Late Mycobacterium bovis spondylitis after intravesical BCG therapy

doi:10.1016/j.jbspin.2008.10.011

Joint Bone Spine

Volume 76, Issue 3, May 2009, Pages 296-300

https://doi.org/10.1016/j.jbspin.2008.10.011 Get rights and content

Summary

A 72-year-old man presented with a 6-month history of low back and leg pain. Past medical history revealed transurethral resection of bladder cancer followed by multiple intravesical BCG instillation 12 years ago. Imaging studies of the thoracolumbar spine showed osteolysis of the L3 and L4 vertebrae and the associated intervertebral disc space, and a large soft tissue mass with signal abnormalities suggesting of an abscess. CT-guided needle biopsy showed Mycobacterium bovis infection. A triple anti-tuberculous chemotherapy regimen including isoniazid, rifampicin, and ethambutol was administered for 12 months. Surgical treatment included drainage of the abscess and L2–L5 spinal instrumentation and fusion. Intravesical BCG therapy may be complicated by late disseminated disease to the bone even many years after initial BCG therapy. Patients having BCG therapy should be closely evaluated thereafter for the possibility of hematogenous spread of mycobacteria to distant sites.

Introduction

Bacillus Calmette–Guérin (BCG) is an attenuated derivative of the virulent strain of Mycobacterium bovis. Until its use in current medical practice as a vaccine and for the prevention of superficial bladder cancer recurrence through intravesical instillation, M. bovis was a forgotten pathogen, accounting for less than 0.1% of all mycobacterial isolates [1], [2], [3]. However, since then, its use has not been without complications. The incidence and the variety of these complications depend on the particular strain, dose, and route of administration; although rare, musculoskeletal complications including arthralgias, reactive arthritis and osteoarticular infections have been reported following vaccination and intravesical BCG therapy [1], [4], [5], [6], [7], [8].

In this article, we present a case of late M. bovis spondylitis that occurred 12 years after intravesical BCG treatment in an immunocompetent patient with carcinoma of the bladder.

Section snippets

Case report

A 72-year-old man was admitted to the authors' institution with a 6-month history of low back and leg pain, anorexia and a 5.2-kg of body weight loss. There was no history of trauma, fever, night sweats, or cough. Past medical history revealed degenerative spondylosis of the lumbar spine, benign hyperplasia of the prostate gland, and bladder cancer diagnosed and treated 12 years ago by six cycles of intravesical BCG instillations at weekly intervals. Fifteen months after the initial diagnosis

Discussion

Since its introduction in the 1970s, intravesical BCG immunotherapy has been a major breakthrough for the treatment of superficial bladder cancer and in situ carcinomas, with low risk of adverse effects, most of which are localized and self-limited. The typical scheme of induction chemotherapy for bladder cancer consists of six bladder instillations of 2 h each, administered at weekly intervals [1], [2], [3], [5], [9], [10].

As the application of BCG intravesical immunotherapy continued to

References (15)

J.L. Casanova
Infections caused by BCG and atypical mycobacteria in children: a new group of immune deficiencies
Arch Pediatr
(1999)
R. Abu-Nader et al.
Mycobacterium bovis vertebral osteomyelitis as a complication of intravesical BCG use
Mayo Clin Proc
(2002)
G. Clavel et al.
Osteoarticular side effects of BCG therapy
Joint Bone Spine
(2006)
J.R. Fishman et al.
Tuberculous spondylitis as a complication of intravesical bacillus Calmette–Guérin therapy
J Urol
(1993)
C. Durek et al.
The fate of bacillus Calmette–Guérin after intravesical instillation
J Urol
(2001)
S. Hakim et al.
Psoas abscess following intravesical bacillus Calmette–Guérin for bladder cancer: a case report
J Urol
(1993)
D.S. Katz et al.
Mycobacterium bovis vertebral osteomyelitis and psoas abscess after intravesical BCG therapy for bladder carcinoma
Urology
(1992)

There are more references available in the full text version of this article.

Cited by (27)

Tuberculous spondylitis following intravesical bcg-instillation in the treatment of transitional cell carcinoma: Case report and systematic review
2020, Clinical Neurology and Neurosurgery
Citation Excerpt :
These pathogens are characterized by there slow growth pattern, making them capable of being dormantly present for a very long time in the affected patient [2]. BCG is an attenuated derivative of the virulent strain of Mycobacterium bovis [1,4,8,10,11,13] and was first introduced by Morales et al. in 1976 in the treatment of superficial TCC [3,7,10]. Nowadays, BCG-instillations form the most effective treatment modality for superficial TCC (Ta, T1 and carcinoma in situ) [3,5,11,14].
Tuberculous spondylitis (TS), also known as Pott’s disease (PD), is a form of tuberculosis in which the vertebral column is affected. Since the first description by Katz et al. in 1992, it became clear that Bacillus Calmette-Guérin (BCG) instillations in the treatment of superficial transitional cell carcinoma (TCC) form a plausible way in which PD is introduced. Nowadays, BCG forms the most effective treatment modality for superficial TCC. The incidence of other than minor complications have been estimated under five per cent. Here we report a case of TS after BCG-instillation in the treatment of TCC. Furthermore, all available literature concerning this topic was gathered into a systematic review. The primary objective was to create an overview of all available literature concerning TS after intravesical BCG-instillations, with an emphasis on the neurosurgical approach of these patients, forming a scaffold at which future case reports can be compared. As a secondary objective, we tried to raise the awareness concerning this very rare complication of intravesical BCG-instillation as a possible cause of low back pain (LBP).
We performed a systematic review, in which patients who developed TS after intravesical BCG-therapy in the treatment of TCC, were examined. A total of twenty-three articles (twenty-four cases) obtained from MEDLINE were included. Search terms included: “tuberculous spondylitis”, “Pott’s disease”, “vertebral osteomyelitis”, “intravesical”, “Bacillus Calmette-Guérin” and “transitional cell carcinoma”. Additional studies were identified by checking reference lists. Furthermore, we present a case concerning one of our own patients who consulted our Neurosurgical department with a similar clinical presentation. This systematic review is in conformity with the PRISMA-guidelines. The case report is in accordance with the CARE statement guidelines.
Results are based on twenty-five cases (twenty-four cases extracted from previous literature and our case report). All included articles are case reports written in English. Publication year and recruitment time varies from 1992 to 2018. Mean age at clinical presentation varies from 35 to 94 years old (mean 74). All patients were male. Surgery was performed in 17 out of 25 cases (68%). A posterior approach was performed in seven cases (41%), zero anterior approaches (0%), a combined approach in five cases (29%) and not specified in five cases (29%). All patients received intravesical BCG-instillation in the treatment of TCC, ranging from one month to twelve years before clinical presentation (mean 26). Radiographic abnormalities were seen in thoracic vertebral segments in thirteen cases (52%), eleven cases in lumbar segments (44%), one at the thoracolumbar transition level (4%) and not in cervical vertebral segments.
Although very rare, TS should be part of the differential diagnosis in patients with LBP, even years after BCG-instillation for TCC. It mostly affects elderly men and involves the thoracolumbar spine through hematogenous spread via Batson’s plexus. Antitubercular therapy remains the mainstay in the treatment of TS. A posterior surgical approach, with debridement and stabilization, should be preferred when surgical intervention seems necessary. To our knowledge, this systematic review forms one of the first comprehensive reviews evaluating neurosurgical intervention for PD following intravesical BCG-therapy in the treatment of TCC.
Severe Infectious Complications of Intravesical Bacillus Calmette-Guérin: A Case Series of 10 Patients
2020, Urology
Citation Excerpt :
Severe local and systemic BCG infections are uncommon, estimated to occur in 3-7% of those treated.2,3,6 BCG reactivation with delayed onset of symptoms is even rarer and has only been reported in isolated case reports.7-10 We now report our experience with severe infectious BCG outcomes over the past 12 years.
To investigate severe infectious complications after intravesical treatment with bacillus Calmette-Guérin (BCG). We examine a retrospective case series of 10 patients between 2006 and 2018 with severe cystitis or systemic infection after BCG.
Patients with BCG cystitis or disseminated infection were retrospectively identified between 2006 and 2018 at our institution. Cases were reviewed for bladder cancer treatments, demographics, treatment of infection, and outcomes.
There was a 0.8% rate of severe BCG cystitis or disseminated infection. Seven patients experienced delayed-onset infections >3 months after last BCG instillation. Four had isolated bladder symptoms, and 5 had diverse systemic manifestations. One patient was asymptomatic and diagnosed on cystoscopic findings. All were treated with varied antibiotic regimens; 9 included antituberculous therapy, and 1 was treated with levofloxacin alone. Two underwent cystectomy for end-stage bladder. The remaining patients are asymptomatic with no residual effects. All are in remission for bladder cancer.
Severe infectious complications after BCG are rare and thus difficult to study. Treatment regimens can vary widely. Thorough reporting of patient outcomes is essential to expand the limited body of knowledge.
Systemic Bacillus Calmette-Guerin sepsis manifesting as autoimmunity, 17 months after an intravesical BCG-therapy
2017, Medecine et Maladies Infectieuses
Mycobacteria Bovis osteomyelitis following intravesical BCG for bladder cancer
2017, IDCases
Mycobacteria Bovis osteomyelitis is a rare adverse effect after Bacillus Calmette-Guerin (BCG) intravesical therapy. A 62-year-old male presented with acute spinal cord compression three months after completing his second course of therapy for bladder cancer. The first course with intravesical BCG was complicated with an episode of hematuria. He reported intermittent subjective fever for 3 weeks thereafter which resolved with Tylenol. Interferon-α2 B was added to the second cycle of intravesical BCG with the indication here being residual tumor, and was tolerated well. His complete blood count and liver function tests were unremarkable on admission. MRI showed features of osteomyelitis with cord compression at T4/T5. Biopsy of the affected bone showed caseating granuloma which was positive for acid fact bacilli, later confirmed to be Mycobacterium Bovis by PCR and pyrazinamide resistance. He was started on intravenous steroids and underwent spinal cord decompression. Rifampin, Isoniazid, and Ethambutol were then commenced. His weakness improved and after two months of therapy he was asymptomatic and back to his baseline function. Osteomyelitis is a rare but serious complication. Early diagnosis and treatment is important as the outcomes are good.
Complications following intravesical Bacillus Calmette-Guérin therapy: Epidemiology, clinical features and medical care
2016, Journal des Anti-Infectieux
Le bacille de Calmette et Guérin (BCG), largement utilisé comme vaccin pour prévenir la tuberculose est aussi utilisé comme immunothérapie, par instillation intravésicale, pour traiter les cancers superficiels de vessie et prévenir les récidives. Actuellement il s’agit du traitement de référence pour le traitement des tumeurs de vessie sans envahissement de la musculeuse classées à risque intermédiaire de progression ou de récurrence après réalisation d’une résection transurétrale de vessie. Le BCG, vaccin vivant atténué de Mycobacterium bovis, interagit localement avec le système immunitaire après instillation, aboutissant à une cascade de réactions immunitaires de type cellulaire qui ont pour cible la cellule tumorale vésicale. Les complications dans les suites d’une instillation de BCG sont le plus souvent des réactions localisées, telles que cystite ou hématurie, mais peuvent plus rarement être généralisées avec des conséquences potentiellement sévères.
Bacillus Calmette-Guérin (BCG) is commonly used as a vaccine to prevent tuberculosis. It is also used as an intravesical immunotherapy to treat superficial bladder cancer and prevent relapses. It is currently the gold standard in the treatment of urothelial carcinoma of the bladder with intermediate or high-risk of progression and recurrence, in case of no muscle involvement after transurethral bladder resection. BCG is a live attenuated strain of Mycobacterium bovis supposed to interact locally with the immune system after intravesical injection, leading to cell-mediated immunity targeting bladder cancer. Complications that may occur after intravesical BCG therapy are mostly local reactions such as cystitis and haematuria but can be systemic and sometimes lead to death.
A thoracic tuberculous spondylodisctis after intravesical BCG immunotherapy of bladder cancer – Case report and literature review
2015, Neurologia i Neurochirurgia Polska
We report a rare case of tuberculosis of the thoracic spine caused by Mycobacterium bovis infection as a complication of BCG (Bacillus Calmette-Guérin) intravesical immunotherapy, which is a well known and acknowledged treatment of superficial bladder cancers applied since 1976. Although this therapy is broadly used in urology and considered to be safe and well tolerated, one should be aware of the potential local and systemic side effects as in the case of our patient, who developed tuberculous spondylodiscitis after intravesical BCG therapy.

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Joint Bone Spine

Summary

Introduction

Section snippets

Case report

Discussion

References (15)

Infections caused by BCG and atypical mycobacteria in children: a new group of immune deficiencies

Arch Pediatr

Mycobacterium bovis vertebral osteomyelitis as a complication of intravesical BCG use

Mayo Clin Proc

Osteoarticular side effects of BCG therapy

Joint Bone Spine

Tuberculous spondylitis as a complication of intravesical bacillus Calmette–Guérin therapy

J Urol

The fate of bacillus Calmette–Guérin after intravesical instillation

J Urol

Psoas abscess following intravesical bacillus Calmette–Guérin for bladder cancer: a case report

J Urol

Mycobacterium bovis vertebral osteomyelitis and psoas abscess after intravesical BCG therapy for bladder carcinoma

Urology

Cited by (27)

Tuberculous spondylitis following intravesical bcg-instillation in the treatment of transitional cell carcinoma: Case report and systematic review

Severe Infectious Complications of Intravesical Bacillus Calmette-Guérin: A Case Series of 10 Patients

Systemic Bacillus Calmette-Guerin sepsis manifesting as autoimmunity, 17 months after an intravesical BCG-therapy

Mycobacteria Bovis osteomyelitis following intravesical BCG for bladder cancer

Complications following intravesical Bacillus Calmette-Guérin therapy: Epidemiology, clinical features and medical care

A thoracic tuberculous spondylodisctis after intravesical BCG immunotherapy of bladder cancer – Case report and literature review

Case reportLate Mycobacterium bovis spondylitis after intravesical BCG therapy

Summary

Introduction

Section snippets

Case report

Discussion

Arch Pediatr

Mayo Clin Proc

Joint Bone Spine

J Urol

J Urol

J Urol

Urology

Case report
Late Mycobacterium bovis spondylitis after intravesical BCG therapy