This document follows up on a 2017 revised international consensus on antineutrophil cytoplasm antibodies (ANCA) testing in granulomatosis with polyangiitis and microscopic polyangiitis and focuses on the clinical and diagnostic value of ANCA detection in patients with connective tissue diseases, idiopathic interstitial pneumonia, autoimmune liver diseases, inflammatory bowel diseases, anti-glomerular basement membrane (GBM) disease, infections, malignancy, and during drug treatment. Current evidence suggests that in certain settings beyond systemic vasculitis, ANCA may have clinical, pathogenic and/or diagnostic relevance.Antigen-specific ANCA targeting proteinase-3 and myeloperoxidase should be tested by solid phase immunoassays in any patient with clinical features suggesting ANCAassociated vasculitis and in all patients with anti-GBM disease, idiopathic interstitial pneumonia, and infective endocarditis associated with nephritis, whereas in patients with other aforementioned disorders routine ANCA testing is not recommended. Among patients with autoimmune liver diseases or inflammatory bowel diseases, ANCA testing may be justified in patients with suspected autoimmune hepatitis type 1 who do not have conventional autoantibodies or in case of diagnostic uncertainty to discriminate ulcerative colitis from Crohn's disease. In these cases, ANCA should be tested by indirect immunofluorescence as the target antigens are not yet well characterized. Many questions concerning the optimal use of ANCA testing in patients without ANCA-associated vasculitis remain to be answered.Testing for anti-neutrophil cytoplasm antibodies (ANCA) directed towards proteinase 3 (PR3) and myeloperoxidase (MPO) is commonly performed to support the diagnosis of ANCA-associated vasculitides (AAV) that encompasses granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). In 2017, a revised international consensus on testing of ANCA in GPA and MPA was proposed [1]. This consensus document focused on ANCA testing in AAV and briefly described other conditions that were reported to be associated with ANCA positivity, mostly in the context of the differential diagnosis of other inflammatory diseases [2]. The current document is a follow-up on the previous consensus statements [1,3,4] and highlights the clinical and diagnostic value of ANCA testing in patients with various autoimmune, infectious and neoplastic diseases. However, the number of high quality studies addressing this issue is limited, and many unresolved issues concerning the optimal use of ANCA testing in non-AAV remain to be elucidated.
MethodsThis Consensus Statement was prepared by a group of experts based on the results of a comprehensive search in PubMed for disorders that can be associated with ANCApositivity, by using a variety of search terms, and all relevant available literature was critical reviewed. Additional publications were identified in the references of the available articles. The resulting manus...