Steven E. Katz, MD
James A. McHale, MD
DESCRIPTION 
Giant cell arteritis (GCA) is a systemic vasculitis characterized by focal granulomatous inflammation of medium and small arteries. Involvement of elastic-containing cranial vessels predominates, including the superficial temporal, ophthalmic, posterior ciliary, occipital, and vertebral arteries. The aorta, carotid, and coronary arteries are less commonly involved. A high degree of suspicion should be maintained for GCA in patients age >60 years because of the risk of acute and severe visual loss. Ocular symptoms complicate approximately 50% of cases.
EPIDEMIOLOGY
Incidence
Average annual incidence was 17.8/100,000 population older than 50 years of age in Olmstead County, Minnesota (1)[A].
RISK FACTORS
- Age: Generally individuals >60 years; incidence increases with age; majority will be in their eighth decade
- Sex: Female to male ratio of 2:1
- Race: Rare in African Americans and Asians
Genetics
A genetic predisposition may exist, as evidenced by an increased prevalence of HLA-DR1, 3, 4, and 5 antigens, along with familial and geographic clustering of cases.
GENERAL PREVENTION
No reports available.
PATHOPHYSIOLOGY
- The inflammatory response is initiated by activated T-lymphocytes that enter the vessel wall via the vaso vasorum.
- Macrophages in the adventitia produce matrix metalloproteinases which cause fragmentation of the internal elastic lamina and tissue destruction.
- The presence of multinucleated giant cells correlates with intimal hyperplasia and occlusion of the vessel lumen by smooth muscle cells (2)[A].
ETIOLOGY
The etiology of GCA is unknown, but an immune-mediated process (cellular more so than humoral) is most widely suspected.
COMMONLY ASSOCIATED CONDITIONS
[Outline]
HISTORY
GCA is a syndrome that may present with any combination of the following:
- Headache (initial manifestation in 50–90% of cases)
- Pain often gradual onset, diffuse, and severe, may be unilateral, usually prominent if not intractable, may be perceived as superficial and may be unresponsive to analgesics
- Temporal scalp tenderness
- Abrupt, progressive monocular visual loss with involvement of the fellow eye in 25–50% of cases, usually within 10 days
- Visual loss may be insidious or preceded by episodes of transient monocular loss of vision
- Partial to complete blindness, largely irreversible
- Less common ophthalmic complaints may include amaurosis fugax, diplopia, periorbital swelling and eye pain
- Polymyalgia rheumatica (>50 years of age, proximal arthralgias and myalgias, morning stiffness, increased erythrocyte sedimentation rate >40)
- Jaw claudication
- Facial pain
- Fatigue, general malaise, night sweats
- Anorexia
- Extremity claudication
- Transient ischemic attack or stroke
PHYSICAL EXAM
- The superficial temporal artery may exhibit point tenderness, diminished pulse, induration, hemorrhagic bullae, or overlying skin necrosis
- Anterior ischemic optic neuropathy (AION) is the most common cause of visual loss; less frequent causes include central and branch retinal artery occlusion, choroidal infarction, and posterior ischemic optic neuropathy
- Signs of optic neuropathy may include decreased visual acuity, decreased color vision, afferent pupillary defect, and visual field loss
- Often altitudinal visual field defect (i.e., respecting the horizontal midline)
- In cases of AION, the optic disc may show pallid swelling, although hyperemic disc swelling is occasionally seen; peripapillary hemorrhages and cotton wool spots may be noted; as optic disc swelling resolves, optic atrophy occurs
- Fever of unknown origin (generally low grade)
- Weight loss
- III, IV, or VI cranial neuropathies
- Orbital inflammatory syndrome
- Ocular ischemic syndrome, hypotony
- Horner's syndrome (i.e., ptosis, miosis +/– anhydrosis)
- Neurologic sequelae (ataxia, confusion, hearing loss, ischemic peripheral neuropathy)
- Myocardial, renal, visceral, or cerebral infarction
- Large-vessel involvement (aortic aneurysm or rupture, most commonly thoracic)
DIAGNOSTIC TESTS AND INTERPRETATION
Lab
Initial Lab Tests
- There is no specific laboratory test for the diagnosis of GCA.
- Westergren erythrocyte sedimentation rate (WESR) often exceeds 70 mm/hour.
- A normal WESR does not rule out the diagnosis of GCA; however, as approximately 15% of biopsy positive GCA cases will have a WESR within normal limits.
- WESR is a general measure of systemic inflammation, as are C-reactive protein (CRP), platelets, fibrinogen, and complement levels, which may also be elevated.
- Additionally, anemia (hypochromic, microcytic or normochromic, normocytic), polyclonal hypergammaglobulinemia, and a mild leukocytosis may be observed. Liver alkaline phosphatase levels may be elevated in GCA.
Follow-Up & Special Considerations
- Drawing the WESR and CRP together is more sensitive than the WESR alone for the diagnosis of GCA (3)[A].
- WESR, CRP, and other acute phase reactants may be used to monitor response to therapy and disease control.
Imaging
Initial Approach
- Fluorescein angiography (FA) of the fundus may demonstrate a delayed or absent choroidal filling pattern suggesting arteritic ischemic optic neuropathy.
- FA in cases of nonarteritic ischemic optic neuropathy may show delayed optic disc filling, yet the choroidal circulation is generally not affected.
- CT or MRI scans are generally not indicated but may be necessary to rule out compressive or infiltrative lesions in atypical cases (e.g., multiple cranial neuropathies, proptosis or seizure).
Follow-Up & Special Considerations
If large-vessel involvement is suspected, ultrasound and/or angiography should be pursued.
Diagnostic Procedures/Other
- Temporal artery biopsy should be taken from the affected side.
- Some authors recommend bilateral temporal artery biopsies; however, biopsy of the symptomatic side usually is adequate.
- A large biopsy (>2 cm) is needed because of the commonly observed “skip” lesions in GCA.
Pathological Findings
- A positive biopsy is diagnostic and demonstrates segmental cellular infiltrates of the vessel wall which are predominantly consisted of T-lymphocytes, plasma cells, and macrophages (4)[A].
- Fragmentation of the internal elastic lamina and the presence of multinucleated giant cells are common, but not necessary to make the diagnosis of GCA.
DIFFERENTIAL DIAGNOSIS
[Outline]
MEDICATION
First Line
- Oral prednisone is given with the initial dose ranging from 40 to 120 mg/day. The overall degree of suspicion and presence of visual involvement influence the dose and route. Some authors recommend IV methylprednisolone 1 g/day for 3 days in cases presenting with visual deficit; however, the benefit is unproven. The goal of therapy is to maintain the lowest dose of corticosteroid that resolves clinical symptoms and maintains WESR <30–40 mm/hour.
- Absolute contraindications to corticosteroid use include hypersensitivity to the drug and systemic fungal infection. Relative contraindications include diabetes, hypertension, tuberculosis, osteoporosis, andcongestive heart failure.
Second Line
In cases where active inflammation is not controlled or intolerable side effects occur, a second immunosuppressive agent (e.g., azathioprine or methotrexate) may be added to spare the steroid dose.
ADDITIONAL TREATMENT
General Measures
Treatment of GCA focuses on the prevention of serious vascular complications, particularly blindness. Corticosteroids are the mainstay of therapy for GCA and should be instituted when the diagnosis is suspected, even in the face of normal WESR and prior to obtaining temporal artery biopsy. Unfortunately, visual loss is often irreversible and may be progressive even when high-dose IV methylprednisolone is given (5)[B]. Headache typically responds to corticosteroid treatment within 1–2 days. Duration of steroid therapy for treatment of GCA may range from 1–3 years.
Issues for Referral
Visual symptoms/loss associated with GCA require that the patient see an ophthalmologist on an emergency basis and may involve hospital admission.
SURGERY/OTHER PROCEDURES
Temporal artery biopsy should be performed to confirm the diagnosis of GCA. It is performed under local anesthetic and on an outpatient basis. A negative biopsy does not rule out the diagnosis of GCA.
IN-PATIENT CONSIDERATIONS
Admission Criteria
- Admission for GCA is indicated for IV steroid therapy, unstable vitals, large vessel involvement, ischemic limb, and renal, gastrointestinal, cardiac, or cerebral complications.
- Alternatively, IV therapy may be given on an outpatient basis.
[Outline]
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
Patients should be seen every 4–6 weeks to assess the response to therapy. Clinical symptoms and signs, ESR, and other acute phase reactants should be followed as corticosteroids are tapered.
DIET
No reports available.
PATIENT EDUCATION
It is necessary to educate each patient regarding the chronic nature of GCA, the spectrum of symptoms, the possibility of relapse, and possible sequelae of long-term steroid therapy.
PROGNOSIS
Relapse most commonly occurs during the initial year of therapy, especially following reduction of steroid dose. Up to 50% of GCA patients may require corticosteroids for >2 years. In general, patients have been reported to have the same life expectancy as age-matched controls; however, profound visual loss in GCA has been found to correlate with decreased quality and duration of life.
COMPLICATIONS
- GCA patients may experience steroid-related complications such as progressive obesity, osteoporosis, hip and spinal compression fractures, immunosuppression, cushingoid appearance, diabetes, hypertension, peptic ulcer disease, gastrointestinal bleed, cataracts, or glaucoma.
- Gastric prophylaxis may include taking steroids with meals or in divided doses. Additionally, ranitidine (Zantac), sucralfate (Carafate), or omeprazole (Prilosec) may be indicated.
- Bisphosphonates have been shown to decrease bone loss and may be indicated for some patients.
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