Arterial occlusive disease may be further subdivided by anatomic location. Disorders that affect large-sized arteries, such as the aortic arch, the innominate, subclavian, axillary, and brachial artery include: atherosclerosis, arterial thoracic outlet syndrome, fibromuscular dysplasia, radiation-induced arteritis, trauma (including iatrogenic injuries ), and vasculitis (primarily giant cell arteritis and Takayasu’s arteritis ). Small-sized arteries such as the radial, ulnar, and digital arteries may be affected by occlusive lesions from atherosclerosis, Buerger’s disease , hypothenar hammer syndrome and other traumatic or occupational injuries , vasculopathies associated with connective tissue disorders, as well as injury from cold exposure, drugs, and toxins.

Arterial embolic events in the upper extremity arise primarily from either cardiac embolism (from cardiac chambers or valvular vegetations) or embolic events from either aneurysms or atherosclerotic lesions in arteries proximal to the affected vessel.

Arterial vasospastic disorders may be a result of excessive systemic vasopressor use, trauma, toxin exposure (such as ergotamine and vinyl chloride), and Raynaud’s syndrome . While vasospastic disorders typically affect the small-sized arteries of the hand and wrist, vasospasm can be seen in larger proximal arteries as had been described with ergotamine in the brachial artery. Raynaud’s syndrome (or phenomenon) results from vasospasm that is limited to the small digital arteries and in its most common idiopathic or primary form is not associated with other pathology proximal to the palmar arch. The causative and associated conditions of secondary Raynaud’s syndrome are myriad and are discussed at greater length in another chapter.

The most common large-vessel arteriopathy is atherosclerosis. Clinical risk factors for atherosclerotic occlusive disease include tobacco use, hypertension, dyslipidemia, diabetes mellitus, male sex, and advanced age, although it must be recognized that many other conditional, predisposing, and novel associations are also recognized as being important in atherosclerosis development [1, 2]. Patients with diabetes mellitus are much more predisposed to cardiovascular disease and accelerated atherosclerosis compared to those with other atherosclerotic risk factors but without diabetes mellitus [1, 3]. Diabetes mellitus has been shown to promote the development and progression of aggressive atherosclerotic lesions through a variety of diabetic-specific mechanisms involving endothelial dysfunction, myeloid cells, reactive oxygen species, and insulin resistance [1]. This accelerated, aggressive atherosclerosis may affect the large and small-sized arteries of the upper extremity and lead to significant ischemia. The combination of end-stage renal disease with diabetes mellitus can result in dramatic examples of severe hand/digital ischemia from multilevel upper extremity occlusive disease (Fig. 10.2).

Thromboangiitis obliterans (TAO) , also known as Buerger’s disease, is a syndrome characterized by segmental thrombotic occlusions of medium-and small-sized arteries of the upper extremities [4]. This clinical syndrome has been shown to be prevalent in young men (onset usually 45 to 50 years of age) who are excessive tobacco smokers. They typically present with signs of severe ischemia of hands and fingers, such as rest pain, trophic changes, digital ulceration, or gangrene [5]. Large-sized arteries such as the aortic arch and cerebral vessels are typically spared. The etiology of Buerger’s disease is unknown; however, many investigators hypothesize an immune-mediated mechanism given that histopathologically the disease is characterized by vessel wall inflammation and linear deposition of immunoglobulins along the elastic lamina [5].

Arterial thoracic outlet syndrome (aTOS) is the least common form of TOS accounting for ~1 % of all cases of TOS. The prevalence of arterial TOS is undefined in the general population; however, published literature suggests that most patients are young, active adults without gender discrepancies. Arterial TOS is associated with various anatomic abnormalities, the most common being a cervical rib. Other bone aberrations may be present, including anomalous first ribs, fibrocartilaginous bands of the anterior scalene muscle, clavicular fractures, and enlarged C7 transverse processes [6]. These anatomic abnormalities may lead to extrinsic compression of the subclavian artery with associated post-stenotic dilatation from turbulent flow hemodynamics, aneurysmal degeneration, and subsequent distal embolization to digital, palmar, or interosseous arteries. Subclavian artery compression may further lead to intimal damage resulting in mural thrombus, embolization or thrombosis, and subsequent acute extremity ischemia. Variants of aTOS that may present with similar athletic, occupational, or repetitive movement risks also exist. Chronic injury of the second portion of the axillary artery injury can occur via compression by the pectoralis minor tendon [7]. Compression of the third portion of the axillary artery by the humeral head can similarly result in arterial injury and subsequent arterial degeneration leading to aneurysm and luminal thrombus formation.

Fibromuscular dysplasia (FMD) affects arterial vessels predominantly in Caucasian women between the ages of 40 and 50 years [8]. The etiology of fibromuscular dysplasia remains unknown, and it remains a distinct entity from atherosclerotic and inflammatory vascular disease. FMD typically affects medium- and small-sized arteries and has been reported most commonly in the renal, carotid, and cerebral arteries [9]. Given the rarity of upper extremity arterial ischemia, especially those affected by FMD, it is not surprising that only a handful of cases have documented FMD affecting the subclavian, axillary, brachial, radial, and ulnar arterial segments. Numerous potential etiologies have been proposed, including endocrine abnormalities, repetitive stress or trauma, as well as relative ischemia to the vasa vasorum. Despite these several hypothetical mechanisms, the final outcome results in medial fibrosis and smoother muscle cell hyperplasia with subsequent aneurysmal degeneration of the affected arterial segment [9]. Turbulent flow results in thrombus formation with the possibility of subsequent distal embolization. Patients with upper extremity fibromuscular dysplasia may present with upper extremity claudication from luminal narrowing or arterial ischemia secondary to distal embolization or thrombosis of the affected arterial segment.

Giant cell arteritis (GCA) and Takayasu’s arteritis (Fig. 10.3) are rare inflammatory arteriopathies affecting large arteries, such as the aorta and its major branches, predominantly affecting young women [10]. There is no clear consensus on the etiology of GCA and Takayasu’s arteritis ; however, hereditary, autoimmune and infectious causes have been suggested to be potential causes in the development of these arteriopathies [10]. It is suspected that an inflammatory process leads to stenoses and aneurysmal degeneration, and subsequent end-organ ischemia. Small-vessel vasculitidies, such as those seen with scleroderma, CREST syndrome, rheumatoid arthritis, and systemic lupus erythematosus (SLE) among others, result in varying degrees of digital ischemia from small-vessel vasculitis and immune-mediated fibrosis. These patients typically have continuous digital artery vasospasm and focal segmental occlusion resulting in Raynaud’s phenomenon and digital ischemic lesions.

Vasospastic arterial disorders, such as Raynaud’s phenomenon, may be primary or secondary to other causes. Primary or idiopathic Raynaud’s phenomenon has been shown to be prevalent in young women in cool climates with reports as high as 20–30 % in otherwise healthy women [11]. Secondary Raynaud’s phenomenon occurs in the context of other local or systemic conditions [12]. A more detailed discussion of secondary Raynaud’s syndrome will be found in Chap. 24. Raynaud’s phenomenon is characterized by vasospastic attacks and is typically triggered by cold temperature exposure and emotional stress. The pathophysiologic mechanism of Raynaud’s phenomenon is believed to be due to a disparity between the vasoconstriction and vasodilator mechanisms, including endothelial dysfunction, abnormalities in circulating mediators, and dysfunction of sympathetic vascular tone [13]. Attacks may involve both hands with discoloration of the digits but generally do not result in tissue necrosis. The discoloration typically follows a classic pattern of pallor and cyanosis when exposed to cold and hyperemia when the attack subsides [13].

Repetitive hand trauma can result in direct arterial injury with resultant digital ischemia from arterial thrombosis or embolization. The most commonly recognized of these rare entities is the hypothenar hammer syndrome (HHS) . This rare vascular overuse condition affects predominantly men employed in physically demanding occupations and involving the dominant hand in the majority of cases. This clinical syndrome has been shown to be prevalent in individuals who use the hypothenar eminence in repetitive activities such as pushing, hammering, or squeezing objects [14]. Industrial workers are at particularly high risk for developing hypothenar hammer syndrome, with predisposed occupational hazards being carpenters, butchers, farmers, metal workers, mechanics, machinists, miners, and sawmill workers [15]. Furthermore, athletic and recreational activities at high risk for the development of hypothenar hammer syndrome include badminton, baseball, golf, hockey, tennis, volleyball, and weight lifting [15]. Given that many individuals participate in these occupations and recreational activities, the low prevalence of HHS may be explained by aberrant ulnar anatomy as well as likely asymptomatic and subclinical disease [16] or genetic abnormalities. While repetitive trauma is the most common setting for the development of hypothenar hammer syndrome, this clinical syndrome has been observed after a single severe blow to the hypothenar eminence [16]. Repetitive palmar trauma results in intimal layer injury of the ulnar artery, which leads to vasospasm, platelet aggregation, and ultimately formation of thrombus, which may lead to distal ischemia. Hemorrhage into the medial layer and medial fibrosis may lead to aneurysmal degeneration of the ulnar artery. Ulnar artery aneurysms may further lead to compressive symptoms such as paresthesias and pain given the proximity to the ulnar nerve [14]. Repetitive trauma injury in the hand is not limited to the ulnar artery at the hypothenar eminence. Repetitive injury has also been described in the radial artery, coined the thenar hammer syndrome [15, 17] as well as in the palmar arch of the hand [15].

Exposure to certain toxins may result in upper extremity ischemia. Ergotamine is an alkaloid produced by a fungus (Claviceps purpurea) and is used for the treatment of severe migraine headaches [18]. Ergotamine-induced upper limb ischemia is an extremely rare occurrence. Ergotamine may cause a direct insult to the vascular endothelium and may further precipitate peripheral arterial vasoconstriction leading to ischemia and gangrene. Toxicity from ergotamine may result from (1) acute ingestion of normal doses in hypersensitive patients, (2) acute ingestion of an excessive dose, or (3) chronic use of therapeutic doses of ergotamine. Certain medications may be responsible for potentiating the effects of ergotamine, such as antibiotics interfering with hepatic metabolism, antiretroviral agents, oral contraceptives, and xanthine derivatives. Furthermore, a number of medical conditions may potentiate vasospasm in combination with the use of ergotamine . These conditions include coronary artery disease, hepatitis, hepatic dysfunction, malnutrition, peripheral arterial disease, pregnancy, renal dysfunction, sepsis, and thyrotoxicosis [18].

Environmental or occupational exposures to heavy metals and vinyl chloride may cause digital ischemia [19]. Vinyl chloride is a gas which is used during the production of polyvinyl chloride (PVC) , a material found in numerous plastic products including pipes, wires, cable coatings, and packaging materials [20]. Some chemotherapeutic agents have been associated with the development of digital ischemia, with direct arterial injury and vasospasm thought to play a role [21].

Iatrogenic injury may result in compartment syndrome or local tissue ischemia. A compartment syndrome in the upper extremity is rare but may be caused by trauma, burns, prolonged compression, and intravenous (IV) extravasation [22]. There are infrequent instances that IV infiltration will lead to compartment syndrome in the adult population, but there have been case reports in the pediatric population [23, 24]. Also, there have been documented cases of local tissue ischemia from peripheral administration of vasopressors secondary to vasoconstriction. In a recent systematic review, norepinephrine (80.4 %), dopamine (9.3 %), and vasopressin (6.9 %) were most commonly administered in instances of local tissue complications, resulting in skin necrosis, tissue necrosis, or gangrene [25]. Given the vasoconstrictive properties of these medications, they should be administered in a central venous catheter, but may be given peripherally in life-saving situations as a temporizing measure as a central venous access is being established.

Evaluation of the hand may reveal signs suggestive of the underlying cause of arterial insufficiency. The identification of pallor and cyanosis is nonspecific but suggests the presence of severe distal ischemia. Atrophy of the intrinsic hand muscles is seen rarely but may indicate the presence of a chronic arterial lesion. Scars in the arm or hand may point to previous trauma and/or surgery , and the presence of visual callus on the hypothenar or thenar aspect of the palm may increase the suspicion of repetitive trauma injury [16]. The presence of frank digital ulceration or gangrene can be seen in severe arterial ischemia [14]. For patients with vasculitis, especially small-vessel variants, there may be signs of sclerodactyly and progressive fibrosis of the extremities, trunk, and face. Splinter hemorrhages in the nail bed may be indicative of embolic events.

Cardiac auscultation is an essential part of the evaluation of patients with upper extremity ischemia as an audible heart murmur may represent underlying embologenic cardiac abnormalities such as valvular disease or atrioventricular septal defects . Bruits may be detected with auscultation of the supraclavicular and infraclavicular fossae. The presence of a bruit in these locations, while nonspecific, indicates turbulent flow and may be a result of either severe arterial stenosis, aneurysm, or an arteriovenous communication [27]. Bilateral brachial blood pressures should be measured in all patients to rule out a proximal upper extremity pressure gradient.