Immune Interactions Unique to Intradermal Microtoxin: Insights From Aesthetic, Therapeutic, and Vaccination Studies

ABSTRACT Introduction Intradermal botulinum toxin type A (BoNT‐A; microtoxin) has been shown to improve skin texture, superficial rhytides, and sweat/sebaceous activity through neuronal (cholinergic) and non‐neuronal pathways. While discussions around immune system interactions for BoNT‐A in aesthetic indications exist for intramuscular injection, the high density of antigen‐presenting cells in the dermis raises the question of whether a different level of concern is warranted. Methods This narrative review was informed by a PubMed search through 2025 identifying studies on intradermal BoNT‐A and immunogenicity using combined/related terms for BoNT‐A, intradermal injection, microtoxin, immunogenicity, and skin immunology. Reference lists were screened for additional studies. Results The number of publications on microtoxin has increased markedly since 2024. While the skin is an immunologically active organ, immunogenicity data remain limited for aesthetic intradermal injection. To date, only a single prospective study has examined immune responses to intradermal BoNT‐A in aesthetic practice. This study showed higher antibody responses with intradermal versus intramuscular delivery. Like data for intramuscular injection, there is a lack of long‐term data on neutralizing antibody (NAb) development; however, in the context of increasing BoNT‐A doses for facial treatment and increasing long‐term exposure, introduction of BoNT‐A into the dermis over a large surface may raise the risk of NAb development. Conclusions Microtoxin techniques may heighten immunogenic potential through dermal antigen exposure and frequent retreatment. IncobotulinumtoxinA is free of complexing proteins and has a low antigenic protein burden, which may favor its use for intradermal injection. However, direct long‐term comparative evidence for aesthetic intradermal treatments is lacking.