The use of botulinum toxin in the treatment of hyperhidrosis

2021-03-30

Let us consider the treatment of such local autonomic (hypersecretory) disorders as hyperhidrosis of the hands, feet, and axillary areas with botulinum toxin type A. The pathogenetic mechanisms of this disorder are considered, injection techniques are presented: schemes, doses, approaches.

Alla Grabchenko , cosmetologist, advisor to the director for the development of the cosmetology direction of Multimed, business coach, consultant in the area of “communication skills in medicine”, member of the International Association for Communication in Healthcare, author of the project #fearlessdoctor (Ukraine)

Normally, sweating is one of the important physiological adaptive mechanisms of the body to changes in environmental conditions, generating heat transfer in the process of evaporation of water from the surface of the body. Two types of physiological increased sweating have been described:

thermoregulatory - occurs on the entire surface of the body as a response to an increase in ambient temperature or during physical activity;
psychogenic – a response to emotional stress, usually locally, less often generalized.

This function is performed by eccrine sweat glands, which are evenly distributed over the entire surface of the body, with the largest accumulation in certain areas (Table 1). Their innervation is carried out by unmyelinated postganglionic sympathetic fibers with the main neurotransmitter acetylcholine.

Apocrine sweat glands play a role in the secretion of ferromones and the creation of body odor. They are not thought to be involved in thermoregulatory processes.

Hyperhidrosis (from “hyper-” and gr. hidros - “sweat”) is increased sweating, or excessive sweating. When we talk about hyperhidrosis, we are talking about the production of excess sweat, exceeding the amount necessary to restore normal body temperature. The normal level of sweating is less than 1 ml per 1 square meter. m of body surface per minute. With hyperhidrosis, the amount of secreted fluid can increase 10 times.

Hyperhidrosis is not a serious pathology that threatens human health, however, it has a significant impact on the quality of life, causing physical discomfort and social maladjustment, leading to significant professional limitations and problems in everyday life.

According to the American Academy of Dermatology, the quality of life of patients suffering from severe hyperhidrosis is significantly lower than even those with severe acne or psoriasis.

Classification of hyperhidrosis

There are different classifications of hyperhidrosis (Table 2).

Primary hyperhidrosis (PH), developing without specific causes (idiopathic hyperhidrosis, or primary). It is focal in nature and is most often characterized as limited visible sweating with the main localization in the armpits (axillary), soles, palms, face (Fig. 1).

In addition, primary local (idiopathic) hyperhidrosis is considered to be a condition that lasts at least six months, occurs for no apparent reason, and is characterized by at least two of the following symptoms:

bilateral and symmetrical;
sweating causes discomfort and interferes with daily activities;
at least one episode of sweating per week;
onset of the disease at a young age;
heredity;
no local increase in sweating during sleep.

PG primarily manifests itself in childhood or adolescence and continues throughout life. Anxiety and nervousness can aggravate or provoke attacks of sweating, but extremely rarely the mechanism of development is truly psychoneurological. Such patients are often considered emotional. But it is excessive sweating that causes embarrassment and discomfort, including social discomfort, and not vice versa. It is important that this condition is easy to treat conservatively.

Secondary (VG). Such hyperhidrosis is part of the symptoms of an underlying neurological or endocrine disease, as well as diseases of a malignant nature. For example, among other variants of the pathogenetic origin of CH, endocrinological disorders such as hyperthyroiditis, hypoglycemia, and pheochromocytoma have been described. And among the neurological ones - diabetic neuropathy, auriculotemporal syndrome, syringomyelia, etc. (Table 3).

Treatment Options

Traditional treatment regimens for hyperhidrosis in dermatology include topical application of aluminum salts (aluminum hexochlorohydrate) as cosmetic antiperspirants, iontophoresis, or oral anticholinergic drugs such as glycopyrrolate. However, the use of oral anticholinergic drugs causes unwanted side effects, such as blurred vision, dry mouth, and is characterized by limited effectiveness against sweating.

Surgical methods of therapy: direct excision of the skin of the axillary fornix with primary closure or with skin grafting and neurosurgical sympathectomy for palmar hyperhidrosis. Some authors have also proposed the use of a cannula for liposuction to scrape out from under the surface layer of skin the axillary area, where eccrine sweat glands are mainly located; there is evidence of the effective use of ultrasound methods (UltheraSystem, USA).

Sympathectomy has its complications in the form of Horner's syndrome, pneumothorax and damage to motor nerves. Limitation of mobility of the upper limb may occur.

Direct excision of the skin results in disfiguring scars and is often associated with a long recovery period and limited mobility. In general, all surgical treatment methods demonstrated an insufficient degree of effectiveness and a high incidence of side effects, including the development of compensatory hyperhidrosis in 64% of cases.

Of the conservative methods of treating hyperhidrosan, the most important is the use of drugs for intradermal injections that prevent the presynaptic release of acetylcholine in sympathetic nerve endings. Botulinum neurotoxin type A has these properties.

Efficacy of BTA for hyperhidrosis

Currently, many clinical studies have been conducted on the use of BTA in patients with local hypersecretory disorders. For example, Hallett M. in 2009 studied patients with body odor associated with excessive sweating. In 16 volunteers, BTA was injected into one axillary region and saline into the second. After 7 days, body odor was assessed using the T-shirttest. So, the odor in the area treated with BTA was rated as less intense and less unpleasant.

The use of BTA has confirmed its high effectiveness against severe hyperhidrosis with single use in low doses. The beginning of the use of BTA in medicine as a method of treating axillary and plantar-palmar hyperhidrosis has made the solution to such a problem as increased sweating accessible and safe.

Preparations based on botulinum toxin type A are today the treatment of choice in the case of hyperhidrosis and are becoming increasingly widespread in the practice of aesthetic medicine specialists.

Mechanism of action of BTA drugs

The mechanism of action of all types of botulinum toxins is the presynaptic blockade of acetylcholine release from the nerve terminal of the peripheral cholinergic synapse.

Acetylcholine is a neurotransmitter at synapses of the parasympathetic nervous system, some synapses of the central nervous system, somatic motor and preganglionic sympathetic nerve endings. Cholinergic receptors are found in skeletal and smooth muscles, internal organs, sympathetic and parasympathetic ganglia; M- and N-cholinergic receptors are distinguished (based on their reaction to muscarine and nicotine). A special type of cholinergic receptors are H-cholinergic receptors of afferent endings located in the autonomic ganglia, where they are essentially sensory fiber receptors.

The transmission of nerve impulses at the cholinergic synapse occurs in several stages. In the presynaptic nerve terminal, acetylcholine is constantly synthesized and accumulated in the form of vesicles, which are transported to the presynaptic membrane so that the transmitter molecules can exit into the synaptic cleft and contact specific cholinergic receptors of the postsynaptic membrane. At this site of the postsynaptic membrane, a membrane potential arises and muscle fiber contraction occurs. The process of transport of acetylcholine vesicles to the presynaptic membrane does not occur spontaneously, but actively with the help of a complex of special transport proteins, the main of which are SNAP-25, syntaxin and synaptobrevin. It is transport proteins that are the target of botulinum neurotoxins. When botulinum toxin enters a muscle or other target organ (with the bloodstream during botulism or for therapeutic purposes during injection), the molecules of the toxin complex reach the nerve terminals of the axons, attach to them, and then the neurotoxin part is introduced into the cytosol of the nerve terminal, where it breaks up into short and long chain. The short chain (which is a zinc-dependent protease) irreversibly and specifically cleaves the transport protein (subtype A blocks SNAP-25), thereby preventing the release of acetylcholine into the synaptic cleft and muscle contraction. The end effect of this process is persistent chemodenervation.

Inhibition of acetylcholine release in cholinergic autonomic ganglia and neuromuscular junctions leads to a long-lasting (up to 12 months) anhidrotic effect.

The advantage of botulinum therapy lies not only in achieving a long-term effect, but also in the absence of such likely undesirable effects as compensatory sweating, scar formation, etc., which often occur after the use of traditional methods.

Full version of the article in the magazine Les Nouvelles Esthetiques Ukraine 2, 2017