ANCA-ASSOCIATED VASCULITIS

Vasculitis refers to inflammation of the blood vessel. This inflammation can cause vessel wall thickening that compromises or occludes the vessel lumen, ultimately resulting in organ ischaemia. This article explores the clinical features, diagnosis, evaluation and treatment of the anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV). The AAV comprise a group of three heterogeneous syndromes: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). All three conditions are characterised by the presence of ANCAs, mainly involve small-vessels and share certain clinical features; however, their immunofluorescence patterns and target antigen specificities differ. The categorisation of vasculitides, based on the predominant vessel size affected by the disease, has been widely accepted since the first Chapel Hill Consensus Conference (CHCC) in 1994 (1). However, although useful, this categorisation was not absolute and many vasculitides can affect a diverse range of vessels. The Chapel-Hill classification was, therefore, revised in 2012, with significant changes in the nomenclature of small-vessel vasculitides, which encompass immune complex vasculitis (anti-glomerular basement membrane [GBM] disease, IgA vasculitis, cryoglobulinaemic vasculitis, hypocomplementaemic urticarial vasculitis) and AAV (2). Within the AAV, the term microscopic polyangiitis has not been changed, but Wegener’s granulomatosis (WG) has been replaced by GPA and Churg-Strauss syndrome by EGPA. The spirit of these changes was to replace eponyms by terms that describe the disease. The change of WG to GPA had already been proposed by three scientific societies (American Society of Nephrology, European League Against Rheumatism and American College of Rheumatology), notably because of concerns about the behaviour of Doctor Friedrich Wegener during the Second World War. The CHCC definitions for the AAV are given in table 1. It is interesting to note that MPA has been differentiated from polyarteritis nodosa (PAN) since the definition of MPA by the first CHCC. Before, the term polyarteritis nodosa encompassed ‘classical PAN’ and ‘microscopic PAN’. PAN is, however, a medium size-vessel vasculitis in which ANCA are not present. For example, the renal involvement in PAN is the result of a vascular nephropathy with frequent cortical infarctions and sometimes reno-vascular hypertension, whereas renal involvement in MPA is a pauci-immune (which means that there are no immunofluorescence deposits) glomerulonephritis, undistinguishable from that observed in GPA, EGPA and ANCA-associated pauci-immune glomerulonephritis. It is important to remember that the CHCC definitions are a nomenclature system, not a classification system nor a diagnostic system for directing clinical management. The main clinical features of the three AAV are given in table 2. Importantly, although EGPA is considered as an ‘AAV’, this specific disease has a unique place within the AAV spectrum, with certain distinctive features, including the lower prevalence of ANCAs than in GPA and MPA and the key-role of tissue hypereosinophilia in its pathophysiology. Hence, in this review article, we will focus on GPA and MPA, which are classically considered to represent a more homogeneous group Table 1: Chapel Hill Consensus Conference Definitions of ANCA-associated vasculitides (adapted from (2))