An Overview of Botulinum Toxins: Past, Present, and Future

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Structure and mechanism of action

Botulinum toxin is produced by various species of gram-positive, spore-forming bacilli of the genus, Clostridium, but chiefly from strains of C botulinum. Seven serotypes of BTX have been identified to date, which are labeled alphabetically, A to G. Many of these possess additional subtypes; for example, there are 4 described distinct subtypes of serotype A toxins.3 All of the serotypes have a similar chemical structure and, except subtype C2, are neurotoxins. Each botulinum toxin is initially

History

Botulism, derived from the Latin botulus meaning sausage, was first described in the 1820s when several cases occurred in Germany associated with the ingestion of improperly preserved smoked sausage. The bacterial etiology was discovered in 1895 and the toxin itself was isolated in the 1940s. In the 1970s, Dr Alan Scott pioneered research on the clinical utility of BTX, treating strabismus in a primate model. He eventually graduated to humans and published the first sizable therapeutic trial in

Botulinum toxins in clinical use

Currently, 4 botulinum toxin products have FDA approval in the United States. Three contain serotype A complexes: OnaA (Botox), AboA (Dysport), and incobotulinumtoxinA (Xeomin). There is also 1 serotype B injectable: rimabotulinumtoxinB (Myobloc). RimabotulinumtoxinB (RimB) is only approved for treatment of cervical dystonia. It has been employed for other conditions of muscular spasticity but has been rarely used for cosmetic purposes. A recent randomized, placebo-controlled trial demonstrated

Reconstitution, supplies, and storage

The package inserts of Botox and Dysport both advise reconstitution in 2.5 mL of unpreserved saline (1.5 mL is also a listed alternative for Dysport). A randomized, double-blind study has shown that there is less pain and equal efficacy with preserved saline, which is possibly secondary to the anesthetic properties of the benzyl alcohol that is added as a bacteriostatic agent.31 A 2004 consensus conference of opinion leaders on the cosmetic use of Botox reported that most injectors use a

Onset and duration of action

Clinically detectable rhytid reduction occurs 3 to 7 days after injection, although the onset of action of OnaA has not been formally studied. In contrast, the self-reported onset of action of AboA was specifically investigated in its 4 phase III FDA trials. Patients were asked to maintain diaries during the initial 7 days following injection. The patients’ self-reported median onset of action ranged from 2 to 4 days with 13.4% to 32.5% responding in the first 24 hours. (Schlessinger J, Kane M,

General Principles

  • 1.

    Dose must be tailored to the individual patient, taking into account idiosyncratic anatomy, individual muscle size, tone and strength, baseline asymmetries, and perhaps most importantly, desired outcome.

  • 2.

    A thorough knowledge of the anatomy in an area of injection is required to optimize efficacy and safety.

  • 3.

    Neurotoxin monotherapy is most gratifying for patients with predominantly dynamic wrinkling or small facial asymmetries or ptoses. Patients with enhanced resting muscle tone that report

Glabellar Lines

Injection of the glabella is the original and by far most common cosmetic usage of BTX-A. Numerous randomized, placebo-controlled trials have demonstrated the efficacy of both AboA and OnaA for this indication.

Treatment of the mid and lower face

As experience with BTX-A increases, many practitioners have ventured beyond the traditional applications of BTX-A in the upper face. Although not as extensively chronicled, BTX-A has definite utility in the rejuvenation of the mid and lower face but, in most patients, is best employed as adjuvant therapy with soft-tissue fillers or resurfacing procedures. The latter point has been highlighted in a recent prospective study. Ninety patients were randomized to receive (1) OnaA to the lips,

Complications

The overall safety record of BTX is exceptional. A recent meta-analysis of placebo-controlled trials with OnaA for either lateral canthal or glabellar rhytids found only 3 adverse events (AEs) were more common than placebo among 1170 subjects: eyelid sensory disorder (2.4%), which includes subjective symptoms of tightness and heaviness; eyelid edema (1.1%), and eyelid ptosis (1.8%).41

Adverse sequelae of BTX administration can be divided into 2 major categories: product-related complications and

Summary

The advent of BTX-A in the 1990s effectively launched the modern era of nonsurgical aesthetic medicine. Many of the components of the senescent face, which previously required surgical intervention, are now readily addressed with neurotoxin. Its wide acceptance paved the way for the adoption of numerous other injectables, which are now commonplace in the cosmetic surgeon’s office.

The two BTX-A products currently approved in the United States for cosmetic use share the same active ingredient and

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    Dr Cartee has no relevant conflicts of interest. Dr Monheit receives funding from Allergan Corporation, consultant and clinical investigator, Juvederm; Dermik Laboratories, clinical investigator, Sculptra; Genzyme Corporation, consultant and clinical investigator, Captique, Prevelle; J & J, consultant; Contura, clinical investigator, Aquamid; Ipsen/Medicis, consultant and clinical investigator, Dysport; Electro-Optical Sciences, Inc, consultant and clinical investigator, Melafind; Revance, consultant and clinical investigator; Kythera, clinical investigator; Galderma, consultant and clinical investigator; Mentor, consultant and clinical investigator; Merz, consultant and clinical investigator.

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