Anhidrosis

Excretion of sweat is a physiological necessity for the human body, because sweat promotes thermoregulation, elimination of toxic and other "unnecessary" substances. But sometimes the sweating mechanism gets lost, starts to work with violations. One of these "failures" is anhidrosis - a condition in which the sweat glands cease to perform their function. Pathology can affect, as any specific area, and the whole body. Anhidrosis is difficult to diagnose in the early stages, so the disease often takes a protracted course. 

Epidemiology

Anhidrosis is a condition that characterizes the disorder of the work of the sweat glands, and in translation from the Greek language literally sounds like "lack of perspiration." Acquired forms of the disease are more common, and congenital forms are much less common (literally in 2-6 cases per hundred thousand newborns).

The acute acquired form of pathology is diagnosed mainly in hot weather, although there are exceptions.

Both women and men are ill the same. In addition to humans, anhidrosis is also found in the animal kingdom - for example, in horses. In particular, off the coast of the Persian Gulf, impaired sweating occurs in one of five horses. [1]

Causes anhidrosis

Anhidrosis can develop against the background of lesions of any of the links that make up the chain from the cerebral cortex to the outlets of the sweat glands. Such lesions can be:

• Central nervous system pathologies.

The generalized form of anhidrosis is a common sign of atrophic processes in the body, along with a decrease in blood pressure, extrapyramidal and cerebellar disorders. Patients may complain of periodic spontaneous sweating, which is asymmetric in the early stages of pathology. Generalized or macular anhidrosis without orthostatic pressure reduction is often found in Parkinson's disease, sporadic parkinsonism, and supranuclear progressive paralysis. Such violations can be accompanied by the perspiration function in the facial area, which can be considered a kind of compensation reaction. [2]

The processes of demyelination of the central thermoregulatory pathways often lead to the appearance of anhidrosis in patients suffering from multiple sclerosis - especially with steadily progressing pathologies. The development of generalized anhidrosis is often noted in the post-stroke period and after thalamotomy surgery. Injury to the spinal cord leads to a disorder of thermoregulation below the affected area, which may be due to disinhibition of certain neural circuits. Since the vasodilating function is simultaneously lost against the background of tetraplegia, anhidrosis can lead to the development of hyperthermia. [3]

• Pathologies affecting the peripheral nervous system.

With physiological age-related processes, the quality of thermoregulation in the body deteriorates, which is associated with the influence of peripheral nervous and other factors. An important role is also played by the genetic predisposition and the quality of the individual adaptation of the organism. Severe anhidrosis is often noted in some pathologies of the peripheral nervous system. In many patients, against the background of an increase in temperature or physical activity, tolerance to thermal effects decreases: general weakness, dizziness, shortness of breath, redness of the skin, tachycardia, and the risk of heat stroke increase.

• Polyneuropathy.

Distal anhidrosis is often diagnosed in the majority of patients with peripheral neuropathy. The most common cause of neuropathy is diabetes mellitus, in which there is a malfunction of thermoregulatory sweating according to the polyneuropathic variant (type "gloves" and "socks"). With the growth of pathology, the development of asymmetric and total anhidrosis is possible. [4],  [5], [6]

Some autoimmune neuropathies are accompanied by selective damage to autonomic neurons. In this case, anhidrosis can be noted along with a decrease in digestive motility, orthostatic hypotension, pathological pupillary reactions, and a neurogenic bladder. In patients, autoantibodies to ganglionic acetylcholine receptors are determined. [7]

Anhidrosis can accompany neuropathies resulting from amyloidosis, alcoholism, vasculitis, Fabry and Tangier diseases,  [8]Negeli-Franceschetti-Jadasson syndrome,  [9] prickly heat. [10]Limited anhidrosis occurs in leprosy.

Sweating disorders are observed in hereditary sensory-motor neuropathies of the fourth and fifth types (lack of pain sensitivity and anhidrosis). [11]

• Ross Syndrome.

Increasing segmental anhidrosis, combined with areflexia and Adie pupils, is a clinical triad characteristic of Ross syndrome. Such anhidrosis is asymmetric. Pathology is caused by defects in postganglionic neurons. [12]

• Chronic form of idiopathic anhidrosis.

Anhidrosis develops in an isolated form, or in conjunction with autonomic disorders. Patients complain of skin redness, a feeling of heat, dizziness, shortness of breath, weakness. Symptoms arise from physical activity or fever.

• Dermatological pathologies.

Burn injuries, radiation, inflammatory skin lesions, scars, etc. - all these factors can cause partial anhidrosis. The violation often becomes a consequence of psoriasis, ichthyosis, lichen, scleroderma, exfoliative dermatitis. Another reason is necrosis of the sweat glands due to drug intoxication, carbon monoxide poisoning. [13]

Temporary anhidrosis may appear as a side effect of anticholinergic drugs, tricyclic antidepressants, phenothiazines. For example, when taking topiramate in patients, there is a suppression of carbonic anhydrase of the sweat glands.

Risk factors

Anhidrosis can develop as a result of various diseases and disorders in the body. However, most often the problem appears against the background of such problems:

• violations of water-electrolyte metabolism or other metabolic processes, prolonged intoxication, digestive disorders, infectious diseases with inadequate fluid replenishment;
• hereditary predisposition associated with impaired activity of the sweating system, autonomic nervous system;
• a tendency to neuropathy, autoimmune diseases, surgical and diagnostic invasive interventions that can lead to damage to the nerve trunks;
• long-term drug therapy, radiation, chemotherapy, taking anticonvulsants, drugs based on belladonna, akrikhin;
• skin pathologies and injuries, trauma (including chemical and thermal burns).

Anhidrosis develops more often in the elderly, as well as in persons suffering from chronic alcoholism.

Pathogenesis

The sweating function of the glands of the same name is one of the key links in thermoregulation in the human body. With an increase in the adequate values of the internal temperature, which determines the hypothalamus, certain parts of the autonomic nervous system are reflexively stimulated, which leads to increased generalized sweating, vasodilation, and increased respiration. This response allows the body to maintain thermal stability and homeostasis. The neuronal direction involved in this reaction starts from the preoptic region of the hypothalamus along the medial region of the lateral cord of the brain stem, to synapses on the preganglionic neurons of the mid-intermediate spinal column. [14]Further, the path of postganglionic sympathetic cholinergic fibers diverges to numerous sweat glands, and there are several million of them. Most of them are found in the palmar and plantar zones, and the smallest in the back. [15]Different parts of the body are innervated by such segments of the spinal cord:

• face and eyelids - T ₁  T ₄;
• hands - T ₂  T ₈;
• torso - T ₄  T ₁₂;
• legs - T ₁₀  L ₂.

Improper sweating usually manifests itself in the form of increased function (hyperhidrosis) and its decrease (hypohidrosis). With complete dysfunction of the sweat glands, they speak of anhidrosis - the absence of perspiration. In severe cases, anhidrosis requires emergency medical intervention, since it can lead to fever, thermal exhaustion, heat stroke, and even death. 

Symptoms anhidrosis

Symptoms of congenital anhidrosis are different, but most often hereditary pathology is characterized by such signs as disorders of the dentition, bone-facial deformity, and lack of hair. During the neonatal period and in infancy, children suffer from numerous violations of thermoregulation, which can lead to the development of hyperthermic complications. In adulthood, the patient's condition can be monitored and compensated for by limiting physical activity, excluding being in hot conditions, ensuring an adequate intake of water into the body.

In chronic generalized anhidrosis, already at an early stage, there is an increased sensitivity to various temperature extremes, which poses a potential danger to the patient. The skin of such patients is thinned and dry, characterized by regional hyperkeratosis, itching, hyperemia, peeling on the face and hands, regardless of the season (the situation is aggravated in winter). With physical activity, sweat is not released, it becomes difficult for the body to maintain a normal temperature. The process involves the lacrimal and mucous glandular system: the patient develops dry eye syndrome, there is dryness of the nasopharyngeal region. A poorly hydrated eyeball leads to symptoms such as burning, gritty eyes. An inflammatory process such as conjunctivitis or blepharitis may develop. Dryness of the nasal mucosa provokes an asthma-like clinical picture.

If an acute generalized form of anhidrosis develops, then they speak of a life-threatening condition. The patient's state of health is rapidly deteriorating, up to a serious condition. Heartbeat increases, breathing becomes more intense. A rapid accumulation of metabolic products occurs in the body. The daily volume of urine increases, the work of the digestive system is interrupted. The patient loses his appetite, but often feels intense thirst, which is especially painful with increasing dehydration. In some cases, thirst is absent - for example, if the anhidrosis is due to some underlying disease. [16]

Intoxication is growing, which further increases the temperature. The general condition is rapidly disrupted, the function of organs and systems in the body is upset. Such a patient requires urgent medical attention.

With the local form of anhidrosis, the general condition of a person does not suffer. The skin in the affected area begins to peel off, dryness and cracking appear. However, the pathology can be directly identified only in the course of a comprehensive diagnosis.

First signs

The first "bells" of the development of anhidrosis most often appear when a person is in hot conditions, or receives intense physical activity. At this time, the following may be noted:

• absence of sweat discharge in typical places (armpits, back, groin, face and forehead);
• dizziness;
• redness of the face;
• spastic muscle contractions, convulsive twitching;
• general weakness;
• increased body temperature.

The affected areas of the skin are easily injured, cracks form that can become infected. As a result of the inability to remove toxic substances from the body, intoxication may develop, accompanied by fever, autonomic disorders. On intact skin areas, a compensatory increase in perspiration is not excluded.

When the first suspicious symptoms are found, you must:

• do not go into hot and stuffy rooms, if possible, turn on the air conditioner;
• wear clothes made of light natural fabrics;
• consult a doctor and tell about the problem.

Forms

Anhidrosis can have a different etiology of development, varying degrees of severity. Depending on this, the disease is divided into several options, which allows the doctor to more accurately and quickly formulate the essence of the pathology, predict possible consequences and correctly prescribe treatment.

Practicing dermatologists usually talk about these types of anhidrosis:

• Congenital anhidrosis is usually observed in people with hypoplastic and aplastic changes in the sweat glands. Pathology is transmitted in an autosomal recessive way, and the first signs can be observed already during the neonatal period. The disease has a chronic generalized course, combined with other congenital disorders.
• Acquired anhidrosis is the result of other pathologies or disorders of certain functions in the body. The acquired form is often clinically diverse, can occur in several variants:
  • the acute form develops against the background of intoxication or metabolic disorders, is accompanied by severe thermoregulatory disorders, general intoxication signs, has an unfavorable prognosis;
  • the chronic form develops with disorders of the autonomic nervous system, with atrophic processes affecting the sweat glands;
  • the tropical form is typical for regions with hot climatic conditions against a background of low fluid intake, accompanied by the appearance of vesicular eruptions, which is due to the clogging of the exits of the sweat glands with microscopic particles of dust, dirt, etc.;
  • the focal form appears on limited areas of the trunk, limbs or face - for example, this option is characteristic of the Bernard-Horner syndrome, accompanied by ptosis, miosis, enophthalmos and anhidrosis;
  • the generalized form spreads to the whole body, it can also affect other glandular systems - in particular, the mucous nasopharyngeal and lacrimal glands (the so-called ocular anhidrosis).

Congenital insensitivity to pain with anhidrosis

This pathology refers to rare hereditary disorders that are transmitted in an autosomal recessive manner. The disease is accompanied by a disorder of the sensitivity of pain receptors. The clinical picture is presented by the following signs:

• insensitivity to painful stimuli;
• failure of thermoregulation;
• oligophrenia;
• tendency to self-harm;
• anhidrosis;
• periodic breathing difficulties;
• spontaneous fever.

Sweating does not occur when exposed to heat, pain, emotional or chemical stimuli.

The essence of the development of pathology is as follows. Mutational changes in the NTRK1 gene cause abnormal development of cholinergic, sympathetic neurons (in particular, those that innervate the sweat glands) and sensory nerve cells localized in the dorsal spinal roots. Incorrect myelination of peripheral fibers occurs. Auxiliary signs of pathology: resistance to pain against the background of preserved tactile and gustatory sensations. Any attempts to induce sweating are in vain, from thermal effects to pilocarpine test or electrical stimulation. When the temperature rises, taking antipyretic drugs is ineffective, but physical cooling techniques "work".

Patients have regular osteomyelitis, aseptonecrosis, and their teeth fall out early. When conducting electromyography, no impaired nerve conduction is noted.

Complications and consequences

The main complication of anhidrosis is considered to be a violation of thermoregulation and overheating of the body, which is a particular danger for children of childhood.

The following adverse symptoms are most often recorded:

• convulsive twitching caused by a violation of thermoregulation (muscle spasms, pulling pains in the limbs, abdomen and back);
• exhaustion as a result of thermal imbalance (accompanied by general weakness, nausea, tachycardia);
• heatstroke (critical overheating of the body, which is accompanied by depression and loss of consciousness, hallucinations and, if no assistance is provided, death).

Since complications in anhidrosis develop quite rapidly, it is necessary to deliver the patient to a medical facility as soon as possible to provide qualified assistance.

A typical adverse event in acute generalized anhidrosis is renal and hepatic dysfunction. Against the background of progressive intoxication, an overload of these organs occurs, which can subsequently cause the development of chronic insufficient function and a state of decompensation. With dehydration and rapid loss of blood plasma, there is a thickening of the blood with the appearance of signs of insufficient cardiac activity.

Diagnostics anhidrosis

It is not difficult to determine the state of anhidrosis in a patient. Difficulties usually arise with identifying the root cause of this violation, and it is extremely necessary to establish the provoking factor: the adequacy of the prescribed treatment and its outcome depend on this. [17]

To avoid mistakes, a comprehensive diagnosis is prescribed, based on the receipt of both laboratory and functional information. For consultation, doctors of other specialties are involved: it can be a neurologist, endocrinologist, gastroenterologist, rheumatologist, dermatologist, geneticist. [18]

First of all, the doctor listens carefully to the patient's complaints. Such complaints may include:

• intense thirst;
• frequent and profuse urination;
• dry skin and mucous tissues, reduced sweat and salivation, headaches, general weakness, nausea, fever, convulsions, increased heart rate, etc.;
• digestive disorders.

During the physical examination, the doctor pays attention to dry skin and mucous membranes, and other characteristic signs. [19]

In general, the diagnostic scheme provides for the following examinations:

• Blood and urine tests, sometimes a coprogram, histological examination of the skin, confocal microscopy or graphite imprints of the palmar surfaces and feet (to exclude genetic pathology).
• Urine analysis according to Zimnitsky.
• Quantitative studies of the functionality of the sweat glands, test of pilocarpine-induced sweating (with the introduction of pilocarpine, sweat production increases).
• Genetic testing - to clarify the likelihood of hereditary pathology.

Instrumental diagnostics is assigned according to individual indications. The following procedures are most often shown:

• contrast-enhanced magnetic resonance imaging of the brain;
• study of the functionality and structure of the kidneys, including to exclude electrolyte-metabolic disorders.

Differential diagnosis

Anhidrosis should be distinguished from such diseases:

• Sjogren's syndrome , ectodermal dysplasia, Van den Bosch syndrome (along with the absence of sweating, sebum secretion decreases, hair, nails and mucous tissue fall out and become thinner, growth retardation and a decrease in intellectual abilities are noted);
• Rothmund-Thomson syndrome;
• congenital pachyonychia ;
• onychogryposis;
• palmar-plantar hyperkeratosis;
• follicular hyperkeratosis;
• family dysautonomy of type 2, congenital insensitivity to pain syndrome (characterized by disturbances in thermoregulation, oligophrenia, a tendency to self-harm, periodic difficulty in breathing, fever). [20]

With family dysautonomy, the diagnosis indicates the following changes:

• improper skin reaction to intradermal administration of histamine;
• miosis of the pupils when instilled with a 2.5% solution of methacholine chloride.

Treatment anhidrosis

Treatment for anhidrosis is reduced to eliminating the causes that provoked the appearance of the problem. It often takes a lot of time and patience to find these reasons. However, an integrated approach to diagnostics helps to find the necessary provoking factor.

Conservative treatment is reduced to the use of general and local measures of influence. The general therapeutic regimen includes the individual prescription of cytostatics, corticosteroids, tranquilizers, non-steroidal anti-inflammatory and vitamin preparations. [21]

Congenital forms of anhidrosis most often cannot be completely cured, therefore, only symptomatic treatment and drugs are prescribed to prevent the development of complications.

Vitamin therapy usually consists of taking multivitamins that contain vitamins A and B ₁₂.

Localized focal anhidrosis is the easiest to treat: sometimes it is enough for the patient to use moisturizing external agents and drink plenty of fluids. But the generalized form usually requires hospitalization of the patient: along with symptomatic therapy, intravenous infusion of saline solutions is performed. [22]

Medicines

If it was possible to establish the cause of anhidrosis, then the treatment is directed specifically to the primary disease:

• with autoimmune pathology - for example, Sjogren's syndrome or systemic sclerosis - therapy is based on taking immunosuppressants;
• neurological diseases are often irreversible, therefore, treatment is prescribed to prevent further aggravation of the problem;
• acquired generalized anhidrosis can disappear on its own, since it has a tendency to spontaneous remission.

There is a lot of information about the effectiveness of systemic use of corticosteroid drugs - for example, methylprednisolone.

In many cases, the following medicines become the drugs of choice:

Methylprednisolone	The drug is taken orally. The dosage and duration of admission is considered by the doctor individually. The daily dose is taken once a day or every other day, preferably in the morning, immediately after meals. Possible side effects: nausea, arrhythmias, dysmenorrhea, increased intracranial pressure.
Mileran	The drug is prescribed as a course or continuously, with an individual selection of dosage depending on clinical symptoms and hematological parameters. Long-term treatment can lead to side effects such as bone marrow suppression, increased blood clots, idiopathic pneumonia.
Methotrexate	The drug is taken orally, in individual dosages. On average, 10-25 mg of the drug is taken orally, once a week. As complications of treatment, the patient may develop inflammatory processes of the mucous tissues and myelosuppression. Such phenomena require a dosage reduction or suspension of the treatment course.
Plaquenil	The hydroxychloroquine drug is taken with food (you can drink a glass of milk). Assign in the minimum effective amount, not more than 6.5 mg / kg of body weight per day. Most likely side effects: skin rash, dyspepsia, dizziness, changes in skin pigmentation.

Prevention

Since anhidrosis is quite difficult to treat, and some forms of the disease are not cured at all, it is important to pay special attention to the prevention of this disorder. Patients with anhidrosis should avoid the use of drugs that can aggravate the pathological condition. These unwanted medications include:

• anticholinergics;
• botulinum toxin;
• opioid drugs;
• Clonidine;
• barbiturates;
• antagonists of α-2 receptors;
• Zonisamide;
• Topiramate.

People with perspiration problems should limit any activity that can raise their core temperature. Increased physical activity is only allowed under the supervision of a medical professional, and exercises should be performed only in a cool and well-ventilated area. Clothes for active exercises should be light, loose, made of natural fabrics. [23]

For the purpose of prevention, it is important to seek medical help in a timely manner, to identify and treat any diseases in the body.

Forecast

The congenital form of anhidrosis practically does not respond to treatment, therefore, it has a relatively poor prognosis. The acquired form of the disease can be eliminated, provided that appropriate adequate therapy is carried out. [24]

The addition of complications, delayed treatment worsen the quality of the prognosis.

To optimize the outcome of the disease, doctors have developed not only appropriate treatment, but also preventive and restorative recommendations for patients:

• it is recommended to adhere to a healthy lifestyle, eat high quality and balanced, exclude alcohol and stimulating drinks;
• refuse to take certain drugs that negatively affect the work of the sweat glands;
• as supportive measures, regularly carry out myostimulation procedures, manual therapy, physiotherapy exercises. [25]

Anhidrosis is a complex disease that can still be controlled. True, for this it is necessary to spend a lot of effort, be patient and strictly follow all the prescriptions of doctors.