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Limited Utility of Serology and Heterophile Test in the Early Diagnosis of Epstein–Barr Virus Mononucleosis in a Child after Renal Transplantation

Background: Epstein–Barr virus (EBV) infection is associated with significant morbidity and mortality in renal transplant (RT) recipients. The spectrum of illness ranges from infectious mononucleosis (IM) to post-transplant lymphoproliferative disorder (PTLD). In association with clinical signs and...

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Autores principales: Byrne, Alexandra, Bush, Rachel, Johns, Felicia, Upadhyay, Kiran
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235840/
https://www.ncbi.nlm.nih.gov/pubmed/32331303
http://dx.doi.org/10.3390/medicines7040021
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author Byrne, Alexandra
Bush, Rachel
Johns, Felicia
Upadhyay, Kiran
author_facet Byrne, Alexandra
Bush, Rachel
Johns, Felicia
Upadhyay, Kiran
author_sort Byrne, Alexandra
collection PubMed
description Background: Epstein–Barr virus (EBV) infection is associated with significant morbidity and mortality in renal transplant (RT) recipients. The spectrum of illness ranges from infectious mononucleosis (IM) to post-transplant lymphoproliferative disorder (PTLD). In association with clinical signs and symptoms, virus-specific serology and heterophile antibody tests are widely used in confirming the diagnosis of IM in the general population. However, these tests may have a limited role in immunosuppressed RT recipients from seropositive donor, especially in children who were EBV-seronegative prior to the transplant. The aim of this study is to evaluate the utility of these tests in the early diagnosis of IM in this subset of patients. Methods: This is a case study with a review of literature. Results: Here, we present a 14-year-old male with hemophilia B who presented with fever, fatigue, sore throat, palatal petechial rash, exudative tonsillitis and cervical lymphadenopathy 3 months post-RT. He was EBV seronegative prior to RT and received a deceased donor kidney transplant from a seropositive donor. Induction was done with Thymoglobulin and maintenance immunosuppression consisted of tacrolimus and mycophenolate. Initial heterophile antibody test (monospot) was negative, but became positive at 5 months and remained positive at 9 months follow-up post-RT. EBV viral capsid antigens (VCA) IgM and IgG, early antigen (EA) and nuclear antigen (EBNA) were all negative at the time of presentation. VCA IgM and IgG both became positive at 5 months and peaked at 9 months follow-up, however the EA and EBNA remained negative. EBV viral load as measured by polymerase chain reaction (PCR) was negative for the first 3 months post-RT but became positive at presentation, peaked at 6 months and started declining thereafter. Peripheral blood smear examination showed no absolute and atypical lymphocytosis. Cytomegalovirus PCR in the blood and throat culture for streptococcus were negative. There was no splenomegaly. He was managed conservatively with intravenous fluids, bed rest, antipyretics and reduction of immunosuppression. Conclusions: EBV serological markers have a limited role in the early diagnosis of EBV-IM following RT in prior seronegative children. Initial heterophile antibody test may also be negative, and hence a repeat test may be necessary. Once becoming positive, the VCA IgM may remain persistently elevated for prolonged duration. In addition to the suppressed cellular immunity secondary to immunosuppression, humoral response to viral infections is also delayed in transplant recipients, especially in the early transplant period. Hence, routine monitoring with PCR is superior to serology in diagnosing IM early and monitoring the EBV infection post-RT for timely evaluation and management.
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spelling pubmed-72358402020-05-22 Limited Utility of Serology and Heterophile Test in the Early Diagnosis of Epstein–Barr Virus Mononucleosis in a Child after Renal Transplantation Byrne, Alexandra Bush, Rachel Johns, Felicia Upadhyay, Kiran Medicines (Basel) Case Report Background: Epstein–Barr virus (EBV) infection is associated with significant morbidity and mortality in renal transplant (RT) recipients. The spectrum of illness ranges from infectious mononucleosis (IM) to post-transplant lymphoproliferative disorder (PTLD). In association with clinical signs and symptoms, virus-specific serology and heterophile antibody tests are widely used in confirming the diagnosis of IM in the general population. However, these tests may have a limited role in immunosuppressed RT recipients from seropositive donor, especially in children who were EBV-seronegative prior to the transplant. The aim of this study is to evaluate the utility of these tests in the early diagnosis of IM in this subset of patients. Methods: This is a case study with a review of literature. Results: Here, we present a 14-year-old male with hemophilia B who presented with fever, fatigue, sore throat, palatal petechial rash, exudative tonsillitis and cervical lymphadenopathy 3 months post-RT. He was EBV seronegative prior to RT and received a deceased donor kidney transplant from a seropositive donor. Induction was done with Thymoglobulin and maintenance immunosuppression consisted of tacrolimus and mycophenolate. Initial heterophile antibody test (monospot) was negative, but became positive at 5 months and remained positive at 9 months follow-up post-RT. EBV viral capsid antigens (VCA) IgM and IgG, early antigen (EA) and nuclear antigen (EBNA) were all negative at the time of presentation. VCA IgM and IgG both became positive at 5 months and peaked at 9 months follow-up, however the EA and EBNA remained negative. EBV viral load as measured by polymerase chain reaction (PCR) was negative for the first 3 months post-RT but became positive at presentation, peaked at 6 months and started declining thereafter. Peripheral blood smear examination showed no absolute and atypical lymphocytosis. Cytomegalovirus PCR in the blood and throat culture for streptococcus were negative. There was no splenomegaly. He was managed conservatively with intravenous fluids, bed rest, antipyretics and reduction of immunosuppression. Conclusions: EBV serological markers have a limited role in the early diagnosis of EBV-IM following RT in prior seronegative children. Initial heterophile antibody test may also be negative, and hence a repeat test may be necessary. Once becoming positive, the VCA IgM may remain persistently elevated for prolonged duration. In addition to the suppressed cellular immunity secondary to immunosuppression, humoral response to viral infections is also delayed in transplant recipients, especially in the early transplant period. Hence, routine monitoring with PCR is superior to serology in diagnosing IM early and monitoring the EBV infection post-RT for timely evaluation and management. MDPI 2020-04-22 /pmc/articles/PMC7235840/ /pubmed/32331303 http://dx.doi.org/10.3390/medicines7040021 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Case Report
Byrne, Alexandra
Bush, Rachel
Johns, Felicia
Upadhyay, Kiran
Limited Utility of Serology and Heterophile Test in the Early Diagnosis of Epstein–Barr Virus Mononucleosis in a Child after Renal Transplantation
title Limited Utility of Serology and Heterophile Test in the Early Diagnosis of Epstein–Barr Virus Mononucleosis in a Child after Renal Transplantation
title_full Limited Utility of Serology and Heterophile Test in the Early Diagnosis of Epstein–Barr Virus Mononucleosis in a Child after Renal Transplantation
title_fullStr Limited Utility of Serology and Heterophile Test in the Early Diagnosis of Epstein–Barr Virus Mononucleosis in a Child after Renal Transplantation
title_full_unstemmed Limited Utility of Serology and Heterophile Test in the Early Diagnosis of Epstein–Barr Virus Mononucleosis in a Child after Renal Transplantation
title_short Limited Utility of Serology and Heterophile Test in the Early Diagnosis of Epstein–Barr Virus Mononucleosis in a Child after Renal Transplantation
title_sort limited utility of serology and heterophile test in the early diagnosis of epstein–barr virus mononucleosis in a child after renal transplantation
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235840/
https://www.ncbi.nlm.nih.gov/pubmed/32331303
http://dx.doi.org/10.3390/medicines7040021
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