Letter to the Editor
Subacute interstitial pneumonitis due to Mycobacterium bovis after intravesical bacillus Calmette-Guérin instillation in a renal transplant patient
Neumonitis intersticial subaguda por Mycobacterium bovis tras instilaciones vesicales de bacilo de Calmette-Guérin en un trasplante renal
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array:6 [ 0 => array:4 [ "nombre" => "Fernando" "apellidos" => "Caravaca-Fontán" "email" => array:1 [ 0 => "fcaravacaf@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Marta" "apellidos" => "Cano Megías" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Matilde" "apellidos" => "Sánchez-Conde" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "Sandra" "apellidos" => "Elías Triviño" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 4 => array:3 [ "nombre" => "Ana" "apellidos" => "Fernández-Rodríguez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 5 => array:3 [ "nombre" => "Fernando" "apellidos" => "Liaño" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Servicio de Nefrología, Hospital Universitario Ramón y Cajal, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Nefrología, Hospital Universitario Príncipe de Asturias, Alcalá de Henares (Madrid), Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario Gregorio Marañón, Madrid, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Neumonitis intersticial subaguda por <span class="elsevierStyleItalic">Mycobacterium bovis</span> tras instilaciones vesicales de bacilo de Calmette-Guérin en un trasplante renal" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The estimated incidence rate of urothelial bladder carcinoma is 1.4–2.2% in kidney transplant (KT) patients.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> However, the clinical course may be more aggressive than in the general population, with higher rates of progression and relapse.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Intravesical administration of bacillus Calmette-Guérin (BCG), an attenuated live strain of <span class="elsevierStyleItalic">Mycobacterium bovis</span>, is one of the main adjuvant therapies for managing non-invasive bladder cancer. BCG instillation produces a massive local immune reaction with antitumour activity.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> However, both local and systemic infectious complications have been reported in relation to this treatment, especially in immunocompromised patients. Disseminated infection as a result of the systemic absorption of BCG may occur in 0.4% of cases and it is usually manifested as fever, weight loss, night sweats or dyspnoea, and even multiple organ failure in severe cases.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">4,5</span></a> Interstitial pulmonary involvement is a rare complication.</p><p id="par0015" class="elsevierStylePara elsevierViewall">We report for the first time a case of interstitial pneumonitis caused by <span class="elsevierStyleItalic">M. bovis</span> after bladder instillations of BCG in a KT patient.</p><p id="par0020" class="elsevierStylePara elsevierViewall">This case involves an 81-year-old woman with a history of chronic kidney disease secondary to polycystic kidney disease, who underwent kidney transplantation 11 years earlier with a normally functioning graft, in maintenance therapy with tacrolimus and everolimus. Ten years after transplantation, she was diagnosed with urothelial bladder carcinoma without muscle invasion and, after transurethral resection of the tumour, she began treatment with intravesical BCG.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Thirty days after the first instillation she began suffering from asthenia, weight loss, sweating and fever mainly at night, and cough without expectoration, which lasted for 2 months. After receiving 2 cycles of empirical antibiotic therapy with amoxicillin–clavulanic acid and levofloxacin without improvement, the patient returned to the emergency department.</p><p id="par0030" class="elsevierStylePara elsevierViewall">On admission she had a temperature of 38<span class="elsevierStyleHsp" style=""></span>°C and 98% oxygen saturation, with no other noticeable findings. The results of laboratory tests and viral serologies revealed only anaemia of chronic disease and elevated C-reactive protein. Broad-spectrum antibiotic therapy with meropenem was initiated, fever and symptoms persisted during the following days.</p><p id="par0035" class="elsevierStylePara elsevierViewall">All bacterial and viral microbiological studies were negative. A CT scan of the chest, abdomen and pelvis was performed, which showed a lung pattern with diffuse bilateral involvement and poorly defined nodules with a centrilobular distribution, suggestive of infection caused by atypical microorganisms or mycobacteria. The study was completed with a bronchoscopy for microbiological sampling, although direct microscopy showed no acid-alcohol resistant bacilli and cultures of mycobacteria obtained from bronchoalveolar lavage were negative at 8 weeks. The study using the polymerase chain reaction technique for <span class="elsevierStyleItalic">Mycobacterium tuberculosis complex</span> sequences in the bronchoalveolar lavage was also negative. No transbronchial biopsy was performed because it was considered a high-risk procedure for the patient.</p><p id="par0040" class="elsevierStylePara elsevierViewall">With the diagnostic suspicion of systemic lung infection caused by <span class="elsevierStyleItalic">M. bovis</span>, treatment with isoniazid, rifampicin and ethambutol was prescribed for 6 months. Fever and associated symptoms gradually disappeared, while acute-phase reactants decreased. A subsequent control CT scan showed that the impairments described had been resolved.</p><p id="par0045" class="elsevierStylePara elsevierViewall">This clinical case demonstrates the risk of developing systemic complications in KT patients treated with bladder instillations of BCG.</p><p id="par0050" class="elsevierStylePara elsevierViewall">The pathophysiology of pulmonary manifestations after intravesical BCG treatment is still controversial. Some authors believe it is a hypersensitivity reaction, based on the histological finding of granulomas without microbiological isolation and a favourable response to corticosteroids.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> Other authors, however, have reported mycobacterial isolation in different tissues,<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> which would demonstrate a haematogenous dissemination of the bacillus. It has therefore been pointed out that the low sensitivity of microbiological studies would be a result of the rapid control of bacillary replication by the host immune system and the attenuated virulence of BCG, which, however, would not prevent the formation of granulomatous lesions.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> Therefore, the diagnosis is made by the presence compatible clinical symptoms and the early response to tuberculostatic treatment.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Some authors argue that intravesical instillation of BCG is safe in immunocompromised patients, however there are no conclusive studies in KT patients.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,4,9</span></a> To that effect, concomitant prophylactic administration of isoniazid alone or in combination with rifampicin has been tested, with favourable results in some cases, although not without adverse effects.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> On the other hand, other authors argue that it should be contraindicated due to an increased risk of systemic dissemination together with a lower local immune response.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">In conclusion, bladder instillations of BCG in kidney transplantation can produce disseminated mycobacterial infection, with a long-term clinical course with few symptoms. Therefore, a high index of suspicion is necessary to begin treatment at an early stage.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0065" class="elsevierStylePara elsevierViewall">The authors declare no conflicts of interest related to the publication of this article.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Caravaca-Fontán F, Cano Megías M, Sánchez-Conde M, Elías Triviño S, Fernández-Rodríguez A, Liaño F. Neumonitis intersticial subaguda por <span class="elsevierStyleItalic">Mycobacterium bovis</span> tras instilaciones vesicales de bacilo de Calmette-Guérin en un trasplante renal. Nefrologia. 2016;36:711–713.</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" => "Intravesical bacillus Calmette-Guèrin for the treatment of superficial bladder cancer in renal transplant patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Palou" 1 => "O. Angerri" 2 => "J. Segarra" 3 => "J. Caparrós" 4 => "L. Guirado" 5 => "J.M. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 4 | 3 | 7 |
| 2024 October | 42 | 40 | 82 |
| 2024 September | 46 | 22 | 68 |
| 2024 August | 60 | 70 | 130 |
| 2024 July | 38 | 35 | 73 |
| 2024 June | 47 | 58 | 105 |
| 2024 May | 69 | 29 | 98 |
| 2024 April | 48 | 30 | 78 |
| 2024 March | 35 | 24 | 59 |
| 2024 February | 43 | 27 | 70 |
| 2024 January | 25 | 24 | 49 |
| 2023 December | 21 | 17 | 38 |
| 2023 November | 39 | 35 | 74 |
| 2023 October | 49 | 32 | 81 |
| 2023 September | 25 | 22 | 47 |
| 2023 August | 35 | 22 | 57 |
| 2023 July | 35 | 31 | 66 |
| 2023 June | 40 | 11 | 51 |
| 2023 May | 50 | 28 | 78 |
| 2023 April | 26 | 16 | 42 |
| 2023 March | 39 | 20 | 59 |
| 2023 February | 41 | 17 | 58 |
| 2023 January | 39 | 31 | 70 |
| 2022 December | 56 | 21 | 77 |
| 2022 November | 38 | 21 | 59 |
| 2022 October | 59 | 40 | 99 |
| 2022 September | 64 | 30 | 94 |
| 2022 August | 55 | 46 | 101 |
| 2022 July | 25 | 54 | 79 |
| 2022 June | 38 | 30 | 68 |
| 2022 May | 50 | 35 | 85 |
| 2022 April | 62 | 54 | 116 |
| 2022 March | 47 | 43 | 90 |
| 2022 February | 47 | 43 | 90 |
| 2022 January | 41 | 32 | 73 |
| 2021 December | 42 | 46 | 88 |
| 2021 November | 32 | 39 | 71 |
| 2021 October | 50 | 54 | 104 |
| 2021 September | 35 | 41 | 76 |
| 2021 August | 64 | 38 | 102 |
| 2021 July | 51 | 46 | 97 |
| 2021 June | 67 | 40 | 107 |
| 2021 May | 63 | 39 | 102 |
| 2021 April | 161 | 96 | 257 |
| 2021 March | 100 | 44 | 144 |
| 2021 February | 65 | 41 | 106 |
| 2021 January | 61 | 30 | 91 |
| 2020 December | 40 | 14 | 54 |
| 2020 November | 45 | 26 | 71 |
| 2020 October | 19 | 23 | 42 |
| 2020 September | 40 | 23 | 63 |
| 2020 August | 40 | 12 | 52 |
| 2020 July | 25 | 13 | 38 |
| 2020 June | 20 | 21 | 41 |
| 2020 May | 46 | 10 | 56 |
| 2020 April | 27 | 21 | 48 |
| 2020 March | 30 | 23 | 53 |
| 2020 February | 35 | 21 | 56 |
| 2020 January | 41 | 28 | 69 |
| 2019 December | 37 | 36 | 73 |
| 2019 November | 46 | 18 | 64 |
| 2019 October | 28 | 10 | 38 |
| 2019 September | 26 | 12 | 38 |
| 2019 August | 24 | 16 | 40 |
| 2019 July | 35 | 26 | 61 |
| 2019 June | 33 | 24 | 57 |
| 2019 May | 25 | 22 | 47 |
| 2019 April | 60 | 35 | 95 |
| 2019 March | 34 | 21 | 55 |
| 2019 February | 26 | 21 | 47 |
| 2019 January | 20 | 22 | 42 |
| 2018 December | 123 | 34 | 157 |
| 2018 November | 173 | 24 | 197 |
| 2018 October | 146 | 14 | 160 |
| 2018 September | 76 | 19 | 95 |
| 2018 August | 41 | 18 | 59 |
| 2018 July | 38 | 13 | 51 |
| 2018 June | 49 | 18 | 67 |
| 2018 May | 46 | 13 | 59 |
| 2018 April | 81 | 7 | 88 |
| 2018 March | 69 | 9 | 78 |
| 2018 February | 88 | 2 | 90 |
| 2018 January | 89 | 4 | 93 |
| 2017 December | 65 | 6 | 71 |
| 2017 November | 65 | 7 | 72 |
| 2017 October | 46 | 10 | 56 |
| 2017 September | 55 | 15 | 70 |
| 2017 August | 59 | 23 | 82 |
| 2017 July | 66 | 28 | 94 |
| 2017 June | 61 | 39 | 100 |
| 2017 May | 65 | 29 | 94 |
| 2017 April | 71 | 39 | 110 |
| 2017 March | 27 | 31 | 58 |
| 2017 February | 42 | 13 | 55 |
| 2017 January | 29 | 11 | 40 |
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