{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:34:10Z","timestamp":1760060050045,"version":"build-2065373602"},"reference-count":78,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T00:00:00Z","timestamp":1754265600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Reports"],"abstract":"<jats:p>Background and Clinical Significance: Hemophagocytic lymphohistiocytosis (HLH) and autoimmune hemolytic anemia (AIHA) are both life-threatening hematologic syndromes that rarely present together outside of malignancy. Advanced acquired immunodeficiency syndrome (AIDS) creates a milieu of profound immune dysregulation and hyperinflammation, predisposing patients to atypical overlaps of these disorders. Case Presentation: A 30-year-old woman with poorly controlled AIDS presented with three weeks of jaundice, fever, and fatigue. Initial labs revealed pancytopenia, hyperbilirubinemia, and elevated ferritin level. Direct anti-globulin testing confirmed warm AIHA (IgG+\/C3d+) with transient cold agglutinins. Despite intravenous immunoglobulin (IVIG), rituximab, and transfusions, she developed hepatosplenomegaly, extreme hyperferritinemia, and sIL-2R &gt; 10,000 pg\/mL, meeting HLH-2004 criteria. Bone marrow biopsy excluded malignancy; further work-up revealed Epstein\u2013Barr virus (EBV) viremia and cytomegalovirus (CMV) reactivation. Dexamethasone plus reduced-dose etoposide transiently reduced soluble interleukin-2 receptor (sIL-2R) but precipitated profound pancytopenia, Acute respiratory distress syndrome (ARDS) from CMV\/parainfluenza pneumonia, bilateral deep vein thrombosis (DVT), and an ST-elevation myocardial infarction (STEMI). She ultimately died of hemorrhagic shock after anticoagulation despite maximal supportive measures. Conclusions: This case underscores the diagnostic challenges of HLH-AIHA overlap in AIDS, where cytopenias and hyperferritinemia mask the underlying cytokine storm. Pathogenesis likely involved IL-6\/IFN-\u03b3 overproduction, impaired cytotoxic T-cell function, and molecular mimicry. While etoposide remains a cornerstone of HLH therapy, its myelotoxicity proved catastrophic in this immunocompromised host, highlighting the urgent need for cytokine-targeted agents to mitigate treatment-related mortality.<\/jats:p>","DOI":"10.3390\/reports8030137","type":"journal-article","created":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T09:41:17Z","timestamp":1754300477000},"page":"137","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fatal Cytokine Collision: HLH\u2013AIHA in Advanced AIDS\u2014Case Report and Literature Review"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-4043-7518","authenticated-orcid":false,"given":"Xiaoyi","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2402-4301","authenticated-orcid":false,"given":"Maria Felix","family":"Torres Nolasco","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wing Fai","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1586-2706","authenticated-orcid":false,"given":"Toru","family":"Yoshino","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manasa","family":"Anipindi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1056\/NEJMra2033982","article-title":"Autoimmune Hemolytic Anemias","volume":"385","author":"Berentsen","year":"2021","journal-title":"N. 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