hereditary causes and risk factors of aneurysms.

Diagnostic Studies

A TAA may be suspected by the presence of a widening of the mediastinal silhouette on chest x-ray. Further evaluation of aneurysms may be obtained through the use of ultrasound, echocardiogram, CT scan with intravenous contrast, MRI, or contrast angiography.

Treatment Options, Expected Outcomes, and Comprehensive Management

Screening for AAAs is recommended for high-risk populations. Men 60 years and older with a family history of an AAA in either a sibling or child should have a screening ultrasound. Men, aged 65 to 75 years, who have a past or present history of smoking, should also be screened for AAA by ultrasound. Aortic imaging to screen for TAAs is recommended for patients with a first-degree relative with a history of a TAA.

Once an aortic aneurysm is diagnosed, treatment, either surgical or monitoring every 4 to 6 months by imaging, should be implemented, along with risk factor modification. The primary care provider should also evaluate these patients for aneurysmal disease elsewhere in the body. Recommendations and guidelines regarding treatment are specific to the size and type of aneurysm discovered. Specifically, location in the body, diameter, and health status of the tissue determines the course of treatment and prognosis (Chaikof et al., 2009; Hiratzka et al., 2010; Hirsch et al., 2006). Patients with an aortic root or ascending aorta >4.0 cm should have yearly imaging to measure aortic size. If the diameter of the aneurysm reaches 5.5 cm, the patient should be referred for surgical repair (Hiratzka et al., 2010).

The goal of treatment is to avoid rupture. The diameter of the aneurysm is positively associated with increased risk of rupture; that is, the greater the diameter, the greater the risk. The first step is to identify risk factors, which include age >60 years, male gender, smoking, race (Caucasians are at increased risk), a positive family history of aortic aneurysm, and a personal history of other large aneurysms, in addition to a history of or risk factors for atherosclerosis. Hypertension and hyperlipidemia should be well controlled to reduce the risk of progression of the size of the aneurysm. Blood pressure should be treated to achieve a goal of <140/90 mmHg. Beta-blockers should be prescribed for patients with Marfan syndrome to reduce the rate of aortic dilation. Smoking cessation should be encouraged. Close monitoring of at-risk patients by a vascular surgeon is important.

GIANT CELL (TEMPORAL) ARTERITIS

Anatomy, Physiology, and Pathology

Giant cell arteritis (GCA) is a chronic inflammation of large- and medium-sized vessels. This systemic compromise is most often expressed in the cranial branches of arteries originating from the aortic arch. Temporal arteritis is a form of GCA that affects branches of the carotid artery. Visual loss is one of the complications of this condition.

Epidemiology

GCA is the most common form of systemic vasculitis. It occurs twice as often in women than in men. It is seen more commonly in persons of Northern European descent older than 50 years, with an incidence of 18.8 cases per 100,000 persons (Warrington & Matteson, 2007). The incidence rises after the age of 50 years, with the highest rate seen between 70 and 80 years of age.

Diagnostic Criteria

For the diagnosis of temporal arteritis, at least three of the following criteria must be present: