33. | Manual of Rheumatology and Outpatient Orthopedic Disorders (LB Spiral Manuals)

Chapter 26 Polymyalgia Rheumatica and Temporal Arteritis

Manual of Rheumatology and Outpatient Orthopedic Disorders

Chapter 26 Polymyalgia Rheumatica and Temporal Arteritis

Richard Stern

Polymyalgia Rheumatica
	Clinical presentation
	Laboratory studies
	Differential diagnosis
	Treatment
Temporal Arteritis
	Clinical presentation
	Laboratory studies
	Pathologic findings
	Differential diagnosis
	Treatment
	Summary of diagnostic and therapeutic approach to temporal arteritis

Polymyalgia Rheumatica

Polymyalgia rheumatica (PMR) is a descriptive term that was first suggested by Barber in 1957 to denote a syndrome of aching, usually in elderly patients with an elevated erythrocyte sedimentation rate (ESR), that could not be attributed to more defined rheumatic, infectious, or neoplastic disorders.

PMR is estimated to affect approximately 1 in 1,000 persons in the U.S. population over 50 years of age. Sixty percent of the patients are female . Most patients present after their fiftieth year, and the peak incidence is between ages 60 and 80. However, there are well-documented reports of PMR (usually in association with temporal arteritis) in patients in their forties. Rarely, cases have been observed in younger patients.

I. Clinical presentation

Proximal myalgias. PMR is characterized by chronic, symmetric aching and stiffness of the proximal muscles . These symptoms are most prominent in the shoulder and pelvic girdles and neck, but distal muscle groups may also be involved. Aching and stiffness are worse in the morning and on exertion and may be severe and incapacitating. Muscles may be tender; disuse may lead to atrophy, and contractures occasionally may develop. Muscle strength is often difficult to evaluate because pain is present; however, it should be normal.
Constitutional symptoms. Patients with PMR frequently complain of malaise and fatigue. Fever is usually low-grade, but temperature may occasionally reach 102 °F. Night sweats may occur. PMR may rarely present as a fever of unknown origin. Anorexia and weight loss may be prominent features and suggest malignancy; however, no direct association of PMR with neoplastic disease has been proven.
Neuropsychiatric manifestations , such as depression, dementia, acute disorientation, and amnesia (without focal neurologic disease), may be seen and occasionally are the presenting manifestations of PMR.
Joints. The majority of patients have poorly localized tenderness over their joints, especially prominent over the shoulders and hips. The original description of the syndrome excluded synovitis as a feature, but moderate bland effusions can be seen in the knees and occasionally other joints, such as the wrists. Carpal tunnel syndrome has also been noted. The presence of synovitis may make differentiation from rheumatoid arthritis difficult. Interpretation of radionuclide scans has suggested the presence of synovitis in proximal joints.
Temporal (cranial) arteritis (TA). A detailed discussion of this syndrome and its relationship to PMR can be found in the second section of this chapter.
The incidence of association of the two syndromes is a subject of controversy; however, in some series, 30% to 50% of patients with PMR have had TA, and 60% to 70% of patients with TA have had PMR.

II. Laboratory studies

Blood studies
1. An elevated Westergren sedimentation rate is the laboratory hallmark of PMR; it is usually in excess of 50 mm/h and may exceed 100 mm/h.
2. Normocytic normochromic anemia is seen in approximately 50% of patients.
3. Immunologic studies. The frequency of rheumatoid factors, antinuclear antibodies, and other autoreactive antibodies is not higher than that of age-matched controls.
4. Muscle enzyme levels (creatine kinase, serum glutamic-oxaloacetic transaminase, lactic dehydrogenase, aldolase) are normal.
Radiographic findings are nonspecific, although erosive lesions in the symphysis pubis and the acromioclavicular and sacroiliac joints have been observed.
Electromyographic findings are within normal limits.
Muscle biopsy histology is nondiagnostic; type 2 muscle fiber atrophy probably represents disuse.
Synovial fluid and tissue studies
1. Leukocyte counts in joint fluid range between 1,000 and 8,000, with a preponderance of lymphocytes.
2. Synovial biopsy specimens, when available, reveal mild synovial proliferation with slight lymphocyte infiltration.

III. Differential diagnosis. PMR should be considered in patients over 50 who complain of proximal arthralgia and myalgia. The Westergren ESR is usually elevated above 50 mm/h. Central to the diagnosis of PMR is a rapid dramatic response to low-dose corticosteroid therapy (see section IV.A ). The diagnosis requires exclusion of other syndromes associated with aching, ESR elevation, or both, such as the following:

Neoplasia.
Infectious syndromes.
Other rheumatic conditions, such as rheumatoid arthritis and systemic lupus erythematosus.
Muscle disease, such as polymyositis or thyroid myopathy.
Plasma cell dyscrasias.
Fibromyalgia (an ill-defined syndrome of aching not associated with an elevated ESR; see Chapter 49).

IV. Treatment

Prednisone. Initial therapy for PMR is usually 10 to 15 mg of prednisone daily. A prompt and dramatic clinical response is considered by some to be an absolute criterion for the diagnosis. Most symptoms resolve in 48 to 72 hours, and the ESR should normalize after 7 to 10 days. Unusually, a patient who fails to respond to prednisone may respond to another corticosteroid, such as methylprednisolone or dexamethasone. If a dramatic response does not occur after several days, steroids should be discontinued. Following control of symptoms, the dose of corticosteroids should be reduced to the lowest level required to suppress symptoms, as the morbidity associated with therapy often exceeds that of the underlying disease. The dose of prednisone should be increased only for a recurrence of symptoms, not for an elevation of the ESR alone. Consideration should be given to ensure an adequate calcium intake in these elderly patients on corticosteroids who are at risk for corticosteroid induced osteoporosis (see Chapter 46).
Low-dose corticosteroid therapy for PMR is not appropriate for patients with features suggestive of TA (see second section of chapter).
Nonsteroidal antiinflammatory agents may suppress rheumatic symptoms, but they do not reduce the risk for blindness if TA is present.

Temporal Arteritis

Also known as giant cell or cranial arteritis, TA is a vascular syndrome that affects predominantly cranial arteries. In the late nineteenth century, Jonathan Hutchinson reported the first case, of a man who had difficulty wearing a hat because his temporal arteries were tender. Since that time, the clinical spectrum of TA has broadened (see section I ). Its incidence is unknown but is probably about half that of PMR. TA occurs about equally in men and women. The age distribution of TA is similar to that of PMR, with a peak incidence from 60 to 80 years of age, and it rarely occurs in patients less than 50 years old.

I. Clinical presentation. TA is a strikingly heterogeneous syndrome. All the features of PMR (myalgia, arthralgia, fatigue, malaise, fever, weight loss, and depression) are common. Whether PMR and TA represent different parts of a single disorder is a subject of continuing debate (see section I.D ).

Earlier descriptions of TA emphasize manifestations attributable to involvement of the ophthalmic artery and branches of the external carotid system, but it is now recognized that arterial lesions may be widespread. The varied expressions of the syndrome can be analyzed according to the anatomic patterns of affected arteries.

Symptoms related to involvement of branches of the external carotid artery
1. Headache is probably the most frequent symptom of TA, occurring in 50% to 75% of patients; it is often the first manifestation of disease. It is described as extracranial, dull, boring, and burning. Classically, patients complain of temporal headaches , and the temporal arteries on physical examination may be prominent, beaded, tender, and pulseless. Patients with occipital artery involvement may have difficulty combing their hair or experience discomfort from the pressure of a pillow on their head.
2. Jaw claudication occurs infrequently in TA, but its presence is highly suggestive of the syndrome. Patients with involvement of the maxillary or lingual arteries may have jaw or tongue pain on chewing or talking. There are rare case reports of tongue gangrene.
3. Pain in the ear canal, pinna, or parotid gland may be secondary to involvement of the posterior auricular artery.
4. Temporomandibular joint pain may be secondary to temporal artery involvement.
Symptoms related to involvement of the internal carotid artery
1. Ocular damage secondary to arteritis is the most common serious consequence of TA. Although it occurs in 20% to 50% of patients and is the presenting symptom at diagnosis in 60% of patients with TA in whom visual loss develops, ocular damage is rarely the earliest symptom. In most patients with visual loss, a careful history will reveal that headache, usually specific enough to suggest the diagnosis, preceded blindness in about 40% of cases. Symptoms characteristic of PMR are early manifestations in about 30% of patients.
  Because loss of vision in TA is often irreversible unless treatment is initiated within several hours following the onset of ocular symptoms, special attention must be directed toward early recognition of the syndrome. Ocular manifestations vary according to the pattern of arterial branch involvement. The retina is supplied by the central retinal artery, which is the terminal branch of the ophthalmic artery. Also derived from the ophthalmic artery are the posterior ciliary arteries, which supply the optic nerve, and the muscular branches, which supply the extraocular muscles. Because the posterior ciliary arteries are the most frequently involved arteries in TA, ischemic optic neuritis is by far the most common lesion. Occlusion of the central retinal artery or its branches occurs in fewer than 10% of patients with eye involvement. Therefore, retinal changes such as exudates, hemorrhages, or vasculitis are infrequent. Results of the funduscopic evaluation will often be normal, or the examination will show only mild edema of the nerve head several days after the onset of symptoms. Optic atrophy is a late finding.
  1. Amaurosis fugax occurs in about 10% of patients with TA, and permanent visual loss will develop in 80% of these if they are not treated.
  2. Unilateral or incomplete blindness occurs in about 30% to 40% of patients and, if untreated, may progress to complete blindness over a period of several days.
  3. Bilateral blindness occurs in 25% of patients with TA and, as noted in a and b, is often preceded by amaurosis fugax or partial blindness.
  4. Diplopia secondary to ischemic paresis of the extraocular muscles occurs in about 5% of patients with TA.
2. Central nervous system disease can occur in TA secondary to involvement of any of the intracerebral arteries and produce seizures, cerebral vascular accidents, or abnormal mental status. Peripheral nerve involvement is rare. As a result of the relative inaccessibility of intracranial vessels and the high prevalence of arteriosclerotic vascular disease in older patients, the frequency with which TA leads to significant ischemic central nervous system disease is not known.
Symptoms related to involvement of large arteries
1. Aortic arch and thoracic aorta. Careful physical examination in patients with TA often reveals bruits over the carotid, axillary, or brachial arteries. Limited pathologic studies have shown giant cell arteritis in such vessels; however, because bruits secondary to arteriosclerotic vascular disease are common in elderly subjects, the frequency of aortic and aortic root involvement in TA is not known. Nevertheless, giant cell arteritis has been documented as a basis for aneurysms, dissections, and stenotic lesions of the aorta and its major branches. In isolated cases, coronary artery disease and a variety of aortic arch syndromes secondary to giant cell arteritis have been demonstrated.
2. Abdominal aorta. Involvement of the abdominal aorta, like that of the thoracic aorta, can produce symptoms secondary to aortic aneurysms and intestinal infarction. For unknown reasons, renal involvement is rare. There are some definite examples of leg claudication secondary to giant cell arteritis, but the relevance of this finding is not clear. There is no indication to use steroids to treat peripheral vascular disease in the usual elderly patient with leg claudication who may, for some other reason, have an elevated ESR. As will be discussed later, even in the patient with known TA, steroids should not be used to treat large-vessel disease without evidence that vasculitis, rather than atheromatous disease, is the cause of symptoms.
Symptoms related to polymyalgia rheumatica. The clinical picture of PMR has already been described in detail (see first section of chapter). Patients with TA, with or without PMR, may have similar systemic complaints, such as fatigue, malaise, fever, weight loss, depression, and arthralgias or transient arthritis. Still at issue is how to predict which patient with PMR has TA. Some physicians advocate treating all patients with PMR as if they had TA. However, this approach involves unnecessary treatment of a large group of patients with high-dose steroids. Because a temporal artery biopsy is a relatively benign procedure, having all patients with suspected PMR undergo a biopsy, rather than treating them all as if they had TA, would clearly be preferable. If a patient with polymyalgia has the classic signs or symptoms of TA, a biopsy should be performed. A temporal artery biopsy can be accomplished on an ambulatory basis and, if the results are positive, can dramatically diminish the number of diagnostic studies that are otherwise needed to evaluate systemically ill patients with an elevated ESR. Several clinical studies have demonstrated that the chance of a positive result in a temporal artery biopsy in PMR patients is greatly enhanced if temporal artery pulses are absent or diminished, even without other localizing signs. Even the presence of a nonspecific headache may increase the yield. No differences have been demonstrated among PMR patients with and without TA in regard to degree of ESR elevation, presence of minor visual symptoms, sex, age, and duration of symptoms. Furthermore, about 10% of patients with PMR and localized temporal artery signs have negative biopsy results (see section IV.A. ). In conclusion, PMR patients without signs or symptoms of TA or histologically demonstrated arteritis should not be empirically treated with steroid regimens that are appropriate for TA.

II. Laboratory studies

Erythrocyte sedimentation rate. As in PMR, the laboratory hallmark of TA is the elevated ESR. The ESR (Westergren) is usually between 50 and 100 mm/h, rarely below 40 mm/h, and commonly above 100 mm/h. A normal ESR does not exclude TA. A mild normocytic, normochromic anemia may be present. As in PMR, muscle enzyme levels are normal. Rheumatoid factor, antinuclear antibodies, and anti-DNA antibodies are negative. Complement levels are normal, and cryoglobulins and monoclonal immunoglobulins are absent.
Radiographs. Temporal artery arteriography has no value. However, arteriography of the aorta may be useful in differentiating giant cell arteritis from arteriosclerotic vascular disease. In the former, the vessels often show slowly tapering stenotic lesions, in contrast to the cobblestone pattern of arteriosclerotic disease. Unfortunately, most TA patients are elderly persons who also have arteriosclerotic disease, which makes this differentiation difficult.

III. Pathologic findings. The biopsy specimen should always be taken from the temporal artery on the symptomatic side of the head. If a specific part of the artery is tender, beaded, or inflamed, the biopsy specimen should include that area. There is no information as to whether the artery trunk or a distal branch specimen is best. At least 1 cm of the artery should be taken. Because the process may be segmental, multiple sections should be taken. Histologically, the following are seen:

An inflammatory infiltrate, predominantly of mononuclear cells , usually involving the entire vessel wall. Fibrinoid necrosis is not a feature of the lesion.
Fragmentation of the internal elastic lamina.
Giant cells are almost always present and often seem to engulf parts of the internal elastic lamina. They are difficult to find in some cases, and their absence does not rule out the diagnosis.
Intimal proliferation is often marked , is a nonspecific feature in this age group, and cannot, if found alone, be considered evidence of past or present arteritis. These findings are in contrast to those of the lesions of polyarteritis nodosa, which are characterized by fibrinoid necrosis of the vessel and neutrophil infiltration. When TA involves larger vessels, the lesions are indistinguishable from those seen in Takayasu's arteritis (see section IV.B ).

IV. Differential diagnosis. The diagnosis of TA is made in a patient with a compatible history and physical findings (see section I , section II and section III ). Polymyalgia need not be present, but the ESR should be above 50 mm/h. A definite diagnosis requires a biopsy specimen showing the histologic changes described in section III. Finally, all symptoms should dramatically improve on steroids; the exception is loss of vision, which is usually irreversible.

Arteriosclerotic vascular disease may be responsible for some clinical signs of TA, including a decrease in the temporal artery pulse, temporal artery thickening, and acute visual loss. Patients have been described with loss of vision, elevated ESR, and absent temporal pulses who had only arteriosclerotic changes on temporal artery biopsy and did not respond to steroid therapy. Similarly, in patients with previously documented and treated TA, symptoms may develop suggesting relapse that are actually secondary to arteriosclerotic vascular disease (see section VI.E ).
Takayasu's arteritis is a large-vessel disease and does not directly involve the temporal artery or other arteries of medium and small size . Although Takayasu's arteritis is pathologically indistinguishable from TA involving large vessels, its clinical picture is different. Female patients predominate, and patients are usually 20 to 50 years old. Although symptoms of arteritis may be preceded by a pre-pulseless stage (arthralgias and fatigue), the characteristic PMR symptoms are not common. Finally, the ESR has no consistent pattern, and the response to steroids is unpredictable.
Systemic necrotizing vasculitis. The temporal arteries may occasionally be histologically involved in patients with polyarteritis (see Chapter 32); however, these arteries are rarely abnormal on physical examination, and clinical signs of TA are rarely seen, even in patients with involvement of the temporal arteries. Finally, kidney and peripheral nervous system involvement is rare in TA, even when large vessels are involved.

V. Treatment. The management of uncomplicated TA is 40 mg of prednisone PO daily in divided doses. However, when acute visual changes thought to be secondary to TA are present, patients should be started on 80 to 100 mg of methylprednisolone IV daily and then tapered to the conventional 40-mg oral dose of prednisone after 7 to 10 days. Alternate-day therapy is not effective in preventing visual loss. Symptoms (e.g., PMR, headache, and lethargy) should disappear in 36 to 72 hours. Elevated ESR and ischemic manifestations, such as temporal headache, jaw claudication, and localized temporal artery inflammation , should diminish in several days. The temporal artery pulse may not return, and visual loss may be permanent. High-dose steroids should be maintained only as long as necessary for symptoms to resolve and then should be tapered during several weeks to a maintenance dose of 5 to 10 mg of prednisone daily. Both clinical signs and ESR may be used to follow the response. In patients with visual involvement, tapering should be slower. The average patient will require continued maintenance therapy with 5 to 10 mg of prednisone daily for 2 years, but some patients may need treatment for as long as 5 years. Because the incidence of new visual damage appears to decrease with duration of disease, patients who relapse after 18 to 24 months should probably undergo a repeated temporal artery biopsy before being restarted on high-dose corticosteroids.

VI. Summary of diagnostic and therapeutic approach to temporal arteritis

Temporal arteritis suspected in a patient with no evidence of ocular involvement. Obtain a biopsy specimen from the symptomatic artery, and if findings are positive, treat with high-dose steroids. If the findings are negative, do not treat with steroids unless clinical suspicion is very strong; in that case, obtain a specimen from the contralateral artery. If the result is still negative but clinical suspicion remains very strong, a short clinical trial of oral prednisone may be warranted. If clinical and laboratory parameters improve, continue therapy (see section V ). If they do not improve dramatically, discontinue the treatment.
Temporal arteritis suspected in a patient with acute visual loss. Immediately institute treatment with IV high-dose steroids (80 to 100 mg of methylprednisolone or equivalent). If subsequent biopsy findings are positive, continue therapy as outlined in section V. If the biopsy result is negative and the picture is strongly suggestive of TA, obtain a specimen from the contralateral artery and proceed as described in A.
Polymyalgia rheumatica
1. Temporal arteritis not suspected. Do not perform a biopsy. Treat with low-dose steroids (10 to 15 mg of prednisone daily).
2. Temporal arteritis suspected. Follow the procedure described in A; however, if the biopsy result is negative, low-dose steroids (10 to 15 mg of prednisone daily) should be instituted.
Large-vessel involvement suspected
1. Patient with previously proven temporal arteritis
  1. If involvement is clinically insignificant (bruits or diminished pulses), no therapy is indicated.
  2. If involvement is clinically significant (claudication, coronary artery disease, or other occlusive arterial disease) and if there is other evidence of active TA, treat as described in section V. Arteriography of the involved artery may be helpful; if it suggests that the vascular symptoms are secondary to arteritis, treat as described in section V.
2. Patient with suspected temporal arteritis. Obtain biopsy specimens from temporal arteries as described in A. If findings are negative, do not institute therapy. If positive, treat as outlined in section V.
Suspected relapse of temporal arteritis
1. If the presentation is similar to that of the original episode, re-treat as outlined in section V with 40 mg of prednisone daily.
2. If the presentation is not similar, perform another biopsy and proceed as described in section A.

Bibliography

Fauchald P, Rygvold O, Oystese, B. Temporal arteritis and polymyalgia rheumatica: clinical and biopsy findings. Ann Intern Med 1977;77:845.

Hamilton CR, Shelley WM, Tumulty PA. Giant cell arteritis and polymyalgia rheumatica. Medicine 1971;50:1.

Hollenhorst RW, et al. Neurological aspects of temporal arteritis. Neurology 1960; 10:490.

Klein RG, et al. Large artery involvement in giant cell (temporal) arteritis. Ann Intern Med 1975;83:806.

Klein RG, et al. Skip lesions in temporal arteritis. Mayo Clin Proc 1976;51:504.

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Copyright 2000 by Lippincott Williams & Wilkins
Stephen A. Paget, M.D., Allan Gibofsky, M.D., J.D. and John F. Beary, III, M.D.
Manual of Rheumatology and Outpatient Orthopedic Disorders

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