Description

• Also known as giant cell arteritis (GCA), Horton disease, and cranial arteritis
• Temporal arteritis is a chronic inflammatory disease involving large- and medium-sized arteries, most commonly cranial arteries originating from aortic arch. Inflammation of the aorta is observed in 50% of cases.
• New headache is a common presenting symptom and occurs in more than 2/3 of patients. Other symptoms include jaw claudication, vision loss, fatigue, fever, weight loss, symptoms of polymyalgia rheumatica (PMR), and aortic arch syndrome (decreased or absent peripheral pulses, discrepancies of blood pressure, arterial bruits). Onset of symptoms is usually subacute; however, acute presentations can also occur.
• Considered medical emergency due to risk of irreversible vision loss if not treated due to arteritic anterior ischemic optic neuropathy, central or branch artery occlusion, posterior ischemic optic neuropathy, or rarely cerebral ischemia

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 approximately 3 times more than men in persons of Northern European descent.
• Most common vasculitis in individuals of Northern European descent

Incidence

• Incidence varies by ethnicity; in the United States, approximately 1% in women and 0.5% in men
• Prevalence in Northern Europeans is 2 per 1,000 persons.
• Peaks in patients 70 to 80 years old, >80% of patients

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 patients with PMR have GCA.