Botulinum toxin A injection has been used successfully to reduce excessive sweating in all of the body areas affected in primary hyperhidrosis: axillary, palmoplantar, and facial/gustatory. Characterized as a “minimally invasive treatment option” compared to local surgery and endoscopic thoracic sympathectomy, the use of botulinum toxin has become an important treatment option for patients not responding to more conservative therapies. [99] Botulinum toxin A has been approved for use in hyperhidrosis in Canada, the U.K. and other countries in Europe and South America (more than 23 countries total). In 2004, the US Food and Drug Administration (FDA) approved botulinum toxin type A for the treatment of severe primary axillary hyperhidrosis in patients unable to obtain relief using antiperspirants. (For complete prescribing information on Botox for hyperhidrosis, click here.)
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History
Characterized by multiple bulbar palsies and flaccid paralysis with no effect on the sensorium, botulism is a disease caused by ingestion of bacterial toxins in spoiled food. Variants such as wound botulism and infant botulism also are recognized, in which the bacteria multiply with symptoms arising from toxin production in vivo.[40]
In the 18th century, botulism was recognized as a disease upon autopsy of German patients having ingested spoiled sausages. The term botulism is derived from the Latin botulus for sausage. [40] In the early 19th century, a German physician, Justinius Kerner, spent much of his career studying botulism and advanced the concept of a bacteria in the sausages being responsible for the symptoms.[40] In 1895, the bacteria Clostridium botulinum was first isolated from spoiled pork and autopsied tissues by a Belgian physician Van Ermengem. A toxin elaborated by the bacteria was thought to cause the symptoms, but the toxin was not isolated until 1946 by Dr. Edward Schantz at Fort Detrick, Maryland.[75] In 1949, the mechanism of action of the toxin was characterized.[76]
Dr. Alan Scott, an ophthalmologist, was pursuing a nonsurgical treatment of strabismus, and using Dr. Schantz’s purified type A toxin he was able to successfully treat monkeys with small amounts of the purified protein injected into extraocular muscles.[76] After approval from the FDA to study botulinum toxin in humans, Schantz’s work eventually led to FDA approval of botulinum toxin A as an orphan drug in 1989 for use in strabismus, blepharospasm, and hemifacial spasm (Botox, Allergan).[75] Another type, A botulinum complex, was approved in the U.K. in 1991 (Dysport, Ipsen Biopharm).[8]
Botulinum toxin A has been tried for many different muscular conditions, including hyperactive sphincter muscles in the GI and GU tracts,[76] cervical dystonia, and spasticity in cerebral palsy, as well as for enhancing appearance by relaxing facial muscles to remove facial wrinkles and lines.[75] The first nonmuscular use of botulinum toxin was suggested by Bushara and Park in 1994, noting that patients treated for hemifacial spasm had decreased sweating in the treated area.[24,76] The first use of botulinum toxin A in hyperhidrosis was for Frey's syndrome (gustatory sweating),[75] and use of the drug in other focal areas soon followed.[98]
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Mechanism of action
Clostridium botulinum produces seven antigenically different toxins: BTX-A, -B, -C, -D, -E, -F and -G.[61] The toxins are 150-kd proteins, which are activated when cleaved into a heavy and light chain by a bacterial protease. The active protein is composed of the 100-kd heavy (H) and 50-kd light (L) chains joined by disulfide bonds and noncovalent bonding.[61]
The protein works by inhibiting release of acetylcholine from the presynaptic terminal of the cholinergic nerve junctions with striated muscle and eccrine glands.[61,75] There are three steps to the neurotoxic process: the toxin binds to cholinergic receptors via the H chain, the neurotoxin is internalized by endocytosis, and finally acetycholine release is blocked. This final step is carried out by the L chain, which has proteolytic activity, cleaving a protein that is part of a complex intracellular platform involved in release of acetylcholine from vesicles through the cell membrane. Each of the toxins is able to cleave a different specific protein that is part of the acetylcholine transport apparatus.[61]
It was originally thought that the prolonged but impermanent chemodenervation caused by botulinum toxin was due to anatomic changes of the motor neuron. The nerve terminal develops sprouts that eventually reach the muscle fiber and become functional. The sprouts regress, though, when the intoxicated nerve terminal is again capable of exocytosis.[8] The neuron once again becomes capable of exocytosis when the proteins that are cleaved by toxin are made anew.[115]
Botulinum toxin A (BTX-A) is the most potent of the seven serotypes and is the form available commercially in two products. Botox (AbbVie, Inc.) is available internationally and in the U.S. Dysport (Ipsen Biopharm, Wrexham, U.K.) is used primarily in Europe [75]. Both products contain BTX-A but are different formulations manufactured by different processes and therefore have different potency. One unit of Botox is said to be equivalent to three to five units of Dysport. [75] However, a study comparing local and systemic effects of the two preparations suggested that the dose ratio will differ when the serotypes diffuse from the injection site and have a systemic effect, which is likely to occur at higher doses. [8]
Xeomin is another BTX-A brand. Conversion ratios between Botox (onabotulinum toxin-A), Dysport (abobotulinum toxin-A) and Xeomin (incobotulinum toxin A) in clinical practice, according to an article in the journal toxins, are:
Botox and Xeomin - 1:1 (dose equivalent units)
Botox/Xeomin and Dysport - 1:2-3
According to the Cleveland Clinic, results may last longer and manifest faster with Xeomin and there may be fewer allergic reactions to Xeomin. Xeomin does not need to be refrigerated. Dysport may diffuse further or spread more. Effects of Dysport can last about the same as Botox but with Dysport effects visible at about 2 days compared to about 1 week with Botox. With all three injectables, FULL results will take a week or two to manifest. Of course results vary from individual to individual as well. Prices for the three injectables vary from practice to practice and should be discussed.
Botulinum toxin B is available commercially as Myobloc (Elan Pharmaceuticals, San Francisco, California, and Dublin, Ireland). Currently Myobloc has FDA approval only for cervical dystonia,[96] and it is not approved by the FDA for treatment of hyperhidrosis.