Letter to the Editor
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
Paula Martín Escuer, Sara Alvarez Tundidor
, Carlos Ruiz-Zorrilla López, Ester Hernández García, Victoria Oviedo Gómez, Fernando Sousa Pérez
Corresponding author
Sección de Nefrología, Hospital Universitario Río Carrión, Palencia, Spain
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To a large extent this is due to the introduction of purine inhibitors in recent years,<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">1</span></a> 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.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a> 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.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">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.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">4,5</span></a> 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used years ago was the determination of antigenaemia, which is an indirect marker of disseminated infection; now it has been replaced by PCR techniques, which are more sensitive (up to 93%).<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">5</span></a> 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.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">6</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">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.</p><p id="par0020" class="elsevierStylePara elsevierViewall">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/mm<span class="elsevierStyleSup">3</span>), thrombocytopenia (platelets 89,000/mm<span class="elsevierStyleSup">3</span>), elevated transaminases (AST 653, ALT 494 and GGT 1924<span class="elsevierStyleHsp" style=""></span>U/l) and impaired kidney function (Cr: 4<span class="elsevierStyleHsp" style=""></span>mg/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.</p><p id="par0025" class="elsevierStylePara elsevierViewall">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.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">7</span></a> In these cases, it is necessary to perform endoscopy to identify the CMV in tissue by immunohistochemistry that has a high diagnostic yield.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">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.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:7 [ 0 => array:3 [ "identificador" => "bib0040" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The influence of mycophenolate mofetil on the incidence and severity of primary cytomegalovirus infections and disease after renal transplantation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "C.G. Ter Meulen" 1 => "J.F. Wetzels" 2 => "L.B. 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Olivares" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "NefroPlus" "fecha" => "2013" "volumen" => "5" "paginaInicial" => "15" "paginaFinal" => "18" ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/20132514/0000003700000005/v2_201710131456/S2013251417301475/v2_201710131456/en/main.assets" "Apartado" => array:4 [ "identificador" => "35436" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letters to the Editor" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/20132514/0000003700000005/v2_201710131456/S2013251417301475/v2_201710131456/en/main.pdf?idApp=UINPBA000064&text.app=https://revistanefrologia.com/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2013251417301475?idApp=UINPBA000064" ]
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| 2021 July | 45 | 32 | 77 |
| 2021 June | 39 | 31 | 70 |
| 2021 May | 54 | 34 | 88 |
| 2021 April | 99 | 61 | 160 |
| 2021 March | 59 | 48 | 107 |
| 2021 February | 57 | 33 | 90 |
| 2021 January | 75 | 15 | 90 |
| 2020 December | 31 | 17 | 48 |
| 2020 November | 50 | 18 | 68 |
| 2020 October | 37 | 22 | 59 |
| 2020 September | 42 | 17 | 59 |
| 2020 August | 51 | 13 | 64 |
| 2020 July | 37 | 19 | 56 |
| 2020 June | 32 | 14 | 46 |
| 2020 May | 48 | 22 | 70 |
| 2020 April | 41 | 22 | 63 |
| 2020 March | 35 | 16 | 51 |
| 2020 February | 27 | 17 | 44 |
| 2020 January | 38 | 19 | 57 |
| 2019 December | 47 | 19 | 66 |
| 2019 November | 45 | 19 | 64 |
| 2019 October | 24 | 12 | 36 |
| 2019 September | 36 | 16 | 52 |
| 2019 August | 31 | 17 | 48 |
| 2019 July | 32 | 16 | 48 |
| 2019 June | 38 | 12 | 50 |
| 2019 May | 29 | 14 | 43 |
| 2019 April | 40 | 23 | 63 |
| 2019 March | 30 | 20 | 50 |
| 2019 February | 26 | 19 | 45 |
| 2019 January | 24 | 25 | 49 |
| 2018 December | 118 | 40 | 158 |
| 2018 November | 214 | 22 | 236 |
| 2018 October | 161 | 11 | 172 |
| 2018 September | 104 | 23 | 127 |
| 2018 August | 50 | 15 | 65 |
| 2018 July | 55 | 15 | 70 |
| 2018 June | 62 | 18 | 80 |
| 2018 May | 93 | 14 | 107 |
| 2018 April | 74 | 11 | 85 |
| 2018 March | 120 | 9 | 129 |
| 2018 February | 82 | 1 | 83 |
| 2018 January | 83 | 9 | 92 |
| 2017 December | 115 | 8 | 123 |
| 2017 November | 36 | 6 | 42 |
| 2017 October | 53 | 13 | 66 |
Show all
