Description

• Technically termed giant cell arteritis (GCA)
• A chronic, generalized, cellular, and humoral immune-mediated vasculitis of large- and medium-sized vessels, predominantly affecting the cranial arteries originating from the aortic arch, although vascular involvement may be widespread. Inflammation of the aorta is observed in 50% of cases.
• Frequent features include fatigue, headaches, jaw claudication, visual symptoms, scalp tenderness, constitutional symptoms, polymyalgia rheumatica (PMR) symptoms, and aortic arch syndrome (decreased or absent peripheral pulses, discrepancies of blood pressure, arterial bruits).
• Considered medical emergency due to risk of irreversible vision loss if not treated due to ophthalmic artery occlusion

Epidemiology

• Most common form of systemic vasculitis affecting persons ≥50 years old
• 80% of cases occur at ages 70 to 80 years.
• Women are affected about 2 to 3 times more than men in persons of Northern European descent.
• Most common vasculitis in individuals of Northern European descent
• Rare in persons of Asian or African descent
• Lower BMI associated with increased risk

Incidence

• Incidence varies by ethnicity
• Prevalence in Northern Europeans is 2 per 1,000 persons.
• Peaks in patients 70 to 80 years old

Etiology and Pathophysiology

• The exact etiology of GCA remains unknown, although current theory suggests that advanced age, ethnicity, and specific genetic predisposition lead to a maladaptive response to endothelial injury, intimal hyperplasia, and ultimately vascular stenosis.
• GCA is a chronic, systemic vasculitis primarily affecting the elastic lamina of medium- and large-sized arteries. Histopathology of affected arteries is marked by transmural inflammation of the intima, media, and adventitia as well as patchy infiltration by lymphocytes, macrophages, and multinucleated giant cells. Mural hyperplasia can result in arterial luminal narrowing, resulting in subsequent distal ischemia.
• Current theory regarding the etiology of GCA is that a maladaptive response to endothelial injury leads to an inappropriate activation of T-cell–mediated immunity via immature antigen-presenting cells. The subsequent release of cytokines within the arterial vessel wall can attract macrophages and multinucleated giant cells, which form granulomatous infiltrates and give diseased vessels their characteristic histology. This also leads to an oligoclonal expansion of T-cells directed against antigens in or near the elastic lamina. Ultimately, this cascade results in vessel wall damage, intimal hyperplasia, and eventual stenotic occlusion.
• In recent years, GCA and PMR have increasingly been considered to be closely related conditions.
• Varicella zoster virus has been proposed as possible immune trigger for GCA; however, this has not been substantiated, and adjunctive treatment with antivirals remains controversial.

Genetics
The gene for HLA-DRB1*04 has been identified as a risk factor for GCA, and polymorphisms of ICAM-1 and PTPN-22 have also been implicated.

Risk Factors

• Increasing age (>70 years) is the greatest risk factor.
• Females
• Genetic predisposition—occasional family clustering has been reported.
• Environmental factors influence susceptibility
• History of smoking
• Early menopause (<43 years) and lower BMI at menopause in women 50 to 69 years old

Commonly Associated Conditions

Population studies have shown 40–60% of patients diagnosed with GCA also have PMR symptoms, and 16–21% of patient with PMR have GCA.