An overlap of antineutrophil cytoplasmic antibody-associated vasculitis and IgG4-related disease: distinct clinicopathologic clues for precise diagnosis

Abstract Background: Both antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and IgG4-related disease (IgG4-RD) are multi-system inflammatory disorders. The coexistent of both diseases present the possibility of a new overlap syndrome which leads to different treatment and outcome. In this study, we aim to investigate the possibility and clinicopathologic clues to the diagnosis of this overlap syndrome.Methods: A case of a 67-year-old man in our hospital who exhibited the clinicopathologic characteristics of both AAV and IgG4-RD was presented. The serial alterations in serum parameters and treatment response of the case were followed up for the next 15 months. Then, a systematic literature review of the overlap syndrome was performed on PUBMED database from 1976 until January 2020.Results: Forty-two patients fully met both AAV and IgG4-RD criteria in the literature. The median age was 60 years ranged from 31 to 73 years at diagnosis. Twenty-eight (66.7%) patients were men. Serum IgG4 concentration increased in 41 (97.6%) patients (median:395 mg/dl; range:177-876mg/dl). Forty-one patients (97.6%) tested positive for ANCA with 37 (90.2%) patients showing a specificity for MPO. Kidney histology of 23 (69.7%) patients presented pauci-immune necrotizing or crescentic glomerulonephritis and IgG4-related tubulointerstitial nephritis. Glucocorticoids combined with cyclophosphamide therapy was commonly prescribed with a high remission rate within 3 months. Four common clinicopathologic features of the overlap syndrome were identified from the case and literature.Conclusion: AAV may overlap with IgG4-RD while presenting atypical manifestations. Four common clinicopathologic characteristics could be used as specific clues to the diagnosis of overlap syndrome.