What is giant cell arteritis?

What is Giant Cell Arteritis?

Giant cell arteritis (GCA) is a granulomatous vasculitis affecting large and medium-sized arteries, primarily occurring in adults over 50 years of age, with the extracranial carotid branches and aorta being the most commonly involved vessels 1, 2.

Disease Characteristics

GCA manifests in two main forms that can overlap 3, 4:

• Cranial GCA: Involves medium-caliber arteries, particularly the temporal arteries, causing temporal arteritis
• Extracranial (large vessel) GCA: Affects the thoracic aorta and its major branches 5

The disease is characterized pathologically by granulomatous inflammation with giant cells as a hallmark feature 3.

Clinical Presentation

Key Clinical Features to Recognize

Specific findings that strongly suggest GCA include 6:

• Jaw claudication
• Limb claudication
• Vision changes (amaurosis fugax, vision loss)
• Temporal artery abnormalities on examination

Common but less specific symptoms include:

• New-onset headache in patients over 50
• Constitutional symptoms (fever, malaise, weight loss)
• Polymyalgia rheumatica symptoms (shoulder and hip girdle pain/stiffness)
• Stroke or cerebrovascular ischemia 1

Critical Pitfall

The extracranial form can be oligosymptomatic and easily missed, presenting primarily with constitutional symptoms without localizing vascular signs 4, 5. Clinicians must actively seek large vessel involvement through imaging, as it often goes unrecognized clinically 5.

Why This Matters: Complications

GCA is a neurologic emergency because of the risk of irreversible vision loss and stroke 2. The main complications include:

• Permanent vision loss from optic nerve ischemia
• Cerebrovascular ischemia and stroke
• Aortic aneurysm formation (develops during follow-up)
• Cardiac and limb ischemia 1, 4

Delay in diagnosis is directly associated with vision loss and other serious complications 6.

Diagnostic Approach

Laboratory Findings

Inflammatory markers are sensitive but not specific 6, 7:

• Elevated erythrocyte sedimentation rate (ESR)
• Elevated C-reactive protein (CRP)
• Both markers together have good sensitivity but must be interpreted in clinical context

Tissue Diagnosis

Temporal artery biopsy remains the gold standard for diagnosis in the US 1. Key recommendations from the 2021 ACR/Vasculitis Foundation guideline 1:

• Obtain a long-segment biopsy (>1 cm) to avoid missing focal disease
• Perform biopsy within 2 weeks of starting glucocorticoids (histologic changes can persist up to 2 weeks after treatment initiation)
• Start with unilateral biopsy; proceed to contralateral side if negative and suspicion remains high

Imaging

For patients with negative temporal artery biopsy or suspected large vessel involvement, noninvasive vascular imaging is conditionally recommended 1. Options include:

• Vascular ultrasound (operator-dependent; requires expertise)
• CT angiography
• MR angiography
• PET-CT with [18F]fluorodeoxyglucose

Imaging is particularly valuable for diagnosing the extracranial/large vessel form and is highly recommended for newly diagnosed GCA to evaluate large vessel involvement 1, 4.

Treatment Principles

Treatment must be initiated urgently when GCA is suspected, even before diagnostic confirmation 6, 7.

Initial Therapy Based on Presentation

For threatened vision loss or cranial ischemia: IV pulse methylprednisolone (500-1,000 mg/day for 3-5 days) is conditionally recommended over oral glucocorticoids 1.

For newly diagnosed GCA without cranial ischemia: High-dose oral glucocorticoids (prednisone 1 mg/kg/day up to 80 mg) are conditionally recommended 1.

Steroid-Sparing Therapy

The treatment paradigm has shifted from glucocorticoid monotherapy to steroid-sparing regimens 2. The 2021 ACR guideline conditionally recommends:

• Tocilizumab (IL-6 blocker) combined with oral glucocorticoids over glucocorticoids alone for newly diagnosed GCA 1
• Non-glucocorticoid immunosuppressive agents combined with glucocorticoids for active extracranial large vessel involvement 1

This approach reduces glucocorticoid-related complications (hypertension, diabetes, osteoporosis, infection, psychosis, peptic ulcer disease) that occur with prolonged high-dose therapy 7.

Population at Risk

GCA affects individuals with genetic predisposition, typically:

• Age over 50 years (essential criterion)
• More common in those of Northern European descent
• Epigenetic and environmental factors contribute to disease onset 3