Case Report: Acquired Disseminated BCG in the Context of a Delayed Immune Reconstitution After Hematological Malignancy

ContextDisseminated infections due to Mycobacterium bovis Bacillus Calmette-Guérin (BCG) are unusual and occur mostly in patients with inborn error of immunity (IEI) or acquired immunodeficiency. However, cases of secondary BCGosis due to intravesical BCG instillation have been described. Herein, we present a case of severe BCGosis occurring in an unusual situation.Case DescriptionWe report one case of severe disseminated BCG disease occurring after hematological malignancy in a 48-year-old man without BCG instillation and previously vaccinated in infancy with no complication. Laboratory investigations demonstrated that he was not affected by any known or candidate gene of IEI or intrinsic cellular defect involving IFNγ pathway. Whole genome sequencing of the BCG strain showed that it was most closely related to the M. bovis BCG Tice strain, suggesting an unexpected relationship between the secondary immunodeficiency of the patient and the acquired BCG infection.ConclusionThis case highlights the fact that, in addition to the IEI, physicians, as well as microbiologists and pharmacists should be aware of possible acquired disseminated BCG disease in secondary immunocompromised patients treated in centers that administrate BCG for bladder cancers.

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Clinical Spectrum of Complications Induced by Intravesical Immunotherapy of Bacillus Calmette-Guérin for Bladder Cancer

Journal of Oncology ◽

10.1155/2019/6230409 ◽

2019 ◽

Vol 2019 ◽

pp. 1-11 ◽

Cited By ~ 4

Author(s):

Yuqing Liu ◽

Jian Lu ◽

Yi Huang ◽

Lulin Ma

Keyword(s):

Bladder Cancer ◽

Adverse Reactions ◽

Clinical Manifestations ◽

Bacillus Calmette Guerin ◽

Bcg Immunotherapy ◽

Bcg Therapy ◽

Intravesical Bcg ◽

Proven Efficacy ◽

Bcg Instillation ◽

Early Establishment

Because of its proven efficacy, intravesical Bacillus Calmette-Guérin (BCG) immunotherapy is an important treatment for nonmuscle invasive bladder cancer at high risk of recurrence or progression. However, approximately 8% of patients have to stop BCG instillation as a result of its complications. Complications induced by BCG therapy can have a variety of clinical manifestations. These adverse reactions may occur in conjunction with BCG instillation or may not develop until months or years after BCG cessation. An essential step in the management complications arising from BCG is early establishment of diagnosis, particularly for distant, disseminated, and obscure infections. Therefore we reviewed the literature on the potential complications after intravesical BCG immunotherapy for bladder cancer and provide an overview on the incidence, diagnosis, and treatment modality of genitourinary and systemic BCG-induced complications.

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BCG instillation versus radical cystectomy for high-risk NMIBC with squamous/glandular histologic variants

Scientific Reports ◽

10.1038/s41598-019-51889-0 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 2

Author(s):

Jungyo Suh ◽

Kyung Chul Moon ◽

Jae Hyun Jung ◽

Junghoon Lee ◽

Won Hoon Song ◽

...

Keyword(s):

High Risk ◽

Radical Cystectomy ◽

Bacillus Calmette Guerin ◽

Large Tumor ◽

Treatment Groups ◽

Appropriate Treatment ◽

Intravesical Bcg ◽

Risk Patients ◽

Cystectomy Group ◽

Bcg Instillation

Abstract This study aims to evaluate the effect of Bacillus Calmette-Guérin (BCG) instillation and radical cystectomy on high-risk NMIBC with squamous or glandular variants. We retrospectively reviewed the data of high-risk (T1 or CIS or HG or TaG1/G2 with multiple, recurrent, large tumor) NMIBC patients from January 2000 to December 2017. Comparative analysis of radical cystectomy, intravesical BCG, and observation groups was conducted in high-risk NMIBC with squamous or glandular histologic variants. Among the 1263 high-risk NMIBC patient, 62 (4.9%) were reported squamous or glandular histologic variants. Thirty patients underwent BCG instillation and 15 patients were subjected to radical cystectomy. Statistically significant differences were found between the three treatment groups in terms of underlying hypertension (p = 0.031), T stage (p = 0.022) and tumor multiplicity (p = 0.019). Similar 5-year OS (p = 0.893) and CSS (p = 0.811) were observed in each of BCG instillation and radical cystectomy group. BCG instillation showed survival benefit in both OS (p = 0.019) and CSS (p = 0.038) than in the observation group. In high-risk patients diagnosed with NMIBC bladder cancer with squamous or glandular histologic variants, both intravesical BCG and radical cystectomy showed survival gain. In conclusion, BCG instillation represents an appropriate treatment option in high-risk NMIBC with squamous or glandular histologic variant.

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A Case of Acquired Rifampin Resistance inMycobacterium bovisBacillus Calmette-Guérin-Induced Cystitis: Necessity for Treatment Guidelines

Canadian Journal of Infectious Diseases and Medical Microbiology ◽

10.1155/2006/263932 ◽

2006 ◽

Vol 17 (3) ◽

pp. 183-185 ◽

Cited By ~ 2

Author(s):

Joyce N Wolfe ◽

Kym S Blackwood-Antonation ◽

Meenu K Sharma ◽

Victoria J Cook

Keyword(s):

Drug Resistance ◽

Target Gene ◽

Treatment Guidelines ◽

Transitional Cell ◽

Bacillus Calmette Guerin ◽

Acquired Drug Resistance ◽

Elderly Female ◽

Intravesical Bcg ◽

Rifampin Resistance ◽

Bcg Instillation

A case of presumed bacillus Calmette-Guérin (BCG) cystitis in an elderly female patient following direct intravesical BCG instillation treatment for papillary transitional cell carcinoma is reported. The organism cultured from urine samples was eventually identified as a rifampin-resistantMycobacterium bovisBCG isolate. Because the patient had received rifampin monotherapy during the course of treatment for presumed BCG disease, the clinical picture favoured acquired rifampin resistance. Sequencing of the target gene for rifampin (rpoB) confirmed a known mutation responsible for conferring high levels of resistance to both rifampin and rifabutin (Ser531Tyr). To the authors' knowledge, this is the first reported case ofM bovisBCG disease in a non-HIV patient where the organism had acquired drug resistance to rifampin, and the second reported case ofM bovisBCG that had acquired drug resistance. The present case demonstrates the necessity to re-evaluate appropriate guidelines for the effective treatment of BCG disease.

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Beware of Drug Interactions Treating Iatrogenic Mycobacterium bovis Endocarditis from Intravesical BCG Instillation

European Journal of Case Reports in Internal Medicine ◽

10.12890/2021_002263 ◽

2021 ◽

Author(s):

Francesca Curri ◽

Andrea Da Porto ◽

Viviana Casarsa ◽

Daria Albini ◽

Giorgio Minen ◽

...

Keyword(s):

Bladder Cancer ◽

Mitral Valve ◽

Minimally Invasive ◽

Bacillus Calmette Guerin ◽

Antituberculous Therapy ◽

Intravesical Bcg ◽

Prosthetic Mitral Valve ◽

Intravesical Instillations ◽

Echocardiographic Evidence ◽

Bcg Instillation

We report a case of mechanical mitral valve endocarditis associated with miliary disseminated bacillus Calmette-Guerin (BCG) infection following intravesical instillations for minimally invasive bladder cancer in a 65-year-old man. The diagnosis was established by echocardiographic evidence of vegetation on the prosthetic mitral valve, miliary lesions in the lungs and evidence of bloodstream infection sustained by Mycobacterium. We successfully treated the patient with the classical regimen of quadruple antituberculous therapy.

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Disseminated Granulomatous Disease from Intravesical Instillation of Bacillus Calmette-Guerin

Case Reports in Oncological Medicine ◽

10.1155/2018/8280527 ◽

2018 ◽

Vol 2018 ◽

pp. 1-4 ◽

Cited By ~ 1

Author(s):

Sayed Ab. Reshad Ghafouri ◽

Alexander Brun ◽

Rohit Bhalla ◽

Craig Margulies ◽

Kevin Skole

Keyword(s):

Bladder Cancer ◽

Drug Toxicity ◽

Standard Treatment ◽

Superficial Bladder Cancer ◽

Treatment Options ◽

Intravesical Instillation ◽

Granulomatous Disease ◽

Bacillus Calmette Guerin ◽

Intravesical Bcg ◽

Bcg Instillation

Intravesical instillation of Bacillus Calmette-Guerin is one of the standard treatment options for superficial bladder cancer. While Bacillus Calmette-Guerin therapy is usually well tolerated with most patients experiencing only cystitis, in rare cases, it can lead to disseminated granulomatous disease. We present a case of a 72-year-old man with disseminated granulomatous disease from intravesical BCG instillation whose treatment was complicated by antimycobacterial drug toxicity.

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Reactive Arthritis – A Rare Complication of Intravesical BCG Instillation

European Journal of Case Reports in Internal Medicine ◽

10.12890/2020_001448 ◽

2020 ◽

Author(s):

Marta Freixa ◽

Sara Úria ◽

Glória Nunes da Silva

Keyword(s):

Effective Treatment ◽

Mycobacterium Bovis ◽

Reactive Arthritis ◽

Carcinoma In Situ ◽

Rare Complication ◽

Bacillus Calmette Guerin ◽

Gastrointestinal Infections ◽

Intravesical Bcg ◽

Bcg Instillation

Reactive arthritis (ReA) with the classic triad of arthritis, conjunctivitis and urethritis, previously termed Reiter’s syndrome, is a systemic illness, usually induced by genitourinary or gastrointestinal infections. However, it can be a rare complication of intravesical Bacillus Calmette-Guérin instillation (iBCG), a therapy prepared from attenuated strains of Mycobacterium bovis, a common and effective treatment for carcinoma in situ of the bladder (CisB). We report a case of a patient with CisB who developed ReA after iBCG. The symptoms resolved completely with corticosteroids. iBCG was stopped with no recurrence of carcinoma within 2 years.

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Disseminated Bacillus Calmette–Guérin (BCG) infection and acute exacerbation of interstitial pneumonitis: an autopsy case report and literature review

BMC Infectious Diseases ◽

10.1186/s12879-020-05396-7 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Gen Shimizu ◽

Ryota Amano ◽

Itaru Nakamura ◽

Akane Wada ◽

Masanobu Kitagawa ◽

...

Keyword(s):

Bone Marrow ◽

Bladder Cancer ◽

Acute Exacerbation ◽

Interstitial Pneumonitis ◽

Giant Cells ◽

Epithelioid Cell ◽

Bacillus Calmette Guerin ◽

Antituberculosis Drugs ◽

First Case ◽

Intravesical Bcg

Abstract Background Intravesical administration of Bacillus Calmette–Guérin (BCG) has proven useful for treatment and prevention of recurrence of superficial bladder cancer and in situ carcinoma. However, fatal side effects such as disseminated infections may occur. Early diagnosis and accurate therapy for interstitial pneumonitis (IP) are important because exacerbation of IP triggered by infections is the major cause of death. Although some fatality reports have suggested newly appeared IP after intravesical BCG treatment, to our knowledge, there are no reports which have demonstrated acute exacerbation of existing IP. Moreover, autopsy is lacking in previous reports. We report the case of a patient with fatal IP exacerbation after BCG instillation and the pathological findings of the autopsy. Case presentation A 77-year-old man with a medical history of IP was referred to our hospital because of fever and malaise. He had received an intravesical injection of BCG 1 day before the admission. His fever reduced after the use of antituberculosis drugs, so he was discharged home. He was referred to our hospital again because of a high fever 7 days after discharge. On hospitalisation, he showed high fever and systemic exanthema. Hepatosplenomegaly and myelosuppression were also observed. Biopsies revealed multiple epithelioid cell granulomas with Langhans giant cells of the liver and bone marrow. Biopsy DNA analyses of Mycobacterium bovis in the bone marrow, sputum, and blood were negative. His oxygen demand worsened drastically, and the ground-glass shadow expanded on the computed tomography scan. He was diagnosed with acute exacerbation of existing IP. We recommenced the antituberculosis drugs with steroid pulse therapy, but he died on day 35 because of respiratory failure. The autopsy revealed a diffuse appearance of multiple epithelioid cell granulomas with Langhans giant cells in multiple organs, although BCG was not evident. Conclusions We report the first case of acute exacerbation of chronic IP by BCG infection. This is also the first case of autopsy of a patient with acute exacerbation of existing IP induced by intravesical BCG treatment. Whether the trigger of acute IP exacerbation is infection or hypersensitivity to BCG is still controversial, because pathological evidence confirming BCG infection is lacking. Physicians who administer BCG against bladder cancer should be vigilant for acute exacerbation of IP.

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Bacillus Calmette-Guérin (BCG) Infection Following Intravesical BCG Administration as Adjunctive Therapy For Bladder Cancer

Medicine ◽

10.1097/md.0000000000000119 ◽

2014 ◽

Vol 93 (17) ◽

pp. 236-254 ◽

Cited By ~ 95

Author(s):

María Asunción Pérez-Jacoiste Asín ◽

Mario Fernández-Ruiz ◽

Francisco López-Medrano ◽

Carlos Lumbreras ◽

Ángel Tejido ◽

...

Keyword(s):

Bladder Cancer ◽

Adjunctive Therapy ◽

Bacillus Calmette Guerin ◽

Intravesical Bcg

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Possibile ruolo della citofluorometria (CFM) nel monitoraggio della risposta alla terapia endocavitaria con BCG nel carcinoma in situ della vescica: Monitoring the response to intravesical BCG in the treatment of cis: A possible role of flow cytometry

Urologia Journal ◽

10.1177/039156039506200212 ◽

1995 ◽

Vol 62 (2) ◽

pp. 245-247

Author(s):

M. De Siati ◽

D. Grassi ◽

N. Franzolin ◽

L.S. Azzolina

Keyword(s):

Flow Cytometry ◽

Carcinoma In Situ ◽

Recurrent Disease ◽

Intravesical Therapy ◽

Urinary Cytology ◽

Bacillus Calmette Guerin ◽

Intravesical Bcg

We report our experience on the treatment of carcinoma in situ (CIS) using intravesical therapy with the Bacillus Calmette-Guerin (BCG). From November 1992 to September 1994, 18 patients received treatment: 6 had associated CIS and 12 secondary CIS. Ploidy of each tumour was determined by flow cytometry. Aneuploidy was found in 12 cases, diploidy in 6 cases. After treatment, a standard bladder mapping was performed: 14 patients showed no evidence of cystoscopic and histological disease and if previously aneuploid, became diploid. 4 patients has recurrent disease after therapy; they were all aneuploid before treatment. One of these showed a persistent aneuploidy, although both voided urinary cytology and histological samples were negative. Six months later, a recurrent CIS was seen at the time of cystoscopy. These results enhance the interest in flow cytometry as a possible predictor of response to BCG in the treatment of CIS.

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An immigrant with acquired immunodeficiency syndrome presenting with a rash: A case report

SAGE Open Medical Case Reports ◽

10.1177/2050313x19829616 ◽

2019 ◽

Vol 7 ◽

pp. 2050313X1982961

Author(s):

Connie Zhang ◽

Megan A Sander

Keyword(s):

Human Immunodeficiency Virus ◽

Acquired Immunodeficiency Syndrome ◽

Systemic Disease ◽

Immunodeficiency Virus ◽

History Of ◽

Acquired Immunodeficiency ◽

Laboratory Investigations ◽

Polymerase Chain ◽

Immunodeficiency Syndrome ◽

Work Up

A 58-year-old woman from Zimbabwe, with a history of untreated human immunodeficiency virus, presented with leonine facies and a diffuse rash. The rash occurred in the context of a 1-year history of constitutional symptoms and cognitive decline. Laboratory investigations confirmed that her human immunodeficiency virus had progressed to acquired immunodeficiency syndrome. Through imaging, tissue biopsies, and polymerase chain reaction, a diagnosis of disseminated histoplasmosis was made. Since there was no history of travel and histoplasmosis is not locally endemic, the patient likely contracted this fungal infection more than 7 years ago, while living in Africa. We speculate that the histoplasmosis remained latent until her immune system began to decline. The work-up and management of this rare cutaneous presentation of a systemic disease, which should be added to the list of “great mimickers” in dermatology, are discussed.

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