OBJECTIVE: Intravesical administration of bacillus Calmette-Guérin is standard adjuvant treatment of non-muscle invasive bladder cancer. In spite of the fact that this immunotherapy is locoregional, there are still risk of some complications. METHODS: We describe two cases of systemic BCG infection after intravesical administration of BCG vaccine in patients with early stage of bladder cancer. RESULTS: Both patients suffered from systemic BCG infection manifesting as BCG pneumonitis. After standard therapy with antituberculotic agents, both of them fully recovered. CONCLUSION: BCG infection can occur as a rare but potentially serious complication of this treatment procedure. Gravity of this side effect and its specific therapy require prompt and right diagnosis.

1st Department of Surgery Faculty of Medicine and Dentistry Palacky University Olomouc and University Hospital Olomouc Olomouc Czech Republic

Department of Oncology Faculty of Medicine and Dentistry Palacky University Olomouc and University Hospital Olomouc Olomouc Czech Republic

Department of Pneumology and Tuberculosis Faculty of Medicine and Dentistry Palacky University Olomouc and University Hospital Olomouc Olomouc Czech Republic

Department of Urology Faculty of Medicine and Dentistry Palacky University Olomouc and University Hospital Olomouc Olomouc Czech Republic

Institute of Molecular and Clinical Pathology Faculty of Medicine and Dentistry Palacky University Olomouc and University Hospital Olomouc Olomouc Czech Republic

Zobrazit více v PubMed

Kirkwood JM, Butterfield LH, Tarhnini AA, Zarour H, Kalinski P, Ferrone S. Immunotherapy of cancer in 2012. CA Cancer J for Clin 2012;62:309-35. DOI

Yamazaki-Nakashimada MA, Unzueta A, Gamez-Gonzalez LB, Gonzalez-Saldana N, Sorensen RU. BCG: a vaccine with multiple faces. Hum Vaccin Immunother 2020;16(8):1841-50. DOI

Braasch MR, Bohle A, O'Donnell MA. Risk-adapted use of intravesical immunotherapy. BJU Int 2008;102(9):1254-64. DOI

Lamm DL. Complications of Bacillus Calmette-Guerin immunotherapy. Urol Clin N Amer 1992;19(3):565-72. DOI

Bartoušková M, Melichar B. Precision medicine in medical oncology: hope, disappointment and reality. Clin Chem Lab Med 2020;58(9):1427-31. DOI

Rischmann P, Desgrandchamps F, Malavaud B, Chopin DK. BCG intravesical instillations: Recommendations for side-effects management. Eur Urol 2000;37:33-6. DOI

Xie J, Codd C, Mo K, He YQ. Differential Adverse Event Profiles Associated with BCG as a Preventive Tuberculosis Vaccine or Therapeutic Bladder Cancer Vaccine Identified by Comparative Ontology-Based VAERS and Literature Meta-Analysis. PLoS One 2016;11(10):e0164792. doi: 10.1371/journal.pone.0164792 PubMed DOI

Clerigo V, Castro A, Mourato T, Gomes C. A Rare Case of Granulomatous Pneumonitis Due to Intravesical BCG for Bladder Cancer. Acta Med Port 2019;32(4):316-20. DOI

Marques M, Vazquez D, Sousa S, Mesquita G, Duarte M, Ferreira R. Disseminated Bacillus Calmette-Guerin (BCG) infection with pulmonary and renal involvement: A rare complication of BCG immunotherapy. A case report and narrative review. Pulmonology 2020;26(6):346-52. DOI

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]. Hinyokika Kiyo 2017;63(10):427-30.

Shimizu G, Amano R, Nakamura I, Wada A, Kitagawa M, Toru S. Disseminated Bacillus Calmette-Guerin (BCG) infection and acute exacerbation of interstitial pneumonitis: an autopsy case report and literature review. BMC Infect Dis 2020; 20(1):708. DOI

Leebeek FWG, Ouwendijk RJT, Kolk AHJ, Dees A, Meek JCE, Nienhuis JE, DingemansDumas AM. Granulomatous hepatitis caused by Bacillus Calmette-Guerin (BCG) infection after BCG bladder instillation. Gut 1996;38(4):616-8. DOI

Lemense GP, Strange C. Granulomatous pneumonitis following intravesical BCG - What therapy is needed. Chest 1994;106(5):1624-6. DOI

Rosati Y, Fabiani A, Taccari T, Ranaldi R, Mammana G, Tubaldi A. Intravesical BCG therapy as cause of miliary pulmonary tuberculosis. Urologia 2016;83(1):49-53. DOI

Katz DS, Wogalter H, Desposito RF, Cunha BA. Mycobacterium bovis vertebral osteomyelitis and psoas absess after intravesical BCG therapy for bladder carcinoma. Urology 1992;40(1):63-6. DOI

Harding GEJ, Lawlor DK. Ruptured mycotic abdominal aortic aneurysm secondary to Mycobacterium bovis after intravesical treatment with bacillus Calmette-Guerin. J Vasc Surg 2007;46(1):131-4. DOI

Delimpoura V, Samitas K, Vamvakaris I, Zervas E, Gaga M. Concurrent granulomatous hepatitis, pneumonitis and sepsis as a complication of intravesical BCG immunotherapy. BMJ Case Rep 2013; 2013:bcr2013200624. doi: 10.1136/bcr-2013-200624 PubMed DOI

Piso RJ, Toniolo M. [Urothelial carcinoma-fever and weight loss after intravesical instillation of BCG]. Praxis (Bern 1994) 2008;97(16):901-4. DOI

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. DOI

Habscheid W, Feise F, Dahm HH. [Miliary pneumonia after the intravesical BCG therapy of a superficial urothelial carcinoma of the bladder]. Dtsch Med Wochenschr 1999;124(34-35):993-7. DOI

Martín Escudero JC, Pérez Paredes G, Asensio Sánchez T, Herreros Fernández V. Granulomatous pneumonitis due to BCG. An Med Interna 2003;20(2):105-6. DOI

Caravaca-Fontán F, Cano Megías M, Sánchez-Conde M, Elías Triviño S, Fernández-Rodríguez A, Liaño F. Subacute interstitial pneumonitis due to Mycobacterium bovis after intravesical bacillus Calmette-Guérin instillation in a renal transplant patient. Nefrologia 2016;36(6):711-3. DOI

Venn RM, Sharma N. Resolution without treatment of granulomatous pneumonitis due to intravesical BCG for bladder cancer. BMJ Case Rep 2014; 2014: bcr2014204440. DOI

Caramori G, Artioli D, Ferrara G, Cazzuffi R, Pasquini C, Libanore M, Guardigni V, Guzzinati I, Contoli M, Rossi R. Severe pneumonia after intravesical BCG instillation in a patient with invasive bladder cancer: case report and literature review. Monaldi Arch Chest Dis 2013;79(1):44-8. DOI

Chanal E, Bouleftour W, Dridi M, Héritier P, Gagneux-Brunon A, Vassal C, Guillot A. [A complex case of miliary pulmonary tuberculosis following intravesical BCG therapy]. Rev Med Liege 2020;75(7-8):518-20.

Rogoziński P, Taracha-Guz D, Pęcikiewicz P, Kachel T, Dubiel G, Wandzel P, Bruliński K. [Granulomatous pneumonia as a complication of intravesical BCG immunotherapy-a case report]. Pneumonol Alergol Pol 2014;82(2):163-9. DOI

Yamamoto A, Koyama R, Kido K, Koike K, Toba M, Takahashi K. [Case of interstitial pneumonia induced by intravesical administration of Bacillus Calmette-Guerin]. Nihon Kokyuki Gakkai Zasshi 2008;46(10):803-7.

To U, Kim J, Chia D. Disseminated BCG: Complications of Intravesical Bladder Cancer Treatment. Case Rep Med 2014; 2014:362845. DOI

Dibs K, Shehadeh I, Abu Atta O. Acute Hepatitis and Pneumonitis Caused by Disseminated Bacillus Calmette-Guérin Infection. ACG Case Rep J 2016;3(2):130-2. DOI

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)]. Nihon Kyobu Shikkan Gakkai Zasshi 1997;35(12):1383-8.

McParland C, Cotton DJ, Gowda KS, Hoeppner VH, Martin WT, Weckworth PF. Miliary Mycobacterium bovis induced by intravesical bacille Calmette-Guérin immunotherapy. Am Rev Respir Dis 1992;146(5 Pt 1):1330-3. DOI

Sakamoto GD, Burden J, Fisher D. Systemic bacillus-Calmette Guerin infection after transurethral administration for superficial bladder carcinoma. J Urol 1989;142(4):1073-4; discussion 1074-5. DOI

Raffray L, Riviere P, Bonnet H, Duffau P, Longy-Boursier M. Granulomatous hepatitis revealing a Mycobacterium bovis widespread infection following intravesical BCG therapy. Rev Med Interne 2015;36(9):626-30. DOI

Gonzalez OY, Musher DM, Brar I, Furgeson S, Boktour MR, Septimus EJ, Hamill RJ, Graviss EA. Spectrum of Bacille Calmette-Guerin (BCG) infection after intravesical BCG immunotherapy. Clin Infect Dis 2003;36(2):140-8. DOI

Gómez-Ferrer Lozano A, Navarro Antón JA, Sala Aznar A, Mola Arizo MJ, Gonzalvo Pérez V, Cantó Faubel E, Polo i Peris AC. Granulomatous pneumonitis secondary to BCG bladder instillation. Actas Urol Esp 2006;30(8):839-42. DOI

Lyons D, Miller I, Jeffers A. Systemic hypersensitivity reaction to intravesical BCG. Scott Med J 1994;39(2):49-50. DOI

Carrasco Hernández L, Castaño Núñez Á L, Rodríguez Portal JA, Colomba C, Di Carlo P, Guadagnino G, Siracusa L, Trizzino M, Gioè C, Cascio A. Hypersensitivity pneumonitis as a complication of intravesical BCG therapy for bladder cancer. Arch Bronconeumol 2016;52(8):445-6. DOI

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. DOI

Paterson DL, Patel A. Bacillus Calmette-Guerin (BCG) immunotherapy for bladder cancer: Review of complications and their treatment. Aust N Z J Surg 1998;68(5):340-4. DOI

Segawa N, Inamoto T, Nomi H, Ibuki N, Azuma H, Katsuoka Y. [Effect of prophylactic intravesical instillation of BCG for superficial bladder cancer]. Hinyokika Kiyo 2009;55(4):175-80.

Kalble T, Beer M, Mendoza E, Ikinger U, Link M, Reichert HE, Frangenheim T, Klein E, Fabricius PG. BCG versus interferon A for recurrence prophylaxis of superficial bladder carcinoma. A prospective randomized study. Urologe A 1994;33(2):133-7.

al Khalifa MA, Elfving P, Månsson W, Colleen S. Bacillus Calmette-Guérin treatment of 39 patients with superficial transitional cell carcinoma of the bladder. Scand J Urol Nephrol 1991;25(2):135-9. DOI

Volkmer BG, Gschwend JE, Maier SH, Seidl-Schlick EM, Bach D, Romics I. T2a transitional cell carcinoma of the bladder: long-term experience with intravesical immunoprophylaxis with bacillus Calmette-Guerin. J Urol 2003;169(3):931-934; discussion 934-935. DOI

Green DB, Kawashima A, Menias CO, Tanaka T, Redelman-Sidi G, Bhalla S, Shah R, King BF. Complications of Intravesical BCG Immunotherapy for Bladder Cancer. Radiographics 2019;39(1):80-94. DOI

Sharma V, Thakur APS, Ramasamy V, Shukla PK, Solanki FS, Choudhary A, Patel P. Complications of intravesical BCG therapy in non-muscle invasive bladder cancer: our tertiary care centre experience. Afr J Urol 2020; 26:90. doi: 10.1186/s12301-020-00099-6 DOI

Agrawal A, Sahni S, Vulisha AK, Gumpeni R, Shah R, Talwar A. Pulmonary manifestations of urothelial carcinoma of the bladder. Respir Med 2017;128:65-9. DOI

Selmi Y, Kheder-Elfekih R, Jebali H, Ben Fatma L, Smaoui W, Krid M, Beji S, Rais L, Zouaghi MK. A Case of Renal Granulomatosis with Polyangiitis Following Intravesical Bacillus Calmette-Guerin Therapy. Saudi J Kidney Dis Transpl 2018;29(1):185-8. DOI

Melichar B, Touskova M, Solichova D, Kralickova P, Kopecky O. CD4+ T-lymphocytopenia and systemic immune activation in patients with primary and secondary liver tumours. Scand J Clin Lab Invest 2001;61:363-70. DOI

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. DOI

Steg A, Adjiman S, Debré B. BCG therapy in superficial bladder tumours-complications and precautions. Eur Urol 1992;21 Suppl 2:35-40. DOI

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-Guérin (BCG) instillation. Nihon Hinyokika Gakkai Zasshi 2011;102(5):691-5. DOI

Orikasa K, Namima T, Ota S, Miura M, Hama H, Kimura N, Ohnuma T. Acute eosinophilic pneumonia associated with intravesical bacillus Calmette-Guérin therapy of carcinoma in situ of the bladder. Int J Urol 2003;10(11):622-4. DOI