Advertisement

Back pain following instillations of BCG for superficial bladder cancer is not a reactive complication: review of 30 Mycobacterium bovis BCG vertebral osteomyelitis cases

  • Simon CadiouEmail author
  • Omar Al Tabaa
  • Chi-Duc Nguyen
  • Marine Faccin
  • Raphaël Guillin
  • Matthieu Revest
  • Pascal Guggenbuhl
  • Eric Houvenagel
  • Edouard Pertuiset
  • Guillaume Coiffier
Case Based Review

Abstract

Mycobacterium bovis Bacillus Calmette-Guérin (BCG) instillations are used in bladder cancer treatment. Adverse effects can occur. Osteoarticular complications are mainly reactive arthritis, but true infections have been described, such as vertebral osteomyelitis. We made a review of M. bovis BCG vertebral osteomyelitis after instillations for bladder cancer using PubMed search. We added three new French cases. Twenty-seven cases of BCG vertebral osteomyelitis had been reported on PubMed. Of the 30 cases, all were male, averaging 73.4 ± 8.7 years old. Median time between diagnosis and first and last instillation was 22.5 and 14 months respectively. Half of vertebral osteomyelitis was thoracic and lumbar in the other half. Sensitivo-motor deficit was present at diagnosis in 42% of cases. Other infectious locations were common, mainly infectious abdominal aortic aneurysms (20%). Rifampicin, ethambutol and isoniazid were the usual therapy. Poor outcomes were reported with 50% of one or more spine surgery. M. bovis BCG vertebral osteomyelitis following bladder instillation for bladder cancer is a rare complication. However, the late onset of back pain after instillations differentiates them from reactive arthritis. Concomitant septic location such as infectious abdominal aortic aneurysms must be known.

Keywords

BCG instillation Bladder cancer Interferon-γ release assay Mycobacterium bovis Vertebral osteomyelitis 

Notes

Compliance with ethical standards

Disclosures

None.

References

  1. 1.
    Gouliouris T, Aliyu SH, Brown NM (2010) Spondylodiscitis: update on diagnosis and management. J Antimicrob Chemother 65(Suppl 3):iii11–iii24.  https://doi.org/10.1093/jac/dkq303 Google Scholar
  2. 2.
    Tuli SM (2002) General principles of osteoarticular tuberculosis. Clin Orthop 398:11–19CrossRefGoogle Scholar
  3. 3.
    Doutchi M, Seng P, Menard A, Meddeb L, Adetchessi T, Fuentes S, Dufour H, Stein A (2015) Changing trends in the epidemiology of vertebral osteomyelitis in Marseille, France. New Microbes New Infect 7:1–7.  https://doi.org/10.1016/j.nmni.2015.04.008 CrossRefGoogle Scholar
  4. 4.
    Morales A, Eidinger D, Bruce AW (1976) Intracavitary Bacillus Calmette-Guerin in the treatment of superficial bladder tumors. J Urol 116:180–183CrossRefGoogle Scholar
  5. 5.
    Lamm DL (2000) Efficacy and safety of bacille Calmette-Guérin immunotherapy in superficial bladder cancer. Clin Infect Dis 31(Suppl 3):S86–S90.  https://doi.org/10.1086/314064 CrossRefGoogle Scholar
  6. 6.
    Bernini L, Manzini CU, Giuggioli D, Sebastiani M, Ferri C (2013) Reactive arthritis induced by intravesical BCG therapy for bladder cancer: our clinical experience and systematic review of the literature. Autoimmun Rev 12:1150–1159.  https://doi.org/10.1016/j.autrev.2013.06.017 CrossRefGoogle Scholar
  7. 7.
    Katz DS, Wogalter H, D’Esposito RF, Cunha BA (1992) Mycobacterium bovis vertebral osteomyelitis and psoas abscess after intravesical BCG therapy for bladder carcinoma. Urology 40:63–66CrossRefGoogle Scholar
  8. 8.
    Stone DR, Estes NA, Klempner MS (1993) Mycobacterium bovis infection of an implantable defibrillator following intravesical therapy with bacille Calmette-Guérin. Clin Infect Dis 16:825–826CrossRefGoogle Scholar
  9. 9.
    Fishman JR, Walton DT, Flynn NM, Benson DR, Devere White RW (1993) Tuberculous spondylitis as a complication of intravesical bacillus Calmette-Guerin therapy. J Urol 149:584–587CrossRefGoogle Scholar
  10. 10.
    Civen R, Berlin G, Panosian C (1994) Vertebral osteomyelitis after intravesical administration of bacille Calmette-Guérin. Clin Infect Dis 18:1013–1014CrossRefGoogle Scholar
  11. 11.
    Morgan MB, Iseman MD (1996) Mycobacterium bovis vertebral osteomyelitis as a complication of intravesical administration of Bacille Calmette-Guérin. Am J Med 100:372–373.  https://doi.org/10.1016/S0002-9343(97)89500-9 CrossRefGoogle Scholar
  12. 12.
    Rozenblit A, Wasserman E, Marin ML, Veith FJ, Cynamon J, Rozenblit G (1996) Infected aortic aneurysm and vertebral osteomyelitis after intravesical bacillus Calmette-Guérin therapy. AJR Am J Roentgenol 167:711–713.  https://doi.org/10.2214/ajr.167.3.8751686 CrossRefGoogle Scholar
  13. 13.
    LaBerge JM, Kerlan RK, Reilly LM, Chuter TA (1999) Diagnosis please. Case 9: mycotic pseudoaneurysm of the abdominal aorta in association with mycobacterial psoas abscess--a complication of BCG therapy. Radiology 211:81–85.  https://doi.org/10.1148/radiology.211.1.r99ap4081 CrossRefGoogle Scholar
  14. 14.
    Aljada IS, Crane JK, Corriere N, Wagle DG, Amsterdam D (1999) Mycobacterium bovis BCG causing vertebral osteomyelitis (Pott’s disease) following intravesical BCG therapy. J Clin Microbiol 37:2106–2108Google Scholar
  15. 15.
    Abu-Nader R, Terrell CL (2002) Mycobacterium bovis vertebral osteomyelitis as a complication of intravesical BCG use. Mayo Clin Proc 77:393–397.  https://doi.org/10.1016/S0025-6196(11)61795-3 CrossRefGoogle Scholar
  16. 16.
    Dahl T, Lange C, Ødegård A et al (2005) Ruptured abdominal aortic aneurysm secondary to tuberculous spondylitis. Int Angiol J Int Union Angiol 24:98–101Google Scholar
  17. 17.
    Nikaido T, Ishibashi K, Otani K, Yabuki S, Konno S, Mori S, Ohashi K, Ishida T, Nakano M, Yamaguchi O, Suzutani T, Kikuchi S (2007) Mycobacterium bovis BCG vertebral osteomyelitis after intravesical BCG therapy, diagnosed by PCR-based genomic deletion analysis. J Clin Microbiol 45:4085–4087.  https://doi.org/10.1128/JCM.01714-07 CrossRefGoogle Scholar
  18. 18.
    Mavrogenis AF, Sakellariou VI, Tsiodras S, Papagelopoulos PJ (2009) Late Mycobacterium bovis spondylitis after intravesical BCG therapy. Joint Bone Spine 76:296–300.  https://doi.org/10.1016/j.jbspin.2008.10.011 CrossRefGoogle Scholar
  19. 19.
    Colebatch AN, Mounce KE (2010) Mycobacterium bovis discitis as a complication of intravesical Bacillus Calmette-Guérin therapy. J Clin Rheumatol 16:74–75.  https://doi.org/10.1097/RHU.0b013e3181d070ea CrossRefGoogle Scholar
  20. 20.
    Josephson CB, Al-Azri S, Smyth DJ et al (2010) A case of Pott’s disease with epidural abscess and probable cerebral tuberculoma following Bacillus Calmette-Guérin therapy for superficial bladder cancer. Can J Infect Dis Med Microbiol 21:e75–e78CrossRefGoogle Scholar
  21. 21.
    Patel AR, Sabanegh ES, Jones JS, Gordon SM, Ballin M, Ruggieri PM, Stephenson AJ (2010) Bacillus Calmette-Guérin osteomyelitis mimicking spinal metastasis from urothelial cell carcinoma of the bladder. Eur Urol 58:934–937.  https://doi.org/10.1016/j.eururo.2009.05.045 CrossRefGoogle Scholar
  22. 22.
    Obaid S, Weil AG, Rahme R et al (2011) Mycobacterium bovis spondylodiscitis after intravesical Bacillus Calmette-Guérin therapy. Surg Neurol Int 2:162.  https://doi.org/10.4103/2152-7806.89879 CrossRefGoogle Scholar
  23. 23.
    Samadian S, Phillips FM, Deeab D (2013) Mycobacterium bovis vertebral osteomyelitis and discitis with adjacent mycotic abdominal aortic aneurysm caused by intravesical BCG therapy: a case report in an elderly gentleman. Age Ageing 42:129–131.  https://doi.org/10.1093/ageing/afs164 CrossRefGoogle Scholar
  24. 24.
    Santbergen B, Vriens PHWE, de Lange WCM, Van Kasteren MEE (2013) Combined infection of vertebroplasty and aortic graft after intravesical BCG treatment. BMJ Case Rep 2013:bcr2012008161.  https://doi.org/10.1136/bcr-2012-008161 CrossRefGoogle Scholar
  25. 25.
    Newman JR, Clough LA, Merino F (2014) Mycobacterium bovis osteomyelitis of the thoracic spine mimicking a metastatic lytic lesion in a patient exposed to intravesicular bacille Calmette-Guérin treatment. Urol Case Rep 2:142–144.  https://doi.org/10.1016/j.eucr.2014.04.005 CrossRefGoogle Scholar
  26. 26.
    Dąbrowska M, Drabarek T, Muraszko-Klaudel A, Sławek J (2015) A thoracic tuberculous spondylodisctis after intravesical BCG immunotherapy of bladder cancer - case report and literature review. Neurol Neurochir Pol 49:460–466.  https://doi.org/10.1016/j.pjnns.2015.09.005 Google Scholar
  27. 27.
    Białecki J, Nowak-Misiak M, Rąpała K, Marczyński W, Suchodolski G, Truszczyńska A (2016) Spinal tuberculosis with severe neurological symptoms as a complication of intravesical BCG therapy for carcinoma of the bladder. Neurol Neurochir Pol 50:131–138.  https://doi.org/10.1016/j.pjnns.2015.12.003 Google Scholar
  28. 28.
    Mackel CE, Burke SM, Huhta T et al (2016) Mycobacterial osteomyelitis of the spine following Intravesical BCG therapy for bladder cancer. Cureus 8.  https://doi.org/10.7759/cureus.545
  29. 29.
    Miyazaki M, Yoshiiwa T, Ishihara T, Kawano M, Tsumura H (2016) Tuberculous spondylitis following intravesical Bacillus Calmette-Guerin for bladder cancer. Case Rep Orthop 2016:1–4.  https://doi.org/10.1155/2016/6741284 CrossRefGoogle Scholar
  30. 30.
    Seegobin K, Maharaj S, Baldeo C, Isache C, Gharia B, Zuberi L (2017) Mycobacteria Bovis osteomyelitis following intravesical BCG for bladder cancer. IDCases 10:75–78.  https://doi.org/10.1016/j.idcr.2017.09.008 CrossRefGoogle Scholar
  31. 31.
    Kusakabe T, Endo K, Nakamura I, Suzuki H, Nishimura H, Fukushima S, Yamamoto K (2018) Bacille Calmette-Guérin (BCG) spondylitis with adjacent mycotic aortic aneurysm after intravesical BCG therapy: a case report and literature review. BMC Infect Dis 18:290.  https://doi.org/10.1186/s12879-018-3205-7 CrossRefGoogle Scholar
  32. 32.
    Stahl T, Engelhardt F, Layer G (2013) Rare, but significant complication after BCG instillation therapy after urothelial carcinoma. Rofo 185:1199–1200.  https://doi.org/10.1055/s-0033-1335877 CrossRefGoogle Scholar
  33. 33.
    Lara-Oya A, Ramírez-Taboada J, Arenas-Miras Mdel M, Rodríguez-Granger J (2015) Spondilodyscitis with medullary and spinal abscess caused by Bacillus Calmette-Guérin (BCG). Rev Chil Infectol 32:706–709.  https://doi.org/10.4067/S0716-10182015000700015 CrossRefGoogle Scholar
  34. 34.
    Bornet P, Pujade B, Lacaine F, Bazelly B, Paquet JC, Roland J, Huguier M (1989) Tuberculous aneurysm of the femoral artery: a complication of bacille Calmette-Guérin vaccine immunotherapy--a case report. J Vasc Surg 10:688–692Google Scholar
  35. 35.
    Nam EY, Na SH, Kim SY, Yoon D, Kim CJ, Park KU, Min SK, Lee SE, Choe PG (2015) Infected aortic aneurysm caused by Mycobacterium bovis after intravesical Bacillus Calmette-Guérin treatment for bladder cancer. Infect Chemother 47:256–260.  https://doi.org/10.3947/ic.2015.47.4.256 CrossRefGoogle Scholar
  36. 36.
    Leeman M, Burgers P, Brehm V, van Brussel JP (2017) Psoas abscess after bacille Calmette-Guérin instillations causing iliac artery contained rupture. J Vasc Surg 66:1236–1238.  https://doi.org/10.1016/j.jvs.2017.02.038 CrossRefGoogle Scholar
  37. 37.
    Sugita Y, Chokyu H, Gotoh A et al (1995) Tuberculous spondylitis after intravesical BCG instillation: a case report. Nihon Hinyokika Gakkai Zasshi 86:1493–1496Google Scholar
  38. 38.
    Choi S, Jung KH, Son H-J, Lee SH, Hong JM, Kim MC, Kim MJ, Chong YP, Sung H, Lee SO, Choi SH, Kim YS, Woo JH, Kim SH (2018) Diagnostic usefulness of the QuantiFERON-TB gold in-tube test (QFT-GIT) for tuberculous vertebral osteomyelitis. Infect Dis Lond Engl 50:346–351.  https://doi.org/10.1080/23744235.2017.1410282 CrossRefGoogle Scholar
  39. 39.
    Berbari EF, Kanj SS, Kowalski TJ, Darouiche RO, Widmer AF, Schmitt SK, Hendershot EF, Holtom PD, Huddleston PM 3rd, Petermann GW, Osmon DR, Infectious Diseases Society of America (2015) 2015 Infectious Diseases Society of America (IDSA) clinical practice guidelines for the diagnosis and treatment of native vertebral osteomyelitis in adults. Clin Infect Dis 61:e26–e46.  https://doi.org/10.1093/cid/civ482 CrossRefGoogle Scholar
  40. 40.
    Scorpio A, Collins D, Whipple D, Cave D, Bates J, Zhang Y (1997) Rapid differentiation of bovine and human tubercle bacilli based on a characteristic mutation in the bovine pyrazinamidase gene. J Clin Microbiol 35:106–110Google Scholar
  41. 41.
    Batirel A, Erdem H, Sengoz G, Pehlivanoglu F, Ramosaco E, Gülsün S, Tekin R, Mete B, Balkan İİ, Sevgi DY, Giannitsioti E, Fragou A, Kaya S, Cetin B, Oktenoglu T, Celik AD, Karaca B, Horasan ES, Ulug M, Senbayrak S, Kaya S, Arslanalp E, Hasbun R, Ates-Guler S, Willke A, Senol S, Inan D, Güclü E, Ertem GT, Koc MM, Tasbakan M, Ocal G, Kocagoz S, Kusoglu H, Güven T, Baran AI, Dede B, Karadag FY, Yilmaz H, Aslan G, al-Gallad DA, Cesur S, el-Sokkary R, Sirmatel F, Savasci U, Karaahmetoglu G, Vahaboglu H (2015) The course of spinal tuberculosis (Pott disease): results of the multinational, multicentre Backbone-2 study. Clin Microbiol Infect 21:1008.e9–1008.e18.  https://doi.org/10.1016/j.cmi.2015.07.013 CrossRefGoogle Scholar
  42. 42.
    Seo M, Langabeer Ii JR (2018) Demographic and survivorship disparities in non-muscle-invasive bladder cancer in the United States. J Prev Med Public Health 51:242–247.  https://doi.org/10.3961/jpmph.18.092 CrossRefGoogle Scholar
  43. 43.
    Higashi Y, Nakamura S, Kidani K, Matumoto K, Kawago K, Isobe J, Kanatani J, Kawagishi Y, Sakamaki I, Yamamoto Y (2018) Mycobacterium bovis-induced aneurysm after intravesical Bacillus Calmette-Guérin therapy: a case study and literature review. Intern Med Tokyo Jpn 57:429–435.  https://doi.org/10.2169/internalmedicine.9102-17 CrossRefGoogle Scholar
  44. 44.
    Geerdes-Fenge HF, Stubbe F, Löbermann M et al (2017) BCGitis with involvement of lung, liver and bone marrow after immunotherapy of urothelial cancer. Dtsch Med Wochenschr 1946 142:1375–1378.  https://doi.org/10.1055/s-0043-115775 Google Scholar
  45. 45.
    Parent M-E, Richer M, Liang P (2018) The first case of bacillus Calmette-Guérin-induced small-vessel central nervous system vasculitis. Clin Rheumatol 37:2297–2302.  https://doi.org/10.1007/s10067-018-4136-9 CrossRefGoogle Scholar
  46. 46.
    Gupte A, Matcha A, Lauzardo M (2018) Mycobacterium bovis BCG spinal osteomyelitis in a patient with bladder cancer without a history of BCG instillation. BMJ Case Rep 2018.  https://doi.org/10.1136/bcr-2018-224462
  47. 47.
    Shields D, Robinson P, Crowley TP (2012) Iliopsoas abscess – a review and update on the literature. Int J Surg 10:466–469.  https://doi.org/10.1016/j.ijsu.2012.08.016 CrossRefGoogle Scholar
  48. 48.
    Quan Z, Haiming T, Xiaoyao C et al (2017) Development of one-tube multiplex polymerase chain reaction (PCR) for detecting Mycobacterium bovis. J Vet Med Sci 78:1873–1876.  https://doi.org/10.1292/jvms.15-0216 CrossRefGoogle Scholar
  49. 49.
    Luo Y, Henning J, O’Donnell MA (2011) Th1 cytokine-secreting recombinant Mycobacterium bovis bacillus Calmette-Guérin and prospective use in immunotherapy of bladder cancer. Clin Dev Immunol 2011:728930.  https://doi.org/10.1155/2011/728930 CrossRefGoogle Scholar
  50. 50.
    Das J, Ren G, Zhang L, Roberts AI, Zhao X, Bothwell ALM, van Kaer L, Shi Y, Das G (2009) Transforming growth factor beta is dispensable for the molecular orchestration of Th17 cell differentiation. J Exp Med 206:2407–2416.  https://doi.org/10.1084/jem.20082286 CrossRefGoogle Scholar

Copyright information

© International League of Associations for Rheumatology (ILAR) 2019

Authors and Affiliations

  • Simon Cadiou
    • 1
    Email author
  • Omar Al Tabaa
    • 2
  • Chi-Duc Nguyen
    • 3
  • Marine Faccin
    • 4
  • Raphaël Guillin
    • 5
  • Matthieu Revest
    • 6
  • Pascal Guggenbuhl
    • 4
    • 7
    • 8
  • Eric Houvenagel
    • 3
  • Edouard Pertuiset
    • 2
  • Guillaume Coiffier
    • 4
    • 8
  1. 1.Department of RheumatologyCentre Hospitalier Universitaire de RennesRennesFrance
  2. 2.Department of RheumatologyCentre Hospitalier René DubosPontoiseFrance
  3. 3.Department of RheumatologyHôpital St Philibert GHICLLommeFrance
  4. 4.Department of RheumatologyCentre Hospitalier Universitaire de RennesRennesFrance
  5. 5.Department of Medical ImagingCentre Hospitalier Universitaire de RennesRennesFrance
  6. 6.Infectious Diseases and Intensive Care UnitCHU Univ RennesRennesFrance
  7. 7.CHU Rennes, Univ Rennes, INSERMInstitut NUMECAN (Nutrition Metabolisms and Cancer)RennesFrance
  8. 8.UMR INSERM U 1241University of Rennes 1RennesFrance

Personalised recommendations