A 66-yr-old male presented initially with gross painless hematuria in January 2008. Cystoscopic evaluation revealed an erythematous area of the bladder, and subsequent directed and random biopsies demonstrated focal urothelial carcinoma in situ (CIS) with no invasion into the lamina propria. Muscularis propria was present in the specimen and was not involved. The patient underwent six weekly installations of intravesical bacillus Calmette-Guérin (BCG) therapy uneventfully from May 2008 to June
Discussion
The standard treatment options for CIS of the bladder are intravesical BCG immunotherapy or immediate cystectomy for selected patients. Complications of BCG immunotherapy include cystitis (up to 90%), fever (3%), and hematuria (up to 34%) [1], [2]. Symptoms of cystitis, including frequency, dysuria, hematuria, and low-grade fevers, usually occur after the third dose and are usually managed with supportive therapy. Local granulomatous infections can include granulomatous prostatitis (clinically
Conflicts of interest
The authors have nothing to disclose.
EU-ACME question
Please visit www.eu-acme.org/europeanurology to answer the following EU-ACME question online (the EU-ACME credits will be attributed automatically). Question: Intravesical bacillus Calmette-Guérin (BCG) is absolutely contraindicated for all of the following patients except:
A.
The patient who is on immunosuppressive medication.
B.
The patient who has a traumatic catheterization and develops hematuria prior to instillation.
MR imaging features of atypical mycobacterium infection are nonspecific and appear similar to tuberculous arthritis [26–28]. Reports describe abnormal, low marrow signal on T1-weighted images with high marrow signal on fat-suppressed sequences, and post contrast marrow enhancement [15,23,24,29]. Initially, atypical mycobacterial infections may show joint effusion, soft tissue swelling, and regional osteopenia [29,30]; as the disease progresses, peripheral marginal and subchondral bony erosions are present [29].
Mycobacterium bovis (M. bovis) Bacillus Calmette-Guerin (BCG) – an attenuated strain of M. bovis – is closely related to Mycobacterium tuberculosis and may be used as a vaccine against tuberculosis as well as a treatment for urinary bladder cancer. Complications of M. bovis BCG administration, while rare, can occur. While a few cases of vertebral osteomyelitis secondary to BCG therapy exist in the literature, and while there are case reports of osteomyelitis and septic arthritis from BCG vaccination (Chen et al., 2017; Huang et al., 2019; Lin et al., 2015 [1–3]), there are no reported cases of osteomyelitis and septic arthritis involving the foot from BCG therapy for urinary bladder cancer. We present an unusual presentation of osteomyelitis and septic arthritis of the tarsometatarsal joints after M. bovis BCG therapy for urinary bladder cancer. We will describe MRI and ultrasound findings in our case of M. bovis BCG osteomyelitis and septic arthritis.
Vesicular epithelial trauma following BCG-instillation forms the major risk factor in developing PD. These risks factors include transurethral prostate resection, bladder biopsy within two weeks after instillation, catheterization of bladder epithelium, urethral injury, bladder outlet obstruction, pelvic radiation, obstructive uropathy, severe cystitis, recent spinal trauma, an immunocompromised state and advanced age [5,7–9,17,19]. A normal bladder mucosa prevents transvesical spread of infection [9,14].
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.
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.
An 80-year-old man with previous intravesicular bacille Calmette-Guérin therapy developed mass lesions of the lower thoracic spine. Metastatic disease was suspected. The patient underwent a course of radiation; however, biopsy later demonstrated fibrosis and cultures grew Mycobacterium bovis. The patient was treated with a course of isoniazid, rifampin, and ethambutol.
