Conditions in subjects with rheumatic diseases: pulmonary manifestations of vasculitides

Pulmonary involvement is a common complication of vasculitides, especially small vessel vasculitides. This review provides an overview of vasculitic manifestations of the lung as well as of other organs involved in vasculitides. Furthermore, it provides the diagnostic procedures required to asses a patient with vasculitic lung involvement and gives an overview of current treatment strategies

Genome-wide association study of eosinophilic granulomatosis with polyangiitis reveals genomic loci stratified by ANCA status

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disease of unknown cause. 30% of patients have anti-neutrophil cytoplasmic antibodies (ANCA) specific for myeloperoxidase (MPO). Here, we describe a genome-wide association study in 676 EGPA cases and 6809 controls, that identifies 4 EGPA-associated loci through conventional case-control analysis, and 4 additional associations through a conditional false discovery rate approach. Many variants are also associated with asthma and six are associated with eosinophil count in the general population. Through Mendelian randomisation, we show that a primary tendency to eosinophilia contributes to EGPA susceptibility. Stratification by ANCA reveals that EGPA comprises two genetically and clinically distinct syndromes. MPO+\u2009ANCA EGPA is an eosinophilic autoimmune disease sharing certain clinical features and an HLA-DQ association with MPO+\u2009ANCA-associated vasculitis, while ANCA-negative EGPA may instead have a mucosal/barrier dysfunction origin. Four candidate genes are targets of therapies in development, supporting their exploration in EGPA

Association of a TNFSF13B (BAFF) regulatory region single nucleotide polymorphism with response to rituximab in antineutrophil cytoplasmic antibody–associated vasculitis

Rituximab is effective at inducing and maintaining remission in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The wide interpatient variability in the duration of B-cell depletion and time to relapse as well as the significant relapse risk after treatment, costs, and adverse event rates necessitate improved patient stratification.This study was supported by the National Institute of Health Research Cambridge Biomedical Research Centre (http://www.cambridge-brc.org.uk). F.A. has been supported by a European Renal Association-European Dialysis and Transplant Association long-term fellowship between September 2012 and September 2013. A.V. and D.M. were supported by the grant “A tailored approach to the immune monitoring and clinical management of viral and autoimmune diseases,” given by the Regione Emilia-Romagna within the Programma di Ricerca Regione-Università 2010–12

EULAR recommendations for the management of ANCA-associated vasculitis : 2022 update

Funding Information: The authors wish to thank the librarian Oliver Weiner (Medical Department of the Kiel University Library, Kiel, Germany) for advice and assistance during the SLR. DJ was supported by the NIHR Cambridge Biomedical Research Centre. Publisher Copyright: © Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.Background: Since the publication of the EULAR recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in 2016, several randomised clinical trials have been published that have the potential to change clinical care and support the need for an update. Methods: Using EULAR standardised operating procedures, the EULAR task force undertook a systematic literature review and sought opinion from 20 experts from 16 countries. We modified existing recommendations and created new recommendations. Results: Four overarching principles and 17 recommendations were formulated. We recommend biopsies and ANCA testing to assist in establishing a diagnosis of AAV. For remission induction in life-threatening or organ-threatening AAV, we recommend a combination of high-dose glucocorticoids (GCs) in combination with either rituximab or cyclophosphamide. We recommend tapering of the GC dose to a target of 5 mg prednisolone equivalent/day within 4-5 months. Avacopan may be considered as part of a strategy to reduce exposure to GC in granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Plasma exchange may be considered in patients with rapidly progressive glomerulonephritis. For remission maintenance of GPA/MPA, we recommend rituximab. In patients with relapsing or refractory eosinophilic GPA, we recommend the use of mepolizumab. Azathioprine and methotrexate are alternatives to biologics for remission maintenance in AAV. Conclusions: In the light of recent advancements, these recommendations provide updated guidance on AAV management. As substantial data gaps still exist, informed decision-making between physicians and patients remains of key relevance.Peer reviewe

Genome-wide association study of eosinophilic granulomatosis with polyangiitis reveals genomic loci stratified by ANCA status.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disease of unknown cause. 30% of patients have anti-neutrophil cytoplasmic antibodies (ANCA) specific for myeloperoxidase (MPO). Here, we describe a genome-wide association study in 676 EGPA cases and 6809 controls, that identifies 4 EGPA-associated loci through conventional case-control analysis, and 4 additional associations through a conditional false discovery rate approach. Many variants are also associated with asthma and six are associated with eosinophil count in the general population. Through Mendelian randomisation, we show that a primary tendency to eosinophilia contributes to EGPA susceptibility. Stratification by ANCA reveals that EGPA comprises two genetically and clinically distinct syndromes. MPO+ ANCA EGPA is an eosinophilic autoimmune disease sharing certain clinical features and an HLA-DQ association with MPO+ ANCA-associated vasculitis, while ANCA-negative EGPA may instead have a mucosal/barrier dysfunction origin. Four candidate genes are targets of therapies in development, supporting their exploration in EGPA

Genome-wide association study of eosinophilic granulomatosis with polyangiitis reveals genomic loci stratified by ANCA status

Abstract: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disease of unknown cause. 30% of patients have anti-neutrophil cytoplasmic antibodies (ANCA) specific for myeloperoxidase (MPO). Here, we describe a genome-wide association study in 676 EGPA cases and 6809 controls, that identifies 4 EGPA-associated loci through conventional case-control analysis, and 4 additional associations through a conditional false discovery rate approach. Many variants are also associated with asthma and six are associated with eosinophil count in the general population. Through Mendelian randomisation, we show that a primary tendency to eosinophilia contributes to EGPA susceptibility. Stratification by ANCA reveals that EGPA comprises two genetically and clinically distinct syndromes. MPO+ ANCA EGPA is an eosinophilic autoimmune disease sharing certain clinical features and an HLA-DQ association with MPO+ ANCA-associated vasculitis, while ANCA-negative EGPA may instead have a mucosal/barrier dysfunction origin. Four candidate genes are targets of therapies in development, supporting their exploration in EGPA

Value of anti-infective chemoprophylaxis in primary systemic vasculitis: what is the evidence?

Although infections are a major concern in patients with primary systemic vasculitis, actual knowledge about risk factors and evidence concerning the use of anti-infective prophylaxis from clinical trials are scarce. The use of high dose glucocorticoids and cyclophosphamide pose a definite risk for infections. Bacterial infections are among the most frequent causes of death, with Staphylococcus aureus being the most common isolate. Concerning viral infections, cytomegalovirus and varicella-zoster virus reactivation represent the most frequent complications. The only prophylactic measure that is widely accepted is trimethoprim/sulfamethoxazole to avoid Pneumocystis jiroveci pneumonia in small vessel vasculitis patients with generalised disease receiving therapy for induction of remission