Giant cell arteritis and polymyalgia rheumatica are closely related clinical conditions that are sometimes considered to represent different manifestations of the same underlying disease process. Substantial impairment of function can occur with polymyalgia rheumatica, and blindness is a serious complication of giant cell arteritis. Because family physicians encounter both of these conditions in their practices, they should have a systematic approach to diagnosis and treatment.

Epidemiology

Giant cell arteritis and polymyalgia rheumatica are rare in persons less than 50 years of age. The incidence of each disorder increases with age, and both conditions are approximately two times more common in women than in men.¹

Prevalences vary considerably in different ethnic and racial groups. Both disorders occur more often in whites than in blacks, Hispanics or Asians.¹ Geographically, prevalences increase as residence moves from southern to northern latitudes.¹

In the United States, the reported annual incidence of giant cell arteritis ranges from 0.49 to 27.3 cases per 100,000 population more than 50 years of age.¹ The annual incidence of polymyalgia rheumatica is approximately three times higher.²

Clinically, considerable overlap exists between the two conditions. Approximately one half of patients with giant cell arteritis meet diagnostic criteria for polymyalgia rheumatica, and 15 to 25 percent of patients with polymyalgia rheumatica have concurrent giant cell arteritis or will develop manifestations of the disorder in the future.³

Little is known about causative factors for giant cell arteritis or polymyalgia rheumatica. The most prevalent speculation is that these disorders result from immunologic responses to infectious triggers in genetically susceptible persons.⁴

Pathology

Giant cell arteritis, also known as temporal arteritis or cranial arteritis, is a vasculitis of the large and medium arteries of the head and neck. Arteries below the aortic arch and veins are rarely involved. Microscopically, the inflammation of arterial walls is often patchy and segmental, and it is characterized by the infiltration of mononuclear cells and the presence of giant cells.¹

In polymyalgia rheumatica, pathologic findings are variable and may be minimal or absent. There is no consistent pathology of muscle. Vasculitis may be present, and lymphocytic synovitis is sometimes found in large joints.²

Diagnosis

GIANT CELL ARTERITIS

The American College of Rheumatology (ACR) has developed diagnostic criteria for giant cell arteritis (Table 1).⁵ Three of the five criteria must be met to support the diagnosis.

Symptoms. Approximately two thirds of patients with giant cell arteritis have new-onset headache. This headache is often present on a daily basis and is quite bothersome. The headache may be generalized, but it is more commonly unilateral and localized to the temporal area. When headache is absent or mild, the index of suspicion for the disorder is frequently low, and the diagnosis may be delayed for weeks or even months.

Patients with giant cell arteritis often have a variety of other symptoms, such as malaise, fatigue, low-grade fever, anorexia, weight loss, myalgias or arthralgias. They may also have various visual symptoms, including blurring and scotomas. The onset of these symptoms may be abrupt or insidious.

Jaw claudication in patients more than 50 years of age has fairly high specificity but only moderate sensitivity (45 to 50 percent) for giant cell arteritis.^1,2 Pain on chewing may be unilateral, but it is more often bilateral and frequently involves the masseter and temporalis muscles.

Physical Findings. In patients with giant cell arteritis, the physical findings are highly variable and frequently nonspecific. Nonetheless, the physical examination is important for detecting signs of neoplasm, infection, connective tissue disease and other conditions that can produce the nonspecific symptoms.

Fever and documented weight loss may be present but frequently are absent. Tenderness of one or both temporal arteries or of the adjacent scalp is often present. Temporal artery pulsations may be decreased or absent, but the classic finding of a nonpulsatile nodular temporal artery is uncommon. The funduscopic examination is usually normal but may show pallor or edema of the optic disc.

Patients with giant cell arteritis have few, if any, objective findings relating to muscles or joints. However, findings of coexisting osteoarthritis are often present. Muscle strength is normal.

Laboratory Findings. The erythrocyte sedimentation rate (ESR) is the most important laboratory test in the evaluation of patients with suspected giant cell arteritis. The ESR is almost always elevated, frequently to greater than 100 mm per hour. Occasionally, the ESR may be as low as 40 or 50 mm per hour; rarely, it may be normal.²

A mild normocytic, normochromic anemia is frequently present. The white blood cell count is usually normal but may be mildly elevated. The serum alkaline phosphatase level may be mildly elevated. Less commonly, mild elevation of aminotransferase levels is present.

Temporal Artery Biopsy. If the clinical picture is confusing, a temporal artery biopsy is crucial to establish the diagnosis of giant cell arteritis. Because of the patchy distribution of the inflammation, an arterial segment at least 3 cm long (preferably 5 cm long) should be obtained for examination.¹ Occasionally, both temporal arteries need to be sampled to resolve the diagnostic dilemma. Biopsy of the temporal artery is a simple, low-risk procedure, and complications are rare.

The role of temporal artery biopsy is less clear when the findings of the history, physical examination and laboratory tests strongly indicate the diagnosis of giant cell arteritis. Some authorities recommend pathologic confirmation of the diagnosis in all patients because of the potentially serious side effects of long-term corticosteroid therapy.^1,2,4 Other authorities believe that biopsy is not necessary when patients have typical symptoms and physical findings with a high ESR.⁵

According to the ACR criteria, giant cell arteritis can be diagnosed without a biopsy. The issue is complicated by the fact that biopsies are not always positive, even when giant cell arteritis is present.¹

Color Duplex Ultrasonography. The use of color duplex ultrasonography of the temporal arteries is under investigation as a diagnostic tool for giant cell arteritis. The sensitivity and specificity of this technique may prove to be sufficiently high to obviate the need for biopsy in some patients.⁶

POLYMYALGIA RHEUMATICA

One set of diagnostic criteria for polymyalgia rheumatica is presented in Table 2.⁴

Symptoms. In patients with polymyalgia rheumatica, symptoms may develop abruptly or insidiously. The most common symptom is aching pain involving large proximal muscle groups. Morning stiffness is often present. Initially, the pain may be unilateral or bilateral. As the condition progresses, pain is almost always bilateral, involves the neck, shoulders, back, hips and thighs, and increasingly interferes with physical function.

Muscle pain is frequently accompanied by malaise, fatigue and a low-grade fever. Some patients experience swelling of their hands and feet.

Physical Findings. On physical examination, patients may have a low-grade fever. Weight loss may be present. Proximal muscles may be tender, but muscle strength is good. The tender points characteristic of fibromyalgia are absent. Occasionally, patients have evidence of synovitis and peripheral edema.⁷

Laboratory Findings. As in giant cell arteritis, the most sensitive laboratory finding is an elevated ESR. However, as many as 20 percent of patients with polymyalgia rheumatica have a normal or only mildly elevated ESR.^8,9 In these situations, the diagnosis is based on an otherwise typical presentation and a rapid response to a corticosteroid given in a low dosage.

Patients with polymyalgia rheumatica may have the nonspecific laboratory abnormalities found in giant cell arteritis. The serum creatine kinase level is normal, which helps differentiate the disorder from polymyositis and primary muscle disorders.²

Differential Diagnosis. The differential diagnosis of polymyalgia rheumatica includes malignancy, acute and chronic infections, thyroid disorders, depression, osteoarthritis, rheumatoid arthritis and polymyositis. The ESR is also increased in many of these conditions. The history, physical examination and laboratory evaluation should focus on distinguishing polymyalgia rheumatica from these disorders. A trial of a corticosteroid given in a low dosage may be helpful, because rapid relief of symptoms is characteristic of polymyalgia rheumatica.

Coexisting Giant Cell Arteritis. As many as one fourth of patients with polymyalgia rheumatica may have coexisting giant cell arteritis. Thus, the question arises: Should a patient with polymyalgia rheumatica and no objective signs of temporal arteritis undergo temporal artery biopsy to assess the possible presence of giant cell arteritis? Although this question continues to be debated in the literature, the general consensus seems to be that a temporal artery biopsy is not necessary in this setting.^1,2,10 Clinical outcomes in patients with concurrent polymyalgia rheumatica and asymptomatic giant cell arteritis are no different than outcomes in patients who only have polymyalgia rheumatica.¹

Natural History and Complications

Virtually all patients with giant cell arteritis or polymyalgia rheumatica are treated. Thus, the natural history of either condition is not well understood. Early experiences suggest that the disorders are self-limited and run their course in one to three years.²

Giant cell arteritis has several serious complications, most notably blindness, which may occur in 10 to 15 percent of untreated or inadequately treated patients.^2,11 Blindness may or may not be preceded by visual symptoms and funduscopic changes.

Patients with giant cell arteritis are also at increased risk for the development of aortic aneurysms, primarily involving the thoracic aorta.⁴ These aneurysms, which may rupture with fatal consequences, are occasionally present at the time of diagnosis but more frequently develop later, often after the cessation of treatment. Giant cell arteritis may also be associated with an increased risk of stroke.

One study¹² suggested that patients with giant cell arteritis are at higher risk of death from cardiovascular disease during the first year after the onset of symptoms. In contrast, other studies^13,14 indicate that long-term survival in patients who are adequately treated for giant cell arteritis is comparable to that in unaffected persons of similar age.

Polymyalgia rheumatica generally is not associated with the serious complications of giant cell arteritis. However, untreated patients with this disorder often feel miserable and have impaired quality of life. With appropriate treatment, survival is similar to that in unaffected persons of the same age.¹⁵

The overlap between polymyalgia rheumatica and late-onset seronegative rheumatoid arthritis has been discussed in the literature.¹⁶ It has been speculated that some patients who are diagnosed with polymyalgia rheumatica actually have rheumatoid arthritis and that their course and response to therapy may differ from those in patients with “pure” polymyalgia rheumatica.

Treatment

Giant cell arteritis and polymyalgia rheumatica are treated with corticosteroids. High dosages (40 to 60 mg per day of prednisone) are used for giant cell arteritis, and low dosages (10 to 20 mg per day of prednisone) are used for polymyalgia rheumatica.^1,2

Therapy is primarily based on empiric experiences because few randomized clinical trials are available to guide treatment decisions. Evidence from one clinical trial¹⁷ indicated that daily dosing is superior to every-other-day dosing.

GIANT CELL ARTERITIS

The use of high dosages of corticosteroids in the treatment of giant cell arteritis is based on the need to suppress vascular inflammation and decrease the risk of blindness. In the absence of good evidence from clinical trials, numerous regimens are used. Several of these approaches are summarized in Table 3.

Patients diagnosed as having giant cell arteritis should be started immediately on 40 to 60 mg of prednisone given once a day or in divided doses. Rapid initiation of therapy is thought to minimize the risk of blindness.

The initiation of corticosteroid therapy within one to two weeks before temporal artery biopsy does not appear to change the characteristic pathologic findings.¹⁸ Hence, treatment should not be delayed for the purpose of obtaining a biopsy.

Symptoms usually resolve quickly, often within two to three days of the initiation of the corticosteroid. Most authorities recommend continuing the high dosage of prednisone until the ESR has declined to a normal level.^1,2,4 This usually occurs within four to six weeks.

Once the ESR has normalized, a steroid taper is begun. One approach is to reduce the prednisone dosage by 2.5 to 5 mg per day every one to two weeks and closely monitor the ESR.⁴ During this time, the patient is also monitored for symptom recurrence.⁴ Another approach is to reduce the dosage by 10 percent every two weeks.^1,2 Once a dosage of 10 mg per day has been achieved, the corticosteroid is tapered at a rate of 1 mg per day each month to avoid adrenal insufficiency.

Many patients have at least one recurrence of disease activity during the course of the taper. Recurrences should result in an increase in the dosage followed by a slower taper. Flexibility should be maintained with respect to the steroid taper, and patients should be managed individually.

Most patients with giant cell arteritis require at least two years of corticosteroid therapy. A few patients remain on a low dosage of corticosteroid indefinitely.

POLYMYALGIA RHEUMATICA

Patients diagnosed as having polymyalgia rheumatica should be started on 10 to 20 mg of prednisone a day (Table 4).¹ No clear evidence supports the superiority of once-daily dosing over twice-daily dosing. Some evidence indicates that the incidence of relapse may be lower with a starting dosage of 20 mg per day than with 10 mg per day.¹⁹

The response to corticosteroid therapy is usually rapid and dramatic. If a patient suspected of having polymyalgia rheumatica does not improve greatly within three to four days after the initiation of treatment, the diagnosis should be reconsidered.

If patients respond to treatment, the initial corticosteroid dosage should be continued until the ESR normalizes. This usually occurs in approximately four weeks. At that time, a slow steroid taper is initiated if the initial prednisone dosage was 15 or 20 mg per day. The approach varies but generally involves decreasing the dosage by 1 to 2.5 mg per day every four weeks.⁴ Symptom recurrences are common and should be treated with a return to the initial dosage.

Patients started on 10 mg per day of prednisone should probably remain on this dosage for one to two months after the ESR has normalized.¹⁹ Tapering should then occur at a rate of not more than 1 mg per day per month.

Patients with polymyalgia rheumatica who develop clear evidence of giant cell arteritis should be treated with a corticosteroid in the high dosage appropriate for giant cell arteritis.

Attempts have been made to treat polymyalgia rheumatica with high dosages of non-steroidal anti-inflammatory drugs (NSAIDs). Adequate control of symptoms is occasionally achieved with these agents. However, most patients do not respond satisfactorily to NSAIDs.^1,2,10

COMPLICATIONS OF LONG-TERM CORTICOSTEROID THERAPY

Patients who are treated for giant cell arteritis or polymyalgia rheumatica are at high risk for one or more complications of long-term corticosteroid therapy. Many patients have suppression of the hypothalamic-pituitary-adrenal axis, and life-threatening adrenal insufficiency may develop after abrupt cessation of corticosteroid therapy. For this reason, prednisone is slowly tapered over an extended period from the dosage of 10 mg per day to the cessation of therapy. Also, patients who are receiving a low dosage should be given a higher dosage when they have an infection, when they must undergo surgery or when they have other periods of increased physiologic stress.

Patients with giant cell arteritis or polymyalgia rheumatica may be at increased risk for serious complications of corticosteroids because of advanced age and coexisting diseases. Osteoporosis, increased susceptibility to infection, impaired wound healing, hyperglycemia, hypertension, cataracts, glaucoma and psychiatric disorders are among the complications that may cause serious problems in these patients.¹

A Mayo Clinic study²⁰ found that at least one complication occurred in 65 percent of patients with polymyalgia rheumatica who were treated with a corticosteroid alone and in 80 percent of patients with the disorder who were treated with a corticosteroid and an NSAID. In addition, the risk of developing diabetes mellitus or incurring a vertebral, femoral neck or hip fracture was two to five times greater in these patients than in control subjects matched by age and gender. Because of higher corticosteroid dosages, complications are even more common in patients with giant cell arteritis.

The toxicity of corticosteroids has led to efforts to identify alternative or adjunctive treatments that reduce exposure to these drugs in patients with giant cell arteritis or polymyalgia rheumatica. Unfortunately, no other treatment has been found to approach the efficacy of corticosteroids.¹ Studies that have assessed the concurrent use of methotrexate and corticosteroids as a steroid-sparing strategy have produced mixed results.^21,22 Concomitant therapy with corticosteroids and dapsone, azathioprine, cyclosporine, anti-malarial drugs, cyclophosphamide or gold salts has not been found to reduce corticosteroid toxicity and still maintain therapeutic effectiveness.^4,10,23

Supplementation of calcium (calcium carbonate in a dosage of 1 to 1.5 g per day) and vitamin D (400 to 800 IU per day) may decrease the risk of osteoporosis and subsequent fractures in patients who are being treated with corticosteroids.¹⁰ Evidence from randomized clinical trials indicates that the bisphosphonates etidronate and alendronate may reduce the incidence of osteoporosis and its complications in patients receiving long-term corticosteroid therapy.^24,25

Therapeutic decisions regarding giant cell arteritis and polymyalgia rheumatica must address the balance of benefits and risks. Both disorders cause significant morbidity that affects quality of life. Corticosteroids constitute the most effective therapy for these conditions. Patients should be informed about the potential benefits and risks of corticosteroid therapy and should participate in treatment decisions.