Updates in ANCA-associated vasculitis

Abstract

Antineutrophil cytoplasm antibody (ANCA)-associated vasculitides are small-vessel vasculitides that include granulomatosis with polyangiitis (formerly Wegener's granulomatosis), microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome). Renal-limited ANCA-associated vasculitides can be considered the fourth entity. Despite their rarity and still unknown cause(s), research pertaining to ANCA-associated vasculitides has been very active over the past decades. The pathogenic role of antimyeloperoxidase ANCA (MPO-ANCA) has been supported using several animal models, but that of antiproteinase 3 ANCA (PR3-ANCA) has not been as strongly demonstrated. Moreover, some MPO-ANCA subsets, which are directed against a few specific MPO epitopes, have recently been found to be better associated with disease activity, but a different method than the one presently used in routine detection is required to detect them. B cells possibly play a major role in the pathogenesis because they produce ANCAs, as well as neutrophil abnormalities and imbalances in different T-cell subtypes [T helper (Th)1, Th2, Th17, regulatory cluster of differentiation (CD)4+ CD25+ forkhead box P3 (FoxP3)+ T cells] and/or cytokine-chemokine networks. The alternative complement pathway is also involved, and its blockade has been shown to prevent renal disease in an MPO-ANCA murine model. Other recent studies suggested strongest genetic associations by ANCA type rather than by clinical diagnosis. The induction treatment for severe granulomatosis with polyangiitis and microscopic polyangiitis is relatively well codified but does not (yet) really differ by precise diagnosis or ANCA type. It comprises glucocorticoids combined with another immunosuppressant, cyclophosphamide or rituximab. The choice between the two immunosuppressants must consider the comorbidities, past exposure to cyclophosphamide for relapsers, plans for pregnancy, and also the cost of rituximab. Once remission is achieved, maintenance strategy following cyclophosphamide-based induction relies on less toxic agents such as azathioprine or methotrexate. The optimal maintenance strategy following rituximab-based induction therapy remains to be determined. Preliminary results on rituximab for maintenance therapy appear promising. Efforts are still under way to determine the optimal duration of maintenance therapy, ideally tailored according to the characteristics of each patient and the previous treatment received.

Keywords: Antineutrophil cytoplasmic antibody-associated vasculitis; Churg-Strauss syndrome (eosinophilic granulomatosis with polyangiitis); cyclophosphamide; granulomatosis with polyangiitis (Wegener’s granulomatosis); microscopic polyangiitis; rituximab.

Conflict of interest statement

Dr. Pagnoux reports having received fees for serving on advisory boards from Roche, Genzyme, Sanofi, ChemoCentryx and GlaxoSmithKline, lecture fees from Roche, Bristol-Myers Squibb, and EuroImmune, and grant support from Roche, Euroimmune and Terumo BCT.

Figures

Figure 1

Saddle-nose deformity in a patient with granulomatosis with polyangiitis (GPA)

Figure 2

Nasal septum perforation in a patient with polyangiitis (GPA) (Note the light going from one nostril to the other through the perforated nasal septum and the crusty bleedy posterior wall of the sino-nasal cavity)

Figure 3

Purpuro-ecchymotic skin lesions on the legs of a patient with eosinophilic granulomatosis with polyangiitis (EGPA) (Legs are the most commonly involved areas for skin lesions in antineutrophil cytoplasm antibody (ANCA)-associated vasculitides)

Figure 4

Nodular cutaneous lesions in a patient with granulomatosis with polyangiitis (GPA) Elbows are a common location for such skin lesions in granulomatosis with polyangiitis (GPA) and eosinophilic granulomatosis with polyangiitis (EGPA).

Figure 5

Computerized tomography (CT) scan of sinuses in a patient with granulomatosis with polyangiitis (GPA) (Note the perforated nasal septum and bilateral fulfillment of maxillary sinuses-sinusitis)

Figure 6

Chest computerized tomography (CT) in a patient with granulomatosis with polyangiitis (GPA) (Note the multiple plain lung nodules surrounded by ground glass opacities suggestive of associated peri-nodular alveolar hemorrhage)

Figure 7

Chest computerized tomography (CT) in a patient with microscopic polyangiitis (MPA) (Note the diffuse ground-glass opacities, which are suggestive of alveolar hemorrhage, with some pseudonodular consolidation appearance in the left lung)

Figure 8

Histology of muscle–nerve biopsy in a patient with eosinophilic granulomatosis with polyangiitis (EGPA) (Note the massive vessel wall and perivascular infiltrate by inflammatory cells, mainly eosinophils, the vessel wall necrosis, and subsequent vessel lumen occlusion)