Volume 51, Number 8

The Pathogenesis of Giant Cell Arteritis

Cornelia M. Weyand, MD
Jörg J Goronzy, MD

Departments of Medicine and Immunology
Mayo Clinic
Rochester, MN

Summary Points

• The pathology of GCA is characterized by intimal proliferation and luminal occlusion and giant cell formation. Molecular components associated with intimal proliferation are IFN-g, IL-1β, PDGF, and VEGF.

• The systemic inflammatory response is indicated by an elevation of IL-6, ESR, and C-reactive protein.

• Treatment with glucocorticoids targets the NF-kB transcription factor suppressing Il-1 and IL-6. Acetylsalicylic acid can suppress IFN-g, which may augment the effects of glucocorticoids. Other therapeutic targets are PDGF and VEGF.

Introduction

Giant cell arteritis (GCA) is an inflammatory vasculopathy feared for its potential to cause total and irreversible blindness. Vascular inflammation is linked with a syndrome of systemic inflammation resulting in constitutional symptoms and elevated levels of erythrocyte sedimentation rate, C-reactive protein, and IL-6. GCA has been ranked as the prime ophthalmic emergency because it is essentially the only syndrome in which prompt diagnosis and treatment can prevent blindness (1,2,3).

GCA has several characteristics that distinguish it from other vasculitides and other autoimmune syndromes. These characteristics include: 1) the territorial involvement of vascular beds despite the systemic nature of GCA – extracranial branches of the carotid and distal portions of the subclavian arteries are preferentially targeted (4); 2) the non-random distribution of incidence rates in distinct geographic locations and populations, which most likely reflects genetic susceptibility factors (5); 3) the explicit sensitivity to immunosuppressant glucocorticoids, which emphasizes the role of the immune system in the pathogenesis; and 4) the stringent age relationship, which restricts the disease to individuals older than 50 years. Age is the single most important risk factor for GCA, likely due to age-induced changes in the immune system that predispose individuals to develop granulomatous inflammation in selected vessel walls.