Rituximab rechallenge caused severe hypersensitivity reaction in a patient with membranous nephropathy

BackgroundRituximab, an anti-CD20 monoclonal antibody, is an established treatment for primary membranous nephropathy (PMN). While generally well-tolerated, its recognized adverse effects include infusion-related reactions and immediate hypersensitivity. Particularly severe manifestations occurring >24 h post-infusion remain rarely reported.Case PresentationA 52-year-old male with a 7-year history of biopsy-proven PMN achieved complete remission after two uneventful courses of rituximab (1 g each) in 2018. He presented in August 2025 with nephrotic syndrome relapse. A third 1 g rituximab infusion was administered without immediate complications. Approximately 24 h post-infusion, he developed generalized urticaria, fever (38 °C), dysphagia, and arthralgia, progressing to hypotension (95/55 mmHg). Examination revealed diffuse, evanescent wheals. Laboratory findings showed elevated C-reactive protein, eosinophilia, and immunoglobulin E. Esophageal CT indicated localized wall edema, while infection was excluded. A diagnosis of severe hypersensitivity reaction (anaphylactic shock, acute urticaria, and angioedema) was made, consistent with Brown grade IV severity. He responded rapidly to intravenous methylprednisolone, antihistamines, and supportive care.ConclusionThis report highlights the potential for life-threatening hypersensitivity upon rituximab re-challenge, even with a remote history of uneventful use. It emphasizes the need for prolonged post-infusion observation, patient education regarding delayed symptoms, and preparedness for immediate management of severe allergic phenomena. Further studies are warranted to elucidate risk factors and mechanisms underlying these rare but serious events.