An Overview of Botulinum Toxins: Past, Present, and Future
Section snippets
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.
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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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Cited by (35)
Botulinum toxin in the management of primary and secondary Raynaud's phenomenon
2021, Best Practice and Research: Clinical RheumatologyCitation Excerpt :The SNARE macromolecule is necessary for the assembly of the synaptic fusion core complex required for vesicle exocytosis. Cleavage of the SNARE components thereby impairs membrane fusion and neurotransmitter release [18,19]. Btx preferentially inhibits cholinergic neurotransmission.
Injectable and topical neurotoxins in dermatology: Indications, adverse events, and controversies
2017, Journal of the American Academy of DermatologyCitation Excerpt :When addressing the frontalis muscle, it is important to maintain the brow in a neutral position with a naturally arched shape. This is accomplished by simultaneously treating the brow depressor muscles in the glabellar complex (corrugator supercilli and procerus) and the lateral fibers of the orbicularis oculi and should be considered.15,102 When treating the sole brow elevator, the frontalis muscle, another untoward result is the “quizzical” or laterally elevated brow (Mr. Spock brow).
Botulinum Toxin Use in the Upper Face
2016, Atlas of the Oral and Maxillofacial Surgery Clinics of North AmericaTen mistakes to avoid when injecting botulinum toxin
2015, Actas Dermo-SifiliograficasCitation Excerpt :According to the American Society of Plastic Surgeons, injection of botulinum toxin is currently the most common cosmetic procedure in the United States. The use of botulinum toxin to eliminate expression lines by relaxing the facial muscles has become—together with dermal fillers—the mainstay of therapy for the prevention and treatment of facial aging.1 Patients considering injectable treatments generally want natural-looking, minimally detectable results.
Self-mutilation of the lower lip in a child with dystonia secondary to megalencephalic leukoencephalopathy treated with botox injections: A case report
2014, Journal of Oral and Maxillofacial SurgeryA pilot study evaluating the efficacy of botulinum toxin A in the treatment of Raynaud phenomenon
2013, Journal of the American Academy of Dermatology
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.