Section 4 Plastic and Reconstructive Problems

Reprinted by permission of Dermatol Surg. 2011; 37(11):1553-1565.

REVIEW ARTICLES

Handling Botulinum Toxins: An Updated Literature Review

A DA R. T RINDADE D E A LMEIDA , MD, L ETICIA C ARDOSO S ECCO , MD, AND A LASTAIR C ARRUTHERS , MD y

BACKGROUND Botulinum toxin (BoNT) has been in use since the late 1970s, and over the last 20 years, its use has been extended to new indications in various areas of medicine. During these years of clinical use, some of the initial ideas have changed, and others have remained stable along with increasing experience with and knowledge about BoNTs. OBJECTIVE To review the literature and prescribing information on all of the available products and to update the concept of handling toxins (preparations, reconstitution, storage, sterility, and dilution). METHODS A review (not Cochrane type analysis) of the medical literature based on relevant databases (MEDLINE, PubMed, Cochrane Library, specialist textbooks, and manufacturer information) was performed. CONCLUSIONS Many of the precautions around BoNT use, often recommended by the manufacturers, are described in the clinical literature as too restrictive. The literature suggests that toxins may be sturdier and more-resistant to degradation than previously understood. Dr. Ada R. Trindade de Almeida has been a consultant to Allergan, Inc. and participated in clinical trials for Allergan and Galderma. Dr. Alastair Carruthers is a consultant to Allergan, Inc. and Merz GmbH and has been paid to do research for both companies .

Background B otulinum toxin (BoNT) has been in use since the late 1970s in ophthalmology, 1 and over the last 20 years, its use has been extended to new indications in various areas of medicine, in particular dermatology. It is an effective treatment for strabis- mus, hemifacial spasm, blepharospasm, cervical dystonia, spasmodic dysphonia, hyperhidrosis, and facial rejuvenation. 2 Clostridium botulinum , a Gram-positive anaerobic bacterium, produces seven antigenically different neurotoxins, but only serotypes A and B are commercially available. 3 Serotype A (BoNTA) appears to be the most potent subtype. 4

glutinin and nontoxin nonhemagglutinin proteins. 3,5 The associated proteins serve to stabilize and protect the neurotoxin molecule from degradation. 6,7 Under physiologic conditions, the core 150-kDa protein dissociates from the toxin complex, binds to synaptic vesicle protein 2 using the heavy chain component, and enters the neuronal cell by internalization. 8 Once in the cytosolic surface membrane, BoNTA binds to and cleaves the 25-kDa synaptosomal-associated protein (SNAP25), whereas BoNTB binds to and cleaves the vesicle associated membrane protein, a component of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor family 9 involved in exocytic release of the neurotransmitters. 10

BoNTA is naturally produced as a complex of a core neurotoxin protein, along with several hemag-

Clı´nica Dermatolo´ gica do Hospital do Servidor Pu´ blico Municipal de Sa˜o Paulo, Sa˜o Paulo, Brazil; y Division of Dermatology, University of British Columbia, Vancouver, British Columbia, Canada.

& 2011 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc. ISSN: 1076-0512 Dermatol Surg ;37:1553–1565 DOI: 10.1111/j.1524-4725.2011.02087.x