Vascular Medicine and Endovascular Interventions - part 2 ppsx

CHAPTER 2 Vasculitis and Connective Tissue Disease 25 b. Drug-induced SLE usually affects the kidneys and central nervous system. c. Monozygotic twins are usually discordant for SLE. d. Women are affected more often than men. Suggested Readings The European TAO Study Group. Oral iloprost in the treatment of thromboangiitis obliterans (Buerger’s disease): a double- blind, randomised, placebo-controlled trial. Eur J Vasc En- dovasc Surg. 1998;15:300-7. Erratum in: Eur J Vasc Endovasc Surg. 1998;16:456. Fiessinger JN, Schafer M. Trial of iloprost versus aspirin treat- ment for critical limb ischaemia of thromboangiitis obliterans: the TAO Study. Lancet. 1990;335:555-7. Guillevin L, Lhote F. Treatment of polyarteritis nodosa and mi- croscopic polyangiitis. Arthritis Rheum. 1998;41:2100-5. Haynes BF, Kaiser-Kupfer MI, Mason P, et al. Cogan syndrome: studies in thirteen patients, long-term follow-up, and a review of the literature. Medicine (Baltimore). 1980;59:426-41. Hellmann DB. Immunopathogenesis, diagnosis, and treatment of giant cell arteritis, temporal arteritis, polymyalgia rheumatica, and Takayasu’s arteritis. Curr Opin Rheumatol. 1993;5:25-32. Hochberg MC. Updating the American College of Rheumatol- ogy revised criteria for the classifi cation of systemic lupus ery- thematosus. Arthritis Rheum. 1997;40:1725. Hoffman GS, Kerr GS, Leavitt RY, et al. Wegener granulomatosis: an analysis of 158 patients. Ann Intern Med. 1992;116:488-98. Hunder GG. Giant cell arteritis in polymyalgia rheumatica. Am J Med. 1997;102:514-6. Hunder GG, Bloch DA, Michel BA, et al. The American College of Rheumatology 1990 criteria for the classifi cation of giant cell arteritis. Arthritis Rheum. 1990;33:1122-8. Ishikawa K. Diagnostic approach and proposed criteria for the clinical diagnosis of Takayasu’s arteriopathy. J Am Coll Car- diol. 1988;12:964-72. Lanham JG, Elkon KB, Pusey CD, et al. Systemic vasculitis with asthma and eosinophilia: a clinical approach to the Churg- Strauss syndrome. Medicine (Baltimore). 1984;63:65-81. Lightfoot RW Jr, Michel BA, Bloch DA, et al. The American Col- lege of Rheumatology 1990 criteria for the classifi cation of poly- arteritis nodosa. Arthritis Rheum. 1990;33:1088-93. Newberger JW, Takahashi M, Beiser AS, et al. A single intrave- nous infusion of gamma globulin as compared with four infu- sions in the treatment of acute Kawasaki syndrome. N Engl J Med. 1991;324:1633-9. Olin JW. Thromboangiitis obliterans (Buerger’s disease). N Engl J Med. 2000;343:864-9. Sakane T, Takeno M, Suzuki N, et al. Behçet’s disease. N Engl J Med. 1999;341:1284-91. 26 3 Upper Extremity Arterial Disease: Raynaud Syndrome, Occlusive Arterial Diseases, and Thoracic Outlet Syndrome Roger F. J. Shepherd, MBBCh Many patients have only one or two color changes with episodic pallor or cyanosis of the digits. It is not necessary to have all three (tricolor) changes for a diagnosis of Ray- naud syndrome. Vasospastic attacks most commonly in- volve the fi ngers but in up to one-third of patients can also affect toes. Less frequently, vasospasm involves the nose, ear, and nipple. Vasospasm can also affect the coronary and cerebral arteries. Patients with Prinzmetal angina are more likely to have Raynaud phenomenon and migraine headaches. In one study of 62 patients with variant angina, 15 had Raynaud phenomenon and 16 had migraine. • Raynaud syndrome is characterized by episodic pallor or cyanosis of one or more fi ngers occurring in response to cold or emotional stress Terminology Since the days of Maurice Raynaud, all patients with vasospasm, by tradition, have been classifi ed into two groups on the basis of the presence or absence of under- lying occlusive arterial disease: Raynaud disease (a pri- mary vasospastic disorder in which no underlying cause is identifi able—idiopathic or pure vasospasm) and Raynaud phenomenon (vasospasm is secondary to some other un- derlying condition or disease). Unfortunately, in clinical practice, use of these diagnostic terms (“Raynaud disease” or “Raynaud phenomenon”) has not been intuitive. They are commonly misunderstood and often mistakenly in- terchanged. John Porter and others therefore advocated replacing the older terms “disease” and “phenomenon” with “Raynaud syndrome.” “Primary Raynaud syndrome” (idiopathic or pure va- sospasm), by Porter’s terminology, refers to a primary va- sospastic disorder with no identifi able underlying cause; formerly known as “Raynaud disease.” “Secondary Ray- naud syndrome,” by Porter’s terminology, refers to va- sospasm secondary to some other underlying condition Introduction Upper extremity arterial disease is a fascinating and often challenging area of vascular medicine. Impaired blood fl ow to the hands and fi ngers can be caused by obstruc- tion of the large arteries, smaller digital arteries, or the microvasculature. Resulting digital ischemia can be acute or chronic and can be due to reversible vasospasm, fi xed obstructive arterial disease, or both. Many diverse disorders are associated with upper ex- tremity arterial disease. In addition to atherosclerosis, the vascular clinician must be familiar with various unusual non-atherosclerotic conditions, including connective tis- sue diseases, vasculitis, thromboangiitis obliterans (TO), hematologic disorders, thoracic outlet syndrome, and occupation-related arterial disease, including the hypothe- nar hammer syndrome. Raynaud Syndrome Defi nition Raynaud syndrome is characterized by episodic pallor or cyanosis of one or more fi ngers occurring in response to cold or emotional stress. Maurice Raynaud fi rst described the digital color changes diagnostic of this syndrome in 1882. A typical vasospastic attack is characterized by the sudden onset of pallor in part or all of one or more digits. Cyanosis follows as static blood in the capillaries becomes desaturated. With relief of vasospasm and return of arte- rial infl ow to the fi nger, digital rubor results from post- ischemic hyperemia, and the skin color gradually returns to normal. Today, these triphasic color changes are often considered to be the hallmark of Raynaud syndrome. © 2007 Society for Vascular Medicine and Biology CHAPTER 3 Upper Extremity Arterial Disease 27 vasodilation causes a slight reopening of arteries to allow enough blood fl ow to the fi ngers to avoid freezing the fi n- gertips. With continued cold exposure, fi nger blood fl ow fl uctuates with a regular rhythmic cycle of 30 seconds to 2 minutes. These alternating periods of vasoconstriction and dilation are called “the hunting response.” • Hand blood fl ow has a substantial effect on body tem- perature These changes in blood fl ow in the fi ngers due to envi- ronmental temperature are effected in part by the cen- tral nervous system with input from the cerebral cortex, hypothalamus, and medullary vasomotor centers. The hypothalamus changes body temperature by altering the sympathetic outfl ow to the digital vessels via the medulla, spinal cord, sympathetic ganglion, and local nerves. The sympathetic nerves innervate vascular smooth muscle in the digital arteries causing digital artery constriction. During cooling of the fi nger, abrupt cessation of blood fl ow can occur due to vasoconstriction. Almost all second- ary causes of RS produce some degree of fi xed obstruction to blood fl ow, and cold-induced vasospasm occurs more readily. If a vessel is narrowed because of preexisting large or small vessel disease, a lower “critical closing pressure” results, and a relatively normal vasoconstrictor response to cold or other stimuli can cause temporary vessel closure. Several systemic diseases may cause decreased digital systolic pressure as a result of “fi xed” arterial obstruction or increased blood viscosity. For example, in scleroderma, a combination of intimal hyperplasia, thrombosis, and fi - brosis results in arterial narrowing. Abnormal plasma pro- teins causing hyperviscosity result in reduced blood fl ow. Primary Raynaud Syndrome Incidence Primary RS is a common disorder. In one large survey con- ducted in South Carolina, 4.6% of 1,752 randomly selected persons indicated they had experienced symptoms of white or blue color changes of the fi ngers. The prevalence is higher in cooler climates, especially in European coun- tries including England, Denmark, and France, where in- cidences as high as 11% in men and 22% in women have been reported. The age of onset in primary RS ranges from 11 to 45 years. A study of 474 patients with RS reported an aver- age age of 31 years. Older patients can also have primary RS, but onset of symptoms at an older age should arouse suspicion of a secondary underlying cause. Although pri- mary RS is said to predominantly affect young women, occurring more often than in men by a ratio of 4:1, more or disease; formerly known as “Raynaud phenomenon.” Usually, those with primary Raynaud syndrome (RS) have pure vasospasm and those with secondary RS have un- derlying occlusive arterial disease predisposing them to vasospastic attacks. This distinction has important clini- cal utility because it underscores the different pathologic mechanisms, treatment options, and prognoses of these two groups. For patients with an underlying disease causing RS, both diagnoses should be used (e.g., “TO with secondary RS”). For patients with known occlusive arterial disease causing chronic digital ischemia (as opposed to episodic vasospasm), the diagnosis should not be labeled as “RS” but as the underlying disease, such as atherosclerosis. Many cases of severe, non-episodic, limb-threatening hand ischemia have been misdiagnosed as vasospastic RS. This can cause a delay in the appropriate management of critical non-reversible hand and digital ischemia. • “Primary Raynaud syndrome” refers to a primary vasospastic disorder with no identifi able underlying cause • “Secondary Raynaud syndrome” refers to vasospasm secondary to some other underlying condition or dis- ease Determinants of Blood Flow in the Fingers Blood fl ow to the fi ngers serves two purposes: ther- moregulatory and nutritional. Only a very small portion of digital blood fl ow (less than 10%) is needed to provide nutrients and oxygen to the tissues. Most of the blood fl ow in the fi ngers serves an important role in thermoregulation to control body temperature. Blood vessels that are superfi cially located in the skin radiate excess heat to the environment, which reduces core body temperature. In response to cold, these arteries constrict to decrease blood fl ow and conserve body heat. Arteriovenous (AV) anastomoses (connecting the arterial and venous circulation) are present in the fi ngers and the palms of the hands. These anastomoses shunt blood to ve- nous circulation before it reaches the distal small capillar- ies. In warm environments the fi ngers are able to dramati- cally increase blood fl ow through these AV fi stulas. More than 50 years ago, Greenfi eld demonstrated that one hand can lose 800 calories of heat per minute, which causes a de- crease in esophageal temperature of 0.6°C in 9 minutes. These AV shunts are under the control of the sympathe- tic nervous system. In response to cold exposure or body cooling, increased sympathetic tone causes the digital AV shunts to close, and with less blood fl ow through the fi n- gers, the core body temperature is maintained. Maximum vasoconstriction to cold exposure occurs at skin tempera- tures of 10°C to 20°C. At lower temperatures, cold-induced Vascular Medicine and Endovascular Interventions 28 recent studies have found that men are affected almost as frequently as women with a ratio closer to 1.6:1. Mechanism of Vasospasm in Primary Raynaud Syndrome The exact cause of vasospastic attacks in primary RS re- mains unknown. No structural abnormality of the dig- ital arteries has been demonstrated. Whether primary RS represents an exaggeration of normal thermoregulatory mechanisms or is due to a specifi c local or systemic ab- normality has remained an area of controversy. Raynaud, in 1888, believed that the central nervous system was re- sponsible and that vasospasm resulted from overactivity of the sympathetic nervous system. This seems plausible because the autonomic nervous system maintains arteri- olar tone and blood pressure and because emotional stress can bring on vasospastic attacks. Lewis, in 1929, believed that a local abnormality was present in the digital arteries of patients which caused an increased sensitivity of the blood vessel to cold. In a series of studies, he could produce ischemic attacks in a single fi nger by local cooling. Nerve blocks or surgical sym- pathectomy could not prevent these cold-induced attacks. Lewis also found that cooling the proximal fi nger, but keeping the distal fi nger warm, caused distal vasospasm. He therefore concluded that the vasospasm was caused by local factors and not entirely sympathetically mediated. We now recognize that several different factors, acting by local, humoral, and nervous system mechanisms, af- fect the normal regulation of blood fl ow to the fi ngers. De- rangement of any of these factors may be responsible for the vasospastic attacks in primary RS. Possible abnormali- ties in primary RS include alterations in neurotransmitters released from sympathetic nerves; increased activation of β 2 -adrenoceptors on the nerve endings; endothelial dys- function with a shift in the balance from endothelium-de- rived relaxing to contracting factors; increased platelet se- rotonin levels or alteration in neurohumoral transmitters released from local nerves; lower systemic blood pressure; or arterial obstruction and changes in blood viscosity. Secondary Causes of Raynaud Syndrome and Occlusive Arterial Disease Many disorders are associated with RS (Table 3.1). The two most common secondary causes are connective tissue dis- eases (CTDs, particularly scleroderma) and atherosclero- sis. Less common but important diseases include vasculi- tis, TO, thromboembolism, and atheroembolism. Diseases unique to the upper extremity include dynamic arterial compression resulting from thoracic outlet syndrome (TOS). Occupational trauma to the hand can cause the hypothenar hammer syndrome or vibration white fi nger. Prescription drug–induced vasospasm is common. Sys- temic disorders leading to increased viscosity can cause vasospasm and include myeloma, cryoglobulinemia, and hepatitis antigenemia. Depending on the thoroughness of clinical evaluation and referral bias, more than half of pa- tients referred for evaluation of RS are ultimately found to have an underlying cause. Approximately 30% to 60% of patients presenting for evaluation of RS have primary disease. In a large series of 615 patients at the Oregon Health & Science University, more than half had pure vasospastic disease. In those with secondary RS, 27% were found to have a CTD. Scleroderma was the most common CTD, followed by undifferentiated and mixed CTD. Other conditions included atherosclero- sis, TO, cancer, and vibration white fi nger. • Approximately 30%-60% of patients presenting for evaluation of RS have primary disease Table 3.1 Conditions Associated With Secondary Raynaud Syndrome Disease type Examples Connective tissue disease Scleroderma, CREST syndrome Systemic lupus erythematosus Rheumatoid arthritis Mixed connective tissue disease Dermatomyositis Small/medium vessel vasculitis Atherosclerosis and occlusive arterial disease Atherosclerosis obliterans Atheroembolism Diabetic distal arterial disease Thromboangiitis obliterans (Buerger disease) Thromboembolism Cardiac embolism Arterial embolism Paradoxic embolism Large vessel vasculitis Takayasu arteritis Extracranial temporal arteritis Dynamic entrapment Thoracic outlet syndrome Occupational arterial trauma Hypothenar hammer syndrome Vibration-induced Raynaud syndrome Drug-induced vasospasm β-Blockers Vasopressors, epinephrine Ergot Cocaine Amphetamines Vinblastine/bleomycin Infections Parvovirus Sepsis/disseminated intravascular coagulation Hepatitis B and C antigenemia Malignancy Multiple myeloma Leukemia Adenocarcinoma Astrocytoma Hematologic Polycythemia vera Thrombocytosis Cold agglutinins Cryoglobulinemia CHAPTER 3 Upper Extremity Arterial Disease 29 Connective Tissue Diseases Systemic and Limited Scleroderma The word “scleroderma” is derived from the words “sk- leros” (meaning “hard”) and “derma” (meaning “skin”). Scleroderma is characterized by progressive fi brosis of the skin and internal organs. The most characteristic feature of scleroderma is thickening of the skin, especially involv- ing the fi ngers and hands. In advanced scleroderma, joint contraction leads to a clawlike hand deformity. Ulcers can form at the fi ngertips and over joints. These ulcers may be refractory to therapy and are slow to heal, which causes considerable ischemic digital pain. The pathogenesis of arterial disease in scleroderma is not well understood, but it is most likely initiated by pro- liferation of smooth muscle cells in blood vessel intima, which causes luminal narrowing. Activated platelets re- lease platelet-derived growth factors and thromboxane A 2 , which can induce vasoconstriction and stimulate growth of endothelial cells and fi broblasts. Fibrin is deposited within and around vessels, causing vessel obstruction. Small arteries, arterioles, and capillaries are affected by these proliferative structural changes in the vessel wall, which results in tissue ischemia. Digital involvement is disabling, as in limited scleroderma (see below), but death results from cardiac and pulmonary complications in those with systemic scleroderma. CREST syndrome (or limited scleroderma) takes its name from the 5 main associated symptoms: Calcinosis, RS, Esophageal dysmotility, Sclerodactyly, and Telangiectasis. Calcinosis refers to subcutaneous calcifi cation found in the fi ngers, forearms, and pressure points. RS occurs in more than 90% of patients with scleroderma and can be the initial presenting symptom in one-third of patients. Esophageal dysmotility leads to dysphagia, regurgitation, and aspiration. Sclerodactyly can present as puffi ness of the fi ngers. Telangiectasis on the fi ngers and hands is a pathognomonic fi nding in scleroderma. Serologic studies may help to confi rm the diagnosis of scleroderma and are also useful in screening for occult un- derlying CTD. Antinuclear antibodies (ANA) are present in 95% of patients with scleroderma but are not specifi c for scleroderma and can be present in several other CTDs. A positive ANA result raises suspicion for a CTD but on its own does not make the diagnosis. To be clinically sig- nifi cant, a positive ANA should have a titer greater than 1:160 or 1:320. By immunofl uorescence, ANA should be >3.0 units (>6.0 units is strongly positive). Autoantibodies specifi c for scleroderma include those against topoisomer- ase 1, centromere, Scl-70, RNA polymerase 1, and U3 ribo- nucleoprotein. The anticentromere antibody is associated with CREST syndrome. As opposed to that in vasculitis, the erythrocyte sedimentation rate is usually normal in systemic scleroderma. • ANAs are present in 95% of patients with scleroderma but are not specifi c for scleroderma and can be present in several other CTDs Mixed and Undifferentiated CTD Mixed CTD is an overlap syndrome with features of at least two CTDs, usually scleroderma and systemic lupus erythematosus (SLE). Undifferentiated CTD can have a mixture of clinical fi ndings including polyarthritis, RS, and lupus-type features. • RS is a frequent manifestation of SLE, occurring in up to 80% of patients Systemic Lupus Erythematosus SLE is a multisystem disease, most frequently occurring in young females. It can affect many organ systems with features of arthralgias, rash, pericarditis, pleuritis, and glomerulonephritis, usually with a positive ANA. RS oc- curs in up to 80% of patients with SLE. Small Vessel Vasculitis Rheumatoid arthritis and Sjögren syndrome can be associ- ated with a small vessel vasculitis. Other small vessel vas- culitides include Wegener granulomatosis, microscopic polyarteritis nodosum, and cutaneous livedo vasculitis. Malignancy can be associated with vasculitis. Risk of Subsequent CTD Development With Raynaud Syndrome The onset of RS can precede the clinical onset of a CTD by up to several years. Patients with RS should be told that the risk of future development of a CTD is low but that follow-up evaluation is suggested. Less than 5% of pa- tients (4 of 87 in one study) with primary RS subsequently had CTD development over a 5-year period. Some pa- tients are at higher risk of a CTD developing—especially if they have subtle abnormalities by history, examination, or blood tests, such as a low-positive ANA or abnormal nailfold microscopy. It has been suggested that all patients be followed up for more than 2 years before confi rming a diagnosis of primary RS (vs secondary RS). Atherosclerosis Atherosclerosis in patients without diabetes mellitus Vascular Medicine and Endovascular Interventions 30 generally affects the larger, more proximal arteries and is unusual distal to the subclavian level. If proximal athero- sclerosis causes digital ischemia, it is more often due to atheroembolism (from an ulcerated plaque in the innomi- nate or subclavian artery) than due to decreased distal per- fusion pressure. As in the lower extremities, infl ow arterial disease in the upper extremity can cause claudication but is less likely to cause critical ischemia. RS can be a presenting symptom of TO. TO is a non- atherosclerotic infl ammatory disorder involving distal, small, and medium-sized arteries in the fi ngers and toes, especially affecting male smokers younger than 40 years of age (Fig. 3.1). It can present with features of chronic ischemia with development of painful fi ngertip necrosis and ulcerations. • TO is a non-atherosclerotic infl ammatory disorder in- volving distal, small, and medium-sized arteries in the fi ngers and toes, especially affecting male smokers younger than 40 years Thromboembolism Most thromboemboli (>70%) traveling to the upper ex- tremities are of cardiac origin. The left atrium is the most common origin of cardiac embolism, usually as a result of atrial fi brillation and stasis of blood in the left atrial ap- pendage. Cardiac embolism can also arise from the left ventricle after a myocardial infarction or less frequently from valvular vegetation occurring in bacterial endocar- ditis. Most cardiac emboli are relatively large and tend to lodge at bifurcation points in the forearm, in the radial and ulnar arteries. Thromboembolic arterial occlusion should always be considered in a patient with paroxysmal atrial fi brillation or history of cardiac disease. • Most thromboemboli (>70%) traveling to the upper ex- tremities are of cardiac origin Hypothenar Hammer Syndrome The ulnar artery has a superfi cial course in the palm as it passes laterally to the hook of the hamate bone, which makes it especially vulnerable to localized trauma. Repeti- tive trauma to the hypothenar eminence of the hand (from using the palm of the hand as a hammer) results in damage to the underlying ulnar artery (Fig. 3.2). Endothelial injury results in intraluminal thrombosis, aneurysm formation, and embolization to one or many fi ngers. The diagnosis is suggested by a history of repetitive occupational hand trauma in a patient with digital ischemia and a positive Allen test. The hypothenar hammer syndrome occurs in mechan- ics, farmers, plumbers, and especially carpenters, who use handheld tools such as wrenches and hammers that exert pressure over the hypothenar eminence of the hand. Pal- mar and digital occlusive diseases have also been reported in players of professional and recreational sports includ- ing golf, tennis, baseball, handball, and volleyball. Vibration-Induced Raynaud Syndrome Prolonged use of vibratory tools such as pneumatic ham- mers or chain saws can cause small-vessel damage to distal vessels. Sympathetic overactivity and endothelial damage are believed to contribute to vibration-induced vasospasm. Chronic vibration may cause structural dam- age to the artery wall with hypertrophy of the intima and media. The formation of microthrombi can lead to fi xed digital ischemia and fi ngertip necrosis. Terms that have been used to describe RS caused by chronic vibration include hand-arm vibration syndrome Fig. 3.1 Contrast angiogram in a patient with thromboangiitis obliterans. Thromboangiitis obliterans begins distally, involving small arteries of the toes and fi ngers in smokers generally younger than 40 years. Angiography may show corkscrew collaterals, but often fi ndings are non-specifi c, as in this case demonstrating severe occlusive disease of all digital arteries. CHAPTER 3 Upper Extremity Arterial Disease 31 and vibration white fi nger. Vibration-induced RS occurs in many different occupations in which workers use chain saws, grinders, sanders, riveters, jack hammers, and pneumatic hammers. A report from Sweden found the prevalence of vibration white fi nger in car mechanics to be 25% among those who had worked for 20 years. Whether vibration-induced RS is reversible in earlier stages is un- known. Early symptoms include tingling and numbness from peripheral nerve damage. Preventive measures, which may minimize damage, include wearing gloves, providing a cushioned surface on handles, and avoiding prolonged exposure. Thoracic Outlet Syndrome TOS is caused by dynamic compression of neurovascular structures, including the subclavian artery, subclavian vein, and brachial plexus, as they traverse through the tho- racic outlet (details regarding TOS discussed below). TOS can be associated with RS, subclavian stenosis, aneurysm formation, thrombosis, and arterial embolization to the hand and fi ngers. Arterial complications of TOS are often associated with a cervical rib, and severe consequences of arterial disease can occur in healthy patients with no his- tory of atherosclerosis. Drug-Induced Raynaud Syndrome and Occlusive Diseases β-Blocking Drugs β-Blocking drugs are well-established medications for arte- rial hypertension and cardiac disease. β-Blockers, however, are a common cause of cool fi ngers and arterial vasospasm due to inhibition of β 2 -mediated arterial vasodilation. The incidence of RS among patients with hypertension treated with β-blockers was 40% in a Scandinavian questionnaire- based study. Approximately 5% of patients treated with β- blocking medications for hypertension require withdrawal of the medication or dose reduction because of RS. Vaso- spasm occurs with selective and non-selective β-blockers. Drugs with combined α- and β-adrenoceptor–blocking activity, such as labetalol, would be expected to cause less symptomatic vasospasm. Despite these concerns, most patients, including many with RS, tolerate β-blockers, and several studies have failed to show any adverse effects of β-blockers on digital blood fl ow. • Vasospasm occurs with selective and non-selective β- blockers Chemotherapy Agents Vinblastine and bleomycin are used for the treatment of testicular cancer and lymphoma and can induce RS in 2.6% of patients on this therapy. Development of ischemic ulceration has been reported in cases of lung cancer treated with carboplatin and gemcitabine (but other factors may be present). α-Interferon is used in the treatment of leuke- mia and melanoma. Rare cases of RS with digital ulcera- tion have been reported, occurring within several months to 3 years of therapy. Other Drugs and Toxins Ergot preparations, used for migraine, are well known to cause severe upper and lower extremity vasospasm and ischemia with absent pulse. Amphetamine abuse can also cause arterial vasoconstriction. Cocaine abuse has been re- ported to cause ischemic fi nger necrosis. The mechanism of vascular damage from cocaine is multifactorial but likely involves initial vasospasm from elevated norepinephrine levels and subsequent arterial thrombosis. Accidental intra-arterial injection of drugs meant for intravenous use Fig. 3.2 Contrast angiogram demonstrating ulnar artery occlusion with extensive disease of palmar and digital arteries. Diagnostic considerations should include the hypothenar hammer syndrome, thromboangiitis obliterans, connective tissue diseases, and small vessel vasculitis. Vascular Medicine and Endovascular Interventions 32 can cause severe vasospasm and digital ischemia with gangrene and digital loss. Infections Purpura fulminans can cause severe digital ischemia, which often requires amputation. Parvovirus infection has also been associated with severe digital ischemia and secondary RS. Endocrine Diseases Hypothyroidism, Graves disease, Addison disease, and Cushing disease are all occasional but rare causes of va- sospasm. Increased Blood Viscosity Any abnormality that increases blood viscosity results in decreased blood fl ow. Disorders that affect blood viscosity include cryoglobulinemia, paraproteinemia in myeloma, and polycythemia. Cold-induced precipitation of proteins increases the viscosity of blood. Cryoglobulins occur with malignancies such as lymphomas and some viral infec- tions and can cause skin necrosis and gangrene of fi ngers, toes, and ears. Hepatitis C, in particular, is associated with secondary cryoglobulinemia. The treatment of cryoglob- ulinemia is plasmapheresis to remove the cryoglobulin, corticosteroids, and chemotherapy to treat the underlying malignancy. Malignancy Digital ischemia is an uncommon but well-recognized paraneoplastic manifestation of malignancy. Possible mechanisms of arterial disease caused by malignancy may include coagulopathy, cryoglobulinemia, or small vessel vasculitis. The most common malignancies associated with RS are: adenocarcinoma of the lung, stomach, colon, pancreas, ovary, testicle, and kidney; hematologic malig- nancies including myeloma, leukemias, lymphomas, and melanoma; and astrocytoma. RS associated with malignancy has a sudden onset at an older age, with severe symptoms and asymmetric digital involvement. Many patients (80%) have disease progres- sion to digital infarcts and gangrene. Treatment of the can- cer can result in remission of the RS symptoms and digital ischemia. Physical Examination in Raynaud Syndrome The diagnosis of RS is often based on the patient’s descrip- tion of a typical vasospastic attack related to cold exposure and involving one or more fi ngers. A focused physical examination and laboratory testing aid in the determina- tion of primary or secondary disease. Vascular examina- tion for upper extremity arterial disease should start with the heart. Cardiac auscultation may detect an increased P2 pulmonary valve closure sound, which suggests pul- monary hypertension, as can occur in scleroderma. Pulse and heart rhythm examination are important for detection of atrial fi brillation. Valvular heart disease such as mitral stenosis may be apparent on cardiac auscultation. Palpation of upper extremity pulses should include sub- clavian, brachial, radial, ulnar, palmar, and digital arteries. Palpation above the clavicle can reveal a cervical rib or an aneurysm of the subclavian artery. A palpable thrill indi- cates high-grade arterial stenosis. Auscultation over large arteries for a bruit, in particular over the sternoclavicular joint and above the clavicle, can identify arch or proximal arterial disease. Pulse examination in the hand should include palpation over the hypothenar eminence to identify the ulnar artery and palpation in the palm to identify the superfi cial pal- mar arch. A digital artery pulse can be appreciated in both the medial and lateral aspects of each fi nger. A palpable ulnar pulse at the wrist level only indicates that the ulnar artery is patent at the wrist level. The most common site of occlusion of the ulnar artery is just distal to the wrist, at the hypothenar eminence where the artery crosses over the hook of the hamate bone. The Allen test should be performed in every patient with RS or digital ischemia to detect the presence of ulnar artery occlusion, as occurs in hypothenar hammer syndrome. A positive Allen test iden- tifi es ulnar blockage in the hand. A positive reverse Allen test can signify occlusion of the radial artery. Close inspection of the skin may show telangiectasis of the fi ngers or hands, or thickening of the skin, which may be suggestive of sclerodactyly, digital ulcerations, pits, mottling, cyanosis, nailfold infarcts, and tight shiny skin. Splinter hemorrhages under the nails are normal fi ndings in manual workers but could also indicate the need to seek a more proximal source of atheroemboli. The main clinical features of primary RS are vasospastic attacks precipitated by exposure to cold or emotional stimuli, symmetrical or bilateral involvement of the extremities, normal vascular examination, symptoms present for a minimum of 2 years, and absence of any other underlying disease. • A positive Allen test identifi es ulnar blockage in the hand Laboratory Evaluation of Raynaud Syndrome Non-invasive vascular laboratory testing complements CHAPTER 3 Upper Extremity Arterial Disease 33 the history and physical examination. Non-invasive tests can provide objectivity to the clinical evaluation and assist in decision making for medical and surgical treatment. It can also help distinguish between primary and secondary vasospasm by detecting the presence of underlying oc- clusive disease. Even though attacks of RS are classically brought on by cold exposure, reproducing such attacks in the vascular laboratory is surprisingly diffi cult, even with digital cooling. The quantitative evaluation of vasospasm has also been diffi cult, and symptoms do not always corre- late with fi nger skin blood fl ow measurements. The diag- nosis of RS is a clinical diagnosis and should not be made on the basis of a laboratory test. Vascular laboratory stud- ies can help distinguish between primary and secondary disease but should not take the place of a complete history and physical examination. Segmental Blood Pressure Measurements Pneumatic cuffs are wrapped around the upper arm, fore- arm, and wrist, and systolic blood pressure measurements are obtained at each level. Pressures are compared with those at adjacent levels; a pressure differential exceeding 10 to 15 mm Hg may indicate proximal occlusive arterial disease. Wrist-to-brachial artery pressure ratio could be calculated but rarely is; the normal values range widely because of variation in cuff size and arm diameter. Finger Systolic Blood Pressures Finger systolic blood pressure measurement is possible using small digital cuffs applied to the proximal fi nger. Although a decreased systolic pressure may indicate arte- rial occlusive disease in that fi nger, the range of normal digital pressure is quite variable and is infl uenced by tem- perature. The normal fi nger brachial index ranges from 0.8 to 1.27. The fi ngers are especially temperature sensitive, however, and cool fi ngers can give falsely low indices. When fi ngers are very cold, digital indices can be unob- tainable because of intense vasoconstriction. Conversely, when the fi ngers are warm, fi nger systolic blood pressure may be lower than arm pressure by 10 mm Hg. Non-com- pressible vessels (similar to the lower extremity) can result in supranormal digital pressures. A difference of more than 15 mm Hg between fi ngers or an absolute fi nger systolic blood pressure of less than 70 mm Hg may indicate oc- clusive disease. Because the digits have dual arteries, early disease with occlusion of one of the digital arteries cannot be detected by fi nger pressure measurement if the contra- lateral artery is normal. The effect of temperature on digital blood pressure can be studied by applying a second cuff on the heated or cooled fi nger. Nielsen devised a double-inlet plastic cuff for local digital cooling. He found a mild progressive de- crease in fi nger systolic pressure with local cooling in nor- mal young women (up to a 15% decrease in digital systolic pressure at 10°C). During further cooling, 60% of women with primary RS showed digital artery occlusion. Fingertip Thermography Skin surface temperature can be used as an indirect index of capillary blood fl ow in the skin. At temperatures less than 30°C, blood fl ow is proportional to skin surface tempera- ture. At temperatures higher than 30°C, larger increases in fl ow may not be appreciated. Patients with vasospasm have increased vascular tone leading to decreased blood fl ow and decreased surface skin temperature. Measure- ment of skin temperature can be combined with cold im- mersion. Cold Recovery Time This time-honored test is used to measure the vasocon- strictor and vasodilator response of the fi ngers to cold exposure. It is based on the principle that patients with RS have greater vasoconstriction in response to cooling of the fi ngers than do normal subjects. After cold exposure, pa- tients with RS require more time for blood fl ow to increase, and consequently the fi ngers take longer to warm back to baseline temperature. The change in blood fl ow induced by temperature change can be indirectly assessed by measuring fi ngertip skin temperatures or by recording laser Doppler fl ux of the fi ngertips. Many variations of the cold immersion test exist, with various immersion times and temperatures. A standard protocol is to record baseline digital tempera- tures at the end of the fi nger pulp using a temperature probe. The hands are then immersed in 4°C water for 20 seconds. The digital skin temperature is recorded for each fi nger as the hands and fi ngers gradually warm up to am- bient room temperature. The length of time it takes for the hands to re-warm to baseline is noted by recording fi nger temperatures or laser Doppler fl ux at 5-minute intervals until recovery of pre-immersion temperatures. A delay in re-warming suggests a vasospasm tendency. Those with RS typically require more than 10 minutes, and sometimes 30 minutes or longer, for resting fi nger temperatures to recover, compared with less than 10 minutes for controls. If resting baseline digital temperatures are less than 30°C, the fi ngers never re-warm in less than 10 minutes after ice water immersion, and no further information is gained from this cold challenge test in these patients. The test cannot distinguish between primary and secondary RS, and some have questioned its ability to diagnose RS at all because of a large overlap with controls. Vascular Medicine and Endovascular Interventions 34 Laser Doppler Flux This non-invasive test measures microvascular skin per- fusion in the fi ngers. A laser Doppler probe transmits a low-powered helium-neon light, which is scattered by both static and moving tissue; most of the moving struc- tures are erythrocytes. Laser light hitting moving erythro- cytes undergoes a frequency shift according to the Dop- pler effect. Baseline measurements are highly variable and are affected by emotion, sympathetic tone (which may be increased in an anxious patient), and environmental tem- perature. Cold stress testing can be combined with laser Doppler by cooling the fi ngers with a laser Doppler probe. With cold-induced digital vasoconstriction, decreased skin blood fl ow and reduced laser Doppler fl ux occurs. With slow re-warming, laser Doppler fl ux increases. Laser Doppler With Thermal Challenge Laser Doppler can be used to measure relative change in digital skin blood fl ow with ambient warming of the hand and fi ngers. Measurement of digital laser Doppler fl ow at rest and after gentle warming of the hands in a hot-air box provides an excellent indication of primary vasospasm. This test can also assist in distinguishing between ob- structive and vasospastic disease. Baseline laser Doppler values are obtained from each digit. The hands are placed in a warming box (at 45°C) for up to 25 minutes or until a fi nger temperature of 37.0°C is reached. Laser Doppler fl ows are again determined in each digit. In general, patients with a history of vasospasm who present with cold fi ngers have low resting laser Doppler blood fl ow because of vasoconstricted vessels. After ambi- ent warming, patients with primary RS can have a marked increase in laser Doppler fl ow in these digits. Failure of Doppler fl ow to increase after warming of the hands indi- cates signifi cant arterial occlusive disease. The response of laser Doppler fl ow to warming correlates well with clini- cal and angiographic fi ndings. Scanning laser Doppler has several potential advan- tages over single-site laser Doppler. Because the Doppler probe does not come in contact with the patient, scanning laser Doppler can be used to assess blood fl ow at the base of ulcers or other wounds. However, interpretation of results varies considerably, and the applicability of this method appears lower than that of the single-digit Dop- pler probes. Imaging Studies Duplex ultrasonography can image the palmar arch and digital arteries for patency. Doppler ultrasonography also can help to determine completeness of the superfi cial pal- mar arch. If no change in Doppler fl ow occurs over the su- perfi cial arch during occlusion of the radial or ulnar artery, the arch is likely to be complete. Magnetic resonance angiographic imaging of upper ex- tremity arteries is useful for larger arteries, including the aortic arch, arm, and some arteries in the hand. Magnetic resonance angiography can accurately diagnose ulnar ar- tery occlusion in hypothenar hammer syndrome. Contrast angiography, however, remains the gold standard, with better resolution for arterial imaging. Contrast angiography is the best imaging modality if a detailed examination is necessary to determine the cause of digital ischemia, such as microembolism from an ulcer- ated plaque, thrombus in an ulnar artery, the corkscrew collaterals of TO, or the tapered arterial narrowing of vas- culitis. Nailfold Capillary Microscopy Capillaries in the nailfold can be visualized by applying a drop of immersion oil over the cuticle of the fi nger to make it translucent and imaging with a low-powered mi- croscope (×10-×20) or an ophthalmoscope at 40 diopters. Structural changes in capillary morphology can be seen. Normal capillaries appear as regularly spaced hairpin loops with a venous and arterial limb. The arterial limb has a diameter of 7 to 12 μm. The venous limb has a larger diameter with slower capillary fl ow. Abnormal capillaries as seen in scleroderma and mixed CTD are enlarged, tor- tuous, and deformed, with “loop dropout” and avascular areas. Treatment of Raynaud Syndrome Management principles may be classifi ed into three groups: non-pharmacologic behavioral therapies, phar- macologic treatment, and interventional-surgical proce- dures. Potential therapies could specifi cally target one of the many underlying abnormalities responsible for RS, including the endothelium, autonomic nervous system, or specifi c neurohumoral and hematologic factors. The approach to therapy for RS should be individualized, de- pending on the severity of symptoms, frequency of vaso- spastic attacks, presence of underlying disease, and risk of development of ischemic ulceration, gangrene, or digital loss. For most patients with primary RS, there is no cure. Preventive measures, with education, reassurance, and avoidance of cold exposure, constitute the basis of therapy for most patients. Behavioral Therapy In primary RS, many persons have only mild symptoms [...]... of the lymphatics London: Arnold; 20 03 p 10 2- 7 8 Browse NL, Burnand KG, Irvine AT, et al Diseases of the veins 2nd ed London: Arnold; 1999 p 38 5-4 27 ; 44 3-5 03; 57 1-6 03 Cooke JP, Rooke TW Lymphedema In: Loscalzo J, Creager MA, Dzau VJ, editors Vascular medicine: a textbook of vascular biology and diseases 2nd ed Boston: Little, Brown and Company; 1996 p 113 3-4 6 Cornu-Thenard A, Boivin P, Baud JM, et al... Angiol 20 05 ;24 : 32 5-9 Barwell JR, Davies CE, Deacon J, et al Comparison of surgery and compression with compression alone in chronic venous ulceration (ESCHAR study): randomised controlled trial Lancet 20 04;363:185 4-9 58 Bradbury AW, Ruckley CV Chronic venous insufficiency In: Creager MA, editor Atlas of vascular disease 2nd ed Philadelphia: Current Medicine, Inc; 20 03 p 22 9-4 0 Browse N, Burnand KG,... 2, 5, 10 mg 1, 2, 4, 8 mg Hypotension Orthostatic syncope 81, 325 mg 75 mg 2 ng⋅kg-1⋅min-1 IV Bleeding … Approved only for pulmonary hypertension in scleroderma Liver hepatotoxicity, birth defects, expensive IV only, given by continual infusion Headache, nausea, flushing Ointment “Steal phenomenon” 62. 5, 125 mg IV, intravenous 35 Vascular Medicine and Endovascular Interventions laboratory setting, and. .. Clin 20 02; 20: 62 3-3 1 Hummers LK, Wigley FM Management of Raynaud’s phenomenon and digital ischemic lesions in scleroderma Rheum Dis Clin North Am 20 03 ;29 :29 3-3 13 Joyce JW Buerger’s disease (thromboangiitis obliterans) Rheum Dis Clin North Am 1990;16:46 3-7 0 Lorelli DR, Shepard AD Hypothenar hammer syndrome: an uncommon and correctable cause of digital ischemia J Cardiovasc Surg (Torino) 20 02; 43:8 3-5 Olin... statement J Vasc Surg 20 04;40: 124 8-5 2 Guex JJ, Allaert FA, Gillet JL, et al Immediate and midterm complications of sclerotherapy: report of a prospective multicenter registry of 12, 173 sclerotherapy sessions Dermatol Surg 20 05;31: 12 3-8 Karkkainen MJ, Saaristo A, Jussila L, et al A model for gene therapy of human hereditary lymphedema Proc Natl Acad Sci U S A 20 01 Oct 23 ;98: 126 7 7-8 2 Epub 20 01 Oct 9 Khaira... for a minute or two A positive test is indicated by symptoms of weakness or numbness and hand pallor after 41 Vascular Medicine and Endovascular Interventions exercise Symptoms and hand pallor immediately resolve by lowering the arms and moving the shoulders forward Most believe that this is the most useful office and vascular laboratory test to help substantiate the clinical diagnosis of TOS In summary,... editor Vascular Surgery 4th ed Philadelphia: WB Saunders Company; 1995 p 96 1-7 6 Rigberg DA, Freischlag JA Thoracic outlet syndrome In: Hallett JW Jr, Mills JL, Earnshaw JJ, et al, editors Comprehensive vascular and endovascular surgery Edinburgh: Mosby; 20 04 p 26 7-8 4 Shepherd RF, Shepherd JT Raynaud’s phenomenon Int Angiol 19 92; 11:4 1-5 Spittell PC, Spittell JA Occlusive arterial disease of the hand due... diseases In: Goldman L, Ben- Upper Extremity Arterial Disease nett JC, editors Cecil textbook of medicine 21 st ed Philadelphia: WB Saunders Company; 20 00 p 36 2- 7 Olin JW Thromboangiitis obliterans (Buerger’s disease) N Engl J Med 20 00;343:86 4-9 Ouriel K Noninvasive diagnosis of upper extremity vascular disease Semin Vasc Surg 1998;11:5 4-9 Porter JM, Edwards JM Occlusive and vasospastic diseases involving... Lipodermatosclerosis and atrophie blanche in a patient with severe left lower extremity venous insufficiency 47 Vascular Medicine and Endovascular Interventions Fig 4 .2 Hyperpigmentation and venous stasis ulcer in a patient with left lower extremity venous insufficiency is made In the Perthes test, a tourniquet is placed at the mid thigh or proximal calf while the leg is elevated As the patient stands and walks,... familial factor in varicose disease: clinical study of 134 families J Dermatol Surg Oncol 1994 ;20 :31 8 -2 6 Donaldson MC Chronic venous disorders In: Loscalzo J, Creager MA, Dzau VJ, editors Vascular medicine: a textbook of vascular biology and diseases 2nd ed Boston: Little, Brown and Company; 1996 p 108 1-1 02 Eklof B, Rutherford RB, Bergan JJ, et al, American Venous Forum International Ad Hoc Committee . disease. Cardiol Clin. 20 02; 20: 62 3-3 1. Hummers LK, Wigley FM. Management of Raynaud’s phenom- enon and digital ischemic lesions in scleroderma. Rheum Dis Clin North Am. 20 03 ;29 :29 3-3 13. Joyce JW. Buerger’s. connective tissue diseases, and small vessel vasculitis. Vascular Medicine and Endovascular Interventions 32 can cause severe vasospasm and digital ischemia with gangrene and digital loss. Infections. numbness and hand pallor after Vascular Medicine and Endovascular Interventions 42 exercise. Symptoms and hand pallor immediately resolve by lowering the arms and moving the shoulders forward. Most