Pathophysiology. The cause of giant cell arteritis is unknown. The dominant force in vascular injury is cellmediated immunity. Resident “sentinel” vascular dendritic cells are thought to present antigen. Migrating dendritic cells, macrophages, and Th1 and Th17 lymphocytes enter the vessel wall via the adventitial vasa vasorum and also play critical roles. Mononuclear cells spread from the vasa vasorum to the media. A small proportion of activated T lymphocytes become clonally expanded. The stimulus for clonal expansion is unknown but may be from an unidentified endogenous or exogenous neoantigen. Weakening of the vessel wall may cause an aneurysm. Luminal narrowing is responsible for ischemic events (e.g., visual loss, stroke, and claudication).

Blood samples before treatment of giant cell arteritis have increased concentrations of IFN-γ and IL-17, as well as IFN-γ–and IL-17–producing T lymphocytes. Corticosteroids suppress Th17 but not Th1 (IFN-γ) components of blood and vascular lesions. Future strategies designed to target corticosteroid-resistant Th1 pathways may allow for more sustained remissions.

Clinical Manifestations. Headache is the most common complaint (75%-95%). Systemic symptoms include fever (<50%), weight loss, malaise, and myalgias and occur in less than 65% of patients. Scalp pain (~25%), jaw pain while chewing (15%-60%), and extremity pain (~20%) may also occur. Visual loss is noted in about 25% of patients. Twenty-five percent of patients develop a clinically apparent aortic aneurysm or large artery stenosis at some point during their illness. Up to one half of patients with aortic aneurysms will experience aortic dissection or rupture. The worst prognostic markers for visual loss are already having had amaurosis or established giant cell arteritis–related visual loss in one eye and not being treated for giant cell arteritis.

A thorough physical examination may reveal a prominent, tender temporal artery (20%-70% cases). Asymmetric extremity blood pressures or pulses, bruits, or a murmur of aortic insufficiency suggest aortic or primary aortic branch involvement.

Diagnosis. No serologic test is diagnostic for giant cell arteritis. The diagnosis is based on clinical symptoms, abnormal acute phase reactants, and a positive biopsy. More than 90% of patients will have an elevated ESR. Temporal artery biopsy is the most specific diagnostic test. The sensitivity of biopsy, in series from medical practitioners, in detecting giant cell arteritis is approximately 50%. The yield of biopsy is a function of pretest probability, which may explain why some ophthalmology series, in which visual abnormalities are common, have higher yields (~80%). Biopsy of the contralateral temporal artery adds very little to the sensitivity of the test. Vascular imaging with arteriography or magnetic resonance angiography (MRA) may reveal vascular abnormalities. The subclavian arteries, carotid arteries, and ascending aorta are the most commonly affected sites.

Treatment/Prognosis. Corticosteroids are the only drugs of unequivocal value in giant cell arteritis. Therapy should start when the disease is first suspected. Waiting to start corticosteroids after a temporal artery biopsy could result in irreversible visual loss. The optimal, initial dose of prednisone is unclear, but most authorities agree that the initial dose should be between 40 and 60 mg/day. Some advocate the intravenous use of methylprednisolone (1000 mg/day for 3 to 5 days) in patients presenting with amaurosis or blindness. After approximately 1 month, tapering of corticosteroids is begun. The ideal goal is to achieve a corticosteroid-free remission. However, it is not unusual for therapy to extend for many years because of recurrence of symptoms at low doses or after discontinuation is attempted.

Although a variety of adjunctive agents have been evaluated in patients with giant cell arteritis, none has been shown to have clear benefit. Case reports have suggested possible utility of blocking IL-6 (tocilizumab), but before this approach can be endorsed, randomized controlled studies will be required to assess risks and benefits.

Recent data have suggested benefit from the use of low doses of aspirin. Patients so treated appear to have a 3- to 5-fold reduction in visual complications or stroke. Adjunctive low-dose aspirin should be considered in all patients who do not have contraindications for its use.

Although overall mortality in giant cell arteritis is similar to that of matched controls, the subset with aortic aneurysms has increased risk of premature death from aneurysm rupture or dissection. If aortic valve murmurs or bruits are noted, imaging to determine the severity of the aortic lesion should follow. Aneurysm size, rate of change, symptoms suggestive of dissection, and possible congestive heart failure will determine whether surgical intervention is appropriate. Long-term use of corticosteroids is almost always associated with some adverse event, including corticosteroid-induced diabetes, mood changes, infection, avascular necrosis, glaucoma, or osteoporosis/fractures.