Letter to the Editor
Hypersensitivity Pneumonitis as a Complication of Intravesical BCG Therapy for Bladder Cancer
Neumonitis por hipersensibilidad como complicación del tratamiento con BCG intravesical por carcinoma de vejiga
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Con ventana de parénquima pulmonar se visualiza un patrón de vidrio deslustrado, así como nodulillos centrolobulillares en ambos campos pulmonares. B) <span class="elsevierStyleItalic">Western blot</span>. En el carril 1 se muestra suero de un individuo asintomático tratado con BCG; en los carriles 2, 3 y 4 se muestran el caso índice después de 3, 7 y 51 días de la terapia con corticosteroides. En el carril 5 se presenta el suero de un individuo con historia de tuberculosis, y en el carril 6 un control sano. La flecha muestra una única banda (anticuerpos específicos anti-BCG). C) Inmunodifusión doble de los sueros 1 y 2. 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"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" => "Ángel Luis" "apellidos" => "Castaño Núñez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "José Antonio" "apellidos" => "Rodríguez Portal" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Neumología, Unidad Médico-Quirúrgica de Enfermedades Respiratorias, Hospital Universitario Virgen del Rocío, Sevilla, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Inmunología, Hospital Universitario Virgen del Rocío, Sevilla, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Neumonitis por hipersensibilidad como complicación del tratamiento con BCG intravesical por carcinoma de vejiga" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 701 "Ancho" => 1800 "Tamanyo" => 185719 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(A) Chest HRCT. Pulmonary parenchymal window shows a ground glass pattern and small centrilobular nodules in both lung fields. (B) Western blot. Lane 1 shows the serum of an asymptomatic individual receiving BCG; lanes 2, 3, and 4 show the index case after 3, 7, and 51 of corticosteroid therapy. Lane 5 shows the serum of an individual with a history of tuberculosis, and lane 6 is that of a healthy control. The arrow indicates a single band (specific anti-BCG antibodies). (C) Double immunodiffusion of sera 1 and 2. Arrows indicate precipitation bands.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Hypersensitivity pneumonitis (HP) or extrinsic allergic alveolitis is a pulmonary interstitial disease mainly caused by sensitization to a variety of inhaled organic particles.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> The airborne antigens which most commonly lead to the development of this hypersensitivity reaction are thermophiles, molds, and avian antigens.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> However, some cases caused by non-inhaled medications have also been reported, including exposure to bacillus Calmette-Guérin (BCG) in the treatment of urothelial bladder carcinoma,<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a> such as the one we describe here.</p><p id="par0010" class="elsevierStylePara elsevierViewall">A 73-year-old man, former smoker (accumulated consumption of 30 pack-years), arterial hypertension, with no known drug allergies. He did not report any occupational or environmental exposure to birds, feathers or other organic substances. He had been diagnosed 3 months previously with superficial papillary urothelial carcinoma and was receiving treatment with intravesical BCG. He was admitted with a 10-day history of acute clinical symptoms, consisting of general malaise, deterioration, and fever 39<span class="elsevierStyleHsp" style=""></span>°C, coinciding with the eighth instillation of BCG. Clinical laboratory results showed leukocytes 11<span class="elsevierStyleHsp" style=""></span>900 (neutrophilos 81%), C-reactive protein 87<span class="elsevierStyleHsp" style=""></span>mg/dl, and elevated liver function markers (GGT and AP). Tumor markers and angiotensin converting enzyme were normal. Cultures of sputum, urine, bronchoalveolar lavage (BAL), and blood, including Löwenstein-Jensen medium, were negative, as were pneumococcal and Legionella urinary antigen testing. Immunoglobulins (Ig) G and M were normal. Serum IgG (precipitins) for molds, birds, and feathers were negative. Chest HRCT revealed a ground glass pattern in both upper lobes, small centrilobular nodules, and consolidations in the lung bases (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>(A)). Cell distribution in BAL was: alveolar macrophages 44% and lymphocytes 56%. Flow cytometry immunophenotyping of the lymphocyte population showed: CD3+ 97.58%; CD4+ 91.88%; CD8+ 5.39%; and CD4/CD8 ratio 17. Mucosa and bronchial cartilage were retrieved by transbronchial biopsy. Spirometry was normal. Serum levels of specific anti-BCG IgG were detected using 2 different immunological techniques, double immunodiffusion (DID), and Western blot.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Treatment began with methylprednisolone 40<span class="elsevierStyleHsp" style=""></span>mg/24<span class="elsevierStyleHsp" style=""></span>h, with improvement of pulmonary lesions, and the BCG instillations were discontinued. The clinical picture did not reappear after withdrawal of the corticosteroid treatment.</p><p id="par0020" class="elsevierStylePara elsevierViewall">BCG is an attenuated live strain of <span class="elsevierStyleItalic">Mycobacterium bovis</span> used in the intravesical treatment of superficial bladder cancer.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> It is well tolerated and effective, but not completely free of side effects. HP as a rare complication of this immunotherapy has been detected in 0.7% of cases.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">For diagnosis, certain clinical, radiological, histological, and immunological criteria are needed. Clinical criteria tend to be non-specific. Chest HRCT shows a ground glass pattern, centrilobular nodules, and areas of consolidation. Lung biopsy obtained by bronchoscopy generally reveals non-caseifying granulomas, and BAL often contains >40% lymphocytes. It is very important to ensure that the patient has not developed miliary pneumonitis due to BCG, so presence of the bacillus must be ruled out using microbiological techniques.</p><p id="par0030" class="elsevierStylePara elsevierViewall">The presence of specific antibodies against BCG is one of the major diagnostic criteria.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">1–5</span></a> For this reason, we performed a specific anti-BCG antibody assay using DID and Western blot (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B and C), which detected a specific band in our patient but not in the controls (a symptom-free bladder cancer patient receiving BCG and a tuberculosis patient). After the patient received steroid treatment, the intensity of the specific bands could be seen to diminish on the DID, and to a lesser extent on the Western blot, indicating a reduction in antibody concentrations.</p><p id="par0035" class="elsevierStylePara elsevierViewall">In our case, then, in the absence of a diagnostic transbronchial biopsy, evidence of high-intensity lymphocytic alveolitis, suggestive clinical symptoms, and the presence of specific anti-BCG antibodies were key to reaching a diagnosis.</p><p id="par0040" class="elsevierStylePara elsevierViewall">A review of PubMed between 1966 and 2013 reveals that this is first time 2 different techniques, along with a control patient receiving the same treatment, have been used to demonstrate the presence of anti-BCG antibodies possibly causative of HP.</p><p id="par0045" class="elsevierStylePara elsevierViewall">As in any HP caused by a known agent, the main treatment is withdrawal of the causative agent and administration of oral corticosteroids.</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: Carrasco Hernández L, Castaño Núñez ÁL, Rodríguez Portal JA. Neumonitis por hipersensibilidad como complicación del tratamiento con BCG intravesical por carcinoma de vejiga. Arch Bronconeumol. 2016;52:445–446.</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" => 701 "Ancho" => 1800 "Tamanyo" => 185719 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(A) Chest HRCT. Pulmonary parenchymal window shows a ground glass pattern and small centrilobular nodules in both lung fields. (B) Western blot. Lane 1 shows the serum of an asymptomatic individual receiving BCG; lanes 2, 3, and 4 show the index case after 3, 7, and 51 of corticosteroid therapy. Lane 5 shows the serum of an individual with a history of tuberculosis, and lane 6 is that of a healthy control. The arrow indicates a single band (specific anti-BCG antibodies). (C) Double immunodiffusion of sera 1 and 2. Arrows indicate precipitation bands.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0030" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hypersensitivity pneumonitis: a broader perspective" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "C. Navarro" 1 => "M. Mejía" 2 => "M. Gaxiola" 3 => "F. Mendoza" 4 => "G. Carrillo" 5 => "M. 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Fanlo" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "An Sist Sanit Navar" "fecha" => "2005" "volumen" => "28" "numero" => "Suppl. 1" "paginaInicial" => "S91" "paginaFinal" => "S99" ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/15792129/0000005200000008/v1_201607230336/S1579212916301203/v1_201607230336/en/main.assets" "Apartado" => array:4 [ "identificador" => "49861" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Scientific letters" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/15792129/0000005200000008/v1_201607230336/S1579212916301203/v1_201607230336/en/main.pdf?idApp=UINPBA00003Z&text.app=https://archbronconeumol.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1579212916301203?idApp=UINPBA00003Z" ]
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| 2024 August | 74 | 53 | 127 |
| 2024 July | 59 | 23 | 82 |
| 2024 June | 98 | 32 | 130 |
| 2024 May | 120 | 29 | 149 |
| 2024 April | 82 | 30 | 112 |
| 2024 March | 50 | 27 | 77 |
| 2024 February | 31 | 21 | 52 |
| 2023 March | 7 | 4 | 11 |
| 2023 February | 52 | 20 | 72 |
| 2023 January | 41 | 32 | 73 |
| 2022 December | 62 | 40 | 102 |
| 2022 November | 64 | 36 | 100 |
| 2022 October | 62 | 38 | 100 |
| 2022 September | 49 | 37 | 86 |
| 2022 August | 48 | 44 | 92 |
| 2022 July | 40 | 38 | 78 |
| 2022 June | 51 | 32 | 83 |
| 2022 May | 49 | 41 | 90 |
| 2022 April | 45 | 29 | 74 |
| 2022 March | 63 | 55 | 118 |
| 2022 February | 53 | 23 | 76 |
| 2022 January | 113 | 46 | 159 |
| 2021 December | 86 | 35 | 121 |
| 2021 November | 53 | 47 | 100 |
| 2021 October | 68 | 46 | 114 |
| 2021 September | 45 | 51 | 96 |
| 2021 August | 38 | 27 | 65 |
| 2021 July | 37 | 28 | 65 |
| 2021 June | 62 | 44 | 106 |
| 2021 May | 66 | 44 | 110 |
| 2021 April | 109 | 128 | 237 |
| 2021 March | 98 | 24 | 122 |
| 2021 February | 57 | 21 | 78 |
| 2021 January | 60 | 22 | 82 |
| 2020 December | 58 | 24 | 82 |
| 2020 November | 67 | 18 | 85 |
| 2020 October | 53 | 22 | 75 |
| 2020 September | 57 | 14 | 71 |
| 2020 August | 35 | 21 | 56 |
| 2020 July | 47 | 23 | 70 |
| 2020 June | 67 | 11 | 78 |
| 2020 May | 63 | 26 | 89 |
| 2020 April | 143 | 28 | 171 |
| 2020 March | 47 | 17 | 64 |
| 2020 February | 59 | 32 | 91 |
| 2020 January | 56 | 27 | 83 |
| 2019 December | 44 | 16 | 60 |
| 2019 November | 45 | 24 | 69 |
| 2019 October | 42 | 18 | 60 |
| 2019 September | 59 | 13 | 72 |
| 2019 August | 49 | 14 | 63 |
| 2019 July | 31 | 19 | 50 |
| 2019 June | 34 | 13 | 47 |
| 2019 May | 52 | 42 | 94 |
| 2019 April | 47 | 27 | 74 |
| 2019 March | 50 | 28 | 78 |
| 2019 February | 45 | 23 | 68 |
| 2019 January | 42 | 19 | 61 |
| 2018 December | 53 | 23 | 76 |
| 2018 November | 66 | 26 | 92 |
| 2018 October | 80 | 26 | 106 |
| 2018 September | 26 | 16 | 42 |
| 2018 May | 14 | 0 | 14 |
| 2018 April | 39 | 3 | 42 |
| 2018 March | 13 | 3 | 16 |
| 2018 February | 32 | 8 | 40 |
| 2018 January | 26 | 7 | 33 |
| 2017 December | 24 | 6 | 30 |
| 2017 November | 19 | 6 | 25 |
| 2017 October | 16 | 3 | 19 |
| 2017 September | 18 | 7 | 25 |
| 2017 August | 20 | 12 | 32 |
| 2017 July | 19 | 9 | 28 |
| 2017 June | 32 | 11 | 43 |
| 2017 May | 34 | 11 | 45 |
| 2017 April | 26 | 9 | 35 |
| 2017 March | 15 | 16 | 31 |
| 2017 February | 15 | 7 | 22 |
| 2017 January | 13 | 4 | 17 |
| 2016 December | 19 | 22 | 41 |
| 2016 November | 38 | 33 | 71 |
| 2016 October | 4 | 5 | 9 |
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