Letter to the Editor
Sever lower gastro-intestinal bleeding by CMV in a kidney transplant with low-dose immunosuppression
Hemorragia digestiva baja masiva por citomegalovirus en un trasplantado renal con bajas dosis de inmunosupresión
Antonio Ríosa,b,c,
, Jose Ruiza,b,c, Jose Manuel Rodrígueza,b,c, Pascual Parrillaa,b,c
Corresponding author
a Departamento de Cirugía, Ginecología, Obstetricia y Pediatría, Universidad de Murcia, Murcia, Spain
b Servicio de Cirugía General y de Aparato Digestivo, Hospital Clínico Universitario Virgen de la Arrixaca, Servicio Murciano de Salud, El Palmar (Murcia), Spain
c Instituto Murciano de Investigación Bio-Sanitaria Virgen de la Arrixaca (IMIB-Arrixaca), Murcia, Spain
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An opening has been made in the resected loop of small intestine and the ulceration that is the source of the bleeding may be observed. B) Histology image with H&E 400×. Cytomegalic inclusions (arrows) in the interior of the mucus-depleted intestinal cells.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Cytomegalovirus (CMV) is an opportunistic virus that affects the majority of immunocompromised patients, including transplant recipients.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> The infection is generally caused by reactivation of a strain in the recipient in a latent state and, more rarely, by infection from an exogenous strain. The period of greatest risk for presenting a CMV infection is during the first 6 months post-transplant. CMV infection is rare starting from the sixth month.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> Since the introduction of new immunosuppressive agents, especially mycophenolate mofetil, an increase in the incidence of CMV infection has been reported.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> However, only exceptionally does a CMV infection start as a serious complication, especially once the first 6 months have passed since the transplant.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> We present the case of a kidney transplant recipient with a long clinical course with low doses of immunosuppressants who developed a severe intestinal disease due to CMV that required emergency surgery.</p><p id="par0010" class="elsevierStylePara elsevierViewall">A 65-year-old woman with hypertension and type 2 diabetes who had received a kidney transplant 12 years earlier, due to polycystic kidney disease, currently with low doses of immunosuppression (ciclosporin 75<span class="elsevierStyleHsp" style=""></span>mg/12<span class="elsevierStyleHsp" style=""></span>h and mycophenolate mofetil 50<span class="elsevierStyleHsp" style=""></span>mg/12<span class="elsevierStyleHsp" style=""></span>h). She visited the emergency department owing to abdominal pain for the past 48<span class="elsevierStyleHsp" style=""></span>h, located in the mesogastrium and associated with vomiting. Laboratory testing revealed a haemoglobin level of 6<span class="elsevierStyleHsp" style=""></span>g/dl and no signs of gastrointestinal bleeding. An upper gastrointestinal endoscopy was normal, and a lower gastrointestinal endoscopy showed multiple superficial ulcers with signs of bleeding in the terminal ileum and ascending colon. A biopsy reported positive immunostaining for CMV. A PCR for CMV was requested and more than 10,000 copies were obtained, and so intravenous treatment was started with ganciclovir and immunoglobulin. At 48<span class="elsevierStyleHsp" style=""></span>h she had severe lower gastrointestinal bleeding that required transfusion of 6 packed red blood cell units. She underwent an arteriogram of both mesenteric arteries, which did not reveal the bleeding point. A colonoscopy showed that the previously detected ulcers had not improved and revealed a penetrating ulcer in the ileum with active bleeding, which was treated with endoscopic sclerosis. At 12<span class="elsevierStyleHsp" style=""></span>h the patient had a new episode of severe gastrointestinal bleeding, and so she underwent a resection of the affected ileum and the caecum. The surgical specimen showed multiple superficial ulcers and an ulcer with a diameter of around 2<span class="elsevierStyleHsp" style=""></span>cm that reached the serosa (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A). The definitive diagnosis was ulcerative enteritis due to CMV (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B). Her postoperative course was favourable and, currently, at 3 years from her signs and symptoms, she has had no recurrence of CMV infection.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">CMV infection represents one of the most common opportunistic infectious diseases after a kidney transplant, and leads to an increase in the recipient's morbidity and mortality. It affects 60–80% of patients, 25–50% of whom develop clinical disease.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,2</span></a> Symptomatic CMV infection in the gastrointestinal tract occurs in 5–10% of patients who receive kidney transplants, and may affect the patient from the oesophagus to the colon. Ulcers occur because CMV causes vasculitis in the gastrointestinal tract, which may cause gastrointestinal bleeding and even intestinal perforation.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> However, late disease due to CMV (after 6 months have passed since the transplant) is uncommon, especially if there is no increase in immunosuppressive treatment due to late acute rejection.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">4,5</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Different studies, including some multi-centre studies, have shown that the use of mycophenolate mofetil decreases the incidence of episodes of acute rejection; however, it seems to increase the frequency and severity of CMV infection,<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3,6</span></a> as was observed in our patient. Cornelis et al.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> indicated that, although it does not bring about an increase in primary CMV infection, it does cause an increase in development of disease due to CMV. Our case was unique with respect to what has been reported by several authors owing to the aggressiveness of the intestinal involvement despite the low doses of immunosuppression and the antiviral treatment started.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">7–10</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The treatment of choice in these cases of late CMV infection is the use of specific antiviral agents, which in the majority of cases is effective.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,8</span></a> Colonoscopy is a good diagnostic and therapeutic method in patients in whom a bleeding point is located. In our case, the lesion was located properly, but the treatment was not effective. Therapy with embolization using interventionist radiology may be used in these cases of massive bleeding; however, a flow rate of 0.5 to 1<span class="elsevierStyleHsp" style=""></span>ml/min is required to show bleeding, and this sometimes brings about a diagnostic problem owing to the intermittent nature of episodes of gastrointestinal bleeding, as occurred in our case. Surgery is reserved for cases in which all the above fails, and its major problem is locating the bleeding point, as a segmental resection, as in our case, is not the same as a massive intestinal resection. The mortality rate of surgery ranges between 10% and 55%.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> In our case, a segmental resection fostered the patient's good clinical course.</p><p id="par0030" class="elsevierStylePara elsevierViewall">In conclusion, late intestinal CMV infection should be suspected in transplant recipients treated with mycophenolate who start with latent gastrointestinal signs and symptoms. Surgery is the last therapeutic step, and locating the bleeding point is essential for managing signs and symptoms.</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: Ríos A, Ruiz J, Rodríguez JM, Parrilla P. Hemorragia digestiva baja masiva por citomegalovirus en un trasplantado renal con bajas dosis de inmunosupresión. Nefrologia. 2016;36:454–455.</p>" ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 642 "Ancho" => 1654 "Tamanyo" => 216980 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(A) Intra-operative image of the resected specimen. An opening has been made in the resected loop of small intestine and the ulceration that is the source of the bleeding may be observed. B) Histology image with H&E 400×. Cytomegalic inclusions (arrows) in the interior of the mucus-depleted intestinal cells.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Updated international consensus guidelines on the management of cytomegalovirus in solid-organ transplantation" "autores" => array:1 [ 0 => array:3 [ "colaboracion" => "Transplantation Society International CMV Consensus Group" "etal" => true "autores" => array:6 [ 0 => "C.N. Kotton" 1 => "D. Kumar" 2 => "A.M. Caliendo" 3 => "A. Asberg" 4 => "S. Chou" 5 => "L. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 2 | 5 | 7 |
| 2024 October | 39 | 41 | 80 |
| 2024 September | 49 | 23 | 72 |
| 2024 August | 77 | 75 | 152 |
| 2024 July | 59 | 25 | 84 |
| 2024 June | 62 | 34 | 96 |
| 2024 May | 85 | 28 | 113 |
| 2024 April | 73 | 29 | 102 |
| 2024 March | 44 | 26 | 70 |
| 2024 February | 41 | 34 | 75 |
| 2024 January | 30 | 26 | 56 |
| 2023 December | 29 | 21 | 50 |
| 2023 November | 55 | 29 | 84 |
| 2023 October | 73 | 27 | 100 |
| 2023 September | 32 | 28 | 60 |
| 2023 August | 44 | 29 | 73 |
| 2023 July | 46 | 23 | 69 |
| 2023 June | 73 | 20 | 93 |
| 2023 May | 75 | 33 | 108 |
| 2023 April | 39 | 12 | 51 |
| 2023 March | 47 | 20 | 67 |
| 2023 February | 56 | 19 | 75 |
| 2023 January | 43 | 30 | 73 |
| 2022 December | 56 | 22 | 78 |
| 2022 November | 38 | 25 | 63 |
| 2022 October | 64 | 31 | 95 |
| 2022 September | 41 | 20 | 61 |
| 2022 August | 56 | 39 | 95 |
| 2022 July | 43 | 42 | 85 |
| 2022 June | 30 | 21 | 51 |
| 2022 May | 56 | 41 | 97 |
| 2022 April | 62 | 39 | 101 |
| 2022 March | 39 | 40 | 79 |
| 2022 February | 53 | 35 | 88 |
| 2022 January | 49 | 32 | 81 |
| 2021 December | 50 | 42 | 92 |
| 2021 November | 40 | 40 | 80 |
| 2021 October | 46 | 42 | 88 |
| 2021 September | 35 | 30 | 65 |
| 2021 August | 49 | 31 | 80 |
| 2021 July | 56 | 35 | 91 |
| 2021 June | 44 | 19 | 63 |
| 2021 May | 62 | 50 | 112 |
| 2021 April | 82 | 42 | 124 |
| 2021 March | 64 | 65 | 129 |
| 2021 February | 78 | 34 | 112 |
| 2021 January | 60 | 16 | 76 |
| 2020 December | 30 | 22 | 52 |
| 2020 November | 37 | 18 | 55 |
| 2020 October | 39 | 22 | 61 |
| 2020 September | 49 | 9 | 58 |
| 2020 August | 50 | 16 | 66 |
| 2020 July | 49 | 14 | 63 |
| 2020 June | 31 | 18 | 49 |
| 2020 May | 51 | 28 | 79 |
| 2020 April | 34 | 15 | 49 |
| 2020 March | 30 | 11 | 41 |
| 2020 February | 44 | 20 | 64 |
| 2020 January | 55 | 19 | 74 |
| 2019 December | 48 | 22 | 70 |
| 2019 November | 45 | 22 | 67 |
| 2019 October | 38 | 8 | 46 |
| 2019 September | 53 | 15 | 68 |
| 2019 August | 45 | 15 | 60 |
| 2019 July | 37 | 22 | 59 |
| 2019 June | 42 | 20 | 62 |
| 2019 May | 43 | 19 | 62 |
| 2019 April | 69 | 35 | 104 |
| 2019 March | 46 | 17 | 63 |
| 2019 February | 43 | 17 | 60 |
| 2019 January | 57 | 18 | 75 |
| 2018 December | 121 | 50 | 171 |
| 2018 November | 196 | 20 | 216 |
| 2018 October | 205 | 21 | 226 |
| 2018 September | 118 | 11 | 129 |
| 2018 August | 71 | 14 | 85 |
| 2018 July | 61 | 11 | 72 |
| 2018 June | 69 | 11 | 80 |
| 2018 May | 110 | 14 | 124 |
| 2018 April | 133 | 11 | 144 |
| 2018 March | 102 | 10 | 112 |
| 2018 February | 144 | 9 | 153 |
| 2018 January | 107 | 8 | 115 |
| 2017 December | 164 | 10 | 174 |
| 2017 November | 77 | 9 | 86 |
| 2017 October | 31 | 5 | 36 |
| 2017 September | 58 | 17 | 75 |
| 2017 August | 77 | 7 | 84 |
| 2017 July | 82 | 10 | 92 |
| 2017 June | 48 | 20 | 68 |
| 2017 May | 62 | 8 | 70 |
| 2017 April | 53 | 13 | 66 |
| 2017 March | 53 | 56 | 109 |
| 2017 February | 40 | 10 | 50 |
| 2017 January | 21 | 7 | 28 |
| 2016 December | 50 | 11 | 61 |
| 2016 November | 27 | 5 | 32 |
| 2016 October | 22 | 6 | 28 |
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