Granulomatous lung disease associated with the use of intravesical mitomycin

López Ramírez, Cecilia; Gómez Izquierdo, Lourdes; Rodríguez Portal, José Antonio

doi:10.1016/j.medcle.2020.05.059

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B) Anatomical pathology of the transbronchial biopsy: image corresponding to a non-necrotising granuloma consisting of cells of histiocytic morphology, some multinucleated cells, and lymphocytes in the periphery." ] ] ] "textoCompleto" => "A wide variety of lung diseases can be associated with the presence of granulomas, mainly granulomatous diseases such as sarcoidosis, hypersensitivity pneumonitis, mycobacterial or fungal lung infections, and a wide variety of causative agents, including certain drugs<a class="elsevierStyleCrossRef" href="#bib0005">1</a>. Intravesical mitomycin C (MMC) chemotherapy is used in the treatment of superficial bladder cancer due to its effect in reducing recurrences<a class="elsevierStyleCrossRef" href="#bib0010">2</a>. Systemic mitomycin-induced pulmonary toxicity is an uncommon side effect, but has been described in the literature, with interstitial lung disease related to intravesical MMC instillation being unusual, as in the case described.We report the case of a 57-year-old male with a personal history of being a former smoker (cumulative consumption of 25 packs/year). Diagnosed in 2008 with superficial papillary urothelial carcinoma, underwent transurethral resections, and since 2014, following multifocal recurrence, on treatment with intravesical MMC instillations in monotherapy for one year. He had not received prior treatments with Bacillus Calmette-Guérin therapy or other chemotherapeutic agents. The patient was referred to the pulmonology department in October 2015 for clinical manifestations consisting of exertional dyspnoea progressing to mMRC grade 3 and dry cough, without fever or associated chest pain. Laboratory tests showed creatinine 1.16 mg/dl, urea and ionogram, normal haematological and coagulation series, normal immunoglobulins, and tumour markers, with an angiotensin-converting enzyme of 127 μg/l. Spirometry showed a restrictive pattern (FVC of 56% with a TLC of 52%) and an abnormal CO diffusion capacity (37%). Chest CT scan showed extensive bilateral interstitial involvement with ground glass pattern, small mediastinal lymphadenopathies and consolidating lesions at the bases, without honeycombing, together with air trapping areas and paraseptal emphysema (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A). A bronchoscopy was performed without endoscopic findings, microorganisms were ruled out through culture and PCR, and bronchoalveolar lavage showed lymphocytic alveolitis with a CD4/CD8 > 6 ratio, confirming non-necrotising granulomatous inflammation in the anatomical pathology study of the transbronchial biopsy (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B). Exposure to organic antigens was ruled out through clinical history, pulmonary infection, including mycobacteria, was ruled out by microbiology and sarcoidosis, given the atypical radiological manifestation and the absence of involvement of other organs. For this reason, treatment with MMC was discontinued and given the patient's clinical situation, there was no possibility of waiting for a response after drug discontinuation alone, so treatment with prednisone 30 mg/24 h with progressive dose reduction had to be started, with improvement of lung lesions and pulmonary function.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>MMC is an agent with antibiotic and cytotoxic properties, produced by the Streptomyces caespitosus bacteria, which acts by inhibiting DNA synthesis. Pulmonary toxicity following MMC treatment is very rare with systemic administration<a class="elsevierStyleCrossRef" href="#bib0015">3</a>, and even rarer with intravesical administration. Like other chemotherapy agents, most adverse reactions to MMC are dose-dependent, with 20 mg/m2 being accepted as the threshold dose at which the likelihood of pulmonary involvement would increase. After a systematic review of the scientific evidence, the occurrence of granulomatous disease in patients treated with MMC has been reported<a class="elsevierStyleCrossRef" href="#bib0020">4</a>. As in our case, a causal relationship between MMC therapy and granulomatous lung disease is accepted due to the improvement in the clinical condition after its discontinuation. However, hypotheses, including immunological reactions with immunocomplex formation, are now being put forward with the aim of elucidating the pathogenetic mechanisms involved in the development of granulomatous disease in patients treated with MMC." "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: López Ramírez C, Gómez Izquierdo L, Rodríguez Portal JA. Enfermedad granulomatosa pulmonar asociada al uso de mitomicina intravesical. Med Clin (Barc). 2020. https://doi.org/10.1016/j.medcli.2020.05.045" ] ] "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 547 "Ancho" => 1600 "Tamanyo" => 204748 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "A) Contrast-enhanced chest CT showing extensive bilateral interstitial involvement, without honeycombing, with areas of increased ground glass density, consolidation lesions, and air trapping. B) Anatomical pathology of the transbronchial biopsy: image corresponding to a non-necrotising granuloma consisting of cells of histiocytic morphology, some multinucleated cells, and lymphocytes in the periphery." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:4 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Differential diagnosis of granulomatous lung disease: clues and pitfalls" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "S. Ohshimo" 1 => "J. Guzmán" 2 => "U. Costabel" 3 => "F. Bonella" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Eur Respir Rev" "fecha" => "2017" "volumen" => "26" "paginaInicial" => "1" "paginaFinal" => "16" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Intravesical Bacillus Calmette-Guérin versus mitomycin C for Ta and T1 bladder cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Schmidt" 1 => "F. Kunath" 2 => "B. Coles" 3 => "D.L. Draeger" 4 => "L.M. Krabbe" 5 => "R. Dersch" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/14651858.CD011935.pub2" "Revista" => array:5 [ "tituloSerie" => "Cochrane Database Syst Rev" "fecha" => "2020" "volumen" => "1" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30707445" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0140673618314855" "estado" => "S300" "issn" => "01406736" ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pulmonary fibrosis and endovesical mitomycin C" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "J.M. Janeiro Pais" 1 => "V.P. Casas Agudo" 2 => "D. López Garcia" 3 => "J. González Dacal" 4 => "C. Lamas Meilán" 5 => "M. González Martín" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/s0210-4806(09)74237-8" "Revista" => array:6 [ "tituloSerie" => "Actas Urol Esp" "fecha" => "2009" "volumen" => "33" "paginaInicial" => "822" "paginaFinal" => "825" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19757670" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Lung sarcoidosis following instillation of mitomycin C in the urinary bladder" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "M.A. Cuervo Pinna" 1 => "C. Cuervo Pinna" 2 => "S. Macías Castillo" 3 => "J.C. Bureo Dacal" 4 => "M.J. Espada Alonso" 5 => "J. Pimentel Leo" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "An Med Interna" "fecha" => "2001" "volumen" => "18" "paginaInicial" => "641" "paginaFinal" => "643" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11852501" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23870206/0000015700000004/v2_202201010719/S2387020621003673/v2_202201010719/en/main.assets" "Apartado" => array:4 [ "identificador" => "43309" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letters to the Editor" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23870206/0000015700000004/v2_202201010719/S2387020621003673/v2_202201010719/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020621003673?idApp=UINPBA00004N"]

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Vol. 157. Issue 4.

Pages 206-207 (August 2021)

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