Botulinum Toxins in Clinical Aesthetic Practice 3E, Volume One

Clinical Adaptations

Anthony V Benedetto

• Publisher: CRC Press
• Year: 2017
• Print ISBN: 9781138301849
• eBook ISBN: 9781351396448
• Topic: Medicine
• Subtopic: Dermatology

This bestselling guide to the complexities of botulinum toxins has now been extensively revised, updated, and expanded. Now in two volumes, Volume 1 examines clinical adaptations in the toxins in use today, use with other injectables, use for other parts of the body and other indications, and legal aspects, while Volume 2 documents in detail the functional anatomy and injection techniques for the face, neck, and upper chest. No practitioner of aesthetic medicine will want to be without this comprehensive and authoritative guide from the international experts.

1

Botulinum toxin and its development in clinical medicine

Jean Carruthers and Alastair Carruthers

Introduction

In the aftermath of the Napoleonic wars (1799–1815) in Europe in the early nineteenth century, Dr. Justinus Kerner, an astute German physician and poet, noted that there seemed to be a substance in sausages that was causing people to die of a mysterious paralytic disease. Dr. Kerner postulated that this substance could possibly be helpful in treating overactive muscle conditions. Subsequent characterization of this substance and research led San Francisco ophthalmologist Dr. Alan Scott to consider using botulinum toxin type A (BoNT-A) as an alternative to surgery in the treatment of strabismus. In 1982, Ophthalmologist/Dermatologist Dr. Jean Carruthers had the opportunity to undertake a Fellowship with Dr. Scott and subsequently with Dr. Joseph Tsui and other Vancouver neurologists and published the first study of treating patients with dystonias with BoNT-A. Drs. Jean and her husband Alastair Carruthers then treated the first cosmetic patient, thus beginning a new era in the use of biologic substances considered to be deadly poisons as safe clinical modalities in the cosmetic as well as in the medical world.

Sausage poisoning and clostridium botulinum

At the end of the eighteenth century, the number of cases of fatal food poisoning throughout the southwest German region of Württemberg increased, likely due to widespread poverty after the devastating Napoleonic Wars (1795–1813) and subsequent unsanitary food production in rural areas.1 In 1793, after 13 people fell ill and after 6 died during an outbreak in the small village of Wildbad in Württemberg, medical officers in the region scrambled to understand and identify the cause. By 1811, the Department of Internal Affairs of the Kingdom of Württemberg had pinpointed prussic acid in undercooked blood sausages as the culprit. In 1820, the district medical officer and poet, Justinus Kerner (1786–1862) published his first monograph on sausage poisoning, with a complete clinical description and summary of 76 case histories.2 In a quest to extract and isolate the unknown toxic substance he called “fat poison” or “fatty acid,” Kerner began to experiment on animals and himself in the pharmacist’s laboratory, eventually publishing the first complete monograph containing the clinical evaluation and summary of 155 cases and accurate descriptions of all gastrointestinal, autonomic, and neuromuscular symptoms and signs of botulism.3 From his experimentation, Kerner deduced that his fat poison acted by an interruption of the peripheral and autonomic nervous signal transmission, leaving the sensory signal transmission intact. In the final paragraph of his monograph, Kerner discussed the potential use of the toxin for the treatment of a variety of disorders characterized by “sympathetic overactivity” (e.g., St. Vitus’ dance or Sydenham’s chorea, a disorder characterized by jerky, uncontrollable movements, either of the face or of the arms and legs) and hypersecretion of bodily fluid, as well as for treating ulcers, delusions, rabies, plague, tuberculosis, and yellow fever. Sausage poisoning was eventually named botulism, after the Latin word botulus, meaning sausage.

In December 1895, 34 people in the small Belgian village of Ellezelles fell ill with symptoms of mydriasis, diplopia, dysphagia, dysarthria, and increasing muscle paralysis after eating pickled and smoked ham.4 After examining the ham and conducting autopsies on the 3 patients who died, microbiologist Emile Pierre Van Ermengem (1851–1922) of the University of Ghent isolated an anaerobic microorganism that he called Bacillus botulinus—later renamed Clostridium botulinum.5

In 1904, an outbreak of food poisoning in Darmstadt, Germany involving canned white beans, led to the discovery of two serologically distinct strains of C. botulinum; these were eventually classified alphabetically as types A and B by Georgina Burke at Stanford University in 1919.6 Over the next decades, cases of botulism became more frequent with the increased popularity of canned food products, and additional strains—types C, D, E, F, and G—were identified.7

Clinical development of botulinum toxin

With the advent of war, the potential uses of botulinum toxins took on a more sinister edge. In 1928, Herman Sommer and colleagues at the University of California, San Francisco isolated pure botulinum toxin type A (BoNT-A) as a stable acid precipitate.8 As World War II approached, the United States government—along with multiple countries engaged in biowarfare programs—began intensive research into biological weapons, assembling bacteriologists and physicians in a laboratory at Camp Detrick (later named Fort Detrick) in Maryland to investigate dangerous and infectious bacteria and toxins.7 In 1946, Carl Lamanna and colleagues developed concentration and crystallization techniques for the toxin that were subsequently used by Edward J. Schantz, a young U.S. army officer stationed at Fort Detrick, to produce the first batch of BoNT-A which was the basis for the later clinical product.9,10 In 1972, President Richard Nixon signed the Biological and Toxic Weapons Convention, effectively putting an end to all investigations on biological agents for use in war, and Fort Detrick was closed. Schantz took his research to the University of Wisconsin, where he produced a large amount (150 mg) of BoNTA (batch 79–11) that remained in clinical use in the United States until December 1997.11

In the late 1960s and early 1970s, Alan Scott (Figure 1.1), an ophthalmologic surgeon at the Smith-Kettlewell Eye Research Foundation in San Francisco, began to experiment with BoNTA, supplied by Schantz, as a potential non-surgical treatment of strabismus.12 Scott published his first primate studies in 1973,13 and human studies with BoNT-A (then named Oculinum®) began in 1977. When he injected the toxin using a newly developed practical electromyographic (EMG) device (Figure 1.2)—a Teflon-coated needle used as an electrode that produced an auditory signal when the tip of the needle came close to motor endplates when the muscle was activated, allowing for pre...

Table of contents

• Cover
• Half Title
• Title Page
• Copyright Page
• Dedication
• Contents
• Preface
• Acknowledgments
• Prologue An anthropological perspective on facial attractiveness and expressivity
• 1. Botulinum toxin and its development in clinical medicine
• 2. Botulinum toxins: Pharmacology, immunology, and current developments
• 3. Pharmacology and immunology of non-complexed botulinum toxin
• 4. Topical botulinum toxin
• 5. The different botulinum toxins and their clinical uses in the West
• 6. The different botulinum toxins from around the world available for clinical use
• 7. Botulinum toxin used in conjunction with other injectables and devices for cosmetic purposes
• 8. Beyond the obvious: Beauty optimization with botulinum toxin
• 9. Botulinum toxin in the management of focal hyperhidrosis
• 10. Botulinum toxin type A treatment for depression, Raynaud’s phenomenon, and other novel dermatologic therapeutic applications
• 11. Medicolegal considerations of cosmetic treatment with botulinum toxin injections
• Appendix 1: Comparison of different consensus reports of botulinum toxin dosing in different Western countries
• Index