Knowledge on rare diseases and orphan drugs

Giant cell arteritis (GCA) is the most common vasculitis in adulthood with an annual incidence of 1/5,000-1/17,000 adults over 50 years old. It is more frequent in populations of northern European background. GCA affects people of more than 50 years of age (median age at diagnosis between 70-75 years old) and occurs twice as frequently in women as in men.

GCA often starts insidiously with constitutional symptoms (fever, weight loss, night sweats, malaise, asthenia), cranial manifestations (headache, jaw claudication, scalp tenderness, visual loss), and, in about 50% of patients, polymyalgia rheumatica. The temporal artery may be swollen and tender. Visual symptoms due to an ischemic optic neuropathy occur in up to 20-30% of patients, and can lead to irreversible blindness if not immediately treated with glucocorticoids. Thoracic aortitis with aneurysms occur in approximately 15% of patients. While aortic complications rarely affect patients at disease onset, they are often a late complication of GCA.

The etiology of giant cell arteritis is unknown. Studies have linked genetic factors, infectious agents and a prior history of cardiovascular disease to the development of giant cell arteritis.

The diagnosis of GCA is made in individuals over 50 years of age by a combination of characteristic symptoms as outlined above, increased acute phase reactants (erythrocyte sedimentation rate, C-reactive protein or both) and characteristic imaging findings (ultrasound, magnetic resonance imaging, computerized tomography or 18-fluorodeoxyglucose positron emission tomography) of temporal and/or other large arteries depicting inflammatory wall swelling. In case imaging is either not available or inconclusive, temporal artery biopsy is a valid alternative. In temporal artery biopsy, the most important (and mandatory) histological criterion for the diagnosis of GCA is a mononuclear cell infiltrate predominating at the media-intima junction or involving the entire vessel wall (panarteritis). Response to glucocorticoid treatment is neither sensitive nor specific enough to consider it as a diagnostic criterion.

In elderly patients presenting with constitutional symptoms and elevated inflammatory markers, cancer and infection need to be ruled out. Symptoms of polymyalgia rheumatica can also point towards diagnoses of isolated polymyalgia rheumatica or rheumatoid arthritis. In some instances, biopsy-proven involvement of the temporal arteries can be seen in other systemic vasculitides, e.g. ANCA associated vasculitis or polyarteritis nodosa.

Glucocorticoids (initial dose 40-60mg/day) are highly effective in GCA but prolonged glucocorticoid therapy is often associated with substantial morbidity in the elderly population. Glucocorticoid pulse therapy (250-1000mg per day for 3 days) may be considered in case of acute visual loss or amaurosis fugax. Tocilizumab, or alternatively methotrexate should be considered in patients with refractory or relapsing GCA as well as in cases with the presence or an increased risk of glucocorticoid related adverse effects or complications. Concomitant prescription of antiplatelet or anticoagulant therapy is not indicated unless required to treat concomitant (e.g. cardiovascular) diseases. Regular monitoring for late vascular complications (e.g. aortic aneurysms) is needed.

The disease is chronic and the clinical course is highly variable. Response to glucocorticoids is usually rapid and complete. However, at least 50% of patients experience subsequent disease flares. Visual loss is the most feared complication but can be prevented by rapid diagnosis and immediate treatment.

Last update: April 2021 - Expert reviewer(s): Pr Christian DEJACO