An 81 y.o. male presents with fatigue. what do you notice on exam?
hint: he has a history of bladder cancer and was treated with BCG; then grew M bovis out of the urine.
Our patient had a history of urothelial cancer treated with R nephrectomy and BCG (the last treatment in 2016). In July 2023 he presented with immune complex hepatitis from his nivolumab which was stopped. He received prednisone and mycophenolate and his liver functions improved. He was tapered off steroids and mycophenolate.
He grew Mycobacterium bovis from a urine culure sent in July that resulted 8/28. Treatment was started with INH, rifampin, ethambutol and Vit B6 in Sept 2023 when he had a follow up with ID.
He developed jaundice because of the treatment for his GU tbc. While most commonly GU tuberculosis is reported after hematogenous spread of chronic latent pulmonary tuberculosis , it has also been reported after BCG treatment for bladder cancer with out pulmonary involvement. Our patient had no evidence of pulmonary tuberculosis.
Mycobacterium bovis infects cattle and can be transmitted in unpasteurized milk.
What is BCG and why is it used to treat urothelial cancer?
In 1904 Calmette isolated M. bovis from the milk of an infected cow and with his partner Guerin ,worked to produce a weakened version of the bacteria that could safely be used as a vaccine. Bacillus Calmette-Guerin(BCG) is the only vaccine for prevention of tuberculosis. It has exised for 80 years and is routinely used in neonates in developing countries. It has a documented protective effect against meningitis and and disseminated tuberculosis in children.
In 1929 studies showed that people with tuberculosis have a lower incidence of cancer of all types. It was also discovered that BCG could be used intradermally to treat melanoma. The therapeutic effect of BCG is based on contact with tumor cells and subsequent immune stimulation inducing an inflammatory response that selectively affects tumor cells. Currently BCG is still used for urothelial cancers.
BCG can cause systemic dissemination similar to M. tuberculosis with spinal infections
What are the complications of BCG?
Prior BCG vaccination will lead to a positive skin test for tuberculosis. The Quantiferon-TB Gold test(the interferon-gamma release assy) will not be positive.
BCG is rarely associated with systemic infection including granulomatous hepatitis, mycotic pseudoaneurysms and lymphadenitis. When instilled in the bladder, local infections can occur in the scrotum, prostate or kidneys. This can occur many years after the initial BCG treatment. The infection may also disseminate.
Treatment is required even if tuberculosis is confined to the GU system, since granulomas caused by BCG can cause calcification and renal destruction.
The INH and rifampin were stopped in our patient. Over a month in the hospital his bilirubin gradually declined. Consulting with a national tuberculosis expert, his regimen changed to moxifloxacin, linezolid and ethambutol( when the bilirubin is < 2). He remains hospitalized with daily EKGs to assess the QT on moxifloxacin.
Green D, Kawashima A, Menias C, et al. Complications of intravesical BCG immunotherapy for bladder cancer. Radiographics vol 39(1).
Lawn S, Zumla A. Tuberculosis (Seminar). Lancet 378,57-72,
Muneer A, Macrae B, Krishnamoorthy S, et al. Urogenital tuberculosis-epidemiology, pathogenesis and clinical features. Nat Rev Urol. 2019 Oct;16910):573-598.