What are the characteristic histologic features of giant cell (temporal) arteritis and the recommended first‑line treatment?

Histologic Features of Giant Cell Arteritis

The characteristic histologic findings of giant cell arteritis include arterial wall thickening with luminal narrowing, mononuclear inflammatory cell infiltration of the media layer, and multinucleated giant cells within the media, though giant cells may be absent in some cases. 1, 2, 3

Key Histopathologic Features

Primary Inflammatory Changes

• Arterial wall thickening with corresponding narrowed lumen is the hallmark structural change 1, 2, 3
• Mononuclear inflammatory infiltrates invading the media layer, typically composed of lymphocytes, plasma cells, and macrophages 1, 2
• Multinucleated giant cells in the media layer—though the name suggests otherwise, these cells are present in only a subset of cases and are not required for diagnosis 1, 2

Vascular Remodeling

• Intimal hyperplasia resulting from progressive arterial wall destruction and remodeling 3
• Fragmentation and calcification of the internal elastic lamina 4
• Luminal thrombus may be present in some cases 4

Distribution Patterns of Inflammation

Four validated histological patterns exist, reflecting sequential progression of disease 5:

1. Adventitial pattern (6% of cases): inflammation confined to the outer arterial layer 5
2. Adventitial invasive pattern (7% of cases): adventitial involvement with some extension into the muscular layer 5
3. Concentric bilayer pattern (18% of cases): adventitial and intimal involvement with relative preservation of the media 5
4. Panarteritic pattern (69% of cases): transmural inflammation affecting all arterial layers 5

Important Histologic Considerations

• Skip lesions occur in approximately 10% of cases, where segments of normal artery alternate with inflamed segments—this is why biopsy specimens must be ≥1 cm in length to minimize false-negative results 6, 1, 5
• Coexistence of multiple patterns in the same artery occurs in 43% of cases, likely representing different stages of inflammatory progression 5
• Bilateral temporal arteries show good correlation in histologic features when both are biopsied (correlation coefficients 0.54-0.83 for various parameters) 4

Recommended First-Line Treatment

Immediate initiation of high-dose oral glucocorticoids (prednisone 40-60 mg daily) is the first-line treatment and must be started as soon as GCA is suspected, without waiting for biopsy confirmation. 6, 1

Treatment Algorithm

For patients WITHOUT vision-threatening symptoms:

• Start oral prednisone 40-60 mg daily immediately upon clinical suspicion 6, 1
• Add tocilizumab (IL-6 receptor antagonist) at diagnosis as glucocorticoid-sparing therapy to reduce cumulative steroid exposure and prevent relapse 1
• Maintain initial high dose for one month, then taper gradually over months to years guided by clinical symptoms and inflammatory markers (ESR/CRP) 1

For patients WITH visual symptoms or threatened vision loss:

• Administer IV methylprednisolone 500-1000 mg daily for 3 consecutive days before transitioning to oral prednisone 1
• This aggressive approach is critical because untreated GCA carries a 14-50% risk of permanent vision loss 1

Adjunctive Therapies

• Low-dose aspirin (75-150 mg daily) for all GCA patients to protect against cardiovascular and cerebrovascular events 1
• Bone protection therapy (calcium, vitamin D, bisphosphonates) for all patients to prevent glucocorticoid-induced osteoporosis 1
• Methotrexate as alternative steroid-sparing agent when tocilizumab is unavailable or contraindicated 1

Critical Diagnostic Pitfalls

• Never delay glucocorticoid initiation while awaiting temporal artery biopsy—histopathologic changes remain detectable for 1-2 weeks after treatment begins, but irreversible vision loss can occur within hours to days 6, 1
• Never obtain biopsy specimens <1 cm in length, as skip lesions lead to false-negative results in up to 10% of cases 6, 1, 5
• Temporal artery biopsy should be performed within 2 weeks of starting glucocorticoids to maximize diagnostic yield, though positive biopsies have been obtained much later 6
• The biopsy must be performed by an experienced surgeon and evaluated by an experienced pathologist to ensure diagnostic accuracy 1