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EBV reactivation is classically associated with infectious mononucleosis and Burkitt lymphoma and rarely associated with cold agglutinin syndrome. Here, we describe a case of minimal change nephrotic syndrome complicated by cold agglutinin syndrome secondary to EBV reactivation in the setting of human immunodeficiency virus (HIV) infection and corticosteroid-induced immunosuppression. A 63-year-old man with well-controlled HIV infection owing to antiretroviral therapy was admitted for nephrotic syndrome. He was treated with prednisolone (80\u00a0mg\/day), and renal biopsy performed on day 9 confirmed minimal change nephrotic syndrome. Complete remission was achieved by day 18; however, the patient subsequently developed hyperbilirubinemia, elevated transaminase and lactate dehydrogenase levels, progressive anemia, and thrombocytopenia, accompanied by pharyngitis, malaise, and fever. Laboratory investigations revealed a positive cold agglutinin test, positive direct Coombs test, reduced haptoglobin level, and positive urine urobilinogen, consistent with cold agglutinin syndrome. CMV reactivation was also suggested by transient CMV antigenemia positivity, although no organ-invasive CMV disease was evident. Although EBV serology indicated a past infection, the EBV DNA load was elevated, which suggested viral reactivation. The patient responded to supportive measures, along with early tapering of the corticosteroid dose to reduce immunosuppression. This case highlights that HIV infection in combination with corticosteroid therapy may create an immunosuppressive milieu, predisposing patients to EBV reactivation and subsequent development of cold agglutinin syndrome. Clinicians should be vigilant for EBV-related complications in patients with minimal change nephrotic syndrome requiring corticosteroid therapy, particularly in those with underlying HIV infection.<\/jats:p>","DOI":"10.1007\/s13730-026-01145-y","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T05:10:11Z","timestamp":1782105011000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Cold agglutinin syndrome secondary to Epstein\u2013Barr virus reactivation during corticosteroid therapy for minimal change nephrotic syndrome in a patient with human immunodeficiency virus infection"],"prefix":"10.1007","volume":"15","author":[{"given":"Harui","family":"Bamba","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1395-2644","authenticated-orcid":false,"given":"Daisuke","family":"Katagiri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiki","family":"Shimada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitomi","family":"Otani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoto","family":"Eriguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuri","family":"Katayama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikako","family":"Koizumi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minami","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Takano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,22]]},"reference":[{"issue":"7","key":"1145_CR1","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1056\/nejm200008173430707","volume":"343","author":"JI Cohen","year":"2000","unstructured":"Cohen JI. 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This study was partially supported by grants from the Japan Society for the Promotion of Science (# 26K11175) and the Ministry of Health, Labour and Welfare(# 24IA2401).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This study was deemed to be outside the scope of the Ethical Guidelines for Medical and Biological Research Involving Human Subjects in Japan and was therefore judged by the Ethics Review Committee of the Japan Institute for Health Security to be exempt from ethical review.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Informed consent was obtained from the patient included in the study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}],"article-number":"102"}}