INTRODUCTION: Immunoglobulin G4-related disease (IgG4-RD) is a systemic, immune-mediated disorder marked by the infiltration of IgG4-positive plasma cells and fibrosis in affected organs. This report presents a rare case of a patient with isolated nodular scleritis as an IgG4-RD (in a more precise way antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis [AAV] and IgG4-RD overlap syndrome). CASE PRESENTATION: A 51-year-old woman was referred with the presumed diagnosis of conjunctival lymphoma due to a painful, salmon-colored lesion in the superior conjunctiva of the right eye. A biopsy of the conjunctiva showed a lymphoplasmacytic infiltrate with multiple IgG4-positive cells (>
200 cells/high power field), elevated IgG4/IgG ratio of 66% and fibrotic tissue without obvious vasculitis, confirming the diagnosis of IgG4-related disease (IgG4-RD). ANCAs directly against myeloperoxidase were also positive, suggesting AAV. Given that the clinical signs align with both disease entities, it was concluded that the case fits in its restricted sense the newly described overlap syndrome. The scleritis was successfully treated with a tapering dose of corticosteroids and rituximab. CONCLUSION: This case illustrates a rare presentation of scleritis as an IgG4-RD (in a more precise way AAV and IgG4-RD overlap syndrome) and demonstrates that rituximab and low dose of corticosteroids can lead to remission.