Cytomegalovirus-associated haemophagocytic syndrome in a kidney transplant patient
Síndrome hemofagocítico reactivo a infección por CMV en paciente trasplantado renal
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"apellidos" => "RIVAS" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "affc" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Servicio de Nefrología, Hospital Universitario La Fe, Valencia, Spain, " "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] 1 => array:3 [ "entidad" => "Servicio de Nefrología, Hospital Universitario La Fe, Valencia, " "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "affb" ] 2 => array:3 [ "entidad" => "Servicio de Anatomía Patológica, Hospital Universitario La Fe, Valencia, " "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "affc" ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Síndrome hemofagocítico reactivo a infección por CMV en paciente trasplantado renal" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig1" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "10639_108_15837_en_10639f1.jpg" "Alto" => 366 "Ancho" => 600 "Tamanyo" => 260246 ] ] "descripcion" => array:1 [ "en" => "Trichrome staining. Histiocytes with red blood cells indicating haematophagous activity in bone marrow." ] ] ] "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">To the Editor, </span></p><p class="elsevierStylePara">Haemophagocytic syndrome is a rare clinical condition characterised by a generalised, benign proliferation of histiocytes with significant haemophagocytic activity.<span class="elsevierStyleSup">1-3</span> The aetiology of these symptoms can be separated into two groups: primary or genetically determined, or secondary: virus, bacteria, fungus, parasites, neoplasia, collagen, immunodeficiency or drugs.<span class="elsevierStyleSup">1-7</span> Clinical symptoms include fever, hepatosplenomegaly, lymphadenomegaly, neurological symptoms, oedema and rashes.<span class="elsevierStyleSup">1,2,8,9</span> The most important laboratory findings are: pancytopaenia, hypertriglyceridaemia, hypofibrinogenaemia, hyponatraemia, hypoproteinaemia, increased levels of hepatic enzymes, increased amount of LDH and ferritin, pleocytosis in LCR and defective activity of natural killer (NK) cells.<span class="elsevierStyleSup">10</span><span class="elsevierStyleSup"> </span>The histological analysis found haemophagocytosis in the bone marrow, spleen and lymph nodes. There were no malignant findings and diagnosis was possible with 2% of haemophagocytic cells.<span class="elsevierStyleSup">1-3</span> Haemophagocytic syndrome has a poor prognosis despite treatment, with an average survival of 2 weeks after the onset of the clinical symptoms. Survival can reach 60% at 5 years if there is an adequate response to treatment.<span class="elsevierStyleSup">11,12</span> Agents that interrupt histiocyte function and macrophage activation are therapeutic alternatives, such as etoposide, steroids, high-dose i.v. Ig, cyclosporine A, anti-thymocyte globulin, anti- TNF antibodies, and in some cases, bone marrow transplant.<span class="elsevierStyleSup">13,14</span></p><p class="elsevierStylePara">We present the case of a 53-year-old man, subjected to kidney transplant, who came to the emergency department with fever, temperature 38.5ºC over a 24-hour period, with shivers, mild diffuse abdominal pain, asthenia, anorexia, and a decrease in diuresis volume. The physical examination was normal and no important pathology was found from the tests performed at the emergency department: normal X-ray; normal blood and urine tests; negative blood and urine cultures; negative cytomegalovirus (CMV) early-antigen (at that time, CMV polymerase chain reaction (PCR) assays were not available in our hospital). The symptoms worsened, abdominal pain increased, and on the CT scan we observed dilated small bowel loops due possibly to ischaemia or infection. Given the findings and the worsening clinical symptoms, we performed an exploratory laparotomy, without observing anomalies. A coagulase-negative staphylococcus grew in the peritoneal fluid, which was treated with meropenem at 500mg every 12 hours. Following the intervention, the clinical symptoms improved despite having developed a post-operative paralytic ileus, which improved spontaneously. After a few days, the patient presented with fever again, and diarrhoea. There were initially no traces of blood, but he then presented with melaena, associated with neurological deterioration, hepatosplenomegaly and hepatic function alterations, anaemia and thrombocytopaenia. New tests were requested: positive CMV early-antigen; CMV PCR assay above 100 000 copies/ml. Eso-Gastro-Duodenoscopy (EGD): infected oesophagus. Analytical tests showed: GOT/GPT: 135/156IU/l; LDH: 558IU/l; sodium: 130mEq/l, fibrinogen:133mg/dl, haemoglobin: 9.2 g/dl; and haematocrit: 26.8%; platelets: 48 000µl with normal leukocytes (normal formula: 5500µl), significant increase in triglycerides (738mg/dl), progressive deterioration of kidney function (creatinine around 4-5mg/dl). Normal haptoglobin, negative indirect Coombs test. Peripheral blood smear: few schistocytes with no reticulocyte. Bone marrow aspiration: compatible with haemophagocytic syndrome (Figure 1).</p><p class="elsevierStylePara">Given these findings, the patient was diagnosed with CMV-associated haemophagocytic syndrome<span class="elsevierStyleBold">. </span>The patient visited infection diseases unit and the following therapeutic regimen was started: anti-CMV with ganciclovir 50mg/12h and non-specific i.v. gamma globulin 30g/48h, and methylprednisolone bolus were indicated for haemophagocytic syndrome. The patient continued to take cyclosporine at low doses (around 50ng/ml). Despite being treated, the patient’s general and neurological condition worsened and he was finally admitted to the ICU for saturation, where he died 12 hours after admission due to multiple organ failure. The autopsy showed: disseminated CMV infection, mainly affecting the digestive tract and lung (Figure 2) and reactive haemophagocytic syndrome (Figure 1).</p><p class="elsevierStylePara">The prevalence of haemophagocytic syndrome in kidney transplant patients is 0.4%,<span class="elsevierStyleSup">11</span> which makes it a rare complication in this patient group. Furthermore, the most common aetiology for these patients is that secondary to an infection.<span class="elsevierStyleSup">14</span> These patients have poor prognosis meaning that early diagnosis is essential to enable starting therapy early. There is no consensus on treatment strategies, and several treatments have been proposed, such as steroids and cyclosporine,<span class="elsevierStyleSup">14</span> specific immunoglobulin, treating the aetiological agent, etc.</p><p class="elsevierStylePara">On the other hand, CMV-associated infections in kidney transplant patients is a common complication, although its incidence and repercussion is decreasing due to the prophylaxis employed.<span class="elsevierStyleSup">15</span> In spite of this, it is a diagnosis that we should take into account when a transplant patient’s general condition deteriorates, because the complications for this infectious profile are all serious. Early diagnosis and starting correct therapy greatly improves prognosis.</p><p class="elsevierStylePara">Haemophagocytic syndrome is a rare complication following kidney transplantation. Furthermore, it is a clinical entity that must be considered during the differential diagnosis of these patients, especially if associated with fever, organomegaly and pancytopenia. Bone marrow aspiration allows for a clearer diagnosis, whereas blood test analyses only enable us to make presumptions (pancytopaenia, hepatic kidney function alteration, increase in LDH, decreased fibrinogen, increased triglycerides, hyponatraemia, etc). Viral infection is the most common triggering agent for immunosuppressed patients. The problem is that there is still no specific treatment, meaning that transplant patient survival is very low, and if patients were to survive, the kidney graft does not often function correctly.</p><p class="elsevierStylePara"><a href="grande/10639_108_15837_en_10639f1.jpg" class="elsevierStyleCrossRefs"><img src="10639_108_15837_en_10639f1.jpg" alt="Trichrome staining. Histiocytes with red blood cells indicating haematophagous activity in bone marrow."></img></a></p><p class="elsevierStylePara">Figure 1. Trichrome staining. Histiocytes with red blood cells indicating haematophagous activity in bone marrow.</p><p class="elsevierStylePara"><a href="grande/10639_108_15838_en_10639f2.jpg" class="elsevierStyleCrossRefs"><img src="10639_108_15838_en_10639f2.jpg" alt="Immunoperoxidase staining. Cells containing CMV in the intestinal tissue."></img></a></p><p class="elsevierStylePara">Figure 2. Immunoperoxidase staining. Cells containing CMV in the intestinal tissue.</p>" "pdfFichero" => "P1-E518-S2912-A10639-EN.pdf" "tienePdf" => true "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "fig1" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "10639_108_15837_en_10639f1.jpg" "Alto" => 366 "Ancho" => 600 "Tamanyo" => 260246 ] ] "descripcion" => array:1 [ "en" => "Trichrome staining. Histiocytes with red blood cells indicating haematophagous activity in bone marrow." ] ] 1 => array:8 [ "identificador" => "fig2" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "10639_108_15838_en_10639f2.jpg" "Alto" => 546 "Ancho" => 600 "Tamanyo" => 376733 ] ] "descripcion" => array:1 [ "en" => "Immunoperoxidase staining. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 5 | 8 | 13 |
| 2024 October | 48 | 28 | 76 |
| 2024 September | 51 | 33 | 84 |
| 2024 August | 60 | 59 | 119 |
| 2024 July | 48 | 26 | 74 |
| 2024 June | 62 | 45 | 107 |
| 2024 May | 52 | 33 | 85 |
| 2024 April | 47 | 36 | 83 |
| 2024 March | 36 | 24 | 60 |
| 2024 February | 37 | 34 | 71 |
| 2024 January | 74 | 19 | 93 |
| 2023 December | 36 | 27 | 63 |
| 2023 November | 47 | 28 | 75 |
| 2023 October | 90 | 31 | 121 |
| 2023 September | 79 | 33 | 112 |
| 2023 August | 51 | 27 | 78 |
| 2023 July | 46 | 29 | 75 |
| 2023 June | 64 | 22 | 86 |
| 2023 May | 64 | 29 | 93 |
| 2023 April | 41 | 17 | 58 |
| 2023 March | 94 | 22 | 116 |
| 2023 February | 41 | 25 | 66 |
| 2023 January | 28 | 20 | 48 |
| 2022 December | 39 | 31 | 70 |
| 2022 November | 38 | 21 | 59 |
| 2022 October | 89 | 36 | 125 |
| 2022 September | 48 | 28 | 76 |
| 2022 August | 49 | 55 | 104 |
| 2022 July | 54 | 39 | 93 |
| 2022 June | 49 | 27 | 76 |
| 2022 May | 49 | 44 | 93 |
| 2022 April | 45 | 51 | 96 |
| 2022 March | 43 | 30 | 73 |
| 2022 February | 40 | 39 | 79 |
| 2022 January | 49 | 34 | 83 |
| 2021 December | 35 | 40 | 75 |
| 2021 November | 35 | 35 | 70 |
| 2021 October | 44 | 43 | 87 |
| 2021 September | 38 | 43 | 81 |
| 2021 August | 34 | 32 | 66 |
| 2021 July | 50 | 40 | 90 |
| 2021 June | 34 | 21 | 55 |
| 2021 May | 29 | 37 | 66 |
| 2021 April | 49 | 32 | 81 |
| 2021 March | 59 | 34 | 93 |
| 2021 February | 80 | 10 | 90 |
| 2021 January | 50 | 28 | 78 |
| 2020 December | 48 | 8 | 56 |
| 2020 November | 38 | 15 | 53 |
| 2020 October | 17 | 22 | 39 |
| 2020 September | 20 | 7 | 27 |
| 2020 August | 32 | 9 | 41 |
| 2020 July | 39 | 9 | 48 |
| 2020 June | 35 | 18 | 53 |
| 2020 May | 31 | 8 | 39 |
| 2020 April | 42 | 19 | 61 |
| 2020 March | 52 | 10 | 62 |
| 2020 February | 38 | 23 | 61 |
| 2020 January | 44 | 17 | 61 |
| 2019 December | 42 | 23 | 65 |
| 2019 November | 35 | 12 | 47 |
| 2019 October | 11 | 9 | 20 |
| 2019 September | 25 | 12 | 37 |
| 2019 August | 11 | 8 | 19 |
| 2019 July | 27 | 24 | 51 |
| 2019 June | 14 | 13 | 27 |
| 2019 May | 20 | 13 | 33 |
| 2019 April | 67 | 36 | 103 |
| 2019 March | 27 | 18 | 45 |
| 2019 February | 24 | 17 | 41 |
| 2019 January | 36 | 13 | 49 |
| 2018 December | 99 | 34 | 133 |
| 2018 November | 123 | 15 | 138 |
| 2018 October | 127 | 14 | 141 |
| 2018 September | 76 | 16 | 92 |
| 2018 August | 39 | 12 | 51 |
| 2018 July | 49 | 11 | 60 |
| 2018 June | 55 | 8 | 63 |
| 2018 May | 46 | 10 | 56 |
| 2018 April | 61 | 11 | 72 |
| 2018 March | 69 | 10 | 79 |
| 2018 February | 56 | 3 | 59 |
| 2018 January | 54 | 6 | 60 |
| 2017 December | 67 | 12 | 79 |
| 2017 November | 53 | 10 | 63 |
| 2017 October | 49 | 9 | 58 |
| 2017 September | 61 | 12 | 73 |
| 2017 August | 53 | 6 | 59 |
| 2017 July | 49 | 12 | 61 |
| 2017 June | 68 | 11 | 79 |
| 2017 May | 69 | 10 | 79 |
| 2017 April | 57 | 9 | 66 |
| 2017 March | 55 | 6 | 61 |
| 2017 February | 114 | 6 | 120 |
| 2017 January | 37 | 12 | 49 |
| 2016 December | 79 | 7 | 86 |
| 2016 November | 73 | 6 | 79 |
| 2016 October | 142 | 11 | 153 |
| 2016 September | 171 | 4 | 175 |
| 2016 August | 229 | 2 | 231 |
| 2016 July | 178 | 9 | 187 |
| 2016 June | 130 | 0 | 130 |
| 2016 May | 124 | 0 | 124 |
| 2016 April | 119 | 0 | 119 |
| 2016 March | 99 | 0 | 99 |
| 2016 February | 99 | 0 | 99 |
| 2016 January | 131 | 0 | 131 |
| 2015 December | 118 | 0 | 118 |
| 2015 November | 106 | 0 | 106 |
| 2015 October | 83 | 0 | 83 |
| 2015 September | 103 | 0 | 103 |
| 2015 August | 82 | 0 | 82 |
| 2015 July | 71 | 0 | 71 |
| 2015 June | 35 | 0 | 35 |
| 2015 May | 54 | 0 | 54 |
| 2015 April | 8 | 0 | 8 |
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