Case Report Acute Cytomegalovirus Illness in an Immunocompetent Adult Causing Intravascular Hemolysis and Suspected Hemophagocytic Lymphohistiocytosis Ross P. Elliott, 1 Brian P. Freeman, 2 Jeffery L. Meier , 3,4 and Rima El-Herte 5 1 Internal Medicine Residency Program, MercyOne Medical Center and Clinics, Des Moines, IA 50314, USA 2 Mission Cancer and Blood, Des Moines, IA 50309, USA 3 Iowa City Veterans Affairs Health Care System, Iowa City, IA 52246, USA 4 Division of Infectious Diseases, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA 5 Division of Infectious Diseases, Department of Medicine, Creighton, University School of Medicine and CHI Health, Omaha, NE 68124, USA Correspondence should be addressed to Rima El-Herte; rimael-herte@creighton.edu Received 14 February 2022; Accepted 15 June 2022; Published 8 July 2022 Academic Editor: Zarrin Basharat Copyright © 2022 Ross P. Elliott et al. is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. Primary cytomegalovirus (CMV) infection of the immunocompetent host usually produces little-to-no illness. Occasionally, the infection results in mononucleosis syndrome, protracted fever, hepatitis, tissue-invasive disease, or Guillain-Barr´esyndrome. Hemolytic anemia and hemophagocytic lymphohistiocytosis (HLH) are rare complications that have not been reported to co-occur. Having hemolytic anemia in conjunction with more common findings of fever and hepatitis complicates the diagnosis of HLH. Case Presentation. A 34-year-old male with previously good health presented with a prolonged febrile illness, jaundice, and anemia. An extensive work-up during hospitalization revealed intravascular hemolytic anemia, leukopenia, hepatosplenomegaly, and biopsy evidence of extensive lymphohistiocytic infiltration of the liver with microgranulomata and sinusoidal hemophagocytosis. Soluble CD25 level was mildly elevated at 1200.3 pg/mL and the HScore calculation (fever, bicytopenia, hepatosplenomegaly, aspartate aminotransaminase 99 IU/L, ferritin 1570 ng/mL, fibrinogen 488 mg/dL, and triglycerides 173 mg/dL) suggested a moderate probability of reactive HLH. Primary CMV infection was diagnosed based on CMV IgM positivity, low CMV IgG avidity index, and low-grade CMV DNAemia. e CMV antigen was not detected in the liver biopsy, and the bone marrow biopsy was unremarkable. e illness began to improve before he received oral valganciclovir for 5 days, and he was in good health 10 months later. Conclusion. Acute CMV illness in an immunocompetent adult can present with hemolytic anemia and clinicopathologic abnormalities consistent with a form fruste of HLH. e illness is likely due to an excessive or unbalanced immune response that may self-correct. 1. Introduction Human cytomegalovirus (CMV) causes debilitating or fatal diseases in people with immature or profoundly defective cellular immune systems. CMV disease of this severity is rarely encountered in people without these immune system abnormalities. While CMV is the most common cause of the heterophile antibody-negative mono syndrome in adolescents and adults, most CMV infections go unnoticed in immunocompetent people. Occasionally, the first epi- sode of CMV infection in an immunocompetent person causes a self-limited prolonged febrile or atypical monolike illness that is usually accompanied by liver test abnor- malities signifying hepatitis [1]. Rarely does the infection progress to a tissue invasive disease that involves the gastrointestinal tract, lung, eye, or other organs [2]. e Hindawi Case Reports in Infectious Diseases Volume 2022, Article ID 7949471, 7 pages https://doi.org/10.1155/2022/7949471