The first case of bacillus Calmette-Guérin-induced small-vessel central nervous system vasculitis

Abstract

To present an unrecognized vascular complication of bacillus Calmette-Guérin (BCG) therapy administered for superficial bladder carcinoma. We also review the potential mimickers for primary angiitis of the central nervous system (PACNS) as well as complications of intravesical BCG therapy. An 89-year-old Caucasian man with a history of relapsing high-grade bladder carcinoma treated with intravesical BCG presented with recurring episodes of right upper limb paresthesia with clumsiness and dysarthria. Magnetic resonance imaging of the head revealed multiple predominantly left-sided frontotemporal micronodular peri-vascular lesions. Left frontal lobe biopsy showed non-necrotizing granulomatous vasculitis. Ziehl staining was negative. Initially, he was treated for PACNS but his symptoms relapsed during every attempt to taper the corticosteroids. Six months later, he developed bilateral mycobacterial endophthalmitis, caused by Mycobacterium bovis. Brain biopsy was reviewed and confirmed the presence of perivascular mycobacteria. A retrospective diagnosis of BCG-induced central nervous system vasculitis was made and he was treated with high-dose corticosteroids, moxifloxacin, isoniazid, ethambutol, and rifampicin. BCG is a live attenuated form of Mycobacterium bovis widely used as tuberculosis vaccination and intravesical therapy for superficial forms of bladder cancer. Systemic complications affect roughly 5% of patients and can manifest months or years after the last instillation. Cases of endophthalmitis, meningitis, aortitis, or mycotic aneurysms have been described, but no reports of CNS vasculitis have been found. In disseminated forms of BCG infections, referred to as BCGitis, histopathology usually reveals granulomatous inflammation. Mycobacterial cultures are often negative, making this a diagnostic challenge. This is the first documented case of BCG-induced small-vessel CNS vasculitis. Mycobacterium bovis infection is rare and findings are often nonspecific, making the diagnosis very difficult. Other infectious and non-infectious causes must be ruled out appropriately before considering this entity.

BCG: a vaccine with multiple faces

“…141 Cases of endophthalmitis, uveitis, vitiligo, meningitis, aortitis, or mycotic aneurysms have been reported as well as central nervous system vasculitis. [142][143][144] BCG administration has also been related to the pathogenesis of Takayasu arteritis or KD. 59,145 Recently, a study in Finland showed that discontinuing universal BCG vaccination did not changed the incidence rates of KD, however the mean age at diagnosis increased, suggesting that the pathogenesis of KD may be associated with immunological priming by BCG vaccination.…”

Brain Tuberculomas as BCGitis Complication Presenting with Epileptic Spasms: A Case Report

“…17 In addition, a case of BCG-induced small-vessel CNS vasculitis was also reported. 18 To our knowledge, the present report is the first to describe a case of BCGitis associated brain tuberculomas in an immunocompetent child. Possible factors, such as impaired Th1 immunity in early life, underlying immunodeficiency, or HIV can cause complications.…”

Progressive Cerebral Small Vessel Disease Caused by an Autoimmune Response to Intravesical Bacille-Calmette-Guérin Treatment

“…Up to 5% of the patients develop serious systemic side effects with inflammation up to life threatening sepsis (2) or immunologic reactions such as myasthenia gravis (3,4). Two recent publications presented cases of small-vessel central nervous system vasculitis caused by BCG, but in contrast to our case, these reports pointed toward an acute BCG infection as underlying cause and patients were treated by either tuberculostatic therapy only (5) or in combination with steroids (6). Based on the pronounced response to immunosuppressive treatment with cyclophosphamide, we conclude an autoimmune etiology due to previous BCG instillations.…”