Hypoplasia of the thymus. Thymus: thymus gland in children

Antipyretics for children are prescribed by a pediatrician. But there are emergency situations with fever when the child needs to be given medicine immediately. Then the parents take responsibility and use antipyretic drugs. What is allowed to be given to infants? How can you lower the temperature in older children? What medications are the safest?

The child, while in the womb, is completely protected from any adverse environmental factors.

The thymus gland in newborns becomes the first cascade of immune defense. Which protects the child from numerous pathogenic microorganisms. The thymus in children begins to work immediately after birth, when an unfamiliar microorganism enters with the first breath of air.

The thymus gland in children under one year old manages to collect information about almost all pathogenic organisms that we encounter during our lives.

Embryology (development of the thymus in the prenatal period)

The thymus in the fetus is formed already in the seventh - eighth week of development. Even during pregnancy, the thymus gland begins to produce immune cells; by the twelfth week, the precursors of future lymphocytes - thymocytes - are already found in it. By the time of birth, the thymus in newborns is fully formed and functionally active.

Anatomy

To understand, you should place three fingers on the top of the manubrium of the sternum (the area between the collarbones). This will be the projection of the thymus gland.

At birth, her weight is 15-45 grams. The normal size of the thymus in children is 4-5 centimeters in length, 3-4 centimeters in width. An intact gland cannot be palpated in a healthy child.

Age characteristics

The thymus is key to the formation of immunity; its growth continues until puberty. At this point the mass reaches 40 grams. After puberty, reverse development (involution) begins. By old age, the thymus gland is completely replaced by adipose tissue, its weight decreases to 6 grams. Each period of life has its own.

Role of the thymus

The thymus produces hormones necessary for normal development immune system. Thanks to them, cells of the immune system learn to recognize harmful microorganisms and launch mechanisms to eliminate them.

Disorders of the thymus

Based on the degree of activity, hypofunction and hyperfunction of the thymus gland are distinguished. According to the morphological structure: (absence), (underdevelopment) and (increase in size).

Congenital pathology of the development of the thymus gland

If there are abnormalities in the genetic code, the formation of the thymus may be disrupted in the early embryonic period. This pathology is always combined with impaired development of other organs. There are several genetic disorders that cause, in which the changes are fatal to the immune system. The body loses its ability to fight infection and is no longer viable.

With genetic developmental defects, the entire immune system suffers. Even with partial activity remaining, hypoplasia of the thymus gland in newborns leads to a persistent deficiency in the content of immune cells in the blood and persistent infections, against which a general developmental delay is noted.

Genetic malformations also include congenital cysts, thymic hyperplasia and thymomas (benign or malignant tumors of the thymus).

Hypofunction and hyperfunction of the thymus

Functional activity does not always depend on the size of the gland itself. With thymoma or cyst, the thymus gland is enlarged, and its activity may be normal or reduced.

Thymic hypoplasia

In the absence of developmental anomalies, thymic hypoplasia in newborns occurs extremely rarely. This is not an independent disease, but a consequence of a severe infection or prolonged fasting. After eliminating the cause, its dimensions are quickly restored.

Thymic hyperplasia

A distinction is made between endogenous hyperplasia, when the enlargement of the thymus is associated with the performance of its functions (primary) and exogenous, when the growth is caused by pathological processes in other organs and tissues.

Why does the baby's thymus gland enlarge?

Causes of primary (endogenous) thymomegaly:

Causes of exogenous thymomegaly:

Generalized disorders of the immune system(autoimmune diseases).
Disturbances in the functioning of regulatory systems in the brain(hypothalamic syndrome).

Symptoms of hyperplasia

Upon external examination, the enlarged thymus gland in an infant is visible when crying, when increased intrathoracic pressure pushes the thymus above the manubrium of the sternum.

Enlargement of the thymus gland in children affects appearance child – enlarged facial features, pale skin. There is a delay in general development. Enlargement of the thymus gland in a 2-year-old child, detected during examination, especially with asthenic physique, should not cause concern. The thymus is a fairly large organ for such a baby and may simply not fit into the space allotted to it.

Enlargement of the thymus gland in a baby with transient jaundice of newborns is also not a pathology.

The simultaneous identification of several signs characteristic of diseases of the thymus gland is of clinical importance:

compression syndrome of nearby organs;
immunodeficiency syndrome;
lymphoproliferative syndrome;
disruption endocrine system.

Syndrome of compression of nearby organs

An enlarged thymus gland in children causes symptoms of compression of nearby organs. When pressure is placed on the trachea, shortness of breath, noise when breathing, and a dry cough appear. By squeezing the lumen of blood vessels, the thymus disrupts the inflow and outflow of blood, causing pale skin and swelling of the neck veins.

If an enlarged thymus gland in a child causes compression of the vagus nerve, which innervates the heart and digestive tract, a persistent slowing of the heartbeat, swallowing problems, belching, and vomiting are noted. It is possible to change the timbre of the voice.

Immunodeficiency syndrome

When the thymus gland is enlarged in a child against the background of its dysfunction, even common diseases proceed differently. Any cold can begin without an increase in temperature, with a sharp jump on the third or fourth day. Such children get sick longer than their peers, and the severity of the disease is higher. Often the infection spreads to the lower sections respiratory system with the development of bronchitis and tracheitis.

Lymphoproliferative syndrome

An increase in the production of hormones in the gland causes hyperstimulation of the entire immune system. Are increasing The lymph nodes, in the general blood test the ratio of immune cells with a predominance of lymphocytes is disturbed. Any external stimulus causes an excessive defensive reaction in the form of allergic reactions. A severe reaction to vaccination may occur.

Disruption of the endocrine system

An enlarged thymus gland in children can lead to disruptions in the functioning of the endocrine system, with the development diabetes mellitus and disruption thyroid gland.

Why is an enlarged thymus gland dangerous in a child?

An enlargement of the thymus gland in an infant, with compression of the trigeminal gland, disrupts the peristalsis of the esophagus and intestines. The child may have difficulty getting food and burping air after feeding. When the trachea is compressed, more effort is required to inhale, and high blood pressure causes rupture of the alveoli in the lungs with the development of atelectasis.

Diagnostics

If there are symptoms of an enlarged thymus gland in a child, consultation with several specialists is necessary - an immunologist, an endocrinologist and a pediatrician. It often turns out that an enlargement of the thymus gland in an infant is not associated with pathology, but is caused by individual anatomical features. Parents often panic that the thymus gland is enlarged in a newborn, since when crying it often protrudes above the manubrium of the sternum. There is also no need to be afraid of inflammation of the thymus gland in a baby; the huge number of immune cells in it does not leave a single chance for the development of infection.

To confirm the diagnosis, it is necessary to undergo a thorough examination, including:

General and detailed blood test.
Chest X-ray.
Ultrasound diagnostics.

A blood test can detect a decrease in the level of T-lymphocytes and an imbalance between immunoglobulins.

An X-ray of the thymus gland in a child will help exclude anomalies in the structure and location of the thymus gland.

Ultrasound allows you to most accurately determine the degree of thymic hyperplasia in newborns. Examination of the adrenal glands and abdominal organs will exclude concomitant pathology.

Additional tests for hormone levels may be required.

The thymus gland in children is the central organ, which is located in the middle of the chest.
It is he who is of great importance in correct formation and the subsequent functioning of the child’s immune system, and any disturbances in its functioning can lead to various complications and the development of pathologies.
What is the thymus?
The thymus gland, or, as it is also called, the thymus, is the main organ of the immune system, as it produces, develops and trains special T cells.
It got its name because of its shape, which is like a fork with two teeth.
Interesting!
The thymus is like a fork healthy person, and with pathologies in this area, the gland becomes like a butterfly, taking on the shape of the thyroid gland. Due to its close location to the latter, it was previously also called the thymus gland.
The thymus gland in newborns weighs 12 g and grows until the age of 10 years. After reaching 18 years of age, it begins to decrease.
The thymus can be easily felt when pressed with two fingers in the area of the upper part of the sternum, slightly below the clavicle fossa.
The thymus gland in children and adults has the same location, but it has the following features due to age:
1. During the time from birth to puberty, the thymus increases approximately 3 times: if in newborns it weighs about 12 g, then in adolescents it reaches a size of up to 40 g.
2. By the age of 16 years, the gland begins to atrophy.
3. Around the age of 24-25, its size is about 25 g.
4. In people aged 60 years, the thymus weighs less than 15 g.
5. After 80 years, its weight does not exceed 6 g.
In old age, atrophy is observed in the areas below and on the sides of the thymus and adipose tissue forms in their place, and the gland itself lengthens. Such changes are currently inexplicable by science.
Many experts believe that solving this mystery could help manage the aging process.
Functions of the thymus
The thymus gland in children forms all systems in the body. Its main functions are the following:
endocrine;
lymphopoietic;
regulating immunity.
The gland destroys aggressive cells because it ensures the production of T cells, which are the main regulators of the immune system.
In addition, the thymus controls the outflow of blood and filters it.
The formation of the gland in the child begins in the 6th week of pregnancy.
Until one year of age, this organ influences the synthesis of T-lymphocytes through the bone marrow. They protect the baby’s body from the following influences:
infections;
bacteria;
viruses.
Hormones produced by the thymus gland take part in the regulation of almost all processes in the body, performing the following important functions:
decrease in heart rate;
increased protein synthesis;
increased cellular growth and skeleton;
slowdown in central nervous system;
improving the functioning of the thyroid gland and pituitary gland;
acceleration of sugar breakdown;
replenishment of energy reserves.
Thymus hormones carry out the metabolism of the following substances:
carbohydrates;
vitamins;
minerals;
fats;
proteins.
Reduction or enlargement of the thymus gland leads to disruption of these processes and provokes various pathologies.
Important!
In most cases, malfunctions of the thymus lead to tumor processes and autoimmune diseases. Timely diagnosis and treatment help prevent complications.
Hyperfunction of the thymus gland
This condition indicates an enlargement of the thymus gland, which is accompanied by its hyperfunction. As a rule, pathology is transmitted genetically.
In newborns, it may be due to one of the following factors:
age of the pregnant woman;
disturbances during childbearing;
diseases of an infectious nature in a pregnant woman.
If hyperfunction of the thymus gland is observed in older children, then the cause may be a lack of proteins in the diet, since with prolonged deficiency, the functions of the organ are disrupted in the form of suppression of the immune system and a decrease in the content of leukocytes.
In addition, thymic hyperplasia in a child can be caused by so-called lymphatic diathesis.
In this condition, the tendency of lymph tissue to pathological growth affects internal organs, including the thymus.
Symptoms in newborns
Diffuse enlargement of the thymus in infants is accompanied by the following manifestations:
1. Birth weight is significantly higher than average.
2. The child rapidly gains and loses weight.
3. The skin is pale, and the mucous membranes have a bluish tint.
4. A network of veins is clearly visible on the chest.
5. There is frequent regurgitation after feeding.
6. There are heart rhythm disturbances.
7. Saved low-grade fever, despite the absence of signs of an inflammatory nature.
Often, thymic hyperplasia in infants is accompanied by a cough without additional cold symptoms and increased sweating.
Symptoms in older children
In this case, the following manifestations are added to the symptoms in newborns with thymic hyperfunction:
swollen lymph nodes;
decreased blood pressure;
obesity with healthy eating;
cold extremities;
hypertrophy of the tissues of the posterior pharyngeal zone.
At the same time, heart rhythm disturbances and increased sweating become more pronounced.
A decrease in immunity provokes other pathologies in the development of the baby.
For reference!
In female children, in some cases, persistent enlargement of the thymus leads to hypoplasia of the organs of the reproductive system, and in male children - to phimosis.
Hypofunction of the thymus gland
Hypofunction of the thymus is usually a congenital or primary underdevelopment of the elements of the organ. This condition can develop against the background of the following factors:
viral diseases;
diabetes;
use of alcoholic beverages during pregnancy.
IN childhood This pathology provokes the following conditions:
accelerated development of the gonads;
reduction of lymphoid organs;
lymphopenia;
weight loss;
malnutrition;
bone growth disorders;
Hypofunction of the thymus gland in children provokes disruptions in immunological reactivity.
Diagnostics
Diseases and pathologies of the thymus in children are detected using x-rays or ultrasound with increased resolution.
The need for diagnostics may arise if the child has the following characteristics:
1. He often suffers from colds, which develop into severe pathologies.
2. There is an increase in lymph nodes.
3. There is a high predisposition to allergies.
When there is a suspicion of an enlargement/reduction of an organ, a specialist may prescribe an endocrine examination and CT scan. The latter method allows us to identify the following thymus diseases:
DiGeorge syndrome;
thymoma;
myasthenia gravis;
T cell lymphoma.
When diagnosing tumors in this area, surgery is usually required.
Important!
Since ultrasound is not inferior in its information content to an x-ray, many experts recommend not exposing children to radiation again and choosing an ultrasound diagnostic method.
Treatment
Pathologies of the thymus gland usually occur before the age of six, after which they go away on their own without special treatment.
In this case, means are used aimed at strengthening the immune system, and a special daily and nutritional regimen is observed.
But in some cases, in order to avoid further complications, measures and therapy are required.
Urgent health care for diseases of the thymus gland in a child, it is required if the following symptoms are present:
weakness of the body;
bradycardia;
apathy.
Treatment for thymus pathologies in children may include the following:
physiotherapeutic procedures;
biostimulant therapy;
use of immunomodulators;
diet high in vitamin C;
the use of drugs to stimulate the respiratory center;
prevention respiratory diseases.
For thymic hyperplasia, in some cases it is prescribed surgery, before which it is necessary to control blood pressure. It is advisable to perform the operation under local anesthesia.
Without preliminary preparation before the intervention, the likelihood of adrenal insufficiency in the child increases.
Parents of children who have been diagnosed with dysfunction of the thymus gland should remember that aspirin is contraindicated for them.

Medical and social examination and disability in thymic hypoplasia

THYMUS APLASIA (hypoplasia) (DiGeorge syndrome) is a congenital underdevelopment of the thymus gland as a result of a violation of the normal embryogenesis of the thymus gland, which is also accompanied by a violation of the formation of neighboring organs - the parathyroid glands, the aorta and other developmental anomalies, which is clinically manifested by primary immunodeficiency and hypoparathyroidism.

Epidemiology: the frequency in children has not been established, but the frequency of all defects in T-cell immunity is 5-10% in the structure of primary immunodeficiencies, and the total frequency of primary forms of immunodeficiency is 2:1000.

Etiology and pathogenesis. The disease is associated with disruption of intrauterine development of the fetus for a period of about 8 weeks; under the influence of a teratogenic factor, the formation of organs developing during this period from the 3-4th pharyngeal slits is disrupted: the thymus gland, parathyroid glands, aorta, as well as the facial skull, central nervous system. In 80-90% of children with this syndrome, a deletion of the 22nd chromosome is detected (partial monosomy on the 22nd chromosome - deficiency of genetic material), combined with the symptom complex: birth defects heart disease, cleft palate and other facial skeletal defects, thymic hypoplasia and hypocalcemia due to hypolalasia of the parathyroid glands.

Clinical picture.
From birth, the child is diagnosed with hypocalcemia syndrome (typical hypocalcemic convulsions), recurrent oral candidiasis with transformation into chronic candidiasis of the skin and mucous membranes, an aortic anomaly (its arch is turned to the right), and sepsis. There may be a congenital heart defect with a corresponding clinical picture, an anomaly of the facial skull; in the future - decreased mental abilities, delayed sexual development.

Complications: heart failure, impaired mental development of varying severity, damage to internal organs by Candida fungi (candidal bronchitis, esophagitis with subsequent development of esophageal stricture).

Laboratory and instrumental methods confirming the diagnosis:
1) study of parathyroid hormone levels in the blood;
2) biochemical blood test (decreased calcium levels in the blood);
3) ECG, EchoCG;
4) consultation with a psychologist, neurologist, psychiatrist;
5) mycological examination;
6) immunogram (decrease in the number and function of T-lymphocytes).

Treatment: compensation for lathyroid gland deficiency with vitamin D preparations, fetal thymus transplantation, use of thymic hormones for replacement purposes, bone marrow transplantation, correction of congenital heart disease, use of antimycotic drugs for the treatment of candidiasis.

The prognosis is relatively favorable - children are viable, do not suffer from viral and bacterial infections, but have chronic candidiasis of the skin and mucous membranes with damage to internal organs, and require constant treatment with antifungal drugs; hypoparathyroidism also requires constant replacement therapy vitamin D preparations; In addition, children are lagging behind mental development.

Disability criteria: mental retardation, requiring the child to study in a auxiliary school, NK from 1-2st grade. and higher in congenital heart disease, recurrent candidiasis of the bronchi, esophagus and other internal organs with disruption of their functions.

Rehabilitation: medical rehabilitation during periods of exacerbation; social, psychological, pedagogical and professional habilitation during the period of remission of the disease.

Description:

Thymic aplasia is a group of diseases caused by genetic defects of the immune system.

Symptoms:

1. DiGeorge syndrome. Along with aplasia of the gland, aplasia of the parathyroid glands with manifestations is possible. In pathogenesis, there is a deficiency of circulating T-lymphocytes, a sharp suppression of the cellular immune response, a relative increase in the number of B-lymphocytes and the preservation of the humoral immune response (normal levels of immunoglobulins in the blood).
Characteristic signs of the disease are, starting from the neonatal period, recurrent respiratory and digestive systems. Usually combined with developmental anomalies of the aortic arch, lower jaw, earlobes, hypoplasia of the lymph nodes and underdevelopment of thymus-dependent areas.

2. Nezelof syndrome - autosomal recessive aplasia of the thymus with lymphopenia, without aplasia of the parathyroid glands, but with underdevelopment of thymus-dependent zones in the lymph nodes and spleen.
A sharp decrease in the reactivity of T-lymphocytes (deficiency of the cellular immune system) is also detected.
From the neonatal period, recurrent bronchitis, enterocolitis of viral or fungal etiology, herpetic rashes, etc. are observed. T-lymphocyte deficiency and suppression of the cellular immune response are more pronounced than in DiGeorge syndrome. Patients die at an early age.

3. Louis-Bar syndrome is an immunological deficiency in telangiectasia, characterized by autosomal recessive inheritance of glandular aplasia, occurring with a decrease in lymphocytes in the thymus-dependent areas of the lymph nodes and spleen, demyelination in the cerebellum.
Multisystem complex disorders:
1) neurological (ataxia, loss of coordination, etc.);
2) vascular (telaniectasia of the skin and conjunctiva);
3) mental (mental retardation);
4) endocrine (dysfunction of the adrenal glands, gonads). Recurrent sinopulmonary infections appear from early childhood.
Violation of cellular immunity is accompanied by damage to the T- and B-immune systems, IgA deficiency. Emoronic proteins (α- and β-fetoproteins) are detected in the blood serum. Such patients more often develop malignant neoplasms (usually lymphogranulomatosis).

4. “Swiss syndrome” - autosomal recessive severe combined immunological deficiency. Lymphopenic agammaglobulinemia, aplasia or hypoplasia of the thymus is combined with hypoplasia of all lymphoid tissue. Severe hypoplasia of the thymus gland, hypoplasia of the lymph nodes and lymphoid formations of the spleen and intestines.
From the neonatal period, recurrent fungal, viral and bacterial lesions of the skin and mucous membranes of the nasopharynx, respiratory tract, intestines. In such children, the thymus gland is difficult to identify.
Along with a sharp inhibition of cellular immunity reactions, a deficiency of humoral immunity (deficiency of T- and B-lymphocytes) is revealed. Children usually die in the first six months of life.

Causes:

This group of diseases is caused by genetic defects of the immune system.
Congenital, or primary, aplasia (or hypoplasia) of the thymus gland is characterized by the complete absence of thymic parenchyma or its extremely weak development, which determines the presence of severe combined immunological deficiency due to a sharp decrease in the content of T- and B-lymphocytes and the absence of thymic bodies.
All these diseases are accompanied by recurrent inflammatory diseases, more often pulmonary or intestinal localization, which are often the direct cause of death of patients. Therefore, children, especially early age patients suffering from recurrent inflammatory diseases should be carefully examined for the functional state of the thymus.
Similar changes are found in children with a number of diseases grouped under the group of immunodeficiency diseases. The most pronounced defects in the development of the thymus gland were found in the following syndromes.

Treatment:

This group of diseases is caused by genetic defects of the immune system.
Congenital, or primary, aplasia (or hypoplasia) of the thymus gland is characterized by the complete absence of thymic parenchyma or its extremely weak development, which determines the presence of severe combined immunological deficiency due to a sharp decrease in the content of T- and B-lymphocytes and the absence of thymic bodies.
All these diseases are accompanied by recurrent inflammatory diseases, most often of pulmonary or intestinal localization, which are often the direct cause of death of patients. Therefore, children, especially young children, suffering from recurrent inflammatory diseases, should be carefully examined for the functional state of the thymus.
Similar changes are found in children with a number of diseases grouped under the group of immunodeficiency diseases. The most pronounced defects in the development of the thymus gland were found in the following syndromes.

1.
DiGeorge syndrome. Along with aplasia of the gland, aplasia of the parathyroid glands is possible with manifestations of hypoparathyroidism. The pathogenesis involves a deficiency of circulating T-lymphocytes, a sharp suppression of the cellular immune response, a relative increase in the number of B-lymphocytes and preservation of the humoral immune response (normal levels of immunoglobulins in the blood, hypocalcemia).
Characteristic signs of the disease are convulsions, starting from the neonatal period, and recurrent infections of the respiratory and digestive systems. Usually combined with developmental anomalies of the aortic arch, lower jaw, earlobes, hypoplasia of the lymph nodes and underdevelopment of thymus-dependent areas.

2. Nezelof's syndrome- autosomal recessive aplasia of the thymus with lymphopenia, without aplasia of the parathyroid glands, but with underdevelopment of thymus-dependent zones in the lymph nodes and spleen.
A sharp decrease in the reactivity of T-lymphocytes (deficiency of the cellular immune system) is also detected.
From the neonatal period, recurrent bronchitis, pneumonia, enterocolitis of viral or fungal etiology, herpetic rashes, and sepsis are noted.
T-lymphocyte deficiency and suppression of the cellular immune response are more pronounced than in DiGeorge syndrome. Patients die at an early age.

3. Louis-Bar syndrome- immunological deficiency in ataxia-telangiectasia, characterized by autosomal recessive inheritance of glandular aplasia, occurs with a decrease in lymphocytes in the thymus-dependent areas of the lymph nodes and spleen, demyelination in the cerebellum.
Multisystem complex disorders:
1) neurological (ataxia, loss of coordination, etc.);
2) vascular (telaniectasia of the skin and conjunctiva);
3) mental (mental retardation);
4) endocrine (dysfunction of the adrenal glands, gonads). Recurrent sinopulmonary infections appear from early childhood.
Violation of cellular immunity is accompanied by damage to the T- and B-immune systems, IgA deficiency. Emoronic proteins (α- and β-fetoproteins) are detected in the blood serum. Such patients more often develop malignant neoplasms (usually lymphosarcoma, lymphogranulomatosis).

4.
"Swiss Syndrome"- autosomal recessive severe combined immunological deficiency. Lymphopenic agammaglobulinemia, aplasia or hypoplasia of the thymus is combined with hypoplasia of all lymphoid tissue. Severe hypoplasia of the thymus gland, hypoplasia of the lymph nodes and lymphoid formations of the spleen and intestines.
From the neonatal period, recurrent fungal, viral and bacterial lesions of the skin and mucous membranes of the nasopharynx, respiratory tract, and intestines. In such children, the thymus gland is difficult to identify.
Along with a sharp inhibition of cellular immunity reactions, a deficiency of humoral immunity (deficiency of T- and B-lymphocytes) is revealed. Children usually die in the first six months of life.

Diagnostics. Congenital aplasia and hypoplasia of the thymus gland is established based on the clinical picture of recurrent infections. To confirm it, immunological studies are used: determining the number of T- and B-lymphocytes and their functional activity, the concentration of immunoglobulins and the level of gland hormone in the blood.
For the purpose of early diagnosis of immunodeficiency conditions caused by thymic aplasia, the determination of the number of lymphocytes in peripheral blood, serum immunoglobulins, and isohemagglutinin titers is used.

Treatment. Restorative and replacement immunotherapy. For this purpose, transplantation of the thymus gland or bone marrow, administration of immunoglobulins, and thymus hormones are performed. The use of corticosteroids with immunosuppressive effects is contraindicated.

– a genetic disease that belongs to the group of primary immunodeficiencies and, along with weakened immunity, is characterized by numerous developmental defects. Symptoms of this condition include frequent bacterial infections with a tendency to become severe, congenital heart defects, facial abnormalities and other disorders. Diagnosis of DiGeorge syndrome is based on examination of the heart, thyroid and parathyroid glands, study of immunological status and data from molecular genetic tests. Treatment is symptomatic only and includes surgical correction of heart defects and facial anomalies, immunological replacement therapy, and the fight against bacterial and fungal infections.

General information

DiGeorge syndrome (hypoplasia of the thymus and parathyroid glands, velocardiofacial syndrome) is a genetic disease caused by impaired embryonic development of the third and fourth pharyngeal sacs. This condition was first described in 1965 by American pediatrician Angelo Di Giorgi, who classified it as congenital aplasia of the thymus and parathyroid glands. Further research in the field of genetics helped determine that the disorders in this disease go far beyond the scope of primary immunodeficiency. This gave rise to another name for DiGeorge syndrome. Taking into account the most commonly affected organs (palate, heart, face), some experts call this pathology velocardiofacial syndrome. A number of modern researchers distinguish between these two conditions and believe that “true” velocardiofacial syndrome is not accompanied by pronounced immunological disorders. The incidence of DiGeorge syndrome is 1:3,000-20,000 - such a significant discrepancy in data is due to the fact that a reliable and clear boundary between this disease and velocardiofacial syndrome has not yet been established. Therefore, the same patient, according to different experts, may have either primary immunodeficiency, accompanied by concomitant disorders, or more developmental defects against the background of decreased immunity.

Causes of DiGeorge syndrome

The genetic nature of DiGeorge syndrome is damage to the central part of the long arm of chromosome 22, where genes encoding a number of important factors transcriptions. It was possible to identify one of these genes - TBX1, the product of its expression is a protein called T-box. It belongs to a family of proteins that control the processes of embryogenesis. Evidence of the relationship between DiGeorge syndrome and TBX1 is the fact that a small percentage of patients do not have significant damage to the 22nd chromosome; only mutations in this gene are present. There have also been suggestions about the role of deletions of other chromosomes in the development of this disease. Thus, manifestations similar to DiGeorge syndrome were detected in the presence of damage to the 10th, 17th and 18th chromosomes.

In most cases of DiGeorge syndrome, the deletion of chromosome 22 spans about 2-3 million base pairs. Most often, this genetic defect occurs spontaneously during the formation of male or female germ cells - that is, it is germinal in nature. Only a tenth of all cases of the disease is a familial form with an autosomal dominant inheritance pattern. The pathogenesis of DiGeorge syndrome comes down to a disruption in the formation of special embryonic formations - pharyngeal sacs (mainly the 3rd and 4th), which are the precursors of a number of tissues and organs. They are mainly responsible for the formation of the palate, parathyroid glands, thymus, mediastinal vessels and heart, therefore, with DiGeorge syndrome, malformations of these organs occur.

Symptoms of DiGeorge syndrome

Many manifestations of DiGeorge syndrome are determined immediately after the birth of a child; certain developmental defects (for example, heart defects) can be detected even earlier - during preventive ultrasound examinations. Most often, the first abnormalities of facial development to be discovered are cleft palate, sometimes in combination with a “cleft lip,” and prognathism of the lower jaw. Often, babies with DiGeorge syndrome have a small mouth, a small nose with a wide nasal bridge, and deformed or underdeveloped cartilage. ears. With a relatively mild course of the disease, all of the above symptoms can be expressed rather weakly, even a cleft of the hard palate can occur only in the posterior part and can only be detected during a thorough examination by an otolaryngologist.

In the first months of life of a patient with DiGeorge syndrome, manifestations of congenital heart defects come to the fore - this can be either tetralogy of Fallot or individual violations: ventricular septal defect, patent ductus arteriosus and a number of others. They are accompanied by cyanosis, cardiovascular failure, and in the absence of qualified medical care (including surgical care) can lead to early death of patients. Another common disorder in children with DiGeorge syndrome is seizures and tetany caused by hypoplasia of the parathyroid glands and subsequent hypocalcemia.

The next most important manifestation of DiGeorge syndrome, which distinguishes it from other types of velocardiofacial syndrome, is pronounced primary immunodeficiency. It develops due to aplasia or underdevelopment of the thymus and therefore affects cellular immunity to a greater extent. However, due to the close relationship between the humoral and cellular parts of the immune system, this leads to a general weakening of the body's defenses. Patients with DiGeorge syndrome are extremely sensitive to viral, fungal and bacterial infections, which often take a protracted and severe course. Some researchers note the presence of mental retardation varying degrees, sometimes seizures of neurological origin may be observed.

Diagnosis of DiGeorge syndrome

To determine DiGeorge syndrome, the method of physical general examination, cardiac studies (EchoCG, electrocardiogram), ultrasound of the thyroid gland and thymus, and immunological tests are used. An auxiliary role is played by conducting general and biochemical analyzes blood, studying the patient's medical history, genetic studies. When examining patients with DiGeorge syndrome, abnormalities characteristic of the disease can be determined - cleft palate, abnormalities of the facial structure, pathologies of the ENT organs. The history, as a rule, reveals frequent episodes of viral and fungal infections that take a severe course, convulsions caused by hypocalcemia, and extensive dental caries is often detected.

Ultrasound examinations of the thymus gland indicate a significant decrease in mass or even complete absence of the organ (agenesis). EchoCG and other cardiac diagnostic methods reveal numerous heart defects (for example, ventricular septal defect) and mediastinal vessels. Immunological studies confirm a significant drop in the level of T-lymphocytes. The same phenomenon is observed in peripheral blood and is often combined with a decrease in the concentration of immunoglobulin proteins. Biochemical study of the blood indicates a decrease in the level of calcium and parathyroid hormones. A geneticist can look for deletions on chromosome 22 using fluorescent DNA hybridization or multiplex polymerase chain reaction.

Treatment of DiGeorge syndrome

There is currently no specific treatment for DiGeorge syndrome; only palliative and symptomatic methods are used. It is very important to identify congenital heart defects as early as possible and, if necessary, perform their surgical correction, since cardiovascular disorders are the most common cause neonatal death due to this disease. Convulsive attacks caused by hypocalcemia pose a significant danger, which requires timely correction electrolyte balance blood plasma. Surgical assistance for DiGeorge syndrome may also be required to correct malformations of the face and palate.

Due to severe immunodeficiency, any signs of a bacterial, viral or fungal infection are a reason for the urgent use of appropriate drugs (antibiotics, antiviral and fungicidal agents). To improve the immune status of a patient with DiGeorge syndrome, a replacement infusion of immunoglobulins obtained from donor plasma can be performed. In some cases, a thymus gland was transplanted, which stimulated the formation of one's own T-lymphocytes - this helped improve the quality of life of patients.

Forecast and prevention of DiGeorge syndrome

The prognosis of DiGeorge syndrome is assessed by most researchers as uncertain, since this disease is characterized by significant variability of symptoms. In severe cases, there is a high risk of early neonatal death due to a combination of cardiovascular and immunological disorders. More benign forms of DiGeorge syndrome require quite intensive palliative therapy, it is especially important to pay attention to the treatment and prevention of viral and fungal infections. The intellectual development of patients is somewhat slowed down, however, with proper pedagogical and psychological correction, the manifestations of developmental delay can be leveled out. Due to the frequent spontaneous nature of mutations, prevention of DiGeorge syndrome has not been developed.

The child, while in the womb, is completely protected from any adverse environmental factors.

The thymus gland in children under one year old manages to collect information about almost all pathogenic organisms that we encounter during our lives.

Embryology (development of the thymus in the prenatal period)

Anatomy

To understand, you should place three fingers on the top of the manubrium of the sternum (the area between the collarbones). This will be the projection of the thymus gland.

At birth, her weight is 15-45 grams. The normal size of the thymus in children is 4-5 centimeters in length, 3-4 centimeters in width. An intact gland cannot be palpated in a healthy child.

Age characteristics

Role of the thymus

The thymus produces hormones necessary for the normal development of the immune system. Thanks to them, cells of the immune system learn to recognize harmful microorganisms and launch mechanisms to eliminate them.

Disorders of the thymus

Based on the degree of activity, hypofunction and hyperfunction of the thymus gland are distinguished. According to the morphological structure: (absence), (underdevelopment) and (increase in size).

Congenital pathology of the development of the thymus gland

If there are abnormalities in the genetic code, the formation of the thymus may be disrupted in the early embryonic period. This pathology is always combined with impaired development of other organs. There are several genetic disorders that cause changes in which the changes are fatal to the immune system. The body loses its ability to fight infection and is no longer viable.

Genetic malformations also include congenital cysts, thymic hyperplasia and thymomas (benign or malignant tumors of the thymus).

Hypofunction and hyperfunction of the thymus

Functional activity does not always depend on the size of the gland itself. With thymoma or cyst, the thymus gland is enlarged, and its activity may be normal or reduced.

Thymic hypoplasia

Thymic hyperplasia

Why does the baby's thymus gland enlarge?

Causes of primary (endogenous) thymomegaly:

Causes of exogenous thymomegaly:

Generalized disorders of the immune system(autoimmune diseases).
Disturbances in the functioning of regulatory systems in the brain(hypothalamic syndrome).

Symptoms of hyperplasia

Upon external examination, the enlarged thymus gland in an infant is visible when crying, when increased intrathoracic pressure pushes the thymus above the manubrium of the sternum.

Enlargement of the thymus gland in children affects the appearance of the child - enlarged facial features, pale skin. There is a delay in general development. An enlargement of the thymus gland in a 2-year-old child, detected during examination, especially with an asthenic physique, should not cause concern. The thymus is a fairly large organ for such a baby and may simply not fit into the space allotted to it.

Enlargement of the thymus gland in a baby with transient jaundice of newborns is also not a pathology.

The simultaneous identification of several signs characteristic of diseases of the thymus gland is of clinical importance:

compression syndrome of nearby organs;
immunodeficiency syndrome;
lymphoproliferative syndrome;
disruption of the endocrine system.

Syndrome of compression of nearby organs

Immunodeficiency syndrome

When the thymus gland is enlarged in a child against the background of its dysfunction, even common diseases proceed differently. Any cold can begin without an increase in temperature, with a sharp jump on the third or fourth day. Such children get sick longer than their peers, and the severity of the disease is higher. Often the infection spreads to the lower parts of the respiratory system with the development of bronchitis and tracheitis.

Lymphoproliferative syndrome

An increase in the production of hormones in the gland causes hyperstimulation of the entire immune system. The lymph nodes are enlarged, and in the general blood test the ratio of immune cells with a predominance of lymphocytes is disturbed. Any external irritant causes an excessive protective reaction in the form of allergic reactions. A severe reaction to vaccination may occur.

Disruption of the endocrine system

An enlarged thymus gland in children can lead to disruptions in the functioning of the endocrine system, with the development of diabetes mellitus and disruption of the thyroid gland.

Why is an enlarged thymus gland dangerous in a child?

An enlargement of the thymus gland in an infant, with compression of the trigeminal gland, disrupts the peristalsis of the esophagus and intestines. The child may have difficulty getting food and burping air after feeding. When the trachea is compressed, inhalation requires more effort, and the increased pressure causes rupture of the alveoli in the lungs with the development of atelectasis.

Diagnostics

To confirm the diagnosis, it is necessary to undergo a thorough examination, including:

General and detailed blood test.
Chest X-ray.
Ultrasound diagnostics.

A blood test can detect a decrease in the level of T-lymphocytes and an imbalance between immunoglobulins.

An X-ray of the thymus gland in a child will help exclude anomalies in the structure and location of the thymus gland.

Ultrasound allows you to most accurately determine the degree of thymic hyperplasia in newborns. Examination of the adrenal glands and abdominal organs will exclude concomitant pathology.

Additional tests for hormone levels may be required.

This group of diseases is caused by genetic defects of the immune system.
Congenital, or primary, aplasia (or hypoplasia) of the thymus gland is characterized by the complete absence of thymic parenchyma or its extremely weak development, which determines the presence of severe combined immunological deficiency due to a sharp decrease in the content of T- and B-lymphocytes and the absence of thymic bodies.
All these diseases are accompanied by recurrent inflammatory diseases, most often of pulmonary or intestinal localization, which are often the direct cause of death of patients. Therefore, children, especially young children, suffering from recurrent inflammatory diseases, should be carefully examined for the functional state of the thymus.
Similar changes are found in children with a number of diseases grouped under the group of immunodeficiency diseases. The most pronounced defects in the development of the thymus gland were found in the following syndromes.

Frequent respiratory and viral diseases of a child have a standard explanation - depressed immunity, which allows pathogens to enter the growing body. Why the protective forces are weakening, parents are at a loss and try to improve the situation by introducing vitamins into the children's diet. But there is a reason for frequent morbidity, it relates to the field of endocrinology and is called thymic hyperplasia.

The role of the thymus in the body

The thymus gland, also known as the thymus gland, is part of the immune system. In a child, the organ is located at the top of the sternum and reaches the root of the tongue. It is formed during intrauterine development. After birth, the thymus in children continues to grow until puberty. The organ is like a fork, its structure is soft and lobed. From the initial 15 g, by the time of puberty it increases to 37 g. The length of the thymus in infancy is about 5 cm, in youth - 16 cm. By old age, the gland decreases and turns into adipose tissue weighing 6 g. The gray-pink color changes to a yellowish tint .

The thymus plays an important role in the life of the body. It regulates the development of T-lymphocytes - immune cells whose task is to fight foreign antigens. Natural protectors protect the child from infection and viral-bacterial damage.

If the thymus becomes enlarged, it does its job worse, causing the immune system to weaken. As a result, the baby becomes more susceptible to pathogens of various pathologies, and his visits to the pediatrician become more frequent.

Reasons for the development of hyperplasia

Thymomegaly is another definition for an enlarged thymus gland and is transmitted genetically. In infants it develops for several reasons:

late pregnancy;
problems with bearing a fetus;
infectious diseases of women while expecting a baby.

Pathological growth of the thymus gland in older children is promoted by protein deficiency in the diet. Prolonged protein starvation of the body affects the functions of the thymus, lowers the level of leukocytes and suppresses the immune system.

Another culprit of thymomegaly may be lymphatic diathesis. If lymph tissue is prone to abnormal growth, it worsens the child's condition and affects internal organs. The thymus gland suffers, and its changes are discovered by chance when studying the responses of an x-ray of the sternum.

External signs of thymomegaly

Some help to understand that the baby’s thymus gland is enlarged characteristic features. In newborns, the problem is recognized by excess weight and fluctuations in body weight up and down.

They happen quite quickly. Mothers may notice increased sweating of the baby, frequent regurgitation and coughing, which unnecessarily plagues the child in a lying position.

On the skin side, hyperplasia is manifested by pallor or cyanosis. The skin acquires a bluish tint when crying or stressing. A specific marble pattern also appears on the tissues and a venous network appears on the chest. Muscle tone weakens. The growth of the thymus gland is accompanied by an enlargement of the lymph nodes, tonsils, and adenoids. The normal rhythm of the heart is disrupted.

The genital area reacts to thymic hyperplasia in its own way. In girls, hypoplasia of the genital organs is observed. Boys suffer from phimosis and cryptorchidism.

How is a thymus abnormality detected?

An informative method for assessing the condition of the thymus gland is ultrasound. Preliminary preparation This type of examination does not require. The specialist treats the child’s sternum with a conductive gel and moves the device’s sensor over the area. Children under two years of age are examined in a sitting or lying position. For older children, sonography is performed standing.

The mother must tell the diagnostician the exact weight of the baby. Normally, the organ under study has a mass equal to 0.3% of body weight. Exceeding this parameter indicates thymomegaly. Hyperplasia occurs in three degrees. They are installed according to the CTTI - cardiothymicothoracic index. In a child, diagnosis is carried out according to the following CTTI boundaries:

0.33 – 0.37 – I degree;
0.37 – 0.42 – II degree;
over 0.42 – III degree.

Despite the anomaly, correction of the size of the thymus gland is usually not carried out - the organ independently returns to normal parameters closer to 6 years. But to strengthen the immune system, doctors prescribe special medications and give parents recommendations regarding the child’s daily routine and nutrition. The organ’s recovery occurs faster with sufficient hours of sleep and long walks in the fresh air.

Conservative and urgent measures

The course of conservative treatment of thymomegaly is based on corticosteroids and a special diet. Vitamin C should dominate the composition of products. The substance is found in oranges and lemons, bell pepper, cauliflower and broccoli. A child's body can obtain useful ascorbic acid from black currant berries, rose hips and sea buckthorn.

If the thymus gland is excessively enlarged and the doctor considers it necessary to get rid of it, he will refer the child for surgery. After thymectomy, the patient is kept under constant monitoring. If hyperplasia occurs without clear clinical symptoms, neither drug nor surgical therapy is carried out. The baby only requires dynamic observation.

Quality of life for children

Dr. Komarovsky tells how a baby’s life will progress when the thymus gland grows. If a baby is diagnosed with stage I of thymomegaly, there is no serious danger yet. This is just a hint that the child needs regular health care.

If the deviation develops to degree II, the child can attend children's groups and social events. You don’t have to think about treating hyperplasia yet, but timely vaccination against various ailments is a mandatory procedure.

The most severe degree is the third, in which the disease can cause complications. The situation becomes critical for children over 6 years old. A weakened immune system cannot cope with the body’s defenses, and malfunctions in the functioning of the adrenal glands are observed. If a specialist detects thymic-adrenal insufficiency in the baby, the baby should be urgently sent to the hospital. In the absence of positive dynamics from drug correction of the condition of the thymus gland, the doctor has the right to insist on surgery.

Do not consider mild thymomegaly to be a minor problem. Be sure to examine the thymus gland in a baby under one year of age and take an immunogram to clarify the diagnosis. After 6 years, a child needs competent correction of the immune background. Make sure your baby’s condition improves as soon as possible, because advanced cases can be fatal.

With this syndrome, embryonic cells from which the parathyroid glands and thymus develop are affected in utero. As a result, the parathyroid glands and thymus are either underdeveloped or completely absent in the child. The tissues from which the face is formed are also affected. This is expressed by underdevelopment of the lower jaw, short upper lip, characteristic palpebral fissures, low location and deformation of the ears. In addition, children have congenital disorders of the heart and large vessels. The disease appears sporadically, but there are suggestions that it is genetically determined and inherited in an autosomal recessive manner.

Clinically, DiGeorge syndrome manifests itself at birth. Facial disproportions and heart defects are characteristic. The most characteristic symptom during the newborn period is hypocalcemic seizures (due to underdevelopment of the parathyroid glands). Immunodeficiency syndrome develops more often in the second half of life infant and is clinically manifested by frequently recurring infections caused by viruses, fungi and opportunistic bacteria, up to severe septic processes. Depending on the degree of underdevelopment of the thymus gland, the symptoms of immune deficiency can be very different (from severe to mild), and therefore in mild cases they speak of partial DiGeorge syndrome. Found in blood reduced level calcium and increased level phosphorus and a decrease or complete absence of parathyroid hormone, which confirms the underdevelopment or absence of the parathyroid glands.

Thymic Hypoplasia (DigeorgeSyndrome)

Hypoplasia or aplasia of the thymus, parathyroid glands and anomalies of other structures are formed simultaneously (for example, heart defects, renal pathologies, anomalies of the facial skull, including cleft palate, etc.) and are caused by a deletion in chromosome 22 q11.

Diagnostic criteria

Involvement in the process > 2 of the system organs listed below:

thymus;
epithelial body;
the cardiovascular system.

Transient hypocalcemia may occur, causing seizures in newborns.

Serum immunoglobulins are usually within the normal range, but may be lower, especially IgA; IgE levels may be higher than normal.

The number of T cells is reduced and the percentage of B cells is relatively increased. The ratio of helpers and suppressors is normal.

When the syndrome is fully expressed, patients are usually susceptible to opportunistic infections (Pneumocystis jiroveci, fungi, viruses), and death is possible due to blood transfusion due to graft-versus-host disease. In partial syndrome (with variable hypoplasia), the development and response to infection may be adequate.

The thymus is often absent; with ectopia of the thymus, histology is normal.

Lymph node follicles are normal, but areas of cellular depletion are observed in the paracortical and thymus-dependent areas. Risk of developing cancer and autoimmune diseases not elevated.

Thymus tumors

More than 40% of thymic tumors are accompanied by parathymic syndromes, which subsequently develop and in a third of cases are multiple in nature.

Associated

Myasthenia major in approximately 35% of cases, and in 5% of cases it can appear in the 6th year after excision of thymoma. Thymoma develops in 15% of patients with myasthenia gravis.

Acquired hypogammaglobulinemia. 7-13% of adult patients have an associated thymoma; after thymectomy the condition does not improve.

True red cell aplasia (TRCA) is detected in approximately 5% of patients with thymoma.

50% of cases of ICCA are associated with thymoma; in 25%, improvement occurs after thymectomy. Thymoma can occur simultaneously or develop subsequently, but not precede granulocytopenia or thrombocytopenia or both in / 3 cases; thymectomy is useless in this case. ICCA occurs in / 3 patients with hypogammaglobulinemia and thymoma.

PRIMARY IMMUNODEFICIENCIES (PIDS).

PIDs are often based on genetic defects of the immune system at the level of the afferent or efferent link. For

PIDS with a predominant defect of cellular (T-) immunity is associated with impaired differentiation of the stem cell precursor of T-cells, with impaired formation of T-lymphocytes due to thymic agenesis, dysplasia or hypoplasia. In case of PIDS with a defect in humoral (B-) immunity, it may be caused by impaired differentiation of the stem cell precursor of B cells, with activation of T-suppressors, cytotoxic T-lymphocytes.

With combined PIDs, one or more of the listed factors of combined damage may occur T-V systems immunity or defect of enzymes that ensure normal functioning of the immune system.

Clinical manifestations of PIDs are: decreased resistance to infections, increased frequency of infectious diseases, severity and duration of their course, development of severe and unusual complications, incidence of infectious diseases caused by microorganisms with low pathogenicity. With a defect in humoral immunity, there is a predisposition to infectious diseases caused by gram-positive bacteria, with a defect in cellular immunity - fungi, viruses, mycobacteria and gram-negative microbes. With PIDs, the incidence of tumor diseases, predominantly of lymphoid tissue, and autoimmune diseases increases.
To understand the pathoanatomical changes in the organs of immunogenesis in case of PIDs, it is necessary to know that the thymus, both in human phylogenesis and ontogenesis, is formed earlier than other immune organs (2 months of intrauterine development), is populated with lymphocytes earlier than other organs, and by the time the child is born is completely formed. Its function as an organ of immunogenesis plays a leading role in the perinatal period and in the first years of a child’s life. Therefore, changes in the thymus are of primary importance in assessing the immune system of children, and, consequently, in deciding the presence of PIDs.
^ AGE CHANGES IN THE THYMUS
In premature newborns and fetuses of 28-30 weeks, the thymus is immature - lobules in the form of layers of reticuloepithelium, not populated or moderately populated by lymphocytes, mature lobules are present, the cortical and medulla layers are clearly distinguishable in them. If an immature thymus is found in a full-term newborn or in a child of the first years of life, this is an indicator of the functional inferiority of the immune system of this child, which may disappear with age. Such immaturity of the thymus is an unfavorable background condition in which infectious diseases with severe course and even death occur .

In postnatal ontogenesis, the thymus undergoes age-related involution, which begins at 5-7 years of age and ends at puberty.
^ AGE INVOLUTION OF THE THYMUS
Adipose tissue develops, which is embedded in the thymus lobules. The lobules decrease in size, the number of lymphocytes in them decreases, the division into the cortex and medulla disappears, Hassal's corpuscles become homogeneous, partially calcify, and their new formation stops. At the same time, thymus lobules in the form of small islands are located among adipose tissue and remain at any age. Adipose tissue is especially developed during puberty and at the age of 18-20 years. In this case, the thymus has the appearance of a large fat body. In old age, the adipose tissue of the thymus gradually atrophies and sclerosis.
^ ACCIDENTAL TRANSFORMATION (or involution) of the THYMUS
A sharp decrease in the mass of the thymus, which occurs under the influence of various diseases, trauma, fasting, and cold, was called accidental involution of the thymus (the Latin word accedentis literally means accident).

The etiology of AT is diverse, which indicates the stereotypical nature of this phenomenon and the absence of any specificity in relation to the agent that caused this thymic reaction. AT is observed when various diseases in children, both infectious and non-infectious in nature, with leukemia and malignant tumors, with metabolic disorders, with protein starvation (kwashiorkor), cystic fibrosis, drug effects, for example, glucocorticoid, cytostatic, radiation therapy. There are 5 phases of AT of the thymus.

Phase I - begins with the proliferation of preT-lymphocytes in the subcapsular zone of the thymic cortex, their differentiation into mature T-lymphocytes increases. Phase II should be considered the beginning of involutive processes.

Phase II – the so-called “starry sky” picture, because in the cortical layer of the thymus there is an increase in the number of macrophages, while in parallel there is a death of T-lymphocytes due to apaptosis.

Phase III - death of lymphocytes in the cortex while lymphocytes are preserved in the medulla. This leads to inversion of the layers of the thymic lobules, and there is a gradual collapse of the cortical layer. The interlobular septa contain many mast cells, eosinophils, macrophages, and fibroblasts. The number of Hassall's bodies increases, they appear in the medulla and even in the cortex, but they are small. Lymphocytes, neutrophils, and eosinophils with symptoms of karyopyknosis and rhexis can accumulate inside thymic bodies.

Phase IV - devastation of the medullary zone due to the death of lymphocytes, thymic lobules collapse, thymic bodies merge, forming cystically dilated cavities filled with homogeneous eosinophilic masses, some become calcified. The connective tissue capsule of the thymus and interlobular connective tissue are expanded, there are islands of adipose tissue, infiltration of lymphocytes, eosinophils, macrophages, and mast cells.

Phase V - the coarsening of the stroma increases, narrow strands of cellular accumulations remain from the thymic lobules with the inclusion of thymic bodies, which are completely calcified. Large vessels and the capsule are sharply sclerotic, and there is adipose tissue among the stroma.

Thus, phases IV - V of AT differ only in the degree of sclerosis of the stroma and its vascular bed.
^ PRIVATE FORMS OF PIDS
M From an orthological point of view, changes in the thymus during PIDs can be characterized as dysplasia and hypoplasia of the organ.
DYSPLASIA - DISRUPTION OF THE FORMATION OF COMPONENT TISSUE ELEMENTS OF THE THYMUS DURING THE INTRAuterine PERIOD (EMBRYONAL AND EARLY FETAL PERIOD) and is characterized by the absence or underdevelopment of the reticuloepithelium, the absence (partial or complete) of colonization of the thymic lobes with lymphocytes, as well as disruption of the formation in the postnatal period with the appearance of signs untimely fatty transformation of the thymus. According to this definition, several variants of thymic dysplasia are distinguished. The subsequent classification is given according to WHO (1978).

^ THYMUS DYSPLASIA
- first option - according to WHO Swiss Glanzmann-Riniker type. Absence or severe underdevelopment of the reticuloepithelium and poor population of the lobules with lymphocytes. Severe combined immunodeficiency (SCID), both cellular and humoral immunity is impaired. The type of inheritance is autosomal recessive. The main pathogenesis is a defect of the lymphoid stem cell. Clinically characterized by unstable lymph and leukopenia. Infectious diseases develop in the first months of life and lead to death at 6-8 months of age. A pathological examination revealed multiple necrosis and inflammatory infiltrates in the skin, which are the source of sepsis. Dermatitis of the Leiner type, exfoliative erythroderma of the Ritter type or histiocytosis X are described. Bacterial infections are combined with viral ones - generalized chickenpox, measles giant cell pneumonia, generalized cytomegaly, herpes simplex, adenoviral infection, fungal infections and pneumocystis. This syndrome can be associated with lymphomas, hemolytic-uremic syndrome, hemolytic autoimmune anemia, cystic fibrosis and hypothyroidism.

The mass of the thymus is reduced by 5-10 times, the reticuloepithelium is underdeveloped, thymic bodies are absent or very small, sporadic. There are very few lymphocytes; there is no division into the cortical and medulla layers. Lymphoid tissue of peripheral organs is in a state of hypoplasia: lymphoid follicles are not developed, zones in the lymph nodes are not distinguishable, the tissue of the nodes consists of reticular stroma, myeloid elements and a small number of lymphocytes.

- second option according to WHO Nezelof syndrome (alimphocytosis). Thymic dysplasia is characterized by the presence of reticuloepithelium, which forms thymic lobules with multiple gland-like structures, Hassall's bodies are absent, lymphocytes are single. Cellular immunity suffers. It is inherited recessively, linked to the X chromosome. The pathogenetic essence comes down to a violation of the differentiation of T-lymphocyte precursors into mature T-lymphocytes, due to thymic dysplasia. Sometimes patients have a lack of serum Ig, due to impaired differentiation of B-lymphocytes. Infectious diseases - pneumonia, candidiasis, measles pneumonia, generalized BCG-itis, herpes simplex, sepsis caused by gram-negative flora. Life expectancy 1-2 years. Thymus mass is reduced. In the lymph nodes and spleen there are few lymphocytes in the thymus-dependent zones; plasmablasts are found. In the bone marrow up to 3% of plasma cells.

- third option according to WHO it is SCID with adenosine deaminase deficiency. Characteristic damage to the B - and T - cell unit. Characterized by recurrent infections caused by Candida, pneumocystis, Pseudomonas aeruginosa, cytomegaloviruses, herpes viruses, chickenpox. Often combined with a disorder of formation cartilage tissue. Without a bone marrow transplant, death occurs in the first year of life.

It has 2 types of inheritance: autosomal recessive (40%) - in this form there is no enzyme adenosine deaminase: in this case, deoxyaminazine accumulates, which is toxic to immature lymphocytes (especially T-l). Recessive, associated with the X chromosome (in 50%) - a mutation that affects the protein that is the receptor for IL-2,4,7. Morphological changes depend on the type of genetic defect. With type 1 of inheritance, the thymus is small, without lymphocytes. In other cases, the lymphoid tissue is hypoplastic with a decrease in T-cell zones and T- and B-zones.
- fourth option according to WHO DiGeorge syndrome

(hypoplasia or agenesis of the thymus). It is caused by a violation of the development of the 3rd and 4th pharyngeal pouches, from which the thymus and parathyroid glands develop. These patients lack cellular immunity, because there is hypoplasia or aplasia of the thymus, tetany develops, because no parathyroid glands, congenital heart defects and large vessels. The appearance of the face may change: hypertelorism, anti-Mongoloid eye shape, low-set ears, as well as esophageal atresia, hypothyroidism, tetrado of Fallot, hypoplasia of the kidneys and ureters. Due to impaired cellular immunity, there is no protection against fungal and viral infections. There are no T-dependent zones in the thymus and spleen. Plasma cells are not affected and the level of immunoglobulins is unchanged. This syndrome is caused by embryogenesis disorders in the 6-8th week of pregnancy.

- fifth variant according to WHO Louis–Bar syndrome ( ataxia-telangiectasia Louis-Bar). Characteristic is a deficiency of cellular and partly humoral immunity in combination with progressive cerebellar ataxia and peribulbar telangiectasia. Morphologically - thymic dysplasia, the lobules consist of reticuloepithelium, there are no Hassall bodies, a decrease in T - lymphocytes, the lobules are not divided into the cortical and medullary zone. Giant cells with hyperchromic nuclei are formed in the reticuloepithelium. In peripheral organs of immunogenesis, hypoplasia of T-dependent zones. In the cerebellum there is cortical atrophy with expansion of the fourth ventricle. Microscopy reveals degeneration or complete disappearance of piriform neurocytes (Purkinje cells) and the granular layer. Such changes are observed in the anterior horns spinal cord, hypothalamus and demylinization of the posterior columns. In the transverse muscles - secondary atrophy, in the liver - focal necrosis, fatty degeneration, lymphocyplasmacytic infiltration of the portal tracts. In the kidneys - chronic pyelonephritis. In the lungs - bronchiectasis, abscesses, pneumosclerosis. The combination of ATE with malignant tumors is typical: lymphomas, lymphogranulomatosis, leukemia, meduloblastomas, adencarcinomas, dysgerminomas.

This defect is caused by a defect in the terminal differentiation of T lymphocytes, as well as an abnormality of the plasma membranes of lymphocytes. Inherited in an autosomal recessive manner. There is often a deficiency of Ig A, Ig E, IgG 2, IgG 4. Ataxia develops from the age of 4 (with gait disturbance) and gradually progresses. Telangiectasias are detected by the 1st year of life on the bulbar conjunctiva, then in other areas. Graying of hair, sweating, atrophic dermatitis, eczema, skin tumors and severe retardation of physical development are noted. Secondary sexual characteristics do not develop. Menstruation is irregular. Patients live up to 39-41 years.

- sixth option according to WHO a Bruton's gammaglobulinemia, X-linked . It is characterized by untimely fatty transformation of the thymus. One of the most common primary IDs. There is no or little serum immunoglobulin IgG. More often in boys, the beginning of 8-9 months: when the amount of immunoglobulins from the mother decreases. Recurrent conjunctevitis, otitis, pharyngitis, bronchitis, pneumonia appear, skin infections (pyoderma) are often caused by staphylococcus or Haemophilus influenzae. Cellular immunity is not impaired. Autoimmune diseases often develop in Bruton's disease ( rheumatoid arthritis, SLE, dermatomyositis). Sharply reduced or absent B-lymphocytes. The lymph node and spleen do not have germinal centers, but the lymph node, spleen, bone marrow and connective tissue, no plasmacytes, palatine tonsils in the form of rudiments, T-lymphocytes remain normal.
- seventh option Chronic granulomatous disease (CGD, fatal granulomatous disease of children) is characterized by a defect in the bactericidal function of phagocytes with repeated purulent-granulomatous processes in the skin, lungs, lymph nodes, liver, with hypergammaglobulinemia, anemia, and leukocytosis.
There are 2 forms of CGD

^ 1. The most common, inherited in a recessive manner, linked to the X chromosome. Boys (up to 4 years old) are affected and the disease is severe.
2. It is rare, inherited in an autosomal recessive manner, affects children of both sexes, and is more mild. First clinical symptoms are skin lesions in the 1st month of life in the form of eczematous changes with suppuration in the area of the ears and around the nose, plus regional lymphadenitis, then the liver, lungs, lymph nodes, bones are involved in the process, in which abscesses are formed. A pathological examination revealed premature fatty transformation of the thymus, during internal organs granulomas consisting of monocytes, neutrophilic leukocytes, followed by purulent melting and scarring. At the same time, macrophages and neutrophils are loaded with GAGs and lipids; these cells are found in the lungs, thymus, spleen, lymph nodes, and liver. Hepato-splenomegaly is noted.
Common variable immunodeficiency. This heterogeneous group may be congenital or acquired, sporadic or familial (with variable mode of inheritance). Typically - hypogammaglobulinemia, a defect of all classes of AT, but sometimes only IgG. In these patients, the content of B-lymphocytes in the blood and lymphoid tissue is not impaired, but the B-lymphocytes are not transformed into plasma cells, and there is no secretion of AT. Clinically - recurrent bacterial infections, enteroviral infections, herpes, giardiasis. Histologically - hyperplasia of the B-cell zones of the l\follicles, l\u, spleen. They have a high incidence of rheumatoid arthritis: pernicious and hemolytic anemia.

^ Isolated IgA deficiency. Low levels of serum and secretory IgA are characteristic. This deficiency can be either familial or acquired after toxoplasmosis, measles and other viral infections. With IgA deficiency, the protection of the mucous membranes is impaired and infections of the respiratory tract, gastrointestinal tract, MPS, respiratory tract allergies and autoimmune diseases (SLE, rheumatoid arthritis) develop. The essence is a defect in the differentiation of B lymphocytes producing IgA. They often develop anaphylactic reactions.

cosiness. Plasma cells are not affected and the level of immunoglobulins is unchanged. This syndrome is caused by embryogenesis disorders in the 8th week of pregnancy.
^ THYMUS HYPOPLASIA

Hypoplasia – characterized by the presence of all the structural elements of the thymus (reticuloepithelium, lymphocytes), but their further development does not occur, which is accompanied by a decrease in the mass of the thymus.

^ Hypoplasia of the thymus is characteristic of and immunodeficiency with thrombocytopenia and eczema (Wiskott-Aldrich syndrome) has a recessive mode of inheritance and is associated with the X chromosome. Characterized by thrombocytopenia, eczema, recurrent infections, and early death. Morphologically, the thymus has a normal structure, but there is a progressive secondary depletion of T-lymphocytes in the peripheral blood and paracortical (thymus-dependent) zones of the lymph node with a decrease in cellular immunity. The level of IgM in the blood serum is low, IgG is normal. The level of IgA and E increases. Malignant lymphomas often develop.

Genetic deficiency of the complement system - congenital deficiency of C1, C2, C4 increases the risk of developing immune complex diseases (SLE).
THYMOMEGALY

TM - an increase in organ weight by 3-4 times compared to the norm, the absence of stereotypical phase changes (including phases III-IV AT) under conditions of stress or antigenic exposure. From a clinical position, TM is diagnosed radiographically on the basis of an increase in the cardiothymicothoracic index > 0.38. TM is observed in children who often suffer from acute respiratory viral infections (4-6 times a year), with infectious-allergic myocarditis, rheumatism, cardiomyopathy, meningococcemia, bronchial asthma. These children are more likely to have rickets, congenital heart defects and central nervous system defects. In infectious diseases in children with TM, death occurs in early dates diseases. Microscopically, the following HMs are distinguished:

In the cortical zone, the proliferation of macrophages and lymphoblasts is determined (the first phase of AT) - a “starry sky” picture, thymic bodies are few in number, small, mainly of a cellular structure (consisting of 3-5 ring-shaped reticuloepithelial cells), localized in the medulla. This variant occurs in children who died from ARVI and meningococcemia in the early stages of illness.
In the cortical zone of the thymus there are large accumulations consisting of lymphocytes, resembling lymphoid follicles, Hassall's bodies are small, either cellular in structure or homogeneously eosinophilic with preserved reticuloepithelial cells located on the periphery. Observed in rheumatism, infectious-allergic myocarditis, bronchial asthma, cardiomyopathy, subacute and chronic allergic reactions.
In the thymus lobules, the division into zones is preserved, but the cortical zone predominates over the cerebral zone. Thymic bodies are small, few in number, and have a cellular structure. It is observed in infectious-allergic myocarditis, acute respiratory viral infections, complicated by pneumonia, in combination with heart defects and central nervous system.

TM in children should be considered as one of the unclassified variants of cell-type immunodeficiency. With age, the size of the thymus may return to normal.

At dysfunction of T-lymphocytes Infectious and other diseases are usually more severe than with antibody deficiency. Patients in such cases usually die in infancy or early childhood. Products of damaged genes have been established only for some primary disorders of T-lymphocyte function. The method of choice for the treatment of these patients is currently transplantation of thymus or bone marrow from HLA-matched siblings or haploidentical (semi-compatible) parents.

Hypoplasia or aplasia of the thymus(due to disruption of its formation in the early stages of embryogenesis) is often accompanied by dysmorphia of the parathyroid glands and other structures that are formed at the same time. Patients have esophageal atresia, cleft uvula, congenital heart defects and large vessels (atrial and ventricular septal defects, right-sided arc aorta, etc.).

Typical facial features of patients with hypoplasia: shortening of the philtrum, hypertelorism, anti-Mongoloid eye shape, micrognathia, low-set ears. Often the first indication of this syndrome is hypocalcemic seizures in newborns. Similar facial features and abnormalities of large vessels leaving the heart are observed in fetal alcohol syndrome.

Genetics and pathogenesis of thymic hypoplasia

DiGeorge syndrome occurs in both boys and girls. Familial cases are rare and therefore it is not considered a hereditary disease. However, in more than 95% of patients, microdeletions of segments of segment qll.2 of chromosome 22 (a DNA region specific for DiGeorge syndrome) were found. These divisions appear to be more often transmitted through the maternal line.

They can be quickly detected by genotyping using PCR of microsatellite DNA markers located in the corresponding region. Anomalies of large vessels and division of sections of the long arm of chromosome 22 combine DiGeorge syndrome with velocardiofacial and conotruncal facial syndrome. Therefore, they are currently talking about CATCH22 syndrome (Cardiac, Abnormal facies, Thymic hypoplasia, Cleft palate, Hypocalcemia - heart defects, abnormalities of facial structure, thymic hypoplasia, cleft palate, hypocalcemia), which includes a wide range of conditions associated with 22q deletions. In DiGeorge syndrome and velocardiofacial syndrome, deletions of sections of the p13 segment of chromosome 10 were also found.

Concentration immunoglobulins in serum with thymic hypoplasia is usually normal, but the level of IgA is reduced, and IgE is increased. The absolute number of lymphocytes is only slightly lower than the age norm. The number of CD T lymphocytes is reduced in accordance with the degree of thymic hypoplasia, and therefore the proportion of B lymphocytes appears to be increased. The response of lymphocytes to mitogens depends on the degree of thymic failure.

In the thymus, if present, small bodies are found Hassalya, normal thymocyte density and a clear boundary between the cortex and medulla. Lymphoid follicles are usually preserved, but the number of cells is usually reduced in the para-aortic lymph nodes and the thymus-dependent region of the spleen.

Clinical manifestations of thymic hypoplasia

More often, there is not complete aplasia, but only of the parathyroid glands, called incomplete DiGeorge syndrome. Such children grow normally and do not suffer too much from infectious diseases. In complete DiGeorge syndrome, as in patients with severe combined immunodeficiency, there is increased susceptibility to opportunistic and opportunistic flora, including fungi, viruses and P. carinii, and graft-versus-host disease often develops with non-irradiated blood transfusions.

Treatment of thymic hypoplasia - DiGeorge syndrome

Immunodeficiency full DiGeorge syndrome corrected by transplanting a tissue culture of the thymus (not necessarily from relatives) or unfractionated bone marrow from HLA-identical siblings.

The child, while in the womb, is completely protected from any adverse environmental factors.

The thymus gland in children under one year old manages to collect information about almost all pathogenic organisms that we encounter during our lives.

Embryology (development of the thymus in the prenatal period)

Anatomy

To understand, you should place three fingers on the top of the manubrium of the sternum (the area between the collarbones). This will be the projection of the thymus gland.

At birth, her weight is 15-45 grams. The normal size of the thymus in children is 4-5 centimeters in length, 3-4 centimeters in width. An intact gland cannot be palpated in a healthy child.

Age characteristics

Role of the thymus

Disorders of the thymus

Based on the degree of activity, hypofunction and hyperfunction of the thymus gland are distinguished. According to the morphological structure: (absence), (underdevelopment) and (increase in size).

Congenital pathology of the development of the thymus gland

If there are abnormalities in the genetic code, the formation of the thymus may be disrupted in the early embryonic period. This pathology is always combined with impaired development of other organs. There are several genetic disorders that cause changes in which the changes are fatal to the immune system. The body loses its ability to fight infection and is no longer viable.

Genetic malformations also include congenital cysts, thymic hyperplasia and thymomas (benign or malignant tumors of the thymus).

Hypofunction and hyperfunction of the thymus

Functional activity does not always depend on the size of the gland itself. With thymoma or cyst, the thymus gland is enlarged, and its activity may be normal or reduced.

Thymic hypoplasia

Thymic hyperplasia

Why does the baby's thymus gland enlarge?

Causes of primary (endogenous) thymomegaly:

Causes of exogenous thymomegaly:

Generalized disorders of the immune system(autoimmune diseases).
Disturbances in the functioning of regulatory systems in the brain(hypothalamic syndrome).

Symptoms of hyperplasia

Upon external examination, the enlarged thymus gland in an infant is visible when crying, when increased intrathoracic pressure pushes the thymus above the manubrium of the sternum.

Enlargement of the thymus gland in a baby with transient jaundice of newborns is also not a pathology.

The simultaneous identification of several signs characteristic of diseases of the thymus gland is of clinical importance:

compression syndrome of nearby organs;
immunodeficiency syndrome;
lymphoproliferative syndrome;
disruption of the endocrine system.

Syndrome of compression of nearby organs

Immunodeficiency syndrome

When the thymus gland is enlarged in a child against the background of its dysfunction, even common diseases proceed differently. Any cold can begin without an increase in temperature, with a sharp jump on the third or fourth day. Such children get sick longer than their peers, and the severity of the disease is higher. Often the infection spreads to the lower parts of the respiratory system with the development of bronchitis and tracheitis.

Lymphoproliferative syndrome

Disruption of the endocrine system

An enlarged thymus gland in children can lead to disruptions in the functioning of the endocrine system, with the development of diabetes mellitus and disruption of the thyroid gland.

Why is an enlarged thymus gland dangerous in a child?

An enlargement of the thymus gland in an infant, with compression of the trigeminal gland, disrupts the peristalsis of the esophagus and intestines. The child may have difficulty getting food and burping air after feeding. When the trachea is compressed, inhalation requires more effort, and the increased pressure causes rupture of the alveoli in the lungs with the development of atelectasis.

Diagnostics

To confirm the diagnosis, it is necessary to undergo a thorough examination, including:

General and detailed blood test.
Chest X-ray.
Ultrasound diagnostics.

A blood test can detect a decrease in the level of T-lymphocytes and an imbalance between immunoglobulins.

An X-ray of the thymus gland in a child will help exclude anomalies in the structure and location of the thymus gland.

Ultrasound allows you to most accurately determine the degree of thymic hyperplasia in newborns. Examination of the adrenal glands and abdominal organs will exclude concomitant pathology.

Additional tests for hormone levels may be required.

CONGENAL (PRIMARY) IMMUNODEFICIENCY Morphological manifestations of primary immune response deficiency are associated, as a rule, with congenital anomalies of the thymus, or a combination of these anomalies with underdevelopment of the spleen and lymph nodes. Aplasia and hypoplasia of the thymus are accompanied by a deficiency of the cellular component of immunity or a combined immune deficiency. With aplasia (agenesis), the thymus is completely absent; with hypoplasia, its size is reduced, division into the cortex and medulla is impaired, and the number of lymphocytes is sharply reduced. In the spleen, the size of the follicles is significantly reduced, light centers and plasma cells are absent. The lymph nodes lack follicles and the cortical layer (B-dependent zones), only the pericortical layer (T-dependent zone) is preserved. Morphological changes in the spleen and lymph nodes are characteristic of hereditary immunodeficiency syndromes associated with a defect in both humoral and cellular immunity. All types of congenital immunodeficiency are rare. Currently the most studied are:

severe combined immunodeficiency (SCI);

thymic hypoplasia (Dai Joja syndrome);

Nezelof's syndrome;

congenital agammaglobulinemia (Bruton's disease);

common variable (variable) immunodeficiency;

isolated IgA deficiency;

immunodeficiencies associated with hereditary diseases (Wiskott-Aldrich syndrome, ataxia-telangiectasia syndrome, Bloom's syndrome)

complement deficiency

Severe combined immunodeficiency (SCI) is one of the most severe forms of congenital immunodeficiency. It is characterized by a defect in lymphoid stem cells (1 in Fig. 5), which leads to disruption of the formation of both T and B lymphocytes. The process of lowering the thymus from the neck into the mediastinum is disrupted. The number of lymphocytes in it is sharply reduced. They are also small in the lymph nodes (Fig. 6B), spleen, intestinal lymphoid tissue and peripheral blood. There are no immunoglobulins in the serum (Table 7). Insufficiency of both cellular and humoral immunity is the cause of a variety of severe infectious (viral, fungal, bacterial) diseases (Table 8) that occur immediately after birth, which leads to early death (usually in the first year of life). Severe combined immunodeficiency represents several different congenital diseases. All of them are characterized by impaired differentiation of stem cells. Most patients have an autosomal recessive form (Swiss type); some have a recessive form associated with the X chromosome. More than half of patients with the autosomal recessive form have a deficiency of the enzyme adenosine deaminase (ADA) in their cells. In this case, the conversion of adenosine to inosine does not occur, which is accompanied by the accumulation of adenosine and its lymphotoxic metabolites. Some patients with severe combined immunodeficiency have a deficiency of nucleotide phospholipase and inosine phospholipase, which also leads to the accumulation of lymphotoxic metabolites. The absence of ADA in amniotic cells allows diagnosis in the prenatal period. Bone marrow transplantation is used to treat these patients. Thymic hypoplasia(Dai Joja syndrome) is characterized by a lack of T-lymphocytes (2 in Fig. 5) in the blood, in the thymus-dependent areas of the lymph nodes and spleen (Fig. 6B). The total number of lymphocytes in the peripheral blood is reduced. Patients show signs of insufficiency of cellular immunity, which manifest themselves in the form of severe viral and fungal infectious diseases in childhood (Table 8). The development of B lymphocytes is usually not impaired. T-helper activity is practically absent, but the concentration of immunoglobulins in the serum is usually normal (Table 7). No genetic defects have been identified in thymic hypoplasia. This condition is also characterized by the absence of the parathyroid glands, abnormal development of the aortic arch and facial skull. In the absence of the parathyroid glands, severe hypocalcemia occurs, leading to death at an early age. T-lymphopenia with Nezelof syndrome combined with a violation of their function. It is believed that this occurs as a result of impaired maturation of T cells in the thymus. Nezeloff syndrome differs from Dai Joja syndrome in the characteristic association of damage to other structures developing from the third and fourth pharyngeal pouches. The parathyroid glands are not damaged in this syndrome. Thymic hypoplasia is successfully treated by transplantation of human fetal thymus, which restores T-cell immunity. Congenital agammaglobulinemia(Bruton's disease) is a genetically determined recessive disease associated with the X chromosome, which is observed mainly in boys and is characterized by a violation of the formation of B-lymphocytes (3 in Fig. 5). Pre-B cells (CD10 positive) are detected, but mature B cells are absent in the peripheral blood and in the B zones of the lymph nodes, tonsils, and spleen. The lymph nodes lack reactive follicles and plasma cells (Fig. 6D). Insufficiency of humoral immunity is manifested in a noticeable decrease or absence of immunoglobulins in the serum. The thymus and T-lymphocytes develop normally and cellular immunity is not impaired (Table 7). The total number of lymphocytes in the peripheral blood is within normal limits because the number of T cells, which typically make up 80-90% of blood lymphocytes, is within normal limits. Infectious diseases in a child usually develop in the second half of the first year of life after the level of passively transmitted maternal antibodies falls (Table 8). Treatment of such patients is carried out by administering immunoglobulins. Common variable immunodeficiency includes several different diseases characterized by a decrease in the level of individual or all classes of immunoglobulins. The number of lymphocytes in the peripheral blood, including the number of B cells, is usually normal. The number of plasma cells is usually reduced, possibly as a result of a defect in B-lymphocyte transformation (4 in Fig. 5). In some cases, there is an excessive increase in T-suppressor cells (5 in Fig. 5), especially in the acquired form of the disease, which develops in adults. In some cases, hereditary transmission of the disease with different types of inheritance has been described. A lack of humoral immune response leads to recurrent bacterial infectious diseases and giardiasis (Table 8). Prophylactic administration of gammaglobulins is less effective than for Bruton's agammaglobulinemia. Isolated IgA deficiency– the most common immunodeficiency, occurring in one in 1000 people. It results from a defect in the terminal differentiation of plasma cells that secrete IgA (4 in Fig. 5). In some patients, this defect is associated with abnormal T-suppressor function (5 in Fig. 5). In most patients, IgA deficiency is asymptomatic. Only a small number of patients have a predisposition to the occurrence of pulmonary and intestinal infections, since they have a lack of secretory IgA in the mucous membranes. In patients with severe IgA deficiency, anti-IgA antibodies are detected in the blood. These antibodies can react with IgA that is present in the transfused blood, leading to the development of type I hypersensitivity.

Immunodeficiencies associated with hereditary diseases Wiskott-Aldrich syndrome is a hereditary recessive disease associated with the X chromosome, which is characterized by eczema, thrombocytopenia and immunodeficiency. T-lymphocyte deficiency may develop during the course of the disease, and serum IgM levels are reduced. Patients develop recurrent viral, fungal and bacterial infectious diseases, and lymphomas often occur. Ataxia-telangiectasia– a hereditary disease, transmitted autosomal recessively, characterized by cerebellar ataxia, cutaneous telangiectasia and deficiencies of T-lymphocytes, IgA and IgE. It is possible that this pathology is associated with the presence of a defect in DNA repair mechanisms, which leads to the appearance of multiple DNA strand breaks, especially in chromosomes 7 and 11 (T-cell receptor genes). Sometimes these patients develop lymphomas. Bloom's syndrome It is transmitted autosomal recessively and manifests itself in the form of other defects in DNA repair. In the clinic, there is a deficiency of immunoglobulin and lymphomas often occur.

Complement deficiency Deficiency various factors complement is rare. The most common deficiency is factor C2. Manifestations of factor C3 deficiency are clinically similar to those of congenital agammaglobulinemia and are characterized by recurrent bacterial infections in childhood. Deficiency of early complement factors (C1, C4, and C2) is associated with the occurrence of autoimmune diseases, especially systemic lupus erythematosus. Deficiency of terminal complement factors (C6, C7 and C8) predisposes to recurrent infectious diseases caused by Neisseria.

SECONDARY (ACQUIRED) IMMUNODEFICIENCY Immunodeficiency of varying degrees is quite common. It occurs as a secondary phenomenon in various diseases, or as a result of drug therapy (Table 9) and is very rarely a primary disease.

	Mechanism
Primary disease	Very rare; typically manifests as hypogammaglobulinemia in the elderly. Usually as a result of an increase in the number of T-suppressor cells.
Secondary to other diseases
Protein-calorie fasting	Hypogammaglobulinemia
Iron deficiency
Post-infectious (leprosy, measles)	Often – lymphopenia, usually transient
Hodgkin's disease	T-lymphocyte dysfunction
Multiple (common) myeloma	Impaired synthesis of immunoglobulins
Lymphoma or lymphocytic leukemia	Decreased number of normal lymphocytes
Late stages of malignant tumors	Decreased T-lymphocyte function, other unknown mechanisms
Thymus tumors	Hypogammaglobulinemia
Chronic renal failure	Unknown
Diabetes	Unknown
Drug-induced immunodeficiency	Occurs frequently; caused by corticosteroids, antineoplastic drugs, radiotherapy, or immunosuppression after organ transplantation
HIV infection (AIDS)	Decrease in the number of T-lymphocytes, especially T-helper cells

The morphology of acquired immunodeficiency syndrome (AIDS) does not have a specific pattern and differs in different stages its development. Changes are observed in both central and peripheral organs of immunogenesis (the most pronounced changes are in the lymph nodes). Accidental involution and atrophy may be detected in the thymus. Accidental involution of the thymus is a rapid decrease in its mass and volume, which is accompanied by a decrease in the number of T-lymphocytes and a decrease in the production of thymic hormones. The most common causes of accidental involution are viral infections, intoxication, and stress. Once the cause is eliminated, this process is reversible. If the outcome is unfavorable, atrophy of the thymus gland occurs. Thymic atrophy is accompanied by collapse of the network of epithelial cells, a decrease in the volume of parenchyma lobules, petrification of thymic bodies, and the proliferation of fibrous connective and adipose tissue. The number of T-lymphocytes is sharply reduced. Lymph nodes are initially enlarged in volume, and then undergo atrophy and sclerosis. There are three morphological stages of changes in secondary immunodeficiency:

follicular hyperplasia;

pseudoangioimmunoblastic hyperplasia;

depletion of lymphoid tissue.

Follicular hyperplasia is characterized by a systemic enlargement of the lymph nodes up to 2-3 cm. Many sharply enlarged follicles fill almost the entire tissue of the lymph node. The follicles are very voluminous, with large germinal centers. Immunoblasts are detected in them. Mitoses are numerous. Morphometrically, it is possible to state a violation of the ratio of T-cell subpopulations, but they are variable and have no diagnostic value. Pseudoangioimmunoblastic hyperplasia is characterized by severe hyperplasia of venules (postcapillaries), the structure of the follicles is fragmented or not determined. The lymph node is diffusely infiltrated with plasma cells, lymphocytes, immunoblasts, and histiocytes. There is a significant decrease of up to 30% of T-lymphocytes. There is a disproportionate disturbance in the ratio of lymphocyte subpopulations, which depends to some extent on the cause of the immunodeficiency. For example, people infected with HIV are characterized not only by a decrease in T-helper cells, but also by a decrease in the CD4/CD8 ratio (helper-suppressor ratio), which is always less than 1.0. This sign is the main feature of the immunological defect in AIDS caused by HIV infection. This stage of immunodeficiency is characterized by the development of opportunistic infections. Depletion of lymphoid tissue replaces lymphoid hyperplasia at the final stage of immunodeficiency. Lymph nodes at this stage are small. The structure of the lymph node along its entire length is not determined; only the capsule and its shape are preserved. Sclerosis and hyalinosis of collagen fiber bundles are pronounced. The population of T-lymphocytes is practically not detected; single immunoblasts, plasmablasts and macrophages are preserved. This stage of immunodeficiency is characterized by the development of malignant tumors. The meaning of secondary (acquired) immunodeficiency. Immunodeficiency is always accompanied by the development of opportunistic infections and, at the final stage, the development of malignant tumors, most often Kaposi's sarcoma and malignant B-cell lymphomas. The occurrence of infectious diseases depends on the type of immunodeficiency:

T cell deficiency predisposes to infectious diseases caused by viruses, mycobacteria, fungi and other intracellular microorganisms, such as Pneumocystis carinii And Toxoplasma gondii.

B-cell deficiency predisposes to purulent bacterial infections.

These infectious diseases reflect the relative importance of cellular and humoral responses in defense against various microbial agents. Kaposi's sarcoma and malignant B-cell lymphomas are the most common malignancies that develop in patients with immunodeficiencies. They can occur in patients with HIV infection, Wiskott-Aldrich syndrome and ataxia-telangiectasia, as well as in patients receiving long-term immunosuppressive therapy after organ transplantation (most often kidney transplantation). The occurrence of malignant neoplasms can be associated either with a violation of the immune response aimed at eliminating developing malignant cells that arise in the body (failure of immune surveillance) or due to immune stimulation of a damaged immune system in which the normal mechanism for controlling cell proliferation is disrupted (this leads to the occurrence of B - cell lymphomas). In some cases, especially ataxia-telangiectasia, immune deficiency is associated with chromosomal fragility, which is believed to predispose to the development of neoplasms. Note that epithelioid thymoma, a primary tumor of thymic epithelial cells, results in secondary immunodeficiency.

Thymic hypoplasia is a congenital underdevelopment of the organ. Due to the reduced number of T-lymphocytes and thymus hormones, children may die in the first days of life or before 2 years of age. Read further in our article about what thymic hypoplasia is, the role of the organ in the lives of children, diagnosis of deviations from the norm, as well as treatment.

Read in this article

The role of the thymus in children

The maturation of T-lymphocytes, which are responsible for cellular immunity, occurs in the thymus gland. Since the formation of protective proteins (immunoglobulins) by B-lymphocytes requires a signal from a T-cell, if the thymus malfunctions, these reactions (humoral immunity) also suffer. Therefore, the gland is considered the main organ that protects the child from the penetration of foreign antigen protein.

The thymus also produces hormones - thymopoietin, thymulin, thymosin, and about 20 biologically active compounds. With their participation, children experience:

body growth;
puberty;
metabolism;
muscle contractions;
formation of blood cells in the bone marrow;
regulation of the pituitary gland and thyroid gland;
maintaining normal level sugar, calcium and phosphorus in the blood and tissues;
the body's immune response.

Manifestations of underdevelopment of the thymus gland

The complete absence of the thymus gland (aplasia) can cause the death of a child in the first days of life or stillbirth. Infants who survive have severe, persistent diarrhea that is difficult to treat. They lead to progressive exhaustion. The addition of any, even the most minor, infection is especially dangerous.

When the thymus is reduced in size, the development of the entire lymphatic system. The body cannot cope not only with external pathogens, but also its own intestinal microflora can cause inflammatory process. Against the background of low immunity, fungi rapidly multiply, causing candidiasis (thrush), pneumocystis, which affects the lungs.

Most children with a significantly enlarged thymus do not survive past age 2 without treatment due to severe infections.

View of the thymus in a child and an adult

With a slight decrease in the size of the organ, manifestations of immune deficiency can occur in adulthood. Signs of thymus dysfunction include:

frequent viral and bacterial infections;
tendency to recurrent fungal infections of the skin, mucous membranes of the mouth and genitals, lungs, and intestines;
periodically worsening herpes;
severe course of “childhood” diseases (measles, rubella, mumps);
severe reaction to vaccinations (fever, convulsions);
presence of tumor processes.

The condition of patients is aggravated by the presence of changes in the liver, spleen and bone marrow, which arise due to insufficient thymus function.

Diagnosis of the disease

Suspicion of thymic hypoplasia appears when a combination of:

frequent viral diseases;
persistent thrush;
difficult-to-treat diarrhea;
pustular skin lesions;
severe infectious diseases with drug resistance.

Ultrasound is used to examine the thymus in children, while in adults computed tomography and magnetic resonance imaging are more informative.

What to do if the thymus gland is enlarged

In children, the most radical treatment is a thymus gland transplant. Parts of the thymus or a whole organ from stillborn fetuses with a normal organ structure are sutured into the area of the rectus abdominis and thigh muscles.

With a successful and timely operation, the content of lymphocytes and immunoglobulins in the blood increases, and the ability for immune reactions appears. Bone marrow transplants and the introduction of drugs that stimulate the development of T-lymphocytes outside the thymus - Neupogen, Leucomax - can also be successful.

In less complex cases, symptomatic treatment of infections is carried out with antibiotics, antiviral and antifungal agents. To correct insufficient thymus function, T-activin, Timalin, Thymogen, and immunoglobulin are administered intravenously.

Thymic hypoplasia is a dangerous pathology in children. With a slight decrease in size, there is a tendency to frequent infections, their severe course, and resistance to antibacterial and antifungal agents.

With a significant or complete absence of the gland, children can die before the age of 2 years. The disease can be suspected by persistent thrush and diarrhea. To detect gland hypoplasia, ultrasound, tomography, and immunological blood tests are performed. In severe cases, only an organ transplant can help; less complex variants of the disease require symptomatic treatment, administration of thymus extracts.

Useful video

Watch the video about DiGeorge, DiGeorge, DiGeorge syndrome, aplasia of the parathyroid glands, dysembryogenesis syndrome of the 3-4 branchial arch:

Thymus gland - what is it?

The iron got its name due to its shape resembling a two-pronged fork. However, this is what a healthy thymus looks like, while a sick one takes on the appearance of a sail or butterfly. Because of its proximity to the thyroid gland, doctors used to call it the thymus gland. What is the thymus? This is the main organ of vertebrate immunity, in which the production, development and training of T-cells of the immune system occurs. The gland begins to grow in a newborn baby before the age of 10, and after the 18th birthday it gradually decreases. The thymus is one of the main organs for the formation and activity of the immune system.

Where is the thymus gland located?

You can detect the thymus gland by placing two folded fingers on the upper part of the sternum below the clavicular notch. The location of the thymus is the same in children and adults, but the anatomy of the organ has age-related characteristics. At birth, the weight of the thymus organ of the immune system is 12 grams, and by puberty it reaches 35-40 g. Atrophy begins at approximately 15-16 years. By the age of 25, the thymus weighs about 25 grams, and by 60 it weighs less than 15 grams.

By the age of 80, the weight of the thymus gland is only 6 grams. By this time, the thymus becomes elongated, the lower and lateral sections of the organ atrophy, which are replaced by adipose tissue. Official science does not explain this phenomenon. This is the biggest mystery in biology today. It is believed that lifting this veil will allow people to defy the aging process.

Structure of the thymus

We have already found out where the thymus is located. We will consider the structure of the thymus gland separately. This small-sized organ has a pinkish-gray color, soft consistency, and lobular structure. The two lobes of the thymus are completely fused or tightly adjacent to each other. The upper part of the organ is wide, and the lower part is narrower. The entire thymus gland is covered with a capsule of connective tissue, under which there are dividing T-lymphoblasts. The bridges that extend from it divide the thymus into lobules.

The blood supply to the lobular surface of the gland comes from the internal mammary artery, thymic branches of the aorta, branches of the thyroid arteries and the brachiocephalic trunk. Venous outflow of blood occurs through the internal mammary arteries and branches of the brachiocephalic veins. The growth of various blood cells occurs in the tissues of the thymus. The lobular structure of the organ contains the cortex and medulla. The first appears as a dark substance and is located on the periphery. Also, the cortex of the thymus gland contains:

hematopoietic cells of the lymphoid series, where T-lymphocytes mature;
hematopoietic macrophages, which contain dendritic cells, interdigitating cells, typical macrophages;
epithelial cells;
supporting cells that form the blood-thymus barrier, which form the tissue framework;
stellate cells – secrete hormones that regulate the development of T cells;
“nanny” cells in which lymphocytes develop.

In addition, the thymus secretes the following substances into the bloodstream:

thymic humoral factor;
insulin-like growth factor-1 (IGF-1);
thymopoietin;
thymosin;
Thymalin.

What is he responsible for?

Thymus forms all body systems in a child, and maintains good immunity in an adult. What is the thymus responsible for in the human body? The thymus gland performs three important functions: lymphopoietic, endocrine, and immunoregulatory. It produces T-lymphocytes, which are the main regulators of the immune system, that is, the thymus kills aggressive cells. In addition to this function, it filters the blood and monitors the outflow of lymph. If any malfunction occurs in the functioning of the organ, this leads to the formation of oncological and autoimmune pathologies.

In children

In a child, the formation of the thymus begins in the sixth week of pregnancy. The thymus gland in children under one year of age is responsible for the production of T-lymphocytes by the bone marrow, which protect the child’s body from bacteria, infections, and viruses. An enlarged thymus gland (hyperfunction) in a child is not the best way affects health because it leads to decreased immunity. Children with this diagnosis are susceptible to various allergic manifestations, viral and infectious diseases.

In adults

The thymus gland begins to involute as a person ages, so it is important to maintain its functions in a timely manner. Rejuvenation of the thymus is possible with a low-calorie diet, taking the drug Ghrelin and using other methods. The thymus gland in adults takes part in modeling two types of immunity: a cellular type response and a humoral response. The first forms the rejection of foreign elements, and the second manifests itself in the production of antibodies.

Hormones and functions

The main polypeptides produced by the thymus gland are thymalin, thymopoietin, and thymosin. They are proteins by nature. When lymphoid tissue develops, lymphocytes are able to take part in immunological processes. Thymus hormones and their functions have a regulatory effect on all physiological processes occurring in the human body:

reduce cardiac output and heart rate;
slow down the functioning of the central nervous system;
replenish energy reserves;
accelerate the breakdown of glucose;
increase the growth of cells and skeletal tissue due to enhanced protein synthesis;
improve the functioning of the pituitary gland and thyroid gland;
exchange vitamins, fats, carbohydrates, proteins, and minerals.

Hormones

Under the influence of thymosin, lymphocytes are formed in the thymus, then, with the help of thymopoietin, the blood cells partially change their structure to ensure maximum protection for the body. Timulin activates T-helper and T-killer cells, increases the intensity of phagocytosis, and accelerates regeneration processes. Thymus hormones are involved in the functioning of the adrenal glands and genital organs. Estrogens activate the production of polypeptides, while progesterone and androgens inhibit the process. A glucocorticoid produced by the adrenal cortex has a similar effect.

Functions

In the tissues of the thymus gland, blood cells proliferate, which enhances the body’s immune response. The resulting T-lymphocytes enter the lymph, then colonize the spleen and lymph nodes. Under stressors (hypothermia, starvation, severe injury, etc.), the functions of the thymus gland weaken due to the massive death of T-lymphocytes. After this, they undergo positive selection, then negative selection of lymphocytes, then regenerate. The functions of the thymus begin to decline by the age of 18, and fade almost completely by the age of 30.

Diseases of the thymus gland

As practice shows, diseases of the thymus gland are rare, but are always accompanied characteristic symptoms. The main manifestations include severe weakness, enlarged lymph nodes, and a decrease in the body’s protective functions. Under the influence of developing diseases of the thymus, lymphoid tissue grows, tumors form, which cause swelling of the extremities, compression of the trachea, borderline sympathetic trunk or vagus nerve. Malfunctions of the organ appear when the function decreases (hypofunction) or when the thymus functions increase (hyperfunction).

Magnification

If the ultrasound photo showed that the central organ of lymphopoiesis is enlarged, then the patient has thymic hyperfunction. Pathology leads to the formation of autoimmune diseases (lupus erythematosus, rheumatoid arthritis, scleroderma, myasthenia gravis). Thymus hyperplasia in infants manifests itself in the following symptoms:

decreased muscle tone;
frequent regurgitation;
weight problems;
heart rhythm disturbances;
pale skin;
profuse sweating;
enlarged adenoids, lymph nodes, tonsils.

Hypoplasia

The central organ of human lymphopoiesis may have congenital or primary aplasia (hypofunction), which is characterized by the absence or weak development of thymic parenchyma. Combined immunological deficiency is diagnosed as congenital DiGeorge disease, in which children experience heart defects, seizures, and abnormalities of the facial skeleton. Hypofunction or hypoplasia of the thymus gland can develop against the background of diabetes mellitus, viral diseases, or alcohol consumption by a woman during pregnancy.

Tumor

Thymomas (tumors of the thymus) occur at any age, but most often such pathologies affect people from 40 to 60 years of age. The cause of the disease is not established, but it is believed that a malignant tumor of the thymus gland arises from epithelial cells. It was noticed that this phenomenon occurs if a person suffered from chronic inflammation or viral infections or has been exposed to ionizing radiation. Depending on which cells are involved in the pathological process, the following types of thymus gland tumors are distinguished:

spindle cell;
granulomatous;
epidermoid;
lymphoepithelial.

Symptoms of thymus disease

When the functioning of the thymus changes, an adult feels breathing problems, heaviness in the eyelids, and muscle fatigue. The first signs of thymus disease are long-term recovery from the simplest infectious diseases. When cellular immunity is impaired, symptoms of a developing disease begin to appear, for example, multiple sclerosis, Basedow's disease. If there is any decrease in immunity and corresponding symptoms, you should immediately contact a doctor.

Thymus gland - how to check

If a child has frequent colds that turn into severe pathologies, there is a high predisposition to allergic processes, or the lymph nodes are enlarged, then a diagnosis of the thymus gland is needed. For this purpose, a sensitive ultrasound machine with high resolution is required, since the thymus is located near the pulmonary trunk and atrium, and is covered by the sternum.

If hyperplasia or aplasia is suspected after histological examination the doctor can refer you to computed tomography and examination by an endocrinologist. A tomograph will help identify the following pathologies of the thymus gland:

MEDAC syndrome;
DiGeorge syndrome;
myasthenia gravis;
thymoma;
T-cell lymphoma;
pre-T-lymphoblastic tumor;
neuroendocrine tumor.

Norms

In a newborn baby, the size of the thymus gland is on average 3 cm wide, 4 cm long and 2 cm thick. The normal average size of the thymus is presented in the table:

	Width(cm)	Length(cm)	Thickness(cm)
1-3 months
10 months - 1 year

Pathology of the thymus

When immunogenesis is disrupted, changes in the gland are observed, which are represented by diseases such as dysplasia, aplasia, accidental involution, atrophy, hyperplasia with lymphoid follicles, thymomegaly. Often, thymus pathology is associated either with an endocrine disorder or with the presence of an autoimmune or cancer. The most common cause of a decline in cellular immunity is age-related involution, in which there is a deficiency of melatonin in the pineal gland.

How to treat the thymus gland

As a rule, thymus pathologies are observed up to 6 years of age. Then they disappear or develop into more serious diseases. If a child has an enlarged thymus gland, then he should be observed by a phthisiatrician, immunologist, pediatrician, endocrinologist and otolaryngologist. Parents should monitor the prevention of respiratory diseases. If symptoms such as bradycardia, weakness and/or apathy are present, urgent medical attention is required. Treatment of the thymus gland in children and adults is carried out with medication or surgical method.

Drug treatment

When the immune system is weakened, biologically active substances must be administered to maintain the body. These are the so-called immunomodulators that thymus therapy offers. Treatment of the thymus gland in most cases is carried out on an outpatient basis and consists of 15-20 injections, which are administered into the gluteal muscle. The treatment regimen for thymus pathologies may vary, depending on clinical picture. In the presence of chronic diseases Therapy can be carried out for 2-3 months, 2 injections per week.

5 ml of thymus extract isolated from animal thymus gland peptides is injected intramuscularly or subcutaneously. This is a natural biological raw material without preservatives or additives. Improvements are noticeable after just 2 weeks general condition patient, since during the treatment the protective blood cells are activated. Thymus therapy has a long-term effect on the body after therapy. A repeat course can be carried out after 4-6 months.

Operation

Thymectomy or removal of the thymus is prescribed if the gland has a tumor (thymoma). The operation is performed under general anesthesia, which keeps the patient asleep throughout the operation. There are three methods of thymectomy:

Transsternal. An incision is made in the skin, after which the sternum bone is separated. The thymus is separated from the tissues and removed. The incision is closed with staples or stitches.
Transcervical. An incision is made along the lower part of the neck, after which the gland is removed.
Video-assisted surgery. Several small incisions are made in the superior mediastinum. A camera is inserted through one of them, displaying an image on a monitor in the operating room. During the operation, robotic manipulators are used that are inserted into the incisions.

Diet therapy

Diet therapy plays an important role in the treatment of thymus pathologies. You need to include foods rich in vitamin D in your diet: egg yolk, brewer's yeast, dairy products, fish fat. It is recommended to eat walnuts, beef, and liver. When developing a diet, doctors advise including in the diet:

parsley;
broccoli, cauliflower;
oranges, lemons;
sea buckthorn;
rosehip syrup or decoction.

Traditional treatment

To improve immunity, children's doctor Komarovsky advises warming up the thymus gland with the help of a special massage. If an adult has an unreduced gland, then he should maintain immunity for prevention by taking herbal teas with rose hips, black currants, raspberries, lingonberries. Thymus treatment folk remedies It is not recommended to carry out this procedure, since the pathology requires strict medical supervision.

Video

Attention! The information presented in the article is for informational purposes only. The materials of the article do not call for self-treatment. Only a qualified doctor can make a diagnosis and make recommendations for treatment based on the individual characteristics of a particular patient.

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