Aging in Granulomatosis with Polyangiitis and Microscopic Polyangiitis: From Pathophysiology to Clinical Management.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) predominantly affect individuals aged 55-75 years, with granulomatosis with polyangiitis (GPA) being diagnosed most often between 55 and 65 years and microscopic polyangiitis (MPA) between 65 and 75 years. Owing to the general increase in life expectancy, the average age at diagnosis increases, encompassing also those over 75 years old. Unfortunately, the exclusion of these older patients from many clinical trials has limited our understanding of the progression of these diseases in older subjects. The role of immunosenescence and aging in AAV pathogenesis and progression is underexplored, despite potential implications in the understanding of the disease, and potentially for disease management. Although AAV manifestations are largely consistent across age groups, certain features, such as renal involvement and the association with interstitial lung disease, may be more prevalent in older patients. Frailty must be a key consideration in therapeutic decision-making, especially when balancing the efficacy of immunosuppressants with potential side effects. Recent evidence supports the use of rituximab in addition to low-dose glucocorticoids for remission induction in life- or organ-threatening AAV, including in older populations. Furthermore, preliminary evidence supports that avacopan might be as efficient as glucocorticoids in these patients. The immunosuppressive treatment of AAV reduces the immune response to environmental pathogens, with rituximab worsening age-related hypogammaglobulinemia. Thus, prophylactic measures, including vaccination and Pneumocystis pneumonia prevention, as well as strategies to mitigate glucocorticoid side effects, should be implemented in AAV management.