AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

In 1957, Barber described polymyalgia rheumatica (PMR) as an aching syndrome that was not associated with other defined rheumatic, infectious, or neoplastic disorders and that usually occurred in elderly patients with constitutional symptoms and an elevated erythrocyte sedimentation rate (ESR). Temporal arteritis, also known as giant cell arteritis (GCA) or cranial arteritis, is a systemic, inflammatory, vascular syndrome that predominantly affects the cranial arteries. In the late 19th century, Jonathan Hutchinson reported on a man who had difficulty wearing a hat because of his tender temporal arteries. Since then, the giant cell arteritis clinical spectrum has been growing.

Pathophysiology

The etiology of giant cell arteritis is unknown, but the pathogenesis involves a chronic inflammatory process, predominantly of large arteries, resulting in the elaboration of various cytokines.

The specific cytokine production by the involved tissues may influence how a disease presents clinically. Cytokine profiles for giant cell arteritis and polymyalgia rheumatica are different. In giant cell arteritis, inflamed temporal arteries contain the T-lymphocyte products interferon-gamma (IFN-gamma) and interleukin (IL)–2. Giant cell arteritis also contains the macrophage products IL-1 beta, IL-6, and transforming growth factor-beta (TGF-beta). In polymyalgia rheumatica, temporal arteries contain transcripts for TGF-beta, IL-1, and IL-2 but not IFN-gamma.

Patients with giant cell arteritis, who present with fever of unknown origin and who do not have ischemic symptoms, typically have low IFN-gamma levels. Arteries that express high IFN-gamma levels typically have multinucleated giant cells (MGCs). Unlike macrophages, MGCs have important secretory functions and do not only remove debris. MGCs secrete platelet-derived growth factor (PDGF), which stimulates intimal hyperplasia. MGCs also secrete vascular endothelial growth factor (VEGF), a critical mediator of angiogenesis in the arterial wall.

Current researchers recently described the topography of inflammatory cells in different regions of the artery as follows:

• Adventitial macrophages produce IL-1 and IL-6.
• Medial macrophages produce metalloproteinase-2, PDGF, and VEGF.
• Intimal macrophages produce nitric oxide synthetase-2 and TGF-beta.
• Adventitial T lymphocytes make IFN-gamma.
• T lymphocytes may enter the arterial wall through the vasa vasorum, which exist in the adventitia.
• The adventitia is the likely site of initial immunologic injury and is considered the immunological center in the pathogenesis of giant cell arteritis.

Concentric intimal hyperplasia is an important underlying pathologic lesion in giant cell arteritis. Researchers assume that intimal hyperplasia occurs when the blood vessel wall responds to injury and that it is a repair mechanism. PDGF is important in stimulating intimal hyperplasia. PDGF derives from macrophages and giant cells, distinguishing giant cell arteritis from other vasculopathies. For example, resident smooth muscle cells, rather than monocytes, produce most of the PDGF in atherosclerotic disease. In giant cell arteritis, the media is the main site of injury. The medial macrophages release the tissue-destroying enzymes and mediate tissue repair by secreting factors (eg, PDGF, VGEF), resulting in a hyperplastic intima that obstructs the blood vessel lumen.

The intima and media layers are the histological center in the pathogenesis of giant cell arteritis. Cell adhesion molecules influence the pathogenesis, and endothelial cells play a pivotal roll. Inflammation is an important process that influences the endothelium and causes neovascularization. This process occurs mainly at the intima-media junction and at the adventitial layer. Adhesion molecules are far more intensely expressed on these neovessels than in the vessel lumen. Using immunochemical staining, Cid et al recently demonstrated that different adhesion molecules might regulate how leukocytes and endothelial cells interact in different temporal artery layers.

Systemic manifestation is likely related to the inflammatory process and cytokine elaboration, while end organ involvement is related to vascular occlusion.

Frequency

United States

Polymyalgia rheumatica affects approximately 1 per 1000 patients older than 50 years. The incidence of giant cell arteritis is unknown, but researchers suggest the rate is 33% of that of polymyalgia rheumatica.

Mortality/Morbidity

• The morbidity of polymyalgia rheumatica relates to the treatment complications associated with long-term steroid therapy (eg, osteoporosis, hypertension, diabetes, cataract formation, increased infection risk). Patients with giant cell arteritis also have steroid-related complications; however, they are also at risk for blindness. Ischemic optic retinopathy develops in approximately 20-50% of patients with giant cell arteritis presenting to the ophthalmologist, and vision loss often is irreversible.
• Very rarely, central nervous system disease can occur, producing seizures, cerebral vascular accidents, or abnormal mental status. This is true even though giant cell arteritis, for the most part, occurs only in vessels with an elastica, a finding that is not present with intradural blood vessels. However, involvement of the aortic arch vessels, including the subclavian arteries, can lead to a subclavian steal syndrome and brain ischemia. Rarely, intracranial vessels can be involved. The frequency of giant cell arteritis leading to significant ischemic central nervous system disease is not known because the intracranial vessels are relatively inaccessible and arteriosclerotic vascular disease is prevalent in older patients. Peripheral nerve involvement is also rare
• Studies show that giant cell arteritis is a basis for aneurysms, dissections, stenotic lesions of the aorta, and stenotic lesions of the major branches of the aorta. Isolated cases of coronary artery disease and various aortic arch syndromes are evident secondary to giant cell arteritis. Involvement of the abdominal aorta, similar to that of the thoracic aorta, can produce symptoms secondary to aortic aneurysms and intestinal infarction. Some clear-cut examples of arm or leg claudication are reported secondary to giant cell arteritis.

Race

• Both polymyalgia rheumatica and giant cell arteritis are much less common in African Americans compared to white persons.

Sex

• Polymyalgia rheumatica and giant cell arteritis affect women twice as often as men.

Age

• Most patients with polymyalgia rheumatica or giant cell arteritis present after their sixth decade, and peak incidence occurs in patients aged 60-80 years. However, studies show that polymyalgia rheumatica, usually in association with giant cell arteritis, can occur in younger patients, as early as the fifth decade, but this is rare. Therefore, consider an alternative diagnosis in patients younger than 50 years.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Giant cell arteritis is a strikingly heterogeneous systemic inflammatory disorder. Presentation varies from fever of unknown origin to visual loss and limb claudication. Arterial lesions may be widespread; therefore, the varied expression of the syndrome can be analyzed according to the anatomical pattern of the arteries affected. Polymyalgia rheumatica and giant cell arteritis may represent 2 parts of a single disease spectrum, with giant cell arteritis at the more severe end. They share certain constitutional symptoms, eg, fatigue, weight loss, and fever. Approximately 50% of patients with giant cell arteritis have features of polymyalgia rheumatica, ie, proximal stiffness, soreness, and pain. Earlier descriptions of giant cell arteritis emphasize manifestations that were attributable to involvement of the ophthalmic artery and branches of the external carotid system, but arterial lesions may be widespread.

• Constitutional symptoms
• • Patients frequently complain of malaise and fatigue. Their temperature usually is low-grade but, especially with giant cell arteritis, may occasionally may reach 102°F. Night sweats may occur. A presentation as fever of unknown origin, thus, is much more common with giant cell arteritis than polymyalgia rheumatica.
  • Anorexia and weight loss may be prominent features suggesting a malignancy, in which case an age-appropriate malignancy evaluation is recommended.
• Proximal myalgias and stiffness
• • Polymyalgia rheumatica is characterized by symmetric proximal joint and muscle aching, soreness, and stiffness. These symptoms are most prominent in the shoulder, neck, and pelvic girdles and may involve the distal joints and muscle groups. The onset of symptoms may be abrupt or insidious over weeks to months.
  • Aching and stiffness are worse in the morning and with exertion, and they may be severe and incapacitating. Muscles may be tender, disuse may lead to atrophy, and contractures may develop. Muscle strength (usually normal) is often difficult to evaluate because of pain.
  • Polymyalgia rheumatica can coexist with giant cell arteritis. In some series, 10-15% of patients with pure polymyalgia rheumatica had associated giant cell arteritis based on findings from biopsy of the temporal artery. Conversely, 50-70% of patients with giant cell arteritis had associated polymyalgia rheumatica.
  • Even when treating patients for isolated polymyalgia rheumatica, instruct the patient to report the development of headache or visual symptoms that could be caused by occult giant cell arteritis.
• Joint symptoms
• • Most patients have poorly localized tenderness over the joints, especially the shoulders and hips.
  • Giant cell arteritis originally excluded synovitis as a feature, but moderate bland effusions can develop in the knees and occasionally other joints (eg, shoulders, wrists).
  • Carpal tunnel syndrome and peripheral synovitis may be present in patients with polymyalgia rheumatica, which can lead to diagnostic confusion.
• Symptoms related to vasculitis involving branches of the external carotid artery
• • Headache and scalp pain are probably the most frequent symptoms of giant cell arteritis, occurring in 50-75% of patients. Headache is often the first manifestation of disease and is described as extracranial, dull, boring, and burning. A classic complaint is persistent and prominent temporal headaches. Patients with occipital artery involvement may have occipital pain and difficulty combing their hair or discomfort from the pressure of a pillow on the head.
  • Ear canal, pinna, or parotid gland pain may occur secondary to involvement of the posterior auricular artery.
  • Jaw claudication and pain (predominantly in the masseter muscles with chewing) are highly specific symptoms of giant cell arteritis and occur in nearly 50% of patients. Patients with involvement of the maxillary or lingual arteries may have jaw or tongue pain when chewing or talking, and tongue gangrene has been reported.
• Symptoms related to vasculitic involvement of the ophthalmic artery and its branches
• • In patients with giant cell arteritis, decreased vision secondary to arteritis is the most common serious consequence. This occurs in 20-50% of patients who present to ophthalmologists and is the presenting symptom at diagnosis in 60% of patients with giant cell arteritis who develop visual loss.
  • A careful history from most patients who present with "sudden" visual loss reveals that headache, constitutional symptoms, and polymyalgia rheumatica (usually specific enough to suggest diagnosis) precede blindness in approximately 40% of patients. Even the evolution of the visual loss is often staggered, with a partial field defect progressing to complete blindness over days. If giant cell arteritis remains untreated, the second eye may become affected within 1-2 weeks.
  • Ocular manifestations vary according to the pattern of arterial branch involvement.
  • The posterior ciliary arteries are the arteries most frequently involved in giant cell arteritis, and thus, ischemic optic neuritis is the most common lesion.
  • The central retinal artery supplies the retina, which is the terminal branch of the ophthalmic artery. Occlusion of the central retinal artery or its branches occurs in fewer than 10% of patients with eye involvement; therefore, retinal changes (eg, exudates, hemorrhages, vasculitis) are infrequent.
  • Amaurosis fugax occurs in approximately 10% of patients with giant cell arteritis, and, if not treated, 80% of those patients develop permanent visual loss.
  • The posterior ciliary arteries that supply the optic nerve and the muscular branches that supply the extraocular muscles also derive from the ophthalmic artery. Thus, diplopia or ptosis, observed in 5% of patients with giant cell arteritis, may precede visual loss.
  • Note that the visual abnormality that occurs can be a composite of many ischemic events occurring together in the optic nerve, extraocular muscles, chiasm, and the brain itself.
• Symptoms related to large artery involvement
• • These symptoms are related to involvement of the aortic arch and thoracic aorta. Limited pathologic studies show giant cell arteritis in vessels with bruits; however, the frequency of aortic and aortic root involvement in giant cell arteritis, based on clinical evidence, is approximately 15%.
  • Certain clinical characteristics distinguish large vessel from cranial giant cell arteritis. Approximately 88% of large vessel involvement occurs in women. Patients typically have a younger age at onset, fewer constitutional symptoms, and a longer interval until diagnosis. Thoracic aneurysms with giant cells in the tissue can develop as late as 15 years after the diagnosis and successful treatment of giant cell arteritis. These patients are less likely to have positive findings after temporal artery biopsy, headache, jaw claudication, or visual changes and are more likely to have arm claudication at disease onset.
  • The major symptoms are arm or leg claudication. Occasionally, symptoms related to intermittent or persistent brain ischemia can be present and are related to a subclavian steal syndrome or narrowing of other aortic arch vessels or, even rarely, intracerebral vascular disease.
  • Abdominal aorta involvement can occur. Giant cell arteritis can present with symptoms of aortic aneurysms and intestinal infarction. For unknown reasons, renal involvement is rare.

Physical

In polymyalgia rheumatica, a striking paucity of findings is encountered during the physical examination relative to the severity of the symptoms. The same may be true for giant cell arteritis, although ocular and funduscopic evidence of ischemic disease is present in symptomatic patients.

• Patients may present with fever.
• Muscles may be tender.
• Joints are tender, especially over the shoulder and pelvic girdles. Mild peripheral synovitis may be present in patients with polymyalgia rheumatica.
• Temporal arteries are prominent, beaded, tender, and pulseless; however, a totally normal appearance of these vessels in no way excludes a diagnosis of giant cell arteritis.
• Funduscopic examination findings typically are normal, although optic atrophy or ischemic optic neuropathy may be observed in patients with symptoms of visual loss.
• Bruits may be heard over the carotid, axillary, or brachial arteries.

Causes

The cause of polymyalgia rheumatica and giant cell arteritis is unknown. Environmental and genetic factors are likely important.

• Genetic factors
• • Polymyalgia rheumatica and giant cell arteritis may aggregate in families.
  • Increased prevalence of polymyalgia rheumatica and giant cell arteritis exists in individuals with a European background, and a decreased incidence and prevalence is noted in African Americans.
  • In polymyalgia rheumatica and giant cell arteritis, the frequency of the human leukocyte antigen DR4 is approximately twice that of normal controls in some series and may be an important susceptibility factor.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Thyroid myopathy

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Blood studies
• • The laboratory hallmark of polymyalgia rheumatica and giant cell arteritis is an elevation in the acute phase reactants, ie, ESR and C-reactive protein (CRP). The ESR is usually in excess of 50 mm/h and may exceed 100 mm/h. However, a sedimentation rate in the low 30s or 20s does not exclude a diagnosis of polymyalgia rheumatica or giant cell arteritis if other characteristic clinical or, in the case of giant cell arteritis, pathological, features are present.
  • Normocytic normochromic anemia and thrombocytosis occur in approximately 50% of patients with polymyalgia rheumatica and are good guides to the state of inflammation. These findings are also common in giant cell arteritis.
  • In both polymyalgia rheumatica and giant cell arteritis, the frequency of rheumatoid factor, antinuclear antibodies, and other autoreactive antibodies is not higher than that of age-matched controls. Complement levels are normal, and cryoglobulins and monoclonal immunoglobulins are absent.
  • Findings from liver function tests, especially the alkaline phosphatase level, may be elevated in approximately one third of patients, most commonly in giant cell arteritis rather than pure polymyalgia rheumatica.
  • Muscle enzyme levels (eg, creatine kinase, aldolase) are normal in both polymyalgia rheumatica and giant cell arteritis.

Imaging Studies

• Researchers have recently explored the role of color duplex ultrasonography in the diagnosis of giant cell arteritis.
• A hypoechoic halo around the temporal artery lumen on color duplex ultrasound images was reported in 22 of 30 patients (73%) with biopsy-proven giant cell arteritis. The halo was observed bilaterally in 17 of these patients and disappeared at a mean of 16 days after the initiation of corticosteroid therapy. The presence of the halo had a sensitivity of 73% and was 100% specific for giant cell arteritis. The halo represents edema in the artery wall. Although some centers consider this finding a major decision-maker in their diagnostic equation, others do not believe that such a halo is definitive for of giant cell arteritis. Results of the superficial temporal artery biopsy, not these ultrasonography findings, remains the criterion standard for the diagnosis.
• Thoracic or abdominal ultrasound may be helpful for diagnosing and monitoring patients with aortic aneurysms.
• In giant cell arteritis, temporal artery arteriography has no diagnostic value and also does not aid in predicting the proper biopsy site for the temporal artery.
• No characteristic imaging abnormalities exist in polymyalgia rheumatica. However, recent magnetic resonance imaging findings of tendinitis and bursitis in the shoulders of patients with polymyalgia rheumatica support the soft tissues as significant sites of inflammation and sources of symptoms in polymyalgia rheumatica.

Other Tests

• Electromyographic studies
• • Results are within normal limits.
  • This study is rarely needed in patients with a clinical presentation of polymyalgia rheumatica.
• Synovial fluid and tissue studies
• • Leukocyte counts in joint fluid, which are rarely available for study, range from 1000-8000/µL, with a preponderance of mononuclear cells.
  • Synovial biopsy findings, when available, reveal mild synovial proliferation with slight lymphocytic infiltration.

Procedures

• Muscle biopsy
• • Histology findings are not diagnostic in polymyalgia rheumatica; type II muscle fiber atrophy probably represents disuse.
  • This study is not indicated because patients with polymyalgia rheumatica do not present with weakness or muscle enzyme abnormalities.
• Temporal artery biopsy
• • Consider this biopsy if a patient with polymyalgia rheumatica has symptoms or signs suggestive of giant cell arteritis or is unresponsive to 15 mg prednisone daily. It may also be indicated in the workup of an elderly patient with fever of unknown origin with a high ESR in whom infection and malignancy testing has been unrevealing.
  • Temporal artery biopsy can be performed on an ambulatory basis and, if findings are positive, can dramatically diminish the diagnostic studies otherwise needed in evaluating systemically ill patients with an elevated ESR.
  • Several clinical studies demonstrate that the chance of positive findings after temporal artery biopsy in patients with giant cell arteritis polymyalgia rheumatica is greatly enhanced if temporal artery pulses are absent or diminished, even in the absence of other localizing signs. The presence of a nonspecific headache may also increase the yield.
  • No difference is evident in the degree of ESR elevation, the presence of minor visual symptoms, sex, age, or the duration of symptoms among patients with polymyalgia rheumatica who do not have giant cell arteritis; furthermore, approximately 10% of patients with polymyalgia rheumatica and localized temporal artery signs have negative biopsy findings.
• Strategies for planning temporal artery biopsies in patients suggested to have giant cell arteritis
• • Always perform the biopsy on the temporal artery on the symptomatic side of the head.
  • If a specific part of the artery is tender, beaded, or inflamed, include that area in the biopsy. No information exists on whether the artery trunk or a distal branch specimen is best. Take at least 2-3 cm of the artery. Make multiple sections because the process may be segmental.
  • Studies performed during the 1970s and 1980s show that bilateral temporal artery biopsies can increase the sensitivity of diagnosing giant cell arteritis by 11-60%. Recent studies prove the efficacy of bilateral versus unilateral temporal artery biopsy. Five of 182 (2.7%) patients with negative temporal artery biopsy findings showed arteritis in their contralateral biopsy specimen and, ultimately, were diagnosed with giant cell arteritis. Therefore, proceed with a contralateral biopsy if clinical evidence for giant cell arteritis is strong and findings are negative after unilateral temporal artery biopsy.
  • Results of temporal artery biopsies remain positive for characteristic giant cell arteritis pathology after as long as 4 weeks while high doses of corticosteroids are administered. Thus, the physician should never delay the institution of steroids because of fear of ruining the chances of finding an inflamed artery on a biopsy sample.

Histologic Findings

An inflammatory infiltrate, predominantly of mononuclear cells, usually involves the entire vessel wall (ie, panarteritis). Fragmentation of the internal elastic lamina is characteristic. Fibrinoid necrosis is not a feature of the lesion. Giant cells are commonly present, and they often seem to engulf parts of the internal elastic lamina. The giant cells are difficult to find in some cases, and their absence does not exclude the diagnosis. Intimal proliferation often is marked, is a nonspecific feature in this age group, and does not suggest past or present arteritis if found alone. When giant cell arteritis involves larger vessels, the lesions are indistinguishable from those observed in Takayasu arteritis.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

• Both polymyalgia rheumatica and giant cell arteritis are clinical diagnoses, with laboratory tests and temporal artery biopsies functioning as supporting, not definitive, data. Thus, the diagnosis should not be held hostage to the finding of an elevated sedimentation rate or positive temporal artery biopsy results in the setting of a clinical picture that overwhelmingly supports the diagnosis. Thus, do not await the results of a temporal artery biopsy before administering corticosteroids, as such an action could leave a patient with giant cell arteritis open to developing irreversible vision loss.
• Corticosteroid therapy is discussed as follows:
• • Prednisone is the preferred therapy for giant cell arteritis and polymyalgia rheumatica. The starting dose for giant cell arteritis is usually 60-80 mg/d and for polymyalgia rheumatica is 10-15 mg/d. Start patients on parenteral methylprednisolone at doses of 250-1,000 mg intravenously daily for 3 days when acute visual changes are present secondary to giant cell arteritis. Alternate-day therapy is not effective in preventing vision loss.
  • Do not offer empirical treatment with high-dose steroid regimens appropriate for CGA to patients with polymyalgia rheumatica who do not have symptoms of giant cell arteritis or who do not demonstrate histologic arteritis. On the other hand, do not delay treatment in patients with visual symptoms or signs (eg, amaurosis fugax, partial or complete visual loss) when giant cell arteritis is strongly suggested. The confirmatory biopsy can be performed after treatment is started, without major alteration in the diagnostic histology for up to 10 days.
  • Usually, symptoms of giant cell arteritis (eg, polymyalgia rheumatica, headache, lethargy) disappear in 36-72 hours. The ESR elevation and ischemic manifestations (eg, temporal headache, jaw claudication, localized temporal artery inflammation) diminish in several days. The temporal artery pulse may not return, and visual loss may be permanent.
  • A prompt and dramatic clinical response to low-dose prednisone (<15 mg/d) is a key feature of polymyalgia rheumatica, and most symptoms resolve in 48-72 hours.
  • After 2-4 weeks, the ESR, anemia, and thrombocytosis usually normalize. If the patient shows no significant improvement in a week, consider an alternative diagnosis, which may include one of the aforementioned disorders or a companion systemic disorder (eg, giant cell arteritis that may require a higher steroid dose).
• Even in patients with known giant cell arteritis, do not use steroids to treat large vessel disease without evidence that vasculitis, rather than atheromatous disease, is responsible. Because cases of aortic aneurysms caused by giant cell arteritis may develop many years after the patient no longer requires steroid therapy, follow-up chest radiographs and thoracic or abdominal ultrasound may be needed over time.
• In refractory cases of polymyalgia rheumatica or giant cell arteritis that require persistent doses of prednisone of more than 5-10 mg/d or in those patients who develop significant steroid-related adverse effects, consider using other anti-inflammatory agents, such as methotrexate (RA doses of 15-25 mg/wk PO) or azathioprine (2 mg/kg/d PO), as potentially steroid-sparing disease-controlling drugs. These agents may suppress rheumatic symptoms but do not reduce the risk of blindness if giant cell arteritis is present. The newer tumor necrosis factor antagonists are being evaluated in clinical trials for the treatment of giant cell arteritis. Initial studies of infliximab have not shown impressive disease-controlling or steroid-sparing effects.
• Recent retrospective but impressive data support the use of low-dose aspirin in patients with giant cell arteritis for prevention of visual loss and stroke.

Consultations

• Consultation with a rheumatologist is helpful.
• Consultation with an ophthalmologist may be useful to help exclude other causes of visual disturbances and to perform temporal artery biopsy.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Corticosteroid therapy for giant cell arteritis is started at high doses with gradual tapering using clinical manifestations and the ESR to gauge disease activity. In general, prednisone is a safe treatment for those patients with the clinical presentation of pure polymyalgia rheumatica, making the need for high-dose steroid therapy or routine biopsy unnecessary. However, instruct all patients with polymyalgia rheumatica to call their physician immediately if they develop headache, visual symptoms, or other manifestations of giant cell arteritis.

This transition from polymyalgia rheumatica to giant cell arteritis is uncommon but can occur within 12-14 months after initial diagnosis. In general, administering low-dose corticosteroids for polymyalgia rheumatica enables protection from visual loss. Some physicians have advocated treating all patients with polymyalgia rheumatica with high-dose corticosteroids to prevent complications of occult giant cell arteritis. This approach leads to unnecessary treatment-related toxicity and is not generally recommended.

Drug Category: Corticosteroids

These agents have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.

Drug Category: Immunosuppressive agents

May be anti-inflammatory for giant cell arteritis and result in steroid sparing in relatively resistant cases.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Outpatient Care

• Symptom control
• • Relapse is common (25-60%).
  • For almost all patients, the physician can significantly decrease the steroid dosage; however, occasionally the dose may need to be briefly increased then decreased again because of the ebb and flow of the inflammatory process.
  • The duration of treatment of polymyalgia rheumatica is highly variable among patients, with some needing corticosteroids for only 1 year and others for more than 5 years. In general, polymyalgia rheumatica is a self-limited disorder lasting approximately 2 years, but some patients may also need low doses of prednisone for a frustratingly longer period. Constantly try to optimally balance the positive and negative effects of steroids in these elderly patients with many comorbid disorders.
  • Following symptom control, reduce the dosage of corticosteroids to the lowest level required to suppress symptoms because the cumulative morbidity associated with long-term therapy often exceeds that of the underlying disease.
  • Increase the dosage of prednisone only if symptoms recur, not based solely on an elevation of the ESR. An elevated ESR without accompanying symptoms or signs of polymyalgia rheumatica or giant cell arteritis could be related to an infection.
  • If the patient improves (as expected) but the ESR does not improve or rises after a prior fall, look for another cause of an elevated ESR (eg, infection). Although uncommon, discontinuing steroid therapy after less than 2 years is possible.
  • Patients with polymyalgia rheumatica may require low-dose steroids (eg, <5 mg/d of prednisone) for 6 months to 5 years.
  • In patients with giant cell arteritis, maintain high-dose steroid therapy only long enough for symptoms to resolve and then taper to a maintenance dosage of prednisone over several months. Both clinical signs and the ESR (or CRP) assist in monitoring the patient's response.
  • Patients with visual involvement usually require slower tapering of corticosteroids. While the average patient requires continued maintenance therapy with prednisone for 2 years, some patients may need treatment for as long as 5 years. Because the incidence of new visual damage appears to decrease with disease duration, consider a repeat temporal artery biopsy before restarting patients who relapse after 18-24 months on corticosteroids.
• Long-term therapy
• • Narvaez et al retrospectively studied the effect of long-term therapy on patients with polymyalgia rheumatica and patients with giant cell arteritis (ie, 10-y period). Among the patients with pure polymyalgia rheumatica, 49% were off steroids in a mean duration of 23 months and they remained symptom-free at 11 months of follow-up. These patients had a higher remission rate than those with polymyalgia rheumatica associated with giant cell arteritis.
  • In the patients with polymyalgia rheumatica associated with giant cell arteritis, 29% were off steroids after a mean duration of 31 months and they remained symptom-free at 14 months of follow-up. The median duration of therapy was 56 months for this group; 50% of these patients required treatment for more than 4 years.
  • Factors that predict the need for prolonged therapy and increased relapse risk are older age at diagnosis, female sex, higher baseline ESR, and rapid taper of prednisone.
• Prophylactic measures
• • Given the high risk of corticosteroid-induced osteoporosis, obtain a baseline bone densitometry value at the start of therapy for polymyalgia rheumatica or giant cell arteritis and administer an aggressive bone-preserving regimen accordingly.
  • Ensure that all patients are on 1500 mg of calcium and 800 IU of vitamin D-3 per day.
  • Consider adding osteoporosis preventive therapy with bisphosphonates, calcitonin, or hormonal therapy if the baseline bone densitometry findings show osteopenia or osteoporosis.
  • Administer age-appropriate vaccinations (eg, influenza, Pneumovax).
  • Low-dose aspirin (81 mg enteric coated) may be used for prevention of visual loss.

Complications

• Loss of vision
• Tongue gangrene (rare)
• Scalp necrosis (rare)
• Cerebrovascular accidents (rare)
• Aortic aneurysm, dissection, or stenosis
• Aortic arch syndromes (rare)
• Coronary involvement (rare)
• Corticosteroid-related complications
• Synovitis
• • The presence of synovitis may make differentiating polymyalgia rheumatica and rheumatoid factor–negative rheumatoid arthritis difficult in elderly patients. In addition, these disorders may occur in the same patient, adding further confusion.
  • Findings from radionuclide scans, imaging studies, and synovial biopsies demonstrate the presence of synovitis in proximal joints.

Prognosis

• Polymyalgia rheumatica: This is generally a self-limited 2-year disorder and rarely progresses to giant cell arteritis.
• Giant cell arteritis: Visual damage is often irreversible. The average duration of treatment is 2 years; however, some patients require treatment for 5 years or more. Morbidity from steroid therapy is often worse than the underlying disease.

Patient Education

• Education is the most important step in allowing the patient to appreciate the clinical facets of this illness, the potential adverse effects of the therapy, and the need for monitoring.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to consider the following:
• • Corticosteroid-related adverse effects
  • Long-term use of high-dose corticosteroid therapy due to the treatment of an elevated ESR in an improved patient
  • Avascular necrosis, cataracts, or osteoporosis with vertebral or peripheral fracture
• Many physicians may observe these patients (eg, ophthalmologists; ear, nose, and throat specialists; neurologists; primary care physicians), and their failure to diagnose giant cell arteritis because they either do not think about it until too late or feel that a normal or low ESR excludes the possibility may lead to blindness in the patient.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Alpers CE, Davis CL, Barr D, et al. Identification of platelet-derived growth factor A and B chains in human renal vascular rejection. Am J Pathol. Feb 1996;148(2):439-51. [Medline].
• Barber HS. Myalgic syndrome with constitutional effects: Polymyalgia rheumatica. Ann Rheum Dis. 1957;16:230.
• Bignon JD, Ferec C, Barrier J, et al. HLA class II genes polymorphism in DR4 giant cell arteritis patients. Tissue Antigens. Nov 1988;32(5):254-8. [Medline].
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Article Last Updated: Feb 16, 2006