Polymyalgia Rheumatica and Giant Cell Arteritis

Polymyalgia rheumatica and giant cell arteritis probably represent a spectrum of one disease.

Both affect the same population (patients > age of 50), and the incidence of the disease increases with each decade of life.

Both show preference for the same HLA haplotypes and show similar patterns of cytokines in blood and arteries.

Giant cell arteritis is a systemic panarteritis affecting medium-sized and large vessels.

Giant cell arteritis was previously called temporal arteritis because the temporal artery is frequently involved, as are other extracranial branches of the carotid artery. However, the aorta and its major branches may be also involved in giant cell arteritis.

Polymyalgia rheumatica and giant cell arteritis frequently coexist.

The important differences between the two conditions are that polymyalgia rheumatica alone is not a systemic vasculitis, does not cause blindness, and responds to low-dose (10–20 mg/day po) prednisone; giant cell arteritis can cause blindness, aortitis, and large artery complications that require high-dose (40–60 mg/day) prednisone.

Diagnostic Essentials

• Age over 50 years.
• Markedly elevated ESR and CRP.
• Polymyalgia rheumatica: pain and stiffness in shoulders and hips lasting for several weeks without other explanation.
• Giant cell arteritis: headache, jaw claudication, polymyalgia rheumatica; without treatment, permanent blindness may occur.

Clinical Findings

Polymyalgia Rheumatica

Polymyalgia rheumatica is a clinical diagnosis based on pain and stiffness of the shoulder and pelvic girdle areas, frequently in association with fever, malaise, and weight loss.

In approximately two-thirds of cases, polymyalgia occurs in the absence of giant cell arteritis.

Because of the stiffness and pain in the shoulders, hips, and lower back, patients have trouble combing their hair, putting on a coat, or rising from a chair.

In contrast to polymyositis and polyarteritis nodosa, polymyalgia rheumatica does not cause muscular weakness either through primary muscle inflammation or secondary to nerve infarction.

Giant Cell Arteritis

The mean age at onset is approximately 79 years.

About 50% of patients with giant cell arteritis also have polymyalgia rheumatica.

The classic symptoms suggesting that a patient has arteritis are headache, scalp tenderness, visual symptoms (particularly amaurosis fugax or diplopia), jaw claudication, or throat pain.

Of these symptoms, jaw claudication has the highest positive predictive value.

The temporal artery can be normal on physical examination but may be nodular, enlarged, tender, or pulseless.

Blindness usually results from anterior ischemic optic neuropathy, caused by occlusive arteritis of the posterior ciliary branch of the ophthalmic artery.

The ischemic optic neuropathy of giant cell arteritis may produce no funduscopic findings for the first 24–48 hours after the onset of blindness.

Asymmetry of pulses in the arms, a murmur of aortic regurgitation, or bruits near the clavicle resulting from subclavian artery stenoses identify patients in whom giant cell arteritis has affected the aorta or its major branches.

Clinically evident large vessel involvement—characterized chiefly by aneurysm of the thoracic aorta or stenosis of the subclavian, vertebral, carotid, and basilar arteries—occurs in approximately 25% of patients with giant cell arteritis, sometimes years after the diagnosis.

Subclinical large artery disease is the rule: PET scans reveal inflammation in the aorta and its major branches in nearly 85% of untreated patients.

Forty percent of patients with giant cell arteritis have nonclassical symptoms at presentation, including large artery involvement causing chiefly aortic regurgitation or arm claudication, respiratory tract problems (most frequently dry cough), mononeuritis multiplex (most frequently with painful paralysis of a shoulder), or fever of unknown origin.

Giant cell arteritis accounts for 15% of all cases of fever of unknown origin in patients > age of 65. The fever can be as high as 40°C (104℉) and is frequently associated with rigors and sweats.

Thus, in an older patient with fever of unknown origin and marked elevations of acute-phase reactants in the absence of an infectious source, giant cell arteritis must be considered even in the absence of specific features such as headache or jaw claudication.

In some cases, instead of having the well-known symptom of jaw claudication, patients complain of vague pain affecting other locations, including the tongue, nose, or ears.

Indeed, unexplained head or neck pain in an older patient may signal the presence of giant cell arteritis.

Laboratory Findings

Polymyalgia Rheumatica

Acute-phase reactants (generally ESR > 30 mm/hour and CRP > 0.5 mg/dL) are universally present.

Giant Cell Arteritis

Nearly 90% of patients with giant cell arteritis have ESRs > 50 mm/hour. The ESR in this disorder is often > 100 mm/hour, but cases in which the ESR is lower or even normal do occur.

In one series, 5% of patients with biopsy-proven giant cell arteritis had ESRs < 40 mm/hour.

Although the CRP is slightly more sensitive, patients with biopsy-proven giant cell arteritis with normal CRP have also been described.

Most patients also have a mild normochromic, normocytic anemia and thrombocytosis.

The alkaline phosphatase (liver source) is elevated in 20% of patients with giant cell arteritis.

Differential Diagnosis

The differential diagnosis of malaise, anemia, and striking acute-phase reactant elevations includes rheumatic diseases (such as rheumatoid arthritis or systemic vasculitides), plasma cell myeloma, other malignant disorders, and chronic infections (such as bacterial endocarditis and osteomyelitis).

Treatment

Polymyalgia Rheumatica

Patients with isolated polymyalgia rheumatica (i.e., those not having “above the neck” symptoms of headache, jaw claudication, scalp tenderness, or visual symptoms) are treated with prednisone, 10–20 mg/day po.

If the patient does not experience a dramatic improvement within 72 hours, the diagnosis should be revisited.

Usually, after 2–4 weeks of treatment, slow tapering of prednisone can be attempted.

Most patients require some dose of prednisone for a minimum of approximately 1 year; 6 months is too short in most cases.

Care must be taken to prevent corticosteroid side effects.

Disease flares are common (50% or more) as prednisone is tapered, which may necessitate increasing prednisone.

Tapering of prednisone should be based on symptoms and not solely on laboratory values because the ESR can fluctuate, and it is not specific for polymyalgia rheumatica disease activity.

Adding weekly methotrexate may increase the chance of successfully tapering prednisone in some patients.

Giant Cell Arteritis

The urgency of early diagnosis and treatment in giant cell arteritis relates to the prevention of blindness. Once blindness develops, it is usually permanent.

Therefore, when a patient has symptoms and findings suggestive of cranial involvement from giant cell arteritis, therapy with prednisone (1 mg/kg/daily or max 80 mg/day po) should be initiated immediately, and a temporal artery biopsy performed promptly thereafter.

For patients who seek medical attention for visual loss, IV pulse methylprednisolone (e.g., 1 g od for 3 days) should be started; unfortunately, few patients recover vision no matter what the initial treatment.

Although it is prudent to obtain a temporal artery biopsy as soon as possible after instituting treatment, diagnostic findings of giant cell arteritis may still be present 2 weeks (or longer) after starting corticosteroids.

An adequate biopsy specimen is essential (at least 2 cm in length), because the disease may be segmental.

Obtaining a unilateral biopsy is recommended in 2021 guidelines (positive in approximately 80–85% of patients) since bilateral biopsies only increase the yield by less than 15%.

The presence of a “halo sign” on temporal artery ultrasonography may obviate the need for temporal artery biopsy, although biopsy remains the gold standard for giant cell arteritis diagnosis.

Temporal artery biopsy is abnormal in only 50% of patients with large artery giant cell arteritis. In these patients, magnetic resonance angiography or CT angiography will establish the diagnosis by demonstrating long stretches of narrowing, thickening, or aneurysmal dilation of the aorta and the subclavian and axillary arteries, or both.

Thoracic aortic aneurysms occur 17 times more frequently in patients with giant cell arteritis than in normal individuals and can cause aortic regurgitation, dissection, or rupture.

The aneurysms can develop at any time but typically occur 7 years after the diagnosis of giant cell arteritis is made; hence, routine screening for this complication in cranial and large vessel giant cell arteritis is recommended.

Prednisone should be continued at a high dose po for about 1 month before tapering.

After 1 month of high-dose prednisone, most patients will have a normal ESR. When tapering and adjusting the dosage of prednisone, the ESR (or CRP) is a useful, but not absolute, guide to disease activity.

A common error is treating the ESR rather than the patient. The ESR often rises slightly as the prednisone is tapered, even as the disease remains quiescent. Because older individuals often have baseline ESRs that are above the normal range, mild ESR elevations should not be an occasion for renewed treatment with prednisone in patients who are asymptomatic.

Tocilizumab, an inhibitor of the IL-6 receptor, is FDA-approved for giant cell arteritis and can reduce the prolonged use of prednisone and decrease the risk of disease flare.