Upper Extremity Arterial Disease: Epidemiology, Etiology, and Diagnostic Evaluation

Upper extremity ischemia accounts for less than 5% of patients presenting for evaluation of limb ischemia, with a vast majority of cases being caused by autoimmune/connective tissue diseases. In contrast to the lower extremity, atherosclerosis is not a major etiology of upper extremity ischemia. According to a Dutch study, only 2.3% of diabetic patients and no nondiabetic patients were found to have abnormal Doppler waveforms in either of the upper extremities. This chapter provides an overview of upper extremity arterial diseases, with emphasis on the epidemiology, diagnosis, and natural history.

Epidemiology

A number of pathologic conditions may contribute to upper extremity arterial disease and, as a result, little comprehensive epidemiologic data are available. One exception is Raynaud syndrome, which is characterized by intermittent digital ischemia, caused by vasoconstriction, in response to cold, caffeine, or emotional stress (see Ch. 142 , Raynaud Phenomenon). The prevalence of Raynaud phenomenon, from population-based surveys is estimated to be 3%–5% of the general population. This increases among people living in cold climates, with up to 20% to 30% of those surveyed complaining of cold-induced digital pain. Most patients with Raynaud syndrome have primary (idiopathic) Raynaud’s, formerly known as Raynaud disease. Patients who have an identifiable arterial pathology or associated disease contributing to their condition are classified as having secondary Raynaud’s, formerly known as Raynaud phenomenon. This distinction has prognostic implications as secondary Raynaud’s is more likely to progress to severe occlusive disease leading to digital rest pain, and ulceration. Diseases associated with secondary Raynaud’s include scleroderma, mixed connective tissue disease (MCTD), systemic lupus erythematosus (SLE), and rheumatoid arthritis. Of these, scleroderma accounts for the majority of secondary Raynaud’s patients diagnosed. It is important to remember a patient may present with Raynaud’s symptoms years before the diagnosis of an underlying systemic disease.

Etiology and Pathogenesis

Upper extremity arterial disease can be broadly categorized based on anatomic location (large vs. small vessel) and etiology (vasospastic vs. occlusive). In general, vasospastic etiologies affect smaller vessels and occlusive affect larger vessels. The clinical appearance of occlusive and vasospastic disease may be similar, but delineating between them is essential for appropriate treatment. Processes leading to upper extremity arterial disease are vast. In addition, there can be both vasospasm of larger vessels, as occurs with ergot-containing medications, and concurrent atherosclerotic disease in patients who also have Raynaud’s. Patients with Raynaud syndrome have normal digital artery pressure at baseline. In response to certain triggers (cold, stress, caffeine), they experience digital artery smooth muscle contraction leading to profound, albeit temporary, digital hypoperfusion. Upon relief of the trigger, the vasoconstriction ceases and normal flow is restored.

The pathophysiological mechanisms underlying Raynaud syndrome remain poorly understood despite the fact that it has been more than a century since it was first described by Maurice Raynaud. Multiple abnormalities including those of the sympathetic nervous system, ^, digital blood vessels, altered sensitivities, numbers of α-adrenoceptors, ^, and β-adrenoceptors, and vasoactive peptides, including calcitonin gene-related peptide, ^, and endothelin have been hypothesized. It is being increasingly recognized that the pathophysiology of Raynaud syndrome, whether primary or secondary, is complex and multifactorial.

The etiology for occlusive disease is primarily atherosclerotic but can include additional more acute entities, such as thromboembolic events and iatrogenic or traumatic related injuries and vasculitides. Atrial fibrillation and proximal atherosclerosis are common etiologies for thromboembolism. Iatrogenic causes include dialysis access resulting in steal phenomenon as well as radial, brachial, or axillary artery access for monitoring lines, endovascular procedures, or conduits. Symptomatic atherosclerotic lesions in the upper extremity are less common than in the lower extremity with the majority of these lesions being in the brachiocephalic trunk and subclavian artery. When found, atherosclerotic lesions in this distribution are significant for overall patient management, even when asymptomatic. For example, in asymptomatic patients a difference in systolic blood pressure of 15 mm Hg or more between arms, indicative of subclavian stenosis, was found to be associated with a 1.7× increased risk of cardiovascular mortality and 2.5× risk of peripheral vascular disease. The same risk factors that apply to lower extremity PAD apply to the upper extremity, such as smoking, hypertension, dyslipidemia, and diabetes.

Small Vessel Arteriopathies

Numerous small vessel arteriopathies in the upper extremity, defined as those distal to the wrist, may lead to hand ischemia. The diseases leading to the most severe upper extremity arterial ischemia are autoimmune or connective tissue diseases such as scleroderma, rheumatoid arthritis, systemic lupus, and others.

Scleroderma

Scleroderma (systemic sclerosis) is the most common connective tissue disorder in patients with secondary Raynaud’s. It is a generalized disorder of connective tissue, the microvasculature, and the small arteries. Early findings include microvasculature damage, mononuclear-cell infiltrates, and fibrosis with later disease showing dense collagen and loss of cells. There is a female-to-male ratio of at least 3:1, and an incidence of approximately 50 per 1 million people in the United States. Cutaneous involvement is almost universal, and the clinical course is characterized by progressive scarring and small vessel occlusions in the skin, gastrointestinal tract, kidneys, lungs, and heart. Serology often reveals anti-centromere or anti-topoisomerase (anti-Scl-70) antibodies. It is postulated that damage seen in scleroderma is mediated through these cytotoxic antibodies to endothelium. Vascular injury, primarily in arterioles, precedes fibrosis.

Systemic Lupus Erythematosus

SLE occurs most often in young females, and damage to affected organs appears to be caused primarily by immune complex deposition from a proinflammatory state. The prevalence is 20–150 cases per 100,000 population with a higher proportion of African, Hispanic, or Asian ancestry affected compared to other groups. The diagnosis is made clinically since the available laboratory tests, while quite sensitive, are not specific. Clinical criteria include fevers, arthralgias, skin rash, Raynaud syndrome, and nephritis. Raynaud syndrome (secondary) is present in as many as 80% of these patients.

Rheumatoid Arthritis

While rheumatoid arthritis is primarily a chronic inflammatory joint disease, there is a subgroup of patients with extra-articular involvement of the skin, eyes, lungs, spleen, and blood vessels. Several types of vasculitis have been described in rheumatoid arthritis, the most severe of which is termed rheumatoid vasculitis, a systemic process that involves both arteries and veins. As treatment for RA has improved, the incidence of rheumatoid vasculitis has dropped from 9.1 to 3.9 cases per million population. The etiology of rheumatoid arthritis is unknown, but it likely results from immune-mediated damage. There is a strong association between rheumatoid vasculitis and specific genotypes of the epitope HLA-DRB1. It has been hypothesized that these genotypes mark a predisposition that in response to an unknown stimulus, such as infection, leads to immune complex deposition and inflammation. Additional risk factors include male sex, current smoking, and longstanding seropositive nodular erosive disease. Hydroxychloroquine and low-dose aspirin have been shown to be protective in preventing development of vasculitis in RA patients.

Sjögren Syndrome

Sjögren syndrome is characterized by dry eyes and mouth and may be primary or secondary to another connective tissue disease. The female to male ratio is 9:1 with an estimated incidence of 7 cases per 100,000 population, although this varies across continents. It may be associated with small vessel arteriopathy, which can then be subdivided into acute necrotizing, leukocytoclastic, and lymphocytic vasculitis. Vasculitis in Sjögren’s is common and usually presents as a rash or peripheral neuropathy. Some patients develop a systemic vasculitis that affects medium-sized vessels and can resemble polyarteritis nodosa.

Mixed Connective Tissue Disease

MCTD is a group of autoimmune disease states that do not fall into a named disease category. Patients characteristically have high titers of antibodies to an extractable nuclear antigen, which consists of ribonucleic acid and protein. MCTD clinically presents as an overlap syndrome with features of two or more connective tissue diseases, such as SLE, rheumatoid arthritis, or scleroderma. There is a high frequency of Raynaud syndrome, arthritis, polymyositis, and interstitial lung disease within this group of patients.

Buerger Disease

Buerger disease (thromboangiitis obliterans) is characterized by segmental thrombotic occlusions of the small- and medium-sized arteries (see Ch. 139 , Thromboangiitis Obliterans). The disease most commonly affects the lower extremities but the upper extremities are involved in as many as 50% of these patients. It classically occurs in young male smokers and is often associated with both migratory thrombophlebitis and secondary Raynaud syndrome. Diagnostic criteria include age less than 45 years, tobacco abuse, exclusion of other diseases with similar clinical findings, normal arteries proximal to the popliteal or brachial arteries, and documentation by objective means of digital arterial occlusion.

Hand–Arm Vibration Syndrome

Hand–arm vibration syndrome (HAVS) refers to the finding of Raynaud syndrome after long-term use of vibrating tools. The initial group of patients were stonecutters, but the disease has been described in various occupations, including welders or grinders in shipyards, timber fellers, and windshield replacement technicians in the auto-glass industry. The exact pathophysiology of this condition is not known, but it is postulated that kinetic energy imparted to the small vessels and nerves of the hand by vibrating tools with power in certain frequency bands is harmful. The damage appears to accumulate over time. Early on, patients have vasospastic Raynaud syndrome, which over a period of time, progresses to digital artery occlusive disease (see Ch. 184 , Conditions Arising from Repetitive Trauma and Occupational Vascular Problems).

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