para>Not common in the elderly
Pediatric Considerations
Rare in children. Consider in adolescent smokers presenting with claudication, digital ulcers, or digital gangrene.
ETIOLOGY AND PATHOPHYSIOLOGY
- Idiopathic, but it demonstrates impaired endothelium-dependent vasorelaxation and decreased peripheral sympathetic outflow. Nonendothelial mechanisms of vasodilation are intact.
- Segmental infiltration of inflammatory cells in vessel wall leads to thrombotic occlusion.
- Highly cellular and inflammatory thrombus with relative sparing of the blood vessel wall
- Smoking predisposes to occurrence.
- Genetic factors implicated
- Autoimmune component which is not fully understood.
- Chronic anaerobic periodontal infection
Genetics
- Greater prevalence of HLA-A54, HLA-A9, and HLA-B5
- HLA-B12 antigen may be associated with disease resistance.
- Familial cases rarely reported
RISK FACTORS
- Smoking as little as 1 to 2 cigarettes daily, chewing tobacco, snuff, and nicotine replacement are all risk factors for thromboangiitis obliterans (TAO).
- Chronic anaerobic periodontal infection also may play a role in the development of TAO.
GENERAL PREVENTION
Tobacco cessation
DIAGNOSIS
- Point scoring systems are available to clarify clinical diagnosis. Two diagnostic tools are most referenced.
- Shionoya criteria:
- Smoking history
- Onset <50 years of age
- Infrapopliteal arterial occlusions
- Either upper limb involvement or phlebitis migrans
- Absence of atherosclerotic risk factors other than smoking
- Diagnosis requires all five elements.
- Olin criteria:
- Age <45 years
- Current (or recent) history of tobacco use
- Presence of distal extremity ischemia (claudication, pain at rest, ischemic ulcers, or gangrene), documented by noninvasive vascular testing
- Exclusion of autoimmune diseases, hypercoagulable states, and diabetes mellitus
- Exclusion of a proximal source of embolization by echocardiography and arteriography
- Consistent arteriographic findings in the clinically involved and noninvolved limbs
- Symptoms tend to wax and wane in early disease and often are asymmetric. Symptoms may be gradual/have a sudden onset related to impaired vasculature. Usually >1 limb is involved (1,2).
HISTORY
- Foot/arch claudication may be the presenting manifestation (less commonly claudication in hand, forearm) and is often mistaken for an orthopedic problem.
- Cold sensitivity
- Paresthesias (e.g., numbness, tingling, burning, hypoesthesia) of feet and/or fingers
- Persistent extremity pain (may be worse at rest) which may be disabling.
- Paroxysmal "electric shock " pain of ischemic neuropathy
- Migratory superficial phlebitis
PHYSICAL EXAM
- Ischemic ulcerations of the digits
- Allen test (performed by occluding the radial and ulnar arteries while the clenched hand is elevated above the level of the heart. The hand is then relaxed and pressure on the ulnar artery is released allowing a return of normal circulation) is often positive (failure of the return of normal color to the hand).
- Raynaud phenomenon (~20% of patients)
- Postural color changes: pallor on elevation; rubor on dependency
- "Buerger color " : cyanosis of hands and feet
- Tender skin nodules on extremities
- Decreased distal pulses
- Proximal pulses normal; Allen test may be abnormal.
- Foot edema
- Gangrene
DIFFERENTIAL DIAGNOSIS
- Peripheral neuropathy, peripheral atherosclerotic disease, arterial thromboembolic disease, idiopathic peripheral thrombosis
- Takayasu arteritis; CREST syndrome (calcinosis, Raynaud phenomenon, esophageal dysfunction, sclerodactyly, telangiectasia)
- Hypercoagulable states; systemic lupus erythematosus; scleroderma
- Necrotizing arteritis
- Occupational trauma; acrocyanosis; frostbite; neurotrophic ulcers
- Reflex sympathetic dystrophy; metatarsalgia; gout
DIAGNOSTIC TESTS & INTERPRETATION
No specific lab finding is purely diagnostic for TAO.
Initial Tests (lab, imaging)
Noninvasive vascular studies, including transcutaneous oxygen tension (TcPO2), ankle brachial index, and simultaneous brachial pressures
- Consider CBC, LFTs, creatinine, fasting glucose, erythrocyte sedimentation rate (ESR), antinuclear antibodies (ANA), rheumatoid factor (RF), anticentromere antibody and Scl70 antibody, and a hypercoagulability screen to rule out other diseases.
- Increased levels of antiendothelial cell antibodies are seen in patients with active TAO.
- Anticardiolipin antibodies may be associated with TAO and may worsen the thrombotic event.
- Homocysteine may be elevated, but lacks specificity.
- Drug screen: Cocaine, amphetamines, and cannabis can mimic TAO.
- A vascular biopsy is usually not necessary unless patients present with unusual characteristics such as large-artery involvement or age >45 years.
- Doppler US (not specific)
- Arteriogram/digital subtraction angiography
- Multiple areas of segmental occlusion of small- to medium-sized arteries of arms and legs
- The disease is confined most often to the distal circulation and is almost always infrapopliteal in the lower extremities and distal to the brachial artery in the upper extremities.
- "Skip " areas may be demonstrated.
- Numerous collateral vessels around occluded segments may give a characteristic corkscrew appearance (Martorell sign).
- Classification by size and pattern has been proposed:
- Type I, artery diameter >2 mm, large helical sign
- Type II, diameter >1.5 mm and ≤2 mm, medium helical sign
- Type III, diameter ≥1 mm and ≤1.5 mm, small helical sign
- Type IV, diameter <1 mm, tiny helical sign
- Larger arteries are spared. More serious disease occurs distally.
- No apparent source of emboli
Follow-Up Tests & Special Considerations
- ESR and CRP are usually normal.
- Commonly measured autoantibodies (e.g., ANA and RF) are normal/negative.
- The prevalence of ischemic ulcers is significantly higher in patients who have small corkscrew patterns (type III and IV) in distal segments of limb collaterals than in patients who have large corkscrew collaterals.
Diagnostic Procedures/Other
- Echocardiography (to exclude emboli)
- Biopsy is only indicated if there are unusual features.
Test Interpretation
- Segmental inflammatory thrombosis of both arteries and veins
- Histologic findings may vary between acute, intermediate, and chronic stages of the disease.
- Histologic sine qua non: granulomas with collections of neutrophils in the organizing thrombus
- Vessel wall is relatively spared.
- Wall sparing distinguishes TAO from arteriosclerosis and other systemic vasculitides, which show wall disruption.
- Acute lesions show occlusive, highly cellular, inflammatory thrombi with less inflammation in vessel wall. Polymorphonuclear neutrophils, microabscesses, and multinucleated giant cells may be present.
- Intermediate lesions show organizing thrombus.
- Chronic lesions show recanalized thrombus and perivascular fibrosis.
TREATMENT
GENERAL MEASURES
- Tobacco cessation (mandatory)
- Eliminate other vasoconstrictive triggers (cold/drugs).
- Eliminate exposure to chemical damage (e.g., iodine, carbolic acid, salicylic acid).
- Avoid trauma (e.g., heel protectors, orthotics for shoes, vascular boots); proper foot care
- Initiate a walking program.
- Lubricate skin with moisturizer.
- Lamb 's wool between toes
MEDICATION
First Line
- Discontinue smoking/tobacco use in any form.
- Wound care
- Amputation for severe disease
- Antibiotics for infected digital ulcers and osteomyelitis
Second Line
- If vasospasm is present, trial of dihydropyridine calcium channel blocker such as amlodipine 5 to 20 mg PO daily or nifedipine 30 to 180 mg PO daily at the highest tolerated dose. Verapamil 120 to 480 mg PO daily has also been found to be helpful in decreasing the pain from intermittent claudication in some patients.
- Iloprost, a prostacyclin analogue and potent vasodilator, given IV promotes both ulcer healing and given PO only decreases analgesic requirement. Unfortunately, this medication is only available by inhalation in the United States and has not yet been shown to be beneficial for TAO.
ISSUES FOR REFERRAL
Consider referral to nicotine addiction program.
ADDITIONAL THERAPIES
- Spinal cord stimulation may play a role.
- Distraction osteogenesis is an emerging therapeutic alternative that is currently investigational.
- Intermittent pneumatic compression enhances calf circulation and may be helpful as an adjunct in patients who are not candidates for revascularization.
- Case studies have shown success with bosentan (off label) (3)[B].
- Hyperbaric oxygen therapy, autologous bone marrow transplant of mononuclear cells, and autologous peripheral blood mononuclear cells (A-PBMNC) implantation are therapy modalities, with small studies suggesting potential use (4,5)[B].
- Basic fibroblast growth factor (bFGF) has been used in a small controlled clinical trial with early success in very small trial (6)[B].
SURGERY/OTHER PROCEDURES
- Amputation
- For nonhealing ulcers, gangrene, or intractable pain
- Should preserve as much limb as possible
- Infrainguinal bypass
- In severe disease, a lumbar sympathectomy increases blood supply to the skin.
- Surgical revascularization may be difficult due to the diffuse segmental involvement and extreme distal nature of the disease.
INPATIENT CONSIDERATIONS
Inpatient nicotine dependence treatment is an alternative for recalcitrant nicotine addiction.
Admission Criteria/Initial Stabilization
Critical limb ischemia
- Inpatient: gangrene
- Inpatient for dorsal/lumbar sympathectomy
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Use a bed cradle (nonheated) to prevent pressure from bed linens.
Patient Monitoring
Ensure tobacco cessation and monitor for recurrence.
PATIENT EDUCATION
- Avoid primary or secondhand smoke.
- Proper skin/foot care
PROGNOSIS
- Average age of death is 52 years ± 8.9 years; significantly lower than matched U.S. population
- In one series, 94% of patients who quit smoking avoided amputation, whereas 43% of patients who continued smoking required at least one amputation.
- Another series reported an amputation rate of 25% at 5 years and 38% at 10 years of follow-up.
- The risk for amputation is eliminated after 8 years of smoking cessation.
COMPLICATIONS
Ulcerations, gangrene, pain, and need for amputation
REFERENCES
11 Piazza G, Creager MA. Thromboangiitis obliterans. Circulation. 2010;121(16):1858 " 1861.22 Weinberg I, Jaff MR. Nonatherosclerotic arterial disorders of the lower extremities. Circulation. 2012;126(2):213 " 222.33 De Haro J, Bleda S, Acin F. An open-label study on long-term outcomes of bosentan for treating ulcers in thromboangiitis obliterans (Buerger 's disease). Int J Cardiol. 2014;177(2):529 " 531.44 De Angelis B, Gentile P, Orlandi F, et al. Limb rescue: a new autologous-peripheral blood mononuclear cells technology in critical limb ischemia and chronic ulcers. Tissue Eng Part C Methods. 2015;21(5):423 " 435.55 Idei N, Soga J, Hata T, et al. Autologous bone-marrow mononuclear cell implantation reduces long-term major amputation risk in patients with critical limb ischemia: a comparison of atherosclerotic peripheral arterial disease and Buerger disease. Circ Cardiovasc Interv. 2011;4(1):15 " 25.66 Kumagai M, Marui A, Tabata Y, et al. Safety and efficacy of sustained release of basic fibroblast growth factor using gelatin hydrogel in patients with critical limb ischemia [published online ahead of print April 11, 2015]. Heart Vessels.
ADDITIONAL READING
- Abeles AM, Nicolescu M, Pinchover Z, et al. Thromboangiitis obliterans successfully treated with phosphodiesterase type 5 inhibitors. Vascular. 2014;22(4):313 " 316.
- Dargon PT, Landry GJ. Buerger 's disease. Ann Vasc Surg. 2012;26(6):871 " 880.
- De Haro J, Acin F, Bleda S, et al. Treatment of thromboangiitis obliterans (Buerger 's disease) with bosentan. BMC Cardiovasc Disord. 2012;12:5.
- Fujii Y, Soga J, Nakamura S, et al. Classification of corkscrew collaterals in thromboangiitis obliterans (Buerger 's disease): relationship between corkscrew type and prevalence of ischemic ulcers. Circ J. 2010;74(8):1684 " 1688.
- Ryu SW, Jeon HJ, Cho SS, et al. Treatment of digit ulcers in a patient with Buerger 's disease by using cervical spinal cord stimulation -a case report-. Korean J Anesthesiol. 2013;65(2):167 " 171.
CODES
ICD10
I73.1 Thromboangiitis obliterans [Buerger 's disease]
ICD9
443.1 Thromboangiitis obliterans [Buerger 's disease]
SNOMED
- Thromboangiitis obliterans (disorder)
- Neuropathy in thromboangiitis obliterans (disorder)
CLINICAL PEARLS
- Tobacco cessation is mandatory. Tobacco cessation decreases the risk of amputation in patients with TAO. Nicotine replacement therapy may keep the disease active.
- Urinary nicotine and cotinine levels are helpful to assess ongoing tobacco use if the disease is still active despite patient 's claims of tobacco cessation.