AUTHOR INFORMATION

Section 1 of 12

Authored by Tarakad S Ramachandran, MD, Chief, Department of Neurology, Crouse Irving Memorial Hospital; Professor, Department of Neurology, State University of New York Upstate Medical University

Coauthored by Richard J Caselli, MD, Professor, Department of Neurology, Mayo Medical School, Rochester, MN; Chair, Department of Neurology, Mayo Clinic of Scottsdale

Tarakad S Ramachandran, MD, is a member of the following medical societies: American Academy of Clinical Electroencephalographers, American Academy of Neurology, American Academy of Pain Medicine, American College of Forensic Examiners, American College of Managed Care Medicine, American College of Physicians, Royal College of Physicians, Royal College of Physicians and Surgeons of Canada, Royal College of Surgeons of England, and Royal Society of Medicine

Edited by Jorge E Mendizabal, MD, Consulting Staff, Corpus Christi Neurology; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Florian P Thomas, MD, MA, PhD, DrMed, Associate Chief of Staff, St Louis VA Medical Center; Associate Director, Neurology Residency Program; Professor, Departments of Neurology, Molecular Virology, and Molecular Microbiology and Immunology, Saint Louis University School of Medicine; Selim R Benbadis, MD, Professor of Neurology, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida College of Medicine, Tampa General Hospital; and Nicholas Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants

Author's Email:	Tarakad S Ramachandran, MD
Editor's Email:	Jorge E Mendizabal, MD

eMedicine Journal, July 10 2006, VOLUME 7, Number 7

INTRODUCTION

Section 2 of 12

Background: Giant cell (temporal) arteritis (GCA) confronts the neurologist in many ways. It should always be considered in the differential diagnosis of a new-onset headache in an elderly patient with an elevated erythrocyte sedimentation rate (ESR). Neuroophthalmologic complications, such as anterior ischemic optic neuropathy (AION), generally are well recognized, but many other neurologic problems can complicate the clinical course of GCA. Timely diagnosis and steroid treatment are essential for the prevention of potentially irreversible ischemic end-organ damage.

Temporal arteritis was first described in the Western literature by Hutchinson in 1890, and the histopathologic features were reported by Horton in 1932. Visual loss associated with temporal arteritis was first reported by Jennings in 1938, and Birkhead first introduced the effectiveness of systemic corticosteroid therapy in preventing blindness.

Pathophysiology: GCA is primarily a disease of cellular immunity. The vasculitic damage is mediated by activated CD4⁺ T helper cells responding to an antigen presented by macrophages. The primary inflammatory response affects the internal elastic lamina. Multinucleated giant cells, which are a histologic hallmark of GCA, may contain elastic fiber fragments. The actual inciting antigen remains unknown, but elastin remains an important suspect.

The superficial temporal artery is involved in most patients, providing a convenient biopsy site, but this is only the "tip of the iceberg." The topographic distribution of GCA, which reflects its predilection for the internal elastic lamina, includes the aortic arch and its branches.

GCA does not cause a widespread intracranial cerebral vasculitis, because intracranial arteries lack an internal elastic lamina. GCA does involve cervicocephalic arteries, including the carotid and vertebral arteries. It commonly affects arteries in the following pattern:

Common, external, and internal carotid artery involvement is usually extracranial; rarely, proximal intracranial segments have been affected.

Intraorbital branches, especially the posterior ciliary and ophthalmic arteries, commonly are affected.

Vertebral arteries are involved as frequently as the superficial temporal arteries in fatal cases, although basilar artery involvement is rare.

Vertebral arteritis is extracranial, but it may extend intracranially for roughly 5 mm beyond dural penetration.

Subclavian, axillary, and proximal brachial arterial involvement produces a characteristic angiographic pattern of vasculitis, consisting of long, smooth, stenotic segments that alternate with nonstenotic segments and tapered occlusions.

Involvement by GCA of the ascending aorta can lead to aortic rupture, and coronary arteritis may result in myocardial infarction (MI).

Less often, the descending aorta and mesenteric, renal, iliac, and femoral arteries can be affected, with attendant complications of intestinal infarction, renal infarction, crural infarction, and ischemic mononeuropathies.

Pulmonary arterial involvement has also been described.

Pathogenesis and histopathologic findings

The pathogenesis of GCA is not known but probably has an idiopathic autoimmune etiology. A cellular immune reaction to elastin and an abnormality of the tunica media of affected vessels have been implicated.

In support of the elastin theory, disease severity has been shown to correlate with the amount of elastic tissue within the vessels, with the arteries most commonly affected being the superficial temporal, ophthalmic, occipital, vertebral, posterior ciliary, and proximal vertebral arteries. The intracranial circulation is typically spared because these arteries have very little elastic tissue. The theory also is supported by histopathologic findings of a disrupted, fragmented internal elastic lamina in affected vessels and the presence of characteristic giant cells close to the internal elastic lamina. Along with elevated serum levels of neutrophil elastase, deposition of elastase along the damaged internal elastic lamina has been described.

In patients with GCA abnormality of the tunica media of affected vessels is probably caused by ischemia, and presumably as a result of an immune-mediated response to the injured smooth muscle cells, secondary damage to the elastic lamina occurs. Histologically, the presence of macrophages and giant cells closely attached to the smooth muscle cells has been shown.

While evidence for humoral immunity includes elevated levels of circulating immunoglobulin and complement, and also immune complex/immunoglobulin and complement deposition in the inflamed vessel wall, support for cellular immunity includes the presence of giant cells, macrophages and monocytes, and lymphocytes in the inflammatory infiltrate. Increased frequencies of the HLA haplotypes B8, DR3, DR4, DR5, and DR(beta)1 are seen in patients with GCA.

Frequency:

• In the US: The incidence of GCA in Olmsted County, Minnesota, increased between 1950 and 1975 from 5.1 to 17.4 incident cases per 100,000 population per year in persons aged 50 years and older. The increase was attributable to greater clinical awareness and improved rate of accurate diagnosis. On January 1, 1975, the prevalence was 133 cases per 100,000 in persons aged 50 years and older.

• Internationally: Few epidemiologic studies of GCA outside the US have been published, but incidence rates are not thought to vary significantly within the defined age-susceptible groups. The highest incidence is reported in Scandinavia, where 23.3-33.6 per 100,000 people older than 50 years are affected.

  Prevalence heavily depends on the number of individuals aged 50 years or older; the mean age of onset is 75 years. Countries with a lower life expectancy have a lower prevalence.

Mortality/Morbidity: GCA has not been associated with a statistically significant increase in rates of death, stroke, or MI compared to an age-matched, community-based control population; however, it can lead to these outcomes.

• GCA leads to death by one of these mechanisms in roughly 2% of cases.

• As would be expected, the topographic extent and severity of the vasculitis is greater in fatal than in nonfatal cases.

• More difficult to quantify are the number of patients whose deaths are related directly or indirectly to chronic corticosteroid use and its attendant complications (eg, hip fracture).

Race: No racial predisposition to GCA is known, although existing epidemiologic studies are limited because they have been performed on predominantly Caucasian populations, suggesting that it is more common among them.

Sex: The female-to-male ratio is roughly 3.7:1.

Age: The median age of onset is 75 years. The age range in one series of 166 cases proven by temporal artery biopsy (TAB) was 55-92 years. Rarely described in those younger than 40 years, it is the most common systemic vasculitis affecting elderly patients.

• The following conditions are histologically similar but nosologically distinct from GCA and occur in different age groups: Juvenile temporal arteritis affects children; primary CNS vasculitis (originally termed granulomatous angiitis of CNS) can strike at any age, but it is far more likely than GCA to affect young adults.

CLINICAL

Section 3 of 12

History: The most commonly reported symptoms are headache (initial symptom in 33%, present in 72%); neck, torso, shoulder, and pelvic girdle pain that is consistent with polymyalgia rheumatica (PMR; initial in 25%, present in 58%); fatigue and malaise (initial in 20%, present in 56%); jaw claudication (initial in 4%, present in 40%); and fever (initial in 11%, present in 35%).

Nonspecific symptoms of cough and sore throat occur in 17% and 11%, respectively, but are rarely the presenting complaints. Amaurosis fugax occurs in 10% overall (initial symptom in 2%), and some degree of permanent visual loss occurs in 8% (initial symptom in 3%).

Less common symptoms, which are almost never the presenting complaint, include limb claudication (8%), transient ischemic attacks (TIAs) or stroke (7%), scintillating scotoma (5%), tongue claudication (4%), diplopia (2%), tongue numbness (2%), and myelopathic symptoms ( <1%).

• Headache and other craniofacial pain syndromes: The headache of GCA has no pathognomonic features, but typically, and most importantly, the headache is either new in a patient without a history of headaches or of a new type in a patient with a history of chronic headaches.


• • It is usually throbbing, generalized, and continuous. Focal temple pain is present with tenderness on direct palpation.
  
  
  
  • Scalp tenderness may be present with hair combing.
  
  
  
  • Less often, the pain may be predominantly occipital or occipitonuchal.
  
  
  
  • Other craniofacial pain complaints can include jaw claudication, tongue claudication, and facial pain (a rare symptom). Jaw claudication is almost pathognomonic of temporal arteritis, and it is a result of ischemia of the maxillary artery supplying the masseter muscles; it causes pain on speaking or chewing.
  
  
  
  • About 15% of patients report symptoms of carotodynia.
  
  
  
• PMR: Neck, torso, shoulder, and pelvic girdle pain may occur within the context of this syndrome.


• • PMR occurs in approximately 58%, and is the initial symptom in 25% of patients with GCA.
  
  
  
  • In typical cases of PMR without vasculitic involvement of the peripheral nervous system, electromyographic (EMG) results are normal.
  
  
  
  • Mild EMG abnormalities in an elderly patient that suggest a mild peripheral neuropathy are generally unrelated to PMR or to a vasculitis.
  
  
  
• Amaurosis fugax and visual loss: Amaurosis fugax occurs in 10-12% of patients with GCA, and permanent loss of vision due to AION occurs in 8-23%.


• • Prior to 1960, most series reported that patients with transient loss of vision went on to develop permanent, bilateral loss of vision due to AION.
  
  
  
  • Following monocular onset, the second eye became affected within days.
  
  
  
  • Today, amaurosis fugax often leads to prompt diagnosis and effective corticosteroid therapy.
  
  
  
• TIAs: Diagnosed entirely on the basis of historical data, TIAs are properly considered in this context.


• • Atherosclerosis, hypertension, and cardiac disease are the most important causes of cerebral infarction in the elderly with or without GCA, but the known propensity of GCA to affect carotid and vertebral arteries should be considered in GCA patients with TIAs and cerebral infarction.
  
  
  
  • Approximately 4% of patients with GCA experience TIA or stroke at some point during their illness, although how many specifically result from GCA is unclear.
  
  
  
  • A greater proportion of TIAs and infarctions occur in the vertebrobasilar territory than the carotid territory in patients with GCA than in the general population.
  
  
  
  • Few clinical features reliably distinguish a vasculitic from an atheromatous cause, although in rare instances, atheroembolic material has been observed funduscopically or angiographically in the setting of active GCA.

  • Vertebrobasilar events sometimes present as acute confusional states or coma as opposed to discrete focal syndromes.

Causes: The cause of this autoimmune disorder is not known. Although mycoplasma and parvovirus B19 infection have been implicated, it is generally accepted that they are only "innocent bystanders."

DIFFERENTIALS

Section 4 of 12

[Atypical Facial Pain]

Cluster Headache
Confusional States and Acute Memory Disorders
Migraine Variants
Multi-infarct Dementia
Polyarteritis Nodosa
Postherpetic Neuralgia
Trigeminal Neuralgia

Other Problems to be Considered:

Dental conditions
Infections
Sinus disease
Granulomatous angiitis of the CNS
Wegener granulomatosis
Horner syndrome
Carotid disease and stroke
Dissection
Connective tissue disease

WORKUP

Section 5 of 12

Lab Studies:

• ESR is elevated in most patients, often to a high level (mean, 85 ± 32 mm in 1 h), although it is normal in roughly 3% of patients. ESR often drops when steroid therapy is started, even in patients with normal baseline.



• CBC reveals mild anemia in most patients, with a mean hemoglobin of 11.7 ± 1.6 g/dL; most have a mild thrombocytosis (mean platelet count, 427 ± 116 x 10 x 10⁹/L).



• Alpha-2 globulin and other acute phase reactants are elevated mildly but nonspecifically in 72%.



• Mild elevations in serum aspartate aminotransferase (AST) and alkaline phosphatase occur in 15%.

Imaging Studies:

• Aortic arch and cerebral angiography


• • Vertebral and external carotid arteries (including the superficial temporal artery) may show vasculitic changes of alternating stenotic segments or occlusion. Superficial temporal artery angiography is less reliable than TAB for establishing a diagnosis.
  
  
  
  • Internal carotid arteries may be occluded, but they rarely have a characteristic vasculitic pattern.
  
  
  
  • Subclavian, axillary, and proximal brachial arterial involvement produces a characteristic angiographic pattern of vasculitis that consists of long, smooth, stenotic segments alternating with nonstenotic segments and tapered occlusions.
  
  
  
• On CT scan and MRI, the brain is typically unaffected by GCA, but in patients with a multiinfarct state due to cervicocephalic arteritis, CT scan and MRI demonstrate multiple areas of infarction.



• Because aortic or other vessel aneurysms are often asymptomatic, unless they rupture, it is prudent to screen all patients with GCA for large vessel disease with CT scanning.

Other Tests:

• Superficial TAB is the confirmatory test that should be obtained, almost without exception, in patients in whom GCA is suspected clinically.


• • TAB is important because of the long, often complicated, treatment course for GCA and since the other diagnostic possibilities that can mimic many of the nonspecific features of GCA (eg, headache, body aches, fatigue) are myriad.
  
  
  
  • In one large clinical series, TAB was confirmatory in only about one third of patients in whom GCA initially was suspected. Because of this high negative rate, and because GCA produces "skip lesions" with normal intervening segments, large (5 cm) and, if necessary, bilateral TAB specimens should be obtained.
  
  
  
  • Biopsy of the most symptomatic side should be performed first and, if frozen sections are negative, a contralateral specimen should also be obtained.
  
  
  
  • In cases in which a large TAB section is obtained from the most symptomatic side, and multiple thin sections obtained, diagnosis can be made in 86% of cases with a unilateral TAB.
  
  
  
  • TAB should be performed as soon as possible after clinical suspicion is raised, but it should not delay therapy when the index of suspicion is high because of the risk of ischemic ocular and cerebral complications.
  
  
  

Involvement of an affected artery is patchy with skip lesions and normal intervening segments. It is commonly accepted that because of the patchy involvement of the arteries, biopsies may be nondiagnostic in many patients, and nondiagnostic biopsy specimens do not exclude the diagnosis of temporal arteritis. Some authors even suggest that biopsy may not be necessary (Pountain, 1995).

Furthermore, corticosteroid therapy, which should be started without delay, rapidly reduces the chance of a positive biopsy result. One week of corticosteroid treatment may reduce the chance of obtaining a positive biopsy result to 10%, further suggesting that biopsy should be performed within the first few days of therapy.

Steroid therapy may change the vasculitic appearance within days, and a previous vasculitic focus may appear normal or show only intimal fibrosis.

TREATMENT

Section 6 of 12

Medical Care: Regardless of extent of neurologic involvement, oral corticosteroids remain the mainstay of treatment.

• Steroid-related adverse effects
  • The frequent and potentially serious consequences of chronic steroid therapy (eg, diabetes mellitus, vertebral compression fractures, steroid myopathy, steroid psychosis, immunosuppression-related infections) have led many to question the use of chronic steroid therapy.
  • Some studies have suggested that much lower doses and more rapid tapering schedules than currently used are sufficient. One such study advocated initiating treatment with 20 mg of prednisolone daily and tapering it to 10 mg daily within 3 months.
  • Many patients may respond to this regimen with symptomatic improvement of headache, PMR, and reduction of ESR; however, a substantial number of patients experience worsening of symptoms.
  • Headache and PMR, although the most common symptoms of GCA, are not reasons for using high doses of steroids.
  • Higher doses of steroids are required to prevent irreversible ischemic ophthalmologic and neurologic complications, which may be an early manifestation of GCA or, less commonly, develop during a flare.
  • Despite the apparent higher incidence of ischemic eye and brain complications in patients with carotid bruits, a bruit is not a sufficient indicator to base a decision between a high- or low-dose steroid regimen.



• Alternative immunosuppressant agents: Trials of other immunosuppressant agents, including azathioprine, methotrexate, dapsone, and cyclophosphamide, have been attempted for their steroid-sparing effects.


• • Steroid dosages have been lowered successfully but inconsistently in some patients on each of these drugs.
  
  
  
  • Toxicity can be a significant problem, particularly with dapsone and cyclophosphamide.
  
  
  
  • Azathioprine has no acute effect, and its steroid-sparing effects may not be evident for a year.

  • Limited experience suggests that cyclophosphamide may be the most consistently effective immunosuppressant. It may permit more rapid steroid tapering when instituted following a relapse.

  • Low-dose aspirin may be used as a prophylactic measure to prevent stroke because stroke may occur despite high-dose corticosteroid therapy and because almost all GCA patients have thrombocytosis.

MEDICATION

Section 7 of 12

Oral corticosteroids are the mainstay of treatment.

Drug Category: Glucocorticoids -- These agents have anti-inflammatory properties. They cause profound and varied metabolic effects. In addition, they modify the body's immune response to diverse stimuli and inhibit the synthesis of TNF-alpha, IL-2, IL-6, and IFN-gamma. In addition, glucocorticoids modulate serum and leukocyte-bound levels of cell adhesion molecules.

Drug Name	Prednisone (Deltasone, Meticorten, Orasone, Sterapred) -- Commonly used oral corticosteroid. Must be metabolized in liver to active metabolite prednisolone. By suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability, decreases inflammation. Typical patients require prednisone for 1-2 y with daily initial doses of 40-60 mg. In acute neurologic syndrome or rapidly worsening neurologic status—whether visual loss, mononeuritis multiplex, or acute encephalopathy—treatment may begin with IV pulses over several days. A patient with GCA who has a relapse may require only a modest dose increment to control flare in symptoms. Following initiation of treatment, ESR may be expected to drop within days and become normal in 1-2 wk. All neurologic deficits can improve, but irreversible end-organ infarction may preclude clinically significant gains in some patients. Neurovascular complications may occur during initial tapering of corticosteroid dosage (often around 1 mo after beginning treatment), underscoring need for ESR monitoring and importance of small steroid decrements. The doses described below are suggested for general consideration. Tailor dosing regimens to medical circumstances confronting patient.
Adult Dose	No neurologic syndrome or stable neurologic status: 60 mg PO qd initially Acute neurologic syndrome or rapidly worsening neurologic status: 120 mg PO qd; taper to approximately 40 mg PO qd by end of first mo; may reduce dose by 2.5-5 mg q2-3wk as tolerated
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity, viral infection, peptic ulcer disease, hepatic dysfunction, connective tissue infections, fungal or tubercular skin infections, GI disease
Interactions	Clearance may decrease when used with estrogens; may increase digitalis toxicity secondary to hypokalemia in patients taking digoxin; metabolism may be increased by phenobarbital, phenytoin, or rifampin—consider increasing maintenance dose; monitor for hypokalemia when taken with diuretics
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Long-term use may predispose patients to hyperglycemia, manifestation of latent diabetes mellitus, nonketotic hyperosmolar state, osteoporosis, avascular necrosis of hip, cataracts, steroid myopathy, cushingoid appearance, weight gain, suppression of pituitary-hypothalamic axis, peptic ulcer disease, suppression of growth (children), unmasking of latent infections (eg, tuberculosis, herpes zoster), increased predisposition to fungal and parasitic infections Water retention resulting from therapy may precipitate congestive heart failure (CHF), hypertension, hypokalemia; suppression of pituitary-hypothalamic axis may cause patients to require higher doses at times of stress (eg, systemic infections, surgery)

Drug Name	Methylprednisolone (Solu-Medrol, Depo-Medrol, Medrol, Adlone) -- Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability. Use in acute neurologic reactions.
Adult Dose	Acute neurologic syndrome or rapidly worsening neurologic status: 1000 mg IV qd; follow with prednisone PO dosing regimen when stable
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; viral, fungal, or tubercular skin infections
Interactions	May increase digitalis toxicity secondary to hypokalemia in patients taking digoxin; levels may be increased by estrogens; levels may be decreased by phenobarbital, phenytoin, and rifampin—may need to adjust dose; monitor patients for hypokalemia when taking with diuretics
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Possible adverse effects include hyperglycemia, edema, osteonecrosis, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, growth suppression, myopathy, and infections

Drug Category: Immunosuppressant agents -- Inhibit key factors of the immune system.

Drug Name	Azathioprine (Imuran) -- Inhibits mitosis and cellular metabolism by antagonizing purine metabolism and inhibiting synthesis of DNA, RNA, and proteins. Reserved for steroid failure or unacceptable adverse effects from prolonged steroid use; can be used for steroid-sparing effects to lower steroid dose.
Adult Dose	2-3 mg/kg/d PO divided ac; adjust dose prn Some experts advocate increasing dose until MCV >100 fL; do not increase dose if leukopenia develops
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	Toxicity increases with allopurinol; ACE inhibitors may induce severe leukopenia; may increase levels of methotrexate metabolites; may decrease effects of anticoagulants, neuromuscular blockers, and cyclosporine
Pregnancy	D - Unsafe in pregnancy
Precautions	Increases risk of neoplasia; caution in liver disease and renal impairment; rarely causes hepatotoxicity (2-3 fold elevation of hepatic enzymes common); hematologic toxic effects include dose-related leukopenia, thrombocytopenia, macrocytic anemia

FOLLOW-UP

Section 8 of 12

Further Outpatient Care:

• GCA is treated primarily in an outpatient setting. The median duration of symptoms before diagnosis is 1 month.


• • Ongoing monitoring of symptoms and ESR are mandatory.
  
  
  
  • ESR often normalizes within days of instituting steroid therapy.
  
  
  
  • With tapering steroid doses, ischemic complications may occur at any time but tend to occur a median of 1 month after beginning therapy.
  
  
  
  • The typical patient with GCA remains on steroid therapy for roughly 2 years.
  
  
  

Deterrence/Prevention:

• No effective prevention strategies are known.

Complications:

• Complications of GCA result from ischemic complications of vasculitis and are discussed in Clinical.



• Sequelae of steroid therapy include acute and chronic adverse effects and are discussed in Treatment and Medication.


• • Because of the high frequency of chronic adverse effects, TAB confirmation of diagnosis is highly desirable.
  
  
  
  • Patients with GCA suffer the following steroid-related complications during the course of their treatment: vertebral body compression fracture (26%), symptomatic steroid myopathy (11%), steroid psychosis (3%).
  
  
  

Prognosis:

• With prompt, adequate therapy, full recovery is the rule.


• • The reduced rate of neuro-ophthalmologic complications in recent years reflects improved recognition and treatment.
  
  
  
  • Blindness is now a rare complication.
  
  
  
• Untreated, the prognosis for the patient with GCA is extremely poor, with blindness or death resulting from myocardial infarction, stroke, or dissecting aortic aneurysm. Vision loss in the second eye may occur even after the initiation of treatment (possibly because those vessels have already been affected by arteritis) in 6-13% of patients.



• While morbidity and mortality have improved significantly with corticosteroid therapy, a higher mortality after treatment and definitely a higher morbidity caused by the corticosteroids have been reported.

Patient Education:

• Symptomatic relapse: Patients must be instructed concerning the seriousness of symptomatic relapses so that prompt medical attention is sought.



• Steroid use: Patients must know the importance of strictly adhering to their steroid dose schedule and, if necessary, must utilize ancillary interventions such as dietary restrictions that can reduce the incidence of steroid-related adverse effects.

MISCELLANEOUS

Section 9 of 12

Medical/Legal Pitfalls:

• GCA causes blindness, and this dread complication can be prevented with prompt diagnosis and institution of therapy. Failure to do so represents a medicolegal pitfall in addition to suboptimal medical practice.



• Steroid-related complications such as vertebral compression fracture can become a source of chronic pain and disability, but they are not prevented easily or reliably. To avoid misunderstandings, inform patients and their families about this and other potential complications that can occur even with proper therapy.

TEST QUESTIONS

Section 10 of 12

CME Question 1: What is the most common symptom of temporal/giant cell arteritis (GCA)?

A: Headache
B: Blindness
C: Low back pain
D: Neck pain
E: Stroke-related symptoms

The correct answer is A: Seventy-two percent of patients with GCA develop headache; in 33% of these people, headache is the first symptom. In contrast, only 10% develop amaurosis fugax, and 8% develop permanent visual loss.

CME Question 2: Which of the following statements is true concerning temporal artery biopsy (TAB) in a patient in whom temporal/giant cell arteritis (GCA) is suspected?

A: TAB is unnecessary if the patient has an elevated erythrocyte sedimentation rate (ESR).
B: TAB must be obtained before starting steroid therapy, even in patients in whom GCA is strongly suggested.
C: TAB should be obtained as soon as possible to confirm a clinical diagnosis.
D: A small unilateral TAB sample ( <1 cm) from the most symptomatic side is sufficient.
E: TAB is a dangerous procedure that is associated with a high risk of scalp infarction.

The correct answer is C: Obtain TAB in all patients in whom GCA is suspected as soon as possible to confirm the clinical diagnosis. The frequency of misdiagnosis is high, and the chronic nature of therapy is fraught with complications. However, TAB should not delay therapy in patients in whom GCA is strongly suggested.

Pearl Question 1 (T/F): Alpha-2 globulin and other acute phase reactants are the most important laboratory tests in an elderly patient with a new type of headache.

The correct answer is False: Erythrocyte sedimentation rate (ESR) should be obtained as soon as possible in such patients, with results available that same day.

Pearl Question 2 (T/F): Two diseases that should always be considered in an elderly patient presenting with amaurosis fugax are temporal/giant cell arteritis (GCA) and transient ischemic attack (TIA).

The correct answer is True: An atherosclerotic TIA and GCA should always be considered in elderly patients with amaurosis fugax.

Pearl Question 3 (T/F): Temporal artery biopsy (TAB) may be safely delayed 1-2 weeks after starting steroid therapy without confounding histologic diagnosis.

The correct answer is False: Although the amount of time that TAB may be delayed safely is not precisely known, 3 days is probably safe. A Friday afternoon patient can be treated over the weekend and biopsied on Monday without fear of masking the diagnosis.

Pearl Question 4 (T/F): A patient on long-term steroid therapy for temporal/giant cell arteritis (GCA) who complains of nonspecific fatigue and pain after a steroid dose reduction should have a complete blood cell (CBC) count checked.

The correct answer is False: A patient who complains of fatigue and pain after a steroid dose reduction needs to have the erythrocyte sedimentation rate (ESR) checked promptly. If elevated, the steroid dose should be boosted to at least the last effective dose. Ensure that the patient becomes asymptomatic again within days and recheck the ESR within 2 weeks.

PICTURES

Section 11 of 12

Caption: Picture 1. Hematoxylin- and eosin-stained superficial temporal artery biopsy specimen, cross section. The hallmark histologic features of GCA shown here include intimal thickening with luminal stenosis, mononuclear inflammatory cell infiltrate with media invasion and necrosis, and giant cell formation in the media.
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Caption: Picture 2. Lumbar angiogram showing stenosis and occlusion of femoral artery branches due to vasculitis in the same patient whose temporal artery biopsy specimen in shown in Image 1.
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Caption: Picture 3. Hematoxylin- and eosin-stained femoral artery branch, cross section, taken from a lower limb amputation specimen from the same patient shown in pictures 1 and 2. Mononuclear cell invasion and necrosis in the media of this large artery can be observed. Extensive lower limb vasculitis from GCA resulted in ischemic necrosis of the lower limb, necessitating amputation.
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BIBLIOGRAPHY

Section 12 of 12

• Bley TA, Wieben O, Leupold J: Images in cardiovascular medicine. Magnetic resonance imaging findings in temporal arteritis. Circulation 2005 Apr 26; 111(16): e260[Medline].
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• Caselli RJ, Hunder GG, Whisnant JP: Neurologic disease in biopsy-proven giant cell (temporal) arteritis. Neurology 1988 Mar; 38(3): 352-9[Medline].
• Caselli RJ, Hunder GG: Neurologic aspects of giant cell (temporal) arteritis. Rheum Dis Clin North Am 1993 Nov; 19(4): 941-53[Medline].
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• Fox GN: Giant cell arteritis. CMAJ 2005 Dec 6; 173(12): 1490; author reply 1490[Medline].
• Gonzalez-Gay MA, Lopez-Diaz MJ, Barros S: Giant cell arteritis: laboratory tests at the time of diagnosis in a series of 240 patients. Medicine (Baltimore) 2005 Sep; 84(5): 277-90[Medline].
• Hollenhorst RW, Brown JR, Wagener HP, Shick RM: Neurologic aspects of temporal arteritis. Neurology 1960 May; 10: 490-8[Medline].
• Huston KA, Hunder GG, Lie JT, et al: Temporal arteritis: a 25-year epidemiologic, clinical, and pathologic study. Ann Intern Med 1978 Feb; 88(2): 162-7[Medline].
• Klein RG, Hunder GG, Stanson AW, Sheps SG: Large artery involvement in giant cell (temporal) arteritis. Ann Intern Med 1975 Dec; 83(6): 806-12[Medline].
• Meyers AD, Said S: Temporal artery biopsy: concise guidelines for otolaryngologists. Laryngoscope 2004 Nov; 114(11): 2056-9[Medline].
• Ostberg G: Morphological changes in the large arteries in polymyalgia arteritica. Acta Med Scand Suppl 1972; 533: 135-59[Medline].
• Polak P, Pokorny V, Stvrtina S, et al: Temporal arteritis presenting with paresis of the oculomotor nerve, and polymyalgia rheumatica, despite a low erythrocyte sedimentation rate. J Clin Rheumatol 2005 Aug; 11(4): 242-4[Medline].
• Pountain G, Hazleman B: ABC of rheumatology. Polymyalgia rheumatica and giant cell arteritis. BMJ 1995 Apr 22; 310(6986): 1057-9[Medline].
• Wilkinson IM, Russell RW: Arteries of the head and neck in giant cell arteritis. A pathological study to show the pattern of arterial involvement. Arch Neurol 1972 Nov; 27(5): 378-91[Medline].

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