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ANCA-associated vasculitis in childhood: recent advances.

ABSTRACT: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides are rare systemic diseases that usually occur in adulthood. They comprise granulomatosis with polyangiitis (GPA, Wegener's), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss syndrome). Their clinical presentation is often heterogeneous, with frequent involvement of the respiratory tract, the kidney, the skin and the joints. ANCA-associated vasculitis is rare in childhood but North-American and European cohort studies performed during the last decade have clarified their phenotype, patterns of renal involvement and their prognostic implications, and outcome. Herein, we review the main clinical and therapeutic aspects of childhood-onset ANCA-associated vasculitis, and provide preliminary data on demographic characteristics and organ manifestations of an Italian multicentre cohort.

SUBMITTER: Calatroni M

PROVIDER: S-EPMC5420084 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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ANCA-associated vasculitis in childhood: recent advances.

Calatroni Marta M Oliva Elena E Gianfreda Davide D Gregorini Gina G Allinovi Marco M Ramirez Giuseppe A GA Bozzolo Enrica P EP Monti Sara S Bracaglia Claudia C Marucci Giulia G Bodria Monica M Sinico Renato A RA Pieruzzi Federico F Moroni Gabriella G Pastore Serena S Emmi Giacomo G Esposito Pasquale P Catanoso Mariagrazia M Barbano Giancarlo G Bonanni Alice A Vaglio Augusto A

Italian journal of pediatrics 20170505 1

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides are rare systemic diseases that usually occur in adulthood. They comprise granulomatosis with polyangiitis (GPA, Wegener's), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss syndrome). Their clinical presentation is often heterogeneous, with frequent involvement of the respiratory tract, the kidney, the skin and the joints. ANCA-associated vasculitis is rare in childhood but N ...[more]

PMID: 28476172

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Project description: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.

Project description:Background and objectivesANCA-associated vasculitis is extremely rare in children. We report the clinicopathologic features, long-term outcomes, and prognostic factors of a large pediatric cohort of patients with ANCA-associated kidney vasculitis.Design, setting, participants, & measurementsThis retrospective study included 85 consecutive patients with kidney biopsy specimen-proven ANCA-associated vasculitis from tertiary referral centers in Italy and Canada. Kidney biopsy specimens were categorized as focal, crescentic, sclerotic, or mixed, according to the Berden classification. The prognostic significance of baseline clinical, laboratory, and histologic findings was analyzed with respect to kidney failure or CKD stage 3-5/kidney failure.ResultsA total of 53 patients had microscopic polyangiitis (62%), and 32 had granulomatosis with polyangiitis (38%). Rapidly progressive GN was the most frequent presentation (39%); a third of the patients also had nephrotic-range proteinuria. Kidney biopsy specimens were classified as focal in 21% of the patients, crescentic in 51%, sclerotic in 15%, and mixed in 13%. Remission-induction therapies included cyclophosphamide in 78% of patients. A total of 25 patients (29%) reached kidney failure. The median (interquartile range) time to kidney failure or last follow-up was 35 (6-89) months in the whole cohort, and 73 (24-109) months among the patients who did not reach this outcome. Patients whose biopsy specimens showed sclerotic histology had significantly shorter kidney survival (hazard ratio, 11.80; 95% confidence interval, 2.49 to 55.99) and survival free of CKD stage 3-5 (hazard ratio, 8.88; 95% confidence interval, 2.43 to 32.48), as compared with those with focal/mixed histology. Baseline eGFR, low serum albumin, hypertension, central nervous system complications, and sclerotic histology, which reflected severe kidney involvement, were associated with both kidney failure and CKD stage 3-5/kidney failure at unadjusted analysis; no independent prognostic factors emerged at multivariable analysis.ConclusionsChildren with ANCA-associated kidney vasculitis often have aggressive presentation; a third of such children progress to kidney failure and this usually occurs early during follow-up. A severe clinical presentation is associated with the development of CKD or kidney failure.

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ANCA-associated vasculitis in childhood: recent advances.

Publications

ANCA-associated vasculitis in childhood: recent advances.

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