eMedicine Specialties > Neurology > Inflammatory and Demyelinating Diseases

Temporal/Giant Cell Arteritis

Author: Tarakad S Ramachandran, MBBS, FRCP(C), FACP, Professor of Neurology, Clinical Professor of Medicine, Clinical Professor of Family Medicine, Clinical Professor of Neurosurgery, State University of New York Upstate Medical University; Chair, Department of Neurology, Crouse Irving Memorial Hospital
Coauthor(s): Arun Ramachandran, State University of New York Upstate Medical University
Contributor Information and Disclosures

Updated: Jun 22, 2009

Introduction

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.

Intimal macrophages produce platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) leading to intimal proliferation. Medial macrophages generate metalloproteinases leading to the destruction of vascular elements, including the internal elastic lamina. Adventitial macrophages produce interleukin-6 (IL-6), augmenting the inflammatory response. This results in inflammation with local vascular damage and intimal hyperplasia leading to stenosis and occlusion.²

The expression of MxA protein in arteries from patients with polymyalgia rheumatica and temporal arteritis shows that noninflamed and inflamed vessel walls are influenced by IFN-I. Further studies are required to elucidate whether IFN-I plays a role in the initiation of polymyalgia rheumatica and/or temporal arteritis.³

Frequency

United States

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.

International

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

History

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.
• The range of neuro-ophthalmologic signs and symptoms in temporal arteritis is broad and includes diverse manifestations of ischemic optic neuropathy, retinal infarction, ophthalmoparesis, pupillary autonomic and anterior ocular segment dysfunction, cortical blindness and associated posterior chiasmal field defects, and complex visual hallucinations.⁵ Oculomotor palsy is an uncommon manifestation of temporal arteritis.
• 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.
• Confusion and encephalopathy: Encephalopathy is a rare complication of GCA; however, the differential diagnosis is extensive.
• Confusion may be due to steroids, either primarily (steroid psychosis) or secondarily from a steroid-induced metabolic derangement, or to systemic or CNS infections (including infections that occur in immunocompromised hosts).
• Unrelated causes include degenerative dementia, chronic subdural hematoma, sedating medications, and other diseases prevalent in the elderly.
• Acute encephalopathy may be caused by GCA itself as a result of cerebral infarction. Presumably, cognitive changes reflect thalamic, mesial temporal, and mesencephalic involvement in most cases. CT scan or, preferably, MRI should be done early in these patients.
• Acute encephalopathy is a poor prognostic sign. Many patients with this complication progress to coma and die.
• With giant cell arteritis, Cerebrovascular accidents can occur during the course of the giant cell arteritis (3-4%), involve both anterior and posterior circulations (either alone or in combination), and may lead to multi-infarct dementia. Solans-Laqué et al report 7 patients with biopsy-proven giant cell arteritis who presented with stroke or multi-infarct dementia.⁶
• When recognized and treated promptly with increased dosages of steroids, patients can stabilize and, over time, experience some recovery.
• Giant cell arteritis may present as an isolated form or a part of systemic disease. Onuma et al described a rare case of giant cell arteritis involving the female genital tract.⁷
• Adams et al described a very unusual presentation of temporal arteritis and an extremely rare manifestation of scalp necrosis.⁸
• Goicochea et al present 3 cases of tongue necrosis due to giant cell granulomatous arteritis. Ischemic necrosis of the tongue is unusual but there appears to be an association between its occurrence and high-dose steroid tapering.⁹

Physical

Physical signs parallel symptoms and are dependent on the organ systems that are damaged by vasculitic ischemia.

• Superficial temporal artery inflammation: Signs are present in 49% of patients, including erythema, pain on palpation, nodularity, thickening, or reduced pulsation on the affected side. Although rare, ischemic necrosis of the scalp and tongue can occur.
• AION is caused by vasculitis of the posterior ciliary artery.
  • Less commonly, optic neuropathy is entirely retrobulbar. On rare occasions, blindness results from central retinal artery occlusion.
  • Ophthalmoscopy in acute AION may show sludging of blood in retinal arterioles, which can be orthostatically sensitive. Vision loss precedes the funduscopic changes of optic nerve infarction by roughly 36 hours. Acutely, the disc is pale with blurred margins.
  • As AION evolves, the absolute amount of disc elevation tends to be modest ( <3 diopters in most cases), with infrequent areas of disc hemorrhage. Edema resolves within 10 days or so; within 2-4 weeks, it is replaced by optic atrophy.
  • Residual visual field defects are usually altitudinal.
  • With retrobulbar involvement, optic pallor and atrophy gradually develop without antecedent papillitis.
  • Central retinal artery occlusion causes pallor and edema of the entire retina and optic disc together with a macular cherry-red spot.
  • Visual loss on presentation was associated with disc swelling and a history of hypertension. Risk factors for progressive visual loss included older age, elevated C-reactive protein, and disc swelling.¹⁰ The r ole of individual risk anticipating treatment regimens and strategies involving the visual prognosis in temporal arteritis remains uncertain.
• Oculomotor impairment: Diplopia occurs in roughly 2-14% of patients with GCA.
  • The oculomotor apparatus can be involved at any level, including the extraocular muscles (EOM), nerves, and brain stem. However, the most common site is the EOM.
  • A characteristic feature of EOM involvement is daily fluctuation of the ocular motility disorder.
  • Horner syndrome is uncommon, judging from a review of several large series; however, ptosis and miosis may occur together, separately, or in conjunction with other oculomotor disturbances.
• Peripheral nerve and muscle signs: The vasculitis of GCA can affect large peripheral arteries and their branches. When it involves the nutrient arteries of peripheral nerves, mononeuropathies or mononeuritis multiplex may result.
  • The incidence of acute ischemic mononeuropathies in patients with GCA is difficult to estimate but is probably around 2%.
  • Essentially all named peripheral nerves can be involved in ischemic mononeuropathies.
  • Among spinal nerve roots, the fifth cervical has been reported to be susceptible to GCA by several authors.
  • Patients with GCA can also develop mononeuropathies (which occur at common compression sites) unrelated to vasculitis. For example, approximately 5% have carpal tunnel syndrome. Some of these cases may be related to median nerve compression by synovitis related to PMR.
  • Elderly patients frequently have mildly abnormal nerve conduction studies and EMG suggesting a mild peripheral neuropathy, regardless of whether they have GCA. Once again, the relationship of such neuropathies to the systemic inflammatory state in some patients is uncertain. In other patients, antecedent ischemic mononeuropathies may occur and eventually resemble a "diffuse," severe, peripheral neuropathy.
  • GCA does not cause an inflammatory myopathy, although rare examples of localized muscular inflammation are known. PMR may lead falsely to the clinical suspicion of a myopathy. Steroid therapy commonly causes a mild, noninflammatory myopathy ("steroid myopathy").
• Myelopathy: A few cases of patients developing an acute cervical myelopathy within the context of active GCA have been reported. The vasculitis presumably extends to the anterior spinal artery from the vertebral arteries.
• Although rare, myelopathic involvement represents a serious complication and may presage a fatal outcome.
• Prompt treatment with corticosteroids may result in neurologic stabilization and improvement.
• Arterial bruits: Bruits in GCA reflect the topographic distribution of GCA.
• Carotid bruits occur in 10-20% of patients with GCA and are frequently bilateral.
• Among patients with bilateral carotid bruits, 60% also have upper limb bruits or claudication.
• Approximately 40% of patients with GCA who have carotid bruits experience an ischemic eye or brain complication (amaurosis fugax, TIA, permanent visual loss, or stroke), although permanent deficits (permanent visual loss and stroke) do not occur more often than in patients with GCA who do not have carotid bruits.
• Altered mental status: Recurrent episodes of acute encephalopathy with progressive cognitive impairment can lead to a chronic dementia in patients with GCA.
• This may occur as steroid dosage is tapered.
• Because these patients are elderly, they may be assumed incorrectly to have Alzheimer disease. Instead, they have a multiinfarct dementia due to cervicocephalic arterial involvement by GCA.
• CT scan and MRI demonstrate multiple areas of infarction, although EEG findings are inconsistent.
• These patients are typically on steroids, and their ESR may or may not be increased during these disease exacerbations. Higher dosages of steroids will not result in immediate cognitive recovery; however, longitudinal follow-up should show no further deterioration and may show modest improvement.
• Currently, encephalopathy or dementia is thought to be a rare occurrence, although earlier literature suggested that it was common.

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."

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