Takayasu arteritis, named for the Japanese ophthalmologist who first described the ocular manifestations in 1908, is a large-vessel vasculitis of unknown cause that chiefly affects women during their reproductive years. The disease often presents two challenges. First, the diagnosis can be delayed for months or even years due to the rarity of the disease, the young age of the (typical) patient, and the protean presenting manifestations. Second, treatment is a challenge. Although Takayasu arteritis is a chronic disease, it usually pursues a waxing and waning course that requires careful monitoring to determine when the disease is active and medical therapy is needed. Treatment with glucocorticoids usually succeeds in halting progression of the vasculitis. Indeed, because of the advances in medical therapy and surgical treatment of vascular complications, such as aortic regurgitation, survival of patients with Takayasu arteritis has increased dramatically.

• Causes vasculitis of the aorta and its major branches.
  
• Preferentially affects young women.
  
• Often presents with absent pulse, bruit, claudication, hypertension, or fever of unknown origin.
  
• Erythrocyte sedimentation rate is usually elevated.
  
• Most patients respond to prednisone.

Although Takayasu arteritis has been most extensively reported in Japan, Korea, China, Southeast Asia, and Mexico, cases have been described worldwide. In North America, the annual incidence is about 1–3 cases per million people. Takayasu arteritis affects women eight times more frequently than men. The average age of diagnosis is in the mid-20s but the disease may begin as early as age 7 or as late as age 70. Symptoms develop before age 20 in nearly one third of patients and after age 40 in about 10%. The age of onset tends to be later in European countries.

The cause of Takayasu arteritis remains elusive. The geographic clustering of cases suggests important genetic or environmental factors, but few have been identified. HLA associations have been found in Japanese patients (who preferentially express Bw52, DR2, Dw12, and DQw1), but not in other populations. The predominance of Takayasu arteritis in women of childbearing age suggests that female hormones may play a permissive role, as in systemic lupus erythematosus. An animal model of Takayasu arteritis has been produced with a herpes virus. In that model, the media of the aorta provides an immunoprivileged site for persistent herpes virus infection, which results in chronic inflammation (arteritis).

However initiated, Takayasu arteritis appears to be propagated by a T-cell–driven immune response that results in a granulomatous inflammation affecting all layers of the vessel. Indeed, the histopathology of Takayasu arteritis cannot be distinguished from that of temporal arteritis (also called giant cell arteritis; see Chapter 30). The inflammatory injury mediated by activated T cells, macrophages, and cytokines often results in proliferation of the intima and of smooth muscle cells in the media, leading to occlusion and stenosis of the artery. Transmural inflammation can also cause aneurysmal dilation of the vessel. Overproduction of inflammatory cytokines, such as interleukin-6, results in fever and other constitutional symptoms.

Symptoms and Signs

Although the presenting features of Takayasu arteritis vary greatly, they can be categorized into two broad groups: those caused by vascular damage (ie, occlusion, stenosis, or dilation of blood vessels), and those caused by systemic inflammation (Table 31–1). The separation of these presenting features is not always neatly maintained; many patients have both vascular complications and constitutional symptoms, and others have a biphasic presentation, with constitutional symptoms dominating early and vascular features becoming more salient later.

Among the vascular manifestations, bruit, claudication, hypertension, light-headedness (associated with vertebral or carotid artery disease), unequal blood pressures in the extremities, carotidynia, aortic regurgitation, and loss of a pulse are most common. Bruits develop most frequently over the carotid arteries, but also often develop in the supraclavicular or infraclavicular space (reflecting subclavian disease), along the flexor surface of the upper arm (from axillary artery disease), or in the abdomen (from renal or mesenteric artery vasculitis). Many patients have multiple bruits. Upper extremity claudication—commonly manifested in young women by fatigue and pain in the arm while exercising or blow-drying hair—develops more often than lower extremity claudication. A widened pulse pressure and diastolic murmur along the right sternal border may signal the aortic regurgitation that develops in 20% of patients. Other cardiac manifestations include angina (most commonly from stenotic lesions at or near the ostia of the coronary arteries), mitral regurgitation (secondary to left ventricular dilatation from aortic regurgitation), or congestive heart failure (early in the course caused by myocarditis or late in the course caused by chronic aortic with or without mitral regurgitation). Stroke affects a significant minority of patients. Glomerulonephritis is quite rare in this form of large vessel vasculitis; renal disease usually results from hypertension which in turns develops because of stenosis of the renal arteries.

The visual symptoms that were first described in 1908 occur rarely today. When present, visual symptoms chiefly result from retinal ischemia produced by narrowing or occlusion of the carotid arteries. Some patients may have such limited blood flow through their carotids and vertebral arteries that merely turning and tilting their head causes light-headedness, dizziness, or visual loss.

Almost half of patients experience constitutional or musculoskeletal symptoms. These constitutional and musculoskeletal features dominate the presentation in approximately one third of all cases of Takayasu arteritis. Asthenia, weight loss, fever, myalgia, and arthralgia occur commonly. Prominent back pain, especially in the thoracic region, develops in a few patients. This pain resembles that seen in older patients with thoracic dissection and probably results from stimulation of nociceptive nerve fibers along the inflamed aorta.

Laboratory Findings