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Published in: BMC Infectious Diseases 1/2020

Open Access 01-12-2020 | Isoniazid | Case report

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

Authors: Gen Shimizu, Ryota Amano, Itaru Nakamura, Akane Wada, Masanobu Kitagawa, Shuta Toru

Published in: BMC Infectious Diseases | Issue 1/2020

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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.
Literature
1.
go back to reference Morales A, Eidinger D, Bruce AW. Intracavitary Bacillus Calmette–Guérin in the treatment of superficial bladder tumors. J Urol. 1976;116(2):180–3.CrossRef Morales A, Eidinger D, Bruce AW. Intracavitary Bacillus Calmette–Guérin in the treatment of superficial bladder tumors. J Urol. 1976;116(2):180–3.CrossRef
2.
go back to reference Koya MP, Simon MA, Soloway MS. Complications of intravesical therapy for urothelial cancer of the bladder. J Urol. 2006;175(6):2004–10.CrossRef Koya MP, Simon MA, Soloway MS. Complications of intravesical therapy for urothelial cancer of the bladder. J Urol. 2006;175(6):2004–10.CrossRef
3.
go back to reference Um SJ, Lee SK, Yang DK. Hypersensitivity pneumonitis following intravesical bacille Calmette–Guerin immunotherapy for superficial bladder cancer. J Investig Allergol Clin Immunol. 2009;19(3):230–2.PubMed Um SJ, Lee SK, Yang DK. Hypersensitivity pneumonitis following intravesical bacille Calmette–Guerin immunotherapy for superficial bladder cancer. J Investig Allergol Clin Immunol. 2009;19(3):230–2.PubMed
4.
go back to reference Perez-Jacoiste Asin MA, Fernandez-Ruiz M, Lopez-Medrano F, Lumbreras C, Tejido A, San Juan R, Arrebola-Pajares A, Lizasoain M, Prieto S, Aguado JM. Bacillus Calmette–Guerin (BCG) infection following intravesical BCG administration as adjunctive therapy for bladder cancer: incidence, risk factors, and outcome in a single-institution series and review of the literature. Medicine (Baltimore). 2014;93(17):236–54.CrossRef Perez-Jacoiste Asin MA, Fernandez-Ruiz M, Lopez-Medrano F, Lumbreras C, Tejido A, San Juan R, Arrebola-Pajares A, Lizasoain M, Prieto S, Aguado JM. Bacillus Calmette–Guerin (BCG) infection following intravesical BCG administration as adjunctive therapy for bladder cancer: incidence, risk factors, and outcome in a single-institution series and review of the literature. Medicine (Baltimore). 2014;93(17):236–54.CrossRef
5.
go back to reference Lamm DL, van der Meijden PM, Morales A, Brosman SA, Catalona WJ, Herr HW, Soloway MS, Steg A, Debruyne FM. Incidence and treatment of complications of bacillus Calmette–Guerin intravesical therapy in superficial bladder cancer. J Urol. 1992;147(3):596–600.CrossRef Lamm DL, van der Meijden PM, Morales A, Brosman SA, Catalona WJ, Herr HW, Soloway MS, Steg A, Debruyne FM. Incidence and treatment of complications of bacillus Calmette–Guerin intravesical therapy in superficial bladder cancer. J Urol. 1992;147(3):596–600.CrossRef
6.
go back to reference Cho JL, McDermott S, Tsibris AM, Mark EJ. Case records of the Massachusetts General Hospital. Case 37-2015. A 76-year-old man with fevers, leukopenia, and pulmonary infiltrates. N Engl J Med. 2015;373(22):2162–72.CrossRef Cho JL, McDermott S, Tsibris AM, Mark EJ. Case records of the Massachusetts General Hospital. Case 37-2015. A 76-year-old man with fevers, leukopenia, and pulmonary infiltrates. N Engl J Med. 2015;373(22):2162–72.CrossRef
7.
go back to reference Glasser RM, Walker RI, Herion JC. The significance of hematologic abnormalities in patients with tuberculosis. Arch Intern Med. 1970;125(4):691–5.CrossRef Glasser RM, Walker RI, Herion JC. The significance of hematologic abnormalities in patients with tuberculosis. Arch Intern Med. 1970;125(4):691–5.CrossRef
8.
go back to reference Molina JM, Rabian C, D'Agay MF, Modai J. Hypersensitivity systemic reaction following intravesical bacillus Calmette–Guerin: successful treatment with steroids. J Urol. 1992;147(3):695–7.CrossRef Molina JM, Rabian C, D'Agay MF, Modai J. Hypersensitivity systemic reaction following intravesical bacillus Calmette–Guerin: successful treatment with steroids. J Urol. 1992;147(3):695–7.CrossRef
9.
go back to reference Israel-Biet D, Venet A, Sandron D, Ziza JM, Chretien J. Pulmonary complications of intravesical Bacille Calmette–Guerin immunotherapy. Am Rev Respir Dis. 1987;135(3):763–5.PubMed Israel-Biet D, Venet A, Sandron D, Ziza JM, Chretien J. Pulmonary complications of intravesical Bacille Calmette–Guerin immunotherapy. Am Rev Respir Dis. 1987;135(3):763–5.PubMed
10.
go back to reference Diner EK, Verghese M. Interstitial pneumonitis secondary to intravesical bacillus Calmette–Guerin for carcinoma in situ of the bladder. Int Braz J Urol. 2004;30(5):400–2.CrossRef Diner EK, Verghese M. Interstitial pneumonitis secondary to intravesical bacillus Calmette–Guerin for carcinoma in situ of the bladder. Int Braz J Urol. 2004;30(5):400–2.CrossRef
11.
go back to reference Lyons D, Miller I, Jeffers A. Systemic hypersensitivity reaction to intravesical BCG. Scott Med J. 1994;39(2):49–50.CrossRef Lyons D, Miller I, Jeffers A. Systemic hypersensitivity reaction to intravesical BCG. Scott Med J. 1994;39(2):49–50.CrossRef
12.
go back to reference Carrasco Hernandez L, Castano Nunez AL, Rodriguez Portal JA. Hypersensitivity pneumonitis as a complication of intravesical BCG therapy for bladder cancer. Arch Bronconeumol. 2016;52(8):445–6.CrossRef Carrasco Hernandez L, Castano Nunez AL, Rodriguez Portal JA. Hypersensitivity pneumonitis as a complication of intravesical BCG therapy for bladder cancer. Arch Bronconeumol. 2016;52(8):445–6.CrossRef
13.
go back to reference Naoki K, Yamaguchi K, Soejima K, Aoki T, Inoue T, Satou N, Shimada H, Fukunaga K, Kudo H, Kanazawa M. A case of interstitial pneumonia induced by intravesical administration of bacillus Calmette–Guerin (BCG). [Japanese with English abstract.]. Nihon Kyobu Shikkan Gakkai Zasshi. 1997;35(12):1383–8.PubMed Naoki K, Yamaguchi K, Soejima K, Aoki T, Inoue T, Satou N, Shimada H, Fukunaga K, Kudo H, Kanazawa M. A case of interstitial pneumonia induced by intravesical administration of bacillus Calmette–Guerin (BCG). [Japanese with English abstract.]. Nihon Kyobu Shikkan Gakkai Zasshi. 1997;35(12):1383–8.PubMed
14.
go back to reference Nitta S, Sakka S, Endo T, Komine M, Tsutsumi M, Nishiyama H. Fever, hepatic dysfunction and interstitial pneumonia caused by intravesical Bacillus Calmette–Guerin (BCG) instillation after urethral bougie: a case report. [Japanese with English abstract.]. Hinyokika Kiyo. 2017;63(10):427–30.PubMed Nitta S, Sakka S, Endo T, Komine M, Tsutsumi M, Nishiyama H. Fever, hepatic dysfunction and interstitial pneumonia caused by intravesical Bacillus Calmette–Guerin (BCG) instillation after urethral bougie: a case report. [Japanese with English abstract.]. Hinyokika Kiyo. 2017;63(10):427–30.PubMed
15.
go back to reference Horinaga M, Nakamura K, Nishiyama T, Murai M. A case of interstitial pneumonitis caused by intravesical bacillus Calmette–Guerin instillation. [Japanese with English abstract.]. Hinyokika Kiyo. 1999;45(7):493–5.PubMed Horinaga M, Nakamura K, Nishiyama T, Murai M. A case of interstitial pneumonitis caused by intravesical bacillus Calmette–Guerin instillation. [Japanese with English abstract.]. Hinyokika Kiyo. 1999;45(7):493–5.PubMed
16.
go back to reference Uetsuki H, Hirama H, Matsuoka Y, Miyauchi Y, Tsunemori H, Yamashita M, Inui M, Sugimoto M, Kakehi Y. A case with hepatitis and interstitial pneumonitis caused by intravesical bacillus Calmette–Guerin (BCG) instillation. [Japanese with English abstract.]. Nihon Hinyokika Gakkai Zasshi. 2011;102(5):691–5.PubMed Uetsuki H, Hirama H, Matsuoka Y, Miyauchi Y, Tsunemori H, Yamashita M, Inui M, Sugimoto M, Kakehi Y. A case with hepatitis and interstitial pneumonitis caused by intravesical bacillus Calmette–Guerin (BCG) instillation. [Japanese with English abstract.]. Nihon Hinyokika Gakkai Zasshi. 2011;102(5):691–5.PubMed
17.
go back to reference Yamamoto A, Koyama R, Kido K, Koike K, Toba M, Takahashi K. Case of interstitial pneumonia induced by intravesical administration of Bacillus Calmette–Guerin. [Japanese with English abstract.]. Nihon Kokyuki Gakkai Zasshi. 2008;46(10):803–7.PubMed Yamamoto A, Koyama R, Kido K, Koike K, Toba M, Takahashi K. Case of interstitial pneumonia induced by intravesical administration of Bacillus Calmette–Guerin. [Japanese with English abstract.]. Nihon Kokyuki Gakkai Zasshi. 2008;46(10):803–7.PubMed
18.
go back to reference Davies B, Ranu H, Jackson M. Pulmonary complications of intravesicular BCG immunotherapy. Thorax. 2012;67(10):933–4.CrossRef Davies B, Ranu H, Jackson M. Pulmonary complications of intravesicular BCG immunotherapy. Thorax. 2012;67(10):933–4.CrossRef
19.
go back to reference Tobiume M, Shinohara T, Kuno T, Mukai S, Naruse K, Hatakeyama N, Ogushi F. BCG-induced pneumonitis with lymphocytic pleurisy in the absence of elevated KL-6. BMC Pulm Med. 2014;14:35.CrossRef Tobiume M, Shinohara T, Kuno T, Mukai S, Naruse K, Hatakeyama N, Ogushi F. BCG-induced pneumonitis with lymphocytic pleurisy in the absence of elevated KL-6. BMC Pulm Med. 2014;14:35.CrossRef
20.
go back to reference Caravaca-Fontan F, Cano Megias M, Sanchez-Conde M, Elias Trivino S, Fernandez-Rodriguez A, Liano F. Subacute interstitial pneumonitis due to Mycobacterium bovis after intravesical bacillus Calmette–Guerin instillation in a renal transplant patient. Nefrologia. 2016;36(6):711–3.CrossRef Caravaca-Fontan F, Cano Megias M, Sanchez-Conde M, Elias Trivino S, Fernandez-Rodriguez A, Liano F. Subacute interstitial pneumonitis due to Mycobacterium bovis after intravesical bacillus Calmette–Guerin instillation in a renal transplant patient. Nefrologia. 2016;36(6):711–3.CrossRef
21.
go back to reference Araki A, Abe K, Komiya A, Ogo Y. A case report of renal tuberculosis and interstitial pneumonitis caused by intravesical Bacillus Calmette–Guerin (BCG) instillation. [Japanese with English abstract]. Jpn J Urol Surg. 2015;28(6):1101–6. Araki A, Abe K, Komiya A, Ogo Y. A case report of renal tuberculosis and interstitial pneumonitis caused by intravesical Bacillus Calmette–Guerin (BCG) instillation. [Japanese with English abstract]. Jpn J Urol Surg. 2015;28(6):1101–6.
22.
go back to reference Kosuke K, Kazumasa H, Koichi M, Kensuke N, Shinsuke H, Yasuyuki H. Interstitial pneumonia induced by instillation of Bacillus Calmette–Guerin (BCG) to upper urinary tract: a case report. [Japanese with English abstract.]. Nishinihon J Urol. 2016;78(12):626–32. Kosuke K, Kazumasa H, Koichi M, Kensuke N, Shinsuke H, Yasuyuki H. Interstitial pneumonia induced by instillation of Bacillus Calmette–Guerin (BCG) to upper urinary tract: a case report. [Japanese with English abstract.]. Nishinihon J Urol. 2016;78(12):626–32.
23.
go back to reference Yamashita K, Tomiyasu K, Ihara Y, Noriko Y, Sonoyama H, Toida I. The status of adverse drug reaction incidence of Immunobladder after marketing. [Japanese with English abstract.]. Ann Soc BCG BRM Immunother. 2000;24:81–8. Yamashita K, Tomiyasu K, Ihara Y, Noriko Y, Sonoyama H, Toida I. The status of adverse drug reaction incidence of Immunobladder after marketing. [Japanese with English abstract.]. Ann Soc BCG BRM Immunother. 2000;24:81–8.
Metadata
Title
Disseminated Bacillus Calmette–Guérin (BCG) infection and acute exacerbation of interstitial pneumonitis: an autopsy case report and literature review
Authors
Gen Shimizu
Ryota Amano
Itaru Nakamura
Akane Wada
Masanobu Kitagawa
Shuta Toru
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2020
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-020-05396-7

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