Recognize mononeuritis multiplex from perinuclear Anti-neutrophil cytoplasmic antibody (ANCA) vasculitis as novel complication of intravesical Calmette–Guérin (BCG).

ANCA vasculitis describes necrotizing inflammation of small- to medium-sized vessels. Perinuclear-ANCA with myeloperoxidase antibodies (MPO) is seen in microscopic polyangiitis and drug-induced vasculitis. While intravesical BCG for urothelial cancer is rarely associated with MPO-ANCA vasculitis causing glomerulonephritis, peripheral neurological manifestations have never been reported. This case describes mononeuritis multiplex as novel complication of BCG-related MPO-ANCA vasculitis.

A 70-year-old man with bladder cancer receiving intravesicular BCG presents with dyspnea and two-month stepwise progression of patchy weakness and painful sensory changes, requiring cane for ambulation.

Initial workup discovered cavitating lung lesions on CT chest and leukocytosis (16.7, 87% neutrophils), prompting broad-spectrum antibiotics. Electromyography confirmed neurological exam, finding severe bilateral common fibular, left tibial, bilateral median axonal sensorimotor mononeuropathies with active denervation in tibialis anterior and gastrocnemius muscles. Further testing noted positive MPO-ANCA, though negative hepatitis panel, HIV, quantiferon gold, and acid-fast sputum smears. Lumbar puncture revealed mild pleocytosis (11, 72% lymphocytes) with normal glucose, protein, cytology, and culture. Given likely MPO vasculitis with pulmonary and neurological involvement, antibiotics were stopped and immunological therapy started with five days IV methylprednisolone followed by prednisone taper with avacoban and rituximab. Three-month follow-up found significant improvement in sensorimotor deficits, now ambulating with bilateral ankle-foot orthotics. 

Systemic complications of BCG are rare, from disseminated infection to immune reaction. In this report, presentation with cavitary lung nodules and mononeuritis multiplex suggested multisystem vasculitis involvement. While exact mechanism of cross-reactivity is unknown, BCG adhesion to urothelium triggers inflammatory cascade activating tumor antigen presentation in adaptive immunity and cell-mediated destruction. In turn, immune hyperactivation and antigen presentation likely predisposed patient to auto-antibody formation. This case suggests consideration of immunotherapy cross-reactivity as a cause for vasculitic mononeuritis multiplex for early diagnosis and management.