Type of ANCA May Be Indispensable in Distinguishing Subphenotypes of Different Clinical Entities in ANCA-Associated Vasculitis

Abstract

The traditional nomenclature system for classifying antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) based on clinical phenotype describes granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA) and microscopic polyangiitis (MPA) as distinct clinical entities. This classification has proved its expedience in clinical trials and everyday clinical practice; yet, a substantial overlap in clinical presentation still exists and often causes difficulties in prompt definition and clinical distinction. Additionally, new insights into the AAV pathogenesis point out that PR3 and MPO-AAV may not represent expressions of the same disease spectrum but rather two distinct disorders, as they display significant differences. Thus, it is supported that a classification based on ANCA serotype (PR3-ANCA, MPO-ANCA or ANCA-negative) could be more accurate and also closer to the nature of the disease compared to the phenotype-based one. This review aims to elucidate the major differences between PR3 and MPO-AAV in terms of epidemiology, pathogenesis, histological and clinical manifestations and response to therapeutic approaches.

EGPA Phenotyping: Not Only ANCA, but Also Eosinophils

“…Traditionally, the EGPA clinical phenotypes, named “Inflammatory” and “Vasculitic” phenotypes, tend to be distinguished according to the ANCA status rather than to the percentage and/or number of eosinophils [ 13 ]. Concerning potential biomarkers useful to predict different clinical phenotypes of EGPA, it has been shown that PNS and renal involvement are more common in ANCA-positive patients, whereas cardiac involvement is typical of ANCA-negative patients [ 24 ]. The analysis of our cohort is in agreement with the literature data, showing the association of ANCA positivity with the systemic phenotype and, specifically, with the presence of gut, PNS, kidney involvement and constitutional symptoms.…”

Polyangiitis overlap syndrome: a rare clinical entity

“…At the same extent, the ANCA pattern is usually different in these two clinical entities, with patients with EGPA being seronegative in up to 50% of cases and presenting with anti-MPO while patients with GPA more frequently show c-ANCA, anti-proteinase (PR)-3 antibodies [5,6]. The ANCA profile appears to be the most relevant factor determining the clinical picture [7,8], since there are several factors that may impede the classification of a patient as GPA or EGPA, such as the lack of histological tissue since biopsies are not obtained routinely in most cases, and classification systems that, even when adopting the novel proposed criteria, may provide discrepant classification for the same patient [9][10][11]. Nonetheless, the identification of patients with polyangiitis overlap syndrome of EGPA/GPA is essential because the treatment modalities and prognosis are different [12].…”