eMedicine Specialties > Neurology > Inflammatory and Demyelinating Diseases

Temporal/Giant Cell Arteritis: Differential Diagnoses & Workup

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

Differential Diagnoses

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

Laboratory Studies

Temporal arteritis is a clinical diagnosis without a criterion standard serological or histological test. According to Ortiz, the lack of a gold standard bedevils the establishment of an accurate diagnosis.¹¹

An elevated erythrocyte sedimentation rate (ESR) is generally well accepted in the diagnosis of giant cell arteritis. Because normal values of ESR are known to increase with age and are higher in women, the ESR should be adequately adjusted.¹²

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. Salvarani et al reported that before treatment, ESR may be normal in 7-20% of patients with giant cell arteritis.¹³ Therefore, a normal ESR does not rule out GCA, and the level of elevation of ESR does not correlate with the severity of the disease.

C-reactive protein (CRP), fibrinogen, complete blood count, and platelets should always be obtained in addition to the ESR.

• The CRP is of hepatic origin, usually rises before ESR in most disease states, and is often elevated in giant cell arteritis. It has higher sensitivity and specificity than ESR (98.6% and 75.7%, respectively) and has relative insensitivity to age, gender, and other hematologic parameters.¹⁴
• Since there can be nonconcordance between those 2 tests (either an elevated ESR with normal CRP or a normal ESR with an elevated CRP), the use of both tests provides a slightly greater sensitivity for the diagnosis of giant cell arteritis (GCA) (sensitivity of 99%) than the use of either test alone.¹⁵
• 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).
• Thrombocytosis (platelets >375,000) is more helpful for ruling in temporal arteritis than an elevated ESR.¹⁶ Conversely, normal platelets are more accurate for ruling out temporal arteritis than a normal ESR.¹⁶
• 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

• The diagnostic power of high-resolution MRI and color-coded Doppler study (CCDS) in detecting giant cell arteritis is comparable. Either of these noninvasive techniques may have value in the evaluation of patients with suspected GCA, and decisions regarding which technique to use may depend on the clinical setting.¹⁷ The ultrasonographic axial plan can show a concentric halo and T2-weigted MRI, a slightly hyperintense vessel wall due to inflammatory mural thickening of arteries.¹⁸  
• On CT and MRI, the brain is typically unaffected by GCA, but in patients with a multi-infarct state due to cervicocephalic arteritis, CT and MRI demonstrate multiple areas of infarction.
  • Because aortic or other vessel aneurysms are often asymptomatic, unless they rupture, screening all patients with GCA for large vessel disease with CT scanning is prudent.
  • In GCA to evaluate aortic involvement. MRI may reveal vessel wall thickening and edema on T2-weighted images and increased mural enhancement on postcontrast T1-weighted images, indicative of regional inflammation. PET scanning with 18-fluorodeoxyglucose uptake has also been used to evaluate the vasculitic process within large vessels such as the thoracic aorta.¹⁹ The use of gallium-67 has been explored with a limited number of reports. The role of MRI and/or PET in establishing a diagnosis or tracking disease activity is under ongoing investigation.
• Aortic arch and cerebral angiography

• In pathologically proven cases, such as GACNS, the sensitivity of cerebral angiography findings is as low as 10–20%. Cerebral angiogram is not the procedure of choice in ascertaining the diagnosis of GACNS. However, involvement of multiple vessels in multiple vascular beds (high-probability angiogram) raises the possibility of RCVS (reversible cerebral vasoconstriction). Documentation of reversibility of the angiographic abnormalities, along the course of the disease, will eventually secure the diagnosis of RCVS.²⁰
• GCA causes granulomatous inflammation in the wall of medium-size and large arteries and preferentially affects extracranial branches of the carotid artery.²¹ Occlusion of the posterior ciliary arteries occur more commonly. Involvement of intracranial arteries is rare, and cerebral infarctions are the hemodynamic consequences of occlusion of cervical arteries. MR angiogram and cerebral angiogram reveal occlusion of the affected arteries. Vertebral arteries are more likely affected than internal carotid arteries, especially in the extradural portion, where there is more elastic tissue.²²
  • 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.
• While MR angiogram can give useful information in GCA, cerebral angiogram is the criterion standard to obtain optimum information, but at the cost of potential complications.

Other Tests

Superficial temporal artery biopsy (TAB) is the confirmatory test that should be obtained, almost without exception, in patients in whom GCA is suspected clinically.

• TAB is the criterion standard for making a diagnosis of temporal arteritis and a positive biopsy is diagnostic (100% specificity). The histopathological changes often correlate with clinical features of severity, but the sensitivity of TAB is relatively low (15–40%). In most patients undergoing TAB, little evidence showed that clinical decision making with respect to corticosteroid therapy was influenced by the TAB result.²³
• 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.
• The clinical significance of giant cells seen on TAB in temporal arteritis is unknown. Armstrong et al found that the presence of giant cells is not a significant factor in determining treatment or clinical progression of temporal arteritis. Their results showed the giant cell group to have 3 times the occurrence of blindness and polymyalgia rheumatica compared with the group with no giant cells, suggesting an association with giant cells and more aggressive disease.²⁴
• Alberts et al report that in clinical practice, bilateral temporal artery duplex served the same function as biopsy, but without subjecting patients to the potential morbidity of a surgical procedure. TAB could be reserved only for situations where the duplex result is inconsistent with the clinical picture, and the biopsy result, if different from the duplex result, might influence the treatment decision.²⁵

Histologic Findings

The histopathology of the diagnostic arterial lesion includes intimal proliferation with resulting luminal stenosis, disruption of the internal elastic lamina by a mononuclear cell infiltrate, invasion and necrosis of the media progressing to panarteritic involvement by mononuclear cells, giant cell formation with granulomata within the mononuclear cell infiltrate and, less consistently, intravascular thrombosis.

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.²⁶

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.

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