Anhidrosis

Sweating is a physiological necessity for the human body, because sweat promotes thermoregulation, the removal of toxic and other "excess" substances. But sometimes the sweat secretion mechanism goes wrong and begins to function abnormally. One of these "failures" is anhidrosis - a condition in which the sweat glands stop performing their function. The pathology can affect either a specific area or the entire 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 a disorder of the sweat glands, and translated from Greek literally sounds like "absence of sweating". Acquired forms of the disease are more common, and congenital ones are much less common (literally in 2-6 cases per hundred thousand newborns).

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

Both women and men are equally affected. In addition to humans, anhidrosis is also found in the animal world – for example, in horses. In particular, off the coast of the Persian Gulf, sweating disorder occurs in one in five horses. [ 1 ]

Causes anhidrosis

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

• Pathologies of the central nervous system.

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

Demyelination processes of the central thermoregulatory pathways often lead to the development of anhidrosis in patients suffering from multiple sclerosis, especially in the case of steadily progressing pathologies. The development of generalized anhidrosis is often observed in the post-stroke period and after thalamotomy surgery. Damage to the spinal cord leads to a disorder of thermoregulation below the affected area, which may be due to the disinhibition of certain neural chains. Since the vasodilatory function is simultaneously lost against the background of tetraplegia, anhidrosis may 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. Genetic predisposition and the quality of individual adaptation of the body also play an important role. Expressed 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, reddening of the skin, tachycardia are noted, the risk of heat stroke increases.

• Polyneuropathy.

Distal anhidrosis is often diagnosed in most patients suffering from peripheral neuropathy. The most common cause of neuropathy is diabetes mellitus, which is characterized by a failure of thermoregulatory sweating according to the polyneuropathic variant (the "glove" and "sock" type). With the increase in pathology, asymmetric and total anhidrosis may develop. [ 4 ], [ 5 ], [ 6 ]

Some autoimmune neuropathies are accompanied by selective damage to autonomic neurons. In this case, anhidrosis may be observed along with decreased digestive peristalsis, orthostatic hypotension, abnormal pupillary reactions, and neurogenic bladder. Patients have autoantibodies to ganglion acetylcholine receptors. [ 7 ]

Anhidrosis may accompany neuropathies resulting from amyloidosis, alcoholism, vasculitis, Fabry and Tangier diseases, [ 8 ] Naegeli-Franceschetti-Jadassohn syndrome, [ 9 ] miliaria. [ 10 ] Limited anhidrosis occurs in leprosy.

Sweating disorders are observed in hereditary sensorimotor neuropathies of the fourth and fifth types (absence of pain sensitivity and anhidrosis). [ 11 ]

• Ross syndrome.

Progressive segmental anhidrosis, combined with areflexia and Adie pupils, is a clinical triad characteristic of Ross syndrome. This anhidrosis is characterized by asymmetry. The pathology is caused by defects in postganglionic neurons. [ 12 ]

• Chronic form of idiopathic anhidrosis.

Anhidrosis develops in an isolated form or together with vegetative disorders. Patients complain of skin redness, a feeling of heat, dizziness, shortness of breath, weakness. Symptoms arise as a result of physical activity or elevated temperature.

• Dermatological pathologies.

Burn injuries, radiation, inflammatory skin lesions, scars, etc. – all these factors can cause partial anhidrosis. The disorder often results from psoriasis, ichthyosis, lichen, scleroderma, exfoliative dermatitis. Another cause is necrosis of sweat glands due to drug intoxication, carbon monoxide poisoning. [ 13 ]

Temporary anhidrosis may occur as a side effect of anticholinergic drugs, tricyclic antidepressants, phenothiazines. For example, when taking topiramate, patients experience suppression of carbonic anhydrase in 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:

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

Anhidrosis most often develops in older people, as well as in people suffering from chronic alcoholism.

Pathogenesis

The sweat-secreting function of the glands of the same name is one of the key links in thermoregulation in the human body. When adequate values of internal temperature, which are determined by the hypothalamus, increase, certain parts of the autonomic nervous system are reflexively stimulated, which leads to increased generalized sweating, vasodilation, and increased breathing. Such a reaction allows the body to maintain temperature stability and homeostasis. The neural direction involved in this reaction starts from the preoptic area of the hypothalamus along the medial part of the lateral funiculus of the brainstem, to the synapses on the preganglionic neurons of the middle-intermediate spinal column. [ 14 ] Then the path of the postganglionic sympathetic cholinergic fibers diverges to numerous sweat glands, and there are several million of them. The greatest number of them is found in the palmar and plantar zones, and the smallest - in the back area. [ 15 ] Different parts of the body are innervated by the following segments of the spinal cord:

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

Incorrect sweat secretion usually manifests itself as increased function (hyperhidrosis) and decreased function (hypohidrosis). With complete dysfunction of the sweat glands, we speak of anhidrosis - the absence of sweat secretion. In severe cases, anhidrosis requires emergency medical intervention, since it can lead to increased temperature, heat exhaustion, heat stroke and even death.

Symptoms anhidrosis

Symptoms of congenital anhidrosis vary, but most often the hereditary pathology is characterized by such signs as dental disorders, bone and facial deformation, and lack of hair. During the neonatal and infancy period, children suffer from numerous thermoregulation disorders, which can lead to the development of hyperthermic complications. In adulthood, the patient's condition can be monitored and compensated by limiting physical activity, excluding exposure to hot conditions, and ensuring sufficient water intake.

In chronic generalized anhidrosis, increased sensitivity to various temperature changes is observed already at an early stage, which poses a potential danger to the patient. The skin of such patients is thin and dry, regional hyperkeratosis, itching, hyperemia, peeling on the face and hands are characteristic, regardless of the season (the situation worsens in winter). Sweat is not secreted during physical activity, it becomes difficult for the body to maintain normal temperature. The lacrimal and mucous glandular system is involved in the process: the patient develops "dry eye" syndrome, dryness of the nasopharyngeal region is observed. Poorly moisturized eyeball leads to symptoms such as burning, a feeling of "sand in the eyes". An inflammatory process such as conjunctivitis or blepharitis can develop. Dryness of the nasal mucosa provokes an asthma-like clinical picture.

If acute generalized anhidrosis develops, then it is a life-threatening condition. The patient's health rapidly deteriorates, up to a serious condition. The heartbeat quickens, breathing movements become more intense. The body rapidly accumulates metabolic products. The daily volume of urine increases, the digestive system is disrupted. The patient loses his appetite, but often feels a strong thirst, which is especially painful with increasing dehydration. In some cases, thirst is absent - for example, if anhidrosis is caused by some primary disease. [ 16 ]

Intoxication increases, which further contributes to the increase in temperature. The general condition is rapidly disrupted, the function of organs and systems in the body is upset. Such a patient requires emergency medical care.

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

First signs

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

• absence of sweat secretion in typical areas (armpits, back, groin, face and forehead);
• dizziness;
• facial flushing;
• spastic contractions of muscles, convulsive twitching;
• general weakness;
• increase in body temperature.

The affected areas of the skin are easily injured, cracks are formed, which can become infected. As a result of the inability to remove toxic substances from the body, intoxication can develop, accompanied by fever, vegetative disorders. In intact areas of the skin, compensatory increase in sweating is not excluded.

When the first suspicious symptoms are detected, it is necessary to:

• do not enter hot and stuffy rooms, turn on the air conditioner if possible;
• wear clothes made of light natural fabrics;
• Contact your doctor and tell him about the problem.

Forms

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

Practicing dermatologists usually talk about the following types of anhidrosis:

• Congenital anhidrosis is usually observed in people with hypoplastic and aplastic changes in the sweat glands. The pathology is transmitted in an autosomal recessive manner, and the first signs can be observed already in 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 and can occur in several variants:
  • the acute form develops against the background of intoxication or metabolic disorders, is accompanied by severe thermoregulatory disorders, general signs of intoxication, and has an unfavorable prognosis;
  • the chronic form develops due to disorders of the autonomic nervous system, with atrophic processes affecting the sweat glands;
  • the tropical form is typical for regions with hot climate conditions against the background of low fluid intake, accompanied by the appearance of vesicular rashes, which is caused by the blockage of the sweat glands by microscopic particles of dust, dirt, etc.;
  • the focal form appears on limited areas of the body, limbs or face - for example, this variant is characteristic of Bernard-Horner syndrome, accompanied by ptosis, miosis, enophthalmos and anhidrosis;
  • The generalized form spreads throughout the body and may 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 is a rare hereditary disorder transmitted in an autosomal recessive manner. The disease is accompanied by a disorder of sensitivity of pain receptors. The clinical picture is represented by the following signs:

• insensitivity to painful stimuli;
• thermoregulation failure;
• oligophrenia;
• tendency to self-harm;
• anhidrosis;
• intermittent difficulty breathing;
• spontaneous fever.

Sweating does not occur when exposed to thermal, painful, emotional or chemical irritants.

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 sweat glands) and sensory nerve cells localized in the posterior spinal roots. Incorrect myelination of peripheral fibers occurs. Auxiliary signs of pathology: insensitivity to pain against the background of preserved tactile and taste sensations. Any attempts to induce sweating are futile, ranging from thermal effects to the pilocarpine test or electrical stimulation. When the temperature rises, taking antipyretic drugs is ineffective, but physical cooling methods "work".

Patients have regular osteomyelitis, aseptonecrosis, and early tooth loss. Electromyography does not show any abnormal nerve conduction.

Complications and consequences

The main complication of anhidrosis is considered to be a violation of thermoregulation and overheating of the body, which is especially dangerous for pediatric patients.

The most frequently recorded adverse symptoms are:

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

Since complications with anhidrosis develop quite rapidly, it is necessary to deliver the patient to a medical facility as quickly as possible to receive qualified assistance.

A typical adverse effect of acute generalized anhidrosis is dysfunction of the kidneys and liver. Against the background of progressive intoxication, these organs become overloaded, which can subsequently cause the development of chronic insufficient function and a state of decompensation. With dehydration and rapid loss of blood plasma, thickening of the blood is observed with the appearance of signs of insufficient cardiac activity.

Diagnostics anhidrosis

Determining the state of anhidrosis in a patient does not seem difficult. Difficulties usually arise with identifying the root cause of this disorder, but it is extremely important 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 obtaining both laboratory and functional information. Doctors of other specialties are involved in the consultation: this may 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, decreased sweating 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 includes the following examinations:

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

Instrumental diagnostics are prescribed according to individual indications. The following procedures are most often indicated:

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

Differential diagnosis

Anhidrosis should be distinguished from the following diseases:

• Sjogren's syndrome, ectodermal dysplasia, Van den Bosch syndrome (along with the absence of sweating, sebum secretion is reduced, hair, nails and mucous tissue fall out and become thinner (normally), growth retardation and decreased intellectual abilities are noted);
• Rothmund-Thomson syndrome;
• congenital pachyonychia;
• onychogryposis;
• palmoplantar hyperkeratosis;
• follicular hyperkeratosis;
• familial dysautonomia type 2, congenital pain insensitivity syndrome (characterized by thermoregulatory disorders, mental retardation, tendency to self-harm, periodic difficulty breathing, fever). [ 20 ]

In familial dysautonomia, diagnostics indicate the following changes:

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

Treatment anhidrosis

Treatment for anhidrosis comes down to eliminating the causes that provoked the problem. Often, finding these causes requires a lot of time and patience. However, a comprehensive 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 scheme includes the individual prescription of cytostatics, corticosteroids, tranquilizers, non-steroidal anti-inflammatory and vitamin preparations. [ 21 ]

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

Vitamin therapy usually involves taking multivitamin supplements 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 carried out. [ 22 ]

Medicines

If the cause of anhidrosis has been established, then treatment is directed specifically at the primary disease:

• in case of autoimmune pathology – for example, Sjogren's syndrome or systemic sclerosis – therapy is based on taking immunosuppressants;
• Neurological diseases are often irreversible, so treatment is prescribed to prevent further worsening of the problem;
• Acquired generalized anhidrosis may disappear on its own, as it has a tendency to spontaneous remission.

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

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

Methylprednisolone	The drug is taken orally. The dosage and duration of administration are 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, arrhythmia, dysmenorrhea, increased intracranial pressure.
Millerand	The drug is prescribed in a course or continuously, with individual dosage selection depending on clinical symptoms and hematological parameters. Long-term treatment can lead to side effects such as bone marrow suppression, increased thrombus formation, 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 reduction in dosage or suspension of the treatment course.
Plaquenil	Hydroxychloroquine is taken with food (can be washed down with a glass of milk). It is prescribed in the minimum effective amount, no more than 6.5 mg/kilogram of weight per day. The most likely side effects are: 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 taking medications that can worsen the pathological condition. Such undesirable medications include:

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

People with problems with sweating should limit any activity that can increase the body's internal temperature. Increased physical activity is allowed only under the supervision of a medical specialist, and exercises should be performed only in a cool and well-ventilated room. Clothing for active activities should be light, loose, made from natural fabrics. [ 23 ]

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

Forecast

The congenital form of anhidrosis is practically untreatable, therefore it has a relatively unfavorable prognosis. The acquired form of the disease can be eliminated, provided that appropriate adequate therapy is carried out. [ 24 ]

The addition of complications and 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 maintain a healthy lifestyle, eat a high-quality and balanced diet, and avoid alcohol and stimulating drinks;
• stop taking certain medications that negatively affect the functioning of sweat glands;
• as supportive measures, regularly carry out procedures of myostimulation, manual therapy, and therapeutic exercise. [ 25 ]

Anhidrosis is a complex disease that can still be kept under control. However, this requires a lot of effort, patience, and strict adherence to all doctor's orders.