Journal Information
Vol. 37. Issue. 5.September - October 2017
Pages 461-562
Vol. 37. Issue. 5.September - October 2017
Pages 461-562
Letter to the Editor
DOI: 10.1016/j.nefroe.2016.10.015
Open Access
The importance of the histological and immunohistochemical evaluation for diagnosis of serious cytomegalovirus disease without detectable viral load
La importancia del estudio histológico e inmunohistoquímico en el diagnóstico de la enfermedad grave por citomegalovirus con carga viral indetectable
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Paula Martín Escuer, Sara Alvarez Tundidor
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salvtund@hotmail.com

Corresponding author.
, Carlos Ruiz-Zorrilla López, Ester Hernández García, Victoria Oviedo Gómez, Fernando Sousa Pérez
Sección de Nefrología, Hospital Universitario Río Carrión, Palencia, Spain
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Dear Editor,

Gastrointestinal disease by cytomegalovirus (CMV) is increasingly common in transplant patients. To a large extent this is due to the introduction of purine inhibitors in recent years,1 which may occur at any time during the follow up. Severe invasive CMV disease is not frequent since the instauration of early prevention and specific treatment strategies.2 Severe invasive CMV disease is defined as the presence of viral syndrome with CMV replication in blood and/or presence of the virus in the affected organ.3

In most cases, clinical suspicion of the disease is confirmed by the presence of viral replication in blood that is directly related to the presence of the disease.4,5 The technique used years ago was the determination of antigenaemia, which is an indirect marker of disseminated infection; now it has been replaced by PCR techniques, which are more sensitive (up to 93%).5 Those cases in with very low viral load in blood with or without viraemia, and with positive tissue immunohistochemistry, indicates reactivation of the disease in the colon mucosa without systemic translation, so cases of severe CMV disease are not common.6

We present the case of a transplant patient treated with mycophenolate mofetil, with severe CMV disease, who had an undetectable viral load by PCR. In this case, the histological and immunohistochemical studies, together with a high clinical suspicion of the disease, led to the diagnosis.

The patient was a 59-year-old man with chronic kidney failure due to IgA nephropathy, with a history of hypertension, hypertensive heart disease, peripheral arteriopathy and posterior/inferior AMI, and with a first cadaveric renal transplant in 2000, with chronic graft nephropathy. He received a second kidney transplant, this time from a living donor, in 2012, requiring boluses of methylprednisolone, thymoglobulin and rituximab for acute antibody-mediated rejection (days +8 and +55 of transplantation), followed by immunosuppressive treatment with prednisone, mycophenolate and tacrolimus. Six months after the transplant, he went to the emergency room for watery diarrhoea during the last 13 days, without blood or mucous, with abdominal pain, fever and severe asthenia. Leukopenia (WBCs 2700/mm3), thrombocytopenia (platelets 89,000/mm3), elevated transaminases (AST 653, ALT 494 and GGT 1924U/l) and impaired kidney function (Cr: 4mg/dl). Stool culture and toxin were negative. The dose of mycophenolate was reduced with no improvement in symptoms, so PCR for CMV was requested which was negative (serum IgM levels: 0.12; negative). In view of the strong clinical suspicion, an endoscopy was performed, in which infectious colitis was observed in the rectum. Microscopic examination provided a clear diagnosis with the presence of large cells observed with eosinophilic cytoplasm, the presence of intranuclear inclusion bodies, and immunohistochemical staining was positive for CMV. Then, treatment with intravenous ganciclovir was initiated, the symptoms disappeared and the lab test parameters improved, with recovery of basal kidney function.

We believe it is important to maintain a high level of suspicion during post-transplant follow up and to keep in mind that the absence of viral replication in plasma does not rule out the diagnosis of disease.7 In these cases, it is necessary to perform endoscopy to identify the CMV in tissue by immunohistochemistry that has a high diagnostic yield.

References
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[2]
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Immunocompromised hosts: perspectives in the treatment and prophylaxis of cytomegalovirus disease in solid-organ transplant recipients.
Clin Infect Dis, 47 (2008), pp. 702-711
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P. Ljungman, P. Griffiths, C. Paya.
Definitions of cytomegalovirus infection and disease in transplant recipients.
Clin Infect Dis, 34 (2002), pp. 1094-1097
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Prediction and diagnosis of cytomegalovirus disease in renal transplant recipients using qualitative and quantitative polymerase chain reaction.
Transplantation, 69 (2000), pp. 985-991
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A. Franco, R. Serrano, A. Gimeno, J. de Juan, E. Merino, L. Jiménez del Cerro, et al.
Estudio de carga viral y antigenemia como valores predictivos de recidiva de infección de CMV en el trasplante renal.
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O. Roncero García-Escribano, M. Legaz Huidobro, E. Bernardos, N. Sánchez Manajavacas.
Reactivación de CMV: ¿dónde está el límite del diagnóstico?.
Enfermedad inflamatoria intestinal al día, 11 (2012), pp. 118-124
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A. Franco-Esteve, D. Tordera-Fuentes, N. Balibrea-Lara, E. Merino, C. del Pozo, J. Olivares.
Enfermedad tardía gastrointestinal por citomegalovirus con carga viral indetectable, un nuevo reto en trasplante renal.
NefroPlus, 5 (2013), pp. 15-18

Please cite this article as: Martín Escuer P, Alvarez Tundidor S, Ruiz-Zorrilla López C, Hernández García E, Oviedo Gómez V, Sousa Pérez F. La importancia del estudio histológico e inmunohistoquímico en el diagnóstico de la enfermedad grave por citomegalovirus con carga viral indetectable. Nefrologia. 2017;37:546–547.

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