Thymus: the thymus gland in children. Thymus hypoplasia in children, symptoms and treatment

Date: 04.07.2020

Medical and social examination and disability in case of hypoplasia of the thymus gland

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

Epidemiology: the frequency in children has not been established, however, 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 a violation of intrauterine development of the fetus for a period of about 8 weeks under the influence of a teratogenic factor, the laying of organs developing during this period from the 3-4th pharyngeal clefts is disturbed: 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 revealed (partial monosomy on the 22nd chromosome - a deficiency of genetic material), combined with a symptom complex: congenital heart defects, “cleft palate” and other defects of the facial skeleton, hypoplasia of the thymus gland and hypocalcemia due to hypolalasia of the parathyroid glands.

The 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, aortic anomaly (its arch is turned to the right), sepsis. There may be a congenital heart disease with a corresponding clinical picture, an anomaly of the facial skull; in the future - a decrease in mental abilities, delayed sexual development.

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

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

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

The prognosis is relatively favorable - children are viable, do not get sick with viral and bacterial infections, but have chronic candidiasis of the skin and mucous membranes with damage and internal organs, they need constant treatment with antimycotic drugs; hypoparathyroidism also requires constant replacement therapy with vitamin D preparations; in addition, children are lagging behind in mental development.

Criteria for disability: mental retardation, requiring the education of the child in an auxiliary school, NK from 1-2st. and higher with congenital heart disease, recurrent candidiasis of the bronchi, esophagus and other internal organs with dysfunction.

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

Description:

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

Symptoms:

1. Di-George syndrome. Along with aplasia of the gland, aplasia of the parathyroid glands with manifestations is possible. In the pathogenesis, there is a deficiency of circulating T-lymphocytes, a sharp inhibition of the cellular immunity reaction, a relative increase in the number of B-lymphocytes and the preservation of the reaction of humoral immunity (normal level of immunoglobulins in the blood).
The characteristic signs of the disease are, starting from the neonatal period, recurrent infections of the respiratory and digestive systems. It is usually combined with abnormalities in the development of the aortic arch, lower jaw, earlobes, hypoplasia of the lymph nodes and underdevelopment of the thymus-dependent zones.

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

3. Louis-Bar syndrome - immunological insufficiency in -teleangiectasia, characterized by autosomal recessive inheritance of aplasia of the gland, proceeds with a decrease in lymphocytes in the thymus-dependent zones of the lymph nodes and spleen, demyelination in the cerebellum.
Multi-system complex disorders:
1) neurological (ataxia, lack of coordination, etc.);
2) vascular (telaniectasias of the skin and conjunctiva);
3) mental (mental retardation);
4) endocrine (dysfunction of the adrenal glands, sex glands). Recurrent sinus-pulmonary infections appear from early childhood.
Violation of cellular immunity is accompanied by damage to the T- and B-systems of immunity, IgA deficiency. In the blood serum, emorional cells (α- and β-fetoproteins) are exposed. Such patients more often develop malignant neoplasms (more often, lymphogranulomatosis).

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

Causes of occurrence:

This group of diseases is caused by genetic defects in 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 insufficiency due to a sharp decrease in the content of T- and B-lymphocytes and the absence of thymus bodies.
All these diseases are accompanied by recurrent inflammatory diseases, more often of pulmonary or intestinal localization, which are often the direct cause of the 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, combined into the immunodeficiency group. The most pronounced defects in the development of the thymus gland are found in the following syndromes.

Treatment:

1.
Dee George's Syndrome. Along with aplasia of the gland, aplasia of the parathyroid glands with manifestations of hypoparathyroidism is possible. In the pathogenesis, there is a deficiency of circulating T-lymphocytes, a sharp inhibition of the cellular immunity reaction, a relative increase in the number of B-lymphocytes and the preservation of the humoral immunity reaction (normal level of immunoglobulins in the blood, hypocalcemia).
The characteristic signs of the disease are convulsions starting from the neonatal period, recurrent infections of the respiratory and digestive systems. It is usually combined with abnormalities in the development of the aortic arch, lower jaw, earlobes, hypoplasia of the lymph nodes and underdevelopment of the thymus-dependent zones.

2. Neselof'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.
There is also a sharp decrease in the reactivity of T-lymphocytes (deficiency of the cellular immune system).
From the neonatal period, recurrent bronchitis, pneumonia, enterocolitis of viral or fungal etiology, herpetic eruptions, sepsis are noted.
Deficiency of T-lymphocytes and suppression of the cellular immune response are more pronounced than in Di-George syndrome. Patients die at an early age.

3. Louis-Bar syndrome- immunological insufficiency in ataxia-telangiectasia, characterized by autosomal recessive inheritance of aplasia of the gland, proceeds with a decrease in lymphocytes in the thymus-dependent zones of the lymph nodes and spleen, demyelination in the cerebellum.
Multi-system complex disorders:
1) neurological (ataxia, lack of coordination, etc.);
2) vascular (telaniectasias of the skin and conjunctiva);
3) mental (mental retardation);
4) endocrine (dysfunction of the adrenal glands, sex glands). Recurrent sinus-pulmonary infections appear from early childhood.
Violation of cellular immunity is accompanied by damage to the T- and B-systems of immunity, IgA deficiency. In the blood serum, emorional cells (α- and β-fetoproteins) are exposed. Such patients more often develop malignant neoplasms (more often lymphosarcomas, lymphogranulomatosis).

4.
"Swiss syndrome" - autosomal recessive severe combined immunological deficiency. Lymphopenic agammaglobulinemia, aplasia or hypoplasia of the thymus are combined with hypoplasia of the entire lymphoid tissue. Sharp hypoplasia of the thymus gland, hypoplasia of lymph nodes and lymphoid formations of the spleen, intestines.
From the neonatal period, recurrent fungal, viral and bacterial lesions of the skin and mucous membranes of the nasopharynx, respiratory tract, intestines. In these children, the thymus gland is difficult to identify.
Along with a sharp suppression of the reactions of cellular immunity, 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 on the basis of the clinic 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 the gland hormone in the blood.
For the purpose of early diagnosis of immunodeficiency states caused by aplasia of the thymus gland, the determination of the number of lymphocytes in the peripheral blood, serum immunoglobulins, isohemagglutinin titer is used.

Treatment.Reconstructive and replacement immunotherapy. For this purpose, transplantation of the thymus gland or bone marrow is carried out, the introduction of immunoglobulins, thymus hormones. The use of immunosuppressive corticosteroids is contraindicated.

- a genetic disease belonging to the group of primary immunodeficiencies and, along with weakening of immunity, characterized by numerous developmental defects. Symptoms of this condition are frequent bacterial infections with a tendency to severe course, congenital heart defects, facial abnormalities and other disorders. Diagnosis of Di Giorgi syndrome is based on an examination of the heart, thyroid and parathyroid glands, the study of the immunological status and data from molecular genetic analyzes. Treatment is only symptomatic, including surgical correction of heart defects and facial anomalies, replacement immunological therapy, and the fight against bacterial and fungal infections.

General information

DiGeorge's 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 the 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 to determine that the disorders in this disease go far beyond the scope of primary immunodeficiency. This gave rise to the emergence of another name for the DiGeorge syndrome. Taking into account the most frequently affected organs (palate, heart, face), some experts refer to this pathology as velocardiofacial syndrome. A number of modern researchers distinguish between these two conditions and believe that the "true" VCFS is not accompanied by pronounced immunological disorders. The incidence of DiGeorge's syndrome is 1: 3,000-20,000 - such a significant discrepancy in the data is due to the fact that a reliable and clear border between this disease and VCFS has not yet been established. Therefore, one and the same patient, according to various experts, may have either primary immunodeficiency, accompanied by concomitant disorders, or more numerous malformations against the background of a decrease in immunity.

Causes of Di Giorgi syndrome

The genetic nature of DiGeorge syndrome lies in the damage to the central part of the long arm of chromosome 22, where genes encoding a number of important transcription factors are believed to be located. We managed to identify one of these genes - TBX1; the product of its expression is a protein called T-box. It belongs to the family of proteins that control the processes of embryogenesis. Proof of the relationship between DiGeorge's syndrome and TBX1 is the fact that a small percentage of patients do not have pronounced damage to chromosome 22, only mutations in this gene are present. There are also suggestions about the role of deletions of other chromosomes in the development of this disease. Thus, manifestations similar to Di Giorgi's 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 is in the order of 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 pattern of inheritance. The pathogenesis of Di Giorgi syndrome is reduced to a violation of the formation of special embryonic formations - pharyngeal sacs (mainly the 3rd and 4th), which are the precursors of a number of tissues and organs. Mainly, they are responsible for the formation of the palate, parathyroid glands, thymus, vessels of the mediastinum and heart, therefore, with DiGeorge syndrome, malformations of these organs occur.

Symptoms of DiGeorge Syndrome

Many manifestations of DiGeorge's syndrome are determined immediately after the birth of a child; individual malformations (for example, heart) can be detected even earlier - on preventive ultrasound examinations. Most often, the first to be found are anomalies in the development of the face - cleft palate, sometimes in combination with a "cleft lip", prognosis of the lower jaw. Often, babies with DiGeorge syndrome have a small mouth, a small nose with a widened bridge of the nose, and deformed or underdeveloped cartilage of the ears. With a relatively mild course of the disease, all of the above symptoms can be rather weak, even the cleavage of the hard palate can occur only in the back of it and be detected only with a thorough examination by an otolaryngologist.

In the first months of the life of a patient with Di Giorgi syndrome, the manifestations of congenital heart defects come to the fore - it can be either Fallot's tetrad or individual disorders: a defect of the interventricular septum, non-closure of the ductus arteriosus and a number of others. They are accompanied by cyanosis, cardiovascular failure, and in the absence of qualified medical care (including surgical) can lead to early death of patients. Another common disorder in children with DiGeorge syndrome is considered to be seizures and tetany, caused by hypoplasia of the parathyroid glands and subsequent hypocalcemia.

The next most important manifestation of Di Giorgi's syndrome, which distinguishes it from other types of VCFS, is a pronounced primary immunodeficiency. It develops due to aplasia or underdevelopment of the thymus and therefore more affects cellular immunity. However, due to the close relationships 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 of varying degrees, sometimes seizures of neurological origin can be observed.

Diagnosing Di Giorgi syndrome

To determine Di Giorgi syndrome, the method of physical general examination, cardiological studies (echocardiography, electrocardiogram), ultrasound of the thyroid gland and thymus, immunological tests are used. An auxiliary role is played by conducting general and biochemical blood tests, studying the patient's anamnesis, and genetic studies. When examining patients with Di Giorgi syndrome, disorders characteristic of the disease can be determined - cleavage of the hard palate, anomalies in the structure of the face, pathology of the ENT organs. The history, as a rule, reveals frequent episodes of viral and fungal infections, taking a severe course, convulsions caused by hypocalcemia, and extensive carious lesions of the teeth are often found.

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

Treatment for Di Giorgi syndrome

Currently, there is no specific treatment for DiGeorge's syndrome; only palliative and symptomatic techniques are used. It is very important to identify congenital heart defects as early as possible and, if necessary, to perform their surgical correction, since it is cardiovascular disorders that are the most common cause of neonatal death in this disease. Convulsive seizures caused by hypocalcemia are a significant danger, which requires timely correction of the electrolyte balance of blood plasma. The help of surgeons with DiGeorge syndrome may also be required to correct malformations of the face and palate.

Due to pronounced immunodeficiency, any signs of a bacterial, viral or fungal infection are a reason for the urgent use of the appropriate drugs (antibiotics, antiviral and fungicidal agents). To improve the immune status of a patient with Di Giorgi syndrome, a replacement infusion of immunoglobulins obtained from donor plasma can be performed. In some cases, a thymus gland transplant was carried out, which stimulated the formation of its own T-lymphocytes - this contributed to an improvement in the quality of life of patients.

Prediction and prevention of Di Giorgi syndrome

The prognosis of DiGeorge syndrome is assessed by most researchers as uncertain, since this disease is characterized by significant variability in 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's syndrome require rather intensive palliative care, 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 the correct pedagogical and psychological correction, the manifestations of developmental delay can be leveled. Due to the frequent spontaneous nature of mutations, prevention of DiGeorge syndrome has not been developed.

The child, being 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 throughout life.

Embryology (development of the thymus in the prenatal period)

The thymus in the fetus is laid already at 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 delivery, the thymus in newborns is fully formed and functionally active.

Anatomy

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

At birth, its weight is 15-45 grams. The size of the thymus in children is normally 4-5 centimeters long, 3-4 centimeters wide. An intact gland in a healthy child cannot be felt.

Age features

The thymus is of key importance for the formation of immunity, its growth continues until puberty. By this time, the mass reaches 40 grams. After puberty, the 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 the normal development of the immune system. Thanks to them, the cells of the immune system learn to recognize harmful microorganisms and start mechanisms to eliminate them.

Thymus dysfunction

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

Congenital pathology of the thymus gland development

With anomalies of the genetic code, the thymus anlage may be disrupted even in the early embryonic period. This pathology is always combined with impaired development of other organs. There are several genetic abnormalities in which the changes are fatal to the immune system. The body loses its ability to fight infection and is not viable.

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

Also, genetic malformations include congenital cysts, hyperplasia of the thymus gland 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 decreased.

Thymus hypoplasia

In the absence of developmental anomalies, thymic hypoplasia in newborns is extremely rare. 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.

Thymus hyperplasia

Distinguish between endogenous hyperplasia, when an increase in the thymus is associated with the performance of its functions (primary) and exogenous, then the growth is caused by pathological processes in other organs and tissues.

Why does the baby have an enlarged thymus gland?

Causes of primary (endogenous) thymomegaly:

Causes of exogenous thymomegaly:

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

Hyperplasia symptoms

On external examination, an enlarged thymus gland in infants is visible when screaming, when increased intrathoracic pressure pushes the thymus above the handle of the sternum.

An enlarged 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 large enough organ for such a baby and may simply not fit into the space allotted to it.

An enlargement of the thymus gland in infants with transient jaundice of newborns is also not a pathology.

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

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

Compression Syndrome

An enlarged thymus in children causes symptoms of compression of nearby organs. With pressure on the trachea, shortness of breath, breathing noises, dry cough appears. Compressing the lumen of the vessels, the thymus disrupts the flow and outflow of blood, pallor of the skin and swelling of the cervical veins are noted.

If an enlarged thymus in a child causes compression of the vagus nerve, which innervates the heart and digestive tract, a persistent slowing of the heart rate, swallowing disorders, belching, 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 habitual diseases proceed differently. Any colds can begin without a rise in temperature, with a sharp jump on the third or fourth day. Such children are sick longer than their peers, and the severity of the disease is higher. Often, the infection spreads to the lower 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. Lymph nodes are enlarged, in the general blood test, the ratio of immune cells with a predominance of lymphocytes is disturbed. Any external irritant causes an overprotective reaction in the form of allergic reactions. A severe reaction to vaccination may occur.

Disruption of the endocrine system

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

Why is an increase in the thymus gland in a child dangerous?

An enlargement of the thymus gland in infants, when the trigeminal is compressed, violates the peristalsis of the esophagus and intestines. The baby may have difficulty eating and belching air after feeding. When the trachea is compressed, more effort is required for inhalation, and the increased pressure causes rupture of the alveoli in the lungs with the development of atelectasis.

Diagnostics

With symptoms of an enlarged thymus gland in a child, it is necessary to consult several specialists - an immunologist, an endocrinologist and a pediatrician. It often turns out that an increase in the thymus gland in infants is not associated with pathology, but is due to individual anatomical characteristics. Often parents panic that the thymus gland is enlarged in a newborn, because when crying, it often protrudes above the handle of the sternum. There is also no need to be afraid of inflammation of the thymus gland in infants, a huge number of immune cells in it does not leave a single chance for the development of infection.

To confirm the diagnosis, you must undergo a thorough examination, including:

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

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

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

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

Additional tests for hormone levels may be required.

Congenital absence of the thymus gland can be the only malformation or be combined with other malformations, in particular with the congenital absence of the parathyroid glands, which is described in the Anglo-American literature as Digeorge syndrome (Dodson et al., 1969; Kirkpatrick, Digeorgie, 1969; Lobdell , 1969). Although cases of detection of the complete absence of the thymus gland in children who died in early infancy have been known for a long time (Bischoff, 1842; Friedleben, 1858), the death of such children until recently was not associated with the absence of a thymus in them.

With hypoplasia, the thymus gland lags behind in its development from the very beginning and at the birth of a child it turns out to be small, not exceeding in weight often 1-2 g. Microscopically, its lobules in this case also turn out to be reduced in size, and due to the almost complete absence of lymphocytes, their division into the cortical and medullary layers are not observed. Hassal's little bodies are usually absent in them.

Changes that characterize the hypoplasia of the thymus gland have been studied only recently in connection with the description by Glanzmann and Riniker in 1950 of a peculiar disease of infants, which they called essential lymphocytophthisis. Due to the fact that this disease often has a familial nature, it was later described under the names of familial (family) lymphopenia (Tobbler, Cottier, 1958) or hereditary lymphoplasmacytic dysgenesis (Hitzig, Willi, 1961).

The disease manifests itself as persistent diarrhea that does not respond to treatment, leading to exhaustion and death in children. In this case, there is a sharp lymphopenia and hypogammaglobulinemia in the blood, and when the deceased is opened, a sharp decrease in the size of the spleen and lymph nodes with an almost complete absence of lymphocytes is found. Initially, proper attention was not paid to the condition of the thymus gland, although already at the first description of the disease, Glanzmann and Riniker (1950) mention that in one of the two children they examined, the thymus gland was small and edematous. However, later changes in the thymus gland in this disease were studied in more detail (Cottier, 1958; Blackburn, Gordon, 1967; Thompson, 1967; Berry, 1968; Berry, Thompson, 1968), which gave reason to consider the entire disease as a manifestation of primary immunological deficiency caused by hypoplasia or aplasia of the thymus gland (Good, Martinez, Gabrielsen, 1964; Sell, 1968).

With aplasia or hypoplasia of the thymus gland, the normal development of all lymphoid tissue is disrupted, and therefore the body remains incapable of immunological reactions. As a consequence, the normal intestinal flora begins to have a pathogenic effect, causing its damage and thus diarrhea, leading to: exhaustion. Often, a secondary infection in the form of candidiasis (Glanzmann, Riniker, 1950; Thompson, 1967), pneumocystis pneumonia (Becroft, Douglas, 1968; Berg, Johansson, 1967), etc., joins.

P. With homotransplantation of skin and other tissues, such patients do not have a rejection reaction (Rosen, Gitlin, Janeway, 1962; Dooren, Bekkum, Cleton, 1968). Thus, the whole picture of the disease fully corresponds to the so-called vasting syndrome that develops in animals after the removal of the thymus gland from them, produced immediately after birth (Miller, 1961; Good et al., 1962; Metcalf, 1966; Hess, 1968). In some cases, in children with hypoplasia of the thymus gland, shortly before death, the phenomena of aplastic anemia were also noted (Glanzmann and Riniker, 1950; Thompson, 1967; Dooren et al., 1968) or granulo- and thrombocytopenia (Lamvik, Moe, 1969).

Most children with thymus aplasia or hypoplasia die within the first 6 months of life. However, in some cases, a longer course of the disease is observed - up to 1 year 7 months (Hitzig, Biro et al., 1958) and more. A more detailed immunological examination of such patients revealed that some of them retain their ability to some extent to some immunological (allergic) reactions (Hitzig, Biro et al., 1958), as well as the preservation of certain fractions of immunoglobulins (Becroft, Douglas, 1968; Berg, Johansson, 1967), which allows distinguishing a number of clinical varieties of this disease (Sell, 1968). Obviously, this depends on the degree of hypoplasia (alimphoplasia) of the thymus gland, which can be expressed in different ways. With a relatively small degree of hypoplasia, due to the partial preservation of the body's ability to immune reactions, the disease can take a protracted course. An example of this, apparently, is the observation by Grote and Fischer-Wasels (1929) of “total alimphocytosis” in a 39-year-old man who died of exhaustion. Autopsy revealed atrophy of the spleen (18.0) and other lymphoid organs. The small intestine had dark-pigmented scars, and the lymph nodes of the mesentery contained foci of “cheesy necrosis”. The thymus gland, unfortunately, was not examined. In the same respect, one of our observations, which is presented below, is of undoubted interest.

Male E., 55 years old. A carpenter. Married, had no children. From early childhood, he often had diarrhea, and therefore strictly followed a diet throughout his life. Smoked a little. I rarely drank alcohol. Over the past 3 years, he was comprehensively examined in many hospitals in Leningrad, but the diagnosis remained unclear. In connection with the growing exhaustion and suspicion of a tumor in the abdominal cavity on 17 / V 1968, he was admitted to the clinic of the faculty surgery of the Military Medical Academy, where on 31 / V he underwent a diagnostic laparotomy, during which no tumor was found. After the operation, the patient's condition began to deteriorate rapidly. Blood test 17 / VI 1968: er. 3700000, Hb 13.2 g% ", color, pok. 1.0, l. 13500, of which pp. 45%, p. 37%, y. 7%, lymph. 11%. ROE 10 mm / h. In previous blood tests, the number of lymphocytes fluctuated between 7-14%. Repeated bacteriological examinations of feces did not reveal the pathogenic flora. The patient died on 17 / VI 1968 with symptoms of increasing exhaustion and associated pneumonia. with extreme exhaustion and severe vitamin deficiency, condition after diagnostic laparotomy, ascites, sacral pressure ulcers, bilateral pneumonia and pulmonary edema.

At autopsy (dissector T, V. Polozova), a sharp exhaustion was noted. Body weight 40 kg with a height of 166 cm. Fresh postoperative scar along the midline of the abdomen. In the region of the sacrum, there is a pressure sore with a dark gray bottom 5x4 cm. The left pleural cavity is free. The right lung in the upper sections is fused with the parietal pleura. In the area of \u200b\u200bits apex there are several dense scars and a small encapsulated calcified focus. In the lower part of the left lung, there are multiple gray-red airless foci of compaction measuring 1-1.5 cm in diameter. The inferior lobe branch of the right pulmonary artery is thrombosed. In the lower lobe of the right lung under the pleura, a black-red airless focus of irregular wedge-shaped shape with dimensions of 5X5X4 cm is determined. Bronchopulmonary lymph nodes are not enlarged, black-gray, with small gray scars. There is a small amount of clear yellowish liquid in the abdominal cavity. On the mucous membrane of the small intestine, transverse superficial ulcers up to 4X2 cm in size with a dark gray pigmented bottom are visible. Two of the same type of ulcer are found in the mucous membrane of the cecum. Peyer's patches and lymphatic follicles are undetectable. The lymph nodes of the mesentery are up to 1 cm in diameter, in many of them yellowish-gray areas are visible on the cut. The spleen weighs 30.0 with a thickened capsule, dark red on the cut. The tonsils are small. Inguinal and axillary lymph nodes up to 1 cm in size, gray on the cut. Heart weighing 250.0, its muscle is brownish-red. The liver, weighing 1500.0, is brownish brown in section. There are multiple small hemorrhages under the pleura of the left lung and in the folds of the gastric mucosa. Other organs and tissues were somewhat reduced in size, otherwise unchanged. The thymus gland is not found in the fiber of the anterior mediastinum.

Results of histological examination.

On the basis of the results of autopsy and histological examination, the diagnosis was made of chronic nonspecific ulcerative enterocolitis, leading to exhaustion and complicated by pneumonia. The development of the disease in this case can be associated with the defective development of the thymus gland and the entire lymphatic system as a whole.

Figure: 10. Alimphoplasia of the thymus gland.

a-axillary lymph node with sclerosis of the central part and preservation of the lymphoid tissue in the form of a narrow layer along the periphery (magnification 60X) "" b-one of the lobules of the extracellular gland with almost complete absence of lymphocytes (magnification 120X); . 400X) ..

Recently, transplantation of the thymus gland from human fetuses has been used to treat such patients with some success (August et al., 1968; Clevelend et al., 1968; Dooren et al., 1968; Good et al., 1969; Koning et al., 1968). others, 1969). Moreover, after transplantation, there is a rapid increase in the number of lymphocytes in the blood, the appearance of immunoglobulins in it. Children develop the ability for cellular and humoral immune reactions, including the reaction of rejection of tissue homografts (August et al., 1968; Koning "et al., 1969). When examining a biopsy lymph node in one of these patients after thymus transplantation gland, the presence of well-defined lymphatic follicles with centers of reproduction was found in it (Clevelend, Fogel, Brown, Kay, 1968).

The child's immune system begins to form long before he is born. In the sixth week of pregnancy, the fetus already has thymus - the central organ of human immunogenesis. Due to the fact that it resembles a fork in shape, the thymus is also called thymus... The younger the child and the more often he gets sick, the more actively the thymus works, and, accordingly, the more intensively it grows. Growth of the thymus gland slows down when a child turns 12. His immune system by this time is already considered to be formed. In adults, only a reminder of the thymus gland remains in the form of a small lump of adipose tissue. And by old age, a person's thymus almost dissolves.

The thymus gland in children - what it is, what it is responsible for and where it is located

The size of the thymus in children: the norm (photo)

The thymus gland of a healthy child should be no more KTTI 0.33 (CTTI - cardiotimycothoracic index - this is how the thymus is measured). If this index is higher, the thymomegaly (increase) , which can be of three degrees:

I. KTTI 0.33-0.37;

II. KTTI 0.37-0.42;

III. KTTI is more than 0.42.

Among the factors that have a direct effect on the increase in the thymus are pathologies of fetal development during time, gene abnormalities, late pregnancy, infectious diseases suffered by the expectant mother.

Ultrasound

Theoretically, the size of the thymus can be determined using X-ray and ultrasound examination of the thymus. For diagnosis in children, X-rays are used in extreme cases, because of the risk of exposure to the child. Usually, an ultrasound scan is sufficient to obtain the desired results.

Immunity and thymus: Komarovsky (video)

Hyperplasia and hypoplasia of the thymus

Among diseases of the thymus gland, in addition to thymomegaly, in children, one can also find hyperplasia and hypoplasia of the thymus. Thymus hyperplasia - this is the proliferation of its tissues with the formation of neoplasms. A hypoplasia - This is a violation of the function of T-lymphocytes due to congenital developmental pathologies. These diseases are recorded much less often than thymomegaly, but they require more serious medical intervention.

Thymomegaly: symptoms for seeking medical attention

What can be the reason for going to the doctor? What symptoms can indicate an enlarged thymus gland in a child?

The baby is rapidly gaining (or losing) weight.
After feeding, the baby often spits up.
The child begins to cough when lying down (false croup).
He often suffers from colds.
When a baby cries, his skin turns blue-purple.
There is a venous mesh on the chest, and the skin is covered with a so-called marble pattern.
With an enlarged thymus, the tonsils, adenoids or lymph nodes can also increase in size.
Often children have arrhythmias and decreased muscle tone.

Treatment of an enlarged gland

Often, when the thymus is enlarged, drug treatment is not required. Exceptions are rare complex cases of thymomegaly.

But you should make every effort for. Doctors recommend:

Vitamin intake and a protein-rich diet.
Hardening and sports.
Compliance with the daily routine.
Vaccinations for thymomegaly can be done, only first you need to give the child an antihistamine prescribed by a pediatrician.
Contact with ARVI patients should be avoided.
Eliminate the use of allergenic foods by the baby.

And a very important point. If your child has an enlarged thymus gland, he should not take acetylsalicylic acid as an antipyretic. Aspirin can accelerate the growth of thymus cells.

Forecasts

The thymus gland works and grows intensively in the first years of a child's life. Then she gets comparatively little work. Accordingly, the rate of its growth decreases markedly. Therefore, most often, an enlarged thymus does not require serious treatment, and up to two years is considered the norm. By the age of 5-6, usually, the thymus gland stops growing. But this does not mean that she should be left without proper supervision. After all, the formation of your child's immunity and his health in the future depends on it.

In the body of children there is a unique and not yet fully understood organ - the thymus, or thymus, gland. It got its name because it really resembles a fork in shape, and is located in the area where the goiter occurs. Its medical name is thymus from the Greek thymus - soul, life force. Apparently, ancient healers already had an idea of \u200b\u200bits role in the body.

What is the thymus gland in children? It is a mixed organ that belongs to both the immune and endocrine systems. Its lymphatic tissue promotes the maturation of the body's main protective cells - T-lymphocytes. The cells of the glandular epithelium produce more than 20 hormones into the blood (thymine, thymosin, thymopoietin, T-activin, and others).

These hormones stimulate various functions of the body: the state of the immune, motor, neuropsychic system, body growth, general well-being, and so on. Therefore, the thymus is called "the point of happiness", and it is believed that it is precisely due to such functions of this gland that children are more mobile, cheerful and cheerful than adults. It is also believed that it is with the disappearance of the thymus that the aging process begins.

Important! If the child is lethargic, tired, inactive, often ill - this may indicate a lack of function of the thymus gland.

What are the normal sizes and location of the gland in children?

The thymus gland is formed even in the fetus at the 7th week of pregnancy, it is actively functioning for the first 5 years of life, after which its gradual atrophy begins. By the age of 25, it completely ceases to function, and by the age of 40 in most people, its tissue is reduced, disappears.

The thymus gland is located behind the sternum at the level of the trachea bifurcation (dividing it into the right and left bronchi), consists of 2 lobes located to the right and left of the trachea. Its size in newborns is 4 × 5 cm, thickness - 5-6 mm, weight 15-20 g, such parameters have the thymus gland in children under one year old.

The thymus normally in children grows in parallel with the growth of the body until the onset of puberty (11-14 years), reaching by this time the size of 8 × 16 cm and weight up to 30-35 g, after which the growth of the organ stops and its reverse development begins. In general, the size of the thymus gland in children depends on their height, and its mass is 1/250 of the body weight.

When does the thymus enlarge in children and how does it manifest?

Parents often have to deal with an increase (hyperplasia) of the thymus gland in a child. Most often this is observed in the first 3 years of life, the causes of hyperplasia of the thymus in children can be:

Lack of amino acids (protein) in the child's diet.
Lack of vitamins.
Diathesis of lymphoid tissue (proliferation of lymph nodes).
Frequent infections.
Allergy.
Hereditary factor.

In infants, the thymus can be enlarged from the prenatal period as a result of adverse effects: infectious diseases of the mother, pathological course of pregnancy.

Thymomegaly (enlargement of the gland) in infants is manifested by an increase in the weight of the child, pallor of the skin, increased sweating, coughing fits, and an increase in body temperature. The child's condition worsens in the supine position - coughing intensifies, cyanosis (cyanosis) of the nose appears, swallowing is difficult, food regurgitation appears. A characteristic is a bluish-purple skin tone when the baby is crying.

Important! An enlarged thymus in infants can resemble a cold, which is rare during this period. Therefore, examination of the thymus in such cases is mandatory.

Why does hypoplasia of the gland develop, what are its symptoms?

Much less common is hypoplasia of the thymus gland in children, that is, its decrease. As a rule, this is a congenital pathology combined with other congenital anomalies:

underdevelopment of the chest;
malformations of the mediastinal organs - heart, respiratory tract;
with Di Giorgi syndrome - an anomaly in the development of the parathyroid glands and thymus;
with Down's syndrome - a chromosomal disorder.

This is a very serious pathology, which manifests itself as a child's lagging behind in height and weight, a decrease in all life processes, the development of convulsive syndrome, intestinal dysbiosis, and the addition of various infections. The mortality rate in such children is very high, if intensive treatment is not started in a timely manner.

What diagnostic methods are used?

The modern method of studying the thymus gland in children is ultrasound scanning. It does not involve radiation and can be safely performed as many times as needed, for example, to monitor treatment. New Doppler technologies for ultrasound of the thymus gland in children provide the most accurate data on the size, location and structure of the gland.

Laboratory research is mandatory: clinical blood test, immunological tests, determination of the amount of protein and trace elements (electrolytes). With congenital pathology, genetic studies are carried out.

How is the gland treated in children?

Treatment of the thymus gland in children depends on the degree of change in its size, the state of immunity, the general condition and age of the child, the presence of concomitant diseases. In general, the treatment algorithm is as follows:

Normalization of the diet (a sufficient amount of protein and vitamins).
A daily regimen with sufficient physical activity and good rest.
Hardening, sports, physical education.
Taking natural immunostimulants.
Mandatory intake of antihistamines during a cold, with the development of allergic reactions.

Important! Aspirin is contraindicated in children with thymic hyperplasia; it enhances the proliferation of the gland and the development of aspirin asthma.

In severe cases of thymic hyperplasia in children, hormone therapy is prescribed (Prednisolone, Hydrocortisone, Cortef).

If the thymus gland is excessively enlarged in a child, according to indications, an operation is performed - resection of the gland (thymectomy). After removal of the thymus, the child is under dispensary supervision for several years.

A child with thymus hyperplasia should be carefully protected from colds and infections, and should be avoided in groups and crowded places. Routine vaccination is carried out as usual, while taking into account the condition of the child so that he does not have colds, allergies, diathesis and other diseases at this time.

The thymus gland plays an important role in maintaining the health of young children. Therefore, children who are often ill need to undergo her examination and, if necessary, treatment.

Thymic hypoplasia is a congenital underdevelopment of an organ. Due to the reduced number of T-lymphocytes and thymus hormones, children can die in the first days of life or up to 2 years. About what is thymus hypoplasia, the role of the organ in the life of children, the diagnosis of deviations from the norm, as well as treatment, read further in our article.

Read in this article

Role of the thymus in children

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

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

body growth;
puberty;
metabolism;
muscle contractions;
the formation of blood cells in the bone marrow;
regulation of the pituitary gland, thyroid gland;
maintaining normal levels of 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 thymus (aplasia) can be the cause of the death of a child in the first days of life or stillbirth. Surviving infants have severe, persistent diarrhea that is difficult to treat. They lead to progressive exhaustion. It is especially dangerous to attach any, even the most insignificant infection.

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

Most children with a significantly reduced thymus gland do not survive until 2 years of age 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 thymic malfunction are:

frequent viral and bacterial infections;
tendency to recurrent fungal infections of the skin, mucous membranes of the mouth and genitals, lungs, intestines;
periodically exacerbated herpes;
severe course of "childhood" diseases (measles, rubella, mumps);
severe reaction to vaccinations (temperature, convulsive syndrome);
the presence of tumor processes.

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

Diagnosis of the disease

Thymus hypoplasia is suspected when combined:

frequent viral diseases;
stubborn thrush;
difficult to treat diarrhea;
pustular skin lesions;
severe course of infectious diseases with drug resistance.

For examination of the thymus in children, ultrasound is used, and in adults, computed, magnetic resonance imaging is more informative.

What to do if the thymus gland is reduced

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

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

In less difficult cases, symptomatic therapy of infections with antibiotics, antiviral and antifungal agents is carried out. To correct the insufficient function of the thymus, T-activin, Timalin, Timogen, and intravenous immunoglobulin are injected.

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

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

Useful video

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

The role of the thymus in the body

The thymus gland, or thymus, 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 puberty, it increases to 37 g. The length of the thymus in infancy is about 5 cm, in adolescence - 16 cm. By old age, iron decreases and turns into adipose tissue weighing 6 g. Gray-pink color changes to a yellowish tint ...

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 against foreign antigens. Natural defenders protect the child from infection and viral and bacterial damage.

In the case of an increase, the thymus does its job worse, which makes the immune system weaker. As a result, the baby becomes more susceptible to pathogens of various pathologies, and his visits to the pediatrician become more frequent.

The reasons for the development of hyperplasia

Thymomegaly - another definition of an overgrown thymus, is transmitted genetically. In infants, it develops for several reasons:

late pregnancy;
problems with bearing a fetus;
infectious diseases of a woman while waiting for a baby.

The pathological proliferation of the thymus gland in older children is facilitated by a 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 in thymomegaly is lymphatic diathesis. If the lymph tissue is prone to abnormal growth, it worsens the condition of the child and affects the internal organs. The thymus gland suffers, and its changes are discovered by chance when studying the responses of the x-ray of the sternum organs.

External signs of thymomegaly

To understand that the baby's thymus gland is enlarged, some characteristic signs help. In newborns, the problem is recognized by overweight and fluctuations in body weight up and down.

They happen pretty quickly. Mothers may notice increased sweating of the crumbs, frequent regurgitation and coughing, for no reason pestering the child in the supine position.

On the part of the skin, hyperplasia is manifested by pallor or cyanosis. The integument acquires a bluish tint with crying or tension. A specific marble pattern also appears on the tissues and a venous mesh appears on the chest. Muscle tone weakens. The proliferation of the thymus gland is accompanied by an increase in lymph nodes, tonsils, adenoids. The normal rhythm of the heart is lost.

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

How is thymus abnormality diagnosed?

An informative method for assessing the condition of the thymus gland is ultrasound. This type of examination does not require preliminary preparation. The specialist processes the baby's sternum with a conductive gel and guides the device's sensor over the area. Babies under the age of two years are examined in a sitting or lying position. For older children, sonography is done while standing.

The mother must inform the diagnostician of the exact weight of the baby. Normally, the test organ has a mass equal to 0.3% of body weight. Exceeding this parameter indicates thymomegaly. Hyperplasia proceeds in three degrees. They are set according to CTTI - cardiotimycothoracic index. In a child, the diagnosis is carried out along the following boundaries of the CTTI:

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 drugs and give parents recommendations regarding the daily regimen and nutrition of the child. The restoration of the organ is faster with a sufficient number of hours of sleep and the organization of long walks in the fresh air.

Conservative and urgent events

The course of conservative treatment for thymomegaly is based on corticosteroids and a special diet. The composition of the products should be dominated by vitamin C. The substance is found in oranges and lemons, bell peppers, cauliflower and broccoli. A child's body can get 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 to surgery. After the thymectomy, the patient is monitored continuously. If the hyperplasia proceeds without vivid clinical symptoms, neither drug nor surgical therapy is performed. The kid only needs dynamic observation.

Children's quality of life

How the baby's life will proceed with the proliferation of the thymus gland, says Dr. Komarovsky. If the baby is diagnosed with stage I thymomegaly, there is still no serious danger. This is just a hint that the child needs regular health improvement.

With the development of a deviation up to grade II, the child can attend children's groups and social events. You can still not think about the treatment of hyperplasia, but the timely passage of 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. Shattered immunity does not cope with the body's defense, there are disruptions in the work of the adrenal glands. If a specialist detects thymus-adrenal insufficiency in a baby, the baby needs to be urgently sent to the hospital. In the absence of positive dynamics from drug correction of the thymus gland, the doctor has the right to insist on surgery.

Do not consider mild thymomegaly as a minor problem. Be sure to examine the thymus of a baby up to one year old and make an immunogram to clarify the diagnosis. After 6 years of age, the child needs a competent correction of the immune background. Improve the baby's condition as soon as possible, because neglected cases are fatal.

Page 5 of 17

Congenital malformations of the thymus should be distinguished from atrophic (involutive) changes in the thymus gland, manifested either by its complete absence - aplasia, agenesis, or underdevelopment with impaired formation of lymphocytes in it - hypoplasia, alimphoplasia.
Congenital absence of the thymus gland may be the only malformation or be combined with other malformations, in particular with the congenital absence of the parathyroid glands, which is described in the Anglo-American literature as Digeorge syndrome (Dodson et al., 1969; Kirkpatrick, Digeorgie, 1969; Lobdell, 1969 ). Although cases of detection of the complete absence of the thymus gland in children who died in early infancy have been known for a long time (Bischoff, 1842; Friedleben, 1858), the death of such children until recently was not associated with the absence of a thymus in them.
With hypoplasia, the thymus gland lags behind in its development from the very beginning and at the birth of a child it turns out to be small, not exceeding in weight often 1-2 g. Microscopically, its lobules in this case also turn out to be reduced in size, and due to the almost complete absence of lymphocytes, their division into the cortical and medullary layers are not observed. Hassal's little bodies are usually absent in them.
The changes characterizing the hypoplasia of the thymus gland have been studied only recently in connection with the description by Glanzmann and Riniker in 1950 of a peculiar disease of young infants, which they called essential lymphocytophthysis. Due to the fact that this disease often has a familial nature, it was later described also under the names of familial (family) lymphopenia (Tobbler, Cottier, 1958) or hereditary lymphoplasmacytic dysgenesis (Hitzig, Willi, 1961).
The disease manifests itself as persistent diarrhea that does not respond to treatment, leading to exhaustion and death in children. In this case, there is a sharp lymphopenia and hypogammaglobulinemia in the blood, and when the deceased is opened, a sharp decrease in the size of the spleen and lymph nodes with an almost complete absence of lymphocytes is found. Initially, proper attention was not paid to the condition of the thymus gland, although already at the first description of the disease, Glanzmann and Riniker (1950) mention that in one of the two children they examined, the thymus gland was small and edematous. However, later changes in the thymus gland in this disease were studied in more detail (Cottier, 1958; Blackburn, Gordon, 1967; Thompson, 1967; Berry, 1968; Berry, Thompson, 1968), which gave reason to consider the entire disease as a manifestation of primary immunological deficiency caused by hypoplasia or aplasia of the thymus gland (Good, Martinez, Gabrielsen, 1964; Sell, 1968).
With aplasia or hypoplasia of the thymus gland, the normal development of all lymphoid tissue is disrupted, and therefore the body remains incapable of immunological reactions. As a consequence, the normal intestinal flora begins to have a pathogenic effect, causing its damage and thus diarrhea, leading to: exhaustion. A secondary infection often joins in the form of candidiasis (Glanzmann, Riniker, 1950; Thompson, 1967), pneumocystic pneumonia (Becroft, Douglas, 1968; Berg, Johansson, 1967), etc. When homotransplanting skin and other tissues in such patients there is no rejection reaction (Rosen, Gitlin, Janeway, 1962; Dooren, Bekkum, Cleton, 1968). Thus, the whole picture of the disease fully corresponds to the so-called vasting syndrome that develops in animals after the removal of the thymus gland from them, produced immediately after birth (Miller, 1961; Good et al., 1962; Metcalf, 1966; Hess, 1968). In some cases, in children with hypoplasia of the thymus gland, shortly before death, the phenomena of aplastic anemia were also noted (Glanzmann and Riniker, 1950; Thompson, 1967; Dooren et al., 1968) or granulo- and thrombocytopenia (Lamvik, Moe, 1969) ...
Most children with thymus aplasia or hypoplasia die within the first 6 months of life. However, in some cases, a longer course of the disease is observed - up to 1 year 7 months (Hitzig, Biro et al., 1958) and more. A more detailed immunological examination of such patients revealed that some of them retain their ability to some extent to some immunological (allergic) reactions (Hitzig, Biro et al., 1958), as well as the preservation of certain fractions of immunoglobulins (Becroft, Douglas, 1968; Berg, Johansson, 1967), which allows distinguishing a number of clinical varieties of this disease (Sell, 1968). Obviously, this depends on the degree of hypoplasia (alimphoplasia) of the thymus gland, which can be expressed in different ways. With a relatively small degree of hypoplasia, due to the partial preservation of the body's ability to immune reactions, the disease can take a protracted course. An example of this, apparently, is the observation by Grote and Fischer-Wasels (1929) of “total alimphocytosis” in a 39-year-old man who died of exhaustion. Autopsy revealed atrophy of the spleen (18.0) and other lymphoid organs. The small intestine had dark-pigmented scars, and the lymph nodes of the mesentery contained foci of “cheesy necrosis”. The thymus gland, unfortunately, was not examined. In the same respect, one of our observations, which is presented below, is of undoubted interest.
Male E., 55 years old. A carpenter. Married, had no children. From early childhood, he often had diarrhea, and therefore strictly followed a diet throughout his life. Smoked a little. I rarely drank alcohol. Over the past 3 years, he was comprehensively examined in many hospitals in Leningrad, but the diagnosis remained unclear. In connection with the growing exhaustion and suspicion of a tumor in the abdominal cavity on 17 / V 1968, he was admitted to the clinic of the faculty surgery of the Military Medical Academy, where on 31 / V he underwent a diagnostic laparotomy, during which no tumor was found. After the operation, the patient's condition began to deteriorate rapidly. Blood test 17 / VI 1968: er. 3700000, Hb 13.2 g%, color, cp. 1.0, l. 13500, of which s. 45%, p. 37%, y. 7%, limf. eleven%. ROE 10 mm / h. In previous blood tests, the lymphocyte count ranged between 7-14%. Repeated bacteriological examinations of feces did not reveal the pathogenic flora. The patient died on 17 / VI 1968 with symptoms of increasing exhaustion and associated pneumonia. He was delivered to the autopsy with a diagnosis of a severe form of sprue disease with extreme exhaustion and severe vitamin deficiency, condition after diagnostic laparotomy, ascites, sacral pressure ulcers, bilateral pneumonia and pulmonary edema.
At autopsy (dissector T, V. Polozova), a sharp exhaustion was noted. Body weight 40 kg with a height of 166 cm. Fresh postoperative scar along the midline of the abdomen. In the region of the sacrum, there is a pressure sore with a dark gray bottom 5x4 cm. The left pleural cavity is free. The right lung in the upper sections is fused with the parietal pleura. In the area of \u200b\u200bits apex there are several dense scars and a small encapsulated calcified focus. In the lower part of the left lung, there are multiple gray-red airless foci of compaction measuring 1-1.5 cm in diameter. The lower-left branch of the right pulmonary artery is thrombotic. In the lower lobe of the right lung under the pleura, a black-red airless lesion of irregular wedge-shaped shape with dimensions 5X5X4 cm is determined. Broi-hopulmoial lymph nodes are not enlarged, black-gray, with small gray scars. There is a small amount of clear yellowish liquid in the abdominal cavity. On the mucous membrane of the small intestine, transversely located superficial ulcers up to 4X2 cm in size with a dark gray pigmented bottom are visible. Two of the same type of ulcer are found in the mucous membrane of the cecum. Peyer's patches and lymphatic follicles are undetectable. The lymph nodes of the mesentery are up to 1 cm in diameter, in many of them yellowish-gray areas are visible on the cut. The spleen weighs 30.0 with a thickened capsule, dark red on the cut. The tonsils are small. Inguinal and axillary lymph nodes up to 1 cm in size, gray on the cut. Heart weighing 250.0, its muscle is brownish-red. The liver, weighing 1500.0, is brownish brown in section. There are multiple small hemorrhages under the pleura of the left lung and in the folds of the gastric mucosa. Other organs and tissues were somewhat reduced in size, otherwise unchanged. The thymus gland is not found in the fiber of the anterior mediastinum.

Results of histological examination.

Small intestine: superficial ulcers with a necrotic bottom containing gram-negative bacilli; in the submucosa and muscle layers - infiltrates from histiocytes and a few lymphocytes. Mesenteric lymph nodes: among the lymphoid tissue, foci of necrosis are visible, without a cellular reaction around; tubercle bacilli and other microbes are not found in them; axillary lymph node with sclerosis in the center and a small amount of lymphoid tissue in the periphery (Fig. 10, a). Spleen: lymphatic follicles are very weak, they are found in small numbers; the pulp is sharply full-blooded. Fiber of the anterior mediastinum: among the adipose tissue, there are few small lobules of the thymus gland that do not have division into cortical and medullary layers and do not contain Gassal's bodies; lymphocytes in the lobules are almost completely absent (Fig. 10, b, a), the lobules consist of reticular and epithelial cells, which in some places form separate glandular cells. Liver: fatty degeneration and brown atrophy. Myocardium: brown atrophy. Kidney: hydropic dystrophy. Lung: foci of pneumonia containing gram-positive cocci.
On the basis of the results of autopsy and histological examination, the diagnosis was made of chronic nonspecific ulcerative enterocolitis, leading to exhaustion and complicated by pneumonia. The development of the disease in this case can be associated with the defective development of the thymus gland and the entire lymphatic system as a whole.
Figure: 10. Alimphoplasia of the thymus gland.
a-axillary lymph node with sclerosis of the central part and preservation of lymphoid tissue in the form of a narrow layer along the periphery (magnification 60X); b-one of the lobules of the thymus gland with almost complete absence of lymphocytes (magnification 120X); in the same (sw. 400X) ..
Recently, transplantation of the thymus gland from human fetuses has been used to treat such patients with some success (August et al., 1968; Clevelend et al., 1968; Dooren et al., 1968; Good et al., 1969; Koning et al., 1968). others, 1969). Moreover, after transplantation, there is a rapid increase in the number of lymphocytes in the blood, the appearance of immunoglobulins in it. Children develop the ability for cellular and humoral immune responses, including the reaction of rejection of tissue homografts (August et al., 1968; Koning et al., 1969). Examination of a biopsy lymph node in one of these patients after thymus transplantation revealed the presence of well-defined lymphatic follicles with multiplication centers in it (Clevelend, Fogel, Brown, Kay, 1968).

When dysfunction of T-lymphocytes infectious and other diseases are usually more severe than in the absence of antibodies. Patients in such cases usually die in infancy or early childhood. The products of damaged genes have been identified only for some primary disorders of T-lymphocyte function. The treatment of choice for these patients is currently thymus or bone marrow transplantation from HLA-compatible siblings or haploidentical (semi-compatible) parents.

Thymus hypoplasia or aplasia (due to a violation of its anlage in the early stages of embryogenesis) is often accompanied by dysmorphism of the parathyroid glands and other structures that are formed at the same time. Patients have esophageal atresia, cleavage of the palatine uvula, congenital defects of the heart and large vessels (atrial and ventricular septal defects, right-sided aortic arch, etc.).

Typical facial features of patients with hypoplasia: shortening of the labial groove, hypertelorism, antimongoloid eye incision, micrognathia, low-set ears. Often, the first indication of this syndrome is hypocalcemic convulsions in newborns. Similar facial features and anomalies of large vessels extending from the heart are observed in fetal alcohol syndrome.

Genetics and pathogenesis of thymic hypoplasia

Dee Georgie Syndrome occurs in both boys and girls. Familial cases are rare, and therefore it is not classified as a hereditary disease. However, more than 95% of patients had microdeletions in the qll.2 segment of chromosome 22 (a DNA region specific for DiGeorge syndrome). These divisions, apparently, are more often transmitted through the maternal line.

They can be quickly detected by genotyping using PCR microsatellite DNA markers located in the appropriate area. 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 now talking about the SATCH22 syndrome (Cardiac, Abnormal facies, Thymic hypoplasia, Cleft palate, Hypocalcemia - heart defects, facial anomalies, thymic hypoplasia, cleft palate, hypocalcemia), which includes a wide range of conditions associated with 22q deletions. Deletions of the p13 segment of chromosome 10 have also been found in Di Giorgi syndrome and VCFS.

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 below the age norm. The number of CD T-lymphocytes is reduced in accordance with the degree of hypoplasia of the thymus, and therefore the proportion of B-lymphocytes is increased. The response of lymphocytes to mitogens depends on the degree of thymic insufficiency.

The thymus, if present, detects little bodies Hassal, normal density of thymocytes and a clear border between the cortical and medulla. Lymphoid follicles are usually preserved, but the number of cells in the para-aortic lymph nodes and the thymus-dependent region of the spleen is usually reduced.

Clinical manifestations of thymic hypoplasia

More often, there is not complete aplasia, but only the parathyroid glands, called incomplete DiGeorge syndrome. Such children grow up normally and do not suffer too much from infectious diseases. In complete Di Giorgi syndrome, as in patients with severe combined immunodeficiency, susceptibility to opportunistic and opportunistic flora, including fungi, viruses, and P. carinii, is increased, and graft versus host reactions are often developed upon transfusion of unirradiated blood.

Treatment of hypoplasia of the thymus - DiGeorge syndrome

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

The role of the thymus in the body

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 against foreign antigens. Natural defenders protect the child from infection and viral and bacterial damage.

The reasons for the development of hyperplasia

Thymomegaly - another definition of an overgrown thymus, is transmitted genetically. In infants, it develops for several reasons:

late pregnancy;
problems with bearing a fetus;
infectious diseases of a woman while waiting for a baby.

External signs of thymomegaly

To understand that the baby's thymus gland is enlarged, some characteristic signs help. In newborns, the problem is recognized by overweight and fluctuations in body weight up and down.

They happen pretty quickly. Mothers may notice increased sweating of the crumbs, frequent regurgitation and coughing, for no reason pestering the child in the supine position.

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

How is thymus abnormality diagnosed?

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

Conservative and urgent events

Children's quality of life

How the baby's life will proceed with the proliferation of the thymus gland, says Dr. Komarovsky. If the baby is diagnosed with stage I thymomegaly, there is still no serious danger. This is just a hint that the child needs regular health improvement.

In this syndrome, the cells of the embryo are intrauterinely affected, from which the parathyroid glands and thymus develop. 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 the underdevelopment of the lower jaw, a short upper lip, characteristic eye slits, low position and deformation of the auricles. In addition, children have congenital disorders of the heart and large vessels. The disease appears sporadically, but there are suggestions that it is caused genetically and is inherited in an autosomal recessive manner.

Clinically, DiGeorge's syndrome manifests itself at birth. Facial imbalances, heart defects are characteristic. The most characteristic symptom during the neonatal period is hypocalcemic convulsions (due to underdevelopment of the parathyroid glands). Immunodeficiency syndrome develops more often in the second half of the life of an 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's syndrome. In the blood, a decreased level of calcium and an increased level of phosphorus and a decrease or complete absence of the hormone of the parathyroid glands are found, 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 at the same time (for example, heart defects, renal pathologies, abnormalities of the facial skull, including cleft palate, etc.) and are caused by a deletion in chromosome 22 q11.

Diagnostic criteria

Involvement in the process of\u003e 2 of the following organs of the system:

thymus;
parathyroid gland;
the cardiovascular system.

Transient hypocalcemia may occur, causing seizures in newborns.

Serum immunoglobulins are usually normal, 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.

With the full severity of the syndrome, patients are usually susceptible to opportunistic infections (.Pneumocystisjiroveci, fungi, viruses), and death is possible with blood transfusion due to a graft versus host reaction. 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.

The lymph node follicles are normal, but areas of cellular depletion are observed in the paracortical and thymus-dependent areas. The risk of developing cancer and autoimmune diseases is not increased.

Thymus tumors

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

Associated

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

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

True red cell aplasia (ICCA) occurs in approximately 5% of patients with thymus.

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

PRIMARY IMMUNODEFICIENCIES (PIDS).

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

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

With combined PIDS, one or more of the listed factors of combined damage to the T-B immune systems or a defect in enzymes that ensure the normal functioning of the immune system may occur.

Clinical manifestations of PIDS are: decreased resistance to infections, an increase in the frequency of infectious diseases, the severity and duration of their course, the development of severe and unusual complications, the 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 - by fungi, viruses, mycobacteria and gram-negative microbes. With PIDS, the incidence of tumor diseases, mainly of lymphoid tissue, and autoimmune diseases increases.
To understand the pathological changes in the organs of immunogenesis with PIDS, it is necessary to know that the thymus, both in phylogenesis and in human ontogenesis, is formed earlier than other organs of immunity (2 months of intrauterine development), before other organs it is populated with lymphocytes and by the time the child is born it 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 OF THIMUS
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 with lymphocytes, mature lobules are present, the cortical and medullary layers are clearly visible in them. If an immature thymus is found in a full-term newborn or in a child in the first years of life, this is an indicator of a functional deficiency of the child's immune system, which may disappear with age.This immaturity of the thymus is an unfavorable background condition in which infectious diseases occur with a severe course and even death. ...

In postnatal ontogenesis, the thymus undergoes age-related involution, which begins at the age of 5-7 years and ends by the period of puberty.
^ AGE INVOLUTION OF THIMUS
Adipose tissue develops, which is introduced into the lobules of the thymus. The lobules decrease in size, the number of lymphocytes in them decreases, the division into the cortical and medullary layers disappears, Gassal's little bodies become homogeneous, partially calcified, their neoplasm stops. At the same time, the thymus lobules in the form of small islets are located among the adipose tissue and are preserved at any age. Adipose tissue is especially developed during puberty and at the age of 18-20 years. In this case, the thymus looks like a large fatty body. In old age, thymic adipose tissue gradually atrophies and hardens.
^ ACCIDENTAL TRANSFORMATION (or involution) of THIMUS
A sharp decrease in the mass of the thymus arising under the influence of various diseases, trauma, starvation, cooling was called an accidental involution of the thymus (the Latin word accedentis literally means accident).

The etiology of AT is diverse, which indicates the stereotype of this phenomenon and the absence of any specificity in relation to the agent that caused this reaction of the thymus. AT is observed in 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 proliferation in the subcapsular zone of the thymus cortex of pre-T-lymphocytes, their differentiation into mature T-lymphocytes increases. Phase II should be considered the beginning of involutive processes.

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

Phase III - death of lymphocytes in the cortical layer with preserved lymphocytes in the medulla. This leads to inversion of the layers of the thymic lobules, and a gradual collapse of the cortical layer occurs. In the interlobular septa, there are many mast cells, eosinophils, macrophages, fibroblasts. The number of Gassal's little bodies increases, they appear in the medulla and even in the cortex, but they are small. Inside thymic bodies, lymphocytes, neutrophils, eosinophils can accumulate with symptoms of karyopycnosis and rexis.

Phase IV - emptying of the medullary zone, due to the death of lymphocytes, thymic lobules collapse, thymic bodies merge, forming cystic expanded cavities filled with homogeneous eosinophilic masses, some calcify. The connective tissue capsule of the thymus and the interlobular connective tissue are expanded, in it islets of adipose tissue, infiltration by lymphocytes, eosinophils, macrophages, and mast cells.

Phase V - coarsening of the stroma increases, narrow strands of cell clusters remain from the thymic lobules with the inclusion of thymic bodies in them, which are completely calcified. Large vessels and capsule are sharply sclerosed, adipose tissue among the stroma.

Thus, the IV - V phases of AT differ only in the degree of sclerosis of the stroma and its vascular bed.
^ PRIVATE PIDS FORMS
Morphological point of view, changes in the thymus in PIDS can be characterized as organ dysplasia and hypoplasia.
DYSPLASIA - IMPAIRMENT OF THE FORMATION OF THE COMPOSITION OF TISSUE ELEMENTS OF THYMUS IN THE INTRAUTERINE PERIOD (EMBRYONIC AND EARLY FETAL PERIOD) and is characterized by the absence or underdevelopment of the reticuloepithelium of fatty tissue, the absence (partial or complete) of the period of the formation of the delayed post-mortem signs of transformation, the absence (partial or complete) of the late formation of the delayed postural signs According to this definition, several variants of thymic dysplasia are distinguished. Subsequent classification is given by WHO (1978).

^ THYMUS DISPLASIA
- first option - according to WHO Swiss type Glanzmann-Riniker. Absence or abrupt underdevelopment of the reticuloepithelium and poor colonization of the lobules with lymphocytes. Severe combined immunodeficiency (TCID), both cellular and humoral immunity is impaired. The type of inheritance is autosomal recessive. The main pathogenesis is the defect of the lymphoid stem cell. Clinically characterized by intermittent lymph and leukopenia. Infectious diseases develop in the first months of life, and lead to death at 6-8 months of age. In the pathological examination, multiple necrosis and inflammatory infiltrates in the skin, which are the source of sepsis. Described are dermatitis of the Leiner type, exfoliative erythroderma of the Ritter type or histiocytosis of X. Bacterial infections are combined with viral infections - generalized chickenpox, measles giant cell pneumonia, generalized cytomegaly, herpes simplex, adenovirus infection, lesions by fungi 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, the thymic bodies are absent or very small, single. There are very few lymphocytes, there is no division into cortical and medullary layers. The lymphoid tissue of peripheral organs in a state of hypoplasia: the lymphoid follicles are not developed, the zones in the lymph nodes are indistinguishable, the tissue of the nodes consists of the reticular stroma, myeloid elements and a small number of lymphocytes.

- second option according to WHO Neselof syndrome (alimphocytosis). Dysplasia of the thymus is characterized by the presence of a reticuloepithelium, which forms lobules of the thymus with multiple glandular-like structures, Gassal's little bodies are absent, lymphocytes are single. Cellular immunity suffers. It is inherited recessively, linked to the X chromosome. The pathogenetic essence is reduced 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-it, herpes simplex, sepsis caused by gram-negative flora. Life expectancy is 1-2 years. The thymus mass is reduced. In the lymph nodes, the 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 the WHO, it is a SCID with adenosine deaminase deficiency. Characterized by the defeat of the B - and T - cell link. Recurrent infections caused by Candida, pneumocystis, Pseudomonas aeruginosa, cytomegalovirus, herpes viruses, chickenpox are characteristic. Often combined with a violation of the formation of cartilage tissue. Without a bone marrow transplant, death occurs in the first year of life.

It has 2 types of inheritance, autosomal recessive (40%) - with this form there is no enzyme adenosine deaminase: while there is an accumulation of deoxyaminazine, which is toxic to immature lymphocytes (especially T-l). Recessive, associated with the X chromosome (50%) - a mutation that affects a protein that is a receptor for IL-2,4,7. Morphological changes depend on the type of genetic defect. With the 1st type of inheritance, the thymus is small, without lymphocytes. In other cases, the lymphoid tissue is hypoplastic with a decrease in the zones of T-cells and T - and B-zones.
- fourth option by WHO Dee George's Syndrome

(hypoplasia or agenesis of the thymus). It is caused by a violation of the development of the 3rd and 4th pharyngeal pockets, 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, antimongoloid eye incision, low-set ears, as well as esophageal atresia, hypothyroidism, tetrado of Fallot, kidney and ureter hypoplasia. Due to impaired cellular immunity, there is no protection against fungal and viral infections. T-dependent zones in the thymus, spleen are absent. Plasma cells are not affected and the level of immunoglobulins is unchanged. This syndrome is caused by impaired embryogenesis at the 6-8th week of pregnancy.

- the fifth variant of the WHO Louis-Bar syndrome (ataxia-telenangiectasia Louis - Bar). Characterized by a deficiency of cellular and partly humoral immunity in combination with progressive cerebellar ataxia and peribulbar telangiectasias. Morphologically - thymic dysplasia, the lobules consist of reticuloepithelium, there are no Gassal bodies, a decrease in T - lymphocytes, the lobules are not divided into cortical and cerebral zones. In the reticuloepithelium, giant cells with hyperchromic nuclei are formed. In the peripheral organs of immunogenesis, hypoplasia of T-dependent zones. In the cerebellum - atrophy of the cortex with the expansion of the IV ventricle. Microscopy - dystrophy or complete disappearance of pear-shaped neurocytes (Purkinje cells) and granular layer. Such changes are observed in the anterior horns of the spinal cord, hypotolamus and diemilinization 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 characteristic: lymphomas, lymphogranulomatosis, leukemia, meduloblastomas, adenocarcinomas, dysgerminomas.

This defect is caused by a defect in the final differentiation of T - lymphocytes, as well as an abnormality of the plasma membranes of lymphocytes. It is 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 found by the 1st year of life on the bulbar conjunctiva, then in other areas. Graying of hair, sweating, atrophic dermatitis, eczema, skin neoplasms and severe physical retardation are noted. Secondary sexual characteristics do not develop. Menses irregular. Patients live up to 39-41 years.

- the sixth option according to WHO a bruton's gamma globulinemia linked to the X chromosome ... It is characterized by untimely fatty transformation of the thymus. One of the most common primary IDs. With it, there is no serum IgG immunoglobulin or it is small. More often in boys, beginning 8-9 months: when the amount of immunoglobulins from the mother decreases. Recurrent conjunctivitis, otitis media, pharyngitis, bronchitis, pneumonia appear, skin infections (pyoderma) are more often caused by staphylococcus or Haemophilus influenzae. Cellular immunity is not compromised. With Bruton's disease, autoimmune diseases (rheumatoid arthritis, SLE, dermatomyositis) often develop. B-lymphocytes are sharply reduced or not. L \\ u and spleen do not have herment centers, and l \\ u, spleen, bone marrow and connective tissue, there are no plasma cells, palatine tonsils in the form of rudiments, T-lymphocytes remain normal.
- seventh optionChronic 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 ill, the course is difficult.
2. It is rare, inherited in an autosomal recessive manner, children of both sexes are ill, it proceeds more easily. The first clinical symptoms are skin lesions in the 1st month of life in the form of eczematous changes with suppuration in the area of \u200b\u200bthe auricles and around the nose, plus regional lymphadenitis, then the liver, lungs, l. Nodes, bones are involved in the process, in which abscesses are formed. In the pathological examination - premature fatty transformation of the thymus, in the internal organs of the granuloma, consisting of monocytes, neutrophilic leukocytes, followed by purulent fusion and scarring. In this case, macrophages and neutrophils are loaded with GAGs and lipids, these cells are found in the lungs, thymus, spleen, l \\ nodes, liver. Hepato-splenomegaly is noted.
Common variable immunodeficiency. This heterogeneous group can be congenital or acquired, sporadic or familial (with a variable mode of inheritance). Typically - hypogammaglobulinemia, a defect of all AT classes, but sometimes only IgG. In these patients, the content of B-lymphocytes in the blood and lymphoid tissue is not disturbed, but the B-lymphocytes are not transformed into plasma cells, and there is no AT secretion. Clinically - recurrent bacterial infections, enterovirus infections, herpes, giardiasis Histologically - hyperplasia of B-cell zones of 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 both familial and acquired after toxoplasmosis, measles, and other viral infections. With a deficiency of IgA, the protection of the mucous membranes is impaired and infections of the respiratory tract, gastrointestinal tract, MPS, respiratory tract allergy and autoimmune diseases (SLE, rheumatoid arthritis) develop. The bottom line is a defect in the differentiation of B-lymphocytes that produce IgA. They often develop anaphylactic reactions.

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

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

^ Thymus hypoplasia is characteristic of and mmunodeficiency with thrombocytopenia and eczema (Wiskott-Aldrich syndrome) has a recessive path of inheritance and is associated with the X chromosome. Typical thrombocytopenia, eczema, recurrent infections, early death occurs. Morphologically, the thymus is of normal structure, but there is a progressive secondary depletion of T-lymphocytes in the peripheral blood and paracortical (thymus-dependent) zones of the l / y with a decrease in cellular immunity. The serum IgM level is low, IgG is normal. IgA and E levels increase. Malignant lymphomas often develop.

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

TM - an increase in the mass of the organ by 3-4 times compared to the norm, the absence of stereotypical phase changes (including phases III-IV AT) under stress or antigenic exposure. From a clinical point of view, TM is diagnosed radiographically based on an increase in the cardiotimicothoracic index\u003e 0.38. TM is observed in children who often suffer from ARVI (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 the central nervous system. In infectious diseases in children with TM, death occurs in the early stages of the disease. The following TMs are isolated microscopically:

In the cortical zone, the proliferation of macrophages and lymphoblasts is determined (the first phase of AT) - a picture of the "starry sky", thymic bodies are few, small, mainly of a cellular structure (consist of 3-5 annular reticuloepithelial cells), localized in the medulla. This option is found in children who died from acute respiratory viral infections and meningococcemia in the early stages of the disease.
In the cortical zone of the thymus, large clusters, consisting of lymphocytes, resembling lymphoid follicles, Gassal's little bodies are small, either of a cellular structure, or homogeneous 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 lobules of the thymus, division into zones is preserved, but the cortical zone prevails over the cerebral zone. Thymic bodies are small, few in number, of cellular structure. It is observed in infectious-allergic myocarditis, acute respiratory viral infections, complicated by pneumonia, in combination with heart and central nervous system defects.

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