HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS SECONDARY TO CYTOMEGALOVIRUS IN AN INFANT: A CASE REPORT
Keywords:
hemophagocytic lymphohistiocytosis; cytomegalovirus; infant; pancytopenia; HLH-2004 protocol; hyperinflammatory syndromeAbstract
DOI: https://doi.org/10.46296/yc.v10i18.0884
Abstract
Hemophagocytic lymphohistiocytosis is a life-threatening hyperinflammatory syndrome characterized by an exaggerated and uncontrolled activation of the immune system. We report the case of a 2-month-old male infant with no significant perinatal history, presenting with an 8-day history of persistent fever, gastrointestinal symptoms, pallor, and abdominal distension. Clinical and laboratory findings revealed pancytopenia, hepatosplenomegaly, hyperferritinemia (18,150 ng/mL), hypofibrinogenemia, and hypertransaminasemia. Bone marrow aspiration confirmed hemophagocytosis, fulfilling 6 of the 8 diagnostic criteria of the HLH-2004 protocol from the Histiocyte Society. CMV PCR/DNA in bone marrow was positive with a viral load of 10,084 copies/mL, establishing the diagnosis of HLH secondary to CMV infection. The patient received multidisciplinary management with the HLH-2004 protocol (dexamethasone 10 mg/m2/day, intravenous immunoglobulin) and valganciclovir (16 mg/kg/dose orally every 12 hours for 28 days). Complications included central venous catheter-related sepsis due to ESBL-producing Klebsiella pneumoniae and methicillin-sensitive Staphylococcus aureus, as well as transient arterial hypertension and renal hyperfiltration. After 34 days of hospitalization in pediatric intensive and intermediate care, the patient was discharged with favorable outcome, without recurrence of cytopenias and with progressive decline of inflammatory markers. This case underscores the importance of including HLH in the differential diagnosis of any infant with prolonged fever, pancytopenia, and hepatosplenomegaly, and highlights CMV as a relevant trigger in this age group.
Keywords: hemophagocytic lymphohistiocytosis; cytomegalovirus; infant; pancytopenia; HLH-2004 protocol; hyperinflammatory syndrome.
Downloads
References
Henter JI, Horne A, Aricó M, Egeler RM, Filipovich AH, Imashuku S, et al. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007;48(2):124–31. doi: 10.1002/pbc.21039
Ravelli A, Minoia F, Davì S, Horne A, Bovis F, Pistorio A, et al. 2016 Classification Criteria for Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis: A European League Against Rheumatism/American College of Rheumatology/Paediatric Rheumatology International Trials Organisation Collaborative Initiative. Ann Rheum Dis. 2016;75(3):481–9. doi: 10.1136/annrheumdis-2015-208982
Brisse E, Wouters CH, Matthys P. Hemophagocytic lymphohistiocytosis (HLH): A heterogeneous spectrum of cytokine-driven immune disorders. Cytokine Growth Factor Rev. 2015;26(3):263–80. doi: 10.1016/j.cytogfr.2014.10.001
Sieni E, Cetica V, Hackmann Y, Coniglio ML, Da Ros M, Ciambotti B, et al. Familial hemophagocytic lymphohistiocytosis: when rare diseases shed light on immune system functioning. Front Immunol. 2014;5:167. doi: 10.3389/fimmu.2014.00167
Bode SF, Lehmberg K, Maul-Pavicic A, Vraetz T, Janka G, Stadt UZ, et al. Recent advances in the diagnosis and treatment of hemophagocytic lymphohistiocytosis. Arthritis Res Ther. 2012;14(3):213. doi: 10.1186/ar3843
Cascio A, Pernice LM, Barberi G, Delfino D, Biondo C, Beninati C, et al. Secondary hemophagocytic lymphohistiocytosis in zoonoses. A systematic review. Eur Rev Med Pharmacol Sci. 2012;16(10):1324–37.
Huang DB, Wu JJ, Hamill RJ. Reactive hemophagocytosis associated with the initiation of highly active antiretroviral therapy (HAART) in a patient with AIDS. Scand J Infect Dis. 2004;36(6–7):516–9. doi: 10.1080/00365540410020532
Histiocyte Society. HLH-2004: Treatment Protocol of the Second International HLH Study. Histiocyte Society; 2004. Disponible en: https://www.histiocytesociety.org
Lehmberg K, Nichols KE, Henter JI, Bhatt S, DeLaat C, Krentz A, et al. Consensus recommendations for the diagnosis and management of hemophagocytic lymphohistiocytosis associated with malignancies. Haematologica. 2015;100(8):997–1004. doi: 10.3324/haematol.2015.123562
Marsh RA, Allen CE, McClain KL, Weinstein JL, Kanter J, Skiles J, et al. Salvage therapy of refractory hemophagocytic lymphohistiocytosis with alemtuzumab. Pediatr Blood Cancer. 2013;60(1):101–9. doi: 10.1002/pbc.24188
Larroche C. Hemophagocytic lymphohistiocytosis in adults: diagnosis and treatment. Joint Bone Spine. 2012;79(4):356–61. doi: 10.1016/j.jbspin.2011.10.015
Fisman DN. Hemophagocytic syndromes and infection. Emerg Infect Dis. 2000;6(6):601–8. doi: 10.3201/eid0606.000608
Allen CE, Yu X, Kozinetz CA, McClain KL. Highly elevated ferritin levels and the diagnosis of hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2008;50(6):1227–35. doi: 10.1002/pbc.21423
Filipovich A, McClain K, Grom A. Histiocytic disorders: recent insights into pathophysiology and practical guidelines. Biol Blood Marrow Transplant. 2010;16(1 Suppl):S82–9. doi: 10.1016/j.bbmt.2009.11.014
Lazzarotto T, Guerra B, Lanari M, Gabrielli L, Landini MP. New advances in the diagnosis of congenital cytomegalovirus infection. J Clin Virol. 2008;41(3):192–7. doi: 10.1016/j.jcv.2007.10.015
Imashuku S. Advances in the management of hemophagocytic lymphohistiocytosis. Expert Opin Orphan Drugs. 2016;4(8):869–79. doi: 10.1080/21678707.2016.1196834
Kimberlin DW, Jester PM, Sánchez PJ, Ahmed A, Arav-Boger R, Michaels MG, et al.; National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. Valganciclovir for symptomatic congenital cytomegalovirus disease. N Engl J Med. 2015;372(10):933–43. doi: 10.1056/NEJMoa1404599
Kadambari S, Williams EJ, Luck S, Griffiths PD, Sharland M. Evidence based management guidelines for the detection and treatment of congenital CMV. Early Hum Dev. 2011;87(11):723–8. doi: 10.1016/j.earlhumdev.2011.08.021
Rajasekaran S, Kruse K, Kovey K, Davis AT, Hassan NE, Ndika AN, et al. Therapeutic role of anakinra, an interleukin-1 receptor antagonist, in the management of secondary hemophagocytic lymphohistiocytosis/sepsis/multiple organ dysfunction/macrophage activating syndrome in critically ill children. Pediatr Crit Care Med. 2014;15(5):401–8. doi: 10.1097/PCC.0000000000000078
Bousfiha A, Jeddane L, Picard C, Al-Herz W, Ailal F, Chatila T, et al. Human Inborn Errors of Immunity: 2019 Update of the IUIS Phenotypical Classification. J Clin Immunol. 2020;40(1):66–81. doi: 10.1007/s10875-020-00758-x
Fowler KB, Boppana SB. Congenital cytomegalovirus infection. Semin Perinatol. 2018;42(3):149–54. doi: 10.1053/j.semperi.2018.02.002
Published
How to Cite
License
Copyright (c) 2026 REVISTA CIENTÍFICA MULTIDISCIPLINARIA ARBITRADA YACHASUN - ISSN: 2697-3456
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
