Eosinophilic granulomatosis with polyangiitis is characterized by asthma, blood and tissue eosinophilia and small-vessel vasculitis. The clinical presentation is variable, but two main clinic-pathologic subsets can be distinguished: one hallmarked by positive ANCA and predominant ‘vasculitic’ manifestations (e.g. glomerulonephritis, purpura and mononeuritis multiplex) and the other by negative ANCA and prominent ‘eosinophilic’ manifestations (e.g. lung infiltrates and cardiomyopathy). The pathogenesis is not fully understood but probably results from the interplay between T and B cells and eosinophils. Eosinophilic granulomatosis with polyangiitis must be differentiated from several conditions, including hypereosinophilic syndromes and other small-vessel vasculitides. The overall survival is good; however, patients frequently relapse and have persistent symptoms. The recently developed monoclonal antibodies targeting B cells and eosinophilopoietic cytokines such as IL-5 are emerging as valid alternatives to conventional immunosuppressive therapies. In this review, we discuss the essential features of eosinophilic granulomatosis with polyangiitis, with particular respect to the most relevant issues concerning clinical presentation and management.

Objective. Adult-onset IgA vasculitis (HenochSch€ onlein) (IgAV) is a rare systemic vasculitis characterized by IgA1-dominant deposits. The treatment of adult-onset IgAV is controversial and is based on the combination of glucocorticoids and immunosuppressive agents, but many patients have refractory or relapsing disease despite treatment. Rituximab (RTX) is a B celldepleting antibody of proven efficacy in antineutrophil cytoplasmic antibody-associated vasculitis. We undertook this study to test the efficacy and safety of RTX in a multicenter cohort of patients with adult-onset IgAV.Methods. In this multicenter observational study, we included patients with adult-onset IgAV who had received RTX either for refractory/relapsing disease or because they had contraindications to conventional glucocorticoid/immunosuppressive therapy. We analyzed the rates of remission (defined on the basis of the Birmingham Vasculitis Activity Score [BVAS]) and relapse as well as the variations over time in estimated glomerular filtration rate (GFR), proteinuria, C-reactive protein (CRP) level, BVAS, and prednisone dose.Results. Twenty-two patients were included; their median duration of follow-up was 24 months (interquartile range 18-48 months). Sixteen patients received RTX as add-on therapy and 6 as monotherapy. Twenty patients (90.9%) achieved remission, and 7 of those 20 patients (35%) had subsequent relapse of disease. There were significant reductions in 24-hour proteinuria (P < 0.0001), CRP level (P = 0.0005), BVAS (P < 0.0001), and prednisone dose (P < 0.0001) from RTX initiation through the last follow-up visit; estimated GFR remained stable. RTX was generally well tolerated. One patient died after 60 months of follow-up.Conclusion. Our data suggest that RTX is an effective and safe therapeutic option for adult-onset IgAV.

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Background Although rapidly progressive glomerulonephritis is the main renal phenotype of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), slow renal disease progression is sometimes observed. These forms have been rarely discussed; we analysed their prevalence, clinico-pathological characteristics and outcome. Methods We screened patients with microscopic  polyangiitis (MPA) and granulomatosis with polyangiitis followed at seven referral centres and selected those with estimated glomerular filtration rate (eGFR) reduction &lt;50% over a 6-month period preceding diagnosis. Data regarding patient features and response to treatment were retrieved. Results Of 856 patients, 41 (5%) had slowly progressive renal AAV. All had MPA and all but one was P-ANCA/myeloperoxidase (MPO) ANCA-positive. At diagnosis, the median age was 70 years [interquartile range (IQR) 64–78] and extra-renal manifestations were absent or subclinical (interstitial lung lesions in 10, 24%). The median (IQR) eGFR was 23 mL/min/1.73 m2 (15–35); six patients (15%) had started renal replacement therapy (RRT). All had proteinuria (median 1180 mg/24 h, IQR 670–2600) and micro-haematuria. Main histologic findings were extracapillary proliferation at chronic stages and glomerulosclerosis; following Berden’s classification, 6/28 biopsies (21%) were ‘focal’, 1/28 (4%) ‘crescentic’, 9/28 (32%) ‘mixed’ and 12/28 (43%) ‘sclerotic’. At last follow-up (median 32 months, IQR 12–52), 20/34 patients (59%) treated with immunosuppression had eGFR improvement &gt;25% as compared with diagnosis, while 4/34 (12%) had started RRT. Conclusions AAV may present with slow renal disease progression; this subset is hallmarked by advanced age at diagnosis, positive MPO-ANCA, subclinical interstitial lung lesions and chronic damage at kidney biopsy. Partial renal recovery may occur following immunosuppression.

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The complement system plays a central role in autoimmune diseases, including anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Although complement deposition is scarce in AAV pathological samples, complement activation is required for the development of necrotizing crescentic glomerulonephritis (NCGN) in mouse models of AAV and occurs via the alternative pathway. The anaphylatoxin C5a, produced by the final complement pathway, is determinant to drive the disease in animal models. C5a primes human neutrophils and enhances their activation induced by ANCA; activated neutrophils, in turn, release factors that lead to C5a generation, establishing a self-amplifying loop. C5a is also significantly increased in the serum of AAV patients with active disease compared to those in remission or healthy controls. Inhibition of the C5a receptor with avacopan is an emerging therapy that will probably allow AAV treatment with glucocorticoid-free regimens.

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