New Treatment Strategies in Large-vessel Vasculitis

Sebastian Unizony; John H. Stone; James R. Stone


Curr Opin Rheumatol. 2013;25(1):3-9. 

In This Article

Giant Cell Arteritis

GCA, the most common form of LVV, occurs primarily in elderly individuals of European ancestry.[1] Inflammation in this disease affects medium to large-sized arteries, and involves the aorta and great vessels, with predilection for the extracranial branches of the carotid arteries. GCA carries a substantial morbidity burden in relation to both the disease itself and its treatment. One of the most feared consequences is vision loss,[2] but several other inflammatory complications can ensue including arterial aneurysms and dissections.[3,4]

Since its first description in the early 1930s, no clearly defined alternative to long-term treatment with glucocorticoids has been defined for GCA.[5] Glucocorticoids are highly effectively at controlling systemic inflammation and preventing acute damage (i.e. vision loss), but generally fail to cure the disease or to induce long-term, treatment-free remissions.[6] More than half of the patients relapse upon weaning steroids, and therefore require prolonged treatments that are invariably associated with an array of toxic effects including bone fractures, cataracts, diabetes, and mood swings.[7] The results of treatment trials with conventional immunosuppressive agents including methotrexate have been generally disappointing, and tumor necrosis factor α (TNF-α) antagonists have failed to spare glucocorticoids.[8]

The antigen that triggers an autoimmune response against the arterial components in GCA has remained elusive. However, disease mechanisms that involve the cellular branch of the adaptive and innate immune systems have been partially clarified.[9] In untreated patients, an expanded repertoire of autoreactive CD4-positive T lymphocytes, including IFN-[gamma] producing T helper (Th) 1 cells and IL-17-secreting Th17 cells, orchestrates the formation of a granulomatous inflammatory process. Moreover, the number of Foxp3+ regulatory T cells (Treg), which normally serve to limit an immunologic response, appears to be decreased.[10] GCA is associated with the upregulation of multiple proinflammatory cytokines, such as IL-6, which is secreted by a wide variety of cell types including T-cells, macrophages, and endothelial cells. Thus, inhibition of IL-6 may be an alternative strategy for treating GCA.