Mycotic aortic aneurysm formation following intravesical BCG treatment for transitional cell carcinoma of the bladder

Background

A multidisciplinary approach to patients with diagnostic dilemmas is important. It allows for collaborative management and investigation of a patient, especially when symptoms are constitutional. This report describes the multidisciplinary approach between infectious diseases, vascular surgery and radiology to investigate and treat a patient with a mycotic infrarenal aortic aneurysm secondary to intravesical BCG treatment for bladder cancer.

Intravesical administration of BCG has been used as a treatment of non-muscle invasive bladder cancer since the 1980s.1 BCG is a live attenuated strain Mycobacterium bovis and was initially developed as a vaccine against M. tuberculosis. The use of BCG as an effective means of treatment for bladder cancer has been demonstrated in several large randomised control trials which has underpinned its widespread use.2 Intravesical BCG has been shown to have a favourable safety profile with a low prevalence of complications. Urinary frequency, cystitis, fever and haematuria are the most common complications encountered.3 Life threatening complications such as sepsis from disseminated TB have been documented, but are exceedingly rare.

The formation of an aortic mycotic aneurysm secondary to M. bovis var. BCG has only been described a handful of times but remains a rare yet devastating complication of intravesical BCG treatment.

Case presentation

A 72-year-old man presented to his general practitioner with a 1-week history of fevers, chills and night sweats. Three weeks earlier, he had completed a 6-weekly regime of intravesical BCG treatment for a recurrent low-grade transitional cell carcinoma of the bladder. The patient’s medical profile also included pernicious anaemia and a recent peptic ulcer. The patient had no recent travel history to tropical or international locations. He was a distant ex-smoker and carer for his wife. The symptoms were investigated by his general practitioner. Initial computed tomography (CT) scan of his abdomen at the time did not demonstrate any evidence of aneurysmal change and was unremarkable. Routine tests and investigations yielded no obvious source. Subsequently, the patient’s symptoms resolved without intervention.

Six months later, the patient’s symptoms recurred. The patient was referred to an infectious disease specialist who organised a repeat CT abdomen scan, which revealed a thickened 2.8 cm infrarenal aorta. The patient had a C reactive protein (CRP) of 15 mg/L (reference range: <5 mg/L) with negative serology and blood cultures. A presumptive diagnosis of non-infectious aortitis was made with a plan to observe with regular imaging.

Several weeks later, the patient presented to the emergency department with increasing abdominal and lower back pain. On examination, the patient was febrile to 38.1°C, normotensive at 130/80 mm Hg with a heart rate of 70 beats/min. The patient exhibited tenderness in the epigastric abdomen without signs of peritonism. General examination was otherwise unremarkable. However, a repeat CT demonstrated expansion of the infrarenal aorta to 3.1 cm with periaortic oedema and a new pseudoaneurysm (figure 1). Serum CRP was elevated to 19 mg/L. The diagnosis of a symptomatic mycotic aneurysm was made, and the patient was urgently referred to vascular surgery. The patient was empirically commenced on meropenem and vancomycin and promptly underwent a bifurcated emergency EVAR with intraoperative aortic sac blood cultures.

Investigations

During the insertion of the EVAR graft, blood cultures were taken from the infrarenal arota, directly adjacent to the aneurysm, via use of angiographic catheter and sent for mycobacterial as well as bacterial cultures.

On admission, the patient had a white cell count (WCC) of 4.6×10⁹ g/L (reference range: 3.6–11.0 g/L), with the remaining full blood count and electrolytes within normal limits. All standard bacterial cultures yielded no growth. HIV, hepatitis, Q-fever and syphilis serology were all negative.

Extractable nuclear antigen antibody and vasculitic screens were also negative. Urine microscopy and mycobacterial-specific culture were negative.

A CT angiogram taken 2 days postoperatively demonstrated a patent, well-positioned EVAR with no endoleak. The mycotic sac size was unchanged from preoperatively.

A positron emission topography (PET) scan undertaken as a baseline 4 days postoperatively demonstrated intense avidity of the aneurysmal segment (figure 2). Percutaneous CT-guided biopsy by interventional radiology of the PET-avid aortocaval lesion demonstrated scar tissue with granular necrotic debris and occasional multinucleate giant cells suggestive of granulomas (figure 3). Acid-fast microscopy using the standard Ziehl-Neilson stain demonstrated positivity. A GeneXpert ULTRA assay performed directly on tissue was positive. At this point, broad-spectrum antibiotics were ceased and isoniazid, rifampicin and ethambutol were started based on the clinical suspicion for M. bovis var. BCG infection. Four weeks later, the tissue mycobacterial cultures confirmed M. bovis var. BCG with sensitivity to streptomycin, isoniazid, rifampicin and ethambutol. Subsequently, the mycobacterial culture collected at the time of EVAR graft insertion also cultured M. bovis var. BCG.

Treatment

Following the confirmation of M. bovis var. BCG and its sensitivities, the patient was commenced on a regime of ethambutol, rifampicin and isoniazid. This was complicated by hepatotoxicity (alanine transaminase (ALT) and aspartate aminotransferase (AST)>10× upper limit of normal (ULN)) which was thought to be due to isoniazid. Therapy was ceased to allow resolution of the patient’s liver enzyme test abnormalities. Ethambutol, rifampicin and moxifloxacin were restarted sequentially without further hepatoxicity. Therapy is planned for a minimum of 12 months.

Outcome and follow-up

Three months after the emergency EVAR, a CT angiogram demonstrated complete resolution of the aneurysm sac. The EVAR was patent without evidence of endoleaks (figure 4). Sequential reviews in both vascular and infectious diseases outpatient clinic were satisfactory with the patient returning to his usual daily activities 2 weeks following discharge. At 8 months post surgery, the patient remains compliant with his ongoing tuberculosis therapy, is systemically well and his CRP and liver function tests have normalised.