Hypersensitivity Reactions Associated With Aesthetic Botulinum Toxin A Injections: A Case Series

Botulinum toxin type A (BoNT/A) is commonly used in aesthetic treatments for indications such as moderate-to-severe glabellar frown lines. While generally considered safe and effective at low doses, hypersensitivity reactions, though extremely rare, can occur and may be clinically significant. We present three cases suggestive of hypersensitivity reactions to BoNT/A and discuss their potential mechanisms and clinical implications. In the first case, a 44-year-old woman developed severe angioedema after resuming abobotulinumtoxinA injections following a 12-month pause. Subsequent intradermal tests with onabotulinumtoxinA and incobotulinumtoxinA produced localized reactions, suggesting hypersensitivity to a shared component across formulations, possibly the 150 kDa BoNT/A neurotoxin itself. In the second case, a 38-year-old woman experienced delayed erythema and swelling after letibotulinumtoxinA treatment but tolerated subsequent incobotulinumtoxinA injections, suggesting possible reactivity to complexing proteins or other non-core components rather than the neurotoxin. In the third case, a 50-year-old woman developed systemic symptoms and localized swelling after prabotulinumtoxinA administration, consistent with a delayed-type hypersensitivity reaction. These cases highlight the importance of considering patients' medical histories, prior BoNT/A exposures, and potential risk factors for hypersensitivity. Although rare, such reactions can range from localized effects to systemic manifestations. Possible allergens include the core neurotoxin, complexing proteins, excipients, or manufacturing contaminants. We discuss the potential immunological mechanisms underlying these reactions and emphasize that highly purified, low-immunogenicity formulations may be preferable, particularly for patients with prior allergic histories or prolonged treatment courses. Overall, this case series underscores the importance of clinical vigilance, appropriate patient selection, and awareness of rare but meaningful hypersensitivity reactions to BoNT/A in aesthetic practice. Routine reporting and further study are essential to improving patient safety and refining the risk profile of these widely used treatments.