(Temporal) Giant Cell Arteritis and Polymyalgia Rheumatica

Giant cell (temporal) arteritis: A chronic inflammatory process involving the extracranial arteries. Polymyalgia rheumatica: A syndrome characterized by pain and stiffness in muscles of the limb girdles.

These disorders occur almost exclusively in the elderly. Although giant cell arteritis and polymyalgia rheumatica may occur separately, 40 to 60% of patients with giant cell arteritis have clinical features of polymyalgia rheumatica, and 10 to 25% of patients with polymyalgia rheumatica have clinical or pathologic features of giant cell arteritis.

The annual incidence, which varies widely among studies, is 0.5 to 4/1000 in persons > 60. The incidence increases strikingly with age: giant cell arteritis and polymyalgia rheumatica are 10 times more common in patients aged > 80 than in those aged 50 to 59. Both disorders cluster in families and are associated with HLA-DR4. They are twice as common in women than in men and are more common in whites than in blacks.

Etiology and Pathology

In giant cell arteritis, round cell infiltration of the intima and inner part of the media is characteristic. Histiocytes, lymphocytes, and monocytes predominate, but the presence of multinucleated Langhans' giant cells is more diagnostic. Many of the lymphocytes are helper T cells. This feature, combined with the rarity of immunoglobulin deposits around elastin fibers, suggests that the arterial lesion results from cellular rather than humoral immunity. Evidence suggests that cytokines from T cells and macrophages are present in unaffected regions of the temporal arteries from patients with both giant cell arteritis and polymyalgia rheumatica, possibly indicating a common pathogenesis for these two disorders.

The inflammatory process involves short segments of the artery and is usually circumferential. Segments of normal artery, which are smooth and often dilated, taper to affected segments, which are smooth and symmetrically stenosed or occluded. Although the superficial temporal artery is most frequently biopsied because it is most accessible, the vertebral, ophthalmic, and posterior ciliary arteries are often concurrently involved. The internal and external carotid and central retinal arteries are less commonly affected, and the intracerebral arteries are rarely affected.

In polymyalgia rheumatica, skeletal muscle is histologically normal. Synovitis characterized by round cell infiltration and synovial proliferation are common, although they are less severe than in rheumatoid arthritis. Usually the hips and shoulders are affected; the knees and sternoclavicular joints may also be affected.

Symptoms, Signs, and Diagnosis

Both disorders are often associated with fatigue, weight loss, and fever. Weight loss or fever sometimes is the only finding. In patients with polymyalgia rheumatica, signs or symptoms of giant cell arteritis must be sought; if such signs and symptoms are present, complications may be sudden and serious and the initial dose of corticosteroids used for treatment is higher.

In giant cell arteritis, the typical presenting feature is a continuous, throbbing temporal headache. Ischemia of the masseter muscles, tongue, and pharynx causes pain during chewing, talking, or swallowing (jaw claudication). Stenosis of the ophthalmic artery and its branches can cause ocular or orbital pain, transient loss of vision (amaurosis fugax), visual field defects, blurring, or sudden, permanent blindness. Ischemia of the orbital muscle may cause diplopia.

Physical examination may reveal characteristic tender, red, swollen, and nodular temporal arteries with diminished pulses. Less commonly, pulses over other head and neck arteries are reduced or absent. Ophthalmic artery involvement generally causes a central scotoma or total blindness; patchy peripheral visual field defects are less common. Ophthalmic artery involvement may produce blockage, which initially results in a pale, swollen optic disk surrounded by pericapillary hemorrhage; the disk later atrophies. Patchy areas of retinal infarction are less common. Patients with orbital muscle damage present with varying degrees of ophthalmoplegia or ptosis.

In polymyalgia rheumatica, bilateral pain and stiffness of the shoulders and thighs are most common; these symptoms are often severe and lead to immobility and other functional losses (eg, inability to wash or dress). Pain is most severe in the morning. Nocturnal pain that disturbs sleep is also common. Stiffness after inactivity and morning stiffness lasting > 1 hour are usually present.

Physical examination may elicit some tenderness over the affected muscles and painful limitation of hip and shoulder movements, but the tenderness is mild compared with the severity of symptoms. The wrists, knees, and fingers may be swollen and tender.

Laboratory tests: The most useful laboratory test is the ESR, which is usually > 40 mm/hour and often > 100 mm/hour. Although this test is very sensitive, the results are occasionally normal, particularly with polymyalgia rheumatica. C-reactive protein and interleukin-6 levels are also usually elevated in both disorders; however, neither of these tests has been proven to be more specific or sensitive than the ESR.

Antibody titers (eg, rheumatoid and antinuclear factors) are not elevated. Liver enzyme levels are mildly elevated in one third of patients. Patients often have a normochromic-normocytic anemia.

Temporal artery biopsy: Temporal artery biopsy is the most specific test for giant cell arteritis and should be performed in all patients with clinical features of this disorder. Treatment with corticosteroids can be started up to 1 week before biopsy without affecting biopsy results. Treatment should not be delayed to accommodate biopsy. A 5-cm section of artery should be excised; a shorter section may miss the affected segment. Round cell and Langhans' giant cell infiltration of the media confirms the diagnosis; if the biopsy findings are negative, there is a 5 to 10% chance that the diagnosis has been missed. In exceptional circumstances, a biopsy of the contralateral artery may be justified.

The role of temporal artery biopsy in patients with symptoms of only polymyalgia rheumatica is controversial. A reasonable approach is to forgo biopsy and instead follow the patient's clinical symptoms, ESR, and response to treatment.

Treatment

Corticosteroids are the treatment of choice for both giant cell arteritis and polymyalgia rheumatica; these drugs produce a dramatic response. A patient who was severely crippled may regain mobility and full independence within the first week of treatment.

The starting dosage for giant cell arteritis should be equivalent to prednisone 60 mg/day; for polymyalgia rheumatica, 15 mg/day. Initial dosages should be maintained for >= 2 months. When giant cell arteritis is suspected, even before the diagnosis is proven by biopsy of the temporal artery, the physician should start treatment with prednisone 60 mg/day to prevent ocular complications.

Efficacy should be monitored by serial ESR measurements and clinical response. The corticosteroid dosage can be gradually reduced (usually to prednisone 5 to 15 mg/day or equivalent) depending on the ESR and clinical symptoms and signs.

Maintenance therapy should be continued for 1 to 2 years. The corticosteroid dosage should be as low as possible to control symptoms. After corticosteroids are discontinued, the patient should be monitored for >= 6 months. If symptoms recur, treatment must be restarted.

Elderly patients started on corticosteroids may experience many adverse effects, including fluid retention, increased appetite, and confusion. Blood sugar must be monitored for hyperglycemia. Dormant tuberculosis should be excluded by history and skin test results. Appropriate preventive treatment for osteoporosis should be implemented. Stress doses of corticosteroids should be given if another medical event occurs.

Nonsteroidal anti-inflammatory drugs have been used for mild polymyalgia rheumatica but are not nearly as effective as corticosteroids.

In addition to drug treatment, physical therapy should be initiated in patients who show muscle weakness or other functional deficits. Restoration and maintenance of muscle function are key to the treatment of elderly persons.