{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T07:02:26Z","timestamp":1780038146531,"version":"3.53.1"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Rituximab, 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 &amp;gt;24\u00a0h post-infusion remain rarely reported.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case Presentation<\/jats:title>\n                    <jats:p>A 52-year-old male with a 7-year history of biopsy-proven PMN achieved complete remission after two uneventful courses of rituximab (1\u00a0g each) in 2018. He presented in August 2025 with nephrotic syndrome relapse. A third 1\u00a0g rituximab infusion was administered without immediate complications. Approximately 24\u00a0h post-infusion, he developed generalized urticaria, fever (38\u00a0\u00b0C), dysphagia, and arthralgia, progressing to hypotension (95\/55\u00a0mmHg). 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This 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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1788362","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T06:11:01Z","timestamp":1780035061000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Severe anaphylactic shock reaction upon rituximab rechallenge in membranous nephropathy: a case report and literature review"],"prefix":"10.3389","volume":"17","author":[{"given":"Weidong","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Nephrology, The Fifth Affiliated Hospital of Wenzhou Medical University","place":["Lishui, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pathology,The Fifth Affiliated Hospital of Wenzhou Medical University","place":["Lishui, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"XiaoXiao","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The Fifth Affiliated Hospital of Wenzhou Medical University","place":["Lishui, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiankun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The Fifth Affiliated Hospital of Wenzhou Medical University","place":["Lishui, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingyan","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Medicine, Liandu District Baiyun Street Community Health Service Center","place":["Lishui, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhui","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, The Fifth Affiliated Hospital of Wenzhou Medical University","place":["Lishui, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1159\/000454808","article-title":"Rapid drug desensitization with biologics: a single-center experience with four biologics","volume":"171","author":"Bavbek","year":"2016","journal-title":"Int. Archives Allergy Immunology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.ejim.2019.06.009","article-title":"Rituximab-induced serum sickness is more frequent in autoimmune diseases as compared to hematological malignancies: a French nationwide study","volume":"67","author":"Bayer","year":"2019","journal-title":"Eur. J. Intern Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1792673","DOI":"10.1080\/19420862.2020.1792673","article-title":"Bivalent binding on cells varies between anti-CD20 antibodies and is dose-dependent","volume":"12","author":"Bondza","year":"2020","journal-title":"mAbs"},{"key":"B4","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1016\/j.jaci.2004.04.029","article-title":"Clinical features and severity grading of anaphylaxis","volume":"114","author":"Brown","year":"2004","journal-title":"J. Allergy Clin. Immunol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1177\/1060028018803587","article-title":"Rituximab exhibits altered pharmacokinetics in patients with membranous nephropathy","volume":"53","author":"Fogueri","year":"2018","journal-title":"Ann. Pharmacother."},{"key":"B6","doi-asserted-by":"publisher","first-page":"572863","DOI":"10.3389\/fphar.2020.572863","article-title":"Rituximab hypersensitivity: from clinical presentation to management","volume":"11","author":"Fouda","year":"2020","journal-title":"Front. Pharmacol."},{"key":"B7","first-page":"1825","article-title":"Clinical significance of autoantibodies in the assessment and treatment of idiopathic membranous nephropathy","volume-title":"Exp. Ther. Med.","author":"Han","year":"2019"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1546465","DOI":"10.3389\/fphar.2025.1546465","article-title":"Effect of hypoalbuminemia on drug pharmacokinetics","volume":"16","author":"Idasiak-Piechocka","year":"2025","journal-title":"Front. Pharmacol."},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2018.02.018","article-title":"Hypersensitivity reactions to therapeutic monoclonal antibodies: phenotypes and endotypes","volume":"142","author":"Isabwe","year":"2018","journal-title":"J. Allergy Clin. Immunol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.anai.2016.05.013","article-title":"Hypersensitivity and immunologic reactions to biologics: opportunities for the allergist","volume":"117","author":"Khan","year":"2016","journal-title":"Am. Coll. Allergy, Asthma, & Immunol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.jfma.2014.11.002","article-title":"Membranous nephropathy: a review on the pathogenesis, diagnosis, and treatment","volume":"114","author":"Lai","year":"2015","journal-title":"J. Formos. Med. Assoc. = Taiwan Yi Zhi"},{"key":"B12","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1016\/j.therap.2022.10.065","article-title":"Adverse effect of Pneumocystis Jirovecii infection associated with rituximab therapy for autoimmune disease are more frequently reported in older vs. younger patient","volume":"78","author":"Lemoine","year":"2023","journal-title":"Therapies"},{"key":"B13","doi-asserted-by":"publisher","first-page":"952235","DOI":"10.3389\/fimmu.2022.952235","article-title":"The alternative pathway is necessary and sufficient for complement activation by Anti-THSD7A autoantibodies, which are predominantly IgG4 in membranous nephropathy","volume":"13","author":"Manral","year":"2022","journal-title":"Front. Immunology"},{"key":"B14","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1177\/1060028020942485","article-title":"Tolerability of highly protein bound targeted oral oncolytic drugs in patients with hypoalbuminemia: a retrospective analysis","volume":"55","author":"Murdock","year":"2020","journal-title":"Ann. Pharmacother."},{"key":"B15","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1007\/s13730-020-00449-x","article-title":"Rituximab-induced serum sickness in a 6-year-old boy with steroid-dependent nephrotic syndrome","volume":"9","author":"Nakamura","year":"2020","journal-title":"Cen. Case Reports"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1326","DOI":"10.3389\/fimmu.2019.01326","article-title":"Membranous Nephropathy (MN) recurrence after renal transplantation","volume":"10","author":"Passerini","year":"2019","journal-title":"Front. Immunology"},{"key":"B17","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1016\/j.iac.2017.01.012","article-title":"Adverse reactions to biologic therapy","volume":"37","author":"Patel","year":"2017","journal-title":"Immunol. Allergy Clin. N. Am."},{"key":"B18","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1097\/MPG.0000000000001653","article-title":"Post-transplant recurrent bile salt export pump disease: a form of antibody-mediated graft dysfunction and utilization of C4d","volume":"65","author":"Patel","year":"2017","journal-title":"J. Pediatric Gastroenterology Nutrition"},{"key":"B19","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1080\/1744666X.2019.1562905","article-title":"Infusion-related reactions to rituximab: frequency, mechanisms and predictors","volume":"15","author":"Paul","year":"2019","journal-title":"Expert Review Clinical Immunology"},{"key":"B20","doi-asserted-by":"publisher","first-page":"912","DOI":"10.1111\/j.1398-9995.2006.01058.x","article-title":"Adverse side\u2010effects to biological agents","volume":"61","author":"Pichler","year":"2006","journal-title":"Allergy"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2023.08.010","article-title":"Ofatumumab in rituximab-resistant and rituximab-intolerant patients with primary membranous nephropathy: a case series","volume":"83","author":"Podest\u00e0","year":"2024","journal-title":"Am. J. Kidney Dis."},{"key":"B22","doi-asserted-by":"publisher","first-page":"761","DOI":"10.3390\/jcm14030761","article-title":"Membranous nephropathy","volume":"14","author":"Ponticelli","year":"2025","journal-title":"J. Clin. Med."},{"key":"B23","doi-asserted-by":"publisher","first-page":"831","DOI":"10.2174\/1389203721666200511094717","article-title":"Protein and antibody engineering: suppressing degranulation of the mast cells and type I hypersensitivity reaction","volume":"21","author":"Rajani","year":"2020","journal-title":"Curr. Protein & Peptide Sci."},{"key":"B24","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1111\/jcpt.12522","article-title":"Anterior ST-elevation myocardial infarction induced by rituximab infusion: a case report and review of the literature","volume":"42","author":"Sharif","year":"2017","journal-title":"J. Clin. Pharm. Ther."},{"key":"B25","doi-asserted-by":"publisher","first-page":"OP2500275","DOI":"10.1200\/OP-25-00275","article-title":"Beyond infusion: real-world insights into infusion-related reactions in monoclonal antibody therapy","author":"Smolders","year":"2025","journal-title":"JCO Oncol. Pract"},{"key":"B26","doi-asserted-by":"publisher","first-page":"47","DOI":"10.4103\/1319-2442.148733","article-title":"Rituximab as a rescue therapy in patients with glomerulonephritis. Saudi journal of kidney diseases and transplantation: an official publication of the Saudi center for organ transplantation, Saudi Arabia","volume":"26","author":"Souqiyyeh","year":"2015","journal-title":"Saudi J. Kidney Dis. Transpl."},{"key":"B27","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1159\/000371587","article-title":"Single-dose rituximab for recurrent glomerulonephritis post-renal transplant","volume":"41","author":"Spinner","year":"2015","journal-title":"Am. Journal Nephrology"},{"key":"B28","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1007\/s00467-016-3498-y","article-title":"Ofatumumab in two pediatric nephrotic syndrome patients allergic to rituximab","volume":"32","author":"Vivarelli","year":"2017","journal-title":"Pediatr. Nephrology Berl. Ger."},{"key":"B29","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1177\/1078155220948596","article-title":"Rituximab desensitization in pediatric acute lymphoblastic leukemia with severe anaphylaxis","volume":"27","author":"Villarreal-Gonz\u00e1lez","year":"2021","journal-title":"J Oncol. Pharm. Pract"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1788362\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T06:11:02Z","timestamp":1780035062000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1788362\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,29]]},"references-count":29,"alternative-id":["10.3389\/fphar.2026.1788362"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1788362","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,29]]},"article-number":"1788362"}}