Giant cell arteritis is the most common primary systemic vasculitis. The disease occurs almost exclusively in people over age 50, with an annual incidence of 15 to 25 per 100,000.1 Incidence rates vary significantly depending on ethnicity. The highest rates are in whites, particularly those of North European descent.2 Incidence rates progressively increase after age 50. The disease is more prevalent in women. Its cause is unknown; both genetic and environmental factors are thought to play a role.
Giant cell arteritis is characterized by a granulomatous inflammatory infiltrate affecting large and medium-size arteries. Not all vessels are equally affected: the most susceptible are the cranial arteries, the aorta, and the aorta’s primary branches, particularly those in the upper extremities.
The disease is usually associated with an intense acute-phase response. Vessel wall inflammation results in intimal hyperplasia, luminal occlusion, and tissue ischemia. Typical histologic features include a mononuclear inflammatory infiltrate primarily composed of CD4+ T cells and activated macrophages. Multinucleated giant cells are seen in only about 50% of positive biopsies; therefore, their presence is not essential for the diagnosis.3
FOUR MAIN PHENOTYPES
Some of the possible symptoms of giant cell arteritis readily point to the correct diagnosis, eg, those due to cranial artery involvement, such as temporal headache, claudication of masticatory muscles, and visual changes. However, the clinical presentation can be quite varied.
There are four predominant clinical phenotypes, which may be present at the onset of disease or appear later as the disease progresses. Although they will be described separately in this review, these clinical presentations often overlap.
Cranial arteritis is the clinical presentation most readily associated with giant cell arteritis. Clinical features result from involvement of branches of the external or internal carotid artery.
Headache, the most frequent symptom, is typically but not exclusively localized to the temporal areas.
Visual loss is due to involvement of the branches of the ophthalmic or posterior ciliary arteries, resulting in ischemia of the optic nerve or its tracts. It occurs in up to 20% of patients.4,5
Other symptoms and complications from cranial arteritis include tenderness of the scalp and temporal areas, claudication of the tongue or jaw muscles, stroke, and more rarely, tongue infarction.
Polymyalgia rheumatica is a clinical syndrome that can occur by itself or in conjunction with giant cell arteritis. It may occur independently of giant cell arteritis, but also occurs in about 40% of patients with giant cell arteritis. It may precede, develop simultaneously with, or develop later during the course of the giant cell arteritis.6,7 It is a common clinical manifestation in relapses of giant cell arteritis, even in those who did not have symptoms of polymyalgia rheumatica at the time giant cell arteritis was diagnosed.
Polymyalgia rheumatica is characterized by aching of the shoulder and hip girdle, with morning stiffness. Fatigue and malaise are often present and may be severe. Some patients with polymyalgia rheumatica may also present with peripheral joint synovitis, which may be mistakenly diagnosed as rheumatoid arthritis.8 Muscle weakness and elevated muscle enzymes are not associated with polymyalgia rheumatica.
Polymyalgia rheumatica is a clinical diagnosis. Approximately 80% of patients with polymyalgia rheumatica have an elevated erythrocyte sedimentation rate or an elevated C-reactive protein level.9 When it occurs in the absence of giant cell arteritis, it is treated differently, with less intense doses of corticosteroids. All patients with polymyalgia rheumatica should be routinely questioned regarding symptoms of giant cell arteritis.
Nonspecific systemic inflammatory disease
Some patients with giant cell arteritis may present with a nonspecific systemic inflammatory disease characterized by some combination of fever, night sweats, fatigue, malaise, and weight loss. In these patients, the diagnosis may be delayed by the lack of localizing symptoms.
Laboratory tests typically show anemia, leukocytosis, and thrombocytosis. The erythrocyte sedimentation rate and the C-reactive protein level are usually very high.
Giant cell arteritis should be in the differential diagnosis when these signs and symptoms are found in patients over age 50.
Although thoracic aortic aneurysm and dissection have been described as late complications of giant cell arteritis, large-vessel vasculitis may precede or occur concomitantly with cranial arteritis early in the disease.10,11
Population-based surveys have shown that large-vessel vasculitis is extremely frequent in patients with giant cell arteritis. In a postmortem study of 11 patients with giant cell arteritis, all of them had evidence of arteritis involving the subclavian artery, the carotid artery, and the aorta.12
Patients may have no symptoms or may present with symptoms or signs of tissue ischemia such as claudication of the extremities, carotid artery tenderness, decreased or absent pulses, and large-vessel bruits on physical examination.