Epstein–Barr Virus Reactivation as a Potential Underlying Contributor to Atypical Features of Microscopic Polyangiitis

Abstract Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a small-vessel vasculitis that damages systemic organs; however, its pathogenesis remains unclear. Epstein–Barr virus (EBV) reactivation has been associated with lymphoproliferative disorders and autoimmune diseases, though its association with AAV is rarely reported. Here, we report a 75-year-old man who presented with fever, muscle stiffness, and limb paresthesia. Laboratory tests revealed eosinophilia and positive myeloperoxidase-ANCA, whereas positron emission tomography–computed tomography demonstrated increased splenic fluorodeoxyglucose uptake. Renal biopsy revealed pauci-immune glomerulonephritis with prominent plasmacytic infiltration, and in situ hybridization confirmed EBV-encoded RNA positivity in infiltrating B cells. The patient was diagnosed with AAV complicated by EBV reactivation. Prednisolone therapy achieved initial improvement, but proteinuria persisted during tapering. Furthermore, we reviewed previously reported cases of small-vessel vasculitis associated with EBV reactivation, most of which occurred in elderly men and presented with glomerulonephritis and atypical features, including plasmacytosis or lymphadenopathy. This case and literature review reveal a potential association between AAV and EBV reactivation. Importantly, clinicians should actively consider EBV reactivation as an underlying contributor and should consider testing circulating EBV-DNA and tissue biopsy with EBV-encoded small ribonucleic acid staining in AAV cases with atypical features, including lymphadenopathy, splenomegaly, plasmacytic infiltration, and eosinophilia