Intravesical BCG Therapy as Cause of Miliary Pulmonary Tuberculosis

Abstract

Immunotherapy with intravesical bacillus Calmette-Guérin (BCG) is considered the most effective adjuvant to endoscopic resection of bladder urothelial carcinoma in the therapeutic management of non-muscle invasive (NMIBC) at intermediate and high risk of recurrence and progression (pTa - pT1 and high-grade carcinoma in situ, CIS). Despite its proven efficacy, this type of treatment can determine local and systemic side effects of moderate or severe gravity, with the histological diagnosis of epithelioid granulomas in different organs, even in the absence of microbiological positivity of BCG. The immunotherapy with BCG is usually well tolerated and the virulence of the attenuated BCG is very low in immuno-competent patients, although only 16% of patients are able to receive all the instillations of the maintenance period (3 years) of treatment provided by the protocols, precisely because of side effects. Minor side effects usually resolve within a few hours or days. They develop in 3-5% of patients and usually consist of local infectious complications. Manifestations of BCG dissemination, such as vascular and ocular complications, are much less common, while BCG-disseminated infections, with granulomatous pneumonia or hepatitis present, are quite rare, representing 0.5-2% of the complications recorded. We present the clinical case of granulomatous lung and possibly liver infection caused by BCG in a patient aged 56 years being treated for several weeks with intravesical BCG for NIMBC pT1 high grade associated with CIS.

Bacillus Calmette-Guérin pneumonitis after intravesical instillation: Report of two cases and a review of the literature

“…However, the distinction between hypersensitivity reaction and systemic infection may be difficult in individual cases 10,27,28 . The identification of mycobacteria in distant organs obviously supports the infectious etiology 33 , but negative findings are more difficult to interpret 14 . The presence of granuloma is considered a hallmark of systemic infection even in the absence of positive microbiological findings.…”

Effectivity of intravescical thermo-chemotherapy prophylaxis for patients with high recurrence and progression risk for non-muscle invasive bladder cancer

“…Thus, intravesical immunotherapy with BCG or MMC is used for preventing recurrence (1). It is well known that BCG can significantly reduce the disease progression and recurrence rate but at the same time can also produce serious side effects such as voiding problems, urinary infection, haematuria up to miliary tubercolosis (10,11). In these cases only MMC can be used as intravescical therapy (12).…”

Systematic Review: Safety of Intravesical Therapy for Bladder Cancer in the Era of COVID-19

“…An interstitial pattern on chest radiography, lymphocytosis on bronchial alveolar lavage (BAL) and absence of granulomas on lung biopsy, as well as negative sputum and tissue cultures, are indicative of hypersensitivity response. [20] Mycobacterial pneumonia is characterized by biopsies revealing granulomata and radiographic evidence of consolidation, although testing for acid-fast bacteria (AFB) may be negative. [20] A large analysis of 2602 patients treated with intravesical BCG revealed 0.4% of patients developed life-threatening BCG sepsis, and 0.7% developed granulomatous pneumonitis.…”

“…[20] Mycobacterial pneumonia is characterized by biopsies revealing granulomata and radiographic evidence of consolidation, although testing for acid-fast bacteria (AFB) may be negative. [20] A large analysis of 2602 patients treated with intravesical BCG revealed 0.4% of patients developed life-threatening BCG sepsis, and 0.7% developed granulomatous pneumonitis. [21] With regard to other intravesical therapy, MMC has little systemic absorption due to low molecular weight, and chemical cystitis is common.…”