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Botulinum Toxin Injections (Botox®)
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.
History
Mechanism of action
Ice Analgesic Technique for Palmar Botox® Injections. Launch Video
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]
Back to top
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 (Allergan, Irvine,
California) 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]
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.
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List your practice or search for colleagues. |
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The makers of BOTOX® Botulinum Toxin Type A generously support
the International Hyperhidrosis Society. |
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