currently a growing interest to physicians diseases associated with a dysfunction of the immune system.Diagnosis "immunodeficiency" is becoming more popular among doctors of different specialties.In the pharmaceutical market offers a wide range of drugs that affect the immune system.In addition to medicines, the effect of a variety of food additives, vehicles, non-traditional methods and regimens represented by their creators in the media as "improving the immune system."
Not having sufficient knowledge in the field of clinical immunology, pediatric safely administered to children immunotropnye preparations of various groups in the absence of any clinical evidence, without a clear statement of the diagnosis, study and correct interpretation of the results of immune status.It seems that often doctors, instead of clearly defined diagnosis and treat the disease in accordance with approved standards prescribed immunotropnye means not representing the effect and consequences of such therapy.
Unjustified immunocorrection most often done to children who attend child care centers and SARS are sick 3-5 times a year.The disease is usually without complications.This is normal and does not require active intervention in the immune system.
second large group - children with allergies to household allergens (house dust mites, mold spores, and others.), Which is manifested perennial allergic rhinitis and asthma.Clinically, children have frequent episodes of sneezing, itchy nose, nasal breathing difficulty, coughing.Often cough and rhinitis particularly pronounced during the night or early in the morning, in dusty environments and SARS.Despite the fact that children are the typical symptoms of allergy patients often for a long time receiving treatment at the "secondary immunodeficiency."
third group - the children, who in laboratory immunological studies revealed some abnormalities.Without any connection with clinical symptoms, based only on laboratory data assigned immunotherapy.
At the same time, congenital immunodeficiency in children diagnosed very bad.The problem of primary immunodeficiencies (PID) will be important for several reasons.
1. Timely and correct diagnosis of PID, and holding pathogenetically substantiated therapy allows patients to retain a sufficiently high quality of life for many years.
2. The diagnosis of PID and verification of gene defects enables genetic counseling of families and prenatal diagnosis.
3. Analysis of the features of medical history and clinical manifestations in patients with different forms of PID in conjunction with the predominant immune disorders will allow doctors to improve their knowledge in clinical immunology.
4. The generalization of clinical symptoms in patients with PID, depending on the type of immune disorders and genetic defects are expanding knowledge of the immune system and the regulation of immune response, determine the prospects for a targeted search for new approaches to therapy.
main function of immunity - to maintain the genetic constancy of the internal environment.First, this function is realized in protecting the body from infections.In addition, the immune system performs antitumor protection, protection from their own modified cells bearing signs of foreignness.
After contact with microorganisms (bacteria, viruses, parasites, etc.) through the skin and mucous membranes into the interior of the human body environment, the first barriers to infection are natural resistance factors: macrophages, neutrophils, natural killer cells, complement.Their protective action is manifested during the first hours after the introduction of the antigen and lasts 96 hours after infection.At this time, it starts to develop a specific immune response which occurs during antigen recognition, the formation of cellular and humoral reactions types aimed at the elimination of the antigen, and eventually - the successful formation and elimination of antigen-specific immunological memory with respect to this foreign agent.To form a full immune response and effective protection against infections important each stage of the immune response .
When primary immunodeficiencies is a violation of the formation of a full-fledged immune response to different levels of development.
At the time, described some 80 PID.Identified the genes responsible for the development of X-linked severe combined immunodeficiency, X-linked agammaglobulinemia, X-linked giperIgM syndrome, Wiskott-Aldrich syndrome, X-linked chronic granulomatous disease and other PID (Table 1).The nature of many of the PID remains unknown [17, 24].
In accordance with the most important components of the immune system are 4 main groups of PID depending on the prevailing immunological defect :
defects in antibody production;combined defects of immunity;Defects of phagocytosis;defects of the complement system.
relatively low prevalence of PID in the population, pathogenetic heterogeneity and lack of specific clinical entities for specific clinical markers greatly complicates their diagnosis.Diagnosis of PID is based primarily on an analysis of the history of the disease and the patient's life, family history data, clinical manifestations of immune deficiency and certain immune defect.
First symptoms of PID tend to occur at the 1st year of life, but it is possible and a later onset of some forms of PID, in particular common variable immune deficiency [5, 10, 13, 17].
Violations of anti-protection developed in almost all currently known primary immunodeficiencies [4, 5, 22].Most of the clinical manifestations of PID is associated with frequent heavy occurring infections.Lesions of the respiratory tract are the most typical.Infectious diseases of respiratory system and ENT - acute and chronic bronchitis, otitis, sinusitis, recurrent pneumonia with formation of bronchiectasis, pleurisy, sinusitis quick tendency to chronicity - is more severe and long lasting, antibacterial therapy is temporary, short-term effect.Surgical treatment of purulent sinusitis, otitis, bronhoetazov does not lead to the expected improvement of [3, 4, 9].
characteristic infections of the skin and mucous membranes of the gastrointestinal tract .Less common severe diseases such as osteomyelitis, sepsis, meningitis, mastoiditis [6, 12, 23].
pathogen type is determined by the nature of the immune defect [17,18]:
- for defects in antibody production is typical of highly pathogenic antimicrobial resistant encapsulated flora (Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae).Patients with predominantly B-cell defect (defective antibody production) are highly susceptible to enteroviruses.Enteroviral encephalomyelitis occur is extremely difficult and pose a serious threat to life ;
- in patients with combined lesions, predominance of T-cell deficiency pathogens are not only bacteria but also viruses (herpes viruses, cytomegalovirus, Epstein-Barr virus, and others.), Fungi (Candida albicans), protozoa (P. carinii);
- with phagocytic defects - staphylococci, gram-negative bacteria, Candida albicans, Aspergillus;
- at deficiency of complement components - pyogenic bacteria and Neisseria.
Infectious diseases characterized by persistent current and insufficient effect of antimicrobial therapy.For most forms of PID characterized by a combination of two or more chronic diseases, chronic intoxication symptoms, delayed physical development [1, 16, 17,19].
Patients with PID, along with severe infectious processes, may develop autoimmune diseases and cancer [10, 25, 28].Among autoimmune diseases most frequently observed arthritis, hepatitis, nephritis, ulcerative colitis and Crohn's disease, sclerosing cholangitis, malabsorption, systemic lupus erythematosus [27, 29].Autoimmune anemia lekopenii, neutropenia, thrombocytopenia are also characteristic of patients with PID .
important point in the diagnosis of PID is the presence of changes in a patient from the lymphoid tissue.Possible hypoplasia of lymphatic tissue, which clinically manifested hypoplasia tonsil and peripheral lymph nodes.When hyperplasia peripheral lymph nodes may be enlarged to the size of a small plum and apple, can be atypical of their localization.Patients with some forms of PID detected hepatosplenomegaly .
The diagnosis of PID can provide substantial assistance to family history.Among currently known PID described with disease X-linked inheritance type (see. Table 1).In these families, the female (mother) line may indicate severe illness or early death of boys from infections of the respiratory or gastrointestinal tract and other serious diseases.If you suspect a particular form of PID should specify the frequency of tumors in a patient relatives;bleeding, as in the syndrome Wiskott-Aldrich;neurological manifestations in relatives of patients with suspected syndrome Louis Barr.A negative family history does not deny the presence of the child's PID.
for pediatricians is important to be clear that the diagnosis of PID involves typical clinical symptoms and related immunological disorders that meet diagnostic criteria for each specific disease.
Defects in the production of antibodies are the most common forms of PID.They differ in the depth of the immune defect, from the total absence of immunoglobulin subclasses to deficit and selective deficiency of specific antibodies.The most severe clinical picture and the forecast is a syndrome with a total lack of immunoglobulin (agammaglobulinemia).These include X-linked agammaglobulinemia (Haqq), common variable immunodeficiency (CVID) and others are characterized by the almost complete absence or a sharp decrease in the concentration of immunoglobulin A, M and G in serum.Typical clinical manifestations of this group of PID are heavy, often recurrent and chronic bacterial infections: suppurative otitis media, conjunctivitis, lesions of the paranasal sinuses that are resistant to antibiotic treatment, bacterial bronchitis, pneumonia and pleurisy.It is highly probable sepsis, osteomyelitis, meningitis, formation of bronchiectasis.Nevertheless, every form of total defect production of antibodies has clinical and immunological features.
We would like to draw particular attention to the principles of early diagnosis of deep antibody defects due to the possibility of maintaining a high, close to a normal quality of life of patients for many years provided an early start and regular immunoglobulin replacement therapy drugs for intravenous administration.
CVID is one of the most frequent primary immunodeficiencies.Its prevalence varies from 1: 50,000 to 1: 200,000.Boys and girls suffer equally often.In children, the disease develops at the age of 2-7 years.There are two age peaks CVID diagnosis: 25-30 and 50-60 years.
patients with CVID decrease in immunoglobulin products due to the violation of T cell regulation of their synthesis [2, 14, 21].
significant reduction in major classes of serum immunoglobulins IgA, IgM and IgG, the total concentration of less than 300 mg / dL.In most patients, the number of circulating B-cell is maintained within the normal range .
As with all PID with the total defeat of the humoral immunity, the main clinical symptoms in patients with CVID are recurrent infections of the respiratory and gastrointestinal tracts.The clinical symptoms characteristic of CVID include high frequency of lymphoreticular and gastrointestinal cancers as well as chronic inflammatory bowel disease - ulcerative colitis nespetsificheskog and Crohn's disease.One-third of patients have splenomegaly and / or generalized lymphadenopathy.Lymphoid hyperplasia in the gastrointestinal tract of clinically malabsorption syndrome (diarrhea, weight loss).Of note manifestations of autoimmune arthritis, anemia, thrombocytopenia, neutropenia.
agammaglobulinemia-deficient B cells - the second most common form of the occurrence of total immunoglobulin deficiency after the common variable immune deficiency.The disease develops due to a gene defect in cell tyrosine kinase (btk), there is a delay in the maturation of cells at the level of pre-B lymphocytes.X-linked inherited, sick boys;early onset of the disease - the first year of life.
Reduced serum IgG concentration of less than 200 mg%, the lack of IgA and IgM.The number of circulating B-cells dramatically reduced (2% or less available).
Repeated bacterial infections of the respiratory tract, gastrointestinal tract, skin.The high sensitivity of the enterovirus, which can cause severe meningoencephalitis.Characterized by hypoplasia of lymph nodes (palpation many patients peripheral lifaticheskie nodes are not palpable) and tonsils.Possible violations of blood (agranulocytosis), and autoimmune disorders such as rheumatoid arthritis, scleroderma.
syndrome comprises a group of diseases with similar clinical manifestations and immunologcheskimi.In 70% of cases, the disease is inherited X-linked, in the other - an autosomal recessive.
Some genetic defects found in patients with hyper-IgM-syndrome, are shown in Table 1.
main criterion of diagnosis of hyper IgM - syndrome is a sharp decline in serum IgG and IgA concentrations with normal or high IgM content.The number of circulating B-cells - normal.
Hyper-IgM syndrome is characterized by recurrent infections, autoimmune disorders, high incidence of complications of cancer and hematological disorders.The first clinical manifestations in most patients develop in infancy and early childhood.Typical lesions of the respiratory tract (sinusitis, bronchitis, pneumonia).Interstitial pneumonia can be caused by not only bacteria, but also intracellular pathogens, primarily Pneumocysta carinii, and Cryptosporidium.Gastrointestinal disorders may also be due to cryptosporidiosis.The high sensitivity of the enterovirus.
When hyper IgM syndrome often develop autoimmune disorders, which are more severe and worsen the prognosis of the disease.Characterized hematological disorders (hemolytic anemia, neutropenia, thrombocytopenia), and autoimmune disorders such as seronegative arthritis, glomerulonephritis .
From the lymphoid tissue is characterized by hyperplasia of normal size or lymph nodes and tonsils are often revealed hepatosplenomegaly.
treatment of all forms of agammaglobulinemia replacement therapy based on immunoglobulin preparations for intravenous administration in combination with antibiotic therapy.Replacement therapy of intravenous immunoglobulin preparations starts from the time of diagnosis and is held 1 time in 3-4 weeks for life.At the beginning of treatment or exacerbation of infections carried saturation therapy - 1-1.5 g / kg of patient weight per month, the maintenance dose is - 0.3-0.4 g / kg 1 time in 3-4 weeks.Dose immunoglobulin 0.3-0.4 g / kg is administered simultaneously at a rate of 20 drops per minute.
aim of replacement therapy - to achieve pretransfuzionnogo IgG level in the serum of the patient & gt;500 mg / dL.This level is normally protects the patient from severe bacterial infection [13, 16, 17, 19].Proc.Proc.Rev.
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