A nearly fatal primary Epstein-Barr virus infection associated with low NK-cell counts in a patient receiving azathioprine : a case report and review of literature

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Honkila , M , Niinimaki , R , Taskinen , M , Kuismin , O , Kettunen , K , Saarela , J , Turunen , S , Renko , M & Tapiainen , T 2019 , ' A nearly fatal primary Epstein-Barr virus infection associated with low NK-cell counts in a patient receiving azathioprine : a case report and review of literature ' , BMC Infectious Diseases , vol. 19 , 404 . https://doi.org/10.1186/s12879-019-4022-3

Title: A nearly fatal primary Epstein-Barr virus infection associated with low NK-cell counts in a patient receiving azathioprine : a case report and review of literature
Author: Honkila, Minna; Niinimaki, Riitta; Taskinen, Mervi; Kuismin, Outi; Kettunen, Kaisa; Saarela, Janna; Turunen, Sami; Renko, Marjo; Tapiainen, Terhi
Contributor: University of Helsinki, Lastentautien yksikkö
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Janna Saarela / Principal Investigator
Date: 2019-05-10
Language: eng
Number of pages: 5
Belongs to series: BMC Infectious Diseases
ISSN: 1471-2334
URI: http://hdl.handle.net/10138/303539
Abstract: BackgroundSymptomatic primary Epstein-Barr virus infection is a usually self-limiting illness in adolescents. We present a case of an adolescent who had been receiving azathioprine for inflammatory bowel disease for four years and developed a life-threatening primary Epstein-Barr virus infection successfully treated with rituximab.Case presentationAn 11-year-old girl presented with chronic, bloody diarrhea. Endoscopic biopsies confirmed a diagnosis of chronic ulcerative colitis with features of Crohn's disease. Azathioprine was initiated after one year due to active colitis. She responded well and remission was achieved. At the age of 16years she developed a life-threatening Epstein-Barr virus infection including severe multiple organ failure and was critically ill for 4weeks in the intensive care unit. Natural killer cells were virtually absent in the lymphocyte subset analysis. Azathioprine was stopped on admission. She was initially treated with corticosteroids, acyclovir and intravenous immunoglobulin. Approximately 30days after admission, she developed signs of severe hepatitis and pneumonitis and received weekly rituximab infusions for 8weeks. Primary immunodeficiency was excluded by whole exome sequencing in two independent laboratories. Persistent viremia stopped when the natural killer cell count started to rise, approximately 90days after the cessation of azathioprine.ConclusionsWe found 17 comparable cases in the literature. None of the previous cases reported in the literature, who had been treated with azathioprine and developed either a severe or a fatal Epstein-Barr virus infection, underwent full genetic and prospective immunological workup to rule out known primary immunodeficiencies. Recently, azathioprine has been shown to cause rather specific immunosuppression, resulting in natural killer cell depletion. Our case demonstrates that slow recovery from azathioprine-induced natural killer cell depletion, 3months after the stopping of azathioprine, coincided with the clearance of viremia and clinical recovery. Finally, our choice of treating the patient with rituximab, as previously used for patients with a severe immunosuppression and Epstein-Barr virus viremia, appeared to be successful in this case. We suggest testing for Epstein-Barr virus serology before starting azathioprine and measuring natural killer cell counts during the treatment to identify patients at risk of developing an unusually severe primary Epstein-Barr virus infection.
Subject: Epstein-Barr virus infections
Azathioprine
Killer cells
natural
Whole exome sequencing
Rituximab
NATURAL-KILLER-CELLS
CROHNS-DISEASE PATIENT
LYMPHOPROLIFERATIVE DISORDER
HEMOPHAGOCYTIC SYNDROME
THIOPURINE TREATMENT
MONONUCLEOSIS
THERAPY
3121 General medicine, internal medicine and other clinical medicine
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