ANCA-Associated Vasculitis: An Update

Abstract

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) represents a group of small vessel vasculitides characterized by granulomatous and neutrophilic tissue inflammation, often associated with the production of antibodies that target neutrophil antigens. The two major antigens targeted by ANCAs are leukocyte proteinase 3 (PR3) and myeloperoxidase (MPO). AAV can be classified into 3 categories based on patterns of clinical involvement: namely, granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic GPA (EGPA). Clinically, AAV involves many organ systems including the lungs, kidneys, skin, and nervous system. The prognosis of AAV has improved dramatically due to advances in the understanding of its pathogenesis and treatment modalities. This review will highlight some of the recent updates in our understanding of the pathogenesis, clinical manifestations, and treatment options in patients with AAV focusing on kidney involvement.

B-Cell-Depleting Therapy Improves Myocarditis in Seronegative Eosinophilic Granulomatosis with Polyangiitis

“…Owing to non-inferiority to CYC, RTX with a 375 mg/m 2 weekly × 4 regimen was approved as a first-line therapy at induction in severe AAV [ 1 , 2 ]. Since RTX is less toxic than CYC and has lower relapse rates than other IS for maintenance, the 2021 ACR/Vasculitis Foundation Guideline has recommended this biologic agent over CYC for remission induction and over other IS for remission maintenance in active, severe AAV patients [ 11 ].…”

“…Eosinophilic granulomatosis with polyangiitis (EGPA), a rare autoimmune disorder occurring exclusively in asthmatic patients, is classified as anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) [ 1 , 2 ]. Among the three AAV-related disorders, cardiac involvement presenting as myocarditis is most commonly observed in EGPA with serious complications, including overt heart failure and sudden cardiac death [ 3 , 4 ].…”

“…Among the three AAV-related disorders, cardiac involvement presenting as myocarditis is most commonly observed in EGPA with serious complications, including overt heart failure and sudden cardiac death [ 3 , 4 ]. AAV therapy can be adapted for the presence of poor prognostic factors, i.e., five-factor score (FFS) [ 1 , 5 ]. In major organ damage with the presence of FFS-like cardiac insufficiency, in addition to initial high-dose corticosteroids (CS), cyclophosphamide (CYC) is usually prescribed to induce disease remission [ 1 , 6 ].…”

“…AAV therapy can be adapted for the presence of poor prognostic factors, i.e., five-factor score (FFS) [ 1 , 5 ]. In major organ damage with the presence of FFS-like cardiac insufficiency, in addition to initial high-dose corticosteroids (CS), cyclophosphamide (CYC) is usually prescribed to induce disease remission [ 1 , 6 ]. Nevertheless, the majority of deaths in EGPA are attributed to disease activity with heart involvement in spite of combined CS and CYC therapy [ 3 , 6 , 7 ].…”

“…Through the presentation of autoantigens and costimulatory signaling to Th2 cells, B cells can participate in the pathogenesis by inducing the release of IL-5, resulting in the activation, maturation, survival and recruitment of eosinophils [ 6 , 7 , 8 , 9 , 10 ]. Therapeutic indications of rituximab (RTX), a B-cell-depleting anti-CD20 monoclonal antibody (mAb), have been approved for induction therapy in AAV-related diseases, not including EGPA [ 1 , 8 ]. This biologic agent is recommended at induction for active or relapsing disease in severe EGPA [ 11 , 12 ].…”