Late Onset Disseminated Mycobacterium bovis in a Patient After Bacillus Calmette-Guerin (BCG) Immunotherapy

Abstract

Introduction: Disseminated Mycobacterium bovis is a rare but recognized complication of intravesical BCG infusion for bladder cancer. We present a patient with pulmonary and bone marrow involvement of M. bovis 1.5 years after completing BCG therapy. CASE PRESENTATION: A 76 year-old male with a history of bladder cancer status post completion of intravesical BCG therapy in October 2013 presented with a 3 month history of night sweats, fatigue, unintentional weight loss, and a dry cough. On admission, he was found to be hypercalcemic and pancytopenic. A bone marrow biopsy demonstrated extensive noncaseating epithelioid granulomas (figure 1A). A PET-CT revealed bilateral ground glass opacification in the dependent portions of the lower lobes and perihilum. There were no nodules, hilar or mediastinal lymphadenopathy, or findings suggestive of interstitial lung disease. Transbronchial lung biopsies of the right lower lobe revealed noncaseating granulomas once again (Figure 1B). The mycobacterium tuberculosis complex returned positive. He was empirically treated for disseminated BCG with isoniazid, ethambutol, rifampin, and prednisone. M. bovis was confirmed from his bone marrow biopsy 6.5 weeks later (Figure 2). DISCUSSION: BCG immunotherapy is an effective alternative to chemotherapy in patients with early stage bladder cancer. Intravesicular BCG infection complication rate is ~4%, and patients typically present within the first 3 months. Sarcoidosis is the one of the main differential diagnoses to consider in a patient presenting with constitutional symptoms, hypercalcemia, and noncaseating granulomas seen on histopathologic specimens. However, in the setting of previous intravesicular BCG therapy, disseminated BCG must be considered as well. The BCG strain used as treatment in bladder cancer remains a viable pathogen, and instillation is not without risk. Our case had further diagnostic complexity as M. tuberculosis was considered, and the positive MTB complex result could have been misleading. MTB complex testing by DNA probe will be positive in both M. tuberculosis and M. bovis, necessitating confirmation by culture. Malignancy was also considered, but was excluded on the basis of histopathology. The timeline of a patient initiating BCG therapy 5 years prior and presenting with disseminated disease 1.5 years after his final treatment made for a unique presentation of this rare complication. Conclusions: In patients with a history of intravesicular BCG therapy presenting with constitutional symptoms and subsequently found to have noncaseating granulomas on biopsy, disseminated M. bovis infection should be strongly considered.