Mycobacterium bovis epidural abscess following Bacillus Calmette-Guerin therapy for bladder cancer

Abstract

Bacillus Calmette-Guerin (BCG) is derived from attenuated Mycobacterium bovis. It is the most common intravesical immunotherapy for treating early stage bladder cancer. Pott’s disease is a form of mycobacterial infection that involves the vertebrae. This case highlights an unusual presentation of epidural abscess infection with M. bovis following BCG therapy for bladder cancer.

Bacillus Calmette-Guerin (BCG) is derived from attenuated Mycobacterium bovis. It is a vaccine used primarily against tuberculosis. M. bovis belongs to the Mycobacterium tuberculosis complex; it induces a robust inflammatory response when injected in the bladder and is used for the treatment and secondary prevention of superficial bladder cancer.¹ Pott’s disease following BCG therapy is rare but has been described; the time of onset can be from 14 days to 12 years after therapy.²

CASE DESCRIPTION

A 79-year-old man presented with severe back pain and lower-extremity weakness for 1 month with known spinal stenosis, dementia, and bladder cancer. He was diagnosed with grade 2 transitional cell carcinoma bladder with stromal invasion in June 2017. He underwent cystoscopy and transurethral resection of the bladder tumor and was treated with intravesical BCG for 12 cycles plus intravesical chemotherapy between cycles of BCG. He underwent cystoscopies with no evidence of residual disease. There was no history of concurrent illness during therapy. He was previously evaluated for back pain of 3 months’ duration, but imaging was negative. This time he presented 8 months after initiating intravesical BCG with complaints of back pain.

Magnetic resonance imaging of the lumbar spine revealed discitis/osteomyelitis with anterior epidural abscess formation extending into the bilateral psoas musculature (Figure 1). He underwent biopsy and aspiration at L1-L2 and biopsy of L2. Operative cultures were initially negative. He was discharged with empiric broad-spectrum antibiotics. His operative acid-fast bacilli cultures turned positive 4 weeks after surgery (Mycobacterium tuberculosis complex by real-time polymerase chain reaction). Therapy was started with isoniazid, rifampin, ethambutol, pyridoxine, and dexamethasone. The isolate was sent to the state lab, where whole-genome sequencing showed M. bovis (BCG strain). He was initially given 2 months of a three-drug regimen and is scheduled to complete 1 year of dual therapy with isoniazid and rifampin with pyridoxine supplementation.

Figure 1.

Magnetic resonance imaging of the lumbar spine.

DISCUSSION

BCG supplanted cystectomy as the treatment of choice for bladder carcinoma in situ in the mid-1980s. BCG therapy also reduces the risk of recurrence, and ongoing maintenance therapy with BCG reduces the risk of progression in patients with high-grade non–muscle-invasive bladder cancer. The adverse effects of intravesical BCG such as cystitis, fever, hematuria, prostatitis, and arthralgias are common, but extravesicular complications are rare.³ Several risk factors are associated with dissemination of the M. bovis bacilli, including urethral injury during BCG instillation, deep bladder tumor resection, pelvic radiation, bladder epithelium injury, potential immunocompromised states, severe cystitis, prostate resection, and bladder biopsy.^4–6 The mechanism of infection is postulated to be either hematogenous dissemination of the BCG infection or an immune-mediated hypersensitivity reaction underlying the granulomatous inflammatory response in the spine.⁷

Early extravesicular infectious complications occur within 8 to 12 weeks of the first BCG treatment, and late infections occur at least 1 year following administration of the first BCG dose. In more than 2000 patients treated with BCG, infectious complications occurred in <5%.⁸ Pott’s disease following BCG therapy is rare but has been described⁹; the time of onset can be from 14 days to 12 years after therapy.² There is no established treatment regimen for the disease caused by the BCG strain, but most case reports state that isoniazid and rifampin with a combination of ethambutol work the best with subsequent holding of the BCG instillations.^10–13 No other measures have been demonstrated to be effective in preventing the occurrence of disseminated BCG infection. With our case, we highlight that in patients treated with BCG for bladder cancer, clinicians must have a high index of suspicion for osteomyelitis, discitis, and epidural abscess if patients present with back pain. Early initiation of therapy yields better outcomes.¹¹