CHAPTER 11 Arterial ulcers
1. Describe etiologic factors, risk factors, pathophysiology, typical presentation, and principles of management for arterial ulcers.
2. Describe essential assessment for the patient with a suspected arterial ulcer, including history, pain assessment, physical assessment, and laboratory studies.
3. Outline a patient teaching plan for the individual with ischemic disease of the lower extremity, including lifestyle changes to maximize perfusion and measures to prevent trauma.
4. Distinguish between critical limb ischemia and acute limb ischemia, including assessment parameters and implications for management.
5. Identify indications and options for surgical revascularization and for amputation.
6. Describe pharmacologic options for management of arterial ulcers.
7. Recommend appropriate topical therapy for each of the following: ischemic ulcer covered with dry eschar and no signs of infection; ischemic ulcer covered with dry eschar and mild erythema and fluctuance of surrounding skin; open ischemic ulcer with and without signs of infection.
Arterial ulcers (also known as ischemic ulcers) occur as a result of severe tissue ischemia and are extremely painful. In addition, ischemic ulcers represent potential limb loss. These lesions are generally refractory to healing unless tissue perfusion can be improved, and they are prone to progress to invasive infection and/or gangrene, which may necessitate amputation (Bonham et al, 2008). Of further concern is the likelihood of coexisting, and possibly unrecognized, cardiovascular or cerebrovascular disease. Thus any patient with an ulcer caused or complicated by arterial insufficiency requires thorough physical assessment and aggressive management. The treatment plan for these patients must be multifaceted, including measures to maximize perfusion and minimize risk of infection, evidence-based wound care, and ongoing assessment and management of ischemic pain. Effective management of ischemic disease frequently requires significant lifestyle modifications; thus patient education and counseling are essential elements of the management plan.
Epidemiology
Many terms are used to describe the anomalies that can affect the peripheral vascular system. Peripheral vascular disease describes noncardiac disease that includes a myriad of conditions affecting the arterial, venous, and lymphatic circulation. Peripheral arterial disease (PAD) specifically refers to a range of noncoronary arterial syndromes caused by an alteration in the structure and function of the arteries that supply the brain, visceral organs, and limbs; it is the preferred term for stenotic, occlusive, and aneurysmal diseases (Hirsch et al, 2006). Peripheral arterial occlusive disease describes arterial disease that is specifically occlusive in nature. Finally, lower extremity arterial disease (LEAD) includes only arterial disease that affects the leg arteries and excludes arterial diseases of the aorta, carotid, upper extremity, or visceral arteries (Hirsch et al, 2006). Most ischemic ulcers develop as a result of LEAD.
Although ischemic ulcers are much less common than those resulting from venous insufficiency or neuropathy, the underlying disease process (LEAD) is quite prevalent, especially among the elderly. Current data suggest prevalence rates ranging from 18% to 29% among those 60 years of age or older; similar prevalence rates have been reported for individuals older than 50 years of age who are high risk due to diabetes or tobacco use. Altogether an estimated 5 to 10 million people in the United States have LEAD, many of whom are undiagnosed; recent data suggest that “silent” disease accounts for almost half of cases (Aronow, 2008; Bonham et al, 2008; Sigvant et al, 2009).
The high prevalence of undiagnosed disease is explained by the fact that vascular disease frequently is asymptomatic until the disease process is advanced; this is true of coronary artery disease and cerebrovascular disease as well as PAD. Unfortunately, the failure to diagnose vascular disease at an earlier time results in failure to treat until the disease is advanced and the patient becomes symptomatic. Advanced (symptomatic) disease is associated with much greater risk of morbidity and mortality (e.g., myocardial infarction, cerebrovascular accident, limb loss), and is much less amenable to effective treatment; thus the focus in management of patients with any form of vascular disease (coronary artery disease, cerebrovascular disease, PAD) must shift to routine screening to detect asymptomatic disease. Because atherosclerotic disease is the most common disease process affecting the arterial system and is a systemic phenomenon, the patient with disease in one vascular bed (e.g., coronary artery bed) is at greater risk for disease in another vascular bed (Hirsch et al, 2006). Studies indicate that patients with PAD are very likely to have coexisting coronary artery disease or cerebrovascular disease and are at significantly greater risk for early death due to a cardiac event (Aronow, 2008; Bonham et al, 2008; Sigvant et al, 2009). Ankle-brachial index (ABI) testing with a handheld Doppler is an effective bedside screening procedure. Because ABI less than 0.9 is an independent predictor for increased risk of cardiovascular death, individuals with ABI less than 0.9 should be referred for further assessment to rule out “silent but treatable” cardiac disease (Bonham et al, 2008; Hopf et al, 2006).
Critical and acute limb ischemia
Critical limb ischemia refers to patients with chronic (more than 2 weeks) ischemic rest pain, ulcers, or gangrene attributable to objectively proven arterial occlusive disease. Acute limb ischemia refers to a quickly developing or sudden decrease in limb perfusion that threatens limb viability (Hirsch et al, 2006; Norgren et al, 2007). Signs of acute limb ischemia include the six Ps: pain, paralysis, paresthesias, pulselessness, pallor, and polar (cold extremity). Arterial embolism, however, can occur without symptoms (Hirsch et al, 2006). Because irreversible nerve and muscle damage may occur within hours, all patients with suspected acute limb ischemia should be evaluated immediately by a vascular specialist (Norgren et al, 2007).
Etiology
Arterial insufficiency and arterial ulcers are most common among older adults and middle-aged adults who have additional risk factors, such as diabetes or tobacco use. The most common causative factor in these cases is atherosclerotic disease. Arterial ulcers also occur with thromboangiitis obliterans (Buerger disease), sickle cell disease, and vasculitis but are less common and can occur among younger individuals. Least common are arterial ulcers that develop as a result of entrapment syndromes, acute embolic syndromes, and arterial trauma (Hirsch et al, 2006).
Atherosclerosis
The most common cause of LEAD and arterial ulceration among older adults is atherosclerosis involving the peripheral circulation. Atherosclerotic disease can occur in any vessel in the body. In the peripheral circulation the aortic, iliac, femoral, and popliteal arteries (see Figure 10-2) are the vessels most commonly affected (Dillavou and Kahn, 2003).
Although the pathology of atherosclerotic disease is not completely understood, it is known to involve two primary processes: plaque formation and enlargement, which cause narrowing of the vessel lumen, and endothelial injury subsequently triggering an inflammatory process that ultimately results in fibrosis and hardening of the vessel wall (Hirsch et al, 2006).
Plaque formation begins with the lesion known as a “fatty streak,” which is a gray or pearly white lesion that adheres to the intima (inner layer of the arterial wall). This lesion consists of a lipid core and a connective tissue covering. As further lipid accumulation occurs, the plaque enlarges, which results in progressive narrowing of the vessel lumen. Over time the plaques harden as a result of deposition of calcium salts and cholesterol crystals, causing loss of vessel elasticity, which further compromises blood flow (Hirsch et al, 2006).
The second process contributing to vessel narrowing and hardening is triggered by damage to the vessel lining. Endothelial damage results in areas where the intimal lining is denuded. Platelets aggregate over these denuded areas, causing clot formation and the subsequent release of growth factors that stimulate mitosis of the vascular smooth muscle cells and promote synthesis of connective tissue proteins such as collagen. The end result is thickening and fibrosis of the vessel wall, which further contributes to narrowing and hardening of the involved arteries. Clinically these changes result in a chronic reduction in blood flow to the tissues and a loss of the ability to respond with increased blood flow when metabolic demands are increased. In addition, acute vessel occlusion may occur as a result of sudden plaque enlargement or plaque rupture (Hirsch et al, 2006).
Thromboangiitis obliterans (buerger’s disease)
Thromboangiitis obliterans, also known as Buerger’s disease and arteriosclerosis obliterans, is a rare condition almost exclusively limited to adults younger than 50 years who are heavy smokers (Hirsch et al, 2006). The disease typically involves the small- and mid-sized arteries in both the upper and lower extremities. The process is always bilateral and frequently involves all four limbs. The cause of the disease is not known but does not involve plaque formation or hypercoagulability. Instead the lesions appear to be inflammatory in origin, which suggests an autoimmune process (Hanly et al, 2009). Patients may complain of cold sensitivity, rest pain, pedal claudication, digital ulceration, or gangrene. Ulceration may occur spontaneously but more commonly is precipitated by minor trauma. The most effective management is elimination of tobacco, which provides consistent interruption of the disease process. Among individuals who continue to use tobacco, digit or limb amputations are common; however, mortality is not increased (Hanly et al, 2009).
Sickle cell disease
Lower extremity arterial ulcers occur in 25% to 75% of patients with sickle cell disease, a hereditary disease primarily affecting those of African American descent. During physiologic stress in a person with sickle cell disease, the red blood cells become deformed into a crescent moon or sickle shape. These abnormal blood cells clump together and cause vascular occlusion and tissue necrosis. In addition, injury to the red blood cells causes increased expression of adhesion molecules on the endothelial surface to which the sickled cells attach, resulting in further occlusion and necrosis. Fortunately, once the sickle crisis is resolved, blood flow typically is restored, and the ulcer slowly heals. Unfortunately, many individuals develop chronic ulcers that are very slow to heal. Many individuals with sickle cell disease also have chronic venous insufficiency, which further delays healing. Because a sickle cell crisis is frequently precipitated by minor trauma, preventive care is a key element of management for these patients (Trent and Kirsner, 2004).
Vasculitis
Another potential cause of ischemic ulceration is vasculitis, which is a general term for inflammation of vessel walls. The inflammation may produce defects in the vessel wall, allowing leakage of blood into the surrounding tissues, or it may produce vessel occlusion and tissue necrosis. The vasculitis “umbrella” comprises a large number of specific conditions that vary significantly in clinical presentation and prognosis, depending on the size and location of the inflamed vessels. The causative factors for vasculitis are not well defined, but the condition is frequently associated with either an acute allergic reaction or an autoimmune process. When the condition is associated with an autoimmune process, the patient commonly presents with systemic symptoms such as malaise, joint pain, and low-grade fever in addition to the specific symptoms produced by the inflamed vessels. Vasculitic conditions producing lower extremity ulcers typically involve mid-sized and small arteries and are characterized by a petechial rash, purpura, tissue necrosis, and extreme pain. Diagnosis is suggested by patient history, clinical presentation, and high serum levels of inflammatory markers and is confirmed by biopsy demonstrating vessel inflammation. Management primarily involves systemic antiinflammatory agents and pain management. Topical therapy is based on the principles of wound bed preparation (elimination of necrotic tissue and control of bacterial burden) and moist wound healing (Xu et al, 2009).
Risk factors for lead
Risk factors for LEAD (Box 11-1) are the same as those for coronary artery disease and include both modifiable factors and predisposing factors. Studies have identified a number of “emerging” risk factors that appear to be associated with the development of atherosclerotic disease, but their impact is not yet well defined (Liapis et al, 2009). While some of these risk factors, such as age, gender, and family history, are irreversible, the majority are very responsive to lifestyle modifications and pharmacologic therapy. A clear understanding of current recommendations for management of risk factors is critical because effective management of the underlying disease process is essential for wound healing, limb salvage, and longterm survival (Aronow, 2008; Bonham et al, 2008; Hopf et al, 2006; Liapis et al, 2009).
Causal modifiable risk factors
The “big four” risk factors are those that appear to play a direct causal role in the development of atherosclerosis: smoking, diabetes mellitus, dyslipidemia, and hypertension. All of these risk factors are modifiable; thus management of these factors should be the clinician’s primary focus. Table 11-1 and Box 11-2 summarize goals and guidelines for the management of modifiable risk factors (Liapis et al, 2009).
TABLE 11-1 Management of Modifiable Risk Factors
| Risk Factor | Management Goals/Guidelines |
|---|---|
| Tobacco use | Goal: Cessation of tobacco use Guidelines: See Box 11-2 |
| Diabetes mellitus | Goal: HbA1C <7.0% (<6% if possible for high-risk patient) Guidelines: |
| Dyslipidemia | Goals: • LDL-C <100 mg/dl (<70 mg/dl for very-high-risk patient) • HDL-C >40 mg/dl for men, >45 mg/dl for women |
| Hypertension | Goals: <140/90 mm Hg (nondiabetic), <130/80 mm Hg (diabetic) Guidelines: • Patient education and counseling regarding diet and exercise • Antihypertensive medications • Thiazide diuretics as initial drug • Angiotension-converting enzyme inhibitor or angiotension receptor blocker for patient with diabetic renal disease (except patient with renal artery stenosis) or congestive heart failure • β-Adrenergic blocker for patient who also has coronary artery disease • Calcium channel blocker as needed for uncontrolled hypertension Note: Multiple agents should be used as needed to maintain blood pressure within accepted range. |
HDL-C, High-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol.
BOX 11-2 Interventions to Promote Cessation of Tobacco Use
1. General education concerning the negative effects of tobacco use on health status.
2. Specific and consistent advice from health care team to eliminate tobacco use.
3. Establishment of patient–provider contracts in which the patient commits to a date on which he or she will eliminate tobacco use.
4. Anticipatory guidance (e.g., counseling to help the patient identify triggers of tobacco use and specific strategies for managing triggering events and situations).
5. General stress management and support.
6. Appropriate use of adequate doses of nicotine replacement agents (nicotine replacement therapy) and/or medications for nicotine addiction.
7. Frequent follow-up during the critical weeks after initial termination of tobacco use (by phone or office visit).
8. Appropriate counseling after any relapse on recognition that most individuals who successfully stop smoking have one to four relapses.
Smoking.
Smoking is a highly significant risk factor for atherosclerotic disease in general and for PAD in particular; smokers have a fourfold increased risk for PAD. Most studies suggest a connection between pack-year history and the number and severity of vascular complications; however, the number of pack-years that constitutes a significant increased risk for vascular disease is unknown (Bonham et al, 2008; Liapis et al, 2009; Sigvant et al, 2009). Smoking may be particularly harmful to women, who reportedly have a significant increase in risk with a 10-year pack history compared to men with a 30-year pack history (Sigvant et al, 2009). The negative effects of tobacco on the vascular system are due to its byproducts: nicotine, carbon monoxide, and hydrogen cyanide. The most significant of these is nicotine, which is a potent vasoconstrictor and also promotes platelet aggregation and clot formation. Smoking cessation can significantly reduce the progression of LEAD as well as mortality rates from other vascular complications; thus smoking cessation (see Box 11-2) should be a primary target of therapy (Aronow, 2008; Bonham et al, 2008; Hopf et al, 2008; Liapis et al, 2009).
Diabetes mellitus.
Diabetes, especially type 2, is one of the strongest predictors of PAD, representing a twofold to fourfold increase in risk. Even more significantly, patients with diabetes are at increased risk for death and limb loss caused by vascular disease; for each 1% increase in hemoglobin A1c (HbA1c) there is a 28% increase in risk of death. Patients with diabetes are 10 times more likely to progress to critical limb ischemia and amputation (Bonham et al, 2008; Hirsch et al, 2006; Liapis et al, 2009). Specific pathologic features associated with diabetes that contribute to LEAD include increased plaque formation, increased red blood cell (RBC) rigidity, increased blood viscosity and coagulability, hypertrophy of vascular smooth muscle, and increased vascular resistance (Gibbons, 2003). Insulin resistance and hyperinsulinemia may be one causative factor for hypertrophy of vascular smooth muscle, even in the early stages of the disease, because insulin is known to be a vascular growth factor. Fortunately, tight glycemic control (HbA1c <7.0) can significantly reduce the risk of microvascular complications and amputation; thus effective diabetes management (through diet, exercise, and pharmacologic therapy) is another key element of effective therapy for the patient with LEAD (Hopf et al, 2008). However, the goals for glycemic control must be individualized based on the patient’s overall clinical profile. Early results from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study suggest that aggressive glycemic control (see Table 11-1) could increase mortality among patients with type 2 diabetes (Aronow, 2008).
Dyslipidemia.
Elevated levels of cholesterol, low-density lipoprotein cholesterol (LDL-C), triglycerides, and lipoprotein(a) are independent risk factors for LEAD. Each 10 mg/dl rise in total cholesterol is associated with a 10% increase in risk (Bonham et al, 2008; Hirsch et al, 2006; Liapis et al, 2009). In contrast, elevated levels of high-density lipoprotein cholesterol (HDL-C) appear to play a protective role. Recommended target levels for lipid management and strategies for maintaining normal lipid levels are provided in Table 11-1.
Hypertension.
Elevated blood pressure (BP) is associated with up to a threefold increase in risk for LEAD in addition to a significant increase in risk for cardiovascular disease. Although treatment with antihypertensive medication has not been shown to improve LEAD outcomes, it is an essential element of care because of its impact on morbidity from cardiovascular and cerebrovascular disease (Lesho et al, 2004). Current goals and guidelines for maintaining BP are listed in Table 11-1 (Aronow, 2008; Bonham et al, 2008; Liapis et al, 2009).
Predisposing risk factors
Although predisposing risk factors may increase risk independently, they primarily act to increase the impact of primary (causative) risk factors. Predisposing risk factors include both modifiable factors (e.g., obesity, inactivity, social isolation, stress) and nonmodifiable factors (e.g., advanced age, male gender, postmenopausal status, family history, African American ethnicity). Clinicians should work with patients and other providers to eliminate or minimize modifiable factors through diet, exercise, and strategies that reduce stress and isolation. Clinicians should educate patients about the impact of nonmodifiable risk factors and the critical importance of attention to smoking cessation, glycemic control, BP control, and correction of dyslipidemia (Bonham et al, 2008; Hopf et al, 2008; Liapis et al, 2009).
Emerging risk factors
Homocystinemia.
Homocystinemia is a rare autosomal dominant disease found in 30% to 40% of individuals with LEAD. Studies suggest that elevated homocysteine levels may cause a mild increase in risk for LEAD; however, whether homocystinemia plays an etiologic role in LEAD is unclear. The abnormal metabolism of homocysteine (a thiol-containing amino acid) can be easily normalized through administration of vitamin B6, vitamin B12, and/or folic acid. Although there are no proven benefits in terms of reduced cardiovascular risk, current recommendations suggest treatment for those at risk for LEAD, with a treatment goal <10 μmol/L (Bonham et al, 2008; Liapis et al, 2009).
Inflammation.
Inflammation is known to play a role in the development of atherosclerotic lesions in that endothelial injury triggers an inflammatory response that ultimately results in fibrosis. Some investigators suggest that repeated episodes of tissue ischemia (as evidenced by claudication) may trigger a low-grade inflammatory response that contributes to disease progression. Others have hypothesized that rapid progression of the disease process in a subset of patients may be the result of an underlying inflammatory disorder. The role of inflammation in the progression of the disease seems to be supported by studies demonstrating elevated levels of inflammatory markers such as C-reactive protein, fibrinogen, and interleukin-6 among patients with advanced PAD. The link between inflammation and the progression of PAD is unclear, and at present there are no recommendations for routine assessment of inflammatory markers such as C-reactive protein levels or for intervention (Bonham et al, 2008; Chaparaia et al, 2009; Liapis et al, 2009).
Infection.
Inflammation, specifically both periodontal disease and Chlamydia pneumoniae (CPN), has been associated with increased risk and severity of LEAD. Acute CPN infections have been associated with increased lipid abnormalities and endothelial dysfunction. Antibiotic treatment of LEAD resulted in better clinical outcomes in patients who were seropositive for CPN than in seropositive controls who did not receive antibiotic therapy. Although more research is needed, prompt treatment of any infectious process is recommended for all patients (Bonham et al, 2008; Liapis et al, 2009).
Renal failure.
Data suggest that there is a parallel between advancement of vascular disease and renal disease, and that renal failure increases the risk of death in patients with advanced LEAD. Although more study is needed, it appears clear that early intervention to preserve both vascular function and renal function is warranted (Liapis et al, 2009).
Pathology of arterial ulceration
The exact pathologic mechanisms producing ulceration in the ischemic limb have not been clearly defined. Spontaneous ulceration typically involves the toes or distal foot and most likely is the result of progressive occlusion leading to cellular ischemia and tissue necrosis. Arterial ulcers may also be precipitated by minor trauma, which results in nonhealing wounds because the damaged vessels are unable to meet the increased demands for oxygen associated with tissue injury and the healing process (Hirsch et al, 2006). Patients with LEAD and compromised mobility are at greater risk for pressure ulcer development because they have an existing baseline of diminished blood flow. Therefore heel ulcers may occur rapidly in a bedbound patient with preexisting vascular impairment. It should be emphasized that pressure ulcers in these patients are not unavoidable; they can be prevented with standard interventions such as heel elevation.
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