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

Temporal arteritis (TA), also known as cranial arteritis or giant cell arteritis, was first clinically recognized in 1890 when Hutchinson described an 80-year-old man whose painful inflamed temporal arteries precluded his wearing a hat. In 1932, Horton et al correlated the histopathologic features with the clinical features and applied the name arteritis temporalis. Other names include arteritis cranialis, Horton disease, granulomatous arteritis, and arteritis of the aged.

Since Horton's first description of TA in the United States, this form of systemic vasculitis has become more widely recognized, as has the potential for serious sequelae, such as blindness and death. In 1960, Paulley and Hughes described the broad clinical spectrum and variable manifestations of the disease. TA is the most common form of systemic vasculitis in adults. TA primarily affects medium-sized arteries of the head and the neck. Most signs and symptoms reflect this distribution and include visual disturbances, headache, jaw claudication, neck pain, and scalp tenderness.

Although varied histopathologic findings have been noted over the years, temporal artery biopsy (TABx) remains the criterion standard for diagnosis of this granulomatous vasculitis. Until discovery of the anti-inflammatory properties of corticosteroids, patients with TA received only supportive symptomatic treatment. Since 1950, steroids have revolutionized the treatment of the disease. Treatment with systemic corticosteroids produces a predictable clinical response and may prevent permanent visual loss, the most feared ischemic complication of the vasculitis.

Pathophysiology

The exact etiology of TA remains unknown, although it is T-cell dependent and antigen driven. TA is classified as a systemic vasculitis, although it primarily affects the extracranial large and medium muscular arteries of the head and the neck. Both renal arteritis and aortic arteritis are rare. The vasculitis primarily damages the media and destroys the internal elastic layer. A panarteritis develops, and intimal proliferation causes luminal occlusion. The granulomatous infiltrate is largely mononuclear and consists primarily of polyclonal CD4⁺ T cells and macrophages. Of these lesions, 50% contain giant cells clustered near the disrupted internal elastic lamina.

Studies by O'Brien and Regan¹ have focused on the pathophysiologic role of actinic damage in persons with TA. Chronic solar damage to elastic fibers may initiate an elastase-mediated degradation of the internal elastic lamina in temporal arteries, which may evoke an autoimmune response, resulting in granulomatous vasculitis.

The model of pathogenesis developed by Weyand and Goronzy² proposes that an as yet undetermined antigen is first encountered in the adventitia. T cells localized to this layer are activated and produce interferon gamma, which stimulates macrophage differentiation and migration. Giant cells are formed and secrete growth factors and metalloproteinases that ultimately degrade the internal elastic lamina and produce occlusive luminal hyperplasia. Potential antigens include elastin, viral or bacterial epitopes, and other extracellular matrix proteins.

Finally, numerous studies now suggest that TA consists of various clinical subsets rather than one uniform disease. Variable expression of different cytokine profiles likely determines the clinical manifestations.

Frequency

United States

TA is one of the most prevalent of the systemic vasculitis syndromes, with an estimated prevalence of 200 cases per 100,000 people older than 50 years and an incidence of 20-30 new cases per 100,000 persons older than 50 years. Although the condition had been considered less common among Hispanic persons, recent evidence has challenged this notion.

International

The incidence, age, and sex distribution in northern Europe is similar to that in the United States, likely because of immigration patterns. Latitude is an important risk factor, with a prevalence in Sweden twice that of Spain or Italy.

Mortality/Morbidity

Mortality from TA is extremely uncommon, especially with timely diagnosis and treatment. In 1972, Wilkinson and Russell³ reviewed 12 autopsy cases and reported a high prevalence of severe involvement of the superficial temporal, vertebral, ophthalmic, and posterior ciliary arteries and less frequent severe disease of the internal carotid, external carotid, and central retinal arteries. Intracranial arteries were never involved. These patients, who died during the active phase of TA, demonstrated a high prevalence of monocular blindness, occipital blindness, and brainstem strokes. Insignificant vasculitis was rarely identified in aortic, suprarenal, and coronary arteries and did not contribute to death. A close correlation existed between the amount of elastic tissue in susceptible arteries and the severity of the vasculitis. Subsequent morbidity and mortality from TA reflect this anatomical distribution of vessels.

An insidious onset of the disease usually progresses to include fatigue, malaise, fever, weight loss, polymyalgia rheumatica, and flulike symptoms. Headache, scalp tenderness, focal arterial tenderness, jaw claudication, and visual loss may develop, and these findings indicate vascular involvement.

Race

TA primarily affects whites, specifically those of northern European descent. Scandinavians have the highest prevalence, and TA is rare in African Americans. The gene for HLA-DRB1-04 has been identified as a risk factor for TA. Although the condition had been considered less common among Hispanic persons, recent evidence has challenged this notion.

Sex

Females are affected in 80% of cases. Smoking increases the TA risk 6-fold in women, while diabetes reduces the risk by half.

Age

TA is extremely uncommon in younger age groups. The average age at onset is in the sixth to seventh decade of life, with a mean age at onset of 69 years. It affects the same older population as the commonly associated polymyalgia rheumatica.

CLINICAL

Section 3 of 10  

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

History

• TA often manifests in an insidious manner with vague constitutional symptoms such as malaise, weight loss, fever, and fatigue.
• The classic manifestations are fever, anemia, headache, and an elevated erythrocyte sedimentation rate (ESR).
• Polymyalgia rheumatica may develop either before or after the arteritis.
• Disease onset may also be abrupt. The diagnosis should be strongly suspected in whites older than 50 years of northern European descent, especially women, who report temporal headache, tender scalp, jaw claudication, and/or visual changes.
• Visual disturbances include diplopia, blurred vision, amaurosis fugax, and blindness in either one eye or both eyes.
• Symptoms signaling peripheral neuropathy or aortic involvement are rare.
• A history of chronic sun exposure may be relevant.
• In 2003, Amor-Dorado et al⁴ reported a previously unrecognized high incidence of audiovestibular disturbances such as vestibular dysfunction and/or hearing impairment in their TA patients. Another rare complication involved lower extremity involvement with rapidly progressive claudication signaling compromised vascular flow. Surgery was often required.

Physical

• The examination should include an assessment of vital signs and blood pressure in both arms to rule out aortic arch involvement.
• • The scalp may be focally or generally tender. Temporal arteries may be tender, inflamed, dilated, thickened, or cordlike.
  • The arteries may be pulsatile, particularly early in the disease course.
  • Bruits may signal partial occlusion.
  • In severe cases, scalp skin or oral mucosal ulceration develops.
• Neurologic examination may reveal a neuropathy.
• Ophthalmologic examination reveals ischemic optic neuropathy in early stages of the disease and optic atrophy later in the disease course. Immediate referral is critical to ensure prompt diagnosis of reversible retinal ischemia from ophthalmic or posterior ciliary artery involvement.
• Audiovestibular examination may be considered.

Causes

The exact etiology of TA remains unknown. See Pathophysiology.

DIFFERENTIALS

Section 4 of 10  

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

Other Problems to be Considered

Polymyalgia rheumatica is a closely correlated process with similar systemic features but without the focal symptoms and signs caused by temporal or ophthalmic artery disease.

Wegener granulomatosis and polyarteritis nodosa may occasionally affect the temporal artery and cause clinical findings similar to TA. Other vasculitides, such as lupus erythematosus, rheumatoid arthritis, and Takayasu arteritis, may have similar signs and symptoms.

Systemic amyloidosis rarely affects temporal arteries and may cause jaw or arm claudication.

WORKUP

Section 5 of 10  

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

Lab Studies

• At the time of diagnosis, the ESR typically ranges from 60-100 mm/h. Rarely, it may be normal. A highly elevated ESR is more characteristic for TA than for other vasculitides and rheumatologic diseases. The ESR may be followed serially to help monitor response to therapy and to titrate steroid dosing.
• Other acute-phase reactant levels are elevated and reflect the underlying inflammatory process. Hepatic enzyme levels, particularly alkaline phosphatase, are elevated in 20-30% of cases.

Imaging Studies

• Serious suspicion for aortic or carotid artery disease may rarely warrant noninvasive studies (eg, CT scanning) or invasive angiography. Angiography is less sensitive, less specific, and more invasive than biopsy. See Temporal Arteritis for additional discussion.
• Color-duplex ultrasonography has recently been suggested as an alternative to TABx for diagnosing TA. Schmidt et al⁵ observed a halo effect surrounding actively involved temporal arteries that was absent in healthy controls. They suggested that TABx might be replaced by ultrasonography when classic symptoms are present. Salvarani et al⁶ confirmed the high specificity of the halo effect, which results from adventitial edema, but reported a sensitivity of only 40%. In particular, early inflammatory changes diagnosed based on TABx findings do not produce the characteristic halo effect. Therefore, ultrasonography should not replace TABx for diagnosing TA in clinical practice.
• Positron emission tomography, MRI, and CT scanning also lack the sensitivity of TABx in the diagnosis of TA. These noninvasive techniques, however, may play a future role in the monitoring and long-term management of TA.

Procedures

• TABx is the criterion standard for diagnosing TA. This procedure may be performed by ophthalmologists, general surgeons, head and neck surgeons, plastic or vascular surgeons, or dermatologic surgeons. With a positive predictive value of greater than 90%, TABx stands out as the definitive test for TA. It has helped to determine appropriate treatment in 94% of suspected cases of TA.
• • The frontal branch of the superficial temporal artery is preoperatively identified by using Doppler ultrasonography. With the patient under local anesthesia, a shallow incision just into the underlying fat is made directly over the artery. The artery is bluntly dissected free from within the superficial temporal fascia. A segment of artery is ligated proximally and distally, removed, and sent for histopathologic review. Hemostasis is obtained with electrocoagulation, and a layered closure is performed.
  • To improve the yield and to avoid complications, proper site selection is important. Focal symptoms or signs, such as erythema, tenderness, inflammation, bruit, or thickening, help guide biopsy site selection and may improve the yield of the biopsy. However, localizing findings are often absent or misleading, and, frequently, a poor correlation is noted between the physical examination findings and the biopsy results. In the absence of localizing findings, the danger zone of the temporal branch of the facial nerve is avoided. Knowledge of the anatomy and careful dissection above and within the superficial temporal fascia help prevent nerve damage during the procedure.
  • Most authors recommend excision of 2-5 cm of artery to provide accurate diagnosis of TA because studies have noted higher positive rates with longer specimens. TA may have a patchy distribution among extracranial arteries and within small segments of these arteries. Longer biopsy specimens provide more tissue in which to demonstrate short, noncontiguous foci of giant cell arteritis, the so-called skip areas. These skip areas are not commonly identified, but patches of arteritis as short as 0.29 mm have been clearly demonstrated on serial sectioning. Serial sectioning, proper tissue handling, and adequate specimen length are critical to ensure maximum yield from the biopsy.
  • Because of the segmental nature of TA, a subsequent TABx from the opposite side of a negative biopsy sample occasionally shows evidence of disease. Therefore, some authors recommend initial bilateral biopsy, while others repeat the procedure only in the setting of further clinical suspicion. Four retrospective reviews have reported that only 1-5% of true positives would be confirmed with a bilateral biopsy in the setting a first negative biopsy result. Many would still recommend bilateral biopsy given the consequences of a missed diagnosis.
  • TABx is a safe procedure; however, risks include temporary or permanent damage to the temporal branch of the facial nerve, infection, bleeding, hematoma, and dehiscence. Isolated case reports of ischemic stroke or skin ulceration from disruption of collateral flow from an asymptomatic carotid occlusion can be found.

Histologic Findings

Involved vessels show a panarteritis that may be patchy and segmental in its distribution. Degeneration of the internal elastic lamina invokes an inflammatory response. The composition of the inflammatory infiltrate changes in a time-dependent manner. Some neutrophils may be noted in early lesions; later, mononuclear cells and giant cells predominate. Macrophages digest the elastic material and evolve into multinucleated giant cells. Lymphocytes infiltrate the vessel at all levels. Despite the inflammation, the arterial wall does not become necrotic. Intimal deposition of fibrinous material causes luminal narrowing and eventual obliteration. Although giant cells are characteristic, they may rarely be absent. Significant regional solar elastosis may prove to be an important histologic finding.

TREATMENT

Section 6 of 10  

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

Medical Care

Medical care is supportive and symptom specific.

Consultations

• Consultation with an ophthalmologist is critical for all patients suspected of having TA in order to prevent any permanent visual deficit.
• Rheumatologists often treat these patients, although referral is not essential.

MEDICATION

Section 7 of 10  

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

Since 1950, the use of systemic corticosteroids has revolutionized the treatment of TA, as well as a legion of other inflammatory diseases. Supportive care was the primary treatment before steroid therapy. Now, patients with TA respond quickly and often completely to systemic steroids.

Despite corticosteroids serving as the mainstay of therapy, no consensus exists regarding a standard initial dose, maintenance dosing, or alternate-day schedules. Authorities do agree that the initiation of steroid therapy should not be delayed because TABx can still confirm the diagnosis and serious sequelae can be avoided.

Steroid-sparing agents, including azathioprine, cyclophosphamide, dapsone, and cyclosporine, have been tested. Generally, none is routinely recommended. Disparate results were obtained in 2 recent studies of methotrexate. Anti–tumor necrosis factor-alpha blockers have shown limited promising results and remain a potential therapeutic agent for the future.

Drug Category: Corticosteroids

Anti-inflammatory action is effective in the treatment of granulomatous vasculitis.

FOLLOW-UP

Section 8 of 10  

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

Deterrence/Prevention

• Sun avoidance and protection of the head and the face from photodamage may eventually prove to be important preventive measures.

Complications

• Ophthalmic complications are common.
• • Clinical manifestations include visual disturbances, amaurosis fugax, diplopia, and blindness.
  • Visual loss may be temporary or permanent and partial or complete in either one eye or both eyes.
  • Blindness usually occurs abruptly and painlessly.
  • Ischemic optic neuritis with eventual optic atrophy is the most common cause of visual loss and occurs in 15% of patients.

Prognosis

• Overall, with prompt diagnosis and treatment, TA is a well-controlled disease. Symptoms from TA improve within days of treatment. Corticosteroids can usually be tapered within the first 4-6 weeks and eventually discontinued. The prognosis for patients is excellent.
• •  Some patients' conditions respond well, but damage prior to treatment is irreversible.
  • Rarely, a response to steroid therapy does not occur or doses cannot be tapered. Cytotoxic or immunosuppressive drugs have been recommended, but their long-term benefit has not been clearly shown in controlled comparative trials.

MISCELLANEOUS

Section 9 of 10  

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

Medical/Legal Pitfalls

• Improper technique during TABx can rarely result in facial nerve damage. Understanding the temporal anatomic danger zone and planning the procedure accordingly, with execution within the superficial temporal fascia, can prevent nerve injury.

REFERENCES

Section 10 of 10

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

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Article Last Updated: Feb 27, 2007