Giant Cell Arteritis

Vasculitis may be localized, multifocal, or widespread. The disorder tends to affect arteries containing elastic tissue, most often the temporal, cranial, or other carotid system arteries. The aortic arch branches, coronary arteries, and peripheral arteries can also be affected. Mononuclear cell infiltrates in the adventitia form granulomas containing activated T cells and macrophages. Multinucleated giant cells, when present, cluster near the disrupted elastic lamina. The intimal layer is markedly thickened, with concentric narrowing and occlusion of the lumen.

Symptoms of giant cell arteritis may begin gradually over several weeks or abruptly.

Patients may present with systemic symptoms such as fever (usually low-grade), fatigue, malaise, unexplained weight loss, and sweats. Some patients are initially diagnosed as having fever of unknown origin. Eventually, most patients develop symptoms related to the affected arteries.

Severe, sometimes throbbing headache (temporal, occipital, frontal, or diffuse) is the most common symptom. It may be accompanied by scalp pain elicited by touching the scalp or combing the hair.

Visual disturbances include diplopia, scotomas, ptosis, blurred vision, and loss of vision (which is an ominous sign). Brief periods of partial or complete vision loss (amaurosis fugax) in one eye may be rapidly followed by irreversible loss of vision. If untreated, the other eye may also be affected. However, complete bilateral blindness is uncommon. Vision loss is caused by arteritis of branches of the ophthalmic artery or posterior ciliary arteries, which leads to ischemia of the optic nerve. Funduscopic findings may include ischemic optic neuritis with pallor and edema of the optic disk, scattered cotton-wool patches, and small hemorrhages. Later, the optic nerve atrophies. Rarely, central blindness results from infarction in the occipital cortex caused by arterial lesions in the distal cervical region or base of the brain.

Intermittent claudication (ischemic muscle pain) may occur in jaw muscles and muscles of the tongue or extremities. Jaw claudication is noted especially when firm foods are chewed. Jaw claudication and diplopia are associated with a higher risk of blindness.

Neurologic manifestations, such as strokes and transient ischemic attacks, can result when the carotid or vertebrobasilar arteries or branches are narrowed or occluded.

Thoracic aortic aneurysms and dissection of the aorta are serious, often late complications of aortitis and may progress in the absence of other symptoms.

• Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and complete blood count (CBC)

• Biopsy, usually of the temporal artery

• Sometimes, temporal artery ultrasound

Giant cell arteritis is suspected in patients > 50 years if any of the following develops, especially if they also have symptoms and laboratory evidence of systemic inflammation:

• A new type of headache

• Any new symptom or sign compatible with ischemia of an artery above the neck

• Jaw muscle pain during chewing

• Temporal artery or scalp tenderness

• Unexplained subacute fever or anemia

The diagnosis of giant cell arteritis is more likely if patients also have symptoms of polymyalgia rheumatica.

Physical examination may detect swelling and tenderness, with or without nodularity or erythema, over the temporal arteries, sometimes with loss of a palpable pulse. Temporal arteries can become prominent. A temporal artery that rolls under the examiner’s fingers, rather than collapses, is abnormal. The large arteries of the neck and branches of the aorta should be evaluated for bruits.

If the diagnosis is suspected, ESR, CRP, and CBC are obtained. In most patients, ESR and CRP are elevated; anemia of chronic disease is common. Occasionally, platelets are elevated, and serum albumin and total protein, if measured, are low. Mild leukocytosis is commonly detected but is nonspecific.

If the diagnosis of giant cell arteritis is suspected, biopsy of an artery is recommended. Because inflamed segments often alternate with normal segments, a segment that appears abnormal should be sampled if possible. Usually, the temporal artery is biopsied from the side that is symptomatic, but the occipital artery can also be biopsied if it appears abnormal. The optimal length of temporal artery to remove is unclear, but longer samples, up to 5 cm, increase the yield. The added diagnostic value of contralateral biopsy is small, with one study finding an improved yield of 7% (1). Treatment should not be delayed to do the biopsy. Because inflammation resolves slowly, the temporal artery biopsy can be done up to 2 weeks after corticosteroid treatment is started (2).

Color Doppler ultrasound of the temporal artery may detect vessel wall edema, seen as a halo, when performed by experts, and can sometimes substitute for temporal artery biopsy in the diagnosis of giant cell arteritis in selected cases (3). Ultrasound of the temporal artery should be done before treatment is started or within 5 days, because corticosteroids decrease the test sensitivity. Among many advantages, the test is noninvasive, involves no exposure to radiation, and can image other cranial vessels. However, the diagnostic usefulness of temporal artery ultrasound is heavily dependent on the ultrasound operator's skills and equipment.

Imaging of the aorta and its branches should be done at the time of diagnosis and then periodically after, even in the absence of suggestive symptoms or signs (see table Imaging Tests Used in Takayasu Arteritis).

• Corticosteroids

• Tocilizumab

• Low-dose aspirin in selected patients

Treatment should be started as soon as giant cell arteritis is suspected. Even if biopsy is delayed for up to 2 weeks, the pathology should still be evident.

Corticosteroids are the cornerstone of treatment. Corticosteroids rapidly reduce symptoms and prevent vision loss in most patients. The optimal initial dose, tapering schedule, and total length of treatment are debated. For most patients, an initial dose of prednisone 40 to 60 mg orally once a day (or equivalent) for 4 weeks, followed by gradual tapering, is effective (1, 2).

If patients have visual disturbances, an initial dose of IV methylprednisolone 500 to 1000 mg once a day for 3 to 5 days should be tried in an attempt to prevent further decline in vision, particularly in the contralateral eye. Preserving vision probably depends more on how rapidly corticosteroid therapy is initiated rather than the dose. Optic nerve infarction, once started, cannot be reversed regardless of corticosteroid dose.

If symptoms resolve after several weeks on monotherapy with prednisone, it can be tapered gradually, decreasing from ~60 mg/day, based on the patient’s response, by 5 to 10 mg a day every week to 40 mg a day, by 2.5 to 5 mg a day every week to 10 to 20 mg a day, then further tapering until it is discontinued. ESR alone should not be used to evaluate patient response (and disease activity). For example, in older patients, other factors, such as monoclonal gammopathies, can elevate ESR. Clinical symptoms must also be used. C-reactive protein can sometimes be more helpful than ESR.

Most patients require at least 2 years of treatment with corticosteroids. Long-term use of corticosteroids can have significant adverse effects and thus should be limited if possible. More than one-half of patients taking corticosteroids have drug-related complications.

Tocilizumab, an interleukin (IL)-6 receptor antagonist, should be considered when treatment with corticosteroids is initiated, which allows for an accelerated corticosteroid tapering regimen. Tocilizumab has been shown to reduce exposure to corticosteroids (3, 4) . Patients treated with corticosteroids plus tocilizumab also have higher rates of sustained remission once corticosteroids are discontinued (3, 4, 5). However, the optimal duration of therapy with tocilizumab has not been determined (6, 7), and the medication should be given with caution to patients with a history of diverticulitis because of the risk of diverticular perforation.

Low-dose methotrexate has been suggested as an alternative to tocilizumab when a steroid-sparing agent is required and tocilizumab is contraindicated. However, the data to support the efficacy are limited (8). Tumor necrosis factor (TNF) inhibitors such as infliximab have not been shown to be effective, and may have potential harms (9).

Older patients taking prednisone long term should be given an antiresorptive medication to increase bone mass and prevent osteoporosis.

Low-dose aspirin (81 to 100 mg orally once a day) may help prevent ischemic events and should be considered for patients who have critical or flow-limiting involvement of the vertebral or carotid arteries.