Management of hepatic granulomatous tuberculosis complicating intravesical BCG for superficial bladder cancer

Abstract

Intravesical bacille Calmette-Guérin (BCG) therapy is the most effective treatmentfor high-risk superficial bladder cancer. Severe systemic complications are rare, but may occur in approximately 1% of cases. We report a severe complicationof intravesical BCG: a disseminated Mycobacterium bovis infectionwith biopsy-proven granulomatous hepatitis in a patient with bladder cancer. We also elaborate on the different management alternatives.

Multi-organ failure with atypical liver granulomas following intravesical Bacillus Calmette-Guerin instillation

“…Disseminated infection ("BCG-itis") following intravesical BCG instillation is a rare, though well-recognized, sideeffect of this treatment modality that may present with an early or late onset [3][4][5][6][7][8][9] . In particular, biopsy-proven, BCGinduced granulomatous hepatitis and pneumonitis may occur in up to 0.7% and 0.2% of cases, respectively [3,4] .…”

“…Liver biopsies have been reported with positive acid-fast staining in less than 10% of liver tuberculosis cases [6] . This should not inhibit physicians from instigating the recommended anti-mycobacterial regimen (a combination of isoniazid, rifampicin and ethambutol; M.bovis strains are usually resistant to pyrazinamide) for three to six months combined with steroids for three months, as this therapeutic scheme has been reported to be effective in most of the cases of suspected M.bovis disseminated infection [3,5,7,8] . Thus, although in this case we could not isolate M.bovis from any of the different biological specimens (blood, urine, sputum, bone marrow and liver), we strongly considered the possibility of a BCG-induced disseminated infection, in agreement with observations by other colleagues [5,10] .…”

“…This response is consistent with that reported by several authors when a possible BCG-related pneumonitis was suspected [7,10] . Usually, the liver is only mildly affected during BCG-related disseminated infection [4,5,8] and this is usually associated with the presence of granulomas containing Langhan's giant cells [5,7,8] . Our patient, however, developed a severe form of acute hepatic failure, early signs of which were evident even before the introduction of anti-mycobacterial therapy ( Figure 1 and Table 1).…”

“…Significant adverse reactions are uncommon (< 5%), but systemic complications such as severe sepsis, pancytopenia, acute respiratory failure, abscess formation, mycotic aneurysms and haemolytic-uremic syndrome have also been reported [3,4] . BCG-induced disseminated M.bovis infection has been associated with the histological appearance of epithelioid granulomas in various organs, such as the liver, prostate, lungs and bone marrow [5][6][7][8] .…”

Complications of Intravesical Bacillus Calmette-Guérin

“…Among these, there were 2 deaths [42][43][44][45]. [36][37][38][39] All 6 patients met the criteria for systemic inflammatory immune response during the course of their illness. Common features include fever, hepatosplenomegaly, transaminitis, and elevated inflammatory markers.…”