Sequential autoimmune and neoplastic manifestations during long-term benralizumab therapy for severe eosinophilic...

Benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, induces near-complete eosinophil depletion and provides substantial benefit in severe eosinophilic asthma. We report an 80-year-old woman with severe eosinophilic asthma who was treated with benralizumab from August 2020. Peripheral blood eosinophils rapidly decreased to 0/μL, asthma exacerbations ceased, and lung function improved. Over the subsequent four years, while asthma remained well controlled, she developed a temporally ordered sequence of clinical events, including elderly-onset seronegative rheumatoid arthritis, biopsy-proven erythema nodosum, a radiologically characteristic pulmonary hamartoma, and early-stage hormone receptor-positive breast cancer. Erythema nodosum resolved completely after mastectomy without changes in immunosuppressive therapy, suggesting a possible paraneoplastic association. Among these events, inflammatory arthritis may represent the most biologically plausible finding potentially associated with prolonged eosinophil depletion, whereas the remaining findings are more appropriately interpreted descriptively and in the context of alternative explanations, including aging, background disease incidence, and coincidence. This case describes a rare temporal association in a single patient and does not establish causality. Rather than challenging the established favorable safety profile of benralizumab, it highlights the importance of careful long-term clinical follow-up and attention to newly emerging systemic manifestations during eosinophil-depleting biologic therapy, particularly in older adults.