A. Characteristics

1. Segmental vascular thrombotic obliterative disease
   1. Non-necrotizing thrombi affecting mainly small and medium sized arteries and veins
   2. Inflammatory thrombi affect arteries and veins in acute phase of disease
   3. In chronic phase, organized thrombus and fibrotic, obliterated blood vessel is found
   4. Internal elastic lamina is intact (contrast with atherosclerosis and systemic vasculitis)
2. Usually affects limbs
3. HLA-B5 and A9 are increased in patients
4. Anti-Collagen Types I and III Abs are found in many patients
5. Endothelium dependent arterial relaxation is dysfunctional
   1. Poor vascular response to acetylcholine
   2. Good vascular dilatory response to nitroprusside (endothelium-independent)

B. Epidemiology

1. Prevalence is declining, ~12 per 100,000 persons at present
2. Usually occurs in young, male cigarette smokers (~80%)
3. Represents <5% of vascular disease in Europe, up to 40% in Middle East
4. Presentation most commonly in age 40-45

C. Symptoms

1. Absent or decreased peripheral pulses / Raynaud's Phenomenon
2. Claudication - vascular anomalies are distal to great vessels, however
3. Ulceration / Gangrene of Digits
4. Superficial Thrombophlebitis
   1. Occurs in ~40% of patients
   2. Usually migratory in nature
   3. Parallel's course of disease
5. All limbs are usually affected based on angiography
6. Patients typically present with symptoms in 1-2 limbs

D. Diagnosis

1. Allen test should be performed in both hands of any suspected patient
   1. Abnormal Allen test in young male smoker with ischemic symptoms strongly suggests thromboangiitis obliterans
   2. Patient makes a fist (removes blood from hand)
   3. Then examiner presses thumbs against both radial and ulnar arteries to occlude them
   4. Patient then releases fist
   5. Examiner removes pressure from ulnar artery
   6. Note whether or not hand fills with blood when pressure is released (normally it should fill)
   7. Repeat test with examiner initially removing pressure from radial artery
   8. Abnormal Allen test (hand not fill with blood after release of pressure) suggests disease
2. No specific serological tests for disease
   1. Standard blood counts and serum chemistries usually normal
   2. C-reactive protein and ESR usually normal
   3. Screening for CREST antibodies (Scl-70, anti-centromere) recommended
   4. Screening for thrombophilia
3. Must rule out other causes of vasculitis

E. Therapy

1. Discontinue smoking
   1. Absolute abstinence from tobacco is required
   2. Patients who abstain from smoking have <5% chance of requiring amputation
   3. Patients who continue to smoke have ~50% chance of requiring amputation
   4. Smoking cessation may be monitored with urine nicotine and cotinine levels
2. Discontinue any vasoconstrictors
3. Vasodilators
   1. Oral agents are largely unproven but often used
   2. Calcium channel blockers: such as nifedipine, amlodipine, felodipine
   3. Alpha-1 adrenergic blockers: such as prazosin, doxazosin
   4. Intravenous iloprost has shown efficacy in severe patients (continuous infusion) [3]
4. Single aspirin (standard 325mg dose) usually given once daily (unclear benefit)
5. Amputation may be required

F. Kohlmeier-Degos Syndrome (Malignant Atrophic Papulosis) []

1. Thrombotic vasculopathy of medium vessels
2. Non-inflammatory vascular occlusive process mainly affecting arterioles
3. Blood vessels with increased intima due to proliferation of endothelial cells
4. Superimposed thrombus may occur
5. Result is ischemia and infarction
6. Most cases with skin involvement with small whitish nodules to pinkish papules
7. Lymphatic obstruction
8. Severe forms may affect central nervous system, gastrointestinal tract, submucosal arteries

References

1. Nuermberger E. 2002. Am J Med. 112(1):71
2. Olin JW. 2000. NEJM. 343(12):864
3. Fiessinger JN and Schafer M. 1990. Lancet. 335:555
4. Caviness VS Jr, Sagar P, Israel EJ, et al. 2006. NEJM. 355(24):2575 (Case Record)