CHAPTER 16

Buerger Disease (Thromboangiitis Obliterans)

Rita C. Clark

OBJECTIVES

Introduction/Overview

Buerger disease or Thromboangiitis Obliterans (TAO) is a “nonatherosclerotic segmental inflammatory disease that most commonly affects the small- and medium-sized arteries, veins, and nerves of the arms and legs” (Olin, 2000). The cause is unknown but it is widely accepted that tobacco use in some form is critical to the onset and progression of Buerger disease (Mills, 2003).

In 1879 von Winter, of the University Clinic in Vienna, published his autopsy findings of a patient with a 12-year history of leg ischemia culminating in “spontaneous gangrene” and limb loss (Mills, 2003). Twenty-nine years later, Leo Buerger, from Mount Sinai Hospital in New York, described detailed pathologic findings of the disease process in 11 amputated limbs of males with ongoing limb ischemia commencing between the ages of 20 and 40 years. Buerger coined the term TAO to describe the clinical and pathologic characteristics of this disease process, which has since taken on the eponym Buerger disease (Mills, 2003).

I. Incidence

A. The True Incidence Worldwide is unknown due to the lack of epidemiologic studies in many countries and inconsistencies in diagnosis.

B. North American incidence estimated at 8 to11.6/100,000/yr (Cooper et al., 2004). Olin (2000) reported annual incidence in the United States to be 12.6/100,000. Prevalence in North American incidence has declined in last 30 years (Olin & Shih, 2006). More prevalent in the Mediterranean, the Middle East, and Asia (Olin & Shih, 2006).

C. Erroneously, Dr. Buerger thought the disease was primarily limited to the Jewish population, but that observation was found to be reflective of his patient population at Mount Sinai Hospital. Authors have quoted an extraordinary high incidence (80%) of Buerger disease among Israeli Jews of Ashkenazi ancestry with peripheral vascular disease (Małecki, Zdrojowy, & Adamiec, 2009; Olin, 2000). In response to Małecki et al., 2009, Adar (2010) claims the incidence among Ashkenazi Jews has been erroneously quoted from the original 1965 article printed in the American Journal of Medicine. In the original source document 80% (63 of 80) was the percent of Ashkenazi Jews studied in Israel for that paper. This preponderance of Ashkenazi Jews was not reflective of incidence or prevalence, but rather imperfect sampling and the inclination of affluent Ashkenazi Jews to participate in scientific studies during the 60s.

D. Strong Association exists between the disease and tobacco use. Type of tobacco used affects prevalence. Cigarette smoking carries the greatest risk. Cigars, chewing tobacco, snuff, and marijuana have also been implicated (Olin & Shih, 2006). Higher prevalence in India among smokers of bidis, homemade cigarettes made of raw tobacco (Olin, 2000). Prevalence higher among Indonesians smoking homegrown Kawung cigarettes (Mills, 2003).

II. Epidemiology

A. Generally presents in young adults before the age of 40 to 45 years (Olin, 2000). Median age at onset of 34 years (Mills, 2003).

B. Historically, more men than women. In early reports women constituted only 1% to 2%; but over the years there has been a relative increase among women, paralleling the increase of tobacco use among young women (Joyce, 1996). Joyce (1996) and Olin (2000) reported increased incidence among women from 11% in 1971 to 23% in 1990.

C. In a Series of 112 Patients evaluated at the Cleveland Clinic between 1970 and 1987, the mean age at diagnosis was 42 (range 20 to 75) with a presence among women of 23% (Olin & Lie, 1992).

D. Mills (2003) cited a men to women ratio of 7.5:1 (13%) compared with a previously documented ratio of 9:1 (11%) in past series, as cited by Olin and Lie in 1992

E. In a Mayo Clinic Review of 111 Buerger patients, the mean age was 33.6 ± 8.4 years; and the percentage of female patients was 40.5%, which had increased from 1976 to 2000 (Cooper et al., 2004).

III. Clinical Features

A. Most Commonly Affects the small- and medium-sized arteries and veins in the arms, hands, legs, and feet.

B. Reports of the Disease affecting cerebral, coronary, pulmonary, renal, mesenteric, aorta, and iliac arteries exist (Olin, 2000). Hoppe, Lu, Thistlewaite, Yi & Mahmud (2002) published a case report of a 39-year-old female with affected left and right internal mammary arteries (IMAs) and the associated implications for coronary artery bypass; hence, coronary angiography to include IMAs in Buerger patients pre CABG is recommended.

C. Typically Presents as Ischemia of the distal small arteries and veins of the digits, hands, and feet, manifested by rest pain, ulceration, or gangrene (Mills, 2003; Olin, 2000).

D. Claudication of the instep of the foot rather than typical calf claudication is also a frequent complaint (Mill, 2003).

E. Calf Claudication may be present as the disease progresses more proximally.

F. Superficial Thrombophlebitis (38%), Raynaud disease (44%), an abnormal Allen test (63%), and nonspecific sensory findings (69%) are frequent signs and symptoms of the disease (Olin & Lie, 1992).

G. Affects any or all of the limbs. Isolated lower-extremity involvement in 50% of patients; isolated upper-extremity involvement in 10%; and both upper- and lower-extremity involvement in 30% to 40% of patients (Mills, 2003).

H. Ischemia of Upper Extremity clinically evident in 40% to 50% of patients. Disease detected in 63% by Allen test, and 91% with arteriography of the hand and forearm (Puéchal & Fiessinger, 2007).

I. Rheumatic Manifestations: Joint manifestations occur in 12.5% of patients in the preocclusive phase. Recurrent episodes of arthritis with local signs of inflammation. Duration of symptoms 2 to 14 days. Nonerosive arthritis. Wrists and knees most frequently involved. Joint problems precede diagnosis of Buerger by about 10 years. Arthritis disappears with appearance of ischemic signs (Puéchal & Fiessinger, 2007).

IV. Pathophysiology

A. Type of Vasculitis. Nonatherosclerotic segmental inflammatory disease of small- and medium-sized arteries, veins, and nerves of arms and legs (Hooten, Burns, & Hays, 1998; Olin, 2000)

B. Segments of Involved Vessels interspersed between segments of normal vessels

C. Three Phases of the Disease (Joyce, 1996)

1. Acute phase lesions

a. Essential for histological diagnosis

b. Artery or vein is swollen

c. Acutely inflamed superficial vein is excellent biopsy source

d. Arterial biopsy jeopardizes blood flow

e. Observations are limited due to contraindications of arterial biopsy

f. Inflammatory cell infiltration throughout adventitia and media

g. Lumen is occluded by a highly cellular, unique thrombus with characteristic microabscesses

h. Lymphocytes exceed neutrophils

i. Occasional giant cells and eosinophils present

2. Subacute lesions

a. Recanalization of lumen begins

b. Cellularity of vessel wall and thrombus lessens

c. Microabscesses disappear

3. Late lesions

a. Organized and recanalized thrombus in fibrotic, small vessels. In all three phases, the normal architecture of vessel wall, including the internal elastic membrane, remains intact, and no necrosis is seen. These findings distinguish Buerger disease from atherosclerosis and other vasculitides that have disruption of the internal elastic membrane (Joyce, 1996)

V. Etiology/Precipitating Factors: Definitive etiology of Buerger disease is unknown, although there is a strong association with exposure to tobacco.

A. Tobacco Use

1. Clear correlation between active tobacco use and disease onset and progression

2. Smoking cessation brings remission

3. Recurrence linked to resumption of tobacco use

4. Persistent tobacco use related to increased frequency of amputation

5. Most reports document the use of 20 to 40 cigarettes daily (Joyce, 1996)

6. Exacerbation noted in patients smoking only 4 to 8 cigarettes a few days a week (Joyce, 1996)

7. Disease has been reported with other forms of tobacco: cigar, pipe, chewing tobacco and snuff, and marijuana (Joyce, 1996; Olin, 2000; Olin & Shih, 2006)

8. Effect of passive smoke unknown

B. Autoimmune Pathogenesis

1. Increased cellular sensitivity to types I and III collagen (Hoppe et al., 2002; Mills, 2003; Szuba & Cooke, 1998; Tanaka, 1998)

2. Cellular and humoral sensitivity to tobacco glycoproteins (Hooten et al., 1998)

3. Elevated antiendothelial cell antibodies (Mills, 2003)

4. Impaired endothelium-dependent vasorelaxation in peripheral vasculature (Olin & Shih, 2006; Piazza & Creager, 2010)

5. Deposition of immunoglobulins and complement factors along the internal elastic lamina (Mills, 2003)

6. Intima infiltration of human leukocyte antigen (HLA)—DR antigen-bearing macrophages and dendritic cells (Mills, 2003)

C. Genetic

1. Increased HLA-AP9 and HLA-B5 haplotypes (Tanaka, 1998)

2. MICA gene polymorphism (Tanaka, 1998)

D. Possible Etiologic link between Buerger disease and periodontal disease and oral bacterial infections. DNA of oral bacteria found in 13 of 14 patient samples of occluded arteries of patients with Buerger disease; all 14 had moderate to severe periodontitis; and none of the control patient arterial samples were positive (Iwai et al., 2005)

VI. Assessment: Risk Factors and Primary/Prevention

A. Diagnostic Criteria (Mills, 2003)

Major criteria

1. Onset of distal extremity ischemic symptoms before 45 years of age

2. Tobacco abuse

3. Exclusion of proximal embolic source, trauma and local lesions, autoimmune disease, hypercoagulable state, atherosclerosis, diabetes, hyperlipidemia, hypertension, and renal failure

4. Undiseased arteries proximal to the popliteal or distal brachial level

5. Objective documentation of distal occlusive disease by means of histopathology, segmental arterial Doppler studies, four-limb plethysmography, and four-limb invasive contrast arteriography. Advances in computed tomography angiography (CTA) and magnetic resonance angiography (MRA) show promise for imaging distal arteries but may not be sufficient for detection of small-artery pathology (Piazza & Creager, 2010)

Minor criteria

1. Migratory superficial phlebitis

2. Raynaud disease present in >40% of patients with Buerger disease and may be asymmetrical (Piazza & Creager, 2010)

3. Upper limb involvement

4. Instep claudication

B. Patient History

1. Subjective findings

a. Arch or forefoot claudication

b. Development of ulcers or gangrene of tips of digits

c. Rest pain of distal extremities, toes, foot, fingers, hand

d. Skin color changes, distal cyanosis

e. Intermittent claudication of hand or forearm

f. Paresthesia: numbness, tingling, aching in extremity

g. Coldness of extremity

2. Objective findings

a. Skin: coldness to touch, dependent rubor, elevation pallor, ulcerations or gangrene

b. Diminished or absent distal pulses

c. Abnormal Allen test

d. Delayed venous filling time

e. Superficial phlebitis (phlebitis migrans)

f. Raynaud disease

g. Tobacco use

h. Neurologic examination to assess for peripheral nerve involvement

C. Physical Examination

1. Inspection of skin

a. Color of extremities, fingers, toes

b. Dependent rubor, elevation pallor

c. Capillary refill time (normal ≤ 3 seconds)

d. Size and symmetry of extremities: muscle atrophy, edema

e. Trophic changes: hair loss, shiny taut skin, thickened nails, tapering of toes or fingers, skin breakdown, ulceration, or gangrene

f. Thrombophlebitis: swollen, erythematous, painful veins

2. Palpation

a. Complete pulse examination, upper and lower extremities

b. Allen test to determine arterial patency of the palmar arch

c. Skin temperature

d. Palpate for cord along phlebitic veins and increased skin temperature

3. Auscultation

a. Bruits over carotid, abdominal vessels and femoral sites for stenosis

b. Continuous wave Doppler assessment of nonpalpable pulses (posterior tibial, dorsalis pedis, radial, ulnar)

c. Ankle–brachial indices (ABI)

d. Wrist pressures

D. Considerations Across the Life Span

1. Generally presents in young adults before the age of 40 to 45 years (Olin, 2000)

2. Life expectancy approximates that of the general population at 5 (97%) and 10 (94%) years (Mills, 2003). However, Cooper et al. (2004) found lower long-term (>10 years after diagnosis) survival rates among TAO cohort compared to matched US population. Fifteen of 111 (13.5%) patients died in median of 14.8 years after diagnosis, at average age of 52.2 years

VII. Pertinent Diagnostic Testing

A. Laboratory Tests (Mills, 2003; Olin & Lie, 1992; Szuba & Cooke, 1998)

There are no serologic tests for diagnosing Buerger disease, and most results are within normal ranges; however, erythrocyte sedimentation rate (ESR), fibrinogen, and platelet count may be elevated in the presence of active ulcer or necrosis. Hematocrit, RBC rigidity, and blood viscosity may be elevated in Buerger disease compared to atherosclerosis. Presence of anticardiolipin antibodies and prothrombin gene mutation 20210 is associated with increased risk of disease. Lupus anticoagulant and anticardiolipin antibodies may be present but could also indicate an isolated thrombophilia (Piazza & Creager, 2010).

1. Exclude hypercoagulable states

a. Protein C and S levels

b. Prothrombin time (PT) and partial thromboplastin time (PTT)

c. Complete blood count (CBC)

d. Antithrombin III

e. Antiphospholipid antibody

f. Activated protein C

g. Homocysteine

h. Factor V Leiden

i. Prothrombin G20210A

j. Lupus anticoagulant

k. Anticardiolipin antibody

2. Exclude autoimmune disorders and vasculitis, such as CREST syndrome, scleroderma, rheumatoid arthritis, systemic lupus erythematous, and antiphospholipid antibody syndrome (Olin, 2000)

a. Antinuclear antibody level

b. ESR

c. Rheumatoid factor

d. C-reactive protein

e. VDRL antigen

f. Hepatitis serology

g. Serum complement levels

h. Cryoglobulins

i. Anticentromere antibody

j. Anti-DNA

k. Anti-SCL-70

B. Noninvasive Tests

1. Vascular laboratory studies

a. Segmental arterial pressures

b. Pulse volume recordings

c. ABI

d. Transcutaneous oximetry (TcPO₂)

e. Digital temperatures and pressures

f. Finger photoplethysmography

g. Laser Doppler

2. Transthoracic echocardiography to rule out cardiac source of emboli

3. Ultrasound to rule out aortic, iliac, femoral, popliteal aneurysm source of emboli

4. CTA or MRA to exclude proximal source of emboli and to define anatomy and extent of disease

C. Invasive Tests

1. Arteriography (Joyce, 1996; Mills, 2003)

a. Diagnostic versus supportive

b. Essential findings are multiple, bilateral focal segments of stenosis or occlusion with normal intervening and proximal vessels. Stenosis may be a few millimeters or several centimeters long

c. Identifies involvement of radial, ulnar, palmar, popliteal, tibial, and pedal arteries

d. Pattern of occlusive disease parallels the distribution and clinical severity of the disease

e. Occlusions abrupt or tapering

f. Generous collaterals, “tree-root,” spiderlike, or corkscrew

g. Arterial calcification and atheroma absent

h. Arteriographic abnormalities may be seen in limbs not yet clinically involved

i. Identifies other arterial abnormalities: aneurysms, atherosclerosis, vasculitides

j. Identifies those patients amenable to bypass surgery

2. Transesophageal echocardiography to rule out proximal source of emboli

VIII. Medical Management (Joyce, 1996; Małecki et al., 2009; Mills, 2003; Olin, 2000; Olin & Lie, 1992; Olin & Shih, 2006; Piazza & Creager, 2010; Puéchal & Fiessinger, 2007)

A. Abstinence from all forms of tobacco is the cornerstone of therapy

1. “Except for discontinuation of tobacco use, there is no other definitive therapy” (Puéchal & Fiessinger, 2007). Critical for therapeutic success. Favorably affects the prognosis of disease at any stage

2. Follow urinary nicotine and cotinine levels for questionable active smoking

3. Consider inpatient nicotine dependence treatment

4. Avoid nicotine replacement therapy as it may contribute to disease activity

5. Use bupropion and varenicline for pharmacotherapy

6. Secondhand smoke exposure may perpetuate disease process

B. Improve Arterial Flow to the Limb

1. Avoid vasoconstriction

2. Encourage vasodilation

3. Use of vasodilating agents: calcium channel blocker, α-blockers, and sildenafil; efficacy not proven (Piazza & Creager, 2010)

4. Antiplatelet drugs, heparinization, thrombolysis of anecdotal success

5. Epidural spinal cord stimulation to improve regional perfusion (Małecki et al., 2009; Olin & Shih, 2006)

6. Intermittent pneumatic compression (IPC)

7. Prostacyclin derivatives: alprostadil alfadex (Prostaglandin E₁) or iloprost (prostacyclin analog). Iloprost more effective than placebo and aspirin for wound healing, relief of rest pain, and reduction in need for amputation. Intravenous iloprost more effective than oral iloprost. Within 28 days of treatment 35% of iloprost group had healed ulcerations versus 13% in the aspirin group. Rest pain was relieved in 63% of iloprost patients versus 28% in aspirin group. Response rate at 6 months was 88% for iloprost group versus 21% for aspirin group. Iloprost more effective than lumbar sympathectomy (Małecki et al. 2009; Piazza & Creager, 2010; Puéchal & Fiessinger, 2007). More studies are needed to support efficacy.

8. Gene therapy: intramuscular injection of vascular endothelial growth factor (VEGF) increases limb perfusion and collateral vessel development, improves clinical symptoms, and promotes ulcer healing (Olin & Shih, 2006; Szuba & Cooke, 1998)

9. Intramuscular transplantation of autologous bone marrow mononuclear cells (BM-MNC), including progenitor cells, into ischemic limbs, promotes ulcer healing, increases collateral vessel development and decreases pain (Miyamoto et al., 2006; Motukuru, Suresh, Vivekanand, Raj, & Girija, 2008; Puéchal & Fiessinger, 2007; Saito et al., 2007). Long-term safety and efficacy is promising. Idei et al. (2011) showed 4-year amputation free survival post BM-MNC transplantation to be 95% in Buerger disease patients with critical limb ischemia (CLI) and 48% in peripheral artery disease (PAD) patients with CLI compared to 6% and 0% in control patients with Buerger disease and PAD, respectively. Four-year overall survival post BM-MNC transplantation was 100% in Buerger patients and 76% in PAD patients, compared to 100% and 67% in control Buerger and PAD patients, respectively. Matoba et al. (2008) showed the safety and efficacy of intramuscular transplantation of BM-MNC was not inferior to conventional revascularization therapies. Primary outcomes of death and amputation-free survival were better in Buerger patients with 3-year overall survival of 100% in the Buerger cohort and 80% in the PAD cohort, and amputation-free survival was 91% and 60%, respectively. Significant secondary outcomes included improvements in leg pain, ulcer healing, and pain-free walking distance. Change in ABIs and TcPO₂ values were not significant. In contrast, Miyamoto et al. (2006) found long-term adverse events in four of eight Buerger patients. Sudden death occurred in a 30 year old at 20 months post transplantation and three developed worsening or recurrence of ischemic symptoms.

10. Autologous whole bone marrow stem cell transplantation by fenestration of tibial bone in affected leg effective in inducing therapeutic angiogenesis, improving ischemic symptoms, and promoting ulcer healing and collateral vessel development (Kim, Kim et al., 2006; Puéchal & Fiessinger, 2007)

11. Stem cell therapy using umbilical cord blood-derived multipotent cells helpful in relieving pain, healing necrotic lesions, and promoting angiogenesis (Kim, Han et al., 2006; Puéchal & Fiessinger, 2007)

12. Feasibility, safety, and efficacy of gene therapy and cell therapy have been established; hence, these are promising new strategies for treatment of CLI. Large-scale, randomized control trials are needed to confirm the effects of gene therapy and cell therapy alone and in combination with one another on clinical symptoms and cardiovascular outcomes (Idei et al., 2011).

C. Treat Concomitant Infection and Cellulitis

1. Antibiotics

2. Drainage and debridement

3. Circulator boot therapy

D. Treat Thrombophlebitis

1. Nonsteroidal anti-inflammatory agents

E. Wound Healing

1. Debridement

2. Appropriate wound agents and dressings

3. IPC

F. Control Pain

1. Narcotic analgesic

2. Prolonged epidural analgesic

IX. Surgical Management (Joyce, 1996; Mills, 2003; Olin & Lie, 1992; Shigehiko, 1995)

A. Amputation of Digit(s) or Limb(s)

1. Unremitting rest pain and/or pain associated with ischemic ulcerations

2. Infection

3. Unsalvageable digit(s) or limb(s) with ulcerations or demarcated gangrene

4. Potential consequence: 85% of Buerger patients who underwent major amputation lost their jobs (Piazza & Creager, 2010)

B. Sympathectomy

1. Removes vasoconstrictor tone in the distal part of the limb

2. Relieves vasomotor symptoms of coolness and mild pain

3. Ischemic ulcers failing to heal

4. Efficacy not proven

5. Ischemia rarely worsens after sympathectomy

6. Performed on about 20% of patients

7. Chemical or surgical

8. Lumbar or thoracic, open versus laparoscopy or thoracoscopy

C. Surgical Revascularization

1. Generally precluded by extensive distal disease

2. Less than 10% of patients have suitable distal target arteries

3. Graft patency rates inferior to bypasses in diabetics and nondiabetics with atherosclerosis

4. Graft patency rates nearly 50% lower in Buerger patients who continue to smoke (Piazza & Creager, 2010)

5. Poor vein quality for conduit because of previous phlebitis

D. Omental Transfer (Olin, 2000)

1. Use for rest pain, nonhealing ischemic ulcers

2. Increases skin temperatures

3. Decreases rest pain

4. Promotes ulcer healing

X. Nursing Management

A. Nursing Diagnoses (Ackley & Ladwig, 2004; Carpenito-Moyet, 2004)

1. Ineffective tissue perfusion related to arterial insufficiency

2. Impaired tissue integrity related to altered circulation

3. Risk for impaired skin integrity related to altered circulation

4. Risk for peripheral neurovascular dysfunction related to vascular obstruction

5. Ineffective health maintenance related to tobacco use

6. Disturbed body image related to disease manifestations and/or amputation

7. Impaired physical mobility related to tissue loss, pain, amputation

8. Pain related to arterial insufficiency, tissue loss, amputation

B. Expected Patient Outcomes

1. Demonstrate adequate tissue perfusion. Verbalize knowledge of treatment regimen. Identify lifestyle changes needed to increase tissue perfusion.

2. Report sensory and pain changes at site of tissue impairment. Verbalize understanding of plan of care to heal tissue and prevent injury. Identify measures to heal and protect the tissue. Attain wound healing with increase in granulation tissue and decrease in wound size.

3. Verbalize understanding of personal risk factors related to impairment of skin integrity.

4. Maintain circulation, sensation, and movement of extremity. Explain signs of neurovascular compromise.

5. Eliminate use of all tobacco products. Demonstrate understanding of short-term and long-term health effects of tobacco use. Describe benefits of abstinence from tobacco use. Verbalize desire to eliminate tobacco use and commitment to personal health. Identify strategies to assist in tobacco cessation.

6. State or demonstrate acceptance of affected and/or lost body parts. State or demonstrate an ability to adjust to lifestyle change.

7. Increase physical activity. Set mutually defined goals and meet those goals. Verbalize feelings of accomplishment. Demonstrate use of adaptive equipment and other aids.

8. Rate intensity of pain using a pain scale. Determine comfort and function goals. Describe pharmacologic and nonpharmacologic pain relief plan. Function at an acceptable activity level with minimal interference from pain and medication side effects

C. Interventions

1. Assessments: pulses, skin color and temperature; capillary refill; skin texture and presence of hair, ulcers, or gangrene; edema; and pain. Do not elevate legs above heart level. Keep extremities warm.

2. Assessment and monitoring of tissue integrity and wound. Initiate and maintain appropriate wound care and dressing changes. Assess nutritional status.

3. Monitor skin condition and skin-care practices. Identify areas at risk and potential causative factors/agents. Prevent pressure over areas at risk. Assess nutritional status.

4. Perform neurovascular assessment using six Ps: pain, pulselessness, pallor/poikilothermia, paresthesia, paralysis, and pressure. Monitor for evidence of compartment syndrome.

5. Discuss risks of smoking; relevance to disease process, and rewards and benefits of cessation. Promote understanding of tobacco use behaviors. Explore strategies for cessation and minimizing weight gain. Discuss withdrawal symptoms and management of symptoms.

6. Acknowledge denial, anger, or depression as normal feelings when adapting to body and lifestyle changes. Encourage patient to make own decisions and to participate in plan of care.

7. Assess mobility skills and limitations. Assess for and treat pain prior to activities. Obtain assistive devices as needed for activity. Increase independence with activities of daily living (ADL) and discourage helplessness.

8. Assess pain level using pain-rating scale. Explore need for pain medication and class of analgesia needed for pain relief. Reassess pain after administration of analgesic and treat unrelieved pain. Explore nonpharmacologic measures for pain control. Explain to the patient the pain management plan that has been ordered.

D. Evaluation

1. Patient implements and adheres to treatment regimen

2. Wound shows signs of healing

3. Patient describes measures to prevent trauma to limb and further tissue loss

4. Patient is able to describe altered sensation and motor function in the limb

5. Patient successfully refrains from all tobacco products

6. Patient verbalizes feelings regarding loss of body part and the associated impact on lifestyle

7. Patient has increased physical activity and exhibits independence with ADL

8. Patient is able to control pain with acceptable types and amounts of medications and to maintain acceptable activity level with minimal interference from pain and medication side effects

XI. Patient Teaching

A. Disease Prevention/Health Promotion/Secondary Prevention

1. Educate, counsel patient repeatedly regarding the importance of discontinuing use of all tobacco products and exposure to tobacco smoke

a. No cigarettes, cigars, or pipe tobacco

b. No smokeless tobacco

c. No nicotine replacement products

d. Avoid passive smoke

2. Tobacco cessation strongly associated with disease progression and amputation rate

3. Patients without gangrene at the time of tobacco cessation usually do not require amputation—94% avoided amputations, whereas 43% of persistent smokers went on to one or more amputations (Olin, 2000)

4. Intermittent claudication, rest pain, ischemic ulceration, thrombophlebitis are most common among patients who continue to smoke (Hooten et al., 1998)

5. Inpatient treatment for tobacco abuse if necessary

6. Avoid illicit drug use and ergotamine

a. Marijuana may have similar effects as tobacco

b. Cocaine may induce vasospasm and acute arterial thrombosis (Marder & Mellinghoff, 2000)

c. Ergotamine tartrate may induce vasospasm (Oppat & Graham, 2004)

B. Home Care Considerations

1. Avoid all tobacco products and passive smoke.

2. Maintain a healthy diet and appropriate caloric intake.

3. Lower-extremity protection.

a. Avoid thermal, mechanical, and chemical trauma.

b. Wear proper-fitting shoes made of soft, flexible leather.

c. Avoid walking barefoot.

d. Wash feet and clean between toes with mild soap and warm water, dry thoroughly, and inspect daily.

e. Use clean cotton or wool socks, unmended and without seams.

f. Avoid constricting socks, stockings, and clothing.

g. Keep feet dry and warm. Hypoallergenic, nonmedicated talcum powder may be used lightly twice daily, avoiding nonintact skin. Rooke boot may be used for warmth.

h. Sparingly apply a lubricating cream to intact skin but not between toes. Avoid perfumed creams.

i. Use lamb’s wool or gauze pads between toes to prevent pressure.

j. Exercise meticulous nail care with podiatry assistance.

k. Avoid heating pads, heat lamps, hot water bottles, and cold packs.

l. Do not use cream hair removers, adhesive corn patches, or any harsh chemicals.

m. Avoid use of tape and adhesive bandages on skin.

4. Upper-extremity protection

a. Avoid vasospastic stimuli. Keep hands warm: wear gloves, mittens, cotton batting, or use warm water baths.

b. Cleanse with mild soap and warm water.

c. Sparingly apply lubricating cream to intact skin.

d. Exercise meticulous nail care.

e. Avoid heating pads, heat lamps, hot water bottles, and cold packs.

f. Avoid irritants, such as cleaning solutions and other chemicals.

g. Avoid use of tape and adhesive bandages on skin.

h. Avoid constricting clothing and jewelry.

5. Wound care

a. Apply wound care agents and dressings as instructed.

b. Inspect wounds daily.

c. Notify health care provider of development of new ulcerations or gangrene.

d. Notify health care provider of worsening of wound; unusual color, amount, or odor of drainage; increase in inflammation, redness, tenderness, or pain.

e. Do not soak the affected areas.

6. Activity

a. Discuss activity restrictions with health care provider.

b. Remain as active as possible and exercise regularly.

7. Postamputation rehabilitation

a. Attend physical therapy and perform exercises at home as directed.

b. Employ residual limb care as directed to control shrinkage, prevent edema, prevent trauma, and reduce wound pain.

c. Use ace wraps, shrinkers, rigid removable dressing, as instructed.

d. Identify functional outcomes and goals that correspond to maximal level of independence, lifestyle, and quality of life.

e. Treat depression.

f. Prosthesis fitting and gait-training when appropriate

g. Determine ability to drive a vehicle, modifications needed to do so, and any required driving license validation.

h. Application for handicap parking permit, as necessary, dependent on level and location of amputation.

i. Phantom limb pain management.

CASE STUDY

Chief complaint: Six-month history of nonhealing left great toe ulceration. Bilateral upper-extremity coolness, discoloration, burning, and tingling paresthesia to all fingers upon cold exposure.

History of present illness: CB was a single White male high school senior referred to our vascular center at age 18 with 6-month history of nonhealing left great toe ulceration following an accidental glass injury to the toe. An episode of infection had been treated with antibiotics, and he had been using Epsom salt soaks to the ulcerative toe. He reported activity restrictions in gym class because of the ulceration and development of bilateral foot pain with exercise, which was relieved after a 5-minute rest. He reported awakening with nocturnal pain in the ulcerative toe, which was relieved by dangling the leg over the side of the bed.

He also had complaints of progressive bilateral upper-extremity coolness, purplish discoloration, burning and tingling paresthesia of all fingers upon cold exposure. Symptoms typically resolved with rewarming after 15 minutes. No prior or current tissue loss was evident on either side. Symptoms were not present during the warmer summer months. Two years previous to presentation, his symptoms had been limited to the right index finger.

Medical and surgical history: none other than the above

Social history: Significant for cigarette smoking of up to seven cigarettes per day for previous 2 years. Quit 5 weeks prior to presentation. His initiation of smoking predated the onset of right index finger symptoms. No alcohol consumption.

Family history: Noncontributory

Medications: Nifedipine, pentoxifylline, meperidine, enoxaparin, aspirin, and vitamin E. Recently completed a course of amoxicillin clavulanate. Previously on prazosin, but discontinued due to dizziness.

Allergies: NKDA

Examination

Heart: Regular, rate with normal S1 and S2 without S3, S4, or murmur.

Vessels: Diminished right radial pulse; normal left radial pulse; absent ulnar pulses bilaterally; normal brachial pulses bilaterally; normal carotid pulses bilaterally without bruits; normal femoral pulses; diminished right popliteal pulse; absent left popliteal; absent dorsalis pedis; and posterior tibial pulses bilaterally. Right foot had reduced biphasic Doppler signals. Left foot had monophasic Doppler signals. No abdominal bruits audible.

Lower extremities: Large, distal left great toe ulceration with eschar and fibrinous debris with associated tenderness to touch. Small superficial ulceration with erythematous base on the bottom of the left fifth toe, which had been debrided by his local physician a few days prior to presentation. Rubor of the toes bilaterally and elevation pallor of the left foot within 30 seconds.

Upper extremities: Digits of both hands were notably cooler than the corresponding wrist and arm. Bilateral Allen test was indeterminate.

Laboratory Studies

Outside Studies 1 Month Prior to Referral

Sedimentation rate normal; antinuclear antibody negative; Factor V Leiden negative; anticardiolipin antibodies negative; protein S and C levels normal; lupus anticoagulant negative; antithrombin III activity normal; homocysteine level normal; total, HDL, and LDL cholesterol levels normal.

Bilateral upper- and lower-extremity arteriography was notable for major arterial occlusions at the wrist and ankle levels; multiple arterial occlusions and stenoses involving the palmar region and the digital arteries of the hands; arterial occlusion within the radial and ulnar arteries and tibial arteries; 8 cm left proximal popliteal segmental occlusion; and right deep femoral artery occlusion. Angiographic findings were consistent with a diagnosis of Buerger disease. Proximal arterial segments of the aorta, renal arteries, superior mesenteric artery, and brachiocephalic arteries were noted to be normal. There was a slight narrowing at the origin of the celiac of indeterminate etiology.

Echocardiogram was noted to be negative for intracardiac thrombus.

Additional Studies upon Presentation

Lipoprotein (a) normal, cryoglobulin (S) negative; cryofibrinogen (P) negative; total complement normal; rheumatoid factor normal; antinuclear antibody negative; extractable nuclear antigen antibody screen normal; IgM phospholipid antibody negative; IgG phospholipid antibody negative; and sensitive thyrotropin normal. Serum protein electrophoresis was notable for polyclonal gammopathy.

Lower-extremity vascular laboratory studies revealed bilateral arterial occlusive disease of moderate severity in the infrapopliteal segments and severe multilevel disease on the left side. Posterior tibial and anterior tibial Doppler signals were biphasic on the right and monophasic on the left. The highest resting ABIs were 0.66 on the right and 0.48 on the left. TcPO₂ values were mildly reduced at the distal right forefoot site with absolute values of 74 (RPI 0.85) and 68 mm Hg (RPI 0.78) in supine position, worsening to 67 (RPI 0.77) and 60 mm Hg (RPI 0.69) with elevation. Oximetries were severely reduced at both left forefoot sites with absolute values of 19 and 5 mm Hg (RPI 0.22 and 0.06, respectively) in supine position, worsening to 0 and 0 with elevation.

Upper-extremity vascular laboratory studies revealed arterial occlusive disease involving the right radial and ulnar arteries and the left radial and possibly the ulnar arteries. The digital pressures were markedly reduced compared to brachial pressures. Triphasic Doppler signals were present at all arterial sites in the arms, hands, and digits. The digital temperatures were noted to be 4ºC to 8ºC cooler than the corresponding wrist temperatures. No vasospastic processes were evident.

A vascular medicine specialist completed his medical evaluation. Vascular surgery consultation was obtained. Surgical revascularization deferred at that time due to suboptimal revascularization potential and the potential for improved wound healing following smoking cessation. Aggressive local wound care, with discontinuation of foot soaks, and a 5-day course of circulator boot therapy with cefazolin ensued, followed by home therapy with IPC 6 to 8 hours per day and local wound care with a Curasol/Iodosorb mixture to the ulceration. He was instructed in the importance of proper foot care and footwear.

He returned for wound care follow-up and local wound debridement over the next few months, with noted improvement in ulcer healing and 100% epithelization of the base. Three months later, his local physician reported worsening of the ulceration following discontinuation of IPC by the patient and resumption of smoking. He returned to the wound care clinic 1 month later, having quit smoking 4 weeks prior to his return. His ulceration was definitely worse, with a dense eschar, evidence of exposed bone, and increased cyanosis of and pain in the left great toe. Bone destruction and osteomyelitis were not evident on radiograph. Repeat vascular laboratory studies revealed worsening of left foot ischemia with a decrease in ABI and TcPO₂ values when compared to studies 6 months previously. Orthopedic consultation ensued for consideration of amputation. Considering the probability of a nonhealing great toe amputation site and infection, IPC was re-instituted in addition to local wound therapy with the Curasol/Iodosorb mixture.

He returned 1 month later with complaints of unrelenting rest pain in the toe unresponsive to increasing dosages of narcotic medications. Despite continued use of the arterial flow pump, local wound care, and continued smoking cessation his ulceration had worsened; and in fact, he had developed an additional ulcer on the dorsum of the toe. Repeat arteriography was recommended to ascertain the feasibility of percutaneous intervention versus surgical revascularization. Patient returned home and thereafter was lost to follow-up at our institution until 34 months later.

Shortly after his return home from our institution 34 months prior to his return, he underwent surgical revascularization with a left femoropopliteal bypass and left great toe amputation, accompanied by good initial success and near complete healing of his wounds during a period of tobacco cessation. Within 6 months of those procedures, he had resumed smoking; and the graft thrombosed culminating in a below-the-knee amputation.

During the intervening years his numerous attempts with permanent smoking cessation had been unsuccessful, despite psychiatric therapy and progression of Buerger disease with limb loss and threatened limb loss. Within the year preceding his return, he had developed persistent atraumatic ulcerations of the right first and left fifth digits of the hands. There was physical evidence of past tissue loss in multiple upper-extremity digits.

A couple of weeks preceding his return, he developed acute ischemia, rest pain, and threatening tissue loss of the right foot requiring hospitalization. At that time, he had been off cigarettes for about 4 weeks. Per report he had absent posterior tibial and dorsalis pedis Doppler signals; and angiography demonstrated right deep femoral, popliteal, and tibial artery occlusions. Repeat studies at our clinic confirmed absence of Doppler signals in the right foot and severe ischemia from the infrapopliteal level downward, as evidenced by critically reduced TcPO₂ values. The left below-knee amputation stump was also noted to have a severely reduced TcPO₂ value in the supine position, with improvement when dependent.

Medical management options discussed included a trial of circulator boot therapy, IPC, or referral to other centers for hyperbaric oxygen treatment, or participation in a clinical trial utilizing vascular growth factor. His pharmacologic regimen had been maximized previously with the use of a calcium channel blocker, platelet inhibitor, hemorheologic agent (blood viscosity modifier, i.e., pentoxifylline), and an anticoagulant.

During the course of his evaluation, he exhibited inappropriate behavior manifested by loud, profane, and abusive language, aggressive actions, and threatening statements directed toward the physicians and other personnel. At that point, intervention by security and the administrative staff was mandated, resulting in cancellation of a vascular surgery consultation. By way of phone the following day, his mother reported additional escalation of his verbally abusive behavior. He was, therefore, referred to the emergency room for an emergency neurology and psychiatric evaluation. He was found to be neurologically intact. Psychiatric evaluation was consistent with an ongoing major depressive disorder related to medical issues with recent insomnia, anhedonia, feelings of excessive guilt, and passive suicidal thoughts. Previous use of Zoloft and Wellbutrin were noted, and a decision was made to resume Wellbutrin. Hospitalization was deemed unnecessary at that time, and he was advised to seek additional psychiatric care in his local area.

Upon his return to the wound care clinic 2 weeks later, he was noted to have progression of his ulcerations and development of “kissing” ulcers between all toes without evidence of any granulation tissue. Dependent rubor, cyanosis, pitting edema, and extensive tenderness in the foot were evident. He complained of ongoing, unrelenting rest pain despite use of a fentanyl patch and hydrocodone for breakthrough pain.

In light of a severely reduced TcPO₂ value below the knee, he would likely need an above-knee amputation. In lieu of amputation, he was admitted to the hospital for reversal of his Coumadin anticoagulation and to be covered transiently with intravenous heparin in preparation for repeat arteriography and thrombolytic therapy in an attempt to lyse any recent thrombus contributing to the acute event 3 weeks previously. Lytic therapy with alteplase into the thrombosed popliteal and peroneal arteries and attempted angioplasty of the popliteal artery were ultimately unsuccessful. The distal popliteal and all tibial arteries and all plantar branches were noted to be occluded, precluding any revascularization options. He was dismissed home with home health care assistance for continuation of IPC to the upper and right lower extremities, local wound care, and antibiotic therapy. Arrangements were made for him to proceed with a right lower-extremity amputation by his local vascular surgeon 3 days later.

Review Questions

1. Buerger disease most commonly affects

a. Medium- to large-sized arteries in the thorax, abdomen, and pelvis

b. Carotid and cerebral arteries

c. Small- to medium-sized arteries and veins in the upper and lower extremities

2. While a definitive etiology of Buerger disease is unknown, possible causes or precipitating factors include

a. Autoimmune process

b. Tobacco use

c. Genetic disorder

d. All of the above

3. Buerger disease most commonly presents in

a. Men before age 40 to 45

b. Men after age 50

c. Women before age 40 to 45

d. Women after age 50

4. The best diagnostic test(s) to support the clinical diagnosis of Buerger disease is

a. Biopsy of an acutely inflamed artery or vein

b. Four-limb arteriography

c. CTA or MRA

d. ABIs, segmental pressures, transcutaneous oximetry, digital pressures, and temperatures

e. Doppler ultrasound

f. a and b

g. a, b, and c

h. All of the above

5. Primary treatment of Buerger disease is

a. Arterial bypass

b. Cessation of all tobacco products

c. Sympathectomy

d. Omental transfer

e. Amputation

6. Manifestations of Buerger disease include

a. Superficial thrombophlebitis

b. Rest pain of distal extremity

c. Atypical claudication of pedal arch, forefoot, hand, or forearm

d. Ulcers or gangrene of tips of digits

e. All of the above

7. Promising gene and cell therapy promoting angiogenesis and ulcer healing for patients with Buerger disease include

a. Intramuscular injection of vascular endothelial growth factor (VEGF)

b. Fenestration of the tibia for autologous whole bone marrow stem cell transplantation

c. Stem-cell therapy using umbilical cord blood-derived multipotent cells

d. Intramuscular transplantation of autologous bone marrow mononuclear cells

e. All of the above

f. None of the above

Answers/Rationale

1. c. The small- to medium-sized vessels of the arms, hands, legs, and feet are the most frequently affected, although there have been reports of the disease affecting other arteries.

2. d. In addition to a strong association with tobacco use, there may be autoimmune and genetic processes contributing to disease onset.

3. a. The disease generally presents before age 40 to 45 years. Historically, men have been afflicted more frequently, but this situation appears to be changing as tobacco use among women increases.

4. f. While all of these tests may be obtained during the investigation, a biopsy of an affected artery or vein in the acute phase and/or arteriography is diagnostic/supportive of the disease. A biopsy may be contraindicated as blood flow to an already-ischemic limb may be further jeopardized. Arteriography is usually attainable, revealing distinctive arterial abnormalities to support the diagnosis or to rule out other causes of ischemia. CTA and MRA may be used to rule out other causes of ischemia but may not be sufficient for imaging of distal arteries and detection of the small artery pathology seen in Buerger disease. This will likely change with improvements in CTA and MRA technology.

5. b. Discontinued use of all tobacco products is essential for disease remission and limb salvage. Avoidance of passive smoke is advised, although exposure to passive smoke has not been proven to affect disease onset or progression. Amputation of digits or limb may be necessary for control of unremitting rest pain, infection, or ulceration/gangrene. Arterial bypass, sympathectomy, and omental transfer are applicable to a minority of Buerger patients.

6. e. All of the above

7. e. All of the above. Feasibility, safety, and efficacy of gene and cell therapy have been established, but further study with large-scale, randomized control trials are needed to confirm effects of gene and cell therapy alone and in combination with one another.

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