Sweating is a natural phenomenon necessary for the regulation of body temperature. The secretion of sweat is mediated through nerve stimuli of the sympathetic nervous system. In some individuals this system works at so much higher level than that required to maintain a constant body temperature.
Hyperhidrosis is excessive sweating that may be primary or secondary to medication or disease. Clinical features supporting primary or secondary etiology have not been well documented.
Primary Hyperhidrosis
The areas most commonly affected by hyperhidrosis are the palms, armpits and sometimes the lower limbs.
Excessive sweating of the hands is generally the most annoying condition between all forms of iperidrosi.In As the hands are the most exposed areas of the body of the individual and excessive sweating in a load of that area of the body could sometimes lead to psychological problems.
The degree of sweating can range from a moderate increase of the 'moisture until the formation of drops. Often, the hyperactivity of nerves that regulate sweating also creates conditions affecting the microcirculation.
A combination of different localizations described above is very frequent, hyperhidrosis sweating attacks may occur with or, less frequently, in a continuous manner.
It can be caused by a high temperature or emotional stress, but it can also occur without any apparent underlying cause.
- Alteration of the sweat glands's function
The pathophysiologic characteristics of primary hyperhidrosis are not well understood: sweat glands are nor- mal in number, size, and function in patients with hyperhidrosis; however several authors have demonstrated abnormal sympathetic skin response in these patients, and its cause seems to be related to a complex sympathetic nervous system (which innervates sweat glands) dysfunction .
In sympathetic ganglia, the main neurotransmitter is acetylcholine, which exerts its function by binding to a postsynaptic neuronaltype nicotinic receptor. This receptor is composed of alpha and beta subunits in various combinations, forming a pentamer. Human autonomic ganglia express alpha-3, alpha-4, alpha-5, alpha-7, beta-2, and beta-4 subunits, with a predominance of the alpha-3 subunit. Usually, such receptors are formed by 2 alpha and 3 beta subunits, and the prevalent compositions are the heteromers alpha-3/beta-4 and alpha-3/beta-2. As an exception, there are receptors formed only by alpha-7 subunits without any beta subunit. Moreover, alpha-4, alpha-5, beta-2, and beta-4 subunits usually appear associated with alpha-3 subunit. Therefore if alpha-3 and alpha-7 subunits are quantified, all the receptors in the ganglion could be studied. Although the resection of 1 or more thoracic sympathetic chain ganglia is the most effective primary hyperhidrosis treatment, the function of sympathetic ganglia in normal individuals and in patients with hyperhidrosis remains unknown to date. Previous studies have demonstrated similar expression of alpha-3 nicotinic acetylcholine receptor subunit in patients with hyperhidrosis compared with individuals without this disorder; however the expression of alpha-7 subunit and acetylcholine itself has not yet been investigated.
Surgical treatment of primary hyperhidrosis by video assisted thoracic sympathectomy has improved the quality of life in a growing number of individuals worldwide every year. This procedure already accounts for a significant portion of the activity of most thoracic surgery services, yet little is known about the target organ of this operation: the sympathetic ganglion, especially among patients with hyperhidrosis, the subgroup of individuals who will be operated on. Even simple data, such as ganglion size, are lacking. This is the first study to show elevated expression of acetylcholine and the alpha-7 nicotinic receptor subunit in sympathetic ganglia of patients with hyperhidrosis, as well as the increased diameter of these ganglia when compared with noncarriers.
- The increased acetylcholine expression
The increased acetylcholine expression in the ganglia of patients with hyperhidrosis found in this study may be related to hyperactivity of the central portion of the sympathetic nervous system (preganglionic neurons located in the lateral column of the spinal cord) releasing a high amount of neurotransmitter in the synaptic clefts within the ganglion. This also may be related to increased production of acetylcholine in the cell bodies of postganglionic neurons that will reach the sweat glands for anterograde flow from the soma to the axon. However such increase was found both in areas of strong expression (marking, in particular, neurotransmitter synthesis areas) and weak expression (analogous to the distribution of synaptic clefts), which appears to demonstrate a combination of both events.
- Innervation of the sweat glands
The sweat glands are innervated in a very sui generis way by cholinergic fibers of the sympathetic nervous system. They also do not have parasympathetic innervation, although they are related to hypothalamic nuclei that are considered parasympathetic. Some results show that the acetylcholine receptor, involved in synaptic transmission at the ganglion of patients with primary hyperhidrosis, also does not obey the rule. The usual conformation of neuronal nicotinic acetylcholine receptors consists of 2 alpha subunits and 3 beta subunits. An exception is a receptor composed of the alpha-7 subunits only, without any beta subunit in its composition, which is the subunit whose expression was found to be increased in patients with hyperhidrosis.
Some results confirm the hypothesis that sympathetic ganglia are able to modulate the nervous stimuli from the central nervous system, presenting high concentrations of acetylcholine and a strain-specific receptor, and play an important role in the pathophysiologic process of primary hyperhidrosis.
Although not readily apparent in daily operative practice, we found larger ganglion diameter in patients with hyperhidrosis. Such a divergence can be justified by the small size of the sympathetic ganglion, in which small variations (2 mm median difference between the groups in our study) are significant in relation to the diameter of the control group but difficult to notice during naked-eye inspection.
It was concluded that there is a higher expression of acetylcholine and alpha-7 neuronal nicotinic acetylcholine receptor subunit in the sympathetic ganglia of patients with hyperhidrosis. Furthermore, the diameter of the sympathetic ganglia is bigger in patients with hyperhidrosis.
(Expression of acetylcholine and its receptor in human sympathetic ganglia in primary hyperhidrosis 2012.)
Secondary Hyperhidrosis
The secondary hyperhidrosis is a disorder that, as already described above is in onset following a other pathology.
The most common diseases that cause an onset of hyperhidrosis are endocrine disease accounted for 57%, including diabetes mellitus , hyperthyroidism , and hyperpituitarism. Neurologic disease accounted for 32%, including peripheral nerve injury, Parkinson's disease , reflex sympathetic dystrophy , spinal injury and Arnold-Chiari malformation.
- Hyperhidrosis and Hyperthyroidism
One of the most frequent triggers of hyperhidrosis is the secondary hyperthyroidism, we know that the excessive production of T3 and T4 hormones cause an excessive stimulus dependent mitochondrial ATP production, overproduction of triiodothyronine and tetraiodothyronine then cause an increase in endogenous body temperature, which will lead to peripheral vasodilation of blood vessels and the opening of the sweat glands of sweat in order to balance the situation.
- Hiperhidrosis an SNC disease
Psychiatric diseases caused by alterations of CNS neurons of which is produced thanks to Acetylcholine enzyme choline-acetyl-transferase which is reacted with choline acetyl CoA producing acetylcholine more coenzyme A. We know that acetylcholine is released as it is a neurotransmitter of the sympathetic system which induces vasodilation of blood and the opening of the sweat glands.
An excessive activity of the enzyme choline acetyltransferase therefore leads to an excessive production of the sympathetic neurotransmitter which will be the actual cause of hyperhidrosis
- Correlation between primary hyperhidrosis of acetylcholine receptors
In addition to the increase of production of acetylcholine was observed a correlation between the increase of glucocorticoids and the presence of hyperhidrosis.
This correlation could be due to increased synthesis of receptors for acetylcholine due to the presence of steroid hormones.
This has led to the assumption that it was not necessary to increase the number of vesicles of ACH to increase sweating in the patient.
In this regard we would like to emphasize that a reduction of acetylcholine itself leads to decreased ATP production, this could lead to the human body, not proficient in the production of new molecules of choline, an increase of neurotransmitter receptors distributed throughout the body in turn would lead to an increase of the efficiency of acetylcholine itself thus inducing inevitably the hyper production of sweat.
(Specific effect of corticoids on acetylcholine receptor expression in rat skeletal muscle cell cultures 2004)
- Other causes of secondary hyperhidrosis
Therapies most frequently used
Is easy to predict that it will be easiest if you do not at least more targeted treatment that will target secondary hyperhidrosis, hyperhidrosis is not lost but rather to the pathology of the background that triggered it, and this is called causal therapy.
It is more difficult to treat primary hyperhidrosis for its obscure causes. Is done here with what is called symptomatic therapy.
Are subjected to this treatment not only patients with essential hyperhidrosis but also patients with secondary hyperhidrosis, which do not respond to initial therapy
Antiperspirants are the first choice therapy. The substance appears to be the most effective aluminum chloride. This substance is able to significantly alleviate the problem if the sweating is not too excessive. To be effective, the substance must be present in concentrations ranging from a low of 15% to 25%. In some patients the aluminum chloride can cause irritation of the skin reactions with itching and redness and the formation of eczema. The treatment must be repeated regularly.
Ionophoresis is a technique that involves passing a low current through the skin into the body part affected by hyperhidrosis, it is assumed that the current causes a thickening of the microscopic surface layer so as to clog the ducts of the sweat glands and interfere with the sensitivity of the receptors that respond to the stimulus of the nervous gland.
The treatment is done with the hands or feet are immersed in containers partially filled with water and connected via electrodes to the generator.
Earlier treatments, lasting 20-30 minutes, repeated daily or go every 2 days. The first few days may be a transient worsening, but in the days after sweating tends to decrease gradually. After ten days or so generally follows a period with hands / feet dry which can last from a few days to 3-4 weeks. As soon as he repeats the humidity is advisable to practice immediately before a maintenance cycle.
(Accidents caused by iontophoresis 1993.)
The toxin of the bacterium Clostridium botulinum is able to block the secretion of sweat from the sweat gland. This effect is determined by the inhibition of the release of the neurotransmitter acetylcholine from presynaptic nerve endings, resulting in arrest of nerve impulses responsible for the stimulation of the sweat gland. Only after several months, the nerve endings regain the ability to release acetylcholine again with gradual recovery of sweating.
There are no specific medications against profuse sweating. Psychotropic drugs are often administered anticholinergics, but given the dosages required to achieve an acceptable effect against hyperhidrosis, the side effects generally become unbearable. For this reason it can not be recommended in most cases.
Andrea Baù, Simone Valsania
