Scientific letter
Infliximab as treatment of severe enteropathy in a patient with common variable immunodeficiency and cytomegalovirus infection
Infliximab como tratamiento de la enteropatía severa en un paciente con inmunodeficiencia común variable e infección por citomegalovirus
Janire Prieto Elordui
, Paz Arreba Gonzalez, Jone Ortiz de Zarate Sagastagoitia, Laura Deiss Pascual, Sonia Blanco Sampascual, Amaia Baranda Martín, Angel Calderón García, Carmen Muñoz Villafranca
Corresponding author
Servicio de Aparato Digestivo, Hospital Universitario de Basurto, Bilbao, Vizcaya, Spain
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Mesenteric and retroperitoneal lymphadenopathy.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Common variable immunodeficiency (CVID) is uncommon, affecting an estimated one in 25,000 people. It is characterised by a deficiency in antibody production, and has a wide variety of clinical features.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">1</span></a> According to the largest European database, the main features were pneumonia (32%), autoimmunity (29%), splenomegaly (26%) and bronchiectasis (23%).<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">This article looks at the case of a patient with CVID who had a cytomegalovirus (CMV) opportunistic infection which resolved satisfactorily after treatment with ganciclovir and an anti-TNF drug.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The patient was a 37-year-old female who was diagnosed with CVID 8 years earlier as a result of recurrent respiratory infections. She was being treated with immunoglobulins and B<span class="elsevierStyleInf">12</span> and was being monitored by the digestive disease department due to having chronic diarrhoea. This was determined to be caused by an immune process and not an infectious process, and was treated with corticosteroids, with a positive response.</p><p id="par0020" class="elsevierStylePara elsevierViewall">She was admitted due to more severe diarrhoea (6–8<span class="elsevierStyleHsp" style=""></span>bowel movements/day) without blood, mucus or pus that was associated with weight loss (10<span class="elsevierStyleHsp" style=""></span>kg). Physical examination revealed: BMI of 17, distended abdomen, tender to touch, no rebound tenderness with normal bowel sounds.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Lab tests, including stool cultures (×3), intestinal parasites (×3), <span class="elsevierStyleItalic">C. difficile</span> toxin (×3), auramine staining in stools, mycobacteria culture and <span class="elsevierStyleItalic">Tropheryma whipplei</span> PCR in saliva and stool specimens, were negative. An endoscopy and colonoscopy showed no abnormalities. However, the duodenal biopsy and random colon biopsies showed oedema and lymphoplasmacytic infiltrate in the lamina propria. A CT scan of the abdomen and pelvis was performed, showing homogeneous hepatomegaly and splenomegaly and hypodense retroperitoneal and mesenteric lymphadenopathy greater than one centimetre in diameter (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">In view of the unfavourable clinical course, persistent diarrhoea and findings of retroperitoneal lymphadenopathy and hepatosplenomegaly, we suggested a differential diagnosis of lymphoma as the entity responsible for the patient's clinical manifestations.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Given the lack of endoscopic ultrasound access to the lymphadenopathies, we decided to perform a laparoscopic mesenteric lymph node biopsy. The histology study, using haematoxylin–eosin staining, showed eosinophilic intranuclear inclusions surrounded by a halo, producing the characteristic owl's-eye appearance. This is compatible with invasive CMV infection.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Prior to routine immunoglobulin infusion, the patient had hypoalbuminaemia and hypogammaglobulinaemia with albumin levels of 2.90<span class="elsevierStyleHsp" style=""></span>g/dl, gamma-globulin levels of 0.46<span class="elsevierStyleHsp" style=""></span>g/dl (IgG: 594, IgA<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>20 and IgM<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>17<span class="elsevierStyleHsp" style=""></span>mg/dl) and a positive CMV viral load in serum, 2895<span class="elsevierStyleHsp" style=""></span>copies/ml, analysed by PCR in peripheral blood.</p><p id="par0045" class="elsevierStylePara elsevierViewall">In view of these findings, treatment for CMV infection was started with ganciclovir for 5 days followed by valganciclovir until 21 days of treatment was completed. The patient showed clinical improvement and was therefore discharged.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Two weeks later, the patient was admitted again suffering from 4 to 5 bowel movements/day and a distended abdomen. Again, the stool tests (stool cultures, intestinal parasites and <span class="elsevierStyleItalic">C. difficile</span>) were negative and serum gamma-globulin levels showed no significant changes. The CMV viral load had decreased to 220<span class="elsevierStyleHsp" style=""></span>copies/ml. It was decided to start treatment with an induction regimen of 5<span class="elsevierStyleHsp" style=""></span>mg/kg of infliximab (weeks 0/2/6) followed by a maintenance dose every 8 weeks.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Upon discharge, the patient continued to attend the clinic for check-ups and showed a favourable clinical response with one bowel movement/day and a 5<span class="elsevierStyleHsp" style=""></span>kg weight gain 8 weeks after starting treatment.</p><p id="par0060" class="elsevierStylePara elsevierViewall">CVID is the most common primary immunodeficiency after selective IgA deficiency. Clinical symptoms start during the second and third decade of life, with no gender predisposition. It is characterised by recurrent infections, particularly of the respiratory tract.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">3</span></a> Gastrointestinal symptoms appear later, with the most common being diarrhoea, malabsorption, giardiasis, vitamin B<span class="elsevierStyleInf">12</span> deficiency, hepatomegaly and splenomegaly. Most cases also require an endoscopy with biopsy in order to reach a diagnosis. Duodenal histology abnormalities are difficult to evaluate in these patients due to bacterial overgrowth, which is common in CVID patients.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">4</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">CVID causes abnormalities in the differentiation of B-cells into plasma cells, which also affects T-cells. Due to dysregulation of the immune system, these patients are more susceptible to non-Hodgkin's lymphoma, gastrointestinal malignancies, autoimmune diseases, opportunistic infections and inflammatory bowel disease.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">5</span></a> The ulcerative colitis and Crohn's disease observed in CVID have different features from usual, and are therefore defined as ulcerative colitis-like and Crohn's disease-like diseases. The fundamental difference is the lack of plasma cells, granulomas and giant cells.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">6</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">After ruling out an infectious origin, treatment of severe, corticosteroid-resistant enteropathy in CVID is not well established. Some cases have been described that have responded well to treatment with anti-TNF drugs, resulting in weight gain and improved quality of life.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">7,8</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">In exceptional cases, such as the case of our patient, treatment with anti-TNF drugs is justified due to the severity of symptoms and the absence of other pathological findings. The efficacy of the drug could be related to the high serum and tissue levels of TNF-α described in some patients with CVID. TNF-α has also been observed to increase CMV replication <span class="elsevierStyleItalic">in vitro</span>,<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">9</span></a> which suggests that infliximab, as an anti-TNF drug, may inhibit CMV reactivation <span class="elsevierStyleItalic">in vivo</span>. This may explain our patient's favourable response to infliximab treatment.</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: Prieto Elordui J, Arreba Gonzalez P, Ortiz de Zarate Sagastagoitia J, Deiss Pascual L, Blanco Sampascual S, Baranda Martín A, et al. Infliximab como tratamiento de la enteropatía severa en un paciente con inmunodeficiencia común variable e infección por citomegalovirus. Gastroenterol Hepatol. 2018;41:163–164.</p>" ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 952 "Ancho" => 950 "Tamanyo" => 79326 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">CT scan of the abdomen and pelvis with IV contrast dye. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 9 | 1 | 10 |
| 2024 October | 26 | 7 | 33 |
| 2024 September | 32 | 5 | 37 |
| 2024 August | 28 | 6 | 34 |
| 2024 July | 33 | 6 | 39 |
| 2024 June | 32 | 2 | 34 |
| 2024 May | 29 | 3 | 32 |
| 2024 April | 29 | 3 | 32 |
| 2024 March | 29 | 11 | 40 |
| 2024 February | 24 | 2 | 26 |
| 2024 January | 40 | 5 | 45 |
| 2023 December | 43 | 6 | 49 |
| 2023 November | 34 | 2 | 36 |
| 2023 October | 34 | 4 | 38 |
| 2023 September | 21 | 0 | 21 |
| 2023 August | 42 | 1 | 43 |
| 2023 July | 32 | 2 | 34 |
| 2023 June | 33 | 2 | 35 |
| 2023 May | 76 | 5 | 81 |
| 2023 April | 64 | 2 | 66 |
| 2023 March | 32 | 4 | 36 |
| 2023 February | 29 | 4 | 33 |
| 2023 January | 42 | 6 | 48 |
| 2022 December | 27 | 10 | 37 |
| 2022 November | 26 | 11 | 37 |
| 2022 October | 38 | 16 | 54 |
| 2022 September | 19 | 8 | 27 |
| 2022 August | 20 | 8 | 28 |
| 2022 July | 22 | 10 | 32 |
| 2022 June | 21 | 14 | 35 |
| 2022 May | 22 | 6 | 28 |
| 2022 April | 30 | 10 | 40 |
| 2022 March | 41 | 10 | 51 |
| 2022 February | 28 | 6 | 34 |
| 2022 January | 46 | 4 | 50 |
| 2021 December | 59 | 15 | 74 |
| 2021 November | 30 | 12 | 42 |
| 2021 October | 30 | 11 | 41 |
| 2021 September | 37 | 14 | 51 |
| 2021 August | 28 | 13 | 41 |
| 2021 July | 42 | 7 | 49 |
| 2021 June | 19 | 14 | 33 |
| 2021 May | 32 | 4 | 36 |
| 2021 April | 83 | 34 | 117 |
| 2021 March | 49 | 6 | 55 |
| 2021 February | 44 | 8 | 52 |
| 2021 January | 30 | 13 | 43 |
| 2020 December | 25 | 11 | 36 |
| 2020 November | 20 | 11 | 31 |
| 2020 October | 12 | 7 | 19 |
| 2020 September | 11 | 8 | 19 |
| 2020 August | 9 | 12 | 21 |
| 2020 July | 9 | 12 | 21 |
| 2020 June | 9 | 6 | 15 |
| 2020 May | 21 | 12 | 33 |
| 2020 April | 4 | 1 | 5 |
| 2020 March | 7 | 9 | 16 |
| 2018 July | 0 | 0 | 0 |
| 2018 June | 1 | 0 | 1 |
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