11-04-2016 | Vasculitis | Review | Article
Giant Cell Arteritis: From Pathogenesis to Therapeutic Management
Journal: Current Treatment Options in Rheumatology
Authors: Ryu Watanabe, MD, PhD, Jörg J. Goronzy, MD, PhD, Gerald Berry, MD, Y. Joyce Liao, MD, PhD, Cornelia M. Weyand, MD, PhD
Publisher: Springer International Publishing
Abstract
Giant cell arteritis (GCA) is a systemic inflammatory vasculopathy mediated by pathogenic responses of a diverse array of innate and adaptive immune cells as well as vascular cells. Current therapy relies on broadly immunosuppressant glucocorticoids, which rapidly control systemic inflammation, but fail to eliminate vascular inflammation. Despite steady growth of the immunosuppressive armamentarium overall, it has been difficult to identify clinically meaningful and steroid-sparing effects of targeted biologic therapies in GCA. Here, we propose that this reflects the multiplicity of pathogenic elements that converge to induce and maintain GCA: (a) GCA is a disease of the elderly, posing additional risks when aggressively disabling immunity. (b) GCA is a chronic disease and persists as smoldering vasculitis. (c) The burden of disease is difficult to measure, complicating adjustments of immunosuppressive therapy. In the absence of objective activity markers, physicians and patients lean toward overutilization of glucocorticoids. (d) Key pathogenic drivers are T cells and macrophages, which assemble in granulomas and are highly diverse in their functional product portfolio. The diversity of vasculitogenic effector functions confounds simple therapeutic targeting. (e) Ultimate vascular complications are dependent on vessel wall cells, requiring therapeutic strategies beyond immunosuppression. Immediate goals in improving the therapeutic management of GCA should focus on optimizing glucocorticoid dosing to avoid overutilization and on adapting therapy to the needs of the immunosenescent host. Building a spectrum of possible therapeutic targets will enable carefully designed multipronged combination therapies.