Severe Pneumonia following intravescical BCG therapy in a patient with bladder cancer.

Objectives: We describe a man with a severe pneumonia secondary to disseminated Mycobacterium bovis-BCG infection after intravesical BCG instillation. This diagnosis was based on positive polymerase chain reaction for mycobacterium tubercolosis complex in bronchoalveolar lavage and on the presence of non necrotizing granulomas in transbronchial biopsy, histopathologically analogous to those found in previous bladder biopsies of the same patient. M. bovis-BCG was confirmed by a real time PCR assay in lung and bladder samples. Methods: A 66 years old man treated with periodical intravesical instillations ofBCGfor a non invasive papillary urothelial bladder cancer, after a traumatic catheterization, complained fever and dysuria; 2 days after he was hospitalized for acute respiratory failure. Chest CT scans were negative for the presence of pulmonary emboli, but showed bilateral interstitial-alveolar areas with ground glass opacities and thickened interlobular septa with crazy paving appearance. Empiric antibiotic therapy and systemic glucocorticoids were started with improvement of respiratory conditions. The patient underwent broncho-alveolar lavage which confirmed giant cells epitheliod microgranulomas and Mycobacterium tuberculosis complex was detected by PCR. A standard anti TB treatment with rifampicin, isoniazid, ethambutol and pyrazinamide (then modified for hepatotoxicity) was given for 9 months. Results: Anti TB treatment led to a complete resolution of clinical condition and a CT scan demonstrated totally disappearance of the lung infiltrate. A real time PCR assay later confirmed the presence of M.bovis-BCG strain, by amplification of primers detecting the peculiar absence of RD1 on mycobacterial genome found in lung and bladder of our patient but not in lung samples of two controls. Conclusions: Disseminated BCG disease is a rare and severe complication of intravesical BCG immunotherapy for bladder cancer; its diagnosis is often delayed or presumptive. We reported one of the few cases of BCG immunotherapy related pneumonia microbiologically confirmed and the first case with demonstration of M. bovis-BCG in involved tissues using a real time PCR. Further studies are necessary to standardize diagnostic methods, to early get a definitive diagnosis and to start a targeted therapy as soon as possible.